多种变异的il－3造血生成融合蛋白的制作方法

专利名称：多种变异的il－3造血生成融合蛋白的制作方法
技术领域：
本发明涉及由人白介素-3(hIL-3)的突变体或变异体组成的融合分子，hIL-3通过或不通过接头与包括细胞因子，淋巴因子，白介素，造血生长因子的第二种集落刺激因子(CSF)或IL-3的变异体融合。
背景技术：
因为刺激骨髓细胞分化和/或增殖的集落刺激因子(CSF)对于恢复降低的造血干细胞来源细胞的水平具有治疗潜力，所以引起人们极大的兴趣。在人和小鼠系统中的CSF都已经鉴定并根据它们的活性区别开来。例如，粒细胞集落刺激因子(G-CSF)和巨噬细胞集落刺激因子(M-CSF)分别刺激在体外中性粒细胞和巨噬细胞集落的形成，而GM-CSF和白介素-3(IL-3)有较宽的活性范围，可刺激巨噬细胞，中性和嗜酸性粒细胞集落的形成。IL-3还刺激肥大细胞，巨核细胞，和纯的以及混合的红系细胞集落的形成。
因为IL-3有刺激多种不同类型细胞增殖及支持祖先细胞生长和增殖的能力，所以它在一些情况下具有恢复造血细胞至正常数量的治疗应用潜力，在这些情况下，由于疾病或如放疗和/或化疗的治疗，细胞数量减小。
白介素-3是一种造血生长因子，具有能够促进造血细胞存活，生长及分化的特性。在IL-3的生物学特征中有如下能力(a)支持已定型为所有或基本上所有的血细胞谱系的祖细胞的生长和分化；(b)与早期的多能干细胞作用；(c)支持多能前体细胞的生长；(d)刺激慢性髓系白血病(CML)细胞的增殖；(e)刺激肥大细胞，嗜酸及嗜碱粒细胞的增殖；(f)刺激人急性髓系白血病(AML)细胞的DNA合成；(g)启动细胞产生白三烯和组织胺；(h)诱导白细胞趋化性；和(i)诱导白细胞粘附所需的表面分子。
成熟的人白介素-3(hIL-3)含有133个氨基酸。它含有一个二硫桥键和两个潜在的糖基化位点(Yang，等.,CELL 47:3(1986))。
小鼠IL-3(mIL-3)最初由Ihle，等.,J.IMMUNOL.126:2184(1981)鉴定为可诱导一种T细胞相关的酶，20-羟基类固醇脱氢酶表达的因子。该因子被纯化至均一状态并且表明该因子可调节多种造血及淋巴样祖细胞亚类的生长和分化。
1984年，分离了编码小鼠IL-3的cDNA克隆(Fung，等.,NATURE307:233(1984)和Yokota，等.,PROC.NATL.ACAD.SCI.USA 81:1070(1984))。小鼠的DNA序列编码包含推定的信号肽的166个氨基酸的多肽。
使用长臂猿cDNA表达文库获得了长臂猿的IL-3序列。接着将长臂猿的IL-3序列用作探针从人基因组文库中获取人的IL-3序列。
小鼠IL-3序列的长臂猿和人基因组DNA同源物由Yang，等.，CELL 47:3(1986)公开。Yang，等.，报道的人的序列在成熟蛋白质序列的第8位包含一个丝氨酸残基。在该报道之后，其它人报道了在蛋白质序列的第8位含脯氨酸的Pro8hIL-3 cDNA的分离。因此，看来有两种等位基因形式的IL-3。
Dorssers，等.，GENE 55:115(1987)，从人cDNA文库中发现了可与mIL-3杂交的克隆。二者能够杂交的原因是由于mIL-3和hIL-33’非编码区的高度同源性。该cDNA编码hIL-3(Pro8)序列。
U.S.4,877,729和U.S.4,959,454公开了人IL-3和长臂猿IL-3的cDNA序列及它们编码的蛋白质序列。公开的hIL-3在蛋白质序列的第8位是丝氨酸而不是脯氨酸。
Clork-Lewis，等.，SCIENCE 231:134(1986)对用自动肽合成仪合成的小鼠IL-3类似物进行了功能分析。作者的结论是完整分子的稳定的四级结构是该分子全活性所必需的。一项有关二硫键功能的研究表明用丙氨酸取代所有四个半胱氨酸所得到的分子只有天然分子活性的1/500。用Ala取代四个Cys残基中的两个(Cys79,Cys140→Ala79,Ala140)可导致活性增加。作者的结论是在小鼠IL-3中半胱氨酸17和80之间的单一的二硫桥键对于该分子接近生理水平的生物活性是必需的，而且该结构可能会稳定蛋白质的四级结构以提供对功能最适的构型(Clarke-Lewis，等.，PROC.NATL.ACAD.SCI.USA 85:7897(1988))。
国际专利申请(PCT,WO88/00598)公开了长臂猿和人类似的IL-3。该hIL-3包括了Ser8→Pro8的取代。建议用Ser取代Cys从而打断二硫键，并在糖基化位点取代一个或多个氨基酸。
EP-A-0275598(WO88/04691)证明缺失Ala1仍可保持其生物学活性。还提供了一些hIL-3突变体的序列，例如，两个双突变体，Ala1→Asp1,Trp13→Arg13(pGB/IL-302)和Ala1→Asp1,Met1→Thr3(pGB/IL-304)和一个三突变体Ala1→Asp1,Leu9→Pro9,Trp13→Arg13(pGB/IL-303)。
WO88/05469描述了如何获得去糖基化的突变体并提示Arg54Arg55和Arg108Arg109Lys110突变体可避免在酿酒酵母中表达时被蛋白酶KEX2降解。未公开突变的蛋白质。本申请中糖基化和蛋白酶KEX2的活性，仅在酵母中表达时才很重要。
WO88/06161提到多种从理论上讲构型和抗原都是中性的突变体。真正实行的突变是Met2→Ile2和Ile131→Leu131。没有公开是否从这两个突变中得到了所期望的中性突变。
WO91/00350公开了非糖基化的hIL-3类似蛋白，例如，hIL-3(Pro8Asp15Asp70),Met3rhuIL-3(Pro8Asp15Asp70),Thr4rhuIL-3(Pro8Asp15Asp70)和Thr6rhuIL-3(Pro8Asp15Asp70)。据报道这些蛋白组合物不表现出与天然hIL-3相关的某些相反的副作用如由于肥大细胞和淋巴细胞侵入真皮所引起的荨麻疹。公开的hIL-3类似物蛋白在Met3,Thr4，或Thr6含有N末端。
WO91/12874公开了IL-3的增加了半胱氨酸的突变体(CAVs)，其中至少有一个半胱氨酸残基取代了天然的氨基酸残基。
U.S.4,810,643公开了编码人G-CSF的DNA序列。
WO91/02754公开了由GM-CSF和IL-3组成的融合蛋白，该融合蛋白与单独的GM-CSF或IL-3相比，生物活性都增加。还公开了将非糖基化的IL-3和GM-CSF类似蛋白作为融合的组份。
WO92/04455公开了由IL-3和从包括IL-3,IL-6,IL-7,IL-9,IL-11,EPO及G-CSF的组中选择的一种淋巴因子融合的融合蛋白。
发明概述本发明包括通过或不通过接头与第二种集落刺激因子(CSF)或IL-3的变异体融合的重组的人白介素-3(hIL-3)变异体或突变的蛋白质(突变蛋白)，第二种集落刺激因子包括，细胞因子，淋巴因子，白介素，造血生长因子(本文统一称为“集落刺激因子”)。这些hIL-3的突变蛋白含有氨基酸取代，也可以在N末端和C末端之任一端或二端具有氨基酸的缺失。本发明包括由共价连接的多肽而形成的混合功能的集落刺激因子，每一个因子又都通过不同的和特异的细胞受体而启动互补的生物学活性。
本发明的新化合物用下式代表R1-L-R2,R2-L-R1,R1-R2,R2-R1,R1-L-R1和R1-R1，其中R1是包含多个氨基酸取代的hIL-3变异体，它也可含有缺失的hIL-3分子的部分，R2是IL-3,IL-3变异体或具有不同的但却互补的活性的CSF。R1多肽或直接或通过一个接头片段与R2多肽融合。因此L代表与R1和R2融合的化学键或多肽片段。本发明的这些突变体IL-3优选含有四个或更多个与天然的hIL-3多肽相应位置的氨基酸所不同的氨基酸。本发明还涉及包含融合分子的药用组合物；编码融合分子的DNA，和使用融合分子的方法。另外，本发明涉及包括编码hIL-3融合分子的核苷酸序列的重组表达载体，相关的微生物表达系统及使用微生物表达系统制备融合分子的方法。
这些融合分子的特征在于它们具有形成融合分子的两种肽的一般活性，或进一步的特征在于具有比IL-3或第二种集落刺激因子单独存在时的加和功能更大的生物或生理活性。融合分子也可能会出人意料的提供效应增强的活性或不同于所预料的在IL-3或第二种集落刺激因子或IL-3变异体存在情况下所出现的活性。融合分子也可能具有增进的活性类型，其中与天然hIL-3分子相关的所不希望的生物活性减小了。
本发明还包括hIL-3的突变体，其中自N末端起1～14氨基酸已缺失和/或自C末端起1～15氨基酸被缺失，还包含多个氨基酸的取代，第二种集落刺激因子或IL-3变异体与上述突变体融合。本发明优选的融合分子之中，氨基酸1～14从N末端缺失，氨基酸126-133从C末端缺失，并在与第二种集落刺激因子或IL-3变异体融合的多肽序列中包含大约四到二十六个氨基酸的取代。
本发明还提供了可用作IL-3拮抗物的融合分子或作为分立的抗原性片段以产生在免疫测定及免疫治疗方法中有用的抗体的融合分子。
hIL-3的拮抗物在阻断一些癌细胞如AML,CML及一些类型的B淋巴癌的生长中特别有用。其它拮抗物有用的情况包括血细胞以不正常的高的数量产生或血细胞由内源性配体激活。拮抗物能有效地与配体竞争，自然生成的红细胞生成素包括但又不限于IL-3,GM-CSF及IL-5，它们也许能诱发或增加癌细胞的生长，因为它们有能力与IL-3受体复合物结合但配体的内在的激活特性却消失了。IL-3,GM-CSF和/或IL-5还在一些气喘反应中起作用。IL-3受体的拮抗物可通过阻断受体介导的炎症细胞的激活和募集而用于治疗这类疾病。
除了在体内应用本发明的融合分子之外，想象融合分子在体外的应用应包括在注入患者体内之前即可刺激骨髓和血细胞激活和生长的能力。
附图简述

图1是用于大肠杆菌表达的人IL-3基因(pMON 5873)，当在大肠杆菌中表达时，编码天然的(野生型)人IL-3多肽序列〔SEQ IDNO:49〕，加一个启始甲硫氨酸，天然的hIL-3氨基酸从N末端计数。
图2是质粒pMON 13018和pMON 13021的构建。质粒pMON 13018是用于构建编码多肽融合体的质粒pMON 13021的中间体质粒。
图3是甲基纤维素测定法中测定的多肽融合体pMON 3988的生物活性。
图4是甲基纤维素测定法中测定的多肽融合体pMON 3987和pMON26430,pMON 3995及pMON 26415的生物活性。
图5是甲基纤维素测定法中测定的多肽融合体pMON 26425的生物活性。
图6是甲基纤维素测定法中测定的多肽融合体pMON 26406和pMON 26433的生物活性。
图7是甲基纤维素测定法中测定的多肽融合体pMON 26431和pMON 26427的生物活性。
发明详述本发明包括通过或不通过接头与其自身IL-3融合，或与第二种包含但不限于细胞因子、淋巴因子、白介素、造血生长因子的集落刺激因子(CSF)或IL-3变异体融合的重组的人白介素-3(hIL-3)变异体或突变的蛋白质(突变蛋白)。本发明包括由共价连接的多肽形成的混合功能的集落刺激因子，每一种集落刺激因子可通过不同的和特异的细胞受体启动互补的生物活性而起作用。在所有主要谱系中血细胞的生成需要一系列复杂的细胞学过程，其中干细胞连续不断地形成大集落集的成熟细胞。现在至少有20个已知的具造血增殖活性的调节物(regulators)。大多数的增殖调节物可在体外刺激一种或另一种类型的集落形成，每一种调节物所刺激的集落形成的精确模式都是完全不同的。用克隆数评价，或更重要是用谱系和组成形成中的集落的细胞的成熟模式评价，没有哪两种调节物刺激集落形成的模式是完全相同的。增殖反应可很方便的在简化的体外培养体系中分析。三种完全不同的参数可被区分集落大小的变化，克隆数的变化及细胞谱系。两种或更多种因子可影响祖先细胞，它们诱导大量后代细胞的产生从而增加集落大小。两种或更多种因子可让增加数量的祖先细胞增殖，要么是因存在只对一种因子起反应的祖先细胞的不同子集，要么是因一些祖先细胞在能起反应之前需要两种或更多种因子的刺激。用两种或更多种因子激活细胞上的另外的受体看来可增强分裂信号，因为开始不同的信号途径合并为最后相同的到达细胞核的信号途径(Metcalf,1989)。其它的机制可解释协作作用。例如，如果一条信号途径受第二种因子的附加的中等程度的激活的限制，结果是一种添加的反应。在一些情况下，一种受体类型的激活可诱导其它受体的增强表达(Metcalf,1993)。两种或更多种的因子与单一因子相比可导致不同的细胞谱系模式。由于任何单个因子不可能有的增殖反应使得融合分子的使用有潜在的临床优势。
造血和其它生长因子的相关受体可被归纳为两个不同的家族(1)酪氨酸激酶受体，包括那些如表皮生长因子，M-CSF(Sherr,1990)和SCF(Yarden等.,1987)和(2)造血生成的受体，这类受体不包含酪氨酸激酶结构域(domain)，但它们的胞外区具明显的同源性(Bazar,1990)。包括在后一组中的受体是红细胞生成素(EPO)(D’Andrea等.,1989),GM-CSF(Gearing等.,1989),IL-3(Kitamura等.,1991),G-CSF(Fukunaga等.,1990),IL-6(Yamasaki等.,1988),IL-7(Goodwin等.,1990),ILF(Gearing等.,1991)和IL-2(Cosman等.,1987)。大多数的后一组受体表现为高亲和性的异二聚体形式。结合配体之后，特异的α链与至少一种另外的受体链(β链，γ链)相连。许多这一类的因子共享相同的受体亚单位。GM-CSF,IL-3及IL-5的α链共享相同的β链(Kitamura等.,1991 Takaki等.,1991)和IL-6,LIF及IL-11的受体复合物共同相同的β链(bp130)(Taga等.,1989；Gearing等.,1992)。IL-2,IL-4及IL-7的受体复合物共用相同的γ链(Kondo等.,1993；Russell等，1993；Noguchi，等，1993)。
多因子的施用在降低对因子产生细胞及它们的诱导系统的要求方面有潜在的优点。如果细胞产生因子的能力有限制的话，那么通过合用降低每一种因子所需的浓度在减轻对因子产生细胞的要求时有用。多因子的使用可降低所需的因子的量。可能是减少了相反反应发生的可能性。
本发明的新化合物由一个通式代表，该通式选自R1-L-R2,R2-L-R1,R1-R2,R2-R1,R1-L-R1及R1-R1其中R1是包含多个氨基酸取代的hIL-3变异体，它也可包括如在共同未决的美国专利申请，申请号第PCT/US 93/11197号中公开的缺失的hIL-3分子的部分，R2是IL-3,IL-3变异体或有不同的但互补活性的集落刺激因子。互补活性指能增强或改变对另一个细胞调制子(modulator)的反应的活性。R1多肽或者直接或者通过一个接头片段与R2多肽融合。术语“直接地”限定的是多肽不通过肽接头相连的融合。因此L代表一个供R1和R2按阅读框融合的化学键或多肽片段，最常见的L是一个线性肽，R1和R2通过酰胺键与之连接，将R1的羧基末端与L的氨基末端相连且将L的羧基末端与R2的氨基末端相连。按“阅读框融合”指在R1和R2的阅读框之间没有翻译终止或中断。符合R2定义的能与本发明的hIL-3变异体融合的其它生长因子，集落刺激因子(CSF)，细胞因子，淋巴因子，白介素，造血生长因子的非限制性的列表包括GM-CSF,CSF-1,G-CSF,Meg-CSF(最近称c-mpl配体),M-CSF，红细胞生成素(EPO),IL-1,IL-4,IL-2,IL-5,IL-6,IL-7,IL-8,IL-9,IL-10,IL-11,IL-12,IL-13,LIF,flt3/flk2，人生长激素，B细胞生长因子，B细胞分化因子，嗜酸性细胞分化因子和也称为钢因子(steel factor)或c-kit配体的干细胞因子(SCF)。另外本发明还包括对修饰的R2分子或突变的或修饰的编码该R2分子的DNA的使用。本发明还包括其中的R2是hIL-3变异体的融合分子，其中变异的hIL-3是指有氨基酸取代且有如PCT/US 93/11197和PCT/US 93/11199中公开的缺失的hIL-3分子部分的IL-3以及本领域中已知的其它变异体。
连接基因(L)一般是长度为1～500个氨基酸的多肽。连接两个分子的接头优选设计为(1)允许两个分子相互独立的折叠和起作用，(2)没有形成可干扰两个蛋白质的功能域有序二级结构的倾向，(3)有最低限度的能与蛋白质功能域相作用的疏水或荷载电荷特征和(4)提供R2和R1的空间分离以使R1和R2可与在它们一个细胞上的相应的受体同时作用。易弯曲的蛋白质区域的典型表面氨基酸包括Gly,Asn及Ser。实际上预计包含Gly,Asn及Ser的氨基酸序列的任何变换，都能满足上述的接头序列标准。其它的中性氨基酸如Thr和Ala也可被用在接头序列中。由于为了方便融合蛋白的构建在接头序列中增加了单一限制性酶切位点，接头中还包括附加的氨基酸。
本发明优选的接头包括的序列选自通式(Gly3Ser)n,(Gly4Ser)n,(Gly5Ser)n,(GlynSer)n或(AlaGluSer)n一种高度易弯曲接头的例子是出现在丝状噬菌体例如M13或fd噬菌体的pⅢ蛋白中的富含(Glyser)的间隔区域(Schaller等.,1975)。该区域在pⅢ表面蛋白的两个结构域之间提供了一个长的易弯曲的间隔区域。该间隔区的氨基酸序列包括GlyGlyGlySerGlyGlyGlySerGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGluGlyGlyGlySerGlyGlyGlySer[SEQ ID NO:50]本发明还包括在其中包含内肽酶识别序列的接头。这类切割位点对于分离融合蛋白的单独的成份以鉴定它们在体外是否正确折叠和是否有活性是有价值的。多种内肽酶的例子包括但又不限于，血纤蛋白溶酶，肠激酶，激肽释放酶，尿激酶，组织血纤蛋白溶酶原激活物，梭菌蛋白酶，凝乳酶，胶原酶，鲁塞尔氏蝰蛇毒蛋白酶，脯氨酸后裂解酶，V8蛋白酶，凝血酶及因子Xa。
来源于免疫球蛋白IgG,IgA,IgM,IgD或IgE重链绞链区的肽接头片段在相接触的多肽之间提供了角度关系。特别有用的是那些已用丝氨酸替换了半胱氨酸的铰链区。本发明优选的接头包括来源于小鼠IgGγ26绞链区的序列，其中半胱氨酸已被换成丝氨酸。这些接头还包含一个内肽酶切割位点。这类接头例子选自下述序列IleSerGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerPro [SEQ ID NO:51]IleGluGlyArgIleSerGluProSerGlyProIleSerThrIleAsnProSerProProSerLysGluSerHisLysSerPro [SEQ ID NO:52]但本发明不受所用接头序列的形式，大小或数目的限制并且对接头的唯一要求是它不会功能性相反作用地影响融合蛋白的独立分子的折叠和功能。
另一种连接两个非造血生长因子的方法是通过非共价的作用。这类复合蛋白可用一种通式表示R1-C1+R2-C2；或C1-R1+C2-R2；C1-R1+R2-C2；或C1-R1+R2-C2其中R1是包含多个氨基酸取代的hIL-3变异体，它也可以具有缺失的hIL-3分子的部分，R2是一个有不同的但却互补活性的集落刺激因子。在R2定义之内的能与本发明中hIL-3变异体融合的其它生长激素，集落刺激因子(CSFs)，细胞因子，淋巴因子，白介素，造血生长因子的非限制性列表包括GM-CSF,CSF-1,G-CSF,Meg-CSF(最近称为c-mpl配体)，M-CSF，红细胞生成素(EPO),IL-1,IL-4,IL-2,IL-5,IL-6,IL-7,IL-8,IL-9,IL-10,IL-11,IL-12,IL-13,LIF,flt3/flk2，人生长激素，B细胞生长因子，B细胞分化因子，嗜酸性细胞分化因子及也称作钢因子(steel factor)或c-kit配体的干细胞因子(SCF)。C1和C2结构域(domain)有典型蛋白质的要么一致要么不一致的化学结构，它们能形成一个非共价的特异的联系。C1和C2之间的复合物导致每一种复合物R1和R2之间一对一的化学计量关系。相关的结构域的例子有转录因子的“亮氨酸抗链”结构域，细菌转录抑制因子的二聚体结构域和免疫球蛋白的恒定区结构域。共价键分别联接R1和C1，和R2与C2。如在通式中所指出的，C1和C2结构域可出现在它们相应的造血生长因子(R)的N末端或C末端。这些多聚化的结构域(C1和C2)包括那些来源于bZIP家族的蛋白(Abel等，1989；Landshulz等，1988；Pu等，1993；Kozarides等，1988)以及来源于螺旋-环-螺旋家族蛋白的多聚化结构域(Abel等，1989；Murr等，1989；Tapscott等，1988；Fisher等，1991)。本发明的优选融合包括集落刺激因子的二聚化，这是由于它们作为翻译融合蛋白与bZIP家族蛋白Fos和Jun亮氨酸拉链二聚化结构域结合。Jun的亮氨酸拉链结构域能与相同的结构域相作用。另一方面，Fos的亮氨酸拉链结构域与Jun的亮氨酸拉链结构域作用，但不与其它的Fos亮氨酸拉链结构域作用。Fos和Jun的混合物绝对会导致Fos-Jun异二聚体的形成。结果，当与集落刺激因子融合时，Jun结构域可被用于指导同或异二聚体的形成。如果集落刺激因子伴侣中的一个被构建或含有Jun亮氨酸拉链结构域而另一个被构建成含有Fos拉链的话，那么即可优选形成异二聚体。
为方便融合蛋白的纯化或鉴定，可增加肽(例如多聚组氨酸)。可增加一个抗原性高的肽，此肽可用特异的单克隆抗体对融合蛋白进行快速的测定和便利的纯化。
本发明涉及由新的人白介素3(hIL-3)变异体组成的新的融合分子，其中的hIL-3变异体在与第二种集落刺激因子或IL-3变异体融合的多肽序列中有四个或更多个位点的氨基酸取代。本发明优选的融合分子是(15-125)hIL-3缺失突变体，其中N末端1～14和C末端126～133的氨基酸缺失以及在与第二种集落刺激因子或IL-3变异体融合的多肽序列中有四个或更多个氨基酸的取代。
本发明包括的突变多肽最低由hIL-315～118氨基酸残基组成并且有或没有添加的氨基酸延伸至N末端和/或C末端，进一步在与另一个集落刺激因子或IL-3的变异体融合的多肽氨基酸序列中包含四个或更多个氨基酸的取代。
本文所用的人白介素3对应于图1所描述的氨基酸序列(1-133),(15-125)hIL-3对应于hIL-3多肽的15～125氨基酸序列。本发明还包括了自然产生的hIL-3多肽氨基酸的变异体(例如，在hIL-3多肽序列中第8位是脯氨酸而不是丝氨酸的等位基因)，如被翻译后修饰(例如糖基化)的变异体hIL-3分子。
“突变的氨基酸序列”，“突变的蛋白质”或“突变的多肽”指含有的氨基酸序列与天然的序列不同的多肽或者由有目的由天然序列突变来的核苷酸序列编码的多肽。“突变的蛋白质”，“变异的蛋白质”或“突变蛋白”意指包括突变体氨基酸序列的蛋白质，它包含与天然hIL-3不同的氨基酸序列的多肽，是因为氨基酸缺失，取代，或二者都有而使该蛋白与天然hIL-3不同。“天然序列”指氨基酸或核苷酸序列与基因或蛋白的野生型或天然形式一致。
人IL-3的特征在于其通过人造血祖细胞的刺激集落形成的能力。所形成的集落表现出包括红细胞的，粒细胞，巨核细胞，粒细胞的巨噬细胞以其混合物等。在最初的灵长类，以后在人当中进行的研究中已证实人IL-3能将骨髓功能及外周血细胞群恢复至对治疗上有益的水平((Gillio,A.P.等，(1990)；Ganser,A.等，(1990)；Falk,S，等，(1991))。hIL-3的其它活性包括刺激白细胞转移和趋化性的能力；引发人白细胞产生高水平的炎症介质如白三烯和组胺的能力；诱导白细胞粘附所需的分子在细胞表面表达的能力；诱导皮肤炎病反应及发热的能力。hIL-3的许多或全部生物活性涉及信号传导和与高亲和性受体结合。本发明的融合分子表现出很多有用的特性，例如与天然hIL-3相比有相同或更高的生物活性或具有半衰期增加或减弱的相反的副作用，或这些特性的组合。它们作为拮抗剂也是有用的。与天然hIL-3相比有很小或没有活性的融合分子仍很有用，如作为拮抗剂，作为产生在免疫学或免疫治疗中有用的抗体的抗原，作为基因探针或作为构建其它有用的hIL-3突变蛋白的中间体。
本发明的新融合分子将优选含有人IL-3和与之融合的其它集落刺激因子或IL-3变异体的至少一种生物活性，而且可有多于一种的IL-3类的生物特性，或一种改善的特性，或一种人IL-3所不希望的生物特性的减小。本发明的一些突变体多肽也表现为改善的副作用类型。例如，当与天然hIL-3或(15-125)hIL-3相比较时，表现为白三烯或组胺的释放减少。这类hIL-3或hIL-3类的生物特性可能包括一种或多种下述的生物特征以及体内和体外的活性。
这类特性的一种是对定型为红细胞的，淋巴样的，和髓系谱系的祖细胞的生长和分化的支持。例如，在标准的人骨髓测定中，IL-3类的生物特性是对粒细胞类集落，巨核细胞类集落，单核细胞/巨噬细胞类集落，及对红细胞爆发的刺激。其它IL-3类的特性是与早期多能干细胞作用，维持多能前体细胞的生长，刺激慢性髓系白血病(CML)细胞增殖的能力，刺激肥大细胞的增殖，支持多种因子依赖的细胞系生长的能力，及诱导非成熟的骨髓细胞祖细胞的能力。在本领域已公开了IL-3的其它生物学特性。人IL-3也有在有些情况下不希望有的生物活性，例如刺激白三烯释放的能力以及在脾细胞和骨髓培养物以及体内刺激组胺合成增加的能力。
本发明的hIL-3及hIL-3融合蛋白的生物活性取决于人急性髓系白血病(AML)细胞的DNA合成。依赖于因子的细胞系AML193适于在测定生物活性中使用。本发明中hIL-3及hIL-3融合蛋白的生物活性也可由骨髓测定法中的克隆形成单位的计数决定。
其它的基于体外细胞的测定法也可在决定依赖于包括融合蛋白在内的集落刺激因子的融合分子的活性中是有用的。
TF-1增殖测定TF-1细胞系来源于红白血病患者的骨髓(Kitamura等，1989)。TF-1细胞对IL-3,GM-CSF,EPO及IL-5起反应。32D增殖测定法32D是依赖于小鼠IL-3的细胞系但不与人IL-3反应，却又不受种属限制地可与人G-CSF反应。T1165增殖测定法T 1165细胞是能与IL-6及IL-11反应的依赖于IL-6的小鼠细胞系(Nordan等，1986)。人血浆凝块meg-CSF测定法用于测定巨核细胞集落形成活性(Mozur等，1981)。
本发明的一个目的是提供在与第二种集落刺激因子或IL-3变异体融合的多肽系列中含有四个或更多的氨基酸取代的hIL-3变异体，该变异体与天然hIL-3相比或与第二种集落刺激因子或与IL-3变异体相比有相似的或改善的生物活性。
本发明的hIL-3变异体融合分子可含有hIL-3或hIL-3类的活性。例如，它们含有天然hIL-3的一种或多种生物活性并在刺激由人或灵长类祖细胞产生造血细胞中有用。本发明的融合分子及包含它们的药用组合物在一些条件下对治疗有用，如由于疾病或治疗如放疗或化疗而使造血细胞群落减少或受到破坏时。本发明的包含融合分子的药用组合物可由非肠道的，静脉的，或皮下途径给药。
天然的hIL-3含有必需考虑的炎症反应活性并已表明可刺激花生四烯酸代谢产物LTC4,LTD4及LTE4的合成；组胺的合成及组胺的释放。天然IL-3的人体临床试验证明有炎症反应((Biesma等，BLOOD,80:1141-1148(1992)及Postmus，等，J.CLIN.ONCOL.10:1131-1140(1992))。最近的研究表明白三烯在IL-3的体内作用中有所涉及并对IL-3治疗的生物效应有明显的贡献(Penzlinger,C，等，BLOOD,81:2466-2470(1993))。
本发明的一些融合分子与天然hIL-3相比有改善的治疗效果。例如，本发明的一些融合分子与天然hIL-3相比有相似的或更有潜力的生长因子活性，但不具有相似的或相应增加的对白三烯或组胺的刺激。这些融合分子有望有更好的治疗效果，因为达到所希望的生长因子活性(例如细胞增殖)所需的多肽的量将会有较少的白三烯或组胺刺激效应。在对天然hIL-3的研究中，对炎症因子的刺激是治疗中所不希望的副作用。减小或去除对介导炎症反应的介质的刺激，对天然的hIL-3的使用有好处。
本发明的新融合分子也可作为拮抗剂使用，它可通过特异性地与之结合并阻止促效剂的结合从而阻断hIL-3受体。
本发明的新的融合分子，特别是那些保留了与天然IL-3相似或更好的活性的融合分子的一种潜在的优点是有可能用较少量的生物活性突变蛋白以产生所希望的治疗效果。这可以减少产生所需治疗效果必需的治疗次数。较小剂量的使用也可减少一些潜在的抗原效应或其它可能发生的而又不希望发生的副作用产生的可能性。例如，如果一个所希望的治疗效果能用较小量的多肽达到，就可能减小或去除与施用天然IL-3相关的副作用如对白三烯和/或组胺的释放的刺激。本发明的新融合分子也可在激活含有低的受体数目的干细胞或祖细胞中有用。
本发明还包括编码融合蛋白的DNA序列，基本上相同或行使基本上相同功能的DNA序列，或者是仅仅因为遗传密码的简并性而与编码本发明的融合分子的DNA序列不同的DNA序列。本发明还包括用于构建突变DNA的寡核苷酸中间体；以及由这些寡核苷酸所编码的多肽。这些多肽可用做拮抗物或作为抗原片段而用于产生在免疫测定法及免疫治疗方法中有用的抗体。
本发明中的化合物优选用本领域中的标准的基因工程技术制备，见美国专利4,935,233和Sambrook等，“分子克隆.实验指南”，ColdSpring Harbor Laboratorg(1989)〕。一种产生优选hIL-3(15-125)突变基因的方法是盒式诱变(cassette mutagensis〔Weus,等.(1985)〕，其中质粒上的hIL-3编码序列的一部分在两个限制性酶切位点之间的基因部分被合成的编码所希望的氨基酸取代的寡核苷酸置换。以相似的方式可进行全长的hIL-3基因或编码变异体hIL-3基因的氨基酸取代，其中hIL-3N末端的1～14氨基酸缺失和/或C末端1～15氨基酸缺失。当装配合适时，这些寡核苷酸能编码含所希望的氨基酸取代和/或从N末端和/或C末端缺失氨基酸的hIL-3变异体。这些和其它的突变可由本领域中的技术人员用其它的诱变方法产生，所述方法包括寡核苷酸定向诱变〔Zoller和Smith(1982,1983,1984),Smith(1985),Kunkel(1985),Taylor，等(1985),Deng和Nickoloff(1992)或聚合酶链式反应(PCR)技术〔Saiki,(1985)〕。
可制备编码所需基因的互补的合成的寡核苷酸对并互相退火，除那些经取代和/或从序列中缺失的DNA序列外，寡核苷酸的DNA序列可编码所需基因的氨基酸序列。
质粒DNA可用所选择的限制性内切酶处理然后与退火的寡核苷酸连接。连接混合物可用于转化对一种合适的抗生素有抗性的感受态JM101细胞。挑选单菌落并用限制性酶切分析检测质粒DNA和/或用DNA测序鉴定含所希望基因的质粒。
hIL-3变异体的DNA序列与其它集落刺激因子或IL-3变异体的DNA序列的融合可通过使用中间载体实现。另外，一个基因也可被直接克隆进一个包含其它基因的载体。接头(linker)和衔接子(adaptor)可用于DNA序列的连接以及替换缺失的序列，其中在所感兴趣的区域插入了一个限制性酶切位点。因此编码一种多肽，肽接头，及其它多肽的遗传物质(DNA)被插入一个合适的表达载体中，该载体用于转化细菌，酵母，昆虫细胞或哺乳动物细胞。培养转化的生物体并用标准技术分离蛋白。因此所得到的产物是一个hIL-3变异体通过接头区与第二种集落刺激因子或IL-3变异体相连接的新蛋白。
本发明的另一方面是提供了在表达这些新的融合分子中使用的质粒DNA载体。这些载体包含上面所描述的编码本发明新的多肽的新的DNA序列。合适的能转化可表达该融合分子的微生物的载体包括包含编码该融合分子的核苷酸序列的表达载体，该核苷酸序列与根据宿主细胞选择的转录和翻译调控序列连接。
掺入上述经修饰序列的载体包括在本发明中，并可用于产生融合多肽。用于此方法中的载体也含有与本发明的DNA编码序列可操作地连接的选定的调控序列，此调控序列可指导选定的宿主细胞中本发明DNA编码序列的复制和表达。
作为本发明的另一个方面，还提供了制备新的融合分子的方法。本发明的方法包括已被载体转化的合适的细胞或细胞系的培养，该载体包含编码新的hIL-3变异体融合分子表达所用的DNA序列。合适的细胞或细胞系可以是细菌细胞，例如，各种大肠杆菌菌株在生物技术领域中作为宿主细胞是众所周知的。这类菌株的例子包括大肠杆菌菌株JM 101〔Yahish-Perron，等，(1985)〕和MON 105〔Obukowicz，等.(1992)〕。本发明还包括用基于噬菌体Mu的大肠杆菌染色体表达载体表达该融合蛋白〔Weinberg等，1993〕。各种枯草芽孢杆菌的菌株也可在该方法中应用。许多对于本领域技术人员所熟知的酵母细胞菌株也可作为宿主细胞表述本发明多肽。当在大肠杆菌细胞质中表达时，可将上面所描述的本发明的突变的变异体hIL-3融合分子的N末端构建成Met-Ala，以使在表达时Met被切割掉，N末端只剩下Ala。本发明的融合分子也包括N末端吸附有Met-,Ala-或Met-Ala-的融合多肽。当融合分子在大肠杆菌细胞质中表达时，可得到N末端带有或不带有Met的多肽。在大肠杆菌细胞质中制备的蛋白质的N末端受甲硫氨酸氨肽酶及其它可能的肽酶翻译后加工的影响(Ben-Bassat等，1987)。这些突变融合分子也可通过在N末端融合一个信号肽以在大肠杆菌中表达。信号肽可作为分泌过程的一个部分而被从多肽上切割下来。由于信号肽酶的精确性，使用大肠杆菌中的分泌可获得N末端正确的氨基酸(例如，在(15-125)hIL-3多肽中的Asn15)。这与常见的在大肠杆菌细胞质中表达的蛋白质N末端观察到的异质性是相反的。
适应在本发明中使用的还有哺乳动物细胞，如中国仓鼠卵巢细胞(CHO)。在哺乳动物细胞中表达外源基因的一般方法综述如下Kaufman,R.J.(1987)High level production of proteins inmammalian cells,in Genetic Engineering,Principles andMethods,Vol.9,J.K.Setlow,editor,plenum press,New York。构建了一个包括一个能在哺乳动物细胞中起作用的强启动子的表达载体，该启动子可驱动的分泌信号肽编码区的转录，其中信号肽编码区与融合分子的编码区翻译融合。例如，可使用的质粒有如pcDNA I/Neo,pRc/RSV，及pRc/CMV(来自Invitroger.Corp.,San Diego,Calitornia)。真核的分泌信号肽编码区可来自hIL-3基因自身或来自其它的分泌的哺乳动物蛋白质(Bayne,M.L.等，(1987)Proc.Natl.Acad.Sci.USA84.2638-2642)。在构建了包含hIL-变异体基因的载体之后，即将载体DNA转染入哺乳动物细胞中。例如，这些细胞可以是，COS7,HeLa,BHK,CHO，或小鼠L细胞系。细胞可在，例如DMEM培养基(JRH Scientific)中培养。在转染细胞或用新霉素抗性筛选获得稳定的细胞系后再连续表达24-72小时之后，即可用标准的生化方法回收分泌在培养基中的hIL-3变异体。合适的哺乳动物宿主细胞的选择及转化，培养，扩增，筛选和产物制备及纯化的方法都是在本领域中熟知的。参见，例如，Gethiag和Sambrook,Nature,293:620-625(1981)，或另外地，Kaufman等，Mol.Cell.Biol.,5(7):1750～1759(1985)或Howley等.,U.S.Pat.No.4,419,446。其它的合适的哺乳动物细胞系是猴COS-1细胞系。相似的有用的哺乳动物细胞系是CV-1细胞系。
在本发明的方法中，如果需要也可用昆虫细胞作为宿主细胞。参见，例如，Miller，等，Genetic Engineering,8:277-298(PlenumPress 1986)及其中所引用的文献。另外，用杆状病毒在昆虫细胞中表达外源基因的一般方法介绍如下Summers,M.D.及Smith,G.E.(1987)-A manual of methods for Baculovirus vectors and insectcell culture procedures,Texas Agricultural Experiment StationBulletin No.1555。构建了一个包括杆状病毒转移载体的表达载体，其中一个强的杆状病毒(例如多角蛋白(polyhedron))启动子驱动真核的分泌信号肽编码区的转录，该信号肽与融合多肽的编码区翻译融合。例如可使用质粒pVL 1392(得自Invitrogen.Corp.,San Dieqo,California)。在构建了携带编码融合多肽的基因的载体之后，2微克这种DNA与1微克杆状病毒DNA一起共转染入昆虫细胞，SF9株(参见Summers & Smith,1987)。纯化的携带融合分子的重组体杆状病毒被用于感染，例如，在Excell 401无血清培养基中培养的细胞(JRHBiosciences,Lenexa,Kansos)。分泌到培养基中的融合分子可用标准的生化方法回收。来自表达该融合蛋白的哺乳动物或昆虫细胞的上清液可先用几种商业化的浓缩设备中任一种进行浓缩。
本发明的融合分子在治疗特征为造血生成系统中髓系，红系，淋巴的，或巨核细胞的减小或它们的减少的组合的疾病中有用。另外，它们可用于激活成熟的髓系和/或淋巴样细胞。对用本发明的多肽的治疗敏感的是白细胞减少，即在外周血中循环的白细胞(白细胞)数目减少。白细胞减少可由暴露于一些病毒或射线而诱发。它常是例如暴露于化疗药物，射线下的各种类型的癌症治疗以及感染或出血的副作用。用本发明的这些融合分子治疗白细胞减少可避免现有可用药物在治疗中所产生的所不希望有的副作用。
本发明的融合分子可在治疗中性白细胞减少中有用以及，例如，在治疗如再生障碍性贫血，周期性白细胞减少，恶性白细胞减少，Chediak-Higashi综合症，系统性红斑狼疮(SLE)，白血病，脊髓发育不良综合症和骨髓纤维化等中有用。
本发明的融合分子也可在治疗或防止血小板减少症中有用。现在唯一的治疗血小板减小症的方法是血小板输注法，该方法花费昂贵并有极大的传染(HIV,HBV)和同体免疫反应(alloimunization)的危险。该融合分子可减少或清除对血小板输注的需求。严重的血小板减少是由遗传缺陷如范康尼氏贫血，Wiscott-Aldrich，或May-Hegglin综合症引起的。获得性血小板减少是由如免疫血小板减少性紫癜，系统性红斑狼疮，溶血性贫血，或胎儿母体不相容性中的自体或异体抗体所引起的。另外，充血性脾大，散布性血管内凝固，血栓形成性血小板减少性紫癜，传染或修补的心脏瓣膜可导致血小板减少。严重的血小板减少也可由化疗和/或放疗或癌症引起。血小板减少也可由肿瘤，淋巴瘤，白血病的骨髓侵染或纤维化引起。
本发明的融合分子可能在将造血生成祖细胞和干细胞转移进入外周血中有用。已证实外周血来源的祖细胞在促进进行自体骨髓移植的病人的恢复中有效。也证实包括G-CSF和GM-CSF的造血生长因子可增加外周血中循环的祖细胞及干细胞数目。这就简化了外周干细胞的收集方法而且通过减小所需的pheresis的量而大大降低了该方法的花费。融合分子可在转移干细胞及进一步增强外周干细胞移植的效率中有用。
生长因子的另一个临床用途是在体外激活供基因治疗用的造血生成祖细胞及干细胞。为了将所感兴趣的基因掺入造血生成祖细胞或干细胞的基因组中，就需要刺激细胞的分裂和DNA复制。造血生成干细胞以很低的频率进入周期，这就意味着生长因子在促进基因转导及因此增强基因治疗的临床应用前景中有用。
很多药物可造成骨髓抑制或造血生成缺陷。这些药物有在化疗中使用的药物AZT,DDI，烷基化试剂及抗代谢药，抗生素例如氯霉素，青霉素，更昔洛韦(gancyelovir)，柔红霉素及磺胺类药物，吩噻嗪(phnothiazones)，镇定药如眠尔通，镇痛药如氨基比林和安乃近，抗惊厥药如苯妥英或氨甲酰氮_，抗甲状腺药如丙基硫氧嘧啶和甲硫咪唑及利尿剂。本发明的融合分子可能在防止或治疗骨髓抑制或造血生成缺陷中有用。这类症状在用上述药物治疗的病人中经常出现。
造血生成缺陷也会由于病毒，微生物或寄生虫感染以及在治疗肾病或肾衰竭(renal failure)例如透析中而产生。本发明的融合分子可在治疗这类造血生成缺陷中有用。
治疗造血生成缺陷可包括对病人施用包含融合分子的药用组合物。本发明的融合分子可在激活及扩增造血生成前体细胞中有用，这可在将细胞输入病人体内之前先用本发明的融合蛋白在体外处理这些细胞。
各种免疫缺陷例如，在T和/或B淋巴细胞，或免疫紊乱中，例如，风湿性关节炎都可受到使用本发明的融合分子的治疗的有益影响。例如HTLⅥ,HTLⅦ,HTLⅧ的病毒感染，严重的射线照射，癌症治疗或其它的医疗处理可导致免疫缺陷。本发明的融合分子也可单独或与其它红细胞生成素一起合用于治疗其它的血细胞缺陷，所述血细胞缺陷包括血小板减少(血小板缺陷)，或贫血。这些新的多肽的其它用途是在体内和体外治疗正从骨髓移植中恢复的病人，以及用标准方法制备供诊断或治疗用的单克隆或多克隆抗体。
本发明的其它方面是治疗上述的疾病的方法及药用组合物。这类组合物包括治疗有效剂量的本发明的一种或多种融合分子与药用载体的混合物。这些组合物可通过非肠道，或静脉内的，或皮下的途径施用。在施用时，在本发明中使用的治疗组合物的优选形式是无热原的非肠道的可接受的水溶液。制备这样的非肠道的可接受的蛋白质溶液要依赖于pH，等渗性，稳定性等，都在本领域的技术范围内。
包含在治疗上述疾病方法中的用药制度由临床医师考虑各种影响药效因素后确定，例如环境，体重，性别和病人的饮食，感染的严重性，给药次数及其它的临床因素。一般地，每天的用药量是每公斤体重0.2～150μg/kg融合蛋白。该用药制度参照生物活性的标准水平制定，所述标准认为天然的IL-3在本文所述的AML增殖测定法中的EC50一般是或大约是10～100皮摩尔。因此，所给定的融合蛋白的剂量应根据它对天然(参照)IL-3的活性进行调整并且应该注意剂量制度可包括低到0.1微克及高到1微克每天每公斤体重也不是不可能的。另外，在一些特定的情况下也可将融合分子的剂量调整的比10～200微克每公斤体重高或低。这些包括与其它的集落刺激因子或IL-3变异体或生长因子合用，与化疗药物和/或射线共同施用，使用糖基化的融合蛋白，以及在此部分文章中早期提到的各种与病人相关的出版物。如上所示，治疗方法及组合物也可包括与其它的人的因子共同施用。一个非限制性的与本发明多肽同时或顺序共同施用的合适的造血生成素，SCF，细胞因子，淋巴因子，造血生长因子及白介素包括GM-CSF,CSF-1,G-CSF,Meg-CSF(最近称为c-mpl配体),M-CSF，红细胞生成素(EPO),IL-1,IL-4,IL-2,IL-5,IL-6,IL-7,IL-8,IL-9,IL-10,IL-11,IL-12,IL-13,LIF,flt3/flk2,B细胞生长因子，B细胞分化因子及嗜酸性粒细胞分化因子，及也称为钢(steel)因子或c-kit配体的干细胞因子(SCF)，或它们的组合。上面所述的剂量应根据治疗用组合物中的添加成分作调整。所治疗的病人的进程可通过对血液学情况的周期性评价进行鉴控，例如，不同的细胞计数等。
本发明也指向如下通式；1．R1-L-R2,R2-L-R1,R1-R2,R2-R1,R1-L-R1及R1-R1其中R1是人白介素3突变体多肽，通式如下Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa5O 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe125 130〔SEQ ID NO:1〕其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln，或Arg；Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg，或Gln；Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala，或Cys；Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro，或Ala；Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,The,Ser或Val；Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val或Gly；Xaa在位点23是Ile,Val,Ala,Leu,Gly,Trp,Lys,Phe,Leu,Ser，或Arg；Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe，或Leu；Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro，或Ala；Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala，或Trp；Xaa在位点27是Leu,Gly,Arg,Thr,Ser，或Ala；Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val或Trp；Xaa在位点29是Gln,Asn,Leu,Pro,Arg，或Val；Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys；Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu，或Gln；Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala，或Gln；Xaa在位点33是Pro,Leu,Gln,Ala,Thr，或Glu；Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile，或Met；Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln，或Val；Xaa在位点36是Asp,Leu，或Val；Xaa在位点37是Phe,Ser,Pro,Trp，或Ile；Xaa在位点38是Asn，或Ala；Xaa在位点40是Leu,Trp，或Arg；Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,或Pro；Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr,Ile,Met或Ala；Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,Gly，或Ser；Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,Ala，或Pro；Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,Arg,Ser,Ala,Ile,Glu，或His；Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,Tyr,Ile,Val，或Gly；Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro，或His；Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Pte,Glu,Lys,Thr,Ala,Met,Val，或Asn；Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp；Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,Phe,Met，或Gln；Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser，或Thr；Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser，或Met；Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或Leu；Xaa在位点55是Arg,Thr,Val,Ser,Leu，或Gly；Xaa在位点56是Pro,Gly,Cys,Ser,Gln,G1u,Arg,His,Thr,Ala,Tyr,Phe,Leu,Val，或Lys；Xaa在位点57是Asn或Gly；Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val，或Cys；Xaa在位点59是Glu,Tyr,His,Leu,Pro，或Arg；Xaa在位点60是Ala,Ser,Pro,Tyr,Asn，或Thr；Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg，或Ser；Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp，或Ile；Xaa在位点63是Arg,Tyr,Trp,Kys,Ser,His,Pro，或Val；Xaa在位点64是Ala,Asn,Pro,Ser，或Lys；Xaa在位点65是Val,Thr,Pro,His,Leu,Phe，或Ser；Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu，或Ser；Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His；Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr，或His；Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly，或Leu；Xaa在位点70是Asn,Leu,Val,Trp,Pro，或Ala；Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp，或Asn；Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp；Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr，或Arg；Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala；Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln，或Leu；Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly，或Asp；Xaa在位点77是Ile,Ser,Arg,Thr，或Leu；Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly，或Arg；Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly，或Asp；Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu，或Arg；Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val，或Lys；Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Ser,Ala,Tyr,Phe,Ile,Met，或Val；Xaa在位点83是Pro,Ala,Thr,Trp,Arg，或Met；Xaa在位点84是Cys,Glu,Gly,Arg,Met，或Val；Xaa在位点85是Leu,Asn,Val，或Gln；Xaa在位点86是Pro,Cys,Arg,Ala，或Lys；Xaa在位点87是Leu,Ser,Trp，或Gly；Xaa在位点88是Ala,Lys,Arg,Val，或Trp；Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn，或Ser；Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile，或Met；Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp，或His；Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile，或Leu；Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg；Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala，或Pro；Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,Trp,Phe,Ile，或Tyr；Xaa在位点96是Pro,Lys,Tyr,Gly,Ile，或Thr；Xaa在位点97是Ile,Val,Lys,Ala，或Asn；Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,Val,Lys,Arg,Tyr，或Pro；Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe，或His；Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln，或Pro；Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,Ala,Gly,Ile,Leu，或Gln；Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro；Xaa在位点103是Asp，或Ser；Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe，或Gly；Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His；Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro；Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala，或Pro；Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser，或Gly；Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,Ala,或Trp；Xaa在位点111是Leu,Ile,Arg,Asp，或Met；Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser，或Phe；Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val，或Asn；Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg，或Leu；Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp，或Met；Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,Asn,His,Ala,Tyr,Phe,Gln，或Ile；Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys，或Pro；Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp，或Tyr；Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr，或Arg；Xaa在位点120是Asn,Ala,Pro,Leu,His,Val，或Gln；Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp，或Gly；Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys；Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；并且可附加性的在位点1前含有Met-氨基酸；并且N末端1～14氨基酸可缺失和/或C末端1～15氨基酸缺失；并且其中用Xaa代表的4～44氨基酸与天然的人白介素3(1-133)相应的氨基酸不同；2．1中的融合蛋白，其中所说人白介素3突变多肽的通式如下Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa Xaa35 40 45Xaa Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu Xaa50 55 60Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile Glu
