CN112543644A

CN112543644A - 一种预防和治疗免疫相关疾病的组合物

Info

Publication number: CN112543644A
Application number: CN201980049336.8A
Authority: CN
Inventors: 金廷镐; 金范锡
Original assignee: Goodall T Cell Co ltd
Current assignee: Goodall T Cell Co ltd; Good T Cells Inc
Priority date: 2018-07-24
Filing date: 2019-07-24
Publication date: 2021-03-23
Also published as: WO2020022782A1; CA3107159A1; US20210347849A1; KR20200011377A; JP7368007B2; EP3827837A4; JP2021532119A; KR102263643B1; AU2019309472A1; EP3827837A1

Abstract

本发明涉及一种预防、改善或治疗免疫相关疾病的组合物，其包含作为活性成分的融合蛋白，所述融合蛋白包含富含亮氨酸和免疫球蛋白样结构域‑1(Lrig‑1)蛋白的胞外结构域和免疫球蛋白Fc区。本发明提供的融合蛋白与活化T细胞中存在的Lrig‑1蛋白的配体相互作用，向活化T细胞提供共抑制信号，从而诱导活化T细胞的死亡或活性抑制，使得有效预防、改善或治疗免疫相关疾病成为可能。

Description

一种预防和治疗免疫相关疾病的组合物

技术领域

本发明涉及一种能够有效预防或治疗免疫相关疾病的组合物。

背景技术

免疫球蛋白由四条多肽链组成，即两条重链和两条轻链，它们通过链间二硫键相互连接。每个轻链有两个区域，即轻链可变区(VL)和轻链恒定区(CL)；每个重链有两个区域，即重链可变区和重链恒定区。重链恒定区(CH)包含由数字(参见，例如US 6,086,875(Blumbberg R.S.等)、US 5,624,821(Winter G.P.等)和US 5,116,964(Capon D.J.和Lasky L.A.))指定的重链恒定区(例如CH1、CH2、CH3等)。免疫球蛋白根据其生物学特性、在生物体中的位置和处理不同抗原的能力被分为不同的同种型(即IgG、IgM、IgA、IgD和IgE)。根据免疫球蛋白的同种型，重链恒定区(CH)可能有3或4个重链恒定区。此外，在一些同种型(IgA、IgD和IgG)中，重链包含增加分子灵活性的铰链区(Janeway等，2001，免疫生物学，纽约加兰出版社，纽约)。

在人类中，有四个IgG亚类(IgG1、2、3和4)，这些IgG按照它们在血清中的浓度高低(即IgG1浓度最高)来命名。IgG同种型由两条轻链和两条重链组成，其中每条重链包括三个重链恒定区(CH1、CH2和CH3)。IgG的两条重链通过二硫键(-S-S-)相互连接，且每条重链通过二硫键与一条轻链连接。IgG的抗原结合位点位于抗原结合片段区(Fab区)，包括轻链(VL)和重链(VH)的可变区以及轻链(CL)和重链(CH1)的恒定区。IgG的可结晶片段区(Fc区)是包含CH2和CH3结构域的重链的一部分，这些结构域与某些细胞表面的Fc受体结合，包括新生Fc受体(FcRn)。IgG的重链在CH1和CH2之间还有一个铰链区，它将Fab区和Fc区分开，并通过二硫键将两条重链连接在一起。铰链区的结构有助于四个IgG亚类中每一个的独特生物特性。

IgG是作为一种体积小的单体分泌的，从而其更容易的渗透进入组织。它是唯一一种具有可以穿过人类胎盘的受体(新生儿Fc受体(FcRn))的同种型，从而为子宫内的胎儿提供保护。通过胎盘吸收的IgG在新生儿自身免疫***发育之前可以为其提供体液免疫。

IgG新生儿Fc受体结合位点位于抗体的Fc区。FcRn通常在人胎盘和上皮细胞中表达，并参与阻止IgG降解的内吞补救途径。这种补救途径是通过在酸性pH下IgG对FcRn的高度pH依赖性的结合亲和力来介导的。在酸性pH下，IgG对FcRn的高度亲和力被认为是导致内化的IgG再被吸收到酸性内体后对FcRn的结合(Goebl NA.等，2008；Junghans R P等，1996)。大多数可溶性蛋白质在内化后被导向溶酶体；然而，内化的FcRn结合的IgG返回到质膜，并被有效地从潜在的降解途径中拯救出来。当暴露于细胞外空间的中性pH环境时，IgG可从FcRn中解离出来并返回到循环中。因此，使得抗体的延长血清半衰期特性保留在Fc片段中。