65 70 75Xaa Xaa Leu Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr Ala80 85 90Xaa Pro Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa Xaa95 100 105Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu Xaa110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe125 130〔SEQ ID NO:2〕其中Xaa在位点17是Ser,Gly,Asp,Met，或Gln；Xaa在位点18是Asn,His，或Ile；Xaa在位点19是Met，或Ile；Xaa在位点21是Asp或Glu；Xaa在位点23是Ile,Ala,Leu，或Gly；Xaa在位点24是Ile,Val，或Leu；Xaa在位点25是Thr,His,Gln，或Ala；Xaa在位点26是His，或Ala；Xaa在位点29是Gln,Asn，或Val；Xaa在位点30是Pro,Gly，或Gln；Xaa在位点31是Pro,Asp,Gly，或Gln；Xaa在位点32是Leu,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点33是Pro或Glu；Xaa在位点34是Leu,Val,Gly,Ser,Lys,Ala,Arg,Gln,Glu,Ile,Phe,Thr或Met；Xaa在位点35是Leu,Ala,Asn,Pro,Gln，或Val；Xaa在位点37是Phe,Ser,Pro，或Trp；Xaa在位点38是Asn或Ala；Xaa在位点42是Gly,Asp,Ser,Cys,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点44是Asp或Glu；Xaa在位点45是Gln,Val,Met,Leu,Thr,Ala,Asn,Glu,Ser或Lys；Xaa在位点46是Asp,Phe,Ser,Thr,Ala,Asn,Gln,Glu,Gis,Ile,Lys,Tyr,Val或Cys；Xaa在位点50是Glu,Ala,Asn,Ser或Asp；Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点54是Arg或Ala；Xaa在位点55是Arg,Thr,Val,Leu，或Gly；Xaa在位点56是Pro,Gly,Ser,Gln,Ala,Arg,Asn,Glu,Leu,Thr,Val或Lys；Xaa在位点60是Ala或Ser；Xaa在位点62是Asn,Pro,Thr，或Ile；Xaa在位点63是Arg或Lys；Xaa在位点64是Ala或Asn；Xaa在位点65是Val或Thr；Xaa在位点66是Lys或Arg；Xaa在位点67是Ser,Phe，或His；Xaa在位点68是Leu,Ile,Phe，或His；Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg，或Gly；Xaa在位点71是Ala,Pro，或Arg；Xaa在位点72是Ser,Glu,Arg，或Asp；Xaa在位点73是Ala或Leu；Xaa在位点76是Ser,Val,Ala,Asn,Glu,Pro，或Gly；Xaa在位点77是Ile或Leu；Xaa在位点79是Lys,Thr,Gly,Asn,Met,Arg,Ile,Gly，或Asp；Xaa在位点80是Asn,Gly,Glu，或Arg；Xaa在位点82是Leu,Gln,Trp,Arg,Asp,Ala,Asn,Glu,His,Ile,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点83是Pro或Thr；Xaa在位点85是Leu或Val；Xaa在位点87是Leu或Ser；Xaa在位点88是Ala或Trp；Xaa在位点91是Ala或Pro；Xaa在位点93是Thr,Asp,Ser,Pro,Ala,Leu，或Arg；Xaa在位点95是His,Pro,Arg,Val,Leu,Gly,Asn,Phe,Ser或Thr；Xaa在位点96是Pro或Tyr；Xaa在位点97是Ile或Val；Xaa在位点98是His,Ile,Asn,Leu,Ala,Thr,Leu,Arg,Gln,Leu,Lys,Met,Ser,Tyr,Val或Pro；Xaa在位点99是Ile,Leu，或Val；Xaa在位点100是Lys,Arg,Ile,Gln,Pro，或Ser；Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Pro,Asn,Ile,Leu或Tyr；Xaa在位点104是Trp或Leu；Xaa在位点105是Asn,Pro,Ala,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His；Xaa在位点106是Glu或Gly；Xaa在位点108是Arg,Ala，或Ser；Xaa在位点109是Arg,Thr,Glu,Leu，或Ser；Xaa在位点112是Thr,Val，或Gln；Xaa在位点114是Tyr或Trp；Xaa在位点115是Leu或Ala；Xaa在位点116是Lys,Thr,Val,Trp,Ser,Ala,His,Met,Phe,Tyr或Ile；Xaa在位点117是Thr或Ser；Xaa在位点120是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Asp，或Gly；Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys；Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；并且可附加性在位点1前含有Met-氨基酸；并且N末端1～14氨基酸可缺失和/或C末端1～15氨基酸缺失；并且其中用Xaa代表的4～35氨基酸与天然的人白介素3(1-133)相应的氨基酸不同；3．2中的融合蛋白，其中所说的人白介素3突变多肽通式如下Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa Xaa20 25 30Pro Xaa Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp Xaa35 40 45Xaa Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu Ala50 55 60Phe Xaa Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile Glu65 70 75Xaa Xaa Leu Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr Ala80 85 90Xaa Pro Xaa Arg Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp Xaa95 100 105Glu Phe Xaa Xaa Lys Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu Xaa110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe125 130〔SEQ ID NO:3〕其中Xaa在位点17是Ser,Gly,Asp，或Gln；Xaa在位点18是Asn,His，或Ile；Xaa在位点23是Ile,Ala,Leu，或Gly；Xaa在位点25是Thr,His，或Gln；Xaa在位点26是His或Ala；Xaa在位点29是Gln或Asn；Xaa在位点30是Pro或Gly；Xaa在位点32是Leu,Arg,Asn，或Ala；Xaa在位点34是Leu,Val,Ser,Ala,Arg,Gln,Glu,Ile,Phe,Thr，或Met；Xaa在位点35是Leu,Ala,Asn，或Pro；Xaa在位点38是Asn或Ala；Xaa在位点42是Gly,Asp,Ser,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点45是Gln,Val,Met,Leu,Ala,Asn,Glu，或Lys；Xaa在位点46是Asp,Phe,Ser,Gln,Glu,His,Val或Thr；Xaa在位点50是Glu,Asn,Ser或Asp；Xaa在位点51是Asn,Arg,Pro,Thr，或His；Xaa在位点55是Arg,Leu，或Gly；Xaa在位点56是Pro,Gly,Ser,Ala,Asn,Val,Leu或Gln；Xaa在位点62是Asn,Pro，或Thr；Xaa在位点64是Ala或Asn；Xaa在位点65是Val或Thr；Xaa在位点67是Ser或Phe；Xaa在位点68是Leu或Phe；Xaa在位点69是Gln,Ala,Glu，或Arg；Xaa在位点76是Ser,Val,Asn,Pro，或Gly；Xaa在位点77是Ile或Leu；Xaa在位点79是Lys,Gly,Asn,Met,Arg,Ile，或Gly；Xaa在位点80是Asn,Gly,Glu，或Arg；Xaa在位点82是Leu,Gln,Trp,Arg,Asp,Asn,Glu,His,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点87是Leu或Ser；Xaa在位点88是Ala或Trp；Xaa在位点91是Ala或Pro；Xaa在位点93是Thr,Asp，或Ala；Xaa在位点95是His,Pro,Arg,Val,Gly,Asn,Ser或Thr；Xaa在位点98是His,Ile,Asn,Ala,Thr,Gln,Glu,Lys,Met,Ser,Tyr,Val或Leu；Xaa在位点99是Ile或Leu；Xaa在位点100是Lys或Arg；Xaa在位点101是Asp,Pro,Met,Lys,Thr,His,Pro,Asn,Ile,Leu或Tyr；Xaa在位点105是Asn,Pro,Ser,Ile或Asp；Xaa在位点108是Arg,Ala，或Ser；Xaa在位点109是Arg,Thr,Glu,Leu，或Ser；Xaa在位点112是Thr或Gln；Xaa在位点116是Lys,Val,Trp,Ala,His,Phe,Tyr或Ile；Xaa在位点117是Thr或Ser；Xaa在位点120是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点121是Ala,Ser,Ile,Pro，或Asp；Xaa在位点122是Gln,Met,Trp,Phe,Pro,His,Ile，或Tyr；Xaa在位点123是Ala,Met,Glu,Ser，或Leu；并且可附加性的在位点1前含有Met-氨基酸；并且N末端1～14氨基酸可缺失和/或C末端1～15氨基酸缺失；并且其中用Xaa代表的4～44氨基酸与天然的人白介素3(1-133)相应的氨基酸不同；4．3中的融合蛋白，其中所说的人白介素3突变体多肽的通式如下Xaa在位点42是Gly,Asp,Ser,Ile,Leu,Met,Tyr，或Ala；Xaa在位点45是Gln,Val,Met或Asn；Xaa在位点46是Asp,Ser,Gln,His或Val；Xaa在位点50是Glu或Asp；Xaa在位点51是Asn,Pro或Thr；Xaa在位点62是Asn或Pro；Xaa在位点76是Ser，或Pro；Xaa在位点82是Leu,Trp,Asp,Asn,Glu,His,Phe,Ser或Tyr；Xaa在位点95是His,Arg,Thr,Asn或Ser；Xaa在位点98是His,Ile,Leu,Ala,Gln,Lys,Met,Ser,Tyr或Val；Xaa在位点100是Lys或Arg；Xaa在位点101是Asp,Pro,His,Asn,Ile或Leu；Xaa在位点105是Asn，或Pro；Xaa在位点108是Arg,Ala，或Ser；Xaa在位点116是Lys,Val,Trp,Ala,His,Phe，或Tyr；Xaa在位点121是Aal，或Ile；Xaa在位点122是Gln，或Ile；和Xaa在位点123是Ala,Met或Glu。
6．含有选自下列通式的融合蛋白R1-L-R2,R2-L-R1,R1-R2,R2-R1,R1-L-R1及R1-R1其中R1是人白介素3突变体多肽，通式如下Asn Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa15 10 15Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa80 85 90Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa95 100 105Xaa Xaa Xaa Xaa Gln Gln [SEQ ID NO:4]110其中Xaa在位点3是Ser,Lys,Gly,Asp,Met,Gln，或Arg；Xaa在位点4是Asn,His,Leu,Ile,Phe,Arg，或Gln；Xaa在位点5是Met,Phe,Ile,Arg,Gly,Ala，或Cys；Xaa在位点6是Ile,Cys,Gln,Glu,Arg,Pro，或Ala；Xaa在位点7是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser或Val；Xaa在位点8是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或Gly；Xaa在位点9是Ile,Val,Ala,Leu,Gly,Trp,Lys,Phe,Leu,Ser，或Arg；Xaa在位点10是Ile,Gly,Val,Arg,Ser,Phe，或Leu；Xaa在位点11是Thr,His,Gln,Arg,Pro，或Ala；Xaa在位点12是His,Thr,Phe,Gly,Arg,Ala，或Trp；Xaa在位点13是Leu,Gly,Arg,Thr,Ser，或Ala；Xaa在位点14是Lys,Arg,Leu,Gln,Gly,Pro,Val或Trp；Xaa在位点15是Gln,Asn,Leu,Pro,Arg，或Val；Xaa在位点16是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys；Xaa在位点17是Pro,Asp,Gly,Ala,Arg,Leu，或Gln；Xaa在位点18是Leu,Val,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点19是Pro,Leu,Gln,Ala,Thr，或Glu；Xaa在位点20是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile或Met；Xaa在位点21是Leu,Ala,Gly,Asn,Pro,Gln，或Val；Xaa在位点22是Asp,Leu，或Val；Xaa在位点23是Phe,Ser,Pro,Trp，或Ile；Xaa在位点24是Asn，或Ala；Xaa在位点26是Leu,Trp，或Arg；Xaa在位点27是Asn,Cys,Arg,Leu,His,Met,Pro；Xaa在位点28是Gly,Asp,Ser,Cys,Ala,Lys,Asn,Thr,Leu,Val,Glu,Phe,Tyr,Ile或Met；Xaa在位点29是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,Gly或Ser；Xaa在位点30是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,Ala或Pro；Xaa在位点31是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Asp,Asn,Arg,Ser,Ala,Ile,Glu,His或Trp；Xaa在位点32是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,Tyr,Ile,Val或Gly；Xaa在位点33是Ile,Gly,Val,Ser,Arg,Pro，或His；Xaa在位点34是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,Val或Asn；Xaa在位点35是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp；Xaa在位点36是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,Phe,Met或Gln；Xaa在位点37是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点38是Asn,His,Arg,Leu,Gly,Ser，或Thr；Xaa在位点39是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,Met，或；Xaa在位点40是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala或Leu；Xaa在位点41是Arg,Thr,Val,Ser,Leu，或Gly；Xaa在位点42是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,Leu,Val或Lys；Xaa在位点43是Asn或Gly；Xaa在位点44是Leu,Ser,Asp,Arg,Gln,Val，或Cys；Xaa在位点45是Glu,Tyr,His,Leu,Pro，或Arg；Xaa在位点46是Ala,Ser,Pro,Tyr,Asn，或Thr；Xaa在位点47是Phe,Asn,Glu,Pro,Lys,Arg，或Ser；Xaa在位点48是Asn,His,Val,Arg,Pro,Thr,Asp，或Ile；Xaa在位点49是Arg,Tyr,Trp,Lys,Ser,His,Pro，或Val；Xaa在位点50是Ala,Asn,Pro,Ser，或Lys；Xaa在位点51是Val,Thr,Pro,His,Leu,Phe，或Ser；Xaa在位点52是Lys,Ile,Arg,Val,Asn,Glu，或Ser；Xaa在位点53是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His；Xaa在位点54是Leu,Val,Trp,Ser,Ile,Phe,Thr，或His；Xaa在位点55是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly，或Leu；Xaa在位点56是Asn,Leu,Val,Trp,Pro，或Ala；Xaa在位点57是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp，或Asn；Xaa在位点58是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp；Xaa在位点59是Ala,Glu,Asp,Leu,Ser,Gly,Thr，或Arg；Xaa在位点60是Ile,Met,Thr,Pro,Arg,Gly,Ala；Xaa在位点61是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln，或Leu；Xaa在位点62是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly，或Asp；Xaa在位点63是Ile,Ser,Arg,Thr，或Leu；Xaa在位点64是Leu,Ala,Ser,Glu,Phe,Gly，或Arg；Xaa在位点65是Lys,Thr,Gly,Asn,Met,Arg,Ile，或Asp；Xaa在位点66是Asn,Trp,Val,Gly,Thr,Leu,Glu，或Arg；Xaa在位点67是Leu,Gln,Gly,Ala,Trp,Arg,Val，或Lys；Xaa在位点68是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,Ala,Tyr,Phe,Ile,Met或Val；Xaa在位点69是Pro,Ala,Thr,Trp,Arg，或Met；Xaa在位点70是Cys,Glu,Gly,Arg,Met，或Val；Xaa在位点71是Leu,Asn,Val，或Gln；Xaa在位点72是Pro,Cys,Arg,Ala，或Lys；Xaa在位点73是Leu,Ser,Trp，或Gly；Xaa在位点74是Ala,Lys,Arg,Val，或Trp；Xaa在位点75是Thr,Asp,Cys,Leu,Val,Glu,His,Asn，或Ser；Xaa在位点76是Ala,Pro,Ser,Thr,Gly,Asp,Ile，或Met；Xaa在位点77是Ala,Pro,Ser,Thr,Phe,Leu,Asp，或His；Xaa在位点78是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile或Leu；Xaa在位点79是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg；Xaa在位点80是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala或Pro；Xaa在位点81是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,Trp,Phe,Ile或Tyr；Xaa在位点82是Pro,Lys,Tyr,Gly,Ile，或Thr；Xaa在位点83是Ile,Val,Lys,Ala，或Asn；Xaa在位点84是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,Val,Lys,Arg,Tyr或Pro；Xaa在位点85是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,ser,Phe，或His；Xaa在位点86是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,Pro；Xaa在位点87是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,Ala,Gly,Ile,Leu或Gln；Xaa在位点88是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro；Xaa在位点89是Asp，或Ser；Xaa在位点90是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe，或Gly；Xaa在位点91是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Tle,Asp或His；Xaa在位点92是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro；Xaa在位点94是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala，或Pro；Xaa在位点95是Arg,Thr,Pro,Glu,Tyr,Leu,Ser，或Gly；Xaa在位点96是Lys,Asn,Thr,Leu,Gln,Arg,His,Glu,Ser,Ala或Trp；Xaa在位点97是Leu,Ile,Arg,Asp，或Met；Xaa在位点98是Thr,Val,Gln,Tyr,Glu,His,Ser，或Phe；Xaa在位点99是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val或Asn；Xaa在位点100是Tyr,Cys,His,Ser,Trp,Arg，或Leu；Xaa在位点101是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp，或Met；Xaa在位点102是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,Asn,His,Ala,Tyr,Phe,Gln，或Ile；Xaa在位点103是Thr,Ser,Asn,Ile,Trp,Lys，或Pro；Xaa在位点104是Leu,Ser,Pro,Ala,Glu,Cys,Asp，或Tyr；Xaa在位点105是Glu,Ser,Lys,Pro,Leu,Thr,Tyr，或Arg；Xaa在位点106是Asn,Ala,Pro,Leu,His,Val，或Gln；Xaa在位点107是Ala,Ser,Ile,Asn,Pro,Lys,Asp，或Gly；Xaa在位点108是Gln,Ser,Met,Trp,Arg,Phe,Prc,His,Ile,Tyr，或Cys；Xaa在位点109是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；并且在位点1前可附加性含有Met-或Met-Ala-氨基酸；其中用Xaa代表的4～44氨基酸与天然的人白介素3相应的氨基酸(1～133)不同；R2是一个集落刺激因子；并且L是一个能将R1与R2相连的接头。
6．5中的融合蛋白，其中所说的人白介素3突变多肽通式如下Asn Cys Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa1 5 10 15Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa20 25 30Xaa Xaa Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu35 40 45Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile50 55 60Glu Xaa Xaa Leu Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr65 70 75Ala Xaa Pro Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa80 85 90Xaa Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu95 100 105Xaa Xaa Xaa Xaa Gln Gln [SEQ ID NO:5]110其中Xaa在位点3是Ser,Gly,Asp,Met，或Gln；Xaa在位点4是Asn,His，或Ile；Xaa在位点5是Met或Ile；Xaa在位点7是Asp或Glu；Xaa在位点9是Ile,Ala,Leu，或Gly；Xaa在位点10是Ile,Val，或Leu；Xaa在位点11是Thr,His,Gln，或Ala；Xaa在位点12是His或Ala；Xaa在位点15是Gln,Asn，或Val；Xaa在位点16是Pro,Gly，或Gln；Xaa在位点17是Pro,Asp,Gly，或Gln；Xaa在位点18是Leu,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点19是Pro或Glu；Xaa在位点20是Leu,Val,Gly,Ser,Lys,Ala,Arg,Gln,Glu,Ile,Phe,Thr或Met；Xaa在位点21是Leu,Ala,Asn,Pro,Gln，或Val；Xaa在位点23是Phe,Ser,Pro，或Trp；Xaa在位点24是Asn或Ala；Xaa在位点28是Gly,Asp,Ser,Cys,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点30是Asp或Glu；Xaa在位点31是Gln,Val,Met,Leu,Thr,Ala,Asn,Glu,Ser或Lys；Xaa在位点32是Asp,Phe,Ser,Thr,Ala,Asn,Gln,Glu,His,Ile,Lys,Tyr,Val或Cys；Xaa在位点36是Glu,Ala,Asn,Ser或Asp；Xaa在位点37是Asn,Arg,Met,Pro,Set,Thr，或His；Xaa在位点40是Arg或Ala；Xaa在位点41是Arg,Thr,Val,Leu，或Gly；Xaa在位点42是Pro,Gly,Ser,Gln,Ala,Arg,Asn,Glu,Leu,Thr,Val或Lys；Xaa在位点46是Ala或Ser；Xaa在位点48是Asn,Pro,Thr，或Ile；Xaa在位点49是Arg或Lys；Xaa在位点50是Ala或Asn；Xaa在位点51是Val或Thr；Xaa在位点52是Lys或Arg；Xaa在位点53是Ser,Phe，或His；Xaa在位点54是Leu,Ile,Phe，或His；Xaa在位点55是Gln,Ala,Pro,Thr,Glu,Arg，或Gly；Xaa在位点57是Ala,Pro，或Arg；Xaa在位点58是Ser,Glu,Arg，或Asp；Xaa在位点59是Ala或Leu；Xaa在位点62是Ser,Val,Ala,Asn,Glu,Pro，或Gly；Xaa在位点63是Ile或Leu；Xaa在位点65是Lys,Thr,Gly,Asn,Met,Arg,Ile,Gly，或Asp；Xaa在位点66是Asn,Gly,Glu，或Arg；Xaa在位点68是Leu,Gln,Trp,Arg,Asp,Ala,Asn,Glu,His,Ile,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点69是Pro或Thr；Xaa在位点71是Leu或Val；Xaa在位点73是Leu或Ser；Xaa在位点74是Ala或Trp；Xaa在位点77是Ala或Pro；Xaa在位点79是Thr,Asp,Ser,Pro,Ala,Leu，或Arg；Xaa在位点81是His,Pro,Arg,Val,Leu,Gly,Asn,Phe,Ser或Thr；Xaa在位点82是Pro或Tyr；Xaa在位点83是Ile或Val；Xaa在位点84是His,Ile,Asn,Leu,Ala,Thr,Leu,Arg,Gln,Leu,Lys,Met,Ser,Tyr,Val或Pro；Xaa在位点85是Ile,Leu，或Val；Xaa在位点86是Lys,Arg,Ile,Gln,Pro，或Ser；Xaa在位点87是Asp,Pro,Met,Lys,His,Thr,Asn,Ile,Leu或Tyr；Xaa在位点90是Trp或Leu；Xaa在位点91是Asn,Pro,Ala,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His；Xaa在位点92是Glu，或Gly；Xaa在位点94是Arg,Ala，或Ser；Xaa在位点95是Arg,Thr,Glu,Leu，或Ser；Xaa在位点98是Thr,Val，或Gln；Xaa在位点100是Tyr或Trp；Xaa在位点101是Leu或Ala；Xaa在位点102是Lys,Thr,Val,Trp,Ser,Ala,His,Met,Phe,Tyr或Ile；Xaa在位点103是Thr或Ser；Xaa在位点106是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点107是Ala,Ser,Ile,Asn,Pro,Asp，或Gly；Xaa在位点108是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys；Xaa在位点109是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；可能在位点1前可附加性含有Met-或Met-Ala-氨基酸；并且其中Xaa所指的4～35氨基酸与天然的人白介素3的相应的氨基酸不同。
7．6中的融合蛋白，其中所说的人白介素3突变多肽的通式如下Asn Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa15 10 15Xaa Pro Xaa Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp20 25 30Xaa Xaa Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu35 40 45Ala Phe Xaa Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile50 55 60Glu Xaa Xaa Leu Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr65 70 75Ala Xaa Pro Xaa Arg Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp80 85 90Xaa Glu Phe Xaa Xaa Lys Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu95 100 105Xaa Xaa Xaa Xaa Gln Gln [SEQ ID NO:6]110其中Xaa在位点3是Ser,Gly,Asp，或Gln；Xaa在位点4是Asn,His，或Ile；Xaa在位点9是Ile,Ala,Leu，或Gly；Xaa在位点11是Thr,His，或Gln；Xaa在位点12是His或Ala；Xaa在位点15是Gln或Asn；Xaa在位点16是Pro或Gly；Xaa在位点18是Leu,Arg,Asn，或Ala；Xaa在位点20是Leu,Val,Ser,Ala,Arg,Gln,Glu,Ile,Phe,Thr或Met；Xaa在位点21是Leu,Ala,Asn，或Pro；Xaa在位点24是Asn或Ala；Xaa在位点28是Gly,Asp,Ser,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点31是Gln,Val,Met,Leu,Ala,Asn,Glu或Lys；Xaa在位点32是Asp,Phe,Ser,Ala,Gln,Glu,His,Val或Thr；Xaa在位点36是Glu,Asn,Ser或Asp；Xaa在位点37是Asn,Arg,Pro,Thr，或His；Xaa在位点41是Arg,Leu，或Gly；Xaa在位点42是Pro,Gly,Ser,Ala,Asn,Val,Leu或Gln；Xaa在位点48是Asn,Pro，或Thr；Xaa在位点50是Ala或Asn；Xaa在位点51是Val或Thr；Xaa在位点53是Ser或Phe；Xaa在位点54是Leu或Phe；Xaa在位点55是Gln,Ala,Glu，或Arg；Xaa在位点62是Ser,Val,Asn,Pro，或Gly；Xaa在位点63是Ile或Leu；Xaa在位点65是Lys,Asn,Met,Arg,Ile，或Gly；Xaa在位点66是Asn,Gly,Glu，或Arg；Xaa在位点68是Leu,Gln,Trp,Arg,Asp,Asn,Glu,His,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点73是Leu或Ser；Xaa在位点74是Ala或Trp；Xaa在位点77是Ala或Pro；Xaa在位点79是Thr,Asp，或Ala；Xaa在位点81是His,Pro,Arg,Val,Gly,Asn,Ser或Thr；Xaa在位点84是His,Ile,Asn,Ala,Thr,Arg,Gln,Glu,Lys,Met,Ser,Tyr,Val或Leu；Xaa在位点85是Ile或Leu；Xaa在位点86是Lys或Arg；Xaa在位点87是Asp,Pro,Met,Lys,His,Pro,Asn,Ile,Leu或Tyr；Xaa在位点91是Asn,Pro,Ser,Ile或Asp；Xaa在位点94是Arg,Ala，或Ser；Xaa在位点95是Arg,Thr,Glu,Leu，或Ser；Xaa在位点98是Thr或Gln；Xaa在位点102是Lys,Val,Trp，或Ile；Xaa在位点103是Thr,Ala,His,Phe,Tyr或Ser；Xaa在位点106是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点107是Ala,Ser,Ile,Pro，或Asp；Xaa在位点108是Gln,Met,Trp,Phe,Pro,His,Ile，或Tyr；Xaa在位点109是Ala,Met,Glu,Ser，或Leu；并且可在位点1′前可附加性含有Met-或Met-Ala-氨基酸；其中用Xaa代表的4～26氨基酸与天然的人白介素3相应的氨基酸(1～133)不同。
8．7中的融合蛋白，其中所说的人白介素3突变多肽的通式如下Xaa在位点17是Ser,Lys,Asp,Met,Gln，或Arg；Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg，或Gln；Xaa在位点19是Met,Arg,Gly,Ala，或Cys；Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro，或Ala；Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly，或Val；Xaa在位点22是Gly,Trp,Pro,Ser,Ala,His，或Gly；Xaa在位点23是Ile,Ala,Gly,Trp,Lys,Leu,Ser，或Arg；Xaa在位点24是Ile,Gly,Arg，或Ser；Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro，或Ala；Xaa在位点26是His,Thr,Phe,Gly,Ala，或Trp；Xaa在位点27是Leu,Gly,Arg,Thr,Ser，或Ala；Xaa在位点28是Lys,Leu,Gln,Gly,Pro,Val或Trp；Xaa在位点29是Gln,Asn,Pro,Arg，或Val；Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys；Xaa在位点31是Pro,Asp,Gly,Arg,Leu，或Gln；Xaa在位点32是Leu,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点33是Pro,Leu,Gln,Thr，或Glu；Xaa在位点34是Leu,Gly,Ser，或Lys；Xaa在位点35是Leu,Ala,Gly,Asn,Pro，或Gln；Xaa在位点36是Asp,Leu，或Val；Xaa在位点37是Phe,Ser，或Pro；Xaa在位点38是Aan，或Ala；Xaa在位点40是Leu,Trp，或Arg；Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,Pro；Xaa在位点42是Gly,Asp,Ser,Cys，或Ala；Xaa在位点42是Gly,Asn,Tyr,Leu,Phe,Asp,Ala,Cys，或Ser；Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp，或Pro；Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys，或Trp；Xaa在位点46是Asp,Phe,Ser,Thr,Cys，或Gly；Xaa在位点47是Ile,Gly,Ser,Arg,Pro，或His；Xaa在位点48是Leu,Ser,Cys,Arg,His,Phe，或Asn；Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp；Xaa在位点50是Glu,Leu,Thr,Asp，或Try；Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser，或Thr；Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser，或；Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln，或Leu；Xaa在位点55是Arg,Thr,Val,Ser,Leu，或Gly；Xaa在位点56是Pro,Gly,Cys,Ser,Gln，或Lys；Xaa在位点57是Asn或Gly；Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val，或Cys；Xaa在位点59是Glu,Tyr,His,Leu,Pro，或Arg；Xaa在位点60是Ala,Ser,Tyr,Asn，或Thr；Xaa在位点61是Phe,Asn,Glu,Prc,Lys,Arg，或Ser；Xaa在位点62是Asn,His,Val,Arg,Pro,Thr，或Ile；Xaa在位点63是Arg,Tyr,Trp,Ser,Pro，或Val；Xaa在位点64是Ala,Asn,Ser，或Lys；Xaa在位点65是Val,Thr,Pro,His,Leu,Phe，或Ser；Xaa在位点66是Lys,Ile,Val,Asn,Glu，或Ser；Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His；Xaa在位点68是Leu,Val,Trp,Ser,Thr，或His；Xaa在位点69是Gln,Ala,Pro,Thr,Arg,Trp,Gly，或Leu；Xaa在位点70是Asn,Leu,Val,Trp,Pro，或Ala；Xaa在位点71是Ala,Met,Leu,Arg,Glu,Thr,Gln,Trp，或Asn；Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp；Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr，或Arg；Xaa在位点74是Ile,Thr,Pro,Arg,Gly,Ala；Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser，或Leu；Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,gly，或Asp；Xaa在位点77是Ile,Ser,Arg，或Thr；Xaa在位点78是Leu,Ala,Ser,Glu,Gly，或Arg；Xaa在位点79是Lys,Thr,Gly,Asn,Met,Ile，或Asp；Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu，或Arg；Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg，或Lys；Xaa在位点82是Leu,Gln,Lys,Trp,Arg，或Asp；Xaa在位点83是Pro,Thr,Trp,Arg，或Met；Xaa在位点84是Cys,Glu,Cly,Arg,Met，或Val；Xaa在位点85是Leu,Asn，或Gln；Xaa在位点86是Pro,Cys,Arg,Ala，或Lys；Xaa在位点87是Leu,Ser,Trp，或Gly；Xaa在位点88是Ala,Lys,Arg,Val，或Trp；Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His，或Asn；Xaa在位点90是Ala,Ser,Asp,Ile，或Met；Xaa在位点91是Ala,Ser,Thr,Phe,Leu,Asp，或His；Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His，或Leu；Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg；Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val，或Pro；Xaa在位点95是His,Gln,Pro,Val,Leu,Thr，或Tyr；Xaa在位点96是Pro,Lys,Tyr,Gly,Ile，或Thr；Xaa在位点97是Ile,Lys,Ala，或Asn；Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr，或Pro；Xaa在位点99是Ile,Arg,Asp,Pro,Gln,Gly,Phr，或His；Xaa在位点100是Lys,Tyr,Leu,His,Ile,Ser,Gln，或Pro；Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr，或Gln；Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro；Xaa在位点103是Asp，或Ser；Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe，或Gly；Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile，或His；Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro；Xaa在位点108是Arg,Asp,Leu,Thr,Ile，或Pro；Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser，或Gly；9．8中的融合蛋白，其中所说的人白介素3突变多肽通式如下1 5 10(Met)m-Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr15 20Ser Trp Val Asn Cys Ser Xaa Xaa Xaa Asp Glu Ile Ile25 3035Xaa His Leu Lys Xaa Pro Pro Xaa Pro Xaa Leu Asp Xaa4045 50Xaa Asn Leu Asn Xaa Glu Asp Xaa Asp Ile Leu Xaa Glu55 60Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa Xaa65 70 75Ala Xaa Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa80 85Ile Leu Xaa Asn Leu Xaa Pro Cys Xaa Pro Xaa Xaa Thr90 95100Ala Xaa Pro Xaa Arg Xaa Pro Ile Xaa Ile Xaa Xaa Gly105110 115Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Xaa Phe Tyr Leu120 125Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln Thr Thr Leu130Ser Leu Ala Ile Phe [SEQ ID NO:7]其中m是0或1；Xaa在位点18是Asn或Ile；Xaa在位点19是Met,Ala或Ile；Xaa在位点20是Ile,Pro或Ile；Xaa在位点23是Ile,Ala或Leu；Xaa在位点25是Thr或His；Xaa在位点29是Gln,Arg,Val或Ile；Xaa在位点32是Leu,Ala,Asn或Arg；Xaa在位点34是Leu或Ser；Xaa在位点37是Pha,Pro，或Ser；Xaa在位点38是Asn或Ala；Xaa在位点42是Gly,Ala,Ser,Asp或Asn；Xaa在位点45是Gln,Val，或Met；Xaa在位点46是Asp或Ser；Xaa在位点49是Met,Ile,Leu或Asp；Xaa在位点50是Glu或Asp；Xaa在位点51是Asn,Arg或Ser；Xaa在位点55是Arg,Leu，或Thr；Xaa在位点56是Pro或Ser；Xaa在位点59是Glu或Leu；Xaa在位点60是Ala或Ser；Xaa在位点62是Asn,Val或Pro；Xaa在位点63是Arg或His；Xaa在位点65是Val或Ser；Xaa在位点67是Ser,Asn,His或Gln；Xaa在位点69是Gln或Glu；Xaa在位点73是Ala或Gly；Xaa在位点76是Ser,Ala或Pro；Xaa在位点79是Lys,Arg或Ser；Xaa在位点82是Leu,Glu,Val或Trp；Xaa在位点85是Leu或Val；Xaa在位点87是Leu,Ser,Tyr；Xaa在位点88是Ala或Trp；Xaa在位点91是Ala或Pro；Xaa在位点93是Pro或Ser；Xaa在位点95是His或Thr；Xaa在位点98是His,Ile,或Thr；Xaa在位点100是Lys或Arg；Xaa在位点101是Asp,Ala或Met；Xaa在位点105是Asn或Glu；Xaa在位点109是Arg,Glu或Leu；Xaa在位点112是Thr或Gln；Xaa在位点116是Lys,Val,Trp或Ser；Xaa在位点117是Thr或Ser；Xaa在位点120是Asn,Gln，或His；Xaa在位点123是Ala或Glu；根据附文Xaa代表的从四到四十四氨基酸与天然人白介素3相应的氨基酸不同。
10．9中的融合蛋白，其中所说的人白介素3突变多肽的通式如下1 5 10(Metm-Alan)p-Asn Cys ser Xaa Xaa Xaa Asp Glu Xaa Ile15 20Xaa His Leu Lys Xaa Pro Pro Xaa Pro Xaa Leu Asp Xaa2530 35Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa Ile Leu Xaa Glu4045Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa Xaa50 5560Ala Xaa Lys Xaa Leu Xaa Asn Ala ser Xaa Ile Glu Xaa6570 75Ile Leu Xaa Asn Xaa Xaa Pro Cys Xaa Pro Xaa Ala Thr80 85Ala Xaa Pro Xaa Arg Xaa Pro Ile Xaa Ile Xaa Xaa Gly90 95 100Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Xaa Phe Tyr Leu105 110Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln [SEQ ID NO:8]其中m是0或1；n是0或1；p是0或1；Xaa在位点4是Asn或Ile；Xaa在位点5是Met,Ala或Ile；Xaa在位点6是Ile,Pro或Leu；Xaa在位点9是Ile,Ala或Leu；Xaa在位点11是Thr或His；Xaa在位点15是Gen,Arg,Val或Ile；Xaa在位点18是Leu,Ala,Asn或Arg；Xaa在位点20是Leu或Ser；Xaa在位点23是Phe,Pro，或Ser；Xaa在位点24是Asn或Ala；Xaa在位点28是Gly,Ala,Ser,Asp或Asn；Xaa在位点31是Gln,Val，或Met；Xaa在位点32是Asp或Ser；Xaa在位点35是Met,Ile或Asp；Xaa在位点36是Glu或Asp；Xaa在位点37是Asn,Arg或Ser；Xaa在位点41是Arg,Leu，或Thr；Xaa在位点42是Pro或Ser；Xaa在位点45是Glu或Leu；Xaa在位点46是Ala或Ser；Xaa在位点48是Asn,Val或Pro；Xaa在位点49是Arg或His；Xaa在位点51是Val或Gly；Xaa在位点53是Ser,Asn,His或Gln；Xaa在位点55是Gln或Glu；Xaa在位点59是Ala或Gly；Xaa在位点62是Ser,Ala或Pro；Xaa在位点65是Lys,Arg或Ser；Xaa在位点67是Leu,Glu，或Val；Xaa在位点68是Leu,Glu,Val或Trp；Xaa在位点71是Leu或Val；Xaa在位点73是Leu,Ser或Tyr；Xaa在位点74是Ala或Trp；Xaa在位点77是Ala或Pro；Xaa在位点79是Pro或Ser；Xaa在位点81是His或Thr；Xaa在位点84是His,Ile，或Thr；Xaa在位点86是Lys或Arg；Xaa在位点87是Asp,Ala或Met；Xaa在位点91是Asn或Glu；Xaa在位点95是Arg,Glu,Leu；Xaa在位点98是Thr或Gln；Xaa在位点102是Lus,Val,Trp或Ser；Xaa在位点103是Thr或Ser；Xaa在位点106是Asn,Gln，或His；Xaa在位点109是Ala或Gly；根据附文Xaa代表的四到四十四氨基酸与天然(15-125)的人白介素3的相应的氨基酸不同。11．10中的融合蛋白，其中所说的人白介素3突变多肽通式如下Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu AsnAla Glu Asp Val Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:9]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu AsnSer Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:10]；
Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu AsnSer Glu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:11]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg LeuPro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu GluAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:12]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg LeuPro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu GluAsn Ala Sar Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:13]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg ThrPro Asn Leu Leu Ala Phe Val ~g Ala Val Lys His Leu GluAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:14]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:15]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleThr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:16]；Asn Cys Sar Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:17]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn. Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln[SEQ ID NO:18]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:19]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleThr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:20]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu AsnGly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg ArgPro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu GlnAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Val ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleThr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln[SEQ ID NO:21]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu AsnAla Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg LeuPro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu GluAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:22]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu AsnSer Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg ThrPro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu GluAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:23]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu AsnSer Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg LeuPro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn Leu GluAsn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu Leu ProCys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg Hls Pro IleHis Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys LeuThr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln[SEQ ID NO:24]；Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr HisLeu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn LeuAsn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu ArgArg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser LeuGln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:25]；Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr HisLeu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn LeuAsn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu ArgArg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser LeuGln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:26]；Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr HisLeu Lys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn LeuAsn Gly Glu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu ArgArg Pro Asn Leu Glu Ala Phe Asn Arg Ala Val Lys Ser LeuGln Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu GlnGln [SEQ ID NO:27]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu LeuPro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His ProIle His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg LysLeu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala GlnGln [SEQ ID NO:28]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu LeuPro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His ProIle His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg LysLeu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala GlnGln [SEQ ID NO:29]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys Asn Leu LeuPro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His ProIle His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg LysLeu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala GlnGln [SEQ ID NO:30]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:31]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:32]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:33]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:34]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:35]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu GlnGln [SEQ ID NO:36]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Sar Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Pha Arg Glu LysLeu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu GlnGln [SEQ ID NO:37]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:38]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Ala Glu Asp Val Asp Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu ValPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu GlnGln [SEQ ID NO:39].Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu ArgLeu Ser Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:40]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His HisLeu Lys Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:41]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:42]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Ala Glu Asp Val Asp Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:43]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:44]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Met Ser Ile Leu Met Glu Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:45]Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp LysAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu ProAsn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu AsnAla Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile IleIle Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu ThrPhe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:46]Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp LysAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr ProAsn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu AsnAla Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile IleIle Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu ThrPhe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:47]和Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His HisLeu Lys Ile Pro pro Asn pro Ser Leu Asp Ser Ala Asn LeuAsn Ser Glu Asp Val Ser Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln[SEQ ID NO:48].
下面是本发明融合蛋白的例子Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:121]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:122]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:123]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:124]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu LeuAsp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu MetGlu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val ArgAla Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala IleLeu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala AlaPro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln [SEQ ID NO:125]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Prs Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu LeuAsp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu MetGlu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val ArgAla Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala IleLeu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala AlaPro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln [SEQ ID NO:126]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu LeuAsp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu MetGlu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val ArgAla Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala IleLeu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala AlaPro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln [SEQ ID NO:127]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Pro Leu Gly Pro AlaSer Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu GlnVal Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu SerSer Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu AspThr Leu Gln Leu Asp Val Ala Asp Phe Ala Tnr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln ArgArg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:128]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Pro Leu Gly Pro AlaSer Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu GlnVal Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu SerSer Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu AspThr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Pne Ala Ser Ala Phe Gln ArgArg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:129]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Pro Leu Gly Pro AlaSer Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu GlnVal Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu SerSer Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu AspThr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln ArgArg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:130]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro LeuLeu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile LeuMet Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe ValArg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu AlaIle Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln [SEQ ID NO:131]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro LeuLeu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile LeuMet Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe ValArg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu AlaIle Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln [SEQ ID NO:132]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro LeuLeu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile LeuMet Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe ValArg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu AlaIle Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln [SEQ ID NO:133]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:134]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:135]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu LeuAsp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe al ArgAla Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala IleLeu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala AlaPro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln [SEQ ID NO:136]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro LeuLeu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile LeuMet Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe ValArg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu AlaIle Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln [SEQ ID NO:137]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Pro Leu Gly Pro AlaSer Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu GlnVal Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly Hls Ser Leu Gly Ile Pro Trp Ala Pro Leu SerSer Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu AspThr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln ArgArg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:138]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gln Pro Pro ValAsn Ala Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly SerGlu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly GlySer Glu Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly AspPhe Asp Tyr Glu Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Sar Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:139]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Pro Ala Arg Ser Pro Ser ProSer Thr Gln Pro Trp Glu His Val Asn Ala Ile Gln Glu AlaArg Arg Leu Leu Asn Leu Ser Arg Asp Thr Ala Ala Glu MetAsn Glu Thr Val Glu Val Ile Ser Glu Met Phe Asp Leu GlnGlu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys GlnGly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu ThrMet Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr ProGlu Thr Ser Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser PheLys Glu Asn Leu Lys Asp Phe Leu Leu Val Ile Pro Phe AspCys Trp Glu Pro Val Gln Glu [SEQ ID NO:141]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gln Pro Pro ValAsn Ala Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly SerGlu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly GlySer Glu Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly AspPhe Asp Tyr Glu Asn Met Ala Pro Ala Arg Ser Pro Ser ProSer Thr Gln Pro Trp Glu His Val Asn Ala Ile Gln Glu AlaArg Arg Leu Leu Asn Leu Ser Arg Asp Thr Ala Ala Glu MetAsn Glu Thr Val Glu Val Ile Ser Glu Met Phe Asp Leu GlnGlu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys GlnGly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu ThrMet Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr ProGlu Thr Ser Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser PheLys Glu Asn Leu Lys Asp Phe Leu Leu Val Ile Pro Phe AspCys Trp Glu Pro Val Gln Glu [SEQ ID NO:142]Met Ala Asn Cys Ser Ile Mer Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Pro Val Asn Ala Gly Gly Gly Ser Gly Gly GlySer Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly GlySer Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Gly Gly GlySer Gly Ser Gly Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ara Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:143]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Pro Ala Arg Ser Pro SerPro Ser Thr Gln Pro Trp Glu His Val Asn Ala Ile Gln GluAla Arg Arg Leu Leu Asn Leu Ser Arg Asp Thr Ala Ala GluMet Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe Asp LeuGln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr LysGln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro LeuThr Met Met Ala Ser His Tyr Lys Gln His Cys Pro Pro ThrPro Glu Thr Ser Cys Ala Thr Gln Ile Ile Thr Phe Glu SerPhe Lys Glu Asn Leu Lys Asp Phe Leu Leu Val Ile Pro PheAsp Cys Trp Glu Pro Val Gln Glu [SEQ ID NO:144]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Pro Val Pro Pro Gly Glu AspSer Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu Thr SerSer Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp GlyIle Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn MetCys Glu Ser Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu AsnLeu Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln Ser GlyPhe Asn Glu Glu Thr Cys Leu Val Lys Ile Ile Thr Gly LeuLeu Glu Phe Glu Val Tyr Leu Glu Tyr Leu Gln Asn Arg PheGlu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln Met Ser ThrLys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn LeuAsp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser LeuLeu Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp MetThr Thr His Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu GlnSer Ser Leu Arg Ala Leu Arg Gln Met [SEQ ID NO:145]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Ile Glu Gly ArgIle Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser Asn Met AlaAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr ProAsn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu AsnAla Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile IleIle Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu ThrPhe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:146]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Ile Glu Gly ArgIle Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser Asn Met AlaAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu ProAsn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu AsnAla Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile IleIle Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu ThrPhe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:147]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Men Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Pro Gln Pro ProVal Asn Ala Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly GlySer Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly GlyGly Ser Glu Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser GlyAsp Phe Asp Tyr Glu Asn Met Ala Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro LeuLeu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile LeuMet Asp Arg Asn Leu Arg Leu Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln [SEQ ID NO:148]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Ile Glu Gly ArgYle Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn MetAla Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu AsnAsp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg LeuPro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu GluAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:149]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Ile Glu Gly ArgIle Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn MetAla Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu AsnSer Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg ThrPro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu GluAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:150]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Sar His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Ile Glu Gly ArgIle Ser Pro Gln Pro Pro Val Asn Ala Gly Gly Gly Ser GlyGly Gly Ser Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu GlyGly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser GlyGly Gly Ser Gly Ser Gly Asp Phe Asp Tyr Glu Asn Met AlaAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr ProAsn Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu AsnAla Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile IleIle Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu ThrPhe Tyr Leu Val Thr Leu Glu Glu Ala Gln Glu Gln Gln[SEQ ID NO:151]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala SerSer Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu Gln ValArg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys LeuCys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val LeuLeu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser SerCys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser GlnLeu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln AlaLeu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp ThrLeu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp GlnGln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg ArgAla Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe LeuGlu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:152]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu LeuAsp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile Leu MetAsp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val ArgAla Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala IleLeu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala AlaPro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln [SEQ ID NO:153]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Gly Gly Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Thr Pro Leu Gly Pro AlaSer Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser Leu Glu GlnVal Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu LysLeu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu ValLeu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu SerSer Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu SerGln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu GlnAla Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu AspThr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln ProThr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln ArgArg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser PheLeu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:154]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn LeuAsn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu ArgLeu Pro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro SerGly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys GluSer His Lys Ser Pro Asn Met Ala Asn Cys Ser Ile Met IleAsp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala Pro LeuLeu Asp Pro Asn Asn Leu Asn Asp Glu Asp Val Ser Ile LeuMet Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe ValArg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu AlaIle Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp TrpGln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr LeuGlu Gln Ala Gln Glu Gln Gln [SEQ ID NO:155]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gly Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Glu Gly Gly GlyGly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn MetAla Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu AsnAsp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg LeuPro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu GluAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:156]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gly Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Glu Gly Gly GlyGly Ser Pro Gly Glu Pro Ser Gly Pro Ile Ser Thr Ile AsnPro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro Asn MetAla Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu AsnAsp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg LeuPro Asn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu GluAsn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln ProCys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro IleIle Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys LeuThr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:157]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gly Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Glu Gly Gly GlyGly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser Asn Met AlaAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu ASp Pro Asn Asn Leu Asn AspGlu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu ProAsn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu AsnAla Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile IleIle Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu ThrPhe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:158]Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln SerPhe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln GlyAsp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr LysLeu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser LeuGly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln AlaLeu Gln Leu Ala Gly Cys Leu Ser Gly Leu His Ser Gly LeuPhe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile SerPro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp ValAla Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu LeuGly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met ProAla Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val LeuVal Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr ArgVal Leu Arg His Leu Ala Gln Pro Tyr Val Glu Gly Gly GlyGly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser Asn Met AlaAsn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu LysArg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu ProAsn Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu AsnAla Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro CysLeu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro Ile IleIle Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu ThrPhe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:159]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Ser Pro Ala Pro Pro Ala CysAsp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His ValLeu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro LeuPro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu GlyGlu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp IleLeu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala AlaArg Gln Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu GlyGln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu GlnSer Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr ThrAla His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln HisLeu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly GlySer Thr Leu Cys Val Arg [SEQ ID NO:165]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His HisLeu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn LeuAsn Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu ArgThr Pro Asn Leu Leu Ala Phe Val Arg Ala Val Lys His LeuGlu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn Leu GlnPro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His ProIle Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu LysLeu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu GlnGln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Ser Pro Ala Pro Pro Ala CysAsp Leu Arg Val Leu Ser Lys Leu Leu Arg Asp Ser His ValLeu His Ser Arg Leu Ser Gln Cys Pro Glu Val His Pro LeuPro Thr Pro Val Leu Leu Pro Ala Val Asp Phe Ser Leu GlyGlu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp IleLeu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala AlaArg Gln Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu GlyGln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu GlnSer Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr ThrAla His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln HisLeu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly GlySer Thr Leu Cys Val Arg [SEQ ID NO:166]Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val LeuSer Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg LeuSer Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val LeuLeu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr GlnMet Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val ThrLeu Leu Leu Glu Gly Val Met Ala Ala Arg Gln Gln Leu GlyPro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly GlnVal Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly ThrGln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp ProAsn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly LysVal Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys ValArg Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly SerGly Gly Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile AspGlu Ile Ile His His Leu Lys Arg Pro Pro Asn Pro Leu LeuAsp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu MetGlu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val ArgAla Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala IleLeu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala AlaPro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu GluGln Ala Gln Glu Gln Gln [SEQ ID NO:167]Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val LeuSer Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg LeuSer Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val LeuLeu Pro Ala Val Asp Phe Ser Leu Gly Glu Trp Lys Thr GlnMet Glu Glu Thr Lys Ala Gln Asp Ile Leu Gly Ala Val ThrLeu Leu Leu Glu Gly Val Met Ala Ala Arg Gln Gln Leu GlyPro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser Gly GlnVal Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly ThrGln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp ProAsn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly LysVal Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys ValArg Glu Phe His Ala Tyr Val Glu Gly Gly Gly Gly Ser ProGly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Asn Cys Serlle Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro ProAsn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp MetAsp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu LeuAla Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser GlyAle Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys AlaGly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr LeuVal Thr Leu Glu Gln Ala Gln Glu Gln Gln[SEQ ID NO:168]融合分子在大肠杆菌中表达的材料和方法除非另外指出，所有特异的化学物质都来自Sigma Co.,(St.Louis,Mo)。限制性内切酶，T4多核苷酸激酶，大肠杆菌DNA聚合酶Ⅰ大片段(Klenow)及T4DNA连接酶来自New England Biolabs(Beverly,Massachusetts)。
大肠杆菌菌株JM 101菌株delta(pro lac),supE,thi,F1(traD36,ropAE,lacI-Q,lacZdeltaM15)(Messing,1979)。该菌株可从美国典型培养物保藏中心(ATCC),12301 Parklawn Drive,Rockville,Maryland 20852获得，登记号33876。MON 105(W 3100 rpoH 358)是W 3100(Bachmann,1972)的衍生物指定的ATCC登记，号为55204。GM 48菌株dam-3,dcm-6,gal,ara,lac,tar,leu,tonA,tsx(Marinus,1973)被用于制备在GATC序列没有甲基化的质粒DNA。
基因和质粒用于在大肠杆菌中生产hIL-3的基因来自British BiotechnologyIncorporated,Carbridage,England，产品目录号BBG 14。该基因被一个称为pP 0518的以pUC为基础的质粒携带。许多其它的人CSF基因包括IL-1α,IL-1β,IL-2,IL-4,IL-5,IL-6,IL-7,IL-8,G-CSF,GM-CSF及LIF可从R & D Systems,Inc.(Minn,MN)得到。
在大肠杆菌中生产hIL-3的质粒包含其用途已公开的遗传因子(Olins等，1988；Olins和Rangwala,1990)。所用的复制子是pBR327的复制子(Covarrubias，等，1981)，其在细胞中的拷贝数维持在大约100个(Sorbern等，1980)。在质粒上有一个编码β-内酰胺酶蛋白的基因。该蛋白赋于细胞对氨苄青霉素的抗性。该抗性被用做质粒在细胞中存在的选择表型。
对细胞质表达载体而言，转录启动子来源于大肠杆菌recA基因(Sancar，等，1980)。该启动子，称为precA，包括RNA聚合酶结合位点及texA抑制子结合位点(操纵基因)。该段DNA可提供高水平的转录，甚至当recA启动子在一个含pBR 327复制起点的质粒上也受到调控(Olinis等，1988)在此被引入作为参考。
所用的核糖体结合位点来自于T7噬菌体的基因10(Olinis等，1988)。该位点在临近precA的100个碱基对(bp)片段中被编码。在本文所用的质粒中，NcoⅠ酶的识别序列(CCATGG)接着g10-L。正是在NcoⅠ位点hIL-3基因被插入质粒中。期望在该连接点的核苷酸序列在mRNA中作为一个功能性的翻译起始位点而被识别(Olinis等，1988)。所用的hIL-3基因在该基因编码区的下游被构建有一个HindⅢ识别位点(AAGCTT)。在该HindⅢ位点是一个包含单链噬菌体T1复制起点的514个碱基对的RsaⅠ片段(Dente等，1983；Olins，等，1990)，二者都在此被引入作为参考。一种包含这些因子的质粒是pMON2341。另一个包含这些因子的质粒pMON 5847已在美国典型培养物保藏中心，12301 Parklawn Drive,Rockville,Maryland 20852保藏，登记号ATCC 68912。
在分泌的表达质粒中，转录启动子来自大肠杆菌的araB,A，及D基因(Greenfield等，1978)。该启动子称为pAraBAD并且被包含在一个323碱基对的SacⅡ,BglⅡ限制性片段中。LamB分泌前导序列(leader)在NcoⅠ酶识别序列处(5’CCATGG 3’)与hIL-3基因的N末端相融合(Wong等，1988；Clement等，1981)。所用的hIL-3基因在接着该基因的编码区处被构建成含有一个HindⅢ识别位点(5’AAGCTT 3’)。
重组DNA的方法合成的基因装配hIL-3突变体基因和其它CSF基因可通过合成的寡核苷酸的装配来构建。合成的寡核苷酸被设计成能以互补碱基对形式，与突出的单键末端退火，并当碱基对装配合适时能得到编码所需基因的一个部分的DNA序列。hIL-3基因的氨基酸取代是通过将寡核苷酸设计为编码所需取代的寡核苷酸而实现的。互补寡核苷酸序列在加有50mM NaCl的连接缓冲液中以每微升1个皮摩尔的浓度退火。样品在沸水中用100ml烧杯加热并慢慢凉至室温。1皮摩尔每种退火的寡核苷酸对与大约0.2皮摩尔质粒DNA连接，用合适的限制性酶消化，在连接缓冲液中(25mMTris pH8.0,10mM MgCl2,10mM二硫苏糖醇，1mM ATP,2mM精胺)与来自New England Biolabs(Benerly,Massuchusetts)的T4DNA连接酶一起以20μl总体积室温过夜。
聚合酶链式反应聚合酶链式反应(以后称为PCR)技术(Saiki,1985)使用Perkin-Elmer Cetus(Norwalk,CT.)的试剂盒和热循环仪。PCR是以来自Thermus aquaticus的热稳定性DNA聚合酶为基础的。PCR技术是一种模仿天然DNA复制过程的DNA扩增方法，其中以一种与体内复制相似的方式在每一个循环后，DNA分子的数目加倍。DNA聚合酶介导的延伸是5’到3’方向的。本文所用的术语“引物”指一段寡核苷酸序列，它提供一个末端以供DNA聚合酶添加与一个寡核苷酸序列互补的核苷酸。后一个寡核苷酸序列称为“模板”，引物与之退火。扩增的PCR产物定义为包括在延伸引物5’端之间的区域。因为引物有给定的序列，产物相对于引物序列也将有不同的末端。引物延伸反应用20个皮摩尔(pmols)的每一种寡核苷酸和1皮克的模板质粒DNA进行35次循环(1次循环限定为94℃一分钟，50℃两分钟及72℃三分钟)。反应混合物用等体积的苯酚/氯仿(50％苯酚及50％氯仿，体积比)抽提去除蛋白。包含扩增的DNA的水相及溶剂相在微型离心机(Model 5414Eppendorf Inc,Fremont CA.)中离心5分钟分离。为了沉淀扩增的DNA而将水相回收并转移到一个新的离心管中，在其中加入1/10体积的3MNaOAc(pH5.2)和2.5倍体积的乙醇(100％贮存在-20℃)。将溶液混合并在干冰上放置20分钟。在微型离心机中离心10分钟沉淀DNA并去除溶液。DNA沉淀用70％乙醇洗涤，去除乙醇并用Speedvacconcentrator(Savant,Farmingdale,New York)干燥。沉淀重悬于25μl TE(20mM Tris-HCl pH7.9,1mM EDTA)。另外DNA也可用加入等体积的4M NH4OAc及1倍体积异丙醇沉淀〔Treco等，(1988)〕。将溶液混合并且在室温保持10分钟后离心。这些方法选择性地沉淀大于～20碱基的DNA片段并用于去除寡核苷酸引物。反应的四分之一被限制性酶消化了〔Higuche,(1989)〕，为了完善本反应而加热到70℃使酶灭活。
从连接混合物中回收重组质粒将大肠杆菌JM 101细胞制备为感受态从而可接受DNA。典型地，20～100ml细胞在LB培养基中生长到大约150 Klett单位的密度然后离心收集。细胞重悬在一半培养体积的CaCl2中并在4℃保持1小时。重新离心收集细胞并将细胞重悬在1/10培养体积的CaCl2中。将DNA加到150微升的这些细胞中，并将样品在4℃保持30分钟。将样品转移到42℃1分钟，加入1毫升LB培养基后，样品在37℃振荡1小时。将这些样品中的细胞涂在含有氨苄青霉素的平板上以挑选转化体。平板在37℃培养过夜。挑取单菌落，在加有氨苄青霉素的LB培养基中37℃搅动培养过夜。分离来自这些培养物的DNA作限制性分析。
培养基LB培养基(Maniatis等，1982)被用作供提取DNA用的细胞的生长。补加有1％酪蛋白水解物，酸水解的酪蛋白，Difco(Detroit,Michigan)的M9最低限度培养基被用于培养在其中生产重组融合分子的微生物细胞。M9培养基的组成如下3g/升KH2PO4,6g/l Na2HPO4,0.5g/l NaCl,1g/l NH4Cl,1.2mM MgSO4,0.025mM CaCl2,0.2％葡萄糖(0.2％甘油和AraBAD启动子),1％酪蛋白水解物，0.1ml/l痕量矿物质(每升108g FeCl3·6H2O,4.0g ZnSO4·7H2O,7.0CoCl2·2H2O,7.0g Na2MoO4·2H2O,8.0g CuSO4·5H2O,2.0gH3BO3,5.0g MnSO4·H2O,100ml浓盐酸)。细菌培养用琼脂被用于固体培养基并且液体和固体LB培养基都加入200微克每毫升的氨苄青霉素。
在大肠杆菌中使用recA启动子的载体对融合分子的生产携有所感兴趣的质粒的大肠杆菌菌株在添加酪蛋白水解物的M9培养基37℃生长，并在一个来自New Brunswick Scientific(Edison,New Jersy)的Gyrotory 76型水浴振荡。生长状况用Klett Summerson仪(绿色54滤光器),Klett Mfg.Co.(New York,New York)监测。当Klett值约为150时，移出培养物的等分试样(通常为1ml)以供蛋白质分析，在剩下的培养物中，加入于0.1N NaOH中的萘啶酮酸(10mg/ml)至终浓度为50μg/ml。加入萘啶酮酸后，将培养物在37℃下振荡3至4小时。为了使所需基因产物的产量达到最高，在细菌生长的始末应保持高度通气。用光学显微镜检查细胞中包涵体的存在，移出1ml培养物的等分试样以供蛋白质含量的分析用。
在大肠杆菌细胞质中产生的融合蛋白的分级分离纯化融合分子的第一步是声处理细胞。培养物的等分试样来自在声处理缓冲液中重悬的细胞沉淀，所述缓冲液的组分为10mM Tris,pH8.0,1mM EDTA,50mM NaCl及0.1mM PMSF。这些重悬的细胞用来自Heat Systems-Ultrasonics Inc.(Farmingdale,New York)的W-375型Sonicator细胞破碎仪(disrupter)的微头(microtip)进行几次重复的声波冲击处理。声处理的程度的监控是通过光学显微镜下检查匀浆液进行的。当差不多所有的细胞都已破碎时，即将匀浆进行离心分级分离。包含大多数包涵体的沉淀颗粒(pellets)中高度富含融合蛋白。
方法在大肠杆菌中以包涵体形式袁达的融合分子的提取，再折叠及纯化这些融合蛋白可用多种标准方法纯化。其中一些方法在Methods inEnzymology,Volume 182‘Guide to Protein Purification’edited byMurray Deutscher,Academic Press,San Diego,CA(1990)中有详细介绍。
在大肠杆菌中以不可溶包涵体形式生产的融合蛋白可在高浓度的变性剂中溶解，所述变性剂包括例如盐酸胍或包含二硫苏糖醇或β-巯基乙醇作为还原剂的尿素。将这些蛋白折叠为活性构型可通过不断的透析而使其中最后只含低浓度的变性剂并不含还原剂来进行。
在一些情况下，已折叠的蛋白可用结合到合适的基质上的亲合试剂例如单克隆抗体或受体亚单位的亲和试剂进行亲和纯化。可替代的，(或另外)可用各种层析方法中的任一种进行纯化，例如离子交换，凝胶过滤或疏水层析或反相HPLC。
hIL-3夹心ELISA融合蛋白的浓度可通过基于一个合适的亲和纯化抗体的夹心ELISA法确定。微量滴定板(Dynatech Immulon Ⅱ)用150μl山羊抗rhIL-3包被，该抗体的浓度是在100mM NaHCO3,pH8.2中大约为1μg/ml。该板在室温100％湿度的培养室中温育过夜。将各个板孔倒空并用200μl溶液在37℃和100％湿度下维持1小时以阻断板上残留的活性位点，所述溶液中包含10mM PBS,3％BSA及0.05％Tween 20,pH7.4。倒空各板孔并用包含0.05％Tween 20的150mM NaCl(洗涤缓冲液)洗4次。然后各孔加入包含rhIL-3标准，对照，样品或只含稀释缓冲液的稀释缓冲液150μl(10mM PBS中含0.1％BSA,0.01％Tween 20,pH7.4)。通过一种rhIL-3的贮存溶液，制备0.125ng/ml～5ng/ml浓度范围的标准曲线(浓度由氨基酸组合物分析确定)。将培养板在37℃及100％湿度下温育2.5小时。将板孔倒空并且每块板都用洗涤缓冲液洗4次。然后在每孔中加入150μl适度稀释(在方格盘测定形式中的确定)的与辣根过氧化物酶偶联的羊抗rhIL-3。将板在37℃及100％湿度温育1.5小时。将板孔倒空并将每块板用洗涤缓冲液洗4次。然后每孔加入150μl ABTS底物溶液(Kirkegaard及Perry)。将板在室温下温育直到包含5ng/ml rhIL-3的标准孔的颜色已变得足以产生0.5～1的光吸收，光吸收是在Dynatech微量滴定板读数器上读出，测定波长为410nm，参考波长为570nm。未知样品的免疫反应的rhIL-3的浓度由滴定板读数器提供的软件根据标准曲线算出。
下面的例子将用于更加详细的说明本发明，但也要明白本发明不限于这些具体的例子。
实施例1构建融合分子的表达质粒编码融合蛋白的质粒的构建由下述组成见于质粒，pMON 13288(美国专利申请系列PCT/US 93/11197号)的IL-3变异体蛋白，接着是因子Xa蛋白水解切割位点，接着是小鼠IgG 2b铰链区，其中用丝氨酸代替了半胱氨酸作为融合蛋白中两个融合蛋白之间的多肽接头序列并且接着是G-CSF。用EcoRⅠ(位于IL-3变异体基因的内部)和HindⅢ(位于IL-3变异体终止密码子之后)消化质粒pMON 13288并纯化3900碱基对的EcoRⅠ,HindⅢ限制性酶切片段。来源于pMON13288的遗传因子有β-内酰胺酶基因(AMP),pBR 327复制起点，recA启动子，g10L核糖体结合位点，编码(15～125)IL-3变异体基因15-105氨基酸的碱基，及噬菌体fl复制起点。设计用合成的寡核苷酸的互补的碱基对去替换IL-3变异体基因EcoRⅠ位点后的部分(编码106～125氨基酸的碱基)，编码因子Xa切割位点的DNA序列，编码多肽接头的DNA序列及用于克隆融合蛋白中第二个基因的AflⅢ限制位点的DNA序列。当寡核苷酸装配合适时，所得到的DNA序列能按读码框编码上述成分，并含有EcoRⅠ和HindⅢ限制性酶切末端。在该DNA序列中还构建有单一的限制性位点，以便后来用有相似功能的序列去替换特定的区域(例如其它的多肽接头区域)。为了可在融合蛋白的C末端位置克隆其它的基因，而在13288基因的末端构建了单一的SnaBⅠ限制性位点。在编码Xa因子切割位点的序列和编码多肽接头的区域之间构建了单一的XmaⅠ位点。在接头区后，构建了单一的AflⅢ位点，即允许进行融合蛋白中N端蛋白的克隆。将来源于pMON 13288的3900碱基对片段与装配的寡核苷酸连接并转化进一个合适的大肠杆菌菌株。所得的克隆用限制性分析进行筛选并进行DNA测序以确定得到了所需的DNA序列。将所得的质粒用做中间体，其它的基因可用NcoⅠ,HindⅢ片段的形式克隆入此质粒的AflⅢ和HindⅢ位点以产生所需的融合蛋白。NcoⅠ和AflⅢ所产生的突出端是相容的，但限制性识别位点的侧翼序列是不同的。克隆的结果导致NcoⅠ和AflⅢ位点的消失。上面所提到的限制性位点只是作为例子并且不限于上面所介绍的。也可将具有可替换该区域的功能的其它的单一限制性位点构建入质粒中。将编码所得的融合蛋白的质粒进行测序以确定获得了所希望的DNA序列。其它的IL-3变异体基因或其它的集落刺激因子基因可用相似的方式通过基因工程技术进行改变以产生合适的限制性位点，从而允许在上面所介绍的融合构建的C末端或N末端位点进行克隆。同样地，其它的肽酶切割位点或多肽接头也可被构建入融合质粒中。
实施例2融合蛋白的表达，提取，再折叠及纯化，例如pMON 13061，在大肠杆菌中以包涵体形式表达携带所感兴趣的质粒的大肠杆菌在37℃培养过夜，并在第二天早上用新鲜的加有酪蛋白水解物的M9培养基以大约1/50稀释。培养物在37℃剧烈振荡培养3～4小时以到达对数中期(mid-log)(OD=～1)。加入溶于0.1N NaOH中的萘啶酮酸(10mg/ml)到终浓度为50μg/ml。培养物在加入萘啶酮酸后再在37℃生长3～4小时。在细菌的整个生长过程中维持高度的通气状态，以使所希望的融合蛋白的生产能达到最大值。在融合蛋白在大肠杆菌中以不可溶的包涵体形式产生的情况下，需要在光学显微镜下检测包涵体的存在。
包含包涵体形式的融合分子的大肠杆菌细胞用声处理裂解。在10mM Tris-HCl pH8.0和1mM EDTA中的10％(w/v)的细胞悬液被每分钟3～4次的脉冲处理，该脉冲通过使用一个来自HeatSystems-Ultrasonics Inc.(Farmingdale,New York)的SonicatorCell disrupter,Model W-375而得到。细胞的裂解程度通过在光学显微镜下检查细胞而进行监测。当基本上所有的细胞都已裂解时，即通过2800×g离心20分钟而收集包涵体。通过将包涵体沉淀以在声处理缓冲液中10％重悬并如上所述而进行离心，将包涵体洗二次。
融合分子的溶解是将1克包涵体放入10ml含50mM Tris-HClpH9.5及5mM DTT的8M尿素中，用Bio Homogenizer混合10～30秒钟然后在4℃轻微搅动1～2小时而实现的。已溶解的融合蛋白在47,000×g离心15分钟进行澄清。
将该蛋白质折叠为活性构型是通过在30分钟时间内用高于10mMTris-HCl pH9.5中的2.3M的尿素将蛋白质稀释8倍以将尿素的浓度降低为3M来实现的。一般在2～3M的尿素中进行融合分子的折叠，尽管较高浓度的尿素也允许折叠。在这些接触空气的条件下轻轻搅动融合分子，直至蛋白质折叠及二硫键的形成完全。折叠的进程用反相高效液相色谱(RP-HPLC)进行监测，条件为0.46×15厘米Vydac C4柱子(Hesperia,California)，线性的35％～65％的乙腈(CH3CN)/0.1％三氟乙酸(TFA)梯度，1ml/min进行25分钟。
折叠完全之后，将融合蛋白溶液的pH值用冰醋酸降到5.0并在4℃保温。1小时后，以47,000×g离心15分钟澄清该溶液。用乙酸将上清的pH降到4.0并用0.45μ的滤器过滤以澄清溶液。滤液对100倍的10mM乙酸铵，pH4.0，透析2次。用NaOH将透析后溶液的pH升为6.5。中和后的溶液然后以每毫升树脂2mg融合蛋白上样到用10mMTris-HCl pH6.5平衡的DEAE Fast Flow柱上(PharmaciaPiscataway,NJ)。融合蛋白用在平衡缓冲液中的50～150mM线性梯度的NaCl用0.28cm/min的线性流速洗脱12小时。通过RP-HPLC分析，收集93％或更高纯度的级分。将收集的级分对100倍的10mMTris-HCl pH7.5透析2次。透析后的蛋白溶液用0.45μ的滤器除菌过滤并在4℃保存。RP-HPLC和阳离子交换层析如CM Fast Flow也可单独使用或与DEAE层析一起使用以纯化融合蛋白。
纯化的融合蛋白用RP-HPLC，电子喷洒质谱仪，IEF，及SDS-PAGE进行分析。蛋白的数量通过氨基酸组合物及Bradford蛋白测定进行。
在一些情况下，折叠的蛋白质可用结合到合适的基质上的亲和试剂如单克隆抗体或受体亚单位进行亲和纯化。可替代地，(或另外)纯化可通过各种层析方法中的任一种进行，例如离心交换，凝胶过滤或疏水层析或反相HPLC。
这些和其它的蛋白质纯化方法在《酶学方法》，182卷‘蛋白质纯化指导’Murray Deutscher编，学术出版社，圣地亚哥，加利福尼亚(1990)中有详细描述。
实施例3融合蛋白体外活性的确定融合蛋白的浓度可通过基于亲和纯化的多克隆抗体的夹心ELISA法确定。另外，蛋白质的浓度可由氨基酸组合物确定。与天然IL-3,IL-3变异体或G-CSF单独或者一起相比，融合分子的生物活性可由多种体外测定法确定。其中一种测定法是AML-193细胞增殖测定。AML-193细胞对IL-3和G-CSF起反应，这就使IL-3变异体/G-CSF融合蛋白的结合的生物活性可以得到确定。另外，其它因子依赖的细胞系，如小鼠IL-3依赖的细胞系M-NFS-60(ATCC.CRL 1838)或32D也可被使用。IL-3的活性是种属特异性的但G-CSF不是，因此IL-3变异体/G-CSF融合蛋白中G-CSF组分的生物活性可以独立地进行确定。甲基纤维素测定法可用于确定IL-3变异体/G-CSF融合蛋白在造血生成祖细胞的扩增及体外各种不同类型造血生成集落的模式中的作用。甲基纤维素测定法可评估前体细胞的频率，因为该方法可测定每100,000输入细胞中祖细胞的频率。长期的，基质依赖的培养物可被用于描绘初始的祖细胞及干细胞。该方法可被用于确定是否融合分子刺激了很初始的祖细胞和/或干细胞的扩增。另外，可进行有限稀释培养以便指示由融合分子所刺激的初始的祖细胞的频率。
因子Xa切割位点在纯化和重折叠后可用于切割融合蛋白以将融合蛋白的IL-3和G-CSF组分分离开。用因子Xa切割之后，融合蛋白的IL-3和G-CSF组分可被纯化为均一的形式，并单独测定以证明两种组分在以融合蛋白形式被表达，再折叠及纯化后是以活性构型存在的。
实施例4pMON 13018的构建构建pMON 13018，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列的质粒。来自pMON 13288的3900碱基对的EcoRⅠ,HindⅢ限制性片段与下面的一对退火的互补的寡核苷酸连接Oligo #88Cterm1[SEQ ID NO:91]Oligo #88Cterm4[SEQ ID NO:92]Oligo #88Xa2[SEQ ID NO:93]Oligo #88Xa5[SEQ ID NO:94]Oligo #Glyn3[SEQ ID NO:95]Oligo #Glyn6[SEQ ID NO:96]装配的寡核苷酸产生EcoRⅠ和HindⅢ限制性末端及编码(15-125)hIL-3变异体13288的106～125氨基酸的DNA序列，以及编码包括因子Xa切割位点和氨基酸序列(Gly2Ser)2的多肽接头1(表1)的DNA序列。连接产物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化体细菌。从生长在LB培养基中的一个菌落中提取质粒DNA。对DNA测序以确定序列是应该有的寡核苷酸组成。构建pMON 13018的简图如图2所示。
实施例5pMON 13019的构建构建pMON 13019，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列的质粒的。来自pMON 13018的4014碱基对的XmaⅠ/AflⅢ限制性片段与下面的一对已退火的互补的寡核苷酸连接Oligo #IgG2b1[SEQ ID NO:97]Oligo #IgG2b2[SEQ ID NO:98]装配的寡核苷酸产生XmaⅠ和AflⅢ限制性末端以及编码由因子Xa切割位点和小鼠IgG2b铰链区组成的多肽接头4(表1)的氨基酸9-33的DNA序列。连接反应物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化体细菌。从生长在LB培养基中的菌落中提取质粒DNA。对DNA测序以确定该序列是上面所说的寡核苷酸。
实施例6pMON 13024的构建构建pMON 13024，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列的质粒。将来自pMON 13010的4091个碱基对的NheⅠ,HindⅢ限制性片段与下面一对已退火的互补的寡核苷酸连接Oligo #GCSFSna1[SEQ ID NO:99]Oligo #GCSFSna2[SEQ ID NO:100]装配的寡核苷酸产生NheⅠ和HindⅢ限制性末端，在G-CSF基因的3’端产生SnaBⅠ限制性位点，以及编码G-CSF 155-175氨基酸的DNA序列。G-CSF基因后的终止密码子被去掉并且SnaBⅠ的识别位点的DNA序列在G-CSF的C-末端读码框内编码氨基酸Tyr,Val。将连接反应物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。从生长在LB培养基中的菌落中提取质粒DNA。对DNA测序以确定DNA序列是上面的寡核苷酸。
实施例7pMON 13027的构建构建pMON 13027，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列的质粒。质粒pMON 13018的DNA被限制性酶NcoⅠ和SnaBⅠ消化，结果产生3704个碱基对的NcoⅠ,SnaBⅠ片段，质粒pMON 13024的DNA被NcoⅠ和SnaBⅠ消化产生528个碱基对的NcoⅠ,SnaBⅠ片段。将限制性片段连接，并将连接混合物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，用限制性分析及测序以确定为正确的插入。
实施例8pMON 13032的构建构建pMON 13032，该质粒是作为一个中间体质粒而用于构建包含编码融合蛋白DNA序列的质粒。pMON 15130质粒的DNA被限制性酶NcoⅠ和SnaBⅠ消化并产生一个29个碱基对的NcoⅠ和SnaBⅠ片段。pMON 13024质粒的DNA被NcoⅠ和SnaBⅠ消化结果产生一个528个碱基对的NcoⅠ,SnaBⅠ片段。将限制性片段连接并将连接混合物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，并用限制性分析，及序列测定以确定为正确的插入。
实施例9pMON 13041的构建构建pMON 13041，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列的质粒。来自pMON 13018的4018个碱基对的SnaBⅠ/XmaⅠ限制性片段与下列已退火的互补的寡核苷酸连接Oligo #Lysxa1[SEQ ID NO:101]Oligo #Lysxa2[SEQ ID NO:102]装配的寡核苷酸产生SnaBⅠ和XmaⅠ限制性末端及编码由因子Xa切割位点，其中的Arg换成了Lys及氨基酸序列(Gly3Ser)2组成的多肽接头2(表1)的氨基酸1～8的DNA序列。连接反应物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。从在LB培养基生长的菌落中提取DNA。进行DNA测序以确定该序列是上述的寡核苷酸。
实施例10pMON 13042的构建构建pMON 13042，该质粒是作为一个中间体质粒而用于构建包含编码融合蛋白的DNA序列的质粒的。来自pMON 13018的4018个碱基对的SnaBⅰ/XmaⅠ限制性片段与下面的一对已退火的互补的寡核苷酸连接Oligo #Glyxa1[SEQ ID NO:103]Oligo #Glyxa2[SEQ ID NO:104]装配的寡核苷酸产生SnaBⅠ和XmaⅠ限制性末端以及编码多肽接头3(表1)的DNA序列。多肽接头3由下列的氨基酸序列组成Tyr Val GluGly Gly Gly Ser Pro(Gly3Ser)2Asn〔SEQ ID NO:190〕。连接反应物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。从在LB培养基中生长的菌落中提取质粒DNA。进行DNA测序以确定该DNA序列是上述的寡核苷酸。
实施例11pMON 13046的构建构建pMON13046，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白DNA序列的质粒的。pMON 13048质粒的DNA被限制性酶NcoⅠ及NsiⅠ消化，结果产生一个3873个碱基对的NcoⅠ,NsiⅠ片段。它编码hIL-3变异体的pMON 13416质粒(美国专利申请系列第PCT/US 93/11197号)，被NcoⅠ和NsiⅠ消化，结果产生170个碱基对的NcoⅠ,NsiⅠ片段。将限制性片段连接，连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，作限制性分析，测序以确定所插入的为正确的序列。
实施例12pMON 13047的构建构建pMON 13047，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白DNA序列的质粒的。pMON 13019质粒的DNA被限制性酶NcoⅠ和NsiⅠ消化，结果产生一个3918个碱基对的NcoⅠ,NsiⅠ片段。pMON13416质粒的DNA被NcoⅠ和NsiⅠ消化，结果产生170个碱基对的NcoⅠ,NsiⅠ片段。将限制性片段连接，并将连接反应混合物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，作限制性分析，测定序列以确定为正确的插入。
实施例13pMON 13478的构建一个以PUC18为基础的包含所操作的编码人粒细胞集落刺激因子(hG-CSF)基因的质粒来自R & D Systems(目录#BBG 13,Minneapolis MN)。将该质粒称为pMON 13457。将来自pMON 13457的3157个碱基对的ApaⅠ,HindⅢ片段与下面的退火的互补的寡核苷酸对连接Oligo #hgcsfma1[SEQ ID NO:111]Oligo #hgcsfma2[SEQ ID NO:112]装配的寡核苷酸产生了HindⅢ和ApaⅠ限制性末端，一个内部的NcoⅠ限制性位点，及编码hG-CSF前四个氨基酸(Thr Pro Leu Gly)的DNA序列并且该编码过程由甲硫氨酸起始，接着是一个丙氨酸。甲硫氨酸和丙氨酸是为了在大肠杆菌中表达而增加的。连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA并测序以确定为正确的插入。所得到的质粒称为pMON 13478。
实施例14pMON 13498的构建来自pMON 13478的3163个碱基对的NcoⅠ,ApaⅠ片段与下面的一对已退火的互补的寡核苷酸连接Oligo #hgcsfat3[SEQ ID NO:115]Oligo #hgcsfat4[SEQ ID NO:116]装配的寡核苷酸产生了NcoⅠ及ApoⅠ限制性末端，并使编码成熟hG-CSF前四个氨基酸(Thr Pro Leu Gly)的DNA序列的A/T含量最大化。改变DNA序列中A/T的含量是为了增加在大肠杆菌中蛋白质的表达水平。将连接反应混合物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA并测序以确定为正确的插入。寡核苷酸的ApaⅠ的限制性末端与ApaⅠ位点相容，但ApaⅠ识别序列发生了变化。所得到的质粒称为pMON 13498。所进行的对hG-CSF基因的修饰见DNA序列〔SEQ ID NO:178〕。
实施例15pMON 13010的构建pMON 5743质粒(Olins及Rangwala)的DNA被限制性酶NcoⅠ和EcoRⅠ消化，结果产生一个3633个碱基对的NcoⅠ,EcoRⅠ片段。质粒pMON 13418的DNA被NcoⅠ及EcoⅠ消化，结果产生一个542个碱基对的NcoⅠ,EcoRⅠ片段。将限制性片段连接，并用连接反应混合物去转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，作限制性分析，并测序以确定是正确的插入。pMON13010质粒编码如下的氨基酸序列肽#Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser PheLeu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg AlaGly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu ValSer Tyr Arg Val Leu ArG His Leu Ala Gln Pro [SEQ ID NO:161]DNA序列#〔SEQ ID NO:178〕编码上述的pMON 13010的多肽。
实施例16pMON 13499的构建来自pMON 13478的3163个碱基对的NcoⅠ,ApaⅠ片段与下面一对已退火的互补的寡核苷酸连接Oligo #hgcsfat1[SEQ ID NO:113]Oligo #hgcsfat2[SEQ ID NO:114]装配的寡核苷酸产生NcoⅠ及ApoⅠ的限制性末端，以及使编码hG-CSF前三个氨基酸(Thr Pro Leu)的DNA序列的A/T含量最大化。DNA序列中A/T含量的改变是为了增加在大肠杆菌中的表达水平。连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，并测序以确定为正确的插入。所得到的质粒称为pMON 13499。所进行的对hG-CSF基因的修饰见DNA序列〔SEQ ID NO:177〕。
实施例17pMON 13033的构建来自pMON 13499的3117个碱基对的ApaⅠ,BstⅪ片段与下面一对已通火的互补的寡核苷酸连接Oligo #gcys18[SEQ ID NO:107]Oligo #gcys1810[SEQ ID NO:108]装配的寡核苷酸产生ApaⅠ和BstⅪ限制性末端，并且编码hG-CSF的5～26氨基酸，但17位氨基酸由丝氨酸替换了半胱氨酸除外。用丝氨酸替换半胱氨酸是为了增加分离自大肠杆菌的蛋白质在体外的再折叠效率。连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA并测序以确定插入序列正确。所得到的质粒称为pMON 13033。所进行的对hG-CSF基因的修饰见DNA序列〔SEQ ID NO:179〕。
实施例18pMON 13037的构建pMON 5743质粒的DNA，用限制性酶NcoⅠ和EcoRⅠ消化，结果产生一个3633个碱基对的NcoⅠ,EcoRⅠ片段。pMON 13033质粒的DNA用NcoⅠ和EcoRⅠ消化，结果产生一个542个碱基对的NcoⅠ,EcoRⅠ片段。将限制性片段连接，并将连接混合物用于转化大肠杆菌K-12菌株JM101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，作限制性分析，并测序以确定插入是正确的。质粒pMON 13037编码如下的氨基酸序列肽#Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser PheLeu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp GlyAla Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys HisPro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro TrpAla Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala GlyCys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly LeuLeu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr LeuAsp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile TrpGln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro ThrGln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg AlaGly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu ValSer Tyr Arg Val Leu Arg His Leu Ala Gln Pro[SEQ ID NO:162]DNA序列#〔SEQ ID NO:179〕编码上述的pMON 13037多肽。
实施例19pMON 13011的构建以pUC 18为基础的包含所操作的编码人抗粒细胞巨噬细胞集落刺激因子(hGM-CSF)的质粒得自R & D Systems(目录#BBG12,Minneapolis MN)。该质粒称为pMON 13458。来自pMON 13458的2986个碱基对的NcoⅠ,BsmⅠ片段与下面一对已退火的互补的寡核苷酸连接Oligo #gm-aup[SEQ ID NO:105]Oligo #gm-alow[SEQ ID NO:106]
装配的寡核苷酸产生了NcoⅠ和BsmⅠ限制性末端及编码hGM-CSF前19个氨基酸的DNA序列。为了增加在大肠杆菌中的表达水平，而将编码3,4,5,7,9,11,12,13及15氨基酸的DNA序列变成大肠杆菌优选的密码子。连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在包含氨苄青霉素的平板上筛选转化株。提取质粒DNA并测序以确定所插入的序列是正确的。所得到的质粒称为pMON13011。所进行的hGM-CSF基因的修饰见DNA序列〔SEQ IDNO:176〕。
实施例20pMON 13012的构建pMON 5743质粒的DNA被限制性酶NcoⅠ和EcoRⅠ消化，结果产生一个3633个碱基对的NcoⅠ和EcoRⅠ片段。pMON 13011质粒的DNA用NcoⅠ和EcoRJ消化，结果产生一个398个碱基对的NcoⅠ,EcoRⅠ片段。将限制性片段连接，并将连接反应混合物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，进行限制性分析，并测序以确定插入是正确的。质粒pMON 13012编码下述的氨基酸序列肽#Met Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp GluHis Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu SerArg Asp Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile SerGlu Meu Phe Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg LeuGlu Leu Tyr Lys Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu LysGly Pro Leu Thr Met Met Ala Ser His Tyr Lys Gln His Cys ProPro Thr Pro Glu Thr Ser Cys Ala Thr Gln Ile Ile Thr Phe GluSer Phe Lys Glu Asn Leu Lys Asp Phe Leu Leu Val Ile Pro PheAsp Cys Trp Glu Pro Val Gln Glu [SEQ ID NO:160]DNA序列#〔SEQ ID NO:176〕编码上述的pMON 13012多肽。
实施例21pMON 5865的构建以pUC 18为基础的包含所操作的编码人白介素6(hIL-6)的基因的质粒得自British Biotech(目录#BBG 17)。来自该质粒的3170个碱基对的HindⅢ/BstⅪ片段与下面一对已退火的互补的寡核苷酸连接Oligo #HIL6231[SEQ ID NO:109]Oligo #HIL6232[SEQ ID NO:110]装配的寡核苷酸产生了HindⅢ和BstⅪ限制性位点以及编码hIL-6前10个氨基酸加上为大肠杆菌蛋白表达所需的N末端Met Ala的DNA序列。该寡核苷酸还在该基因的5’末端产生了一个NcoⅠ位点。为了增加在大肠杆菌中的表达水平，而将编码前10个氨基酸的密码子变成了大肠杆菌优选的密码子。连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化菌。提取质粒DNA并测序以确定所插入的序列是正确的。所得到的质粒称为pMON 5865。所进行的hG-CSF基因的修饰见DNA序列〔SEQ ID NO:175〕。
实施例22pMON 13040的构建质粒pMON 5743的DNA用限制性酶NcoⅠ和EcoRⅠ消化，结果产生一个3633个碱基对的NcoⅠ,EcoRⅠ片段。质粒pMON 5865的DNA用NcoⅠ和EcoRⅠ消化，结果产生一个572个碱基对NcoⅠ,EcoRⅠ片段。将限制性片段连接，并将连接反应混合物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化菌。提取质粒DNA，作限制性分析，以及测序以确定插入是正确的。质粒13040编码下面的氨基酸序列肽#Met Ala Pro Val Pro Pro Gly Glu Asp Ser Lys Asp Val Ala AlaPro His Arg Gln Pro Leu Thr Ser Ser Glu Arg Ile Asp Lys GlnIle Arg Tyr Ile Leu Asp Gly Ile Ser Ala Leu Arg Lys Glu ThrCys Asn Lys Ser Asn Met Cys Glu Ser Ser Lys Glu Ala Leu AlaGlu Asn Asn Leu Asn Leu Pro Lys Met Ala Glu Lys Asp Gly CysPhe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu Val Lys Ile IleThr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr Leu Gln AsnArg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln Met SerThr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn LeuAsp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu LeuThr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr ThrHis Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser LeuArg Ala Leu Arg Gln Met [SEQ ID NO:163]DNA序列#〔SEQ ID NO:175〕编码上述的pMON 13040多肽。
实施例23pMON 15931的构建构建pMON 15931，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列质粒的。将编码丝状噬菌体fd(Schaller等，1975)的pⅢ蛋白的富含(Gly-Ser)的间隔区的DNA序列用PCR技术扩增。一个包含编码丝状噬菌体fd pⅢ蛋白基因的质粒被用作PCR反应的模板，并用下面的寡核苷酸做为引物Oligo # prefor[SEQ ID NO:117]Oligo # revpre[SEQ ID NO:118]PCR的引物扩增反应产生如下的DNA序列CCTGTCAACC CGGGCGGCGG CTCTGGTGGT GGTTCTGGTG GCGGCTCTGAGGGTGGCGGC TCTGAGGGTG GCGGTTCTGA GGGTGGCGGC TCTGAGGGTGGCGGTTCCGG TGGCGGCTCC GGTTCCGGTA ACATGTATTA TGA[SEQ ID NO:181]所说的DNA序列编码由因子Xa切割位点和fd噬菌体pⅢ蛋白富含(Gly-Ser)已组成的多肽接头7(表1)的9～49氨基酸。PCR产生的片段用XmaⅠ和AflⅢ消化并与来自pMON 13018的4014个碱基对的XmaⅠ,AflⅢ片段连接。连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化菌。提取质粒DNA，做限制性分析，以及测序以确定插入是正确的。
实施例24pMON 15930的构建构建pMON 15930，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列的质粒的。编码丝状噬菌体fd(Schaller等，1975)pⅢ蛋白的富含(Gly-Ser)的间隔区及一些侧翼氨基酸的DNA序列用PCR技术扩增。一个包含编码丝状噬菌体fd pⅢ蛋白基因的质粒被用做PCR反应的模板，用下面的寡核苷酸作为引物Oligo # forxtra[SEQ ID NO:119]Oligo # xtrarev[SEQ ID NO:120]PCR引物扩增反应产生如下的DNA序列ATCGTCTGAC CTCCCGGGCC TCCTGTCAAT GCTGGCGGCG GCTCTGGTGGTGGTTCTGGT GGCGGCTCTG AGGGTGGCGG CTCTGAGGGT GGCGGTTCTGAGGGTGGCGG CTCTGAGGGT GGCGGTTCCG GTGGCGGCTC CGGTTCCGGTGATTTTGATT ATGAAAACAT GTCAAACGCT [SEQ ID NO:182]上述的DNA序列编码由因子Xa切割位点和fd噬菌体pⅢ蛋白富含(Gly-Ser)区所组成的多肽接头8(表1)的9～70个氨基酸。将PCR产生的片段用XmaⅠ和AflⅢ消化并与来自pMON 13018的4014个碱基对的XmaⅠ,AflⅢ片段连接。在含氨苄青霉素的平板上筛选转化菌。提取质粒DNA，作限制性分析，以及测序以确定插入序列是正确的。
实施例25pMON 13038的构建构建pMON 13038，该质粒是作为一个中间体质粒用于构建包含编码融合蛋白的DNA序列的质粒的。pMON 13019质粒的DNA被限制性酶NcoⅠ和SnaBⅠ消化，结果产生一个3749个碱基对的NcoⅠ,SnaBⅠ片段。pMON 13024质粒的DNA用NcoⅠ和SnaBⅠ消化，结果产生一个528个碱基对的NcoⅠ,SnaBⅠ片段。将限制性片段连接，并用连接反应混合物去转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化菌。提取质粒DNA，做限制性分析，以及测序以确定插入正确的。所得到的质粒称为pMON 13038。
实施例26pMNO 13021的构建质粒pMON 13018的DBA用限制性酶AflⅢ和Hind消化，结果产生一个4023个碱基对的AflⅢ,HindⅢ片段。质粒pMON 13288的DNA用NcoⅠ和HindⅢ消化，结果产生一个345个碱基对的NcoⅠ,HindⅢ片段。限制性片段被连接，并将连接反应混合物用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化菌。提取质粒DNA，做限制性分析，以及测序确定插入是正确的。一个构建该质粒pMON13021的简图如图2所示。质粒pMON 13021编码是如下氨基酸序列的融合蛋白肽#〔SEQ ID NO:125〕DNA序列#〔SEQ ID NO:54〕编码所述的pMON 13021多肽。
实施例27pMON 13022的构建质粒pMON 13018的DNA被限制性酶AflⅢ和HindⅢ消化，结果产生一个4023个碱基对的AflⅢ,HindⅢ片段。质粒pMON 13012的DNA用NcoⅠ和HindⅢ消化，结果产生一个586个碱基对的Nco,HindⅢ片段。限制性片段被连接，连接反应混合物被用于转化大肠杆菌K-12菌株JM 101。在含氨苄青霉素的平板上筛选转化株。提取质粒DNA，作限制性分析，以及测序以确定插入是正确的。质粒pMON 13022编码是下列氨基酸序列的融合蛋白肽#〔SEQ ID NO:141〕DNA序列#〔SEQ ID NO:55〕编码所述的pMON 13022多肽。
实施例28-62融合蛋白的进一步的例子，部分包括如表2所示的hIL-3变异体。包含编码表2中融合蛋白基因的质粒由材料与方法及本文所包含的实施例尤其是实施例1,9,10,26及27中所述的方法构建。如表2所示的DNA限制性片段被连接，并用所得到的大肠杆菌表达质粒(表2)包含编码所指的多肽融合分子(表2)DNA序列。多肽融合分子由两个集落刺激因子(R1和R2)通过一个多肽接头(L)(表1)融合而成，以通式R1-L-R2表示。表2中的一些编码多肽融合分子的基因以一个NcoⅠ,HindⅢ限制性片段的形式从大肠杆菌表达载体中转移到一个哺乳动物细胞(BHK)表达载体pMON 3934中。大肠杆菌和BHK表达质粒如表2所示。表2中的一些多肽融合分子在AML 193.1细胞中的生物活性，生长启动活性如表3所示。表2中的一些多肽融合分子的在甲基纤维法测定的生物活性如图3-7所示。
表1多肽接头名称及氨基酸序列
表2
表2(续)
表2(续)
>表2(续)
表2(续)
实施例63c-mp1配体(Meg-CSF)的1-332和1-153氨基酸形式的分离A．逆转录反应(c-mp1配体的序列以Genbank登记号#L33410为基础)。人胎儿肝A+RNA得自Clontech(Palo Alto,CA)。第一条链的cDNA反应使用一个来自A Invitrogen(San Diego,CA)的cDNACycleTM试剂盒进行。
B．聚合酶链式反应在逆转录反应(RT)之后，经使用寡核苷酸引物的PCR扩增1-332 c-mp1配体，引物c-mp1 NcoⅠ〔SEQ ID NO:169〕在紧接基因的5’末端之前产生一个NcoⅠ位点，而引物c-mp1 EcoRⅠ〔SEQID NO:169〕紧接3’末端终止密码产生一个EcoRⅠ位点。在RT反应之后，用引物c-mp1 NcoⅠ〔SEQ ID NO:169〕和3’端引物c-mp1 HindⅢ〔SEQ ID NO:171〕扩增1-153 c-mp1配体，其中3’端引物能紧接氨基酸153的密码子产生一个终止密码子和一个HindⅢ位点。
实施例64pMON 26448的构建1-153 c-mp1配体的PCR产物为了被亚克隆入pMON 3934而被限制性酶NcoⅠ和HindⅢ消化。pMON 3944是一个来自pMON 3359〔Hippenmeyer等，(1993)〕的哺乳动物表达载体，但它在IE 110启动子和poly-A信号之外还包括一个修饰的人IL-3信号肽序列。该信号肽序列两侧由BamHⅠ和NcoⅠ限制性酶位点包围，这就方便了NcoⅠ,HindⅢ片段形式的基因的克隆和表达。HindⅢ位点在NcoⅠ位点的3’端。信号肽的DNA序列如下所示(限制性酶位点如上所示)。NcoⅠ位点内的ATG(甲硫氨酸)密码子也位于信号肽起始ATG的阅读框内(下划线的)；BamHⅠGGATCCACCATGAGCCGCCTGCCCGTCCTGCTCCTGCTCCAACTCCTGGTCCGCCCCMetSerArgLeuProValLeuLeuLeuLeuGlnLeuLeuValArgProNcoⅠGCCATGG [SEQ ID NO:140]AlaMet [SEQ ID NO:187]
所得到的质粒称为pMON 26448。质粒pMON 26448编码是下列氨基酸序列的融合分子肽#Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu SerLys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser GlnCys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro AlaVal Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu ThrLys Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu GlyVal Met Ala Ala Arg Gln Gln Leu Gly Pro Thr Cys Leu Ser SerLeu Leu Gly Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly AlaLeu Gln Ser Leu Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg ThrThr Ala His Lys Asp Pro Asn Ala Ile Phe Leu Ser Phe Gln HisLeu Leu Arg Gly Lys Val Arg Phe Leu Met Leu Val Gly Gly SerThr Leu Cys Val Arg [SEQ ID NO:164]DNA序列#〔SEQ ID NO:180〕编码所述的pMON 26448多肽。