补救途径为开发下一代蛋白质药物提供了一种机制，与未修饰的蛋白质药物相比，这种药物在血液循环中具有更长的半衰期。特别地，未修饰的蛋白质药物具有较短的循环半衰期，因此需要在所需的长期治疗期间内频繁给药。目前已经进行了大量的努力、使用了大量的方法来延长蛋白质药物的半衰期，包括聚乙二醇化和融合蛋白技术(美国食品和药物管理局；Osborn BL等，2002)；然而，这些努力并没有产生理想的结果。

免疫疾病是由哺乳动物免疫***的成分引起、介导或以其他方式导致哺乳动物病理状况的疾病。特别的，炎症性疾病是世界上最重要的健康问题之一。炎症通常是身体组织对外来物质或有害刺激入侵宿主的局部保护性反应。炎症的诱因包括传染性物质，如细菌、病毒和寄生虫等；物理因素，如烧伤或辐射；化学品，如毒素、药物或工业制剂；免疫反应，如过敏和自身免疫反应；或与氧化应激相关的疾病。

炎症的特征是疼痛、发红现象、肿胀、发热以及炎症区域最终功能的丧失。这些症状是免疫***中细胞之间一系列复杂相互作用的结果。细胞反应使得几组炎症介质之间形成相互作用的网络，所述炎症介质包括：蛋白质(例如细胞因子、酶(例如蛋白酶、过氧化物酶))、主要碱性蛋白、粘附分子(ICAM、VCAM)、脂质介质(例如类花生酸、***素、白三烯、血小板活化因子(PAF))、活性氧(例如氢过氧化物、超氧阴离子O2-、一氧化氮(NO)等)。然而，大多数炎症介质也是正常细胞活动的调节剂。因此，炎症反应的缺乏将导致宿主处于不受控制的状态，从而使宿主受损(即被感染)。因此，慢性炎症部分导致上述几种介质的过量产生，从而导致炎症性疾病。

此外，自身免疫性疾病作为免疫性疾病之一，其特征是免疫***攻击自身器官引起的自发反应。这些反应是由于T淋巴细胞对自身抗原的识别，从而引起的体液免疫反应(产生自身抗原)和细胞免疫反应(淋巴细胞和巨噬细胞的细胞毒性活性的增加)。自身免疫性疾病的示例可以包括：风湿性疾病、牛皮癣、***性皮肌炎、多发性硬化、红斑狼疮、或由抗原引起的免疫反应恶化，即哮喘、药物或食物过敏等。所有这些疾病都是限制性疾病和慢性疾病，其在某些情况下是致命的。迄今为止，还没有有效的治疗方法可以治疗上述疾病。因此，能够在疾病发展过程中减少或缓解这些疾病的药物、药剂或介质将是对患者健康的重要解决方案。

技术问题

通过寻找自身免疫性疾病的治疗方法，许多研究人员一直在努力寻找合适的药物和方法。如今，自身免疫性疾病的治疗主要基于免疫抑制药物的使用，如糖皮质激素、钙调神经磷酸酶抑制剂和抗增殖药-抗代谢药物。然而，这种药物疗法作用于多个靶点，因此可能导致整体免疫功能的下降。另外，在长期使用这种药物疗法的情况下，多种细胞毒性反应会引起问题并以非特异性的方式抑制免疫***，使得患者可能有感染疾病或免疫相关疾病的风险。由于钙调神经磷酸酶和糖皮质激素的肾毒性和致糖尿病特性，其可能引起其他问题，因此它们被限制仅在某些临床症状(例如，肾功能不全、糖尿病等)下使用。

因此，作为能够治疗免疫相关疾病如自身免疫性疾病、炎性疾病和移植排斥反应的物质，需要开发新的具有优异的治疗效果而没有副作用的治疗剂。

发明内容

本发明的目的是提供一种预防、改善或治疗免疫相关疾病的组合物，其包含作为活性成分的融合蛋白，所述融合蛋白包含富含亮氨酸和免疫球蛋白样结构域-1(Lrig-1)蛋白的胞外结构域和免疫球蛋白Fc区。