实施例65分离有修饰的C末端的c-mp1配体(Meg-CSF氨基酸1～153形式的cDNA序列A．逆转录酶反应(c-mp1配体序列以Genbank登记号#33410为基础)。人胎儿肝A+RNA得自Clontech(Palo Alto,CA)。第一条链的cDNA反应用一个得自Invitrogen(San Diego,CA)的cDNACycleTM试剂盒进行。
B．聚合酶链式反应在逆转录酶(RT)反应之后，经使用寡核苷酸引物的PCR扩增1-332 c-mp1配体，其中引物c-mp1 NcoⅠ〔SEQ ID NO:169〕紧接基因的5’末端之前产生一个NcoⅠ位点，而引物c-mpⅠ EcoRⅠ〔SEQID NO:170〕紧接终止密码子产生一个EcoRⅠ位点。用上面的PCR反应做为模板，再用引物c-mp1 NcoⅠ〔SEQ ID NO:169〕和3’端引物，Eco-mp1〔SEQ ID NO:172〕扩增1-153 c-mp1配体，其中3’引物紧接3’端153氨基酸密码子产生一个EcoRⅠ位点并编码该基因C末端读码框内的Glu Phe氨基酸。1-153 c-mp1配体的PCR产物被NcoⅠ和EcoRⅠ消化。所得的467碱基对的NcoⅠ,EcoRⅠ限制性片段接着被克隆进一个中间体质粒中以产生融合多肽，该质粒在本文中实施例中有介绍。
实施例66pMON 26460的构建质粒pMON 13018的DNA用限制性酶AflⅢ和HindⅢ消化，结果产生一个4023个碱基对AflⅢ,HindⅢ片段。质粒pMON 26448的DNA用限制性酶NcoⅠ和HindⅢ消化，结果产生一个468个碱基对的NcoⅠ,HindⅢ片段。将限制性片段连接，并将连接混合物用于转化大肠杆菌。在含氨苄青霉素的平板上筛选转化菌，提取质粒DNA，作限制性分析，以及测序以确定插入是正确的。大肠杆菌表达质粒pMON 26460编码是下列氨基酸序列的融合分子肽#〔SEQ ID NO:165〕DNA序列#〔SEQ ID NO:183〕编码所述的pMON 20460多肽。
编码融合分子的基因以NcoⅠ,HindⅢ片段的形式被转移到哺乳动物表达载体pMON 3934中，所得到的质粒称为pMON 26463。
实施例67pMON 26461的构建将来自pMON 13057的4029碱基对的NcoⅠ,SnaBⅠ片段与来自实施例65的PCR产生的467碱基对的NcoⅠ,EcoRⅠ片段以及两个寡核苷酸(Ecosna1〔SEQ ID NO:173〕,Ecosna2〔SEQ ID NO:174〕)连接。连接反应的混合物被用于转化大肠杆菌。在含氨苄青霉素的平板上筛选转化菌。提取质粒DNA，作限制性分析，以及测序以确定插入是正确的。大肠杆菌表达质粒，pMON 26461编码是下列氨基酸序列的融合分子肽#〔SEQ ID NO:168〕DNA序列#〔SEQ ID NO:186〕编码上述的pMON 26461多肽。
将编码融合分子的基因以NcoⅠ,HindⅢ片段的形式转移到哺乳动物表达载体pMON3934中，所得到的质粒称为pMON 26464。
实施例68pMON 26471的构建将来自pMON 3935的3285个碱基对的NcoⅠ,HindⅢ片段与来自pMON 26462的362个碱基对的NcoⅠ,SmaⅠ限制性片段以及来自pMON26460的494个碱基对的SmaⅠ,HindⅢ片段连接，并将连接反应混合物用于转化大肠杆菌。在含链霉素的平板上筛选转化菌。提取质粒DNA，作限制性分析，以及测序以确定插入是正确的。大肠杆菌表达质粒pMON26471编码是下列氨基酸序列的融合分子肽#〔SEQ ID NO:166〕DNA序列#〔SEQ ID NO:184〕编码所述的pMON 26471多肽。
将编码融合分子的基因以NcoⅠ,HindⅢ片段的形式转移到哺乳动物表达载体pMON 3934中，所得到的质粒称为pMON26473。
实施例69pMON 26472的构建将来自pMON 3935的3285碱基对NcoⅠ,HindⅢ片段与来自pMON26461的481个碱基对Nco,SnaBⅠ限制性片段及来自pMON 3988的399个碱基对的SnaBⅠ,HindⅢ限制性片段连接，并将连接反应混合物用于转化大肠杆菌。在含链霉素的平板上筛选转化菌。分离质粒DNA，作限制性分析，并测序以确定插入序列是正确的。大肠杆菌表达质粒，pMON26472，编码是下列氨基酸序列的融合分子肽#〔SEQ ID NO:167〕DNA序列#〔SEQ ID NO:185〕编码所述的pMON 26472多肽。将编码融合分子的基因以NcoⅠ,HindⅢ片段的形式转移到哺乳动物表达载体pMON 3943中，所得到的质粒称为pMON 26474。
在不背离本发明的精神实质和发明范围的情况下，在读过这些内容之后，对于本领域的技术人员来讲，各种基本类型的例子将是显而易见的。希望所有其它的实施例都包括在所附的权利要求的范围之内。
有生物活性人白介素3的AML增殖测定法依赖于因子的细胞系AML 193得自美国典型培养物保藏中心(ATCC,Rockyille,MD)。该细胞系建自一个患有急性髓系白血病的患者，它是一个依赖生长因子的细胞系，它在补加有GM-CSF的培养基中显示出生长增强(Lange,B.,等.,(1987)；Valtieri,M.,等，(1987)。也有报道AML 193细胞有能在人IL-3存在下增殖的能力(Santeli,D.,等.,(1987))。一个该细胞系的变异体，AML193 1.3被使用，该变异体是在去除生长因子并使依赖细胞因子的AML细胞对生长因子饥饿24小时，然后在IL-3中做长时间的适应而获得。该细胞然后在含100U/ml IL-3的培养基的24孔培养板中以1×105细胞/孔重新种植。使细胞能在IL-3快速生长大约需3个月时间。这些细胞以后就在补加有人IL-3的组织培养基(见下)中以AML193 1.3细胞保存。
将AML 193 1.3细胞在冷的Hanks平衡盐溶液(HBSS,Gibco,GrandIsland,NY)中洗6次，方法是以250×g离心细胞悬液10分钟，然后倒掉上清液。沉淀细胞在HBSS中重悬，重复该操作直到完成了6次洗涤。用这种方法洗过6次的细胞，在组织培养培养基中以2×105～5×105活细胞/ml的密度重悬。该培养基的制备是在Iscove改良Dulbecco’s培养基(IMDM,Hazelton,Lenexa,KS)中加入白蛋白，转铁因子，脂类，2-巯基乙醇。加入牛白蛋白(Boehringer-Mannheim,Indianapolis,IN)浓度为500μg/ml；加入人转铁因子(Boehringer-Mannheim,Indianapolis,IN)的浓度为100μg/ml，加入大豆脂类(Boehringer-Mannheim,Indianapolis,IN)的浓度为50μg/ml；及加入2-巯基乙醇(Sigma,St.Louis,MO)的浓度5×10-5M。
如上所述在Costar 3596 96孔组织培养板中做三组人白介素3或融合蛋白(hIL-3突变蛋白)的系列稀释。在系列稀释完成后，每孔含50μl包含白介素3或融合蛋白的培养基。对照孔只含组织培养基(阴性对照)。通过在每孔中吸入50μl(2.5×104细胞)将如上所述所制备的AML 193 1.3细胞悬液加到各孔中。组织培养板在37℃,5％CO2饱和湿度下培养3天。在第3天，在50μl组织培养基中加入0.5μCi3H胸腺嘧啶(2Ci/mM,New England Nuclear,Boston,MA)。在37℃ 5％CO2潮湿空气下温育18-24小时。用一个TOMTEC细胞收获器(TOMTEC,Orange,CT)将细胞DNA收获到玻璃滤垫上(filtermats)(Pharmacial LKB,Gaithersburg,MD)，该收集器使用一个水洗循环，接着一个70％乙醇洗涤循环。将滤垫(filter mats)空气干燥并放入加有闪烁液(Scintiverse Ⅱ,Fisher Scientific St.Louis,MO或Betaplate Scintillation Fluid,Pharmacia LKB,Gaithersburg,MD)的样品袋中。在LKB Betaplate 1205型闪烁计数仪(PharmaciaLKB,Gaithersburg,MD)上计数每个组织培养孔的β发射，并将数值表示为掺入到每个组织培养孔细胞中的3H胸腺嘧啶的每分钟的计数。通过测定梯度浓度的白介素3或融合蛋白诱导的细胞增殖(3H胸腺嘧啶掺入)来定量每一个人白介素3样品或融合蛋白样品的活性。典型地，0.05pM-105pM的范围可在这些方法中闪烁测定。活性由测量能达到50％最大增殖的白介素3或融合分子的量确定〔EC50=0.5×(在所有测试的白介素3浓度的三个培养物中每孔3H胸腺嘧啶的掺入的每分钟的计数的最大平均值-有三个缺少白介素3的培养物中观察到的3H胸腺嘧啶掺入测定背景增殖〕。该EC50值也等于1个单位的生物活性。每一个测定中都用天然的白介素3作为一个对照标准，以便指定相对的活性水平。
一般地，融合蛋白在2000pM～0.06pM的浓度范围在系列的2倍的稀释液中滴定。融合分子生物活性与下面所介绍的标准相比较部分包含G-CSF,pMON 3987,pMON 3995,pMON 3997,pMON 26406,pMON 26433,pMON 26415,pMON 26416及pMON26430的蛋白融合物与等摩尔浓度的hG-CSF及pMON 13288或pMON13416的测量反应曲线相比较。部分包含GM-CSF,pMON 3989及pMON 3998的蛋白融合物与等摩尔浓度的hGM-CSF及pMON 13288的剂量反应曲线相比较。包含hIL-3变异体，二聚体，pMON 3988,pMON 26425,pMON 26427,pMON 26420,pMON 26429及pMON26431的蛋白融合物与pMON 13288或pMON 13416的剂量反应曲线相比。
每个样品的活性由给出50％最大反应的浓度通过给该数据提供一个四参数的计算模型而确定。发现样品的上平台(最大反应)与用于比较的标准没有不同。因此，每个样品相对效力的计算由对每个样品EC50的估算及上面所指的标准来确定。表3中所报道相对效力(标准的EC50被样品的EC50相除)除非特别指出是至少两次独立的测定的平均值。AML 193.1.3细胞的增殖对hIL-3,hGM-CSF及hG-CSF反应。因此，下面的其它的测定法是用于证明融合蛋白的G-CSF或GM-CSF部分是有活性的。增殖测定在使用pMON 13288的中和多克隆抗体的情况下进行。另外，含因子Xa切割位点的融合分子被切割然后纯化，并测定该两部分的增殖活性。这些实验表明融合蛋白的两部分都是有活性的。表3 AML细胞增殖测定
甲基纤维素测定法该测定法给出了集落刺激因子在体外刺激正常骨髓细胞产生不同的造血生成集落生长活性的合适的近似值(Bradley，等，1966,Pluznik，等，1965)。
方法从个体得到大约30ml新鲜的，正常的，健康的骨髓提取物。在无菌条件下，样品用在50ml圆锥形管(#25339-50 Corning,Corning MD)中的1×PBS溶液(#14040.059 Life technologies,Gaithersourg,MD.)进行1∶5的稀释。将Ficoll(Histopague 1077 Sigma H-8889)铺在稀释样品的底部并在300×g离心30分钟。回收单核细胞层并用1×PBS洗二次及1％BSA PBS(Cellpro.Co.,Bothel,WA)洗一次。计数单核细胞并用Ceprate LC(CD 34)试剂盒(Cellpro Co.,Bothel,WA)柱选择CD 34+细胞。这种分离能够进行，是因为在骨髓中所有的干细胞及祖细胞都显露出CD 34表面抗原。
培养分三组以1.0ml的终体积在一个35×10mm的培养皿中进行(Nunc # 174926)。培养用培养基购自Terry Fox Labs,。(HCC-4230培养基(Terry Fox Labs,Vancouver,B.C.,Canada)并将红细胞生成素)Amgen,Thousands Oaks,CA.)加入到培养基中。每皿加入3,000～10,000个CD 34+细胞。加入天然的IL-3和融合分子使终浓度为.001nM 10nM。天然IL-3和融合分子由自己制备。G-SCF(Neupogen)来自Amgen。培养物用一个3cc的注射器重悬并且是每皿分液1.0ml。对照(基线反应)培养物不加入集落刺激因子。阳性对照培养物加入条件培养基(PHA刺激的人细胞Terry Fox Lab,H2400)。培养物在37℃,5％CO2饱和湿度下温育。用40×物镜的Nikon倒置相差显微镜，在峰反应的天数上(10～11)计数定义为大于50个细胞的造血细胞集落。包含少于50个细胞的集落称为簇。另外，可将集落铺在载片上染色进行鉴定或挑取集落，重悬并甩到一个细胞甩片载片上进行染色。
人脐带血造血生长因子测定法一般用骨髓细胞作体外的造血细胞集落刺激因子(CSF)活性的测定。但是，人外周血并不是总能供应上，而且在供体之间有应该考虑的变异性。脐带血作为造血生成干细胞和祖细胞的来源，与骨髓是相似的(Broxmeyer等，1992；Mayani等，1993)。但与骨髓相反，在一般情况下，脐带血可更加方便的得到。通过从几个供体收集新鲜的细胞，或为此目的而建立一个低温保存细胞库，还有可能减小该测定法的变异性。通过改良培养条件，和/或分析谱系特异的标记，就有可能特异性地测定粒细胞/巨噬细胞集落(CFU-GM)，巨核细胞CSF活性，或高增殖潜力克隆形成细胞(HRP-CFC)的活性。
方法在脐带血收集的24小时内，用一个标准的密度梯度(1.077g/mlHistopaque)分离单核细胞。用几种方法进一步富集脐带血MNC中的干细胞和祖细胞，所述方法包括CD14-,CD34+细胞的免疫磁性选择；用来自Applied Immue Science(Santa Clare,CA)的镀层烧瓶淘洗筛选SBA-,CD34+级分；以及用Cellpro(Bothell,WA)抗生物素蛋白质柱做CD34+筛选。或者是新鲜分离的，或者是低温保藏的CD34+富集的级分都可用于该测定法中。对样品的每个系列稀释(浓度范围1pM～1204pM)的双重培养的准备都是在1ml包含不加生长因子的培养基的9％甲基纤维素中加入1×104细胞(来自Stem Cell Technologies,Vancouver,BC.Methocult H 4230)。在一些实验中，用包含红细胞生成素(EPO)的Methocult H 4330代替Methocult，或加入干细胞因子(SCF),50ng/ml(Biosource International,Camarillo,CA)。在培养7-9天之后，计数包含＞30个细胞的集落。为了排除在计数中的有目的倾向性，测定计数是随机的。
c-mp1配体增殖活性的分析方法1．骨髓增殖测定a．CD34+细胞的纯化在获得同意后，可从正常的同种骨髓供体得到15-20ml骨髓提取物。细胞在磷酸缓冲盐溶液中(PBS,Gibco-BRL)以1∶3稀释，在15ml Histopaque-1077(Sigma)上铺上30ml稀释液并以300 RCF离心30分钟。收集单核细胞层并在PBS中洗涤。按厂家的说明用亲和柱(Cellpro,Inc,Bothell WA)从单核细胞样品中富集CD34+细胞。在富集后，用结合荧光素的抗CD34单克隆抗体和结合藻红蛋白的CD38(Becton Dickinson,San Jose CA)做流式细胞术测定，CD34+细胞的纯度平均是70％。
将细胞在X-Vivo 10培养基(Bio-Wnittaker,Walkersville,MD)中以40,000细胞/ml重悬并在12孔组织培养板(Costar)中加入1ml。在一些孔中加入100ng/ml(pMON 5873)生长因子rhIL-3。变异体hIL-3,pMON 13288的使用浓度是10ng/ml或100ng/ml。通过将100μl上清液加入到1ml培养物中(大约10％稀释)，测定来自转染有编码c-mp1配体的质粒的BHK细胞的条件培养基。细胞在5％CO2,37％，饱和湿度的培养器中培养8-14天。
b．细胞收获和分析在培养阶段的末期，将会得到每一种条件下的总细胞计数。为了作荧光分析及倍性确定而将细胞在巨核细胞缓冲液中洗涤(MK缓冲液，13.6mM柠檬酸钠，1mM茶碱，2.2μM PGEI,11mM葡萄糖，3％w/v BSA，在PBS中，pH7.4)〔Tomer等，(1987)〕，重悬在500μl包含FITC标记的抗CD41a的抗体的MK缓冲液中并在MK缓冲液(1∶200,AMAC Westbrook,ME)中洗涤。为做DNA分析而将细胞在含0.5％Tween 20的MK缓冲液(Fisher,Fair Lawn NJ)中在冰上渗透20分钟，然后在0.5％Tween-20和1％多聚甲醛中(FisherChemical)中固定30分钟，接着在冰上在含RNA-ase(400U/ml)的55％v/v MK缓冲液(200mOsm)的碘化丙锭(Calbiochem,LaJolla Ca)(50μg/ml)中保温1～2小时。细胞在一个FACScan或Vantage流式细胞仪(Becton Dickison,San Jose,CA)上做分析。与红色荧光(PI)的线性和log信号一起收集绿色荧光(CD41a-FITC)以确定DNA的倍性。收集所有的细胞以确定CD41+细胞的百分比例。用LYSIS软件(Becton Dickison,San Jose,CA)进行数据分析。从流式细胞术分析中可得到表达CD41抗原的细胞的百分比(百分比)。CD41+细胞的绝对数(Abs)/ml计算如下(Abs)=(细胞计数)*(百分比)/100。
2．巨核细胞血纤蛋白凝块测定法如上所述分离富含CD34+的群落。将细胞在含/不含细胞因子的培养基中以25,000细胞/ml悬浮，所述培养基含有补加有0.3％BSA,0.4mg/ml去-转铁蛋白，6.67μM FeCl2,25μg/ml L-天门冬氨酸，500μg/ml E-氨基-n-己酸及青霉素/链霉素的基本IscovesIMDM培养基。在种入35mm平板之前，加入凝血酶)0.25单位/ml)以启动凝块形成。将细胞在37℃的潮湿的培养器中37℃5％CO2下培养13天。
在培养阶段结束时用甲醇∶丙酮(1∶3)固定平板，空气干燥并保存在-200C直到染色。一种应用包括抗CD41a,CD42及CD61的初级单克隆抗体的混合物(cocktail)的过氧化物酶免疫细胞化学染色方法被使用(Zymed,Histostain-SP.San Francisco,CA)。在染色后进行集落计数并分类如下阴性的，CFU-MK(小集落，1～2中心并大约少于25个细胞)，BFU-MK(大的，多中心集落大于25个细胞)或混合集落(阳性及阴性细胞二者的混合物)。
实施例70hIL-变异体，pMON 13288，及c-mp1配体融合分子的施用对巨核细胞的扩大比两个细胞因子之一的单用有大于加性的效应巨核细胞血纤蛋白凝块培养物的获得按方法部分所介绍的进行。pMON 26448是c-mp1配体(Meg-CSF)的1-153氨基酸形式。pMON 26463是一个包括hIL 3变异体，pMON 13288及1-153氨基酸形式的c-mp1配体的融合分子。在hIL 3变异体，pMON 13288存在下的培养，使除少数小的CFU-MK集落(23/114)外，主要增加的是巨核细胞标记阴性的集落(86/114，(表4))。pMON 26448单独使用除少数几个阴性集落(3/175)外，主要增加CFU-MK集落(172/175)。hIL3变异体，pMON 13288及pMON 26448的合用，大量增加的主要是BFU-MK型态的阳性集落(295/414)。同时还有阴性集落(119/414)。合用的阳性集落的总数要比两种细胞因子之一单独使用的集落数的加和要多。pMON 26463融合分子，得到与hIL3变异体，pMON 13288及pMON 26448三者合用相似的结果。阴性细胞的数目比hIL3变异体，pMON 13288少，可能是由于pMON 13288在制品中的较低的浓度所致(大约是作为融合分子的一部分10ng/ml对100ng/mlhIL3变异体，pMON13288)。表4
IL-3介导的人单核细胞硫化白三烯(Sulfidoleukotriene)的释放下述方法用于测定IL-3介导的人单核细胞硫化白三烯(Sulfidoleukotriene)的释放。
收集含肝素的人血并将其铺在一个等体积的便于使用培养基(密度1.077g/ml)的Ficoll-Paque(Pharmacia #17-,0840-02)上。Ficoll在使用前先加热到室温并使用干净的50ml的聚苯乙烯管。将Ficoll梯度使用一个H1000B转头在一个Sorvall RT6000B冷冻离心机中在室温以300×g旋转30分钟。仔细回收包含单核细胞的带，用Dulbecco’s磷酸缓冲盐溶液(Gib co Labotatories Cat.# 310-4040RK)将体积调整为50mls，在4℃以400×g旋转10分钟并小心上清。将细胞沉淀用HA缓冲液〔20mM Hepes(Sigma # H-3375),125mM NaCl(Fisher # S271-500),5mM KCl(Sigma # P-9541),0.5mM葡萄糖(Sigma # G-5000),0.025％人血清白蛋白(Calbiochem#126654)洗两次并在300×g,4℃离心10分钟。将细胞在HACM缓冲液中(HA缓冲液补加有1mM CaCl2(Fisher # C79-500)及1mM MgCl2(Fisher # M-33)以1×106细胞/ml重悬并转移到96孔组织培养板中，每孔180μl。使细胞在37℃适应15分钟。细胞被加入到每孔的10μls 20x储备的各种浓度的细胞因子所激活(典型地，100000,20000,4000,800,160,32,6.4,1.28,0 fM IL3)。将细胞在37℃温育15分钟。硫化白三烯的释放由添加的10μls 20X(1000nM)fmet-leu-phe(Calbiochem # 344252)终浓度50nMFMLP所激活并在37℃温育10分钟。将平板在4℃以350×g旋转20分钟。回收上清液并按厂家的说明用Cayman’s Leukotriene C4 EIA试剂盒(Cat.#420211)测定硫化白三烯(Sulfidoleukotrine)。在每个测定中，用天然hIL-3作为一个标准对照。
对本领域的技术人员进一步的细节可见T.Maniatis，等，MolecularCloning,A Laboratory Manual,Cold Spring Harbor Laboratory(1982)以及在本文引入作为参考的曾在书中作为参考文献所引用的参考文献；和J.Sambrook，等，Moleeular Cloning,A LaboratoryManual，第二版，Cold Spring Harbor Laboratory(1989)及在此处引入作为参考的曾在书中作为参考文献所引用的。
如何制备融合蛋白的补充的细节可见WO92/04455及WO91/02754。
关于淋巴因子和变异体的补充细节可参见美国专利4,810,643，及5,218,092；欧洲专利申请02174004。
所有的参考文献，专利或申请都在此全文引入作为参考，就好象已在本文写出来的一样。
下面给出标准的氨基酸的单字母或三字母缩写简称氨基酸A Ala丙氨酸C Cys半胱氨酸D Asp天冬氨酸E Glu谷氨酸F Phe苯丙氨酸G Gly甘氨酸H His组氨酸I Ile异亮氨酸K Lys赖氨酸L Leu亮氨酸M Met甲硫氨酸
N Asn天冬酰胺P Pro脯氨酸Q Gln谷氨酰胺R Arg精氨酸S Ser丝氨酸T The苏氨酸V Val缬氨酸W Trp色氨酸Y Tyr酪氨酸表5寡核苷酸88CTERM1.REQ 长度000041AATTCCGGGA AAAACTGACG TTCTATCTGG TTACCCTTGA G [SEQ ID NO:91]88CTERM4.REQ 长度000046CTGCGCTTGC TCAAGGGTAA CCAGATAGAA CGTCAGTTTT TCCCGG[SEQ ID NO:92]88XA2.REQ长度000039CAAGCGCAGG AACAACAGTA CGTAATCGAG GGAAGGATT[SEQ ID NO:93]88XA5.REQ长度000039ACCCGGGGAA ATCCTTCCCT CGATTACGTA CTGTTGTTC[SEQ ID NO:94]GLYN3.REQ长度000063TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGTAAG GTACCGCATGCAAGCTTAGA TCT[SEQ ID NO:95]GLYN6.REQ长度000058AGCTAGATCT AAGCTTGCAT GCGGTACCTT ACATGTTGGA GCCGCCGCCAGAACCACC [SEQ ID NO:96]IGG2B1.REQ长度000074CCGGGTGAAC CGTCTGGTCC AATCTCTACT ATCAACCCGT CTCTTCCGTCTAAAGAATCT CATAAATCTC CAAA [SEQ ID NO:97]IGG2B2.REQ长度000074CATGTTTGGA GATTTATGAG ATTCTTTAGA CGGAGGAGAC GGGTTGATAGTAGAGATTGG ACCAGACGGT TCAC [SEQ ID NO:98]GCSFSNA1.REQ 长度000068CTAGCCATCT GCAGAGCTTC CTGGAGGTGT CGTACCGCGT TCTACGCCACCTTGCGCAGC CCTACGTA [SEQ ID NO:99]GCSFSNA2.REQ 长度000068AGCtTACGTA GGGCTGCGCA AGGTGGCGTA GAACGCGGTA CGACACCTCCAGGAAGCTCT GCAGATGG [SEQ ID NO:100]LYSXA1.REQ长度000021GTAATCGAGG GAAAGATTTC C[SEQ ID NO:101]LYSXA2.REQ长度000025CCGGGGAAAT CTTTCCCTCG ATTAC [SEQ ID NO:102]GLYXA1.REQ长度000021GTAGAGGGCG GTGGAGGCTC C [SEQ ID NO:103]GLYXA2.REQ长度000025CCGGGGAGCC TCCACCGCCC TCTAC [SEQ ID NO:104]GM-AUP.REQ长度000058CATGGCACCA GCAAGATCAC CATCACCATC AACTCAACCT TGGGAACATGTGAATGCC [SEQ ID NO:105]GM-ALOW.REQ 长度000052CATTCACATG TTCCCAAGGT TGAGTTGATG GTGATGGTGA TCTTGCTGGTGC [SEQ ID NO:106]G-CYS18.REQ 长度000066CTGCCAGCTC CCTGCCCCAG AGCTTCCTGC TCAAGTCTTT AGAGCAAGTGAGGAAGATCC AGGGCG [SEQ ID NO:107]GCYS18LO.REQ 长度000066CTGGATCTTC CTCACTTGCT CTAAAGACTT GAGCAGGAAG CTCTGGGGCAGGGAGCTGGC AGGGCC [SEQ ID NO:108]HIL6231.REQ 长度000048AGCTTACCTG CCATGGCTCC AGTACCACCA GGTGAAGATT CCAAAGAT[SEQ ID NO:109]HIL6232.REQ 长度000040TTGGAATCTT CACCTGGTGG TACTGGAGCC ATGGCAGGTA [SEQ ID NO:110]HGCSFMA1.REQ长度000026AGCTTCCATG GCTACCCCCC TGGGCC [SEQ ID NO:111]HGCSFMA2.REQ长度000018CAGGGGGGTA GCCATGGA [SEQ ID NO:112]HGCSFAT1.REQ长度000020CATGGCTACA CCATTGGGCC [SEQ ID NO:113]HGCSFAT2.REQ长度000012CAATGGTGTA GC[SEQ ID NO:114]HGCSFAT3.REQ长度000020CATGGCTACA CCATTAGGAC [SEQ ID NO:115]HGCSFAT4.REQ长度000012TAATGGTGTA GC(SEQ ID NO:116]PREFOR.REQCCTGTCAACC CGGGCGGCGG CTCTGGTGGT[SEQ ID NO:117]REVPRE.REQTCATAATACA TGTTACCGGA ACGGAGCCGC C[SEQ ID NO:118]FORXTRA.REQATCGTCTGAC CTCCCGGGAC CTCCTGTCAA TGCT[SEQ ID NO:119]XTRAREV.REQAGCGTTTGAC ATGTTTTCAT AATCAAATC [SEQ ID NO:120]c-mp1NcoⅠACGTCCATGGCNTCNCCNGCNCCNCCTGCTTGTGACCTCCGAGTC[SEQ ID NO:169(其中N=G,C,T or A)c-mp1EcoRⅠATAGCTGAATTCTTACCCTTCCTGAGACAGATT[SEQ ID NO:170]c-mp1HindⅢTGACAAGCTTACCTGACGCAGAGGGTGGACCCT[SEQ ID NO:171]Eco-mp1ATGCACGAATTCCCTGACGCAGAGGGTGGA [SEQ ID NO:172]EcoSna1AATTCCATGCATAC [SEQ ID NO:173]ECOSNA2GGTACGTATG [SEQ ID NO:174]表6DNA序列pMON13023ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTACACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTGCTTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAAGCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCGGACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAGGCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCTCTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTCCCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATCTAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTG CCATGCCGGCCTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG GTTGCTAGCCATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCGCAGCCC [SEQ ID NO:53]pMON13021
ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTAACTGCTCTAT AATGATCGAT GAAATTATAC ATCACTTAAA GAGACCACCTAACCCTTTGC TGGACCCGAA CAACCTCAAT TCTGAAGACA TGGATATCCTGATGGAACGA AACCTTCGAA CTCCAAACCT GCTCGCATTC GTAAGGGCTGTCAAGCACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTCCAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCATCATCAAGGCA GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATCTGGTTACCCT TGAGCAAGCG CAGGAACAAC AG [SEQ ID NO:54]pMON13022ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCACCGGCTCGTTC CCCGTCCCCG TCTACCCAGC CGTGGGAACA CGTGAATGCCATCCAGGAGG CCCGGCGTCT CCTGAACCTG AGTAGAGACA CTGCTGCTGAGATGAATGAA ACAGTAGAAG TGATATCAGA AATGTTTGAC CTCCAGGAGCCGACTTGCCT ACAGACCCGC CTGGAGCTGT ACAAGCAGGG CCTGCGGGGCAGCCTCACCA AGCTCAAGGG CCCCTTGACC ATGATGGCCA GCCACTACAA
GCAGCACTGC CCTCCAACCC CGGAAACTTC CTGTGCAACC CAGATTATCACCTTTGAAAG TTTCAAAGAG AACCTGAAGG ACTTCCTGCT TGTCATCCCCTTTGACTGCT GGGAGCCAGT CCAGGAG [SEQ ID NO:55]pMON13039ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTACACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCTTTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAAGCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCGGACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAGGCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCTCTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTCCCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATCTGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCAGGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGGTCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTTCTACGCCACC TTGCGCAGCC C [SEQ ID NO:56]pMON13049ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC
CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTTCAGTACCACC AGGTGAAGAT TCCAAAGATG TGGCCGCCCC ACACAGACAGCCACTCACCT CTTCAGAACG AATTGACAAA CAAATTCGGT ACATCCTCGACGGGATATCA GCCCTGAGAA AGGAGACATG TAACAAGAGT AACATGTGTGAAAGCAGCAA AGAGGCGCTA GCAGAAAACA ACCTGAACCT TCCAAAGATGGCTGAAAAAG ATGGATGCTT CCAATCCGGA TTCAATGAGG AGACTTGCCTGGTGAAAATC ATCACTGGTC TTTTGGAGTT TGAGGTATAC CTCGAGTACCTCCAGAACAG ATTTGAGAGT AGTGAGGAAC AAGCCAGAGC TGTGCAGATGTCGACAAAAG TCCTGATCCA GTTCCTGCAG AAAAAGGCAA AGAATCTAGATGCAATAACC ACCCCTGACC CAACCACAAA TGCATCCCTG CTGACGAAGCTGCAGGCACA GAACCAGTGG CTGCAGGACA TGACAACTCA TCTCATTCTGCGCAGCTTTA AGGAGTTCCT GCAGTCCAGC CTGAGGGCTC TTCGGCAAATG [SEQ ID NO:57]pMON13055ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAAGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTAACTGCTCTAT AATGATCGAT GAAATTATAC ATCACTTAAA GAGACCACCTAACCCTTTGC TGGACCCGAA CAACCTCAAT TCTGAAGACA TGGATATCCTGATGGAACGA AACCTTCGAA CTCCAAACCT GCTCGCATTC GTAAGGGCTGTCAAGCACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTCCAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCATCATCAAGGCA GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC
TGGTTACCCT TGAGCAAGCG CAGGAACAAC AG [SEQ ID NO:58]pMON13054ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAAGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGTTACACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCTTTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAAGCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCGGACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAGGCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCTCTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTCCCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATCTGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCAGGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGGTCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTTCTACGCCACC TTGCGCAGCC C [SEQ ID NO:59]pMON13056ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG
TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTACACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCTTTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAAGCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCGGACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAGGCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCTCTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTCCCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATCTGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCAGGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGGTCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTTCTACGCCACC TTGCGCAGCC C [SEQ ID NO:60]pMON13057ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTTTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTAACTGCTCTAT AATGATCGAT GAAATTATAC ATCACTTAAA GAGACCACCTAACCCTTTGC TGGACCCGAA CAACCTCAAT TCTGAAGACA TGGATATCCTGATGGAACGA AACCTTCGAA CTCCAAACCT GCTCGCATTC GTAAGGGCTGTCAAGCACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTCCAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCATCATCAAGGCA GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATCTGGTTACCCT TGAGCAAGCG CAGGAACAAC AG [SEQ ID NO:61]pMON13036ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTAACTGCTCTATAATGA TCGATGAAAT TATACATCAC TTAAAGAGAC CACCTAACCCTTTGCTGGAC CCGAACAACC TCAATTCTGA AGACATGGAT ATCCTGATGGAACGAAACCT TCGAACTCCA AACCTGCTC CATTCGTAAG GGCTGTCAAGCACTTAGAAA ATGCATCAGG TATTGAGGC. ATTCTTCGTA ATCTCCAACCATGTCTGCCC TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCAAGGCAGGTGA CTGGCAAGAA TTCCGGGAAA AACTGACGTT CTATCTGGTTACCCTTGAGC AAGCGCAGGA ACAACAG [SEQ ID NO:62]pMON13059ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAAGATT TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTAACTGCTCTATAATGA TCGATGAAAT TATACATCAC TTAAAGAGAC CACCTAACCCTTTGCTGGAC CCGAACAACC TCAATTCTGA AGACATGGAT ATCCTGATGGAACGAAACCT TCGAACTCCA AACCTGCTCG CATTCGTAAG GGCTGTCAAG
CACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACCATGTCTGCCC TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCAAGGCAGGTGA CTGGCAAGAA TTCCGGGAAA AACTGACGTT CTATCTGGTTACCCTTGAGC AAGCGCAGGA ACAACAG [SEQ ID NO:63]pMON13061ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTAACTGCTCTATAATGA TCGATGAAAT TATACATCAC TTAAAGAGAC CACCTAACCCTTTGCTGGAC CCGAACAACC TCAATTCTGA AGACATGGAT ATCCTGATGGAACGAAACCT TCGAACTCCA AACCTGCTCG CATTCGTAAG GGCTGTCAAGCACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACCATGTCTGCCC TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCAAGGCAGGTGA CTGGCAAGAA TTCCGGGAAA AACTGACGTT CTATCTGGTTACCCTTGAGC AAGCGCAGGA ACAACAG [SEQ ID NO:64]pMON13062ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA
GGGAAGGATT TCCCCCGGGC CTCCTGTCAA TGCTGGCGGC GGCTCTGGTGGTGGTTCTGG TGGCGGCTCT GAGGGTGGCG GCTCTGAGGG TGGCGGTTCTGAGGGTGGCG GCTCTGAGGG TGGCGGTTCC GGTGGCGGCT CCGGTTCCGGTGATTTTGAT TATGAAAACA TGGCTACACC ATTGGGCCCT GCCAGCTCCCTGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG GAAGATCCAGGGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTGCCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGGCTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC AGGCTGCTTGAGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCTGGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGGACGTCGCCGA CTTTGCCACC ACCATCTGGC AGCAGATGGA AGAACTGGGAATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTCTGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATGTGCAGAGCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC GCA. CC[SEQ ID NO:65]pMON13031ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAAGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCCGGGC CTCCTGTCAA TGCTGGCGGC GGCTCTGGTGGTGGTTCTGG TGGCGGCTCT GAGGGTGGCG GCTCTGAGGG TGGCGGTTCTGAGGGTGGCG GCTCTGAGGG TGGCGGTTCC GGTGGCGGCT CCGGTTCCGGTGATTTTGAT TATGAAAACA TGGCACCGGC TCGTTCCCCG TCCCCGTCTACCCAGCCGTG GGAACACGTG AATGCCATCC AGGAGGCCCG GCGTCTCCTGAACCTGAGTA GAGACACTGC TGCTGAGATG AATGAAACAG TAGAAGTGATATCAGAAATG TTTGACCTCC AGGAGCCGAC TTGCCTACAG ACCCGCCTGG
AGCTGTACAA GCAGGGCCTG CGGGGCAGCC TCACCAAGCT CAAGGGCCCCTTGACCATGA TGGCCAGCCA CTACAAGCAG CACTGCCCTC CAACCCCGGAAACTTCCTGT GCAACCCAGA TTATCACCTT TGAAAGTTTC AAAGAGAACCTGAAGGACTT CCTGCTTGTC ATCCCCTTTG ACTGCTGGGA GCCAGTCCAGGAG[SEQ ID NO:66]PMON15937ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCCGGTG GCGGCGGCTC TGGTGGTGGT TCTGGTGGCGGCTCTGAGGG TGGCGGCTCT GAGGGTGGCG GTTCTGAGGG TGGCGGCTCTGAGGGTGGCG GTTCCGGTGG CGGCTCCGGT TCCGGTAACA TGGCTACACCATTAGGCCCT GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC AAGTGCTTAGAGCAAGTGAG GAAGATCCAG GGCGATGGCG CAGCGCTCCA GGAGAAGCTGTGTGCCACCT ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACACTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCCTGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTACCAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCACCTTGGACACA CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTGGCAGCAGATGGA AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGTGCCATGCCGG CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCTGGTTGCTAGC CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTACGCCACCTTGC GCAGCCC [SEQ ID NO: 67]PMON13034ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG
ACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTCCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTCAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACACCATTAGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTGCTTAGAGCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGTGTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT QCTCGGACACTCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCTGCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACCAGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACCTTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCAGCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTGCCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTGGTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACGCCACCTTGCG CAGCCC [SEQ ID NO:68]PMON13035ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCACCGGCT
CGTTCCCCGT CCCCGTCTAC CCAGCCGTGG GAACACGTGA ATGCCATCCAGGAGGCCCGG CGTCTCCTGA ACCTGAGTAG AGACACTGCT GCTGAGATGAATGAAACAGT AGAAGTGATA TCAGAAATGT TTGACCTCCA GGAGCCGACTTGCCTACAGA CCCGCCTGGA GCTGTACAAG CAGGGCCTGC GGGGCAGCCTCACCAAGCTC AAGGGCCCCT TGACCATGAT GGCCAGCCAC TACAAGCAGCACTGCCCTCC AACCCCGGAA ACTTCCTGTG CAACCCAGAT TATCACCTTTGAAAGTTTCA AAGAGAACCT GAAGGACTTC CTGCTTGTCA TCCCCTTTGACTGCTGGGAG CCAGTCCAGG AG [SEQ ID NO:69]PMON13058ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAAGATT TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACACCATTAGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTGCTTAGAGCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGTGTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACACTCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCTGCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACCAGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACCTTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCAGCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTGCCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTGGTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACGCCACCTTGCG CAGCCC [SEQ ID NO:70]PMON13060ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACACCATTAGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTGCTTAGAGCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGTGTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACACTCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCTGCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACCAGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACCTTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCAGCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTGCCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTGGTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACGCCACCTTGCG CAGCCC [SEQ ID NO:71]PMON13026ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC
CACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG GGAAGGATTTCCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATAATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTA ACCCTTTGCTGGACCCGAAC AACCTCAATT CTGAAGACAT GGATATCCTG ATGGAACGAAACCTTCGAAC TCCAAACCTG CTCGCATTCG TAAGGGCTGT CAAGCACTTAGAAAATGCAT CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCTGCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAGGTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTTGAGCAAGCGC AGGAACAACA G [SEQ ID NO:72]PMON13063ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG GGAAGGATTTCCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCGTCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGATCGATGAAATT ATACATCACT TAAAGAGACC ACCTAACCCT TTGCTGGACCCGAACAACCT CAATTCTGAA GACATGGATA TCCTGATGGA ACGAAACCTTCGAACTCCAA ACCTGCTCGC ATTCGTAAGG GCTGTCAAGC ACTTAGAAAA
TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCTCTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGACTGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCAAGCGCAGGAA CAACAG [SEQ ID NO:73]PMON13064ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG GGAAGGATTTCCCCCGGGCC TCCTGTCAAT GCTGGCGGCG GCTCTGGTGG TGGTTCTGGTGGCGGCTCTG AGGGTGGCGG CTCTGAGGGT GGCGGTTCTG AGGGTGGCGGCTCTGAGGGT GGCGGTTCCG GTGGCGGCTC CGGTTCCGGT GATTTTGATTATGAAAACAT GGCTAACTGC TCTATAATGA TCGATGAAAT TATACATCACTTAAAGAGAC CACCTAACCC TTTGCTGGAC CCGAACAACC TCAATTCTGAAGACATGGAT ATCCTGATGG AACGAAACCT TCGAACTCCA AACCTGCTCGCATTCGTAAG GGCTGTCAAG CACTTAGAAA ATGCATCAGG TATTGAGGCAATTCTTCGTA ATCTCCAACC ATGTCTGCCC TCTGCCACGG CCGCACCCTCTCGACATCCA ATCATCATCA AGGCAGGTGA CTGGCAAGAA TTCCGGGAAAAACTGACGTT CTATCTGGTT ACCCTTGAGC AAGCGCAGGA ACAACAG[SEQ ID NO:74]PMON13043ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC
AGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG GGAAGGATTTCCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATAATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG CACCTTTGCTGGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGAACGAAACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTAGAAAATGCAT CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCTGCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAGGTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTTGAGCAAGCGC AGGAACAACA G [SEQ ID NO:75]PMON13044ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG GGAAGGATTT
CCCCCGGGCC TCCTGTCAAT GCTCGCGGCG GCTCTGGTGG TGGTTCTGGTGGCGGCTCTG AGGGTGGCGG CTCTGAGGGT GGCGGTTCTG AGGGTGGCGGCTCTGAGGGT GGCGGTTCCG GTGGCGGCTC CGGTTCCGGT GATTTTGATTATGAAAACAT GGCTAACTGC TCTATAATGA TCGATGAAAT TATACATCACTTAAAGAGAC CACCTGCACC TTTGCTGGAC CCGAACAACC TCAATGACGAAGACGTCTCT ATCCTGATGG AACGAAACCT TCGACTTCCA AACCTGGAGAGCTTCGTAAG GGCTGTCAAG AACTTAGAAA ATGCATCAGG TATTGAGGCAATTCTTCGTA ATCTCCAACC ATGTCTGCCC TCTGCCACGG CCGCACCCTCTCGACATCCA ATCATCATCA AGGCAGGTGA CTGGCAAGAA TTCCGGGAAAAACTGACGTT CTATCTGGTT ACCCTTGAGC AAGCGCAGGA ACAACAG[SEQ ID NO:76]PMON13045ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG GGAAGGATTTCCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCGTCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGATCGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACCCGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA ACGAAACCTTCGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAATGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCTCTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGAC
TGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCAAGCGCAGGAA CAACAG [SEQ ID NO:77]PMON13151ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC GGTGGAGGCTCCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATAATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG CACCTTTGCTGGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGAACGAAACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTAGAAAATGCAT CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCTGCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAGGTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTTGAGCAAGCGC AGGAACAACA G [SEQ ID NO:78]PMON13152ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTCCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGQT ATCCCCCGAG
TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC GGTGGAGGCTCCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCGTCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGATCGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACCCGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA ACGAAACCTTCGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAATGCATCACGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCTCTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGACTGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCAAGCGCAGGAA CAACAG [SEQ ID NO:79]PMON13149ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTCTTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC GGTGGAGGCTCCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATAATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG CACCTTTGCTGGACCCGAAC AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGAACGAAACCTTCGACT TCCAAACCTG GAGAGCTTCG TAAGGGCTGT CAAGAACTTA
GAAAATGCAT CAGGTATTGA GGCAATTCTT CGTAATCTCC AACCATGTCTGCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC ATCAAGGCAGGTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTTGAGCAAGCGC AGGAACAACA G [SEQ ID NO:80]PMON13150ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTCTTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC GGTGGAGGCTCCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCGTCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGATCGATGAAATT ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACCCGAACAACCT CAATGACGAA GACGTCTCTA TCCTGATGGA ACGAAACCTTCGACTTCCAA ACCTGGAGAG CTTCGTAAGG GCTGTCAAGA ACTTAGAAAATGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA TGTCTGCCCTCTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGACTGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCAAGCGCAGGAA CAACAG [SEQ ID NO:81]PMON13052ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA
AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTAACTGCTCTATAATGA TCGATGAAAT TATACATCAC TTAAAGAGAC CACCTGCACCTTTGCTGGAC CCGAACAACC TCAATGACGA AGACGTCTCT ATCCTGATGGAACGAAACCT TCGACTTCCA AACCTGGAGA GCTTCGTAAG GGCTGTCAAGAACTTAGAAA ATGCATCAGG TATTGAGGGA ATTCTTCGTA ATCTCCAACCATGTCTGCCC TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCAAGGCAGGTGA CTGGCAAGAA TTCCGGGAAA AACTGACGTT CTATCTGGTTACCCTTGAGC AAGCGCAGGA ACAACAG [SEQ ID NO:82]PMON13053ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTAAGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACACCATTGGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTCTTTAGAGCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGTGTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACACTCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCTGCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACCAGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACC
TTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCAGCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTGCCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTGGTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACGCCACCTTGCG CAGCCCTGAT AAGGATCCGA ATTC [SEQ ID NO:83]PMON13066ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTAAGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTACACCATTAGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTGCTTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAAGCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCGGACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAGGCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCTCTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTCCCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATCTGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCAGGGTGCCATG CCGGCCTTCG CCTCTGCGTT CCAGCGCCGG GCAGGAGGGGTCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTTCTACGCCACC TTGCGCAGCC C [SEQ ID NO:84]PMON13051ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTA
AGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTACACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCTTTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAAGCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCGGACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAGGCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCTCTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTCCCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATCTGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCAGGGTGCCATC CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGGTCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTTCTACGCCACC TTGCGCAGCC C [SEQ ID NO:85]PMON13050ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTAAGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTAACTGCTCTAT AATGATCGAT GAAATTATAC ATCACTTAAA GAGACCACCTGCACCTTTGC TGGACCCGAA CAACCTCAAT GACGAAGACG TCTCTATCCTGATGGAACGA AACCTTCGAC TTCCAAACCT GGAGAGCTTC GTAAGGGCTGTCAAGAACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTC
CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCATCATCAAGGCA GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATCTGGTTACCCT TGAGCAAGCG CAGGAACAAC AG [SEQ ID NO:86]PMON13145ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTAAGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTACACCATTGGG CCCTGCCAGC TCCCTGCCCC AGAGCTTCCT GCTCAAGTCTTTAGAGCAAG TGAGGAAGAT CCAGGGCGAT GGCGCAGCGC TCCAGGAGAAGCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG GTGCTGCTCGGACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAGGCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCTCTACCAGGGG CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTCCCACCTTGGA CACACTGCAG CTGGACGTCG CCGACTTTGC CACCACCATCTGGCAGCAGA TGGAAGAACT GGGAATGGCC CCTGCCCTGC AGCCCACCCAGGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG GCAGGAGGGGTCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTTCTACGCCACC TTGCGCAGCC C [SEQ ID NO: 87]PMON13147ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTAAGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATC
CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTAACTGCTCTAT AATGATCGAT GAAATTATAC ATCACTTAAA GAGACCACCTGCACCTTTGC TGGACCCGAA CAACCTCAAT GACGAAGACG TCTCTATCCTGATGGAACGA AACCTTCGAC TTCCAAACCT GGAGAGCTTC GTAAGGGCTGTCAAGAACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTCCAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCATCATCAAGGCA GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATCTGGTTACCCT TGAGCAAGCG CAGGAACAAC AG [SEQ ID NO:88]PMON13146ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTAAGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTCA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTACACCATTGGGCCCTG CCAGCTCCCT GCCCCAGAGC TTCCTGCTCA AGTCTTTAGAGCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG GAGAAGCTGTGTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACACTCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCTGCAGCTGGCA GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACCAGGGGCTCCT GCAGGCCCTG GAAGGGATAT CCCCCGAGTT GGGTCCCACCTTGGACACAC TGCAGCTGGA CGTCGCCGAC TTTGCCACCA CCATCTGGCAGCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC ACCCAGGGTGCCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTGGTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG
CCACCTTGCG CAGCCC [SEQ ID NO:89]PMON13148ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTGCA CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCTCTATCCTGAT GGAACGAAAC CTTCGACTTC CAAACCTGGA GAGCTTCGTAAGGGCTGTCA AGAACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACCCGTCTCCTCC GTCTAAAGAA TCTCATAAAT CTCCAAACAT GGCTAACTGCTCTATAATGA TCGATGAAAT TATACATCAC TTAAAGAGAC CACCTGCACCTTTGCTGGAC CCGAACAACC TCAATGACGA AGACGTCTCT ATCCTGATGGAACGAAACCT TCGACTTCCA AACCTGGAGA GCTTCGTAAG GGCTGTCAAGAACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACCATGTCTGCCC TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCAAGGCAGGTGA CTGGCAAGAA TTCCGGGAAA AACTGACGTT CTATCTGGTTACCCTTGAGC AAGCGCAGGA ACAACAG [SEQ ID NO:90]pMON13040ATGGCTCCAG TACCACCAGG TGAAGATTCC AAAGATGTGG CCGCCCCACACAGACAGCCA CTCACCTCTT CAGAACGAAT TGACAAACAA ATTCGGTACATCCTCGACGG GATATCAGCC CTGAGAAAGG AGACATGTAA CAAGAGTAACATGTGTGAAA GCAGCAAAGA GGCGCTAGCA GAAAACAACC TGAACCTTCCAAAGATGGCT GAAAAAGATG GATGCTTCCA ATCCGGATTC AATGAGGAGACTTGCCTGGT GAAAATCATC ACTGGTCTTT TGGAGTTTGA GGTATACCTCGAGTACCTCC AGAACAGATT TGAGAGTAGT GAGGAACAAG CCAGAGCTGTGCAGATGTCG ACAAAAGTCC TGATCCAGTT CCTGCAGAAA AAGGCAAAGAATCTAGATGC AATAACCACC CCTGACCCAA CCACAAATGC ATCCCTGCTGACGAAGCTGC AGGCACAGAA CCAGTGGCTG CAGGACATGA CAACTCATCTCATTCTGCGC AGCTTTAAGG AGTTCCTGCA GTCCAGCCTG AGGGCTCTTCGGCAAATGTA G [SEQ ID NO:175]pMON13012ATGGCACCGG CTCGTTCCCC GTCCCCGTCT ACCCAGCCGT GGGAACACGTGAATGCCATC CAGGAGGCCC GGCGTCTCCT GAACCTGAGT AGAGACACTGCTGCTGAGAT GAATGAAACA GTAGAAGTGA TATCAGAAAT GTTTGACCTCCAGGAGCCGA CTTGCCTACA GACCCGCCTG GAGCTGTACA AGCAGGGCCTGCGGGGCAGC CTCACCAAGC TCAAGGGCCC CTTGACCATG ATGGCCAGCCACTACAAGCA GCACTGCCCT CCAACCCCGG AAACTTCCTG TGCAACCCAGATTATCACCT TTGAAAGTTT CAAAGAGAAC CTGAAGGACT TCCTGCTTGTCATCCCCTTT GACTGCTGGG AGCCAGTCCA GGAGTGATAA GGATCCGAATTC [SEQ ID NO:176]pMON13499ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTG ATAAGGATCC GAATTC[SEQ ID NO:177]pMON13498/pMON13010ATGGCTACAC CATTAGGACC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTGCTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTG ATAAGGATCC GAATTC[SEQ ID NO:178]pMON13033/pMON13037ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCTCAAGTCTTTA GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCCAGGAGAAGCT GTGTGCCACC TACAAGCTGT GCCACCCCGA GGAGCTGGTGCTGCTCGGAC ACTCTCTGGG CATCCCCTGG GCTCCCCTGA GCTCCTGCCCCAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC CATAGCGGCCTTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAGTTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCACCACCATCTGG CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGCCCACCCAGGG TGCCATGCCG GCCTTCGCCT CTGCTTTCCA GCGCCGGGCAGGAGGGGTCC TGGTTGCTAG CCATCTGCAG AGCTTCCTGG AGGTGTCGTACCGCGTTCTA CGCCACCTTG CGCAGCCCTG ATAAGGATCC GAATTC[SEQ ID NO:179]pMON26448ATGGCGTCTC CGGCGCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACTGCTTCGTGAC TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGGTTCACCCTTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTGGGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGGAGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGGGACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGTCTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACAGGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCCAACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCCACCCTCTGCG TCAGG [SEQ ID NO:180]pMON26463ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGAGGGAAGGATT TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCGTCTCCGGCGCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGTGACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCCTTTGCCTACA CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAATGGAAAACCCA GATGGAGGAG ACCAAGGCAC AGGACATTCT GGGAGCAGTGACCCTTCTGC TGGAGGGAGT GATGGCAGCA CGGGGACAAC TGGGACCCACTTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC CGTCTCCTCCTTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC ACAGGGCAGGACCACAGCTC ACAAGGATCC CAATGCCATC TTCCTGAGCT TCCAACACCTGCTCCGAGGA AAGGTGCGTT TCCTGATGCT TGTAGGAGGG TCCACCCTCTGCGTCAGG [SEQ ID NO:183]pMON26473ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAGACCACCTAAC CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGGATATCCTGAT GGAACGAAAC CTTCGAACTC CAAACCTGCT CGCATTCGTAAGGGCTGTCA AGCACTTAGA AAATGCATCA GGTATTGAGG CAATTCTTCGTAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC TCTCGACATCCAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACGTTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGGCGGTGGAGGC TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCGTCTCCGGCGCC GCCTGCTTGT GACCTCCGAG TCCTCAGTAA ACTGCTTCGTGACTCCCATG TCCTTCACAG CAGACTGAGC CAGTGCCCAG AGGTTCACCCTTTGCCTACA CCTGTCCTGC TGCCTGCTGT GGACTTTAGC TTGGGAGAATGGAAAACCCA GATGGAGGAG ACCAAGGCAC AGGACATTCT GGGAGCAGTGACCCTTCTGC TGGAGGGAGT GATGGCAGCA CGGGGACAAC TGGGACCCACTTGCCTCTCA TCCCTCCTGG GGCAGCTTTC TGGACAGGTC CGTCTCCTCCTTGGGGCCCT GCAGAGCCTC CTTGGAACCC AGCTTCCTCC ACAGGGCAGGACCACAGCTC ACAAGGATCC CAATGCCATC TTCCTGAGCT TCCAACACCTGCTCCGAGGA AAGGTGCGTT TCCTGATGCT TGTAGGAGGG TCCACCCTCTGCGTCAGG [SEQ ID NO:184]pMON26474ATGGCGTCTC CGGCGCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACTGCTTCGTGAC TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGGTTCACCCTTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTGGGAGAATGGA AAACCCAGAT GGAGGAGACC AAGGCACAGG ACATTCTGGGAGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGGGACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGTCTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACAGGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCCAACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCCACCCTCTGCG TCAGGATCGA GGGAAGGATT TCCCCGGGTG GTGGTTCTGGCGGCGGCTCC AACATGGCTA ACTGCTCTAT AATGATCGAT GAAATTATACATCACTTAAA GAGACCACCT AACCCTTTGC TGGACCCGAA CAACCTCAATTCTGAAGACA TGGATATCCT GATGGAACGA AACCTTCGAA CTCCAAACCTGCTCGCATTC GTAAGGGCTG TCAAGCACTT AGAAAATGCA TCAGGTATTGAGGCAATTCT TCGTAATCTC CAACCATGTC TGCCCTCTGC CACGGCCGCACCCTCTCGAC ATCCAATCAT CATCAAGGCA GGTGACTGGC AAGAATTCCGGGAAAAACTG ACGTTCTATC TGGTTACCCT TGAGCAAGCG CAGGAACAACAG [SEQ ID NO:185]PMON26464ATGGCGTCTC CGGCGCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACTGCTTCGTGAC TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGGTTCACCCTTT GCCTACACCT GTCCTGCTGC CTGCTGTGGA CTTTAGCTTGGGAGAATGGA AAACCCAGAT GGAAGAGACC AAGGCACAGG ACATTCTGGGAGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG GGACAACTGGGACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGTCTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC WTCCTCCACAGGGCAGGACC ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCCAACACCTGCT CCGAGGAAAG GTGCGTTTCC TGATGCTTGT AGGAGGGTCCACCCTCTGCG TCAGGGAATT CCATGCATAC GTAGAGGGCG GTGGAGGCTCCCCGGGTGGT GGTTCTGGCG GCGGCTCCAA CATGGCTAAC TGCTCTATAATGATCGATGA AATTATACAT CACTTAAAGA GACCACCTAA CCCTTTGCTGGACCCGAACA ACCTCAATTC TGAAGACATG GATATCCTGA TGGAACGAAACCTTCGAACT CCAAACCTGC TCGCATTCGT AAGGGCTGTC AAGCACTTAGAAAATGCATC AGGTATTGAG GCAATTCTTC GTAATCTCCA ACCATGTCTGCCCTCTGCCA CGGCCGCACC CTCTCGACAT CCAATCATCA TCAAGGCAGGTGACTGGCAA GAATTCCGGG AAAAACTGAC GTTCTATCTG GTTACCCTTGAGCAAGCGCA GGAACAACAG [SEQ ID NO:186]
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序列表(1)一般信息(ⅰ)申请人(A)姓名G.D.Searle & Co.
(B)街道P.O.Box 5100(C)城市芝加哥(D)州依利诺斯(E)国家美国(F)邮编(ZIP):60680(G)电话(708)470-6501(H)电传(708)470-6881(A)姓名Monsanto Company(B)街道800 North Lindbergh Boulevard(C)城市圣路易斯(D)州密西西比(E)国家美利坚合众国(F)邮编(ZIP):63167(G)电话(314)694-3131(H)电传(314)694-5435(ⅱ)发明题目多种变异的IL-3造血生成融合蛋白(ⅲ)序列数196(ⅳ)计算机可读形式(A)介质类型软盘(B)计算机IBM PC兼容机(C)操作系统PC-DOS/MS-DOS(D)软件PatentIn Release # 1.0,Version#1.30(EPO)(ⅵ)现有申请资料(A)申请号US 08/192325(B)提交日14-FEB-1994(2)SEQ ID NO:1的信息(ⅰ)序列特征
(A)长度133氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点1(D)其它信息/注释=“可在或不在位点1氨基酸前含有Met-”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点17(D)其它信息/注释=“Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点19(D)其它信息/注释=“Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点20(D)其它信息/注释=“Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点21
(D)其它信息/注释=“Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点22(D)其它信息/注释=“Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点23(D)其它信息/注释=“Xaa在位点23是Ile,Val,Ala,Leu,Gly,Trp,Lys,Phe,Ser，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点24(D)其它信息/注释=“Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点25(D)其它信息/注释=“Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点26(D)其它信息/注释=“Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点27
(D)其它信息/注释=“Xaa在位点27是Leu,Gly,Arg,Thr,Ser，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点28(D)其它信息/注释=“Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点29(D)其它信息/注释=“Xaa在位点29是Gln,Asn,Leu,Pro,Arg，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点30(D)其它信息/注释=“Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点31(D)其它信息/注释=“Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala，或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点33(D)其它信息/注释=“Xaa在位点33是Pro,Leu,Gln,Ala,Thr，或Glu”
(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点34(D)其它信息/注释=“Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点35(D)其它信息/注释=“Xaa在位点35是Leu,Ala,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点36(D)其它信息/注释=“Xaa在位点36是Asp,Leu，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点37(D)其它信息/注释=“Xaa在位点37是Phe,Ser,Pro,Trp，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点38(D)其它信息/注释=“Xaa在位点38是Asn，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点40(D)其它信息/注释=“Xaa在位点40是Leu,Trp，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点41(D)其它信息/注释=“Xaa在位点41是Asn,Gys,Arg,Leu,His,Met，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点42(D)其它信息/注释=“Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr,Ile,Met，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点43(D)其它信息/注释=“Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Gys,Gln,Arg,Thr,Gly,或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点44(D)其它信息/注释=“Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,Ala,或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点45(D)其它信息/注释=“Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,Arg,Ser,Ala,Ile,Glu，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点46
(D)其它信息/注释=“Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,Tyr,Ile,Val，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点47(D)其它信息/注释=“Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点48(D)其它信息/注释=“Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,Val，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点49(D)其它信息/注释=“Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点50(D)其它信息/注释=“Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,Phe,Met，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点52(D)其它信息/注释=“Xaa位点52是Asn,His,Arg,Leu,Gly,Ser，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点53(D)其它信息/注释=“Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点54(D)其它信息/注释=“Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Arg,Thr,Val,Ser,Leu，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点56(D)其它信息/注释=“Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,Leu,Val，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点57(D)其它信息/注释=“Xaa在位点57是Asn或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点58
(D)其它信息/注释=“Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点59(D)其它信息/注释=“Xaa在位点59是Glu,Tyr,His,Leu,Pro，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点60(D)其它信息/注释=“Xaa在位点60是Ala,Ser,Pro,Tyr,Asn，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点61(D)其它信息/注释=“Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点63(D)其它信息/注释=“Xaa在位点63是Arg,Tyr,Trp,Lys,Ser,His,Pro，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点64(D)其它信息/注释=“Xaa在位点64是Ala,Asn,Pro,Ser，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Val,Thr,Pro,His,Leu,Phe，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点66(D)其它信息/注释=“Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点67(D)其它信息/注释=“Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点68(D)其它信息/注释=“Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点69(D)其它信息/注释=“Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Glu,Trp,Gly，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点70(D)其它信息/注释=“Xaa在位点70是Asn,Leu,Val,Trp,Pro，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点71(D)其它信息/注释=“Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点72(D)其它信息/注释=“Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点73(D)其它信息/注释=“Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Thr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点74(D)其它信息/注释=“Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点75(D)其它信息/注释=“Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点76(D)其它信息/注释=“Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点77
(D)其它信息/注释=“Xaa在位点77是Ile,Ser,Arg,Thr，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点78(D)其它信息/注释=“Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点80(D)其它信息/注释=“Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点81(D)其它信息/注释=“Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点82(D)其它信息/注释=“Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,Ala,Tyr,Phe,Ile,Met，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点83
(D)其它信息/注释=“Xaa在位点83是Pro,Ala,Thr,Trp,Arg，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点84(D)其它信息/注释=“Xaa在位点84是Cys,Glu,Gly,Arg,Met，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点85(D)其它信息/注释=“Xaa在位点85是Leu,Asn,Val,或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点86(D)其它信息/注释=“Xaa在位点86是Pro,Cys,Arg,Ala，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点87(D)其它信息/注释=“Xaa在位点87是Leu,Ser,Trp,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点88(D)其它信息/注释=“Xaa在位点88是Ala,Lys,Arg,Val，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点89(D)其它信息/注释=“Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点90(D)其它信息/注释=“Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91(D)其它信息/注释=“Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点92(D)其它信息/注释=“Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点93(D)其它信息/注释=“Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点94(D)其它信息/注释=“Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,Trp,Phe,Ile，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点96(D)其它信息/注释=“Xaa在位点96是Pro,Lys,Tyr,Gly,Ile，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点97(D)其它信息/注释=“Xaa在位点97是Ile,Val,Lys,Ala，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,Val,Lys,Arg,Tyr，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点99(D)其它信息/注释=“Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点100(D)其它信息/注释=“Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点101(D)其它信息/注释=“Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,Ala,Gly,Ile,Leu，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点102(D)其它信息/注释=“Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点103(D)其它信息/注释=“Xaa在位点103是Asp，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点104(D)其它信息/注释=“Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点105(D)其它信息/注释=“Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp,或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点106(D)其它信息/注释=“Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点108(D)其它信息/注释=“Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,ser，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点110(D)其它信息/注释=“Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Leg,Gln,His,Glu,Ser,Ala，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点111(D)其它信息/注释=“Xaa在位点111是Leu,Ile,Arg,Asp，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点112(D)其它信息/注释=“Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser，或Phe”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点113(D)其它信息/注释=“Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点114(D)其它信息/注释=“Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点115(D)其它信息/注释=“Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点116(D)其它信息/注释=“Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,Asn,His,Ala,Tyr,Phe,Gln，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点117(D)其它信息/注释=“Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点118(D)其它信息/注释=“Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点119(D)其它信息/注释=“Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点120(D)其它信息/注释=“Xaa在位点120是Asn,Ala,Pro,Leu,His,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点121(D)其它信息/注释=“Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点122(D)其它信息/注释=“Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点123(D)其它信息/注释=“Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu”(ⅹⅰ)序列描述SEQ ID NO1Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa65 70 75 80Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa85 90 95Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa100 105 110Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu115 120 125Ser Leu Ala Ile Phe130(2)SEQ ID NO2的信息(ⅰ)序列特征(A)长度133氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点1(D)其它信息/注释=“Met=可或不在位点1启始氨基酸”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点17(D)其它信息/注释=“Xaa在位点17是Ser,Gly,Asp,Met，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Asn,His，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点19(D)其它信息/注释=“Xaa在位点19是Met或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点21(D)其它信息/注释=“Xaa在位点21是Asp或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点23
(D)其它信息/注释=“Xaa在位点23是Ile,Ala,Leu,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点24(D)其它信息/注释=“Xaa在位点24是Ile,Val，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点25(D)其它信息/注释=“Xaa在位点25是Thr,His,Gln,或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点26(D)其它信息/注释=“Xaa在位点26是His或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点29(D)其它信息/注释=“Xaa在位点29是Gln,Asn，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点30(D)其它信息/注释=“Xaa在位点30是Pro,Gly，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点31(D)其它信息/注释=“Xaa在位点31是Pro,Asp,Gly,或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Leu,Arg,Gln,Asn,Gly,Ala，或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点33(D)其它信息/注释=“Xaa在位点33是Pro或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点34(D)其它信息/注释=“Xaa在位点34是Leu,Val,Gly,Ser,Lys,Ala,Ala,Gln,Glu,Ile,Phr,Thr,或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点35(D)其它信息/注释=“Xaa在位点35是Leu,Ala,Asn,Pro,Gln，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点37(D)其它信息/注释=“Xaa在位点37是Phe,Ser,Pro,或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点38(D)其它信息/注释=“Xaa在位点38是Asn或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点42
(D)其它信息/注释=“Xaa在位点42是Gly,Asp,Ser,Cys,Ala,Asn,Ile,Leu,Met,Tyr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点44(D)其它信息/注释=“Xaa在位点44是Asp或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点45(D)其它信息/注释=“Xaa在位点45是Gln,Val,Met,Leu,Thr,Ala,Asn,Glu,Ser，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点46(D)其它信息/注释=“Xaa在位点46是Asp,Phe,Ser,Thr,Ala,Asn,Gln,Glu,His,Ile,Lys,Tyr,Val，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点50(D)其它信息/注释=“Xaa在位点50是Glu,Ala,Asn,Ser，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点54(D)其它信息/注释=“Xaa在位点54是Arg或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Arg,Thr,Val,Leu，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点56(D)其它信息/注释=“Xaa在位点56是Pro,Gly,Ser,Gln,Ala,Arg,Asn,Glu,Leu,Thr,Val，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点60(D)其它信息/注释=“Xaa在位点60是Ala或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Asn,Pro,Thr,或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点63(D)其它信息/注释=“Xaa在位点63是Arg或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点64(D)其它信息/注释=“Xaa在位点64是Ala或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Val或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点66(D)其它信息/注释=“Xaa在位点66是Lys或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点67(D)其它信息/注释=“Xaa在位点67是Ser,Phe或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点68(D)其它信息/注释=“Xaa在位点68是Leu,Ile,Phe,或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点69(D)其它信息/注释=“Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点71(D)其它信息/注释=“Xaa在位点71是Ala,Pro，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点72(D)其它信息/注释=“Xaa在位点72是Ser,Glu,Arg,或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点73
(D)其它信息/注释=“Xaa在位点73是Ala或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点76(D)其它信息/注释=“Xaa在位点76是Ser,Val,Ala,Asn,Glu,Pro，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点77(D)其它信息/注释=“Xaa在位点77是Ile或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Lys,Thr,Gly,Asn,Met,Arg,Ile,Gly，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点80(D)其它信息/注释=“Xaa在位点80是Asn,Gly,Glu,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点82(D)其它信息/注释=“Xaa在位点82是Leu,Gln,Trp,Arg,Asp,Ala,Asn,Glu,His,Ile,Met,Phe,Ser,Thr,Tyr，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点83(D)其它信息/注释=“Xaa在位点83是Pro或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点85(D)其它信息/注释=“Xaa在位点85是Leu或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点87(D)其它信息/注释=“Xaa在位点87是Leu或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点88(D)其它信息/注释=“Xaa在位点88是Ala或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91(D)其它信息/注释=“Xaa在位点91是Ala或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点93(D)其它信息/注释=“Xaa在位点93是Thr,Asp,Ser,Pro,Ala,Leu，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是His,Pro,Arg,Val,Leu,Gly,Asn,Phe,Ser，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点96(D)其它信息/注释=“Xaa在位点96是Pro或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点97(D)其它信息/注释=“Xaa在位点97是Ile或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是His,Ile,Asn,Leu,Ala,Thr,Arg,Gln,Lys,Met,Ser,Tyr,Val，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点99(D)其它信息/注释=“Xaa在位点99是Ile,Leu，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点100(D)其它信息/注释=“Xaa在位点100是Lys,Arg,Ile,Gln,Pro，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点101(D)其它信息/注释=“Xaa在位点101是Asp,Pro,Met,Lys,Thr,His,Asn,Ile,Leu，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点104(D)其它信息/注释=“Xaa在位点104是Trp或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点105(D)其它信息/注释=“Xaa在位点105是Asn,Pro,Ala,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点106(D)其它信息/注释=“Xaa在位点106是Glu或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点108(D)其它信息/注释=“Xaa在位点108是Arg,Ala，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Arg,Thr,Glu,Leu，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点112(D)其它信息/注释=“Xaa在位点112是Thr,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点114(D)其它信息/注释=“Xaa在位点114是Tyr或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点115(D)其它信息/注释=“Xaa在位点115是Leu或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点116(D)其它信息/注释=“Xaa在位点116是Lys,Thr,Val,Trp,Ser,Ala,His,Met,Phe,Tyr，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点117(D)其它信息/注释=“Xaa在位点117是Thr或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点120(D)其它信息/注释=“Xaa在位点120是Asn,Pro,Leu,His,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点121(D)其它信息/注释=“Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Asp，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点122(D)其它信息/注释=“Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点123(D)其它信息/注释=“Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu”(ⅸ)序列描述SEQ ID NO2Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa Xaa Xaa Xaa20 25 30Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa Xaa Xaa Ile Leu35 40 45Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu Xaa Phe Xaa Xaa Xaa50 55 60Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile Glu Xaa Xaa Leu Xaa Xaa65 70 75 80Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg Xaa Xaa85 90 95Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa Xaa Xaa Phe Xaa Xaa Lys Leu Xaa100 105 110Phe Xaa Xaa Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu115 120 125Ser Leu Ala Ile Phe130(2)SEQ ID NO3的信息(ⅰ)序列特征(A)长度133氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点1(D)其它信息/注释=“可在或不在位点1氨基酸前含有Met-”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点17(D)其它信息/注释=“Xaa在位点17是Ser，Gly，Asp，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Asn,His，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点23
(D)其它信息/注释=“Xaa在位点23是Ile,Ala,Leu,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点25(D)其它信息/注释=“Xaa在位点25是Thr,His，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点26(D)其它信息/注释=“Xaa在位点26是His或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点29(D)其它信息/注释=“Xaa在位点29是Gln或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点30(D)其它信息/注释=“Xaa在位点30是Pro或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Leu,Arg,Asn,或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点34(D)其它信息/注释=“Xaa在位点34是Leu,Val,Ser,Ala,Arg,Gln,Glu,Ile,Phe,Thr，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点35
(D)其它信息/注释=“Xaa在位点35是Leu,Ala,Asn,或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点38(D)其它信息/注释=“Xaa在位点38是Asn或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点42(D)其它信息/注释=“Xaa在位点42是Gly,Asp,Ser,Ala,Asn,Ile,Leu,Met,Tyr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点45(D)其它信息/注释=“Xaa在位点45是Gln,Val,Met,Leu,Ala,Asn,Glu，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点46(D)其它信息/注释=“Xaa在位点46是Asp,Phe,Ser,Gln,Glu,His,Val，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点50(D)其它信息/注释=“Xaa在位点50是Glu,Asn,Ser,或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Asn,Arg,Pro,Thr，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Arg,Leu，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点56(D)其它信息/注释=“Xaa在位点56是Pro,Gly,Ser,Ala,Asn,Val,Leu，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Asn,Pro，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点64(D)其它信息/注释=“Xaa在位点64是Ala或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Val或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点67(D)其它信息/注释=“Xaa在位点67是Ser或Phe”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点68(D)其它信息/注释=“Xaa在位点68是Leu或Phe”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点69(D)其它信息/注释=“Xaa在位点69是Gln,Ala,Glu,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点76(D)其它信息/注释=“Xaa在位点76是Ser,Val,Asn,Pro，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点77(D)其它信息/注释=“Xaa在位点77是Ile或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Lys,Asn,Met,Arg,Ile，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点80(D)其它信息/注释=“Xaa在位点80是Asn,Gly,Glu,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点82(D)其它信息/注释=“Xaa在位点82是Leu,Gln,Trp,Arg,Asp,Asn,Glu,His,Met,Phe,Ser,Thr,Tyr，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点87(D)其它信息/注释=“Xaa在位点87是Leu或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点88(D)其它信息/注释=“Xaa在位点88是Ala或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91(D)其它信息/注释=“Xaa在位点91是Ala或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点93(D)其它信息/注释=“Xaa在位点93是Thr,Asp，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是His,Pro,Arg,Val,Gly,Asn,Ser，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是His,Ile,Asn,Ala,Thr,Gln,Glu,Lys,Met,Ser,Tyr,Val,或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点99(D)其它信息/注释=“Xaa在位点99是Ile或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点100(D)其它信息/注释=“Xaa在位点100是Lys或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点101(D)其它信息/注释=“Xaa在位点101是Asp,Pro,Met,Lys,Thr,His,Asn,Ile,Leu，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点105(D)其它信息/注释=“Xaa在位点105是Asn,Pro,Ser,Ile，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点108(D)其它信息/注释=“Xaa在位点108是Arg,Ala，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Arg,Thr,Glu,Leu，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点112(D)其它信息/注释=“Xaa在位点112是Thr或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点116(D)其它信息/注释=“Xaa在位点116是Lys,Val,Trp,Ala,His,Phe,Tyr，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点117(D)其它信息/注释=“Xaa在位点117是Thr或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点120(D)其它信息/注释=“Xaa在位点120是Asn,Pro,Leu,His,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点121(D)其它信息/注释=“Xaa在位点121是Ala,Ser,Ile,Pro，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点122(D)其它信息/注释=“Xaa在位点122是Gln,Met,Trp,Phe,Pro,His,Ile，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点123(D)其它信息/注释=“Xaa在位点123是Ala,Met,Glu,Ser，或Leu”(ⅹⅰ)序列描述SEQ ID NO3P224Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa Xaa Pro Xaa20 25 30Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa Ile Leu35 40 45Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu Ala Phe Xaa Arg Xaa50 55 60Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile Glu Xaa Xaa Leu Xaa Xaa65 70 75 80Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg Xaa Pro85 90 95Ile Xaa Xaa Xaa Xaa Gly Asp Trp Xaa Glu Phe Xaa Xaa Lys Leu Xaa100 105 110Phe Tyr Leu Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln Thr Thr Leu115 120 125Ser Leu Ala Ile Phe130(2)SEQ ID NO4的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点1(D)其它信息/注释=“Met-或Met-Ala-可或不在位点1启始氨基酸”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点3(D)其它信息/注释=“Xaa在位点3是Ser,Lys,Gly,Asp,Met,Gln，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点4(D)其它信息/注释=“Xaa在位点4是Asn,His,Leu,Ile,Phe,Arg，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点5(D)其它信息/注释=“Xaa在位点5是Met,Phe,Ile,Arg,Gly,Ala，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点6(D)其它信息/注释=“Xaa在位点6是Ile,Cys,Gln,Glu,Arg,Pro，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点7(D)其它信息/注释=“Xaa在位点7是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点8(D)其它信息/注释=“Xaa在位点8是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点9(D)其它信息/注释=“Xaa在位点9是Ile,Val,Ala,Leu,Gly,Trp,Lys,Phe,Leu,Ser或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点10(D)其它信息/注释=“Xaa在位点10是Ile,Gly,Val,Arg,Ser,Phe，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点11(D)其它信息/注释=“Xaa在位点11是Thr,His,Gly,Gln,Arg,Pro，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点12(D)其它信息/注释=“Xaa在位点12是His,Thr,Phe,Gly,Arg,Ala，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点13(D)其它信息/注释=“Xaa在位点13是Leu,Gly,Arg,Thr,Ser，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点14(D)其它信息/注释=“Xaa在位点14是Lys,Arg,Leu,Gln,Gly,Pro,Val，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点15(D)其它信息/注释=“Xaa在位点15是Gln,Asn,Leu,Pro,Arg，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点16(D)其它信息/注释=“Xaa在位点16是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点17(D)其它信息/注释=“Xaa在位点17是Pro,Asp,Gly,
Ala,Arg,Leu，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Leu,Val,Arg,Gln,Asn,Gly,Ala，或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点19(D)其它信息/注释=“Xaa在位点19是Pro,Leu,Gln,Ala,Thr，或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点20(D)其它信息/注释=“Xaa在位点20是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile,或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点21(D)其它信息/注释=“Xaa在位点21是Leu,Ala,Gly,Asn,Pro,Gln，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点22(D)其它信息/注释=“Xaa在位点22是Asp,Leu，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点23(D)其它信息/注释=“Xaa在位点23是Phe,Ser,Pro,Trp，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点24(D)其它信息/注释=“Xaa在位点24是Asn或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点26(D)其它信息/注释=“Xaa在位点26是Leu,Trp，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点27(D)其它信息/注释=“Xaa在位点27是Asn,Cys,Arg,Leu,His,Met，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点28(D)其它信息/注释=“Xaa在位点28是Gly,Asp,Ser,Cys,Ala,Lys,Asn,Thr,Leu,Val,Glu,Phe,Tyr,Ile，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点29(D)其它信息/注释=“Xaa在位点29是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,Gly,或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点30(D)其它信息/注释=“Xaa在位点30是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,Ala,
或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点3l(D)其它信息/注释=“Xaa在位点31是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Asp,Asn,Arg,Ser,Ala,Ile,Glu,His，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,Tys,Ile,Val，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点33(D)其它信息/注释=“Xaa在位点33是Ile,Gly,Val,Ser,Arg,Pro，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点34(D)其它信息/注释=“Xaa在位点34是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,Val，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点35(D)其它信息/注释=“Xaa在位点35是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点36
(D)其它信息/注释=“Xaa在位点36是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,Phe,Met，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点37(D)其它信息/注释=“Xaa在位点37是Asn,Arg,Met,Pro,Ser,Thr，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点38(D)其它信息/注释=“Xaa在位点38是Asn,His,Arg,Leu,Gly,Ser，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点39(D)其它信息/注释=“Xaa在位点39是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点40(D)其它信息/注释=“Xaa在位点40是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点41(D)其它信息/注释=“Xaa在位点41是Arg,Thr,Val,Ser,Leu，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点42(D)其它信息/注释=“Xaa在位点42是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,Leu,Val，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点43(D)其它信息/注释=“Xaa在位点43是Asn或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点44(D)其它信息/注释=“Xaa在位点44是Leu,Ser,Asp,Arg,Gln,Val，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点45(D)其它信息/注释=“Xaa在位点45是Glu,Tyr,His,Leu,Pro，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点46(D)其它信息/注释=“Xaa在位点46是Ala,Ser,Pro,Tyr,Asn，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点47(D)其它信息/注释=“Xaa在位点47是Phe,Asn,Glu,Pro,Lys,Arg，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点48(D)其它信息/注释=“Xaa在位点48是Asn,His,Val,
Arg,Pro,Thr,Asp，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点49(D)其它信息/注释=“Xaa在位点49是Arg,Tyr,Trp,Lys,Ser,His,Pro，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点50(D)其它信息/注释=“Xaa在位点50是Ala,Asn,Pro,Ser，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Val,Thr,Pro,His,Leu,Phe，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点52(D)其它信息/注释=“Xaa在位点52是Lys,Ile,Arg,Val,Asn,Glu，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点53(D)其它信息/注释=“Xaa在位点53是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点54(D)其它信息/注释=“Xaa在位点54是Leu,Val,Trp,Ser,Ile,Phe,Thr，或His”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点56(D)其它信息/注释=“Xaa在位点56是Asn,Leu,Val,Trp,Pro，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点57(D)其它信息/注释=“Xaa在位点57是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点58(D)其它信息/注释=“Xaa在位点58是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点59(D)其它信息/注释=“Xaa在位点59是Ala,Glu,Asp,Leu,Ser,Gly,Thr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点60(D)其它信息/注释=“Xaa在位点60是Ile,Met,Thr,Pro,Arg,Gly,Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点61
(D)其它信息/注释=“Xaa在位点61是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点63(D)其它信息/注释=“Xaa在位点63是Ile,Ser,Arg,Thr，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点64(D)其它信息/注释=“Xaa在位点64是Leu,Ala,Ser,Glu,Phe,Gly，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Lys,Thr,Gly,Asn,Met,Arg,Ile，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点66(D)其它信息/注释=“Xaa在位点66是Asn,Trp,Val,Gly,Thr,Leu,Glu，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点67(D)其它信息/注释=“Xaa在位点67是Leu,Gln,Gly,
Ala,Trp,Arg,Val，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点68(D)其它信息/注释=“Xaa在位点68是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,Ala,Tyr,Phr,Ile,Met，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点69(D)其它信息/注释=“Xaa在位点69是Pro,Ala,Thr,Trp,Arg，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点70(D)其它信息/注释=“Xaa在位点70是Cys,Glu,Gly,Arg,Met，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点71(D)其它信息/注释=“Xaa在位点71是Leu,Asn,Val,或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点72(D)其它信息/注释=“Xaa在位点72是Pro,Cys,Arg,Ala，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点73(D)其它信息/注释=“Xaa在位点73是Leu,Ser,Trp,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点74(D)其它信息/注释=“Xaa在位点74是Ala,Lys,Arg,Val，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点75(D)其它信息/注释=“Xaa在位点75是Thr,Asp,Cys,Leu,Val,Glu,His,Asn，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点76(D)其它信息/注释=“Xaa在位点76是Ala,Pro,Ser,Thr,Gly,Asp,Ile，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点77(D)其它信息/注释=“Xaa在位点77是Ala,Pro,Ser,Thr,Phe,Leu,Asp，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点78(D)其它信息/注释=“Xaa在位点78是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点80(D)其它信息/注释=“Xaa在位点80是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点81(D)其它信息/注释=“Xaa在位点81是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,Trp,Phe,Ile，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点82(D)其它信息/注释=“Xaa在位点82是Pro,Lys,Tyr,Gly,Ile，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点83(D)其它信息/注释=“Xaa在位点83是Ile,Val,Lys,Ala，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点84(D)其它信息/注释=“Xaa在位点84是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,Val,Lys,Arg,Tyr，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点85(D)其它信息/注释=“Xaa在位点85是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe，或His”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点86(D)其它信息/注释=“Xaa在位点86是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点87(D)其它信息/注释=“Xaa在位点87是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,Ala,Gly,Ile,Leu，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点88(D)其它信息/注释=“Xaa在位点88是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点89(D)其它信息/注释=“Xaa在位点89是Asp或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点90(D)其它信息/注释=“Xaa在位点90是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91(D)其它信息/注释=“Xaa在位点91是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp,或His”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点92(D)其它信息/注释=“Xaa在位点92是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点94(D)其它信息/注释=“Xaa在位点94是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是Arg,Thr,Pro,Glu,Tyr,Leu,Ser，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点96(D)其它信息/注释=“Xaa在位点96是Lys,Asn,Thr,Leu,Gln,Arg,His,Glu,Ser,Ala，或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点97(D)其它信息/注释=“Xaa在位点97是Leu,Ile,Arg,Asp，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是Thr,Val,Gln,Tyr,Glu,His,Ser，或Phe”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点99
(D)其它信息/注释=“Xaa在位点99是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val,或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点100(D)其它信息/注释=“Xaa在位点100是Tyr,Cys,His,Ser,Trp,Arg，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点101(D)其它信息/注释=“Xaa在位点101是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点102(D)其它信息/注释=“Xaa在位点102是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,Asn,His,Ala,Tyr,Phe,Gln，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点103(D)其它信息/注释=“Xaa在位点103是Thr,Ser,Asn,Ile,Trp,Lys，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点104(D)其它信息/注释=“Xaa在位点104是Leu,Ser,Pro,Ala,Glu,Cys,Asp，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点105(D)其它信息/注释=“Xaa在位点105是Glu,Ser,Lys,Pro,Leu,Thr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点106(D)其它信息/注释=“Xaa在位点106是Asn,Ala,Pro,Leu,His,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点107(D)其它信息/注释=“Xaa在位点107是Ala,Ser,Ile,Asn,Pro,Lys,Asp，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点108(D)其它信息/注释=“Xaa在位点108是Gln,Ser,Met,Trp,Arg,Phe,His,Ile,Tyr，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu”(ⅹⅰ)序列描述SEQ ID NO4Asn Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa1 5 10 15Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa65 70 75 80Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa85 90 95Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gln Gln100 105 110(2)SEQ ID NO5的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点1(D)其它信息/注释=“可在或不在位点1氨基酸前含有Met-或Met-Ala-”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点3(D)其它信息/注释=“Xaa在位点3是Ser,Gly,Asp,Met，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点4(D)其它信息/注释=“Xaa在位点4是Asn,His，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点5(D)其它信息/注释=“Xaa在位点5是Met或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点7(D)其它信息/注释=“Xaa在位点7是Asp或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点9(p)其它信息/注释=“Xaa在位点9是Ile,Ala,Leu,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点10(D)其它信息/注释=“Xaa在位点10是Ile,Val，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点11(D)其它信息/注释=“Xaa在位点11是Thr,His,Gln,或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点12(D)其它信息/注释=“Xaa在位点12是His或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点15(D)其它信息/注释=“Xaa在位点15是Gln,Asn，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点16(D)其它信息/注释=“Xaa在位点16是Pro,Gly，或Gln”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点17(D)其它信息/注释=“Xaa在位点17是Pro,Asp,Gly,或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Leu,Arg,Gln,Asn,Gly,Ala，或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点19(D)其它信息/注释=“Xaa在位点19是Pro或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点20(D)其它信息/注释=“Xaa在位点20是Leu,Val,Gly,Ser,Lys,Ala,Arg,Gln,Glu,Ile,Phe,Thr,或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点21(D)其它信息/注释=“Xaa在位点21是Leu,Ala,Asn,Pro,Gln，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点23(D)其它信息/注释=“Xaa在位点23是Phe,Ser,Pro,或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点24
(D)其它信息/注释=“Xaa在位点24是Asn或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点28(D)其它信息/注释=“Xaa在位点28是Gly,Asp,Ser,Cys,Ala,Asn,Ile,Leu,Met,Tyr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点30(D)其它信息/注释=“Xaa在位点30是Asp或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点31(D)其它信息/注释=“Xaa在位点31是Gln,Val,Met,Leu,Thr,Ala,Asn,Glu,Ser，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Asp,Phe,Ser,Thr,Ala,Asn,Gln,Glu,His,Ele,Lys,Tyr,Val，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点36(D)其它信息/注释=“Xaa在位点36是Glu,Ala,Asn,Ser，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点37(D)其它信息/注释=“Xaa在位点37是Asn,Arg,Met,Pro,Ser,Thr，或His”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点40(D)其它信息/注释=“Xaa在位点40是Arg或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点41(D)其它信息/注释=“Xaa在位点41是Arg,Thr,Val,Leu，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点42(D)其它信息/注释=“Xaa在位点42是Pro,Gly,Ser,Gln,Ala,Arg,Asn,Glu,Leu,Thr,Val，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点46(D)其它信息/注释=“Xaa在位点46是Ala或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点48(D)其它信息/注释=“Xaa在位点48是Asn,Pro,Thr,或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点49(D)其它信息/注释=“Xaa在位点49是Arg或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点50(D)其它信息/注释=“Xaa在位点50是Ala或Asn”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Val或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点52(D)其它信息/注释=“Xaa在位点52是Lys或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点53(D)其它信息/注释=“Xaa在位点53是Ser,Phe，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点54(D)其它信息/注释=“Xaa在位点54是Leu,Ile,Phe,或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Gln,Ala,Pro,Thr,Glu,Arg，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点57(D)其它信息/注释=“Xaa在位点57是Ala,Pro，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点58(D)其它信息/注释=“Xaa在位点58是Ser,Glu,Arg,或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点59(D)其它信息/注释=“Xaa在位点59是Ala或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Ser,Val,Ala,Asn,Glu,Pro，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点63(D)其它信息/注释=“Xaa在位点63是Ile或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Lys,Thr,Gly,Asn,Met,Arg,Ile,Gly，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点66(D)其它信息/注释=“Xaa在位点66是Asn,Gly,Glu,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点68(D)其它信息/注释=“Xaa在位点68是Leu,Gln,Trp,Arg,Asp,Ala,Asn,Glu,His,Ile,Met,Phe,Ser,Thr,Tyr，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点69(D)其它信息/注释=“Xaa在位点69是Pro或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点71(D)其它信息/注释=“Xaa在位点71是Leu或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点73(D)其它信息/注释=“Xaa在位点73是Leu或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点74(D)其它信息/注释=“Xaa在位点74是Ala或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点77(D)其它信息/注释=“Xaa在位点77是Ala或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Thr,Asp,Ser,Pro,Ala,Leu，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点81(D)其它信息/注释=“Xaa在位点81是His,Pro,Arg,Val,Leu,Gly,Asn,Phe,Ser，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点82(D)其它信息/注释=“Xaa在位点82是Pro或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点83(D)其它信息/注释=“Xaa在位点83是Ile或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点84(D)其它信息/注释=“Xaa在位点84是His,Ile,Asn,Leu,Ala,Thr,Arg,Gln,Lys,Met,Ser,Tyr,Val，或Pro”，(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点85(D)其它信息/注释=“Xaa在位点85是Ile,Leu，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点86(D)其它信息/注释=“Xaa在位点86是Lys,Arg,Ile,Gln,Pro，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点87(D)其它信息/注释=“Xaa在位点87是Asp,Pro,Met,Lys,His,Thr,Asn,Ile,Leu，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点90(D)其它信息/注释=“Xaa在位点90是Trp或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91
(D)其它信息/注释=“Xaa在位点91是Asn,Pro,Ala,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点92(D)其它信息/注释=“Xaa在位点92是Glu或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点94(D)其它信息/注释=“Xaa在位点94是Arg,Ala，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是Arg,Thr,Glu,Leu，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是Thr,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点100(D)其它信息/注释=“Xaa在位点100是Tyr或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点101(D)其它信息/注释=“Xaa在位点101是Leu或Ala”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点102(D)其它信息/注释=“Xaa在位点102是Lys,Thr,Val,Trp,Ser,Ala,His,Met,Phe,Tyr，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点103(D)其它信息/注释=“Xaa在位点103是Thr或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点106(D)其它信息/注释=“Xaa在位点106是Asn,Pro,Leu,His,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点107(D)其它信息/注释=“Xaa在位点107是Ala,Ser,Ile,Asn,Pro,Asp，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点108(D)其它信息/注释=“Xaa在位点108是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu”(ⅹⅰ)序列描述SEQ ID NO5Asn Cys Xaa Xaa Xaa ILe Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa Xaa1 5 10 15Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa Xaa Xaa20 25 30Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu Xaa Phe Xaa35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile Glu Xaa Xaa Leu50 55 60Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg65 70 75 80Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa Xaa Xaa Phe Xaa Xaa Lys85 90 95Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln100 105 110(2 SEQ ID NO6的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点1(D)其它信息/注释=“可在或不在位点1氨基酸前含有Met-或Met-Ala-”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点3(D)其它信息/注释=“Xaa在位点3是Ser,Gly,Asp,或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点4(D)其它信息/注释=“Xaa在位点4是Asn,His，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点9(D)其它信息/注释=“Xaa在位点9是Ile,Ala,Leu,或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点11(D)其它信息/注释=“Xaa在位点11是Thr,His，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点12(D)其它信息/注释=“Xaa在位点12是His或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点15(D)其它信息/注释=“Xaa在位点15是Gln或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点16(D)其它信息/注释=“Xaa在位点16是Pro或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Leu,Arg,Asn,或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点20(D)其它信息/注释=“Xaa在位点20是Leu,Val,Ser,Ala,Arg,Gln,Glu,Ile,Phe,Thr，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点21(D)其它信息/注释=“Xaa在位点21是Leu,Ala,Asn,或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点24(D)其它信息/注释=“Xaa在位点24是Asn或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点28(D)其它信息/注释=“Xaa在位点28是Gly,Asp,Ser,Ala,Asn,Ile,Leu,Met,Tyr，或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点31(D)其它信息/注释=“Xaa在位点31是Gln,Val,Met,Leu,Ala,Asn,Glu，或Lys”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Asp,Phe,Ser,Ala,Gln,Glu,His,Val，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点36(D)其它信息/注释=“Xaa在位点36是Glu,Asn,Ser,或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点37(D)其它信息/注释=“Xaa在位点37是Asn,Arg,Pro,Thr，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点41(D)其它信息/注释=“Xaa在位点41是Arg,Leu，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点42(D)其它信息/注释=“Xaa在位点42是Pro,Gly,Ser,Ala,Asn,Val,Leu，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点48(D)其它信息/注释=“Xaa在位点48是Asn,Pro，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点50(D)其它信息/注释=“Xaa在位点50是Ala或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Val或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点53(D)其它信息/注释=“Xaa在位点53是Ser或Phe”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点54(D)其它信息/注释=“Xaa在位点54是Leu或Phe”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Gln,Ala,Glu,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Ser,Val,Asn,Pro，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点63(D)其它信息/注释=“Xaa在位点63是Ile或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Lys,Asn,Met,Arg,Ile，或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点66(D)其它信息/注释=“Xaa在位点66是Asn,Gly,Glu,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点68(D)其它信息/注释=“Xaa在位点68是Leu,Gln,Trp,Arg,Asp,Asn,Glu,His,Met,Phe,Ser,Thr,Tyr，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点73
(D)其它信息/注释=“Xaa在位点73是Leu或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点74(D)其它信息/注释=“Xaa在位点74是Ala或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点77(D)其它信息/注释=“Xaa在位点77是Ala或Prp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Thr,Asp，或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点81(D)其它信息/注释=“Xaa在位点81是His,Pro,Arg,Val,Gly,Asn,Ser，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点84(D)其它信息/注释=“Xaa在位点84是His,Ile,Asn,Leu,Ala,Thr,Arg,Gln,Glu,Lys,Met,Ser,Tyr,Val，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点85(D)其它信息/注释=“Xaa在位点85是Ile或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点86
(D)其它信息/注释=“Xaa在位点86是Lys或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点87(D)其它信息/注释=“Xaa在位点87是Asp,Pro,Met,Lys,His,Pro,Asn,Ile,Leu，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91(D)其它信息/注释=“Xaa在位点91是Asn,Pro,Ser,Ile，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点94(D)其它信息/注释=“Xaa在位点94是Arg,Ala，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是Arg,Thr,Glu,Leu，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是Thr或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点102(D)其它信息/注释=“Xaa在位点102是Lys,Val,Trp,或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点103(D)其它信息/注释=“Xaa在位点103是Thr,Ala,His,Phe,Tyr，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点106(D)其它信息/注释=“Xaa在位点106是Asn,Pro,Leu,His,Val，或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点107(D)其它信息/注释=“Xaa在位点107是Ala,Ser,Ile,Pro，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点108(D)其它信息/注释=“Xaa在位点108是Gln,Met,Trp,Phe,Pro,His,Ile，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Ala,Met,Glu,Ser，或Leu”(ⅹⅰ)序列描述SEQ ID NO6Asn Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa Xaa1 5 10 15Pro Xaa Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa20 25 30Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu Ala Phe Xaa35 40 45Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile Glu Xaa Xaa Leu50 55 60Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg65 70 75 80Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp Xaa Glu Phe Xaa Xaa Lys85 90 95Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu Xaa Xaa Xaa Xaa Gln Gln100 105 110(2)SEQ ID NO7的信息(ⅰ)序列特征(A)长度133氨基酸(B)类型氨基(D)拓扑学线性(ⅱ)分子类型肽(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点(D)其它信息/注释=“可在或不在位点1氨基酸前含有Met-”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Asn或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点19(D)其它信息/注释=“Xaa在位点19是Met,Ala，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点20(D)其它信息/注释=“Xaa在位点20是Ile,Pro，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点23(D)其它信息/注释=“Xaa在位点23是Ile,Ala，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点25(D)其它信息/注释=“Xaa在位点25是Thr或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点29(D)其它信息/注释=“Xaa在位点29是Gln,Arg,Val,或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Leu,Ala,Asn,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点34(D)其它信息/注释=“Xaa在位点34是Leu或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点37(D)其它信息/注释=“Xaa在位点37是Phe,Pro，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点38(D)其它信息/注释=“Xaa在位点38是Asn或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点42(D)其它信息/注释=“Xaa在位点42是Gly,Ala,SetAsp，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点45(D)其它信息/注释=“Xaa在位点45是Gln,Val，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点46(D)其它信息/注释=“Xaa在位点46是Asp或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点49(D)其它信息/注释=“Xaa在位点49是Met,Ile,Leu,或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点50(D)其它信息/注释=“Xaa在位点50是Glu或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Asn,Arg，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Arg,Leu，或Thr”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点56(D)其它信息/注释=“Xaa在位点56是Pro或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点59(D)其它信息/注释=“Xaa在位点59是Glu或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点60(D)其它信息/注释=“Xaa在位点60是Ala或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Asn,Val，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点63(D)其它信息/注释=“Xaa在位点63是Arg或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Val或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点67(D)其它信息/注释=“Xaa在位点67是Ser,Asn,His,或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点69