本发明的另一个目的是提供一种预防、改善或治疗免疫相关疾病的方法。

然而，本发明要实现的技术问题不限于上述问题，并且本领域普通技术人员将从以下描述中清楚地理解未提及的其他问题。

1.预防、改善或治疗免疫相关疾病的组合物

在本发明的一个实施方式中，提供了一种预防、改善或治疗免疫相关疾病的组合物。

本发明的组合物可以用作药物组合物、食物组合物、或者化妆品组合物。

本发明的组合物包含作为活性成分的：融合蛋白，所述融合蛋白包含富含亮氨酸和免疫球蛋白样结构域-1(Lrig-1)蛋白的胞外结构域和免疫球蛋白Fc区；编码融合蛋白的核酸分子；包含核酸分子的表达载体；或者用表达载体转化的宿主细胞。

在下文中，将对本发明的每个配置进行详细描述。

活性成分

1)融合蛋白

Lrig-1蛋白的胞外结构域

在本发明中，Lrig-1蛋白是由存在于调节性T免疫细胞表面的1091个氨基酸组成的跨膜蛋白，其是由富含亮氨酸的重复序列(LRRs)和细胞外或管腔侧的三个免疫球蛋白样结构域、细胞跨膜序列和胞质尾区组成。LRIG基因家族包括LRIG1、LRIG2和LRIG3，它们之间的氨基酸高度保守。LRIG1基因在正常皮肤中高度表达，并可在基底细胞和毛囊细胞中表达，以调节上皮干细胞的增殖。

在本发明的一个示例中，Lrig-1蛋白的胞外结构域可以是来源于哺乳动物的Lrig-1蛋白的胞外结构域，所述哺乳动物包括灵长类动物如人类和猴子，啮齿类动物如小鼠和大鼠等。就本发明的目的来说，Lrig-1蛋白的胞外蛋白可以是，但不限于，来源于人或小鼠的Lrig-1蛋白的胞外结构域。

在本发明的一个实例中，Lrig-1蛋白的胞外结构域可以由，但不限于，SEQ ID NO:1表示，其对应于人源性Lrig-1蛋白的氨基酸35～794的序列，并且可以由SEQ ID NO:2表示的核酸序列编码(见表1)。

[表1]

在本发明的另一个示例中，Lrig-1蛋白的胞外结构域可以由，但不限于，SEQ IDNO:3表示，其对应于小鼠来源的Lrig-1蛋白的氨基酸35～794的序列，并且可以由SEQ IDNO:4表示的核酸序列编码(见表2)。

[表2]

免疫球蛋白Fc区

如本文所用，术语“免疫球蛋白Fc区”是指免疫球蛋白的一个区域，其包括重链恒定区2(CH2)和/或重链恒定区3(CH3)，不包括重链可变区和轻链可变区。免疫球蛋白Fc区可以是构成本发明蛋白质组合的一部分的组分。

在本发明中，免疫球蛋白Fc区可以包括重链恒定区中的铰链部分，以便不仅可以影响最终制备的融合蛋白的结构灵活性，而且可以进一步增加融合蛋白的生产率和稳定性。然而，本发明不限于此。

此外，本发明的免疫球蛋白Fc区可以是免疫球蛋白的延伸Fc区，其包括重链恒定区1(CH1)和/或轻链恒定区1(CL1)中的部分或全部，仅不包括重链可变区和轻链可变区，只要免疫球蛋白Fc区与其原生型相比具有基本相同或改善的效果。此外，免疫球蛋白Fc区可以是通过除去相当长的对应于CH2和/或CH3的部分氨基酸序列而获得的区域。

例如，本发明的免疫球蛋白Fc区可以是：1)CH1结构域、CH2结构域、CH3结构域和CH4结构域；2)CH1结构域和CH2结构域；3)CH1结构域和CH3结构域；4)CH2结构域和CH3结构域；5)免疫球蛋白铰链区(或铰链区的一部分)与CH1结构域、CH2结构域、CH3结构域和CH4结构域的一个或两个或多个结构域的组合；和6)由重链恒定区和轻链恒定区中的每个结构域形成的二聚体。然而，本发明不限于此。

在本发明中，本发明的免疫球蛋白Fc区包括其天然氨基酸序列及其序列衍生物。氨基酸序列衍生物是指通过缺失、***或至少一个氨基酸残基的非保守或保守取代或其组合而不同于其天然氨基酸序列的氨基酸序列。

在本发明中，例如，对于IgG Fc来说，已知对结合十分重要的214～238、297～299、318～322或327～331位的氨基酸残基可用作合适的修饰位点。

在本发明中，多种类型的衍生物都是可行的，包括通过缺失能够形成二硫键的位点获得的衍生物、通过缺失天然Fc的N末端的一些氨基酸残基获得的衍生物、通过在天然Fc的N末端添加甲硫氨酸残基获得的衍生物等。此外，为了去除其中的效应子功能，可以删除补体结合位点，例如C1q结合位点，或者可以删除抗体依赖性细胞介导的细胞毒性(ADCC)位点。公开号为WO 97/34631和WO 96/32478等的国际专利公开了制备免疫球蛋白Fc区的这种序列衍生物的技术。