(D)其它信息/注释=“Xaa在位点69是Gln或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点73(D)其它信息/注释=“Xaa在位点73是Ala或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点76(D)其它信息/注释=“Xaa在位点76是Ser,Ala，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Lys,Arg，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点82(D)其它信息/注释=“Xaa在位点82是Leu,Glu,Val,或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点85(D)其它信息/注释=“Xaa在位点85是Leu或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点87(D)其它信息/注释=“Xaa在位点87是Leu,Ser，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点88
(D)其它信息/注释=“Xaa在位点88是Ala或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91(D)其它信息/注释=“Xaa在位点91是Ala或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点93(D)其它信息/注释=“Xaa在位点93是Pro或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是His或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是His,Ile，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点100(D)其它信息/注释=“Xaa在位点100是Lys或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点101(D)其它信息/注释=“Xaa在位点101是Asp,Ala，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点105(D)其它信息/注释=“Xaa在位点105是Asn或Glu”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Arg,Glu，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点112(D)其它信息/注释=“Xaa在位点112是Thr或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点116(D)其它信息/注释=“Xaa在位点116是Lys,Val,Trp,或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点117(D)其它信息/注释=“Xaa在位点117是Thr或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点120(D)其它信息/注释=“Xaa在位点120是Asn,Gln，或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点123(D)其它信息/注释=“Xaa在位点123是Ala或Glu”(ⅹⅰ)序列描述SEQ ID NO7Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn Cys1 5 10 15Ser Xaa Xaa Xaa Asp Glu Xaa Ile Xaa His Leu Lys Xaa Pro Pro Xaa20 25 30Pro Xaa Leu Asp Xaa Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa Ile Leu35 40 45Xaa Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa Xaa Ala50 55 60Xaa Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa Ile Leu Xaa Asn65 70 75 80Leu Xaa Pro Cys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg Xaa Pro85 90 95Ile Xaa Ile Xaa Xaa Gly Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Xaa100 105 110Phe Tyr Leu Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln Thr Thr Leu115 120 125Ser Leu Ala Ile Phe130(2)SEQ ID NO8的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点1(D)其它信息/注释=“Met-或Met-Ala可或不在位点1启始氨基酸”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点4(D)其它信息/注释=“Xaa在位点4是Asn或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点5(D)其它信息/注释=“Xaa在位点5是Met,Ala，或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点
(B)位点6(D)其它信息/注释=“Xaa在位点6是Ile,Pro，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点9(D)其它信息/注释=“Xaa在位点9是Ile,Ala，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点11(D)其它信息/注释=“Xaa在位点11是Thr或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点15(D)其它信息/注释=“Xaa在位点15是Gln,Arg,Val,或Ile”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点18(D)其它信息/注释=“Xaa在位点18是Leu,Ala,Asn,或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点20(D)其它信息/注释=“Xaa在位点20是Leu或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点23(D)其它信息/注释=“Xaa在位点23是Phe,Pro，或Ser”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点24(D)其它信息/注释=“Xaa在位点24是Asn或Ala”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点28(D)其它信息/注释=“Xaa在位点28是Gly,Ala,Ser,Asp，或Asn”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点31(D)其它信息/注释=“Xaa在位点31是Gln,Val，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点32(D)其它信息/注释=“Xaa在位点32是Asp或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点35(D)其它信息/注释=“Xaa在位点35是Met,Ile，或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点36(D)其它信息/注释=“Xaa在位点36是Glu或Asp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点37(D)其它信息/注释=“Xaa在位点37是Asn,Arg，或Ser”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点41(D)其它信息/注释=“Xaa在位点41是Arg,Leu，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点42(D)其它信息/注释=“Xaa在位点42是Pro或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点45(D)其它信息/注释=“Xaa在位点45是Glu或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点46(D)其它信息/注释=“Xaa在位点46是Ala或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点48(D)其它信息/注释=“Xaa在位点48是Asn,Val，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点49(D)其它信息/注释=“Xaa在位点49是Arg或His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点51(D)其它信息/注释=“Xaa在位点51是Val或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点53
(D)其它信息/注释=“Xaa在位点53是Ser,Asn,His,或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点55(D)其它信息/注释=“Xaa在位点55是Gln或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点59(D)其它信息/注释=“Xaa在位点59是Ala或Gly”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点62(D)其它信息/注释=“Xaa在位点62是Ser,Ala，或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点65(D)其它信息/注释=“Xaa在位点65是Lys,Arg，或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点67(D)其它信息/注释=“Xaa在位点67是Leu,Glu，或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点68(D)其它信息/注释=“Xaa在位点68是Leu,Glu,Val,或Trp”(ⅸ)特征
(A)名称/关键词已修饰的位点(B)位点71(p)其它信息/注释=“Xaa在位点71是Leu或Val”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点73(D)其它信息/注释=“Xaa在位点73是Leu,Ser，或Tyr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点74(D)其它信息/注释=“Xaa在位点74是Ala或Trp”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点77(D)其它信息/注释=“Xaa在位点77是Ala或Pro”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点79(D)其它信息/注释=“Xaa在位点79是Pro或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点81(D)其它信息/注释=“Xaa在位点81是His或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点84(D )其它信息/注释=“Xaa在位点84是His,Ile，或Thr”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点86
(D)其它信息/注释=“Xaa在位点86是Lys或Arg”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点87(D)其它信息/注释=“Xaa在位点87是Asp,Ala，或Met”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点91(D)其它信息/注释=“Xaa在位点91是Asn或Glu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点95(D)其它信息/注释=“Xaa在位点95是Arg,Glu，或Leu”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点98(D)其它信息/注释=“Xaa在位点98是Thr或Gln”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点102(D)其它信息/注释=“Xaa在位点102是Lys,Val,Trp,或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点103(D)其它信息/注释=“Xaa在位点103是Thr或Ser”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点106(D)其它信息/注释=“Xaa在位点106是Asn,Gln，或
His”(ⅸ)特征(A)名称/关键词已修饰的位点(B)位点109(D)其它信息/注释=“Xaa在位点109是Ala或Glu”(ⅹⅰ)序列描述SEQ ID NO8Asn Cys Ser Xaa Xaa Xaa Asp Glu Xaa Ile Xaa His Leu Lys Xaa Pro1 5 10 15Pro Xaa Pro Xaa Leu Asp Xaa Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa20 25 30Ile Leu Xaa Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa35 40 45Xaa Ala Xaa Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa Ile Leu50 55 60Xaa Asn Xaa Xaa Pro Gys Xaa Pro Xaa Xaa Thr Ala Xaa Pro Xaa Arg65 70 75 80Xaa Pro Ile Xaa Ile Xaa Xaa Gly Asp Trp Xaa Glu Phe Arg Xaa Lys85 90 95Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln100 105 110(2)SEQ ID NO9的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO9Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO10的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO10Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO11的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽
(ⅹⅰ)序列描述SEQ ID NO11Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro1 5 10 15Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO12的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO12Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO13的信息(ⅰ)序列特征
(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO13Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO14的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO14Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val35 40 45Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys
85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO15的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO15Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO16的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO16Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu50 55 60Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO17的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO17Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln100 105 110(2)SEQ ID NO18的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽
(ⅹⅰ)序列描述SEQ ID NO18Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Glu Lys85 90 95Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln100 105 110(2)SEQ ID NO19的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO19Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu50 55 60Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln100 105 110(2)SEQ ID NO20的信息
(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO20Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro1 5 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu50 55 60Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys85 90 95Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln100 105 110(2)SEQ ID NO21的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO21Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro15 10 15Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp20 25 30Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn35 40 45Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala Ile Leu50 55 60Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg65 70 75 80His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys85 90 95Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln Gln100 105 110(2)SEQ ID NO22的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO22Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO23的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO23Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro1 5 10 15Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp20 25 30Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val35 40 45Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO24的信息(ⅰ)序列特征(A)长度111氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO24Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Val Pro1 5 10 15Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp Met Asp20 25 30Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala Phe Val35 40 45Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser Ile Leu50 55 60Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg65 70 75 80His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys85 90 95Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln100 105 110(2)SEQ ID NO25的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽
(ⅹⅰ)序列描述SEQ ID NO25Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp20 25 30Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO26的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO26Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lye1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp20 25 30Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO27的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO27Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys1 5 10 15Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp20 25 30Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala35 40 45Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO28的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO28Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 510 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln100 105 110Gln(2)SEQ ID NO29的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO29Met Ala Asn Cys Ser Ils Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Ala Ile Glu Ser50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln100 105 110Gln(2)SEQ ID NO30的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO30Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Aan Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Ala Ile Glu Ser50 55 60Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro65 70 75 80Thr Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg85 90 95Arg Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln100 105 110Gln(2)SEQ ID NO31的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO31Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO32的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO32Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO33的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO33Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lye Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO34的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO34Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro60 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO35的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO35Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp20 25 30Met Aap Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO36的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO36Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60lle Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln100 105 110
Gln(2)SEQ ID NO37的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO37Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO38的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO38Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO39的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO39Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp20 25 30Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Val Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Thr Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Ser Leu Glu His Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO40的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO40Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp20 25 30Val Aep Ile Leu Met Asp Arg Asn Leu Arg Leu Ser Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO41的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO41Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lya Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO42的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO42Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO43的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO43Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp20 25 30Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Als Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO44的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO44Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO45的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽
(ⅹⅰ)序列描述SEQ ID NO45Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO46的信息(ⅰ)序列特征(A)长度125氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO46Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys1 5 10 15Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Ala20 25 30Pro Leu Leu Asp Pro Asn Asn Leu Asn Ala Glu Asp Val Asp Ile Leu35 40 45Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser Phe Val Arg Ala50 55 60Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn65 70 75 80Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro85 90 95Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr100 105 110Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln115 120 125(2)SEQ ID NO47的信息(ⅰ)序列特征(A)长度125氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO47Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys Asn Cys1 5 10 15Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn20 25 30Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu35 40 45Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala50 55 60Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn65 70 75 80Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro85 90 95Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr100 105 110Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln115 120 125(2)SEQ ID NO48的信息(ⅰ)序列特征(A)长度113氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO48Met Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His Leu Lys1 5 10 15Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn Ser Glu Asp20 25 30Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln(2)SEQ ID NO49的信息(ⅰ)序列特征(A)长度134氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO49Met Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln Pro Pro20 25 30Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln Asp Ile35 40 45Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe Asn Arg50 55 60Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile Leu Lys65 70 75 80Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr Arg His85 90 95Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg Lys Leu100 105 110Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln Thr Thr115 120 125Leu Ser Leu Ala Ile Phe130(2)SEQ ID NO50的信息(ⅰ)序列特征
(A)长度36氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO50Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Gly Gly Gly1 5 10 15Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser20 25 30Gly Gly Gly Ser35(2)SEQ ID NO5l的信息(ⅰ)序列特征(A)长度24氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO51Ile Ser Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn Pro Ser Pro Pro1 5 10 15Ser Lys Glu Ser His Lys Ser Pro20(2)SEQ ID NO52的信息(ⅰ)序列特征(A)长度28氨基酸(B)类型氨基酸(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO52Ile Glu Gly Arg Ile Ser Glu Pro Ser Gly Pro Ile Ser Thr Ile Asn1 5 10 15Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro20 25(2)SEQ ID NO53的信息(ⅰ)序列特征(A)长度906碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO53ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CACCATTAGG CCCTGCCAGC 420TCCCTGCCCC AGAGCTTCCT GCTCAAGTGC TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT 480GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG 540GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG 600GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG 660CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CACACTGCAG 720CTGGACGTCG CCGACTTTGC CACCACCATC TAACTGGGAA TGGCCCCTGC CCTGCAGCCC 780ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 840GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 900CAGCCC 906(2)SEQ ID NO54的信息(ⅰ)序列特征(A)长度732碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)
(ⅹⅰ)序列描述SEQ ID NO54ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA ACTGCTCTAT AATGATCGAT 420GAAATTATAC ATCACTTAAA GAGACCACCT AACCCTTTGC TGGACCCGAA CAACCTCAAT 480TCTGAAGACA TGGATATCCT GATGGAACGA AACCTTCGAA CTCCAAACCT GCTCGCATTC 540GTAAGGGCTG TCAAGCACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTC 600CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CATCAAGGCA 660GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TGAGCAAGCG 720CAGGAACAAC AG 732(2)SEQ ID NO55的信息(ⅰ)序列特征(A)长度777碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO55ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCAC CGGCTCGTTC CCCGTCCCCG 420TCTACCCAGC CGTGGGAACA CGTGAATGCC ATCCAGGAGG CCCGGCGTCT CCTGAACCTG 480AGTAGAGACA CTGCTGCTGA GATGAATGAA ACAGTAGAAG TGATATCAGA AATGTTTGAC 540CTCCAGGAGC CGACTTGCCT ACAGACCCGC CTGGAGCTGT ACAAGCAGGG CCTGCGGGGC 600AGCCTCACCA AGCTCAAGGG CCCCTTGACC ATGATGGCCA GCCACTACAA GCAGCACTGC 660CCTCCAACCC CGGAAACTTC CTGTGCAACC CAGATTATCA CCTTTGAAAG TTTCAAAGAG 720AACCTGAAGG ACTTCCTGCT TGTCATCCCC TTTGACTGCT GGGAGCCAGT CCAGGAG 777(2)SEQ ID NO56的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO56ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CACCATTGGG CCCTGCCAGC 420TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT 480GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG 540GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG 600GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG 660CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CACACTGCAG 720CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT GGGAATGGCC 780CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG 840GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT 900CTACGCCACC TTGCGCAGCC C 920(2)SEQ ID NO57的信息(ⅰ)序列特征(A)长度951碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO57ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTC CAGTACCACC AGGTGAAGAT 420TCCAAAGATG TGGCCGCCCC ACACAGACAG CCACTCACCT CTTCAGAACG AATTGACAAA 480CAAATTCGGT ACATCCTCGA CGGGATATCA GCCCTGAGAA AGGAGACATG TAACAAGAGT 540AACATGTGTG AAAGCAGCAA AGAGGCGCTA GCAGAAAACA ACCTGAACCT TCCAAAGATG 600GCTGAAAAAG ATGGATGCTT CCAATCCGGA TTCAATGAGG AGACTTGCCT GGTGAAAATC 660ATCACTGGTC TTTTGGAGTT TGAGGTATAC CTCGAGTACC TCCAGAACAG ATTTGAGAGT 720AGTGAGGAAC AAGCCAGAGC TGTGCAGATG TCGACAAAAG TCCTGATCCA GTTCCTGCAG 780AAAAAGGCAA AGAATCTAGA TGCAATAACC ACCCCTGACC CAACCACAAA TGCATCCCTG 840CTGACGAAGC TGCAGGCACA GAACCAGTGG CTGCAGGACA TGACAACTCA TCTCATTCTG 900CGCAGCTTTA AGGAGTTCCT GCAGTCCAGC CTGAGGGCTC TTCGGCAAAT G 951(2)SEQ ID NO58的信息(ⅰ)序列特征(A)长度732碱基对(B)类型核酸(C)链型双(D)拓扑学线性
(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO58ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAAGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA ACTGCTCTAT AATGATCGAT 420GAAATTATAC ATCACTTAAA GAGACCACCT AACCCTTTGC TGGACCCGAA CAACCTCAAT 480TCTGAAGACA TGGATATCCT GATGGAACGA AACCTTCGAA CTCCAAACCT GCTCGCATTC 540GTAAGGGCTG TCAAGCACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTC 600CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CATCAAGGCA 660GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TGAGCAAGCG 720CAGGAACAAC AG 732(2)SEQ ID NO59的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO59ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGGAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAAGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CACCATTGGG CCCTGCCAGC 420TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT 480GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG 540GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG 600GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG 660CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CACACTGCAG 720CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT GGGAATGGCC 780CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG 840GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT 900CTACGCCACC TTGCGCAGCC C 921(2)SEQ ID NO60的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO60ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CACCATTGGG CCCTGCCAGC 420TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT 480GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG 540GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG 600GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG 660CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CACACTGCAG 720CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT GGGAATGGCC 780CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG 840GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT 900CTACGCCACC TTGCGCAGCC C(2)SEQ ID NO61的信息(ⅰ)序列特征(A)长度732碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO61CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA ACTGCTCTAT AATGATCGAT 420GAAATTATAC ATCACTTAAA GAGACCACCT AACCCTTTGC TGGACCCGAA CAACCTCAAT 480TCTGAAGACA TGGATATCCT GATGGAACGA AACCTTCGAA CTCCAAACCT GCTCGCATTC 540GTAAGGGCTG TCAAGCACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTC 600CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CATCAAGGCA 660GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TGAGCAAGCG 720CAGGAACAAC AG 732(2)SEQ ID NO62的信息(ⅰ)序列特征(A)长度777碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO62ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTAACTGC TCTATAATGA TCGATGAAAT TATACATCAC 480TTAAAGAGAC CACCTAACCC TTTGCTGGAC CCGAACAACC TCAATTCTGA AGACATGGAT 540ATCCTGATGG AACGAAACCT TCGAACTCCA AACCTGCTCG CATTCGTAAG GGCTGTCAAG 600CACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACC ATGTCTGCCC 660TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCA AGGCAGGTGA CTGGCAAGAA 720TTCCGGGAAA AACTGACGTT CTATCTGGTT ACCCTTGAGC AAGCGCAGGA ACAACAG 777(2)SEQ ID NO63的信息(ⅰ)序列特征(A)长度777碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO63ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAAGATT360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA420TCTCATAAAT CTCCAAACAT GGCTAACTGC TCTATAATGA TCGATGAAAT TATACATCAC480TTAAAGAGAC CACCTAACCC TTTGCTGGAC CCGAACAACC TCAATTCTGA AGACATGGAT540ATCCTGATGG AACGAAACCT TCGAACTCCA AACCTGCTCG CATTCGTAAG GGCTGTCAAG600CACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACC ATGTCTGCCC660TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCA AGGCAGGTGA CTGGCAAGAA720TTCCGGGAAA AACTGACGTT CTATCTGGTT ACCCTTGAGC AAGCGCAGGA ACAACAG 777(2)SEQ ID NO64的信息(ⅰ)序列特征(A)长度777碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO64ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTAACTGC TCTATAATGA TCGATGAAAT TATACATCAC 480TTAAAGAGAC CACCTAACCC TTTGCTGGAC CCGAACAACC TCAATTCTGA AGACATGGAT 540ATCCTGATGG AACGAAACCT TCGAACTCCA AACCTGCTCG CATTCGTAAG GGCTGTCAAG 600CACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACC ATGTCTGCCC 660TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCA AGGCAGGTGA CTGGCAAGAA 720TTCCGGGAAA AACTGACGTT CTATCTGGTT ACCCTTGAGC AAGCGCAGGA ACAACAG 777(2)SEQ ID NO65的信息(ⅰ)序列特征(A)长度1047碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)
(ⅹⅰ)序列描述SEQ ID NO65ATGGCTAACT GCTCTATAAT GATGGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCCGGGC CTCCTGTCAA TGCTGGCGGC GGCTCTGGTG GTGGTTCTGG TGGCGGCTCT 420GAGGGTGGCG GCTCTGAGGG TGGCGGTTCT GAGGGTGGCG GCTCTGAGGG TGGCGGTTCC 480GGTGGCGGCT CCGGTTCCGG TGATTTTGAT TATGAAACATGGCTACACC ATTGGGCCCT 540GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC AAGTCTTTAG AGCAAGTGAG GAAGATCCAG 600GGCGATGGCG CAGCGCTCCA GGAGAAGCTG TGTGCCACCT ACAAGCTGTG CCACCCCGAG 660GAGCTGGTGC TGCTCGGACA CTCTCTGGGC ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC 720AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG AGCCAACTCC ATAGCGGCCT TTTCCTCTAC 780CAGGGGCTCC TGCAGGCCCT GGAAGGGATA TCCCCCGAGT TGGGTCCCAC CTTGGACACA 840CTGCAGCTGG ACGTCGCCGA CTTTGCCACC ACCATCTCGC AGCAGATGGA AGAACTGGGA 900ATGGCCCCTG CCCTGCAGCC CACCCAGGGT GCCATGCCGG CCTTCGCCTC TGCTTTCCAG 960CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC CATCTGCAGA GCTTCCTGGA GGTGTCGTAC 1020CGCGTTCTAC GCCACCTTGC GCAGCCC 1047(2)SEQ ID NO66的信息(ⅰ)序列特征(A)长度903碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO66ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAG60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCCGGGC CTCCTGTCAA TGCTGGCGGC GGCTCTGGTG GTGGTTCTGG TGGCGGCTCT 420GAGGGTGGCG GCTCTGAGGG TGGCGGTTCT GAGGGTGGCG GCTCTGAGGG TGGCGGTTCC 480GGTGGCGGCT CCGGTTCCGG TGATTTTGAT TATGAAAACA TGGCACCGGC TCGTTCCCCG 540TCCCCGTCTA CCCAGCCGTG GGAACACGTG AATGCCATCC AGGAGGCCCG GCGTCTCCTG 600AACCTGAGTA GAGACACTGC TGCTGAGATG AATGAAACAG TAGAAGTGAT ATCAGAAATG 660TTTGACCTCC AGGAGCCGAC TTGCCTACAG ACCCGCCTGG AGCTGTACAA GCAGGGCCTG 720CGGGGCAGCC TCACCAAGCT CAAGGGCCCC TTGACCATGA TGGCCAGCCA CTACAAGCAG 780CACTGCCCTC CAACCCCGGA AACTTCCTGT GCAACCCAGA TTATCACCTT TGAAAGTTTC 840AAAGAGAACC TGAAGGACTT CCTGCTTGTC ATCCCCTTTG ACTGCTGGGA GCCAGTCCAG 900GAG 903(2)SEQ ID NO67的信息(ⅰ)序列特征(A)长度1017碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO67ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCCGGTG GCGGCGGCTC TGGTGGTGGT TCTGGTGGCG GCTCTGAGGG TGGCGGCTCT 420GAGGGTGGCG GTTCTGAGGG TGGCGGCTCT GAGGGTGGCG GTTCCGGTGG CGGCTCCGGT 480TCCGGTAACA TGGCTACACC ATTAGGCCCT GCCAGCTCCC TGCCCCAGAG CTTCCTGCTC 540AAGTGCTTAG AGCAAGTGAG GAAGATCCAG GGCGATGGCG CAGCGCTCCA GGAGAAGCTG 600TGTGCCACCT ACAAGCTGTG CCACCCCGAG GAGCTGGTGC TGCTCGGACA CTCTCTGGGC 660ATCCCCTGGG CTCCCCTGAG CTCCTGCCCC AGCCAGGCCC TGCAGCTGGC AGGCTGCTTG 720AGCCAACTCC ATAGCGGCCT TTTCCTCTAC CAGGGGCTCC TGCAGGCCCT GGAAGGGATA 780TCCCCCGAGT TGGGTCCCAC CTTGGACACA CTGCAGCTGG ACGTCGCCGA CTTTGCCACC 840ACCATCTGGC AGCAGATGGA AGAACTGGGA ATGGCCCCTG CCCTGCAGCC CACCCAGGGT 900GCCATGCCGG CCTTCGCCTC TGCTTTCCAG CGCCGGGCAG GAGGGGTCCT GGTTGCTAGC 960CATCTGCAGA GCTTCCTGGA GGTGTCGTAC CGCGTTCTAC GCCACCTTGC GCAGCCC 1017(2)SEQ ID NO68的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO68ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC 480TTCCTGCTCA AGTGCTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG 540GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC 600TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA 660GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 720GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC 780TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC 840ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 900GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 960CAGCCC 966(2)SEQ ID NO69的信息(ⅰ)序列特征(A)长度822碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO69ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCACCGGCT CGTTCCCCGT CCCCGTCTAC CCAGCCGTGG 480GAACACGTGA ATGCCATCCA GGAGGCCCGG CGTCTCCTGA ACCTGAGTAG AGACACTGCT 540GCTGAGATGA ATGAAACAGT AGAAGTGATA TCAGAAATGT TTGACCTCCA GGAGCCGACT 600TGCCTACAGA CCCGCCTGGA GCTGTACAAG CAGGGCCTGC GGGGCAGCCT CACCAAGCTC 660AAGGGCCCCT TGACCATGAT GGCCAGCCAC TACAAGCAGC ACTGCCCTCC AACCCCGGAA 720ACTTCCTGTG CAACCCAGAT TATCACCTTT GAAAGTTTCA AAGAGAACCT GAAGGACTTC 780CTGCTTGTCA TCCCCTTTGA CTGCTGGGAG CCAGTCCAGG AG822(2)SEQ ID NO70的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸(C)链型双(D)拓扑学线性
(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO70ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAAGATT 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC 480TTCCTGCTCA AGTGCTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG 540GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC 600TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA 660GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 720GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC 780TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC 840ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 900GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 960CAGCCC966(2)SEQ ID NO71的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO71ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC 60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTACACCA TTAGGCCCTG CCAGCTCCCT GCCCCAGAGC 480TTCCTGCTCA AGTGCTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG 540GAGAAGGTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC 600TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA 660GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 720GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC 780TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC 840ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 900GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 960CAGCCC966(2)SEQ ID NO72的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO72ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG 540GGAAGGATTT CCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATA 600ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTA ACCCTTTGCT GGACCCGAAC 660AACCTCAATT CTGAAGACAT GGATATCCTG ATGGAACGAA ACCTTCGAAC TCCAAACCTG 720CTCGCATTCG TAAGGGCTGT CAAGCACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT 780CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC 840ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT 900GAGCAAGCGC AGGAACAACA G 921(2)SEQ ID NO73的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO73ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG 540GGAAGGATTT CCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCG 600TCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGAT CGATGAAATT 660ATACATCACT TAAAGAGACC ACCTAACCCT TTGCTGGACC CGAACAACCT CAATTCTGAA 720GACATGGATA TCCTGATGGA ACGAAACCTT CGAACTCCAA ACCTGCTCGC ATTCGTAAGG 780GCTGTCAAGC ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA 840TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGAC900TGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCA AGCGCAGGAA960CAACAG 966(2)SEQ ID NO74的信息(ⅰ)序列特征(A)长度1047碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO74ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG 540GGAAGGATTT CCCCCGGGCC TCCTGTCAAT GCTGGCGGCG GCTCTGGTGG TGGTTCTGGT 600GGCGGCTCTG AGGGTGGCGG CTCTGAGGGT GGCGGTTCTG AGGGTGGCGG CTCTGAGGGT 660GGCGGTTCCG GTGGCGGCTC CGGTTCCGGT GATTTTGATT ATGAAAACAT GGCTAACTGC 720TCTATAATGA TCGATGAAAT TATACATCAC TTAAAGAGAC CACCTAACCC TTTGCTGGAC 780CCGAACAACC TCAATTCTGA AGACATGGAT ATCCTGATGG AACGAAACCT TCGAACTCCA 840AACCTGCTCG CATTCGTAAG GGCTGTCAAG CACTTAGAAA ATGCATCAGG TATTGAGGCA 900ATTCTTCGTA ATCTCCAACC ATGTCTGCCC TCTGCCACGG CCGCACCCTC TCGACATCCA 960ATCATCATCA AGGCAGGTGA CTGGCAAGAA TTCCGGGAAA AACTGACGTT CTATCTGGTT 1020ACCCTTGAGC AAGCGCAGGA ACAACAG1047(2)SEQ ID NO75的信息
(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO75ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG 540GGAAGGATTT CCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATA 600ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG CACCTTTGCT GGACCCGAAC 660AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGAACGAA ACCTTCGACT TCCAAACCTG 720GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT 780CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC 840ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT 900GAGCAAGCGC AGGAACAACA G 921(2)SEQ ID NO76的信息(ⅰ)序列特征(A)长度1047碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO76ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG 540GGAAGGATTT CCCCCGGGCC TCCTGTCAAT GCTGGCGGCG GCTCTGGTGG TGGTTCTGGT 600GGCGGCTCTG AGGGTGGCGG CTCTGAGGGT GGCGGTTCTG AGGGTGGCGG CTCTGAGGGT 660GGCGGTTCCG GTGGCGGCTC CGGTTCCGGT GATTTTGATT ATGAAAACAT GGCTAACTGC 720TCTATAATGA TCGATGAAAT TATACATCAC TTAAAGAGAC CACCTGCACC TTTGCTGGAC 780CCGAACAACC TCAATGACGA AGACGTCTCT ATCCTGATGG AACGAAACCT TCGACTTCCA 840AACCTGGAGA GCTTCGTAAG GGCTGTCAAG AACTTAGAAA ATGCATCAGG TATTGAGGCA 900ATTCTTCGTA ATCTCCAACC ATGTCTGCCC TCTGCCACGG CCGCACCCTC TCGACATCCA 960ATCATCATCA AGGCAGGTGA CTGGCAAGAA TTCCGGGAAA AACTGACGTT CTATCTGGTT 1020ACCCTTGAGC AAGCGCAGGA ACAACAG1047(2)SEQ ID NO77的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO77ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAATCGAG 540GGAAGGATTT CCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCG 600TCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGAT CGATGAAATT 660ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT CAATGACGAA 720GACGTCTCTA TCCTGATGGA ACGAAACCTT CGACTTCCAA ACCTGGAGAG CTTCGTAAGG 780GCTGTCAAGA ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA 840TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGAC 900TGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCA AGCGCAGGAA 960CAACAG966(2)SEQ ID NO78的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO78ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC 540GGTGGAGGCT CCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATA 600ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG CACCTTTGCT GGACCCGAAC 660AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGAACGAA ACCTTCGACT TCCAAACCTG 720GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT 780CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC 840ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT 900GAGCAAGCGC AGGAACAACA G 921(2)SEQ ID NO79的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO79ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC 540GGTGGAGGCT CCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCG 600TCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGAT CGATGAAATT 660ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT CAATGACGAA 720GACGTCTCTA TCCTGATGGA ACGAAACCTT CGACTTCCAA ACCTGGAGAG CTTCGTAAGG 780GCTGTCAAGA ACTTAGAAAA TGCATCAGGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA 840TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGAC 900TGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCA AGCGCAGGAA 960CAACAG966(2)SEQ ID NO80的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO80ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC 540GGTGGAGGCT CCCCGGGTGG TGGTTCTGGC GGCGGCTCCA ACATGGCTAA CTGCTCTATA 600ATGATCGATG AAATTATACA TCACTTAAAG AGACCACCTG CACCTTTGCT GGACCCGAAC 660AACCTCAATG ACGAAGACGT CTCTATCCTG ATGGAACGAA ACCTTCGACT TCCAAACCTG 720GAGAGCTTCG TAAGGGCTGT CAAGAACTTA GAAAATGCAT CAGGTATTGA GGCAATTCTT 780CGTAATCTCC AACCATGTCT GCCCTCTGCC ACGGCCGCAC CCTCTCGACA TCCAATCATC 840ATCAAGGCAG GTGACTGGCA AGAATTCCGG GAAAAACTGA CGTTCTATCT GGTTACCCTT 900GAGCAAGCGC AGGAACAACA G 921(2)SEQ ID NO81的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸(C)链型双(D)拓扑学线性
(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO81ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTA CGTAGAGGGC 540GGTGGAGGCT CCCCGGGTGA ACCGTCTGGT CCAATCTCTA CTATCAACCC GTCTCCTCCG 600TCTAAAGAAT CTCATAAATC TCCAAACATG GCTAACTGCT CTATAATGAT CGATGAAATT 660ATACATCACT TAAAGAGACC ACCTGCACCT TTGCTGGACC CGAACAACCT CAATGACGAA 720GACGTCTCTA TCCTGATGGA ACGAAACCTT CGACTTCCAA ACCTGGAGAG CTTCGTAAGG 780GCTGTCAAGA ACTTAGAAAA TGCATCACGT ATTGAGGCAA TTCTTCGTAA TCTCCAACCA 840TGTCTGCCCT CTGCCACGGC CGCACCCTCT CGACATCCAA TCATCATCAA GGCAGGTGAC 900TGGCAAGAAT TCCGGGAAAA ACTGACGTTC TATCTGGTTA CCCTTGAGCA AGCGCAGGAA 960CAACAG966(2)SEQ ID NO82的信息(ⅰ)序列特征(A)长度777碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO82ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTAACTGC TCTATAATGA TCGATGAAAT TATACATCAC 480TTAAAGAGAC CACCTGCACC TTTGCTGGAC CCGAACAACC TCAATGACGA AGACGTCTCT 540ATCCTGATGG AACGAAACCT TCGACTTCCA AACCTGGAGA GCTTCGTAAG GGCTGTCAAG 600AACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACC ATGTCTGCCC 660TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCA AGGCAGGTGA CTGGCAAGAA 720TTCCGGGAAA AACTGACGTT CTATCTGGTT ACCCTTGAGC AAGCGCAGGA ACAACAG777(2)SEQ ID NO83的信息(ⅰ)序列特征(A)长度984碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO83ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTACACCA TTGGGCCCTG CCAGCTCCCT GCCCCAGAGC 480TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG 540GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC 600TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA 660GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 720GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC 780TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC840ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG900GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG960CAGCCCTGAT AAGGATCCGA ATTC 984(2)SEQ ID NO84的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO84ATGGCTAACT GCTCTATAAT GATCCATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTCC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CACCATTAGG CCCTGCCAGC 420TCCCTGCCCC AGAGCTTCCT GCTCAAGTGC TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT 480GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG 540GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG 600GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG 660CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CACACTGCAG 720CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT GGGAATGGCC 780CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG 840GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT 900CTACGCCACC TTGCGCAGCC C 921(2)SEQ ID NO85的信息(ⅰ)序列特征
(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO85ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CACCATTGGG CCCTGCCAGC 420TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT 480GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGACGAGCTG 540GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG 600GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG 660CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CACACTGCAG 720CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT GGGAATGGCC 780CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG 840GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT 900CTACGCCACC TTGCGCAGCC C 921(2)SEQ ID NO86的信息(ⅰ)序列特征(A)长度732碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO86ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA ACTGCTCTAT AATGATCGAT 420GAAATTATAC ATCACTTAAA GAGACCACCT GCACCTTTGC TGGACCCGAA CAACCTCAAT 480GACGAAGACG TCTCTATCCT GATGGAACGA AACCTTCGAC TTCCAAACCT GGAGAGCTTC 540GTAAGGGCTG TCAAGAACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTC 600CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CATCAAGGCA 660GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TGAGCAAGCG 720CAGGAACAAC AG 732(2)SEQ ID NO87的信息(ⅰ)序列特征(A)长度921碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO87ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA CACCATTGGG CCCTGCCAGC420TCCCTGCCCC AGAGCTTCCT GCTCAAGTCT TTAGAGCAAG TGAGGAAGAT CCAGGGCGAT480GGCGCAGCGC TCCAGGAGAA GCTGTGTGCC ACCTACAAGC TGTGCCACCC CGAGGAGCTG540GTGCTGCTCG GACACTCTCT GGGCATCCCC TGGGCTCCCC TGAGCTCCTG CCCCAGCCAG600GCCCTGCAGC TGGCAGGCTG CTTGAGCCAA CTCCATAGCG GCCTTTTCCT CTACCAGGGG660CTCCTGCAGG CCCTGGAAGG GATATCCCCC GAGTTGGGTC CCACCTTGGA CACACTGCAG720CTGGACGTCG CCGACTTTGC CACCACCATC TGGCAGCAGA TGGAAGAACT GGGAATGGCC780CCTGCCCTGC AGCCCACCCA GGGTGCCATG CCGGCCTTCG CCTCTGCTTT CCAGCGCCGG840GCAGGAGGGG TCCTGGTTGC TAGCCATCTG CAGAGCTTCC TGGAGGTGTC GTACCGCGTT900CTACGCCACC TTGCGCAGCC C921(2)SEQ ID NO88的信息(ⅰ)序列特征(A)长度732碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO88ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA ACTGCTCTAT AATGATCGAT 420GAAATTATAC ATCACTTAAA GAGACCACCT GCACCTTTGC TGGACCCGAA CAACCTCAAT 480GACGAAGACG TCTCTATCCT GATGGAACGA AACCTTCGAC TTCCAAACCT GGAGAGCTTC 540GTAAGGGCTG TCAAGAACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTC 600CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CATCAAGGCA 660GGTGACTGGC AAGAATTCCG GGAAAA CTG ACGTTCTATC TGGTTACCCT TGAGCAAGCG 720CAGGAACAAC AG 732(2)SEQ ID NO89的信息(ⅰ)序列特征(A)长度966碱基对(B)类型核酸
(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO89ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTACACCA TTGGGCCCTG CCAGCTCCCT GCCCCAGAGC 480TTCCTGCTCA AGTCTTTAGA GCAAGTGAGG AAGATCCAGG GCGATGGCGC AGCGCTCCAG 540GAGAAGCTGT GTGCCACCTA CAAGCTGTGC CACCCCGAGG AGCTGGTGCT GCTCGGACAC 600TCTCTGGGCA TCCCCTGGGC TCCCCTGAGC TCCTGCCCCA GCCAGGCCCT GCAGCTGGCA 660GGCTGCTTGA GCCAACTCCA TAGCGGCCTT TTCCTCTACC AGGGGCTCCT GCAGGCCCTG 720GAAGGGATAT CCCCCGAGTT GGGTCCCACC TTGGACACAC TGCAGCTGGA CGTCGCCGAC 780TTTGCCACCA CCATCTGGCA GCAGATGGAA GAACTGGGAA TGGCCCCTGC CCTGCAGCCC 840ACCCAGGGTG CCATGCCGGC CTTCGCCTCT GCTTTCCAGC GCCGGGCAGG AGGGGTCCTG 900GTTGCTAGCC ATCTGCAGAG CTTCCTGGAG GTGTCGTACC GCGTTCTACG CCACCTTGCG 960CAGCCC 966(2)SEQ ID NO90的信息(ⅰ)序列特征(A)长度777碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO90ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTGCA 60CCTTTGCTGG ACCCGAACAA CCTCAATGAC GAAGACGTCT CTATCCTGAT GGAACGAAAC 120CTTCGACTTC CAAACCTGGA GAGCTTCGTA AGGGCTGTCA AGAACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGCGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG AACCGTCTGG TCCAATCTCT ACTATCAACC CGTCTCCTCC GTCTAAAGAA 420TCTCATAAAT CTCCAAACAT GGCTAACTGC TCTATAATGA TCGATGAAAT TATACATCAC 480TTAAAGAGAC CACCTGCACC TTTGCTGGAC CCGAACAACC TCAATGACGA AGACGTCTCT 540ATCCTGATGG AACGAAACCT TCGACTTCCA AACCTGGAGA GCTTCGTAAG GGCTGTCAAG 600AACTTAGAAA ATGCATCAGG TATTGAGGCA ATTCTTCGTA ATCTCCAACC ATGTCTGCCC 660TCTGCCACGG CCGCACCCTC TCGACATCCA ATCATCATCA AGGCAGGTGA CTGGCAAGAA 720TTCCGGGAAA AACTGACGTT CTATCTGGTT ACCCTTGAGC AAGCGCAGGA ACAACAG 777(2)SEQ ID NO91的信息(ⅰ)序列特征(A)长度41碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO91AATTCCGGGA AAAACTGACG TTCTATCTGG TTACCCTTGA G 41(2)SEQ ID NO92的信息(ⅰ)序列特征(A)长度46碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO92CTGCGCTTGC TCAAGGGTAA CCAGATAGAA CGTCACTTTT TCCCGG 46(2)SEQ ID NO93的信息(ⅰ)序列特征(A)长度39碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO93CAAGCGCAGG AACAACAGTA CGTAATCGAG GGAAGGATT 39(2)SEQ ID NO94的信息(ⅰ)序列特征(A)长度39碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO94ACCCGGGGAA ATCCTTCCCT CGATTACGTA CTGTTGTTC 39(2)SEQ ID NO95的信息(ⅰ)序列特征(A)长度58碱基对(B)类型核酸(C)链型单(D)拓扑学线性
(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO95TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGTAAG GTACCGCATG CAAGCTTAGA60TCT63(2)SEQ ID NO96的信息(ⅰ)序列特征(A)长度58碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO96(2)SEQ ID NO97的信息(ⅰ)序列特征(A)长度74碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO97(2)SEQ ID NO98的信息(ⅰ)序列特征
(A)长度74碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO98(2)SEQ ID NO99的信息(ⅰ)序列特征(A)长度68碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO99(2)SEQ ID NO100的信息(ⅰ)序列特征(A)长度68碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO100(2)SEQ ID NO101的信息(ⅰ)序列特征(A)长度21碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO101(2)SEQ ID NO102的信息(ⅰ)序列特征(A)长度25碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO102(2)SEQ ID NO103的信息(ⅰ)序列特征(A)长度21碱基对(B)类型核酸(C)链型单(D)拓扑学线性
(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO103(2)SEQ ID NO104的信息(ⅰ)序列特征(A)长度25碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO104(2)SEQ ID NO105的信息(ⅰ)序列特征(A)长度58碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO105(2)SEQ ID NO106的信息(ⅰ)序列特征(A)长度52碱基对(B)类型核酸
(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO106(2)SEQ ID NO107的信息(ⅰ)序列特征(A)长度66碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO107(2)SEQ ID NO108的信息(ⅰ)序列特征(A)长度66碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO108(2)SEQ ID NO109的信息
(ⅰ)序列特征(A)长度48碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO109(2)SEQ ID NO110的信息(ⅰ)序列特征(A)长度40碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO110(2)SEQ ID NO111的信息(ⅰ)序列特征(A)长度26碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO111(2)SEQ ID NO112的信息(ⅰ)序列特征(A)长度18碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO112(2)SEQ ID NO113的信息(ⅰ)序列特征(A)长度20碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc =“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO113(2)SEQ ID NO114的信息(ⅰ)序列特征(A)长度12碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”
(ⅹⅰ)序列描述SEQ ID NO114(2)SEQ ID NO115的信息(ⅰ)序列特征(A)长度20碱基对(B)类型核酸(C)链型 单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO115(2)SEQ ID NO116的信息(ⅰ)序列特征(A)长度12碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO116TAATGGTGTA GC(2)SEQ ID NO117的信息(ⅰ)序列特征(A)长度30碱基对(B)类型核酸(C)链型单(D)拓扑学线性
(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO117CCTGTCAACC CGGGCGGCGG CTCTGGTGGT 30(2)SEQ ID NO118的信息(ⅰ)序列特征(A)长度31碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO118TCATAATACA TGTTACCGGA ACGGAGCCGC C 31(2)SEQ ID NO119的信息(ⅰ)序列特征(A)长度34碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO119ATCGTCTGAC CTCCCGGGAC CTCCTGTCAA TGCT 34(2)SEQ ID NO120的信息(ⅰ)序列特征(A)长度30碱基对(B)类型核酸
(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/dese=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO120AGCGTTTGAC ATGTTTTCAT AATCAAAATC 30(2)SEQ ID NO121的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO121Men Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln130 135 140Sar Phe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp145 150 155 160Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His165 170 175Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala180 185 190Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu195 200 205Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala210 215 220Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln225 230 235 240Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu245 250 255Leu Gly Het Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala260 265 270Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser275 280 285His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu290 295 300Ala Gln Pro305(2)SEQ ID NO122的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO122Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln130 135 140Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp145 150 155 160Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His165 170 175Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala180 185 190Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu195 200 205Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala210 215 220Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln225 230 235 240Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu245 250 255Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala260 265 270Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser275 280 285His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu290 295 300Ala Gln Pro305(2)SEQ ID NO123的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO123Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln130 135 140Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp145 150 155 160Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His165 170 175Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala180 185 190Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu195 200 205Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala210 215 220Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln225 230 235 240Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu245 250 255Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala260 265 270Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser275 280 285His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu290 295 300Ala Gln Pro(2)SEQ ID NO124的信息(ⅰ)序列特征
(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO124Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln130 135 140Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp145 150 155 160Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His165 170 175Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala180 185 190Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu195 200 205Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala210 215 220Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln225 230 235 240Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu245 250 255Leu Gly Met Ala Pro Ala Lsu Gln Pro Thr Gln Gly Ala Met Pro Ala260 265 270Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser275 280 285His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu290 295 300Ala Gln Pro305(2)SEQ ID NO125的信息(ⅰ)序列特征(A)长度244氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO125Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lya His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Glnl00 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His130 135 140His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn145 150 155 160Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn
165 170 175Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly180 185 190Ils Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr195 200 205Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln210 215 220Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala225 230 235 240Gln Glu Gln Gln(2)SEQ ID NO126的信息(ⅰ)序列特征(A)长度244氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO126Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Aan Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His130 135 140His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn145 150 155 160Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn165 170 175Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly180 185 190Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr195 200 205Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln210 215 220Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala225 230 235 240Gln Glu Gln Gln(2)SEQ ID NO127的信息(ⅰ)序列特征(A)长度244氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO127Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His130 135 140His Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn145 150 155 160Ser Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn165 170 175Leu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly180 185 190Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr195 200 205Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln210 215 220Glu Phe Arg Glu Lys Leu Thr Pha Tyr Leu Val Thr Leu Glu Gln Ala225 230 235 240Gln Glu Gln Gln(2)SEQ ID NO128的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO128Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly AspTrp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser145 150 155 160Phe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly165 170 175Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro180 185 190Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro195 200 205Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser210 215 220Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu225 230 235 240Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu245 250 255Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu260 265 270Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe275 280 285Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His290 295 300Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala305310 315 320Gln Pro(2)SEQ ID NO129的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO129Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala
50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lye Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lye Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser145 150 155 160Phe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly165 170 175Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro180 185 190Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro195 200 205Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser210 215 220Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu225 230 235 240Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu245 250 255Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu260 265 270Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe275 280 285Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His290 295 300Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala305 310 315 320Gln Pro(2)SEQ ID NO130的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性
(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO130Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Aan Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro SerLys Glu Ser His Lys Ser130 135140Pro Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser145 150 155 160Phe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly165 170 175Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro180 185 190Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Prol95 200 205Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu ser210 215 220Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu225 230 235 240Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu245 250 255Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu260 265 270Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe275 280 285Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His290 295 300Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala305 310 315 320Gln Pro(2)SEQ ID NO131的信息(ⅰ)序列特征(A)长度259氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO131Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Sar Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His145 150 155 160Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser165 170 175Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu180 185 190Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile195 200 205Glu Ala Ile Leu Arg Ash Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala210 215 220Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu225 230 235 240Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln245 250 255Glu Gln Gln(2)SEQ ID NO132的信息(ⅰ)序列特征(A)长度259氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO132Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His145 150 155 160Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser165 170 175Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu180 185 190Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile195 200 205Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala210 215 220Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Aap Trp Gln Glu225 230 235 240Phe Arg Glu Lya Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln245 250 255Glu Gln Gln(2)SEQ ID NO133的信息(ⅰ)序列特征(A)长度259氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO133Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His145 150 155 160Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser165 170 175Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu180 185 190Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile195 200 205Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala210 215 220Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu225 230 235 240Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln245 250 255Glu Gln Gln(2)SEQ ID NO134的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO134Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Len Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln130 135 140Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp145 150 155 160Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His165 170 175Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala180 185 190Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu195 200 205Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala210 215 220Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln25 230 235 240Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu245 250 255Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala260 265 270Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser275 280 285Mis Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu290 295 300Ala Gln Pro305(2)SEQ ID NO135的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO135Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala
50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln130 135 140Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp145 150 155 160Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His165 170 175Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala180 185 190Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu195 200 205Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala210 215 220Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln225 230 235 240Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu245 250 255Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala260 265 270Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser275 280 285His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu290 295 300Ala Gln Pro305(2)SEQ ID NO136的信息(ⅰ)序列特征(A)长度244氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性
(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO136Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His130 135 140His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn145 150 155 160Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn165 170 175Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly180 185 190Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr195 200 205Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln210 215 220Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala225 230 235 240Gln Glu Gln Gln(2)SEQ ID NO137的信息(ⅰ)序列特征(A)长度259氨基酸(B)类型氨基酸(C)链型
(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO137Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Aan Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His145 150 155 160Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp165 170 175Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu180 185 190Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile195 200 205Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala210 215 220Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu225 230 235 240Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln245 250 255Glu Gln Gln(2)SEQ ID NO138的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸
(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO138Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser145 150 155 160Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly165 170 175Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro180 185 190Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro195 200 205Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser210 215 220Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu225 230 235 240Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu245 250 255Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu260 265 270Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe
275 280 285Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His290 295 300Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala305 310 315 320Gln Pro(2)SEQ ID NO139的信息(ⅰ)序列特征(A)长度349氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO139Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg Mis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gln Pro Pro Val Asn Ala115 120 125Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Gly Gly Gly130 135 140Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser145 150 155 160Gly Gly Gly Ser Gly Ser Gly Asp Phe Asp Tyr Glu Asn Met Ala Thr165 170 175Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Ser180 185 190Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu195 200 205Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu210 215 220Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro225 230 235 240Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly245 250 255Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro260 265 270Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe275 280 285Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala290 295 300Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln305 310 315 320Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu325 330 335Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro340 345(2)SEQ ID NO:140的信息(ⅰ)序列特征(A)长度64碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(ⅹⅰ)序列描述SEQ ID NO140GGATCCACCA TGAGCCGCCT GCCCGTCCTG CTCCTGCTCC AACTCCTGGT CCGCCCCGCC60ATGG 64(2)SEQ ID NO141的信息(ⅰ)序列特征(A)长度259氨基酸(B)类型氨基酸(C)链型
(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO141Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met GluArg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Meu Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro130 135 140Trp Glu His Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu145 150 155 160Ser Arg Asp Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser165 170 175Glu Met Phe Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu180 185 190Leu Tyr Lys Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro195 200 205Leu Thr Met Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro210 215 220Glu Thr ser Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu225 230 235 240Asn Leu Lys Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro245 250 255Val Gln Glu(2)SEQ ID NO142的信息(ⅰ)序列特征(A)长度301氨基酸
(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO142Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gln Pro Pro Val Asn Ala115 120 125Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Gly Gly Gly130 135 140Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser145 150 155 160Gly Gly Gly Ser Gly Ser Gly Asp Phe Asp Tyr Glu Asn Met Ala Pro165 170 175Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His Val Asn Ala180 185 190Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp Thr Ala Ala195 200 205Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe Asp Leu Gln210 215 220Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys Gln Gly Leu225 230 235 240Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met Met Ala Ser245 250 255Mis Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser Cys Ala Thr260 265 270Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys Asp Phe Leu275 280 285Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu290 295 300(2)SEQ ID NO143的信息(ⅰ)序列特征(A)长度335氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO143Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Pro Val Asn Ala Gly Gly Gly Ser Gly Gly Gly Ser Gly115 120 125Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly130 135 140Gly Ser Glu Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly Asn Met145 150 155 160Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu165 170 175Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu180 185 190Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu195 200 205Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser210 215 220Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His225 230 235 240Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile245 250 255Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala260 265 270Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala275 280 285Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala290 295 300Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser305 310 315 320Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro325 330 335(2)SEQ ID NO144的信息(ⅰ)序列特征(A)长度274氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO144Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile Mis His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp145 150 155 160Glu His Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser165 170 175Arg Asp Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu180 185 190Met Phe Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu195 200 205Tyr Lys Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu210 215 220Thr Met Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu225 230 235 240Thr Ser Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn245 250 255Leu Lys Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val260 265 270Gln Glu(2)SEQ ID NO145的信息(ⅰ)序列特征(A)长度317氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO145Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60lie Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln
100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Pro Val Pro Pro Gly Glu Asp Ser Lys Asp Val130 135 140Ala Ala Pro His Arg Gln Pro Leu Thr Ser Ser Glu Arg Ile Asp Lys145 150 155 160Gln Ile Arg Tyr Ile Leu Asp Gly Ile Ser Ala Leu Arg Lys Glu Thr165 170 175Cys Asn Lys Ser Asn Met Cys Glu Ser Ser Lys Glu Ala Leu Ala Glu180 185 190Asn Asn Leu Asn Leu Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln195 200 205Ser Gly Phe Asn Glu Glu Thr Cys Leu Val Lys Ile Ile Thr Gly Leu210 215 220Leu Glu Phe Glu Val Tyr Leu Glu Tyr Leu Gln Asn Arg Phe Glu Ser225 230 235 240Ser Glu Glu Gln Ala Arg Ala Val Gln Met Ser Thr Lys Val Leu Ile245 250 255Gln Phe Leu Gln Lys Lys Ala Lys Asn Leu Asp Ala Ile Thr Thr Pro260 265 270Asp Pro Thr Thr Asn Ala Ser Leu Leu Thr Lys Leu Gln Ala Gln Asn275 280 285Gln Trp Leu Gln Asp Met Thr Thr His Leu Ile Leu Arg Ser Phe Lys290 295 300Glu Phe Leu Gln Ser Ser Leu Arg Ala Leu Arg Gln Met305 310 315(2)SEQ ID NO146的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO146Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly Gly180 185 190Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His195 200 205Leu Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser210 215 220Glu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu225 230 235 240Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile245 250 255Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala260 265 270Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu275 280 285Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln290 295 300Glu Gln Gln305(2)SEQ ID NO147的信息(ⅰ)序列特征(A)长度307氨基酸
(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO147Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly Gly180 185 190Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His195 200 205Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp210 215 220Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu225 230 235 240Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile245 250 255Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala260 265 270Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu275 280 285Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln290 295 300Glu Gln Gln305(2)SEQ ID NO148的信息(ⅰ)序列特征(A)长度337氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO148Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Pro Gln Pro Pro Val Asn Ala Gly Gly Gly Ser Gly Gly Gly180 185 190Ser Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu195 200 205Gly Gly Gly Ser Glu Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly210 215 220Asp Phe Asp Tyr Glu Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu225 230 235 240Ile Ile His His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn245 250 255Asn Leu Asn Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg260 265 270Leu Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala275 280 285Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro290 295 300Ser Arg Mis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg305 310 315 320Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln325 330 335Gln(2)SEQ ID NO149的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO149Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leul 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Men Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro Ile180 185 190Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro195 200 205Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu210 215 220Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu225 230 235 240Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu245 250 255Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu260 265 270Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala275 280 285Pro Ser Arg Mis Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe290 295 300Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu305 310 315 320Gln Gln(2)SEQ ID NO150的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO150Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala
20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro Ile180 185 190Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro195 200 205Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu210 215 220Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu225 230 235 240Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu245 250 255Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu260 265 270Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala275 280 285Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe290 295 300Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu305 310 315 320Gln Gln(2)SEQ ID NO151的信息(ⅰ)序列特征
(A)长度349氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO151Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Clu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser CyS Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Ile Glu Gly Arg Ile Ser Pro Gln Pro Pro Val Asn Ala Gly180 185 190Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Gly Gly Gly Ser195 200 205Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Gly210 215 220Gly Gly Ser Gly Ser Gly Asp Phe Asp Tyr Glu Asn Met Ala Asn Cys225 230 235 240Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro Asn245 250 255Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile Leu260 265 270Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg Ala275 280 285Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg Asn290 295 300Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His Pro305 310 315 320Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu Thr325 330335Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln340 345(2)SEQ ID NO152的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO151Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln130 135 140Ser Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp145 150 155 160Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His165 170 175Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala180 185 190Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu195 200 205Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala210215 220Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln225 230 235 240Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu245 250 255Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala260 265 270Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser275 280 285His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu290 295 300Ala Gln Pro305(2)SEQ ID NO153的信息(ⅰ)序列特征(A)长度244氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO153Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Ash Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Asn Cys Ser Ile Men Ile Asp Glu Ile Ile His130 135 140His Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn145 150 155 160Asp Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn165 170 175Leu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly180 185 190Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr195 200 205Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln210 215 220Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala225 230 235 240Gln Glu Gln Gln(2)SEQ ID NO154的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO154Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser145 150 155 160Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly165 170 175Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro180 185 190Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro195 200 205Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser210 215 220Gln Leu Mis Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu225 230 235 240Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu245 250 255Asp Val Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu260 265 270Gly Met Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe275 280 285Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His290 295 300Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala305 310 315 320Gln Pro(2)SEQ ID NO155的信息(ⅰ)序列特征(A)长度259氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO155Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu Asp20 25 30Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu Ser35 40 45Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro115 120 125Ile Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser130 135 140Pro Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His145150 155 160Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp165 170 175Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu180 185 190Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile195 200 205Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala210 215 220Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu225 230 235 240Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln245 250 255Glu Gln Gln(2)SEQ ID NO156的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型
(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO156Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gly Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile180 185 190Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro195 200 205Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu210 215 220Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu225 230 235 240Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu245 250 255Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu260 265 270Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala275 280 285Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe290 295 300Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu305 310 315 320Gln Gln(2)SEQ ID NO157的信息(ⅰ)序列特征(A)长度322氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO157Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gly Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile180 185 190Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro195 200 205Asn Met Ala Asn Cys Ser Ile Mer Ile Asp Glu Ile Ile His His Leu210 215 220Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp Glu225 230 235 240Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu Glu245 250 255Ser Phs Vsl Arg Als Val Lys Asn Leu Glu Asn Ala Ser Gly Ile Glu260 265 270Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala275 280 285Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe290 295 300Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu305 310 315 320Gln Gln(2)SEQ ID NO158的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO158Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gly Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly180 185 190Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His195 200 205Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp210 215 220Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu225 230 235 240Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile245 250 255Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala260 265 270Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu275 280 285Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln290 295 300Glu Gln Gln305(2)SEQ ID NO159的信息(ⅰ)序列特征(A)长度307氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO159Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Sar Phe Leu1 5 10 15Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gly Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Glyl80 185 190Ser Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His195 200 205Leu Lys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn Asp210 215 220Glu Asp Val Ser Ile Leu Met Asp Arg Asn Leu Arg Leu Pro Asn Leu225 230 235 240Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile245 250 255Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala260 265 270Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu275 280 285Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln290 295 300Glu Gln Gln305(2)SEQ ID NO160的信息(ⅰ)序列特征(A)长度128氨基酸(B)类型氨基酸
(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO160Met Ala Pro Ala Arg Ser Pro Ser Pro Ser Thr Gln Pro Trp Glu His1 5 10 15Val Asn Ala Ile Gln Glu Ala Arg Arg Leu Leu Asn Leu Ser Arg Asp20 25 30Thr Ala Ala Glu Met Asn Glu Thr Val Glu Val Ile Ser Glu Met Phe35 40 45Asp Leu Gln Glu Pro Thr Cys Leu Gln Thr Arg Leu Glu Leu Tyr Lys50 55 60Gln Gly Leu Arg Gly Ser Leu Thr Lys Leu Lys Gly Pro Leu Thr Met65 70 75 80Met Ala Ser His Tyr Lys Gln His Cys Pro Pro Thr Pro Glu Thr Ser85 90 95Cys Ala Thr Gln Ile Ile Thr Phe Glu Ser Phe Lys Glu Asn Leu Lys100 105 110Asp Phe Leu Leu Val Ile Pro Phe Asp Cys Trp Glu Pro Val Gln Glu115 120 125(2)SEQ ID NO161的信息(ⅰ)序列特征(A)长度176氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO161Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Cys Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175(2)SEQ ID NO162的信息(ⅰ)序列特征(A)长度176氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO162Met Ala Thr Pro Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu1 5 10 15Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala20 25 30Leu Gln Glu Lys Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu35 40 45Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser50 55 60Ser Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu65 70 75 80His Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly85 90 95Ile Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val100 105 110Ala Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met115 120 125Ala Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser130 135 140Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln145 150 155 160Ser Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro165 170 175(2)SEQ ID NO163的信息(ⅰ)序列特征(A)长度186氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO163Met Ala Pro Val Pro Pro Gly Glu Asp Ser Lys Asp Val Ala Ala Pro1 5 10 15His Arg Gln Pro Leu Thr Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg20 25 30Tyr Ile Leu Asp Gly Ile Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys35 40 45Ser Asn Mer Cys Glu Ser Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu50 55 60Asn Leu Pro Lys Met Ala Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe65 70 75 80Asn Glu Glu Thr Cys Leu Val Lys Ile Ile Thr Gly Leu Leu Glu Phe85 90 95Glu Val Tyr Leu Glu Tyr Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu100 105 110Gln Ala Arg Ala Val Gln Met Ser Thr Lys Val Leu Ile Gln Phe Leu115 120 125Gln Lys Lys Ala Lys Asn Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr130 135 140Thr Asn Ala Ser Leu Leu Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu145 150 155 160Gln Asp Met Thr Thr His Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu165 170 175Gln Ser Ser Leu Arg Ala Leu Arg Gln Met180 185(2)SEQ ID NO164的信息(ⅰ)序列特征(A)长度155氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO164Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lysl 5 10 15Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro20 25 30Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe35 40 45Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp50 55 60Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg65 70 75 80Gln Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser85 90 95Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr100 105 110Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala115 120 125Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu130 135 140Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg145 150 155(2)SEQ ID NO165的信息(ⅰ)序列特征(A)长度286氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO165Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cye Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val130 135 140Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser145 150 155 160Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala165 170 175Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys180 185 190Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met195 200 205Ala Ala Arg Gln Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly210 215220Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu225 230 235 240Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp245 250 255Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val260 265 270Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg275 280 285(2)SEQ ID NO166的信息(ⅰ)序列特征(A)长度286氨基酸
(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO166Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys1 5 10 15Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp20 25 30Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala35 40 45Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala50 55 60Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro65 70 75 80Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg85 90 95Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln100 105 110Gln Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly115 120 125Gly Ser Asn Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val130 135 140Leu Ser Lys Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser145 150 155 160Gln Cys Pro Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala165 170 175Val Asp Phe Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys180 185 190Ala Gln Asp Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met195 200 205Ala Ala Arg Gln Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly210 215 220Gln Leu Ser Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu225 230 235 240Leu Gly Thr Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp245 250 255Pro Asn Ala Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val260 265 270Arg Phe Leu Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg275 280 285(2)SEQ ID NO167的信息(ⅰ)序列特征(A)长度286氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO167Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys1 5 10 15Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro20 25 30Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe35 40 45Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp50 55 60Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg65 70 75 80Gln Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser85 90 95Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr100 105 110Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala115 120 125Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu130 135 140Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Tyr Val Ile Glu Gly145 150 155 160Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser Asn Met Ala Asn165 170 175Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg Pro Pro180 185 190Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp Met Asp Ile195 200 205Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu Ala Phe Val Arg210 215 220Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu Ala Ile Leu Arg225 230 235 240Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala Pro Ser Arg His245 250 255Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe Arg Glu Lys Leu260 265 270Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu Gln Gln275 280 285(2)SEQ ID NO168的信息(ⅰ)序列特征(A)长度290氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型蛋白质(ⅹⅰ)序列描述SEQ ID NO168Met Ala Ser Pro Ala Pro Pro Ala Cys Asp Leu Arg Val Leu Ser Lys1 5 10 15Leu Leu Arg Asp Ser His Val Leu His Ser Arg Leu Ser Gln Cys Pro20 25 30Glu Val His Pro Leu Pro Thr Pro Val Leu Leu Pro Ala Val Asp Phe35 40 45Ser Leu Gly Glu Trp Lys Thr Gln Met Glu Glu Thr Lys Ala Gln Asp50 55 60Ile Leu Gly Ala Val Thr Leu Leu Leu Glu Gly Val Met Ala Ala Arg65 70 75 80Gln Gln Leu Gly Pro Thr Cys Leu Ser Ser Leu Leu Gly Gln Leu Ser85 90 95Gly Gln Val Arg Leu Leu Leu Gly Ala Leu Gln Ser Leu Leu Gly Thr100 105 110Gln Leu Pro Pro Gln Gly Arg Thr Thr Ala His Lys Asp Pro Asn Ala115 120 125Ile Phe Leu Ser Phe Gln His Leu Leu Arg Gly Lys Val Arg Phe Leu130 135 140Met Leu Val Gly Gly Ser Thr Leu Cys Val Arg Glu Phe His Ala Tyr145 150 155 160Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly Ser165 170 175Asn Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His Leu180 185 190Lys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu195 200 205Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu210 215 220Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile Glu225 230 235 240Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr Ala Ala245 250 255Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp Gln Glu Phe260 265 270Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu Gln Ala Gln Glu275 280 285Gln Gln290(2)SEQ ID NO169的信息(ⅰ)序列特征(A)长度45碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO169ACGTCCATGG CNTCNCCNGC NCCNCCTGCT TGTGACCTCC GAGTC 45(2)SEQ ID NO170的信息(ⅰ)序列特征(A)长度34碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”
(ⅹⅰ)序列描述SEQ ID NO170AATAGCTGAA TTCTTACCCT TCCTGAGACA GATT 34(2)SEQ ID NO171的信息(ⅰ)序列特征(A)长度33碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO171TGACAAGCTT ACCTGACGCA GAGGGTGGAC CCT 33(2)SEQ ID NO172的信息(ⅰ)序列特征(A)长度30碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO172ATGCACGAAT TCCCTGACGC AGAGGGTGGA 30(2)SEQ ID NO173的信息(ⅰ)序列特征(A)长度14碱基对(B)类型核酸(C)链型单(D)拓扑学线性