在本发明中，本领域公知的，蛋白质和肽中的氨基酸交换在整体上不改变分子活性(H.Neurath,R.L.Hill，《蛋白质》，学术出版社，纽约，1979)。最常见的交换发生在氨基酸残基Ala/Ser、Val/Ile、Asp/Glu、Thr/Ser、Ala/Gly、Ala/Thr、Ser/Asn、Ala/Val、Ser/Gly、Thy/Phe、Ala/Pro、Lys/Arg、Asp/Asn、Leu/Ile、Leu/Val、Ala/Glu或Asp/Gly之间。根据具体情况，修饰可以通过磷酸化反应、硫酸化反应、丙烯酰化反应、糖基化反应、甲基化反应、法尼基化反应、乙酰化反应、酰胺化反应等来实现。

在本发明中，上述Fc衍生物表现出了与本发明的Fc区等同的生物活性，并且其可以是那些对热、pH等具有增强的结构稳定性的衍生物。

在本发明中，Fc区可以从动物体内分离的原生型中获得，所述动物如人、牛、山羊、猪、小鼠、兔子、仓鼠、大鼠或豚鼠的，或者可以是从转化的动物细胞或微生物或其衍生物中获得的重组体。这里，从原生型获得Fc区的方法可以是从活的人或动物体中分离整个免疫球蛋白，然后用蛋白酶处理以获得Fc区的方法。在用木瓜蛋白酶处理的情况下，整个免疫球蛋白被切割成Fab和Fc；在用胃蛋白酶处理的情况下，整个免疫球蛋白被切割成pF'c和F(ab)₂。可以使用尺寸排阻色谱法等分离Fc或pF'c。在一个更具体的实施方式中，免疫球蛋白Fc区是使用人源化的或小鼠衍生的Fc区从微生物中获得的重组免疫球蛋白Fc区。

在本发明中，免疫球蛋白Fc区可以具有原生型聚糖，或者具有与原生型相比更高的或更低的聚糖水平，或者可以是去糖基化的形式。常规方法如化学方法、酶方法和使用微生物的基因工程方法可用于增加或减少免疫球蛋白Fc中的聚糖或去糖基化。此处，已经去除聚糖的免疫球蛋白Fc区表现出显著降低的与补体(C1q)结合的能力，并降低或消除了抗体依赖性细胞毒性或补体依赖性细胞毒性；因此不会在体内引起任何不必要的免疫反应。从这个观点来看，去糖基化或糖基化的免疫球蛋白Fc区将是更适合作为本发明的原始目的，即药物载体。

如本文所用，术语“去糖基化”是指被酶促去除糖的Fc区，术语“糖基化”是指在更具体的实施方式中，在原核生物即大肠杆菌中产生的未糖基化的Fc区。

同时，免疫球蛋白Fc区可以源自人或其他动物，如牛、山羊、猪、小鼠、兔子、仓鼠、大鼠和豚鼠。在一个更具体的实施方式中，其来源于人类或小鼠。

此外，本发明的免疫球蛋白Fc区可以是IgG-，IgA-，IgD-，IgE-，或IgM-衍生的Fc区，重链恒定区2(CH2)，重链恒定区3(CH3)，铰链区及其片段，或其组合，或包括该组合的杂化Fc。

同时，如本文所用，术语“组合”是指编码相同来源的单链免疫球蛋白Fc区、重链恒定区2(CH2)或重链恒定区3(CH3)的多肽，其具有相同的来源，当它们形成二聚体或多聚体时，与不同来源的单链多肽形成键。也就是说，可以从选自IgG-、IgA-、IgM-、IgD-或IgE-衍生的Fc区、重链恒定区2(CH2)或重链恒定区3(CH3)的两个或多个片段制备二聚体或多聚体。

在本发明中，“杂化Fc”可以来源于人IgG亚类的组合或人IgD和IgG的组合。在一个实施方式中，杂化Fc可以包括例如IgD铰链区和CH2氮端区+IG4 CH2和CH3区。例如，在No.0897938号韩国专利(该专利在此引入作为参考)中公开的杂化Fc形式可以以相同的方式被采用和使用。在本发明中，在杂化Fc结合生物活性分子、多肽等的情况下，当多肽由编码Fc-多肽融合蛋白的核苷酸序列表达时，它具有增加生物活性分子的血清半衰期的效果以及增加多肽表达水平的效果。