(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO173AATTCCATGC ATAC14(2)SEQ ID NO174的信息(ⅰ)序列特征(A)长度10碱基对(B)类型核酸(C)链型单(D)拓扑学线性(ⅱ)分子类型其它核酸(A)描述/desc=“合成的DNA”(ⅹⅰ)序列描述SEQ ID NO174GGTACGTATG10(2)SEQ ID NO175的信息(ⅰ)序列特征(A)长度561碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO175ATGGCTCCAG TACCACCAGG TGAAGATTCC AAAGATGTGG CCGCCCCACA CAGACAGCCA 60CTCACCTCTT CAGAACGAAT TGACAAACAA ATTCGGTACA TCCTCGACGG GATATCAGCC 120CTGAGAAAGG AGACATGTAA CAAGAGTAAC ATGTGTGAAA GCAGCAAAGA GGCGCTAGCA 180GAAAACAACC TGAACCTTCC AAAGATGGCT GAAAAAGATG GATGCTTCCA ATCCGGATTC 240AATGAGGAGA CTTGCCTGGT GAAAATCATC ACTGGTCTTT TGGAGTTTGA GGTATACCTC 300GAGTACCTCC AGAACAGATT TGAGAGTAGT GAGGAACAAG CCAGAGCTGT GCAGATGTCG 360ACAAAAGTCC TGATCCAGTT CCTGCAGAAA AAGGCAAAGA ATCTAGATGC AATAACCACC 420CCTGACCCAA CCACAAATGC ATCCCTGCTG ACGAAGCTGC AGGCACAGAA CCAGTGGCTG 480CAGGACATGA CAACTCATCT CATTCTGCGC AGCTTTAAGG AGTTCCTGCA GTCCAGCCTG 540AGGGCTCTTC GGCAAATGTA G 561(2)SEQ ID NO176的信息(ⅰ)序列特征(A)长度402碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO176ATGGCACCGG CTCGTTCCCC GTCCCCGTCT ACCCAGCCGT GGGAACACGT GAATGCCATC60CAGGAGGCCC GGCGTCTCCT GAACCTGAGT AGAGACACTG CTGCTGAGAT GAATGAAACA120GTAGAAGTGA TATCAGAAAT GTTTGACCTC CAGGAGCCGA CTTGCCTACA GACCCGCCTG180GAGCTGTACA AGCAGGGCCT GCGGGGCAGC CTCACCAAGC TCAAGGGCCC CTTGACCATG240ATGGCCAGCC ACTACAAGCA GCACTGCCCT CCAACCCCGG AAACTTCCTG TGCAACCCAG300ATTATCACCT TTGAAAGTTT CAAAGAGAAC CTGAAGGACT TCCTGCTTGT CATCCCCTTT360GACTGCTGGG AGCCAGTCCA GGAGTGATAA GGATCCGAAT TC 402(2)SEQ ID NO177的信息(ⅰ)序列特征(A)长度546碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO177ATGGCTACAC CATTAGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTG ATAAGGATCC540GAATTC 546(2)SEQ ID NO178的信息(ⅰ)序列特征(A)长度546碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO178ATGGCTACAC CATTAGGACC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTGCTTA 60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTG ATAAGGATCC 540GAATTC 546(2)SEQ ID NO179的信息(ⅰ)序列特征(A)长度546碱基对(B)类型核酸(C)链型双
(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO179ATGGCTACAC CATTGGGCCC TGCCAGCTCC CTGCCCCAGA GCTTCCTGCT CAAGTCTTTA60GAGCAAGTGA GGAAGATCCA GGGCGATGGC GCAGCGCTCC AGGAGAAGCT GTGTGCCACC 120TACAAGCTGT GCCACCCCGA GGAGCTGGTG CTGCTCGGAC ACTCTCTGGG CATCCCCTGG 180GCTCCCCTGA GCTCCTGCCC CAGCCAGGCC CTGCAGCTGG CAGGCTGCTT GAGCCAACTC 240CATAGCGGCC TTTTCCTCTA CCAGGGGCTC CTGCAGGCCC TGGAAGGGAT ATCCCCCGAG 300TTGGGTCCCA CCTTGGACAC ACTGCAGCTG GACGTCGCCG ACTTTGCCAC CACCATCTGG 360CAGCAGATGG AAGAACTGGG AATGGCCCCT GCCCTGCAGC CCACCCAGGG TGCCATGCCG 420GCCTTCGCCT CTGCTTTCCA GCGCCGGGCA GGAGGGGTCC TGGTTGCTAG CCATCTGCAG 480AGCTTCCTGG AGGTGTCGTA CCGCGTTCTA CGCCACCTTG CGCAGCCCTG ATAAGGATCC 540GAATTC 546(2)SEQ ID NO180的信息(ⅰ)序列特征(A)长度465碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO180ATGGCGTCTC CGGCGCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACT GCTTCGTGAC 60TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGG TTCACCCTTT GCCTACACCT 120GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC 180AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG 240GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT 300CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC 360ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG 420GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGG 465(2)SEQ ID NO181的信息
(ⅰ)序列特征(A)长度143碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO181CCTGTCAACC CGGGCGGCGG CTCTGGTGGT GGTTCTGGTG GCGGCTCTGA GGGTGGCGGC 60TCTGAGGGTG GCGGTTCTGA GGGTGGCGGC TCTGAGGGTG GCGGTTCCGG TGGCGGCTCC 120GGTTCCGGTA ACATGTATTA TGA 143(2)SEQ ID NO182的信息(ⅰ)序列特征(A)长度180碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO182ATCGTCTGAC CTCCCGGGCC TCCTGTCAAT GCTGGCGGCG GCTCTGGTGG TGGTTCTGGT60GGCGGCTCTG AGGGTGGCGG CTCTGAGGGT GGCGGTTETG AGGGTGGCGG CTCTGAGGGT 120GGCGGTTCCG GTGGCGGCTC CGGTTCCGGT GATTTTGATT ATGAAAACAT GTCAAACGCT 180(2)SEQ ID NO183的信息(ⅰ)序列特征(A)长度858碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO183ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAATCGA GGGAAGGATT 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCGT CTCCGGCGCC GCCTGCTTGT 420GACCTCCGAG TCCTCAGTAA ACTGCTTCGT GACTCCCATG TCCTTCACAG CAGACTGAGC 480CAGTGCCCAG AGGTTCACCC TTTGCCTACA CCTGTCCTGC TGCCTGCTGT GGACTTTAGC 540TTGGGAGAAT GGAAAACCCA GATGGAGGAG ACCAAGGCAC AGGACATTCT GGGAGCAGTG 600ACCCTTCTGC TGGAGGGAGT GATGGCAGCA CGGGGACAAC TGGGACCCAC TTGCCTCTCA 660TCCCTCCTGG GGCAGCTTTC TGGACAGGTC CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC 720CTTGGAACCC AGCTTCCTCC ACAGGGCAGG ACCACAGCTC ACAAGGATCC CAATGCCATC 780TTCCTGAGCT TCCAACACCT GCTCCGAGGA AAGGTGCGTT TCCTGATGCT TGTAGGAGGG 840TCCACCCTCT GCGTCAGG 858(2)SEQ ID NO184的信息(ⅰ)序列特征(A)长度858碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO184ATGGCTAACT GCTCTATAAT GATCGATGAA ATTATACATC ACTTAAAGAG ACCACCTAAC60CCTTTGCTGG ACCCGAACAA CCTCAATTCT GAAGACATGG ATATCCTGAT GGAACGAAAC 120CTTCGAACTC CAAACCTGCT CGCATTCGTA AGGGCTGTCA AGCACTTAGA AAATGCATCA 180GGTATTGAGG CAATTCTTCG TAATCTCCAA CCATGTCTGC CCTCTGCCAC GGCCGCACCC 240TCTCGACATC CAATCATCAT CAAGGCAGGT GACTGGCAAG AATTCCGGGA AAAACTGACG 300TTCTATCTGG TTACCCTTGA GCAAGCGCAG GAACAACAGT ACGTAGAGGG CGGTGGAGGC 360TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCGT CTCCGGCGCC GCCTGCTTGT 420GACCTCCGAG TCCTCAGTAA ACTGCTTCGT GACTCCCATG TCCTTCACAG CAGACTGAGC 480CAGTGCCCAG AGGTTCACCC TTTGCCTACA CCTGTCCTGC TGCCTGCTGT GGACTTTAGC 540TTGGGAGAAT GGAAAACCCA GATGGAGGAG ACCAAGGCAC AGGACATTCT GGGAGCAGTG 600ACCCTTCTGC TGGAGGGAGT GATGGCAGCA CGGGGACAAC TGGGACCCAC TTGCCTCTCA 660TCCCTCCTGG GGCAGCTTTC TGGACAGGTC CGTCTCCTCC TTGGGGCCCT GCAGAGCCTC 720CTTGGAACCC AGCTTCCTCC ACAGGGCAGG ACCACAGCTC ACAAGGATCC CAATGCCATC 780TTCCTGAGCT TCCAACACCT GCTCCGAGGA AAGGTGCGTT TCCTGATGCT TGTAGGAGGG 840TCCACCCTCT GCGTCAGG 858(2)SEQ ID NO185的信息(ⅰ)序列特征(A)长度852碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO185ATGGCGTCTC CGGCGCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACT GCTTCGTGAC60TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGG TTCACCCTTT GCCTACACCT 120GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC 180AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG 240GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT 300CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCACGACC 360ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG 420GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGATCGA GGGAAGGATT 480TCCCCGGGTG GTGGTTCTGG CGGCGGCTCC AACATGGCTA ACTGCTCTAT AATGATCGAT 540GAAATTATAC ATCACTTAAA GAGACCACCT AACCCTTTGC TGGACCCGAA CAACCTCAAT 600TCTGAAGACA TGGATATCCT GATGGAACGA AACCTTCGAA CTCCAAACCT GCTCGCATTC 660GTAAGGGCTG TCAAGCACTT AGAAAATGCA TCAGGTATTG AGGCAATTCT TCGTAATCTC 720CAACCATGTC TGCCCTCTGC CACGGCCGCA CCCTCTCGAC ATCCAATCAT CATCAAGGCA 780GGTGACTGGC AAGAATTCCG GGAAAAACTG ACGTTCTATC TGGTTACCCT TGAGCAAGCG 840CAGGAACAAC AG 852(2)SEQ ID NO186的信息(ⅰ)序列特征(A)长度870碱基对(B)类型核酸(C)链型双(D)拓扑学线性(ⅱ)分子类型DNA(基因组)(ⅹⅰ)序列描述SEQ ID NO1 86ATGGCGTCTC CGGCGCCGCC TGCTTGTGAC CTCCGAGTCC TCAGTAAACT GCTTCGTGAC 60TCCCATGTCC TTCACAGCAG ACTGAGCCAG TGCCCAGAGG TTCACCCTTT GCCTACACCT 120GTCCTGCTGC CTGCTGTGGA CTTTAGCTTG GGAGAATGGA AAACCCAGAT GGAGGAGACC 180AAGGCACAGG ACATTCTGGG AGCAGTGACC CTTCTGCTGG AGGGAGTGAT GGCAGCACGG 240GGACAACTGG GACCCACTTG CCTCTCATCC CTCCTGGGGC AGCTTTCTGG ACAGGTCCGT 300CTCCTCCTTG GGGCCCTGCA GAGCCTCCTT GGAACCCAGC TTCCTCCACA GGGCAGGACC 360ACAGCTCACA AGGATCCCAA TGCCATCTTC CTGAGCTTCC AACACCTGCT CCGAGGAAAG 420GTGCGTTTCC TGATGCTTGT AGGAGGGTCC ACCCTCTGCG TCAGGGAATT CCATGCATAC 480GTAGAGGGCG GTGGAGGCTC CCCGGGTGGT GGTTCTGGCG GCGGCTCCAA CATGGCTAAC 540TGCTCTATAA TGATCGATGA AATTATACAT CACTTAAAGA GACCACCTAA CCCTTTGCTG 600GACCCGAACA ACCTCAATTC TGAAGACATG GATATCCTGA TGGAACGAAA CCTTCGAACT 660CCAAACCTGC TCGCATTCGT AAGGGCTGTC AAGCACTTAG AAAATGCATC AGGTATTGAG 720GCAATTCTTC GTAATCTCCA ACCATGTCTG CCCTCTGCCA CGGCCGCACC CTCTCGACAT 780CCAATCATCA TCAAGGCAGG TGACTGGCAA GAATTCCGGG AAAAACTGAC GTTCTATCTG 840GTTACCCTTG AGCAAGCGCA GGAACAACAG870(2)SEQ ID NO187的信息(ⅰ)序列特征(A)长度18氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO187Met Ser Arg Leu Pro Val Leu Leu Leu Leu Gln Leu Leu Val Arg Pro1 5 10 15Ala Met(2)SEQ ID NO188的信息(ⅰ)序列特征(A)长度18氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO188Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly Gly1 5 10 15Ser Asn(2)SEQ ID NO189的信息(ⅰ)序列特征(A)长度18氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO189Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Gly Gly Ser Gly Gly Gly1 5 10 15Ser Asn(2)SEQ ID NO190的信息(ⅰ)序列特征(A)长度18氨基酸(B)类型氨基酸
(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO190Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly Ser Gly Gly Gly1 5 10 15Ser Asn(2)SEQ ID NO191的信息(ⅰ)序列特征(A)长度33氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO191Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Glu Pro Ser Gly Pro Ile1 5 10 15Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro20 25 30Asn(2)SEQ ID NO192的信息(ⅰ)序列特征(A)长度33氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO192Tyr Val Ile Glu Gly Lys Ile Ser Pro Gly Glu Pro Ser Gly Pro Ile1 5 10 15Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro20 25 30Asn(2)SEQ ID NO193的信息(ⅰ)序列特征(A)长度33氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO193Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Glu Pro Ser Gly Pro Ile1 5 l0 15Ser Thr Ile Asn Pro Ser Pro Pro Ser Lys Glu Ser His Lys Ser Pro20 25 30Asn(2)SEQ ID NO194的信息(ⅰ)序列特征(A)长度49氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO194Tyr Val Ile Glu Gly Arg Ile Ser Pro Gly Gly Gly Ser Gly Gly Gly1 5 10 15Ser Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu20 25 30Gly Gly Gly Ser Glu Gly Gly Gly Ser Gly Gly Gly Ser Gly Ser Gly35 40 45Asn(2)SEQ ID NO195的信息(ⅰ)序列特征(A)长度60氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO195Tyr Val Ile Glu Gly Arg Ile Ser Pro Gln Pro Pro Val Asn Ala Gly1 5 10 15Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Gly Gly Gly Ser20 25 30Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Glu Gly Gly Gly Ser Gly35 40 45Gly Gly Ser Gly Ser Gly Asp Phe Asp Tyr Glu Asn50 55 60(2)SEQ ID NO196的信息(ⅰ)序列特征(A)长度22氨基酸(B)类型氨基酸(C)链型(D)拓扑学线性(ⅱ)分子类型肽(ⅹⅰ)序列描述SEQ ID NO196Glu Pne His Ala Tyr Val Glu Gly Gly Gly Gly Ser Pro Gly Gly Gly1 5 10 15Ser Gly Gly Gly Ser Asn20
权利要求
1．一种选自如下通式的融合蛋白R1-L-R2,R2-L-R1,R1-R2,R2-R1,R1-L-R1及R1-R1其中R1是人白介素3突变多肽，其通式如下Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn15 10 15Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa Xaa35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa80 85 90Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa95 100 105Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe〔SEQ ID NO:1〕其中Xaa在位点17是Ser,Lys,Gly,Asp,Met,Gln，或Arg；Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg，或Gln；Xaa在位点19是Met,Phe,Ile,Arg,Gly,Ala，或Cys；Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro，或Ala；Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,The,Ser或Val；Xaa在位点22是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val或Gly；Xaa在位点23是Ile,Val,Ala,Leu,Gly,Trp,Lys,Phe,Leu,Ser，或Arg；Xaa在位点24是Ile,Gly,Val,Arg,Ser,Phe，或Leu；Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro，或Ala；Xaa在位点26是His,Thr,Phe,Gly,Arg,Ala，或Trp；Xaa在位点27是Leu,Gly,Arg,Thr,Ser，或Ala；Xaa在位点28是Lys,Arg,Leu,Gln,Gly,Pro,Val或Trp；Xaa在位点29是Gln,Asn,Leu,Pro,Arg，或Val；Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys；Xaa在位点31是Pro,Asp,Gly,Ala,Arg,Leu，或Gln；Xaa在位点32是Leu,Val,Arg,Gln,Asn,Gly,Ala，或Gln；Xaa在位点33是Pro,Leu,Gln,Ala,Thr，或Glu；Xaa在位点34是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile，或Met；Xaa在位点35是Leu,Ala,Gly,Asn,Pro,Gln，或Val；Xaa在位点36是Asp,Leu，或Val；Xaa在位点37是Phe,Ser,Pro,Trp，或Ile；Xaa在位点38是Asn，或Ala；Xaa在位点40是Leu,Trp，或Arg；Xaa在位点41是Asn,Cys,Arg,Leu,His,Met，或Pro；Xaa在位点42是Gly,Asp,Ser,Cys,Asn,Lys,Thr,Leu,Val,Glu,Phe,Tyr,Ile,Met或Ala；Xaa在位点43是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,Gly，或Ser；Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,Ala，或Pro；Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Trp,Asp,Asn,Arg,Ser,Ala,Ile,Glu，或His；Xaa在位点46是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,Tyr,Ile,Val，或Gly；Xaa在位点47是Ile,Gly,Val,Ser,Arg,Pro，或His；Xaa在位点48是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,Val，或Asn；Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp；Xaa在位点50是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,Phe,Met，或Gln；Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser，或Thr；Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser，或Met；Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala,或Leu；Xaa在位点55是Arg,Thr,Val,Ser,Leu，或Gly；Xaa在位点56是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,Leu,Val，或Lys；Xaa在位点57是Asn或Gly；Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val，或Cys；Xaa在位点59是Glu,Tyr,His,Leu,Pro，或Arg；Xaa在位点60是Ala,Ser,Pro,Tyr,Asn，或Thr；Xaa在位点61是Phe,Asn,Glu,Pro,Lys,Arg，或Ser；Xaa在位点62是Asn,His,Val,Arg,Pro,Thr,Asp，或Ile；Xaa在位点63是Arg,Tyr,Trp,Kys,Ser,His,Pro，或Val；Xaa在位点64是Ala,Asn,Pro,Ser，或Lys；Xaa在位点65是Val,Thr,Pro,His,Leu,Phe，或Ser；Xaa在位点66是Lys,Ile,Arg,Val,Asn,Glu，或Ser；Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His；Xaa在位点68是Leu,Val,Trp,Ser,Ile,Phe,Thr，或His；Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly，或Leu；Xaa在位点70是Asn,Leu,Val,Trp,Pro，或Ala；Xaa在位点71是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp，或Asn；Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp；Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr，或Arg；Xaa在位点74是Ile,Met,Thr,Pro,Arg,Gly,Ala；Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln，或Leu；Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly，或Asp；Xaa在位点77是Ile,Ser,Arg,Thr，或Leu；Xaa在位点78是Leu,Ala,Ser,Glu,Phe,Gly，或Arg；Xaa在位点79是Lys,Thr,Asn,Met,Arg,Ile,Gly，或Asp；Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu,Glu，或Arg；Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg,Val，或Lys；Xaa在位点82是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Ser,Ala,Tyr,Phe,Ile,Met，或Val；Xaa在位点83是Pro,Ala,Thr,Trp,Arg，或Met；Xaa在位点84是Cys,Glu,Gly,Arg,Met，或Val；Xaa在位点85是Leu,Asn,Val，或Gln；Xaa在位点86是Pro,Cys,Arg,Ala，或Lys；Xaa在位点87是Leu,Ser,Trp，或Gly；Xaa在位点88是Ala,Lys,Arg,Val，或Trp；Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His,Asn，或Ser；Xaa在位点90是Ala,Pro,Ser,Thr,Gly,Asp,Ile，或Met；Xaa在位点91是Ala,Pro,Ser,Thr,Phe,Leu,Asp，或His；Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile，或Leu；Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg；Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala，或Pro；Xaa在位点95是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,Trp,Phe,Ile，或Tyr；Xaa在位点96是Pro,Lys,Tyr,Gly,Ile，或Thr；Xaa在位点97是Ile,Val,Lys,Ala，或Asn；Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,Val,Lys,Arg,Tyr，或Pro；Xaa在位点99是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,Ser,Phe，或His；Xaa在位点100是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln，或Pro；Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,Ala,Gly,Ile,Leu，或Gln；Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro；Xaa在位点103是Asp，或Ser；Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe，或Gly；Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His；Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro；Xaa在位点108是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala，或Pro；Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser，或Gly；Xaa在位点110是Lys,Ala,Asn,Thr,Leu,Arg,Gln,His,Glu,Ser,Ala,或Trp；Xaa在位点111是Leu,Ile,Arg,Asp，或Met；Xaa在位点112是Thr,Val,Gln,Tyr,Glu,His,Ser，或Phe；Xaa在位点113是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val，或Asn；Xaa在位点114是Tyr,Cys,His,Ser,Trp,Arg，或Leu；Xaa在位点115是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp，或Met；Xaa在位点116是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,Asn,His,Ala,Tyr,Phe,Gln，或Ile；Xaa在位点117是Thr,Ser,Asn,Ile,Trp,Lys，或Pro；Xaa在位点118是Leu,Ser,Pro,Ala,Glu,Cys,Asp，或Tyr；Xaa在位点119是Glu,Ser,Lys,Pro,Leu,Thr,Tyr，或Arg；Xaa在位点120是Asn,Ala,Pro,Leu,His,Val，或Gln；Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Lys,Asp，或Gly；Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys；Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；并且另外可在位点1的氨基酸前含有Met-；并且其中N末端1～14氨基酸可被缺失和/或C末端1～15氨基酸可被缺失；并且其中以Xaa代表的4～44氨基酸与天然(1-133)人白介素3的相应的氨基酸不同；R2是一种IL-3,IL-3变异体或一种集落刺激因子；而L是能将R1与R2连接的接头。
2．权利要求1的融合蛋白，其中所说的集落刺激因子选自GM-CSF,CSF-1,G-CSF,Meg-CSF(最近称为c-mp1配体)，M-CSF，红细胞生成素(EPO),IL-1,IL-4,IL-2,IL-5,IL-6,IL-7,IL-8,IL-9,IL-10,IL-11,IL-12,IL-13,LIF,flt3/flk2，人生长激素，B细胞生长因子，B细胞分化因子，嗜酸性细胞分化因子及干细胞因子(CSF)。
3．权利要求2的融合蛋白，其中R1的通式是Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa Xaa35 40 45Xaa Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu Xaa50 55 60Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile Glu65 70 75Xaa Xaa Leu Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr Ala80 85 90Xaa Pro Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa Xaa95 100 105Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu Xaa110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe125 130〔SEQ ID NO:2〕其中Xaa在位点17是Ser,Gly,Asp,Met，或Gln；Xaa在位点18是Asn,His，或Ile；Xaa在位点19是Met，或Ile；Xaa在位点21是Asp或Glu；Xaa在位点23是Ile,Ala,Leu，或Gly；Xaa在位点24是Ile,Val，或Leu；Xaa在位点25是Thr,His,Gln，或Ala；Xaa在位点26是His，或Ala；Xaa在位点29是Gln,Asn，或Val；Xaa在位点30是Pro,Gly，或Gln；Xaa在位点31是Pro,Asp,Gly，或Gln；Xaa在位点32是Leu,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点33是Pro或Glu；Xaa在位点34是Leu,Val,Gly,Ser,Lys,Ala,Arg,Gln,Glu,Ile,Phe,Thr或Met；Xaa在位点35是Leu,Ala,Asn,Pro,Gln，或Val；Xaa在位点37是Phe,Ser,Pro，或Trp；Xaa在位点38是Asn或Ala；Xaa在位点42是Gly,Asp,Ser,Cys,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点44是Asp或Glu；Xaa在位点45是Gln,Val,Met,Leu,Thr,Ala,Asn,Glu,Ser或Lys；Xaa在位点46是Asp,Phe,Ser,Thr,Ala,Asn,Gln,Glu,Gis,Ile,Lys,Tyr,Val或Cys；Xaa在位点50是Glu,Ala,Asn,Ser或Asp；Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点54是Arg或Ala；Xaa在位点55是Arg,Thr,Val,Leu，或Gly；Xaa在位点56是Pro,Gly,Ser,Gln,Ala,Arg,Asn,Glu,Leu,Thr,Val或Lys；Xaa在位点60是Ala或Ser；Xaa在位点62是Asn,Pro,Thr，或Ile；Xaa在位点63是Arg或Lys；Xaa在位点64是Ala或Asn；Xaa在位点65是Val或Thr；Xaa在位点66是Lys或Arg；Xaa在位点67是Ser,Phe，或His；Xaa在位点68是Leu,Ile,Phe，或His；Xaa在位点69是Gln,Ala,Pro,Thr,Glu,Arg，或Gly；Xaa在位点71是Ala,Pro，或Arg；Xaa在位点72是Ser,Glu,Arg，或Asp；Xaa在位点73是Ala或Leu；Xaa在位点76是Ser,Val,Ala,Asn,Glu,Pro，或Gly；Xaa在位点77是Ile或Leu；Xaa在位点79是Lys,Thr,Gly,Asn,Met,Arg,Ile,Gly，或Asp；Xaa在位点80是Asn,Gly,Glu，或Arg；Xaa在位点82是Leu,Gln,Trp,Arg,Asp,Ala,Asn,Glu,His,Ile,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点83是Pro或Thr；Xaa在位点85是Leu或Val；Xaa在位点87是Leu或Ser；Xaa在位点88是Ala或Trp；Xaa在位点91是Ala或Pro；Xaa在位点93是Thr,Asp,Ser,Pro,Ala,Leu，或Arg；Xaa在位点95是His,Pro,Arg,Val,Leu,Gly,Asn,Phe,Ser或Thr；Xaa在位点96是Pro或Tyr；Xaa在位点97是Ile或Val；Xaa在位点98是His,Ile,Asn,Leu,Ala,Thr,Leu,Arg,Gln,Leu,Lys,Met,Ser,Tyr,Val或Pro；Xaa在位点99是Ile,Leu，或Val；Xaa在位点100是Lys,Arg,Ile,Gln,Pro，或Ser；Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Pro,Asn,Ile,Leu或Tyr；Xaa在位点104是Trp或Leu；Xaa在位点105是Asn,Pro,Ala,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His；Xaa在位点106是Glu或Gly；Xaa在位点108是Arg,Ala，或Ser；Xaa在位点109是Arg,Thr,Glu,Leu，或Ser；Xaa在位点112是Thr,Val，或Gln；Xaa在位点114是Tyr或Trp；Xaa在位点115是Leu或Ala；Xaa在位点116是Lys,Thr,Val,Trp,Ser,Ala,His,Met,Phe,Tyr或Ile；Xaa在位点117是Thr或Ser；Xaa在位点120是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点121是Ala,Ser,Ile,Asn,Pro,Asp，或Gly；Xaa在位点122是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys；Xaa在位点123是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；并且另外可在位点1的氨基酸前含有Met-；并且其中N末端的1～14氨基酸可被缺失和/或C末端1～15氨基酸可被缺失；并且其中以Xaa代替的4～35氨基酸与天然(1-133)人白介素3相应的氨基酸不同。
4．权利要求3的融合蛋白，其中R1的通式是Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp Val Asn1 5 10 15Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa Xaa20 25 30Pro Xaa Pro Xaa Xaa Asp Phe Xaa Asn Leu Asn Xaa Glu Asp Xaa35 40 45Xaa Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu Ala50 55 60Phe Xaa Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile Glu65 70 75Xaa Xaa Leu Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr Ala80 85 90Xaa Pro Xaa Arg Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp Xaa95 100 105Glu Phe Xaa Xaa Lys Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu Xaa110 115 120Xaa Xaa Xaa Gln Gln Thr Thr Leu Ser Leu Ala Ile Phe125 130〔SEQ ID NO:3〕其中Xaa在位点17是Ser,Gly,Asp，或Gln；Xaa在位点18是Asn,His，或Ile；Xaa在位点23是Ile,Ala,Leu，或Gly；Xaa在位点25是Thr,His，或Gln；Xaa在位点26是His或Ala；Xaa在位点29是Gln或Asn；Xaa在位点30是Pro或Gly；Xaa在位点32是Leu,Arg,Asn，或Ala；Xaa在位点34是Leu,Val,Ser,Ala,Arg,Gln,Glu,Ile,Phe,Thr，或Met；Xaa在位点35是Leu,Ala,Asn，或Pro；Xaa在位点38是Asn或Ala；Xaa在位点42是Gly,Asp,Ser,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点45是Gln,Val,Met,Leu,Ala,Asn,Glu，或Lys；Xaa在位点46是Asp,Phe,Ser,Gln,Glu,His,Val或Thr；Xaa在位点50是Glu,Asn,Ser或Asp；Xaa在位点51是Asn,Arg,Pro,Thr，或His；Xaa在位点55是Arg,Leu，或Gly；Xaa在位点56是Pro,Gly,Ser,Ala,Asn,Val,Leu或Gln；Xaa在位点62是Asn,Pro，或Thr；Xaa在位点64是Ala或Asn；Xaa在位点65是Val或Thr；Xaa在位点67是Ser或Phe；Xaa在位点68是Leu或Phe；Xaa在位点69是Gln,Ala,Glu，或Arg；Xaa在位点76是Ser,Val,Asn,Pro，或Gly；Xaa在位点77是Ile或Leu；Xaa在位点79是Lys,Gly,Asn,Met,Arg,Ile，或Gly；Xaa在位点80是Asn,Gly,Glu，或Arg；Xaa在位点82是Leu,Gln,Trp,Arg,Asp,Asn,Glu,His,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点87是Leu或Ser；Xaa在位点88是Ala或Trp；Xaa在位点91是Ala或Pro；Xaa在位点93是Thr,Asp，或Ala；Xaa在位点95是His,Pro,Arg,Val,Gly,Asn,Ser或Thr；Xaa在位点98是His,Ile,Asn,Ala,Thr,Gln,Glu,Lys,Met,Ser,Tyr,Val或Leu；Xaa在位点99是Ile或Leu；Xaa在位点100是Lys或Arg；Xaa在位点101是Asp,Pro,Met,Lys,Thr,His,Pro,Asn,Ile,Leu或Tyr；Xaa在位点105是Asn,Pro,Ser,Ile或Asp；Xaa在位点108是Arg,Ala，或Ser；Xaa在位点109是Arg,Thr,Glu,Leu，或Ser；Xaa在位点112是Thr或Gln；Xaa在位点116是Lys,Val,Trp,Ala,His,Phe,Tyr或Ile；Xaa在位点117是Thr或Ser；Xaa在位点120是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点121是Ala,Ser,Ile,Pro，或Asp；Xaa在位点122是Gln,Met,Trp,Phe,Pro,His,Ile，或Tyr；Xaa在位点123是Ala,Met,Glu,Ser，或Leu；并且另外可在位点1的氨基酸前含有Met-；并且其中N末端的1～14氨基酸可被缺失和/或C末端的1～15氨基酸可被缺失；并且其中以Xaa代替的4～44氨基酸与天然(1-133)人白介素3的相应的氨基酸不同。
5．权利要求4的融合蛋白，其中R1的通式是Xaa在位点42是Gly,Asp,Ser,Ile,Leu,Met,Tyr，或Ala；Xaa在位点45是Gln,Val,Met或Asn；Xaa在位点46是Asp,Ser,Gln,His或Val；Xaa在位点50是Glu或Asp；Xaa在位点51是Asn,Pro，或Thr；Xaa在位点62是Asn或Pro；Xaa在位点76是Ser，或Pro；Xaa在位点82是Leu,Trp,Asp,Asn,Glu,His,Phe,Ser或Tyr；Xaa在位点95是His,Arg,Thr,Asn或Ser；Xaa在位点98是His,Ile,Leu,Ala,Gln,Lys,Met,Ser,Tyr或Val；Xaa在位点100是Lys或Arg；Xaa在位点101是Asp,Pro,His,Asn,Ile或Leu；Xaa在位点105是Asn，或Pro；Xaa在位点108是Arg,Ala，或Ser；Xaa在位点116是Lys,Val,Trp,Ala,His,Phe，或Tyr；Xaa在位点121是Aal，或Ile；Xaa在位点122是Gln，或Ile；和Xaa在位点123是Ala,Met或Glu。
6．一种融合蛋白，其通式选自R1-L-R2,R2-L-R1,R1-R2,R2-R1,R1-L-R1及R1-R1其中R1是有如下通式的人白介素3突变多肽Asn Cys Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa1 5 10 15Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Xaa Xaa20 25 30Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa35 40 45Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa50 55 60Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa65 70 75Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa80 85 90Xaa Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa95 100 105Xaa Xaa Xaa Xaa Gln Gln [SEQ ID NO:4]110其中Xaa在位点3是Ser,Lys,Gly,Asp,Met,Gln，或Arg；Xaa在位点4是Asn,His,Leu,Ile,Phe,Arg，或Gln；Xaa在位点5是Met,Phe,Ile,Arg,Gly,Ala，或Cys；Xaa在位点6是Ile,Cys,Gln,Glu,Arg,Pro，或Ala；Xaa在位点7是Asp,Phe,Lys,Arg,Ala,Gly,Glu,Gln,Asn,Thr,Ser或Val；Xaa在位点8是Glu,Trp,Pro,Ser,Ala,His,Asp,Asn,Gln,Leu,Val,或Gly；Xaa在位点9是Ile,Val,Ala,Leu,Gly,Trp,Lys,Phe,Leu,Ser，或Arg；Xaa在位点10是Ile,Gly,Val,Arg,Ser,Phe，或Leu；Xaa在位点11是Thr,His,Gln,Arg,Pro，或Ala；Xaa在位点12是His,Thr,Phe,Gly,Arg,Ala，或Trp；Xaa在位点13是Leu,Gly,Arg,Thr,Ser，或Ala；Xaa在位点14是Lys,Arg,Leu,Gln,Gly,Pro,Val或Trp；Xaa在位点15是Gln,Asn,Leu,Pro,Arg，或Val；Xaa在位点16是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys；Xaa在位点17是Pro,Asp,Gly,Ala,Arg,Leu，或Gln；Xaa在位点18是Leu,Val,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点19是Pro,Leu,Gln,Ala,Thr，或Glu；Xaa在位点20是Leu,Val,Gly,Ser,Lys,Glu,Gln,Thr,Arg,Ala,Phe,Ile或Met；Xaa在位点21是Leu,Ala,Gly,Asn,Pro,Gln，或Val；Xaa在位点22是Asp,Leu，或Val；Xaa在位点23是Phe,Ser,Pro,Trp，或Ile；Xaa在位点24是Asn，或Ala；Xaa在位点26是Leu,Trp，或Arg；Xaa在位点27是Asn,Cys,Arg,Leu,His,Met,Pro；Xaa在位点28是Gly,Asp,Ser,Cys,Ala,Lys,Asn,Thr,Leu,Val,Glu,Phe,Tyr,Ile或Met；Xaa在位点29是Glu,Asn,Tyr,Leu,Phe,Asp,Ala,Cys,Gln,Arg,Thr,Gly或Ser；Xaa在位点30是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp,Glu,Asn,Gln,Ala或Pro；Xaa在位点31是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys,Asp,Asn,Arg,Ser,Ala,Ile,Glu,His或Trp；Xaa在位点32是Asp,Phe,Ser,Thr,Cys,Glu,Asn,Gln,Lys,His,Ala,Tyr,Ile,Val或Gly；Xaa在位点33是Ile,Gly,Val,Ser,Arg,Pro，或His；Xaa在位点34是Leu,Ser,Cys,Arg,Ile,His,Phe,Glu,Lys,Thr,Ala,Met,Val或Asn；Xaa在位点35是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp；Xaa在位点36是Glu,Leu,Thr,Asp,Tyr,Lys,Asn,Ser,Ala,Ile,Val,His,Phe,Met或Gln；Xaa在位点37是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点38是Asn,His,Arg,Leu,Gly,Ser，或Thr；Xaa在位点39是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser,Met，或；Xaa在位点40是Arg,Asp,Ile,Ser,Val,Thr,Gln,Asn,Lys,His,Ala或Leu；Xaa在位点41是Arg,Thr,Val,Ser,Leu，或Gly；Xaa在位点42是Pro,Gly,Cys,Ser,Gln,Glu,Arg,His,Thr,Ala,Tyr,Phe,Leu,Val或Lys；Xaa在位点43是Asn或Gly；Xaa在位点44是Leu,Ser,Asp,Arg,Gln,Val，或Cys；Xaa在位点45是Glu,Tyr,His,Leu,Pro，或Arg；Xaa在位点46是Ala,Ser,Pro,Tyr,Asn，或Thr；Xaa在位点47是Phe,Asn,Glu,Pro,Lys,Arg，或Ser；Xaa在位点48是Asn,His,Val,Arg,Pro,Thr,Asp，或Ile；Xaa在位点49是Arg,Tyr,Trp,Lys,Ser,His,Pro，或Val；Xaa在位点50是Ala,Asn,Pro,Ser，或Lys；Xaa在位点51是Val,Thr,Pro,His,Leu,Phe，或Ser；Xaa在位点52是Lys,Ile,Arg,Val,Asn,Glu，或Ser；Xaa在位点53是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His；Xaa在位点54是Leu,Val,Trp,Ser,Ile,Phe,Thr，或His；Xaa在位点55是Gln,Ala,Pro,Thr,Glu,Arg,Trp,Gly，或Leu；Xaa在位点56是Asn,Leu,Val,Trp,Pro，或Ala；Xaa在位点57是Ala,Met,Leu,Pro,Arg,Glu,Thr,Gln,Trp，或Asn；Xaa在位点58是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp；Xaa在位点59是Ala,Glu,Asp,Leu,Ser,Gly,Thr，或Arg；Xaa在位点60是Ile,Met,Thr,Pro,Arg,Gly,Ala；Xaa在位点61是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser,Gln，或Leu；Xaa在位点62是Ser,Val,Ala,Asn,Trp,Glu,Pro,Gly，或Asp；Xaa在位点63是Ile,Ser,Arg,Thr，或Leu；Xaa在位点64是Leu,Ala,Ser,Glu,Phe,Gly，或Arg；Xaa在位点65是Lys,Thr,Gly,Asn,Met,Arg,Ile，或Asp；Xaa在位点66是Asn,Trp,Val,Gly,Thr,Leu,Glu，或Arg；Xaa在位点67是Leu,Gln,Gly,Ala,Trp,Arg,Val，或Lys；Xaa在位点68是Leu,Gln,Lys,Trp,Arg,Asp,Glu,Asn,His,Thr,Ser,Ala,Tyr,Phe,Ile,Met或Val；Xaa在位点69是Pro,Ala,Thr,Trp,Arg，或Met；Xaa在位点70是Cys,Glu,Gly,Arg,Met，或Val；Xaa在位点71是Leu,Asn,Val，或Gln；Xaa在位点72是Pro,Cys,Arg,Ala，或Lys；Xaa在位点73是Leu,Ser,Trp，或Gly；Xaa在位点74是Ala,Lys,Arg,Val，或Trp；Xaa在位点75是Thr,Asp,Cys,Leu,Val,Glu,His,Asn，或Ser；Xaa在位点76是Ala,Pro,Ser,Thr,Gly,Asp,Ile，或Met；Xaa在位点77是Ala,Pro,Ser,Thr,Phe,Leu,Asp，或His；Xaa在位点78是Pro,Phe,Arg,Ser,Lys,His,Ala,Gly,Ile或Leu；Xaa在位点79是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg；Xaa在位点80是Arg,Ile,Ser,Glu,Leu,Val,Gln,Lys,His,Ala或Pro；Xaa在位点81是His,Gln,Pro,Arg,Val,Leu,Gly,Thr,Asn,Lys,Ser,Ala,Trp,Phe,Ile或Tyr；Xaa在位点82是Pro,Lys,Tyr,Gly,Ile，或Thr；Xaa在位点83是Ile,Val,Lys,Ala，或Asn；Xaa在位点84是His,Ile,Asn,Leu,Asp,Ala,Thr,Glu,Gln,Ser,Phe,Met,Val,Lys,Arg,Tyr或Pro；Xaa在位点85是Ile,Leu,Arg,Asp,Val,Pro,Gln,Gly,ser,Phe，或His；Xaa在位点86是Lys,Tyr,Leu,His,Arg,Ile,Ser,Gln,Pro；Xaa在位点87是Asp,Pro,Met,Lys,His,Thr,Val,Tyr,Glu,Asn,Ser,Ala,Gly,Ile,Leu或Gln；Xaa在位点88是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro；Xaa在位点89是Asp，或Ser；Xaa在位点90是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe，或Gly；Xaa在位点91是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Tle,Asp或His；Xaa在位点92是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro；Xaa在位点94是Arg,Lys,Asp,Leu,Thr,Ile,Gln,His,Ser,Ala，或Pro；Xaa在位点95是Arg,Thr,Pro,Glu,Tyr,Leu,Ser，或Gly；Xaa在位点96是Lys,Asn,Thr,Leu,Gln,Arg,His,Glu,Ser,Ala或Trp；Xaa在位点97是Leu,Ile,Arg,Asp，或Met；Xaa在位点98是Thr,Val,Gln,Tyr,Glu,His,Ser，或Phe；Xaa在位点99是Phe,Ser,Cys,His,Gly,Trp,Tyr,Asp,Lys,Leu,Ile,Val或Asn；Xaa在位点100是Tyr,Cys,His,Ser,Trp,Arg，或Leu；Xaa在位点101是Leu,Asn,Val,Pro,Arg,Ala,His,Thr,Trp，或Met；Xaa在位点102是Lys,Leu,Pro,Thr,Met,Asp,Val,Glu,Arg,Trp,Ser,Asn,His,Ala,Tyr,Phe,Gln，或Ile；Xaa在位点103是Thr,Ser,Asn,Ile,Trp,Lys，或Pro；Xaa在位点104是Leu,Ser,Pro,Ala,Glu,Cys,Asp，或Tyr；Xaa在位点105是Glu,Ser,Lys,Pro,Leu,Thr,Tyr，或Arg；Xaa在位点106是Asn,Ala,Pro,Leu,His,Val，或Gln；Xaa在位点107是Ala,Ser,Ile,Asn,Pro,Lys,Asp，或Gly；Xaa在位点108是Gln,Ser,Met,Trp,Arg,Phe,Prc,His,Ile,Tyr，或Cys；Xaa在位点109是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；并且另外可在位点1的氨基酸前含有Met-或Met-Ala-；并且其中以Xaa代表的4～44氨基酸与天然的(1～133)人白介素3相应的氨基酸不同；R2是一种集落刺激因子；以及L是一个能将R1与R2连接的接头。
7．权利要求6的融合蛋白，其中所说的集落刺激因子选自GM-CSF,CSF-1,G-CSF,Meg-CSF(最近称为c-mpl配体)，M-CSF，红细胞生成素(EPO),IL-1,IL-4,IL-2,IL-5,IL-6,IL-7,IL-8,IL-9,IL-10,IL-11,IL-12,IL-13,LIF,flt3/flk2，人生长激素，B细胞生长因子，B细胞分化因子，嗜酸性细胞分化因子及干细胞因子(CSF)。
8．权利要求7的融合蛋白，其中R1的通式为Asn Cys Xaa Xaa Xaa Ile Xaa Glu Xaa Xaa Xaa Xaa Leu Lys Xaa1 5 10 15Xaa Xaa Xaa Xaa Xaa Xaa Asp Xaa Xaa Asn Leu Asn Xaa Glu Xaa20 25 30Xaa Xaa Ile Leu Met Xaa Xaa Asn Leu Xaa Xaa Xaa Asn Leu Glu35 40 45Xaa Phe Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Asn Xaa Xaa Xaa Ile50 55 60Glu Xaa Xaa Leu Xaa Xaa Leu Xaa Xaa Cys Xaa Pro Xaa Xaa Thr65 70 75Ala Xaa Pro Xaa Arg Xaa Xaa Xaa Xaa Xaa Xaa Xaa Gly Asp Xaa80 85 90Xaa Xaa Phe Xaa Xaa Lys Leu Xaa Phe Xaa Xaa Xaa Xaa Leu Glu95 100 105Xaa Xaa Xaa Xaa Gln Gln [SEQ ID NO:5]110其中Xaa在位点3是Ser,Gly,Asp,Met，或Gln；Xaa在位点4是Asn,His，或Ile；Xaa在位点5是Met或Ile；Xaa在位点7是Asp或Glu；Xaa在位点9是Ile,Ala,Leu，或Gly；Xaa在位点10是Ile,Val，或Leu；Xaa在位点11是Thr,His,Gln，或Ala；Xaa在位点12是His或Ala；Xaa在位点15是Gln,Asn，或Val；Xaa在位点16是Pro,Gly，或Gln；Xaa在位点17是Pro,Asp,Gly，或Gln；Xaa在位点18是Leu,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点19是Pro或Glu；Xaa在位点20是Leu,Val,Gly,Ser,Lys,Ala,Arg,Gln,Glu,Ile,Phe,Thr或Met；Xaa在位点21是Leu,Ala,Asn,Pro,Gln，或Val；Xaa在位点23是Phe,Ser,Pro，或Trp；Xaa在位点24是Asn或Ala；Xaa在位点28是Gly,Asp,Ser,Cys,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点30是Asp或Glu；Xaa在位点31是Gln,Val,Met,Leu,Thr,Ala,Asn,Glu,Ser或Lys；Xaa在位点32是Asp,Phe,Ser,Thr,Ala,Asn,Gln,Glu,His,Ile,Lys,Tyr,Val或Cys；Xaa在位点36是Glu,Ala,Asn,ser或Asp；Xaa在位点37是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点40是Arg或Ala；Xaa在位点41是Arg,Thr,Val,Leu，或Gly；Xaa在位点42是Pro,Gly,Ser,Gln,Ala,Arg,Asn,Glu,Leu,Thr,Val或Lys；Xaa在位点46是Ala或Ser；Xaa在位点48是Asn,Pro,Thr，或Ile；Xaa在位点49是Arg或Lys；Xaa在位点50是Ala或Asn；Xaa在位点51是Val或Thr；Xaa在位点52是Lys或Arg；Xaa在位点53是Ser,Phe，或His；Xaa在位点54是Leu,Ile,Phe，或His；Xaa在位点55是Gln,Ala,Pro,Thr,Glu,Arg，或Gly；Xaa在位点57是Ala,Pro，或Arg；Xaa在位点58是Ser,Glu,Arg，或Asp；Xaa在位点59是Ala或Leu；Xaa在位点62是Ser,Val,Ala,Asn,Glu,Pro，或Gly；Xaa在位点63是Ile或Leu；Xaa在位点65是Lys,Thr,Gly,Asn,Met,Arg,Ile,Gly，或Asp；Xaa在位点66是Asn,Gly,Glu，或Arg；Xaa在位点68是Leu,Gln,Trp,Arg,Asp,Ala,Asn,Glu,His,Ile,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点69是Pro或Thr；Xaa在位点71是Leu或Val；Xaa在位点73是Leu或Ser；Xaa在位点74是Ala或Trp；Xaa在位点77是Ala或Pro；Xaa在位点79是Thr,Asp,Ser,Pro,Ala,Leu，或Arg；Xaa在位点81是His,Pro,Arg,Val,Leu,Gly,Asn,Phe,Ser或Thr；Xaa在位点82是Pro或Tyr；Xaa在位点83是Ile或Val；Xaa在位点84是His,Ile,Asn,Leu,Ala,Thr,Leu,Arg,Gln,Leu,Lys,Met,Ser,Tyr,Val或Pro；Xaa在位点85是Ile,Leu，或Val；Xaa在位点86是Lys,Arg,Ile,Gln,Pro，或Ser；Xaa在位点87是Asp,Pro,Met,Lys,His,Thr,Asn,Ile,Leu或Tyr；Xaa在位点90是Trp或Leu；Xaa在位点91是Asn,Pro,Ala,Ser,Trp,Gln,Tyr,Leu,Lys,Ile,Asp，或His；Xaa在位点92是Glu，或Gly；Xaa在位点94是Arg,Ala，或Ser；Xaa在位点95是Arg,Thr,Glu,Leu，或Ser；Xaa在位点98是Thr,Val，或Gln；Xaa在位点100是Tyr或Trp；Xaa在位点101是Leu或Ala；Xaa在位点102是Lys,Thr,Val,Trp,Ser,Ala,His,Met,Phe,Tyr或Ile；Xaa在位点103是Thr或Ser；Xaa在位点106是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点107是Ala,Ser,Ile,Asn,Pro,Asp，或Gly；Xaa在位点108是Gln,Ser,Met,Trp,Arg,Phe,Pro,His,Ile,Tyr，或Cys；Xaa在位点109是Ala,Met,Glu,His,Ser,Pro,Tyr，或Leu；它另外可在位点1的氨基酸前含有Met-或Met-Ala-；并且其中以Xaa代表的4-35氨基酸与天然人白介素3的相应的氨基酸不同。
9．权利要求8的融合蛋白，其中R1的通式是Asn Cys Xaa Xaa Met Ile Asp Glu Xaa Ile Xaa Xaa Leu Lys Xaa1 5 10 15Xaa Pro Xaa Pro Xaa Xaa Asp phe Xaa Asn Leu Asn Xaa Glu Asp20 25 30Xaa Xaa Ile Leu Met Xaa Xaa Asn Leu Arg Xaa Xaa Asn Leu Glu35 40 45Ala Phe Xaa Arg Xaa Xaa Lys Xaa Xaa Xaa Asn Ala Ser Ala Ile50 55 60Glu Xaa Xaa Leu Xaa Xaa Leu Xaa Pro Cys Leu Pro Xaa Xaa Thr65 70 75Ala Xaa Pro Xaa Arg Xaa Pro Ile Xaa Xaa Xaa Xaa Gly Asp Trp80 85 90Xaa Glu Phe Xaa Xaa Lys Leu Xaa Phe Tyr Leu Xaa Xaa Leu Glu95 100 105Xaa Xaa Xaa Xaa Gln Gln [SEQ ID NO:6]110其中Xaa在位点3是Ser,Gly,Asp，或Gln；Xaa在位点4是Asn,His，或Ile；Xaa在位点9是Ile,Ala,Leu，或Gly；Xaa在位点11是Thr,His，或Gln；Xaa在位点12是His或Ala；Xaa在位点15是Gln或Asn；Xaa在位点16是Pro或Gly；Xaa在位点18是Leu,Arg,Asn，或Ala；Xaa在位点20是Leu,Val,Ser,Ala,Arg,Gln,Glu,Ile,Phe,Thr或Met；Xaa在位点21是Leu,Ala,Asn，或Pro；Xaa在位点24是Asn或Ala；Xaa在位点28是Gly,Asp,Ser,Ala,Asn,Ile,Leu,Met,Tyr或Arg；Xaa在位点31是Gln,Val,Met,Leu,Ala,Asn,Glu或Lys；Xaa在位点32是Asp,Phe,Ser,Ala,Gln,Glu,His,Val或Thr；Xaa在位点36是Glu,Asn,Ser或Asp；Xaa在位点37是Asn,Arg,Pro,Thr，或His；Xaa在位点41是Arg,Leu，或Gly；Xaa在位点42是Pro,Gly,Ser,Ala,Asn,Val,Leu或Gln；Xaa在位点48是Asn,Pro，或Thr；Xaa在位点50是Ala或Asn；Xaa在位点51是Val或Thr；Xaa在位点53是Ser或Phe；Xaa在位点54是Leu或Phe；Xaa在位点55是Gln,Ala,Glu，或Arg；Xaa在位点62是Ser,Val,Asn,Pro，或Gly；Xaa在位点63是Ile或Leu；Xaa在位点65是Lys,Asn,Met,Arg,Ile，或Gly；Xaa在位点66是Asn,Gly,Glu，或Arg；Xaa在位点68是Leu,Gln,Trp,Arg,Asp,Asn,Glu,His,Met,Phe,Ser,Thr,Tyr或Val；Xaa在位点73是Leu或Ser；Xaa在位点74是Ala或Trp；Xaa在位点77是Ala或Pro；Xaa在位点79是Thr,Asp，或Ala；Xaa在位点81是His,Pro,Arg,Val,Gly,Asn,Ser或Thr；Xaa在位点84是His,Ile,Asn,Ala,Thr,Arg,Gln,Glu,Lys,Met,Ser,Tyr,Val或Leu；Xaa在位点85是Ile或Leu；Xaa在位点86是Lys或Arg；Xaa在位点87是Asp,Pro,Met,Lys,His,Pro,Asn,Ile,Leu或Tyr；Xaa在位点91是Asn,Pro,Ser,Ile或Asp；Xaa在位点94是Arg,Ala，或Ser；Xaa在位点95是Arg,Thr,Glu,Leu，或Ser；Xaa在位点98是Thr或Gln；Xaa在位点102是Lys,Val,Trp，或Ile；Xaa在位点103是Thr,Ala,His,Phe,Tyr或Ser；Xaa在位点106是Asn,Pro,Leu,His,Val，或Gln；Xaa在位点107是Ala,Ser,Ile,Pro，或Asp；Xaa在位点108是Gln,Met,Trp,Phe,Pro,His,Ile，或Tyr；Xaa在位点109是Ala,Met,Glu,Ser，或Leu；并且另外可在位点1的氨基酸前含有Met-或Met-Ala-；并且其中以Xaa代表的4～26氨基酸与天然(1～133)人白介素3相应的氨基酸不同。
10．权利要求9的融合蛋白，其中R1的通式是Xaa在位点17是Ser,Lys,Asp,Met,Gln，或Arg；Xaa在位点18是Asn,His,Leu,Ile,Phe,Arg，或Gln；Xaa在位点19是Met,Arg,Gly,Ala，或Cys；Xaa在位点20是Ile,Cys,Gln,Glu,Arg,Pro，或Ala；Xaa在位点21是Asp,Phe,Lys,Arg,Ala,Gly，或Val；Xaa在位点22是Gly,Trp,Pro,Ser,Ala,His，或Gly；Xaa在位点23是Ile,Ala,Gly,Trp,Lys,Leu,Ser，或Arg；Xaa在位点24是Ile,Gly,Arg，或Ser；Xaa在位点25是Thr,His,Gly,Gln,Arg,Pro，或Ala；Xaa在位点26是His,Thr,Phe,Gly,Ala，或Trp；Xaa在位点27是Leu,Gly,Arg,Thr,Ser，或Ala；Xaa在位点28是Lys,Leu,Gln,Gly,Pro,Val或Trp；Xaa在位点29是Gln,Asn,Pro,Arg，或Val；Xaa在位点30是Pro,His,Thr,Gly,Asp,Gln,Ser,Leu，或Lys；Xaa在位点31是Pro,Asp,Gly,Arg,Leu，或Gln；Xaa在位点32是Leu,Arg,Gln,Asn,Gly,Ala，或Glu；Xaa在位点33是Pro,Leu,Gln,Thr，或Glu；Xaa在位点34是Leu,Gly,Ser，或Lys；Xaa在位点35是Leu,Ala,Gly,Asn,Pro，或Gln；Xaa在位点36是Asp,Leu，或Val；Xaa在位点37是Phe,Ser，或Pro；Xaa在位点38是Aan，或Ala；Xaa在位点40是Leu,Trp，或Arg；Xaa在位点41是Asn,Cys,Arg,Leu,His,Met,Pro；Xaa在位点42是Gly,Asp,Ser,Cys，或Ala；Xaa在位点42是Gly,Asn,Tyr,Leu,Phe,Asp,Ala,Cys，或Ser；Xaa在位点44是Asp,Ser,Leu,Arg,Lys,Thr,Met,Trp，或Pro；Xaa在位点45是Gln,Pro,Phe,Val,Met,Leu,Thr,Lys，或Trp；Xaa在位点46是Asp,Phe,Ser,Thr,Cys，或Gly；Xaa在位点47是Ile,Gly,Ser,Arg,Pro，或His；Xaa在位点48是Leu,Ser,Cys,Arg,His,Phe，或Asn；Xaa在位点49是Met,Arg,Ala,Gly,Pro,Asn,His，或Asp；Xaa在位点50是Glu,Leu,Thr,Asp，或Try；Xaa在位点51是Asn,Arg,Met,Pro,Ser,Thr，或His；Xaa在位点52是Asn,His,Arg,Leu,Gly,Ser，或Thr；Xaa在位点53是Leu,Thr,Ala,Gly,Glu,Pro,Lys,Ser，或；Xaa在位点54是Arg,Asp,Ile,Ser,Val,Thr,Gln，或Leu；Xaa在位点55是Arg,Thr,Val,Ser,Leu，或Gly；Xaa在位点56是Pro,Gly,Cys,Ser,Gln，或Lys；Xaa在位点57是Asn或Gly；Xaa在位点58是Leu,Ser,Asp,Arg,Gln,Val，或Cys；Xaa在位点59是Glu,Tyr,His,Leu,Pro，或Arg；Xaa在位点60是Ala,Ser,Tyr,Asn，或Thr；Xaa在位点61是Phe,Asn,Glu,Prc,Lys,Arg，或Ser；Xaa在位点62是Asn,His,Val,Arg,Pro,Thr，或Ile；Xaa在位点63是Arg,Tyr,Trp,Ser,Pro，或Val；Xaa在位点64是Ala,Asn,Ser，或Lys；Xaa在位点65是Val,Thr,Pro,His,Leu,Phe，或Ser；Xaa在位点66是Lys,Ile,Val,Asn,Glu，或Ser；Xaa在位点67是Ser,Ala,Phe,Val,Gly,Asn,Ile,Pro，或His；Xaa在位点68是Leu,Val,Trp,Ser,Thr，或His；Xaa在位点69是Gln,Ala,Pro,Thr,Arg,Trp,Gly，或Leu；Xaa在位点70是Asn,Leu,Val,Trp,Pro，或Ala；Xaa在位点71是Ala,Met,Leu,Arg,Glu,Thr,Gln,Trp，或Asn；Xaa在位点72是Ser,Glu,Met,Ala,His,Asn,Arg，或Asp；Xaa在位点73是Ala,Glu,Asp,Leu,Ser,Gly,Thr，或Arg；Xaa在位点74是Ile,Thr,Pro,Arg,Gly,Ala；Xaa在位点75是Glu,Lys,Gly,Asp,Pro,Trp,Arg,Ser，或Leu；Xaa在位点76是Ser,Val,Ala,Asn,Trp,Glu,Pro,gly，或Asp；Xaa在位点77是Ile,Ser,Arg，或Thr；Xaa在位点78是Leu,Ala,Ser,Glu,Gly，或Arg；Xaa在位点79是Lys,Thr,Gly,Asn,Met,Ile，或Asp；Xaa在位点80是Asn,Trp,Val,Gly,Thr,Leu，或Arg；Xaa在位点81是Leu,Gln,Gly,Ala,Trp,Arg，或Lys；Xaa在位点82是Leu,Gln,Lys,Trp,Arg，或Asp；Xaa在位点83是Pro,Thr,Trp,Arg，或Met；Xaa在位点84是Cys,Glu,Cly,Arg,Met，或Val；Xaa在位点85是Leu,Asn，或Gln；Xaa在位点86是Pro,Cys,Arg,Ala，或Lys；Xaa在位点87是Leu,Ser,Trp，或Gly；Xaa在位点88是Ala,Lys,Arg,Val，或Trp；Xaa在位点89是Thr,Asp,Cys,Leu,Val,Glu,His，或Asn；Xaa在位点90是Ala,Ser,Asp,Ile，或Met；Xaa在位点91是Ala,Ser,Thr,Phe,Leu,Asp，或His；Xaa在位点92是Pro,Phe,Arg,Ser,Lys,His，或Leu；Xaa在位点93是Thr,Asp,Ser,Asn,Pro,Ala,Leu，或Arg；Xaa在位点94是Arg,Ile,Ser,Glu,Leu,Val，或Pro；Xaa在位点95是His,Gln,Pro,Val,Leu,Thr，或Tyr；Xaa在位点96是Pro,Lys,Tyr,Gly,Ile，或Thr；Xaa在位点97是Ile,Lys,Ala，或Asn；Xaa在位点98是His,Ile,Asn,Leu,Asp,Ala,Thr，或Pro；Xaa在位点99是Ile,Arg,Asp,Pro,Gln,Gly,Phr，或His；Xaa在位点100是Lys,Tyr,Leu,His,Ile,Ser,Gln，或Pro；Xaa在位点101是Asp,Pro,Met,Lys,His,Thr,Val,Tyr，或Gln；Xaa在位点102是Gly,Leu,Glu,Lys,Ser,Tyr，或Pro；Xaa在位点103是Asp，或Ser；Xaa在位点104是Trp,Val,Cys,Tyr,Thr,Met,Pro,Leu,Gln,Lys,Ala,Phe，或Gly；Xaa在位点105是Asn,Pro,Ala,Phe,Ser,Trp,Gln,Tyr,Leu,Lys,Ile，或His；Xaa在位点106是Glu,Ser,Ala,Lys,Thr,Ile,Gly，或Pro；Xaa在位点108是Arg,Asp,Leu,Thr,Ile，或Pro；Xaa在位点109是Arg,Thr,Pro,Glu,Tyr,Leu,Ser，或Gly；
11．权利要求10的融合蛋白，其中R1的通式是1 5 10(Met)m-Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr15 20Ser Trp Val Asn Cys Ser Xaa Xaa Xaa Asp Glu Ile Ile25 30 35Xaa His Leu Lys Xaa Pro Pro Xaa Pro Xaa Leu Asp Xaa40 4550Xaa Asn Leu Asn Xaa Glu Asp Xaa Asp Ile Leu Xaa Glu55 60Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa Xaa65 70 75Ala Xaa Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa80 85Ile Leu Xaa Asn Leu Xaa Pro Cys Xaa Pro Xaa Xaa Thr90 95 100Ala Xaa Pro Xaa Arg Xaa Pro Ile Xaa Ile Xaa Xaa Gly105110 115Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Xaa Phe Tyr Leu120125Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln Thr Thr Leu130Ser Leu Ala Ile Phe [SEQ ID NO:7]其中m是0或1；Xaa在位点18是Asn或Ile；Xaa在位点19是Met,Ala或Ile；Xaa在位点20是Ile,Pro或Ile；Xaa在位点23是Ile,Ala或Leu；Xaa在位点25是Thr或His；Xaa在位点29是Gln,Arg,Val或Ile；Xaa在位点32是Leu,Ala,Asn或Arg；Xaa在位点34是Leu或Ser；Xaa在位点37是Pha,Pro，或Ser；Xaa在位点38是Asn或Ala；Xaa在位点42是Gly,Ala,Ser,Asp或Asn；Xaa在位点45是Gln,Val，或Met；Xaa在位点46是Asp或Ser；Xaa在位点49是Met,Ile,Leu或Asp；Xaa在位点50是Glu或Asp；Xaa在位点51是Asn,Arg或Ser；Xaa在位点55是Arg,Leu，或Thr；Xaa在位点56是Pro或Ser；Xaa在位点59是Glu或Leu；Xaa在位点60是Ala或Ser；Xaa在位点62是Asn,Val或Pro；Xaa在位点63是Arg或His；Xaa在位点65是Val或Ser；Xaa在位点67是Ser,Asn,His或Gln；Xaa在位点69是Gln或Glu；Xaa在位点73是Ala或Gly；Xaa在位点76是Ser,Ala或Pro；Xaa在位点79是Lys,Arg或Ser；Xaa在位点82是Leu,Glu,Val或Trp；Xaa在位点85是Leu或Val；Xaa在位点87是Leu,Ser,Tyr；Xaa在位点88是Ala或Trp；Xaa在位点91是Ala或Pro；Xaa在位点93是Pro或Ser；Xaa在位点95是His或Thr；Xaa在位点98是His,Ile,或Thr；Xaa在位点100是Lys或Arg；Xaa在位点101是Asp,Ala或Met；Xaa在位点105是Asn或Glu；Xaa在位点109是Arg,Glu或Leu；Xaa在位点112是Thr或Gln；Xaa在位点116是Lys,Val,Trp或Ser；Xaa在位点117是Thr或Ser；Xaa在位点120是Asn,Gln，或His；Xaa在位点123是Ala或Glu；以用Xaa代表的4～44氨基酸与天然的人白介素3相应的氨基酸不同为条件。
12．权利要求11的融合蛋白，其中R1的通式是1 5 10(Metm-Alan)p-Asn Cys Ser Xaa Xaa Xaa Asp Glu Xaa Ile15 20Xaa His Leu Lys Xaa Pro Pro Xaa Pro Xaa Leu Asp Xaa25 30 35Xaa Asn Leu Asn Xaa Glu Asp Xaa Xaa Ile Leu Xaa Glu40 45Xaa Asn Leu Arg Xaa Xaa Asn Leu Xaa Xaa Phe Xaa Xaa50 55 60Ala Xaa Lys Xaa Leu Xaa Asn Ala Ser Xaa Ile Glu Xaa65 70 75Ile Leu Xaa Asn Xaa Xaa Pro Cys Xaa Pro Xaa Ala Thr80 85Ala Xaa Pro Xaa Arg Xaa Pro Ile Xaa Ile Xaa Xaa Gly90 95 100Asp Trp Xaa Glu Phe Arg Xaa Lys Leu Xaa Phe Tyr Leu105110Xaa Xaa Leu Glu Xaa Ala Gln Xaa Gln Gln [SEQ ID NO:8]其中m是0或1；n是0或1；p是0或1；Xaa在位点4是Asn或Ile；Xaa在位点5是Met,Ala或Ile；Xaa在位点6是Ile,Pro或Leu；Xaa在位点9是Ile,Ala或Leu；Xaa在位点11是Thr或His；Xaa在位点15是Gen,Arg,Val或Ile；Xaa在位点18是Leu,Ala,Asn或Arg；Xaa在位点20是Leu或Ser；Xaa在位点23是Phe,Pro，或Ser；Xaa在位点24是Asn或Ala；Xaa在位点28是Gly,Ala,Ser,Asp或Asn；Xaa在位点31是Gln,Val，或Met；Xaa在位点32是Asp或Ser；Xaa在位点35是Met,Ile或Asp；Xaa在位点36是Glu或Asp；Xaa在位点37是Asn,Arg或Ser；Xaa在位点41是Arg,Leu，或Thr；Xaa在位点42是Pro或Ser；Xaa在位点45是Glu或Leu；Xaa在位点46是Ala或Ser；Xaa在位点48是Asn,Val或Pro；Xaa在位点49是Arg或His；Xaa在位点51是Val或Gly；Xaa在位点53是Ser,Asn,His或Gln；Xaa在位点55是Gln或Glu；Xaa在位点59是Ala或Gly；Xaa在位点62是Ser,Ala或Pro；Xaa在位点65是Lys,Arg或Ser；Xaa在位点67是Leu,Glu，或Val；Xaa在位点68是Leu,Glu,Val或Trp；Xaa在位点71是Leu或Val；Xaa在位点73是Leu,Ser或Tyr；Xaa在位点74是Ala或Trp；Xaa在位点77是Ala或Pro；Xaa在位点79是Pro或Ser；Xaa在位点81是His或Thr；Xaa在位点84是His,Ile，或Thr；Xaa在位点86是Lys或Arg；Xaa在位点87是Asp,Ala或Met；Xaa在位点91是Asn或Glu；Xaa在位点95是Arg,Glu,Leu；Xaa在位点98是Thr或Gln；Xaa在位点102是Lys,Val,Trp或Ser；Xaa在位点103是Thr或Ser；Xaa在位点106是Asn,Gln，或His；Xaa在位点109是Ala或Glu；以用Xaa代表的4～44氨基酸与天然(15-125)人白介素3相应的氨基酸不同为条件。
13．权利要求12的融合蛋白，其中R1的通式是Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:9]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:10]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:11]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:12]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Aia Val Lys Asn Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:13]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:14]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:15]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:16]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:17]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val SerLeu Glu His Ala Gln Glu Gln Gln [SEQ ID NO:18]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:19]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:20]；Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His ProIle Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val SerLeu Glu His Ala Gln Glu Gln Gln [SEQ ID NO:21]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:22]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:23]；Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Set Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:24]；Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:25]；Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:26]；Met Ala Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His LeuLys Gln Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn GlyGlu Asp Gln Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro AsnLeu Glu Ala Phe Asn Arg Ala Val Lys Ser Leu Gln Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val SerLeu Glu His Ala Gln Glu Gln Gln [SEQ ID NO:27]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:28]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:29]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerAla Ile Glu Ser Ile Leu Lys Asn Leu Leu Pro Cys Leu Pro LeuAla Thr Ala Ala Pro Thr Arg His Pro Ile His Ile Lys Asp GlyAsp Trp Asn Glu Phe Arg Arg Lys Leu Thr Phe Tyr Leu Lys ThrLeu Glu Asn Ala Gln Ala Gln Gln [SEQ ID NO:30]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:31]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:32]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:33]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:34]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:35]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val SerLeu Glu His Ala Gln Glu Gln Gln [SEQ ID NO:36]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Val Pro Pro Ala Pro Leu Leu Asp Ser Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val SerLeu Glu His Ala Gln Glu Gln Gln [SEQ ID NO:37]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:38]；Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Val Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Thr Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val SerLeu Glu His Ala Gln Glu Gln Gln [SEQ ID NO:39].Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Ser AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:40]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ala Ile His His LeuLys Arg Pro Pro Ala Pro Ser Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:41]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:42]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AlaGlu Asp Val Asp Ile Leu Met Asp Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:43]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:44]Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Ala Pro Leu Leu Asp Pro Asn Asn Leu Asn AspGlu Asp Met Ser Ile Leu Met Glu Arg Asn Leu Arg Leu Pro AsnLeu Glu Ser Phe Val Arg Ala Val Lys Asn Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:45]Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys AsnCys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg ProPro Ala Pro Leu Leu Asp Pro Asn Ash Leu Asn Ala Glu Asp ValAsp Ile Leu Met Glu Arg Asn Leu Arg Leu Pro Asn Leu Glu SerPhe Val Arg Ala Val Lys Asn Leu Glu Asn Ala Ser Gly Ile GluAla Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu GlnAla Gln Glu Gln Gln[SEQ ID NO:46]Met Ala Tyr Pro Glu Thr Asp Tyr Lys Asp Asp Asp Asp Lys AsnCys Ser Ile Met Ile Asp Glu Ile Ile His His Leu Lys Arg ProPro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn Ser Glu Asp MetAsp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro Asn Leu Leu AlaPhe Val Arg Ala Val Lys His Leu Glu Asn Ala Ser Gly Ile GluAla Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro Ser Ala Thr AlaAla Pro Ser Arg His Pro Ile Ile Ile Lys Ala Gly Asp Trp GlnGlu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val Thr Leu Glu GlnAla Gln Glu Gln Gln[SEQ ID NO:47] andMet Ala Asn Cys Ser Ile Met Ile Asp Glu Leu Ile His His LeuLys Ile Pro Pro Asn Pro Ser Leu Asp Ser Ala Asn Leu Asn SerGlu Asp Val Ser Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:48].
14．权利要求13的融合蛋白，其中R1的通式是Met Ala Asn Cys Ser Ile Met Ile Asp Glu Ile Ile His His LeuLys Arg Pro Pro Asn Pro Leu Leu Asp Pro Asn Asn Leu Asn SerGlu Asp Met Asp Ile Leu Met Glu Arg Asn Leu Arg Thr Pro AsnLeu Leu Ala Phe Val Arg Ala Val Lys His Leu Glu Asn Ala SerGly Ile Glu Ala Ile Leu Arg Asn Leu Gln Pro Cys Leu Pro SerAla Thr Ala Ala Pro Ser Arg His Pro Ile Ile Ile Lys Ala GlyAsp Trp Gln Glu Phe Arg Glu Lys Leu Thr Phe Tyr Leu Val ThrLeu Glu Gln Ala Gln Glu Gln Gln [SEQ ID NO:30].
15．权利要求1,2,3,4,5,6,7,8,9,10,11,12,13，或14的融合蛋白，其中的集落刺激因子是G-CSF或GM-CSF。
16．权利要求1的融合蛋白，选自相应于SEQ.ID.NO:121～159及165～168的氨基酸序列。
17．权利要求1的融合蛋白，选自相应于SEQ.ID.NO:133,124,154和155的氨基酸序列。
18．一种包括治疗有效剂量的权利要求1,2,3,4,5,6,7,8,9,10,11,12,13,14,16或17的融合蛋白和一种药用载体的药用组合物。
19．一种包括一种治疗有效剂量的权利要求15的融合蛋白和一种药用载体的药用组合物。
20．一种在有这种需求的哺乳动物中增加造血生成细胞产量的方法，此方法包括施用治疗有效剂量的权利要求1,2,3,4,5,6,7,8,9,10,11,12,13,14,16或17的融合蛋白。
21．一种在有这种需求的哺乳动物中增加造血生成细胞产量的方法，此方法包括施用治疗有效剂量的权利要求15的融合蛋白。
22．包括载体DNA和编码选自相应于SEQ.ID.NO:53～90和183～186的核苷酸序列多肽的DNA的重组DNA。
23．权利要求22的重组DNA，选自相应于SEQ.ID.NO:60,64,89及98的核苷酸序列。
全文摘要
本发明涉及与其他集落刺激因子(CSF)，细胞因子、淋巴因子、白介素、造血生长因子或IL－3变异体融合的人白介素－3(hIL－3)变异体或突变体蛋白(突变蛋白)。
文档编号C12N15/24GK1227604SQ95192254
公开日1999年9月1日 申请日期1995年2月2日 优先权日1994年2月4日
发明者C·S·包尔, M·A·阿布兰斯, S·R·布拉福－戈堡, M·H·卡帕龙, A·M·伊斯顿, B·K·克莱恩, J·P·麦基恩, P·O·奥林斯, K·派克, J·W·托马斯 申请人:G·D·瑟尔公司