作为本发明的一个示例，免疫球蛋白Fc区可以是IgG-、IgA-、IgM-、IgD-或IgE-衍生的Fc区，或者可以包括IgG-、IgA-、IgM-、IgD-或IgE-衍生的重链恒定区2(CH2)和重链恒定区3(CH3)。然而，本发明不限于此。

作为本发明的一个示例，免疫球蛋白Fc区可以是在人血液中最丰富的IgG-或IgM-衍生的Fc区，或者可以包括IgG-或IgM-衍生的重链恒定区2(CH2)和重链恒定区3(CH3)。作为另一个示例，免疫球蛋白Fc区可以是已知可以增强配体结合蛋白半衰期的IgG衍生的Fc区，或者可以包括IgG衍生的重链恒定区2(CH2)和重链恒定区3(CH3)。作为又一个示例，免疫球蛋白Fc区可以是IgG1-、IgG2-、IgG3-、或IgG4-衍生的Fc区，或者可以包括IgG1-、IgG2-、IgG3-、或IgG4-衍生的重链恒定区2(CH2)和重链恒定区3(CH3)。作为又一个示例，免疫球蛋白Fc区可以包括IgG1-或IgG2-衍生的重链恒定区2(CH2)和重链恒定区3(CH3)。

作为本发明的优选示例，免疫球蛋白Fc区可包括，但不限于，人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)，其由SEQ ID NO:5表示，或包括小鼠IgG2衍生的重链恒定区2(CH2)和重链恒定区3(CH3)，其由SEQ ID NO:6表示(见下表3)。

[表3]

作为本发明的一个示例，免疫球蛋白Fc区可以包括IgG-、IgA-、IgM-、IgD-、IgE-、或阿巴西普(Abatacept)衍生的铰链区；作为另一个示例，免疫球蛋白Fc区可以包括IgG-、IgD-、或阿巴西普衍生的铰链区，或者可以包括IgG1-、IgG2-、IgG3-、IgG4-、IgD-、或阿巴西普衍生的铰链区。然而，本发明不限于此。

作为本发明的优选实例，免疫球蛋白Fc区可以包括一个或多个选自下组的区域，该组包括：由SEQ ID NO:7表示的人IgG1衍生的铰链区、由SEQ ID NO:8表示的小鼠IgG2衍生的铰链区、由SEQ ID NO:9表示的人类IgD衍生的铰链区、和由SEQ ID NO:10表示的阿巴西普的铰链区(见下表4)，从而增加最终制备的融合蛋白的结构灵活性，并显著提高融合蛋白的生产率和稳定性。然而，本发明不限于此。

[表4]

在本发明中，在Lrig-1蛋白的胞外结构域和Fc区通过接头连接的情况下，接头可以连接到Fc片段的氮末端、碳末端或自由基，并且可以连接到Lrig-1蛋白的胞外结构域的氮末端、碳末端或自由基。在接头是肽接头的情况下，连接可以发生在任何位点。例如，接头可以连接到Lrig-1蛋白胞外结构域的碳末端和免疫球蛋白Fc区的氮末端，或者可以连接到免疫球蛋白Fc区的碳末端和Lrig-1蛋白胞外结构域的氮末端。

连接物

在本发明中，“接头”可以减少融合蛋白中Lrig-1蛋白胞外结构域和免疫球蛋白Fc区之间的干扰，从而增加目标细胞中Lrig-1蛋白胞外结构域的所需活性。此外，在本发明中，接头可包括可被目标疾病组织或细胞中过表达的酶切割的序列。在接头可以被上述过表达的酶切割的情况下，可以有效地防止多肽的活性由于Fc部分而降低的情况。

作为本发明的实例，接头优选具有1～100个氨基酸；然而，本发明不限于此。可以使用任何能够从免疫球蛋白Fc区分离Lrig-1蛋白胞外结构域的肽。虽然对构成接头的氨基酸序列没有特别的限制，但是优选包括甘氨酸和丝氨酸，或者以重复或随机的方式包括它们。作为这样的示例，接头可以包括由SEQ ID NO:11和SEQ ID NO:12表示的肽接头中的至少一种(见下表5)，或者可以是选自包含肽接头的组中的至少一种，每个肽接头包含式1至式4中任一个表示的氨基酸序列。

[式1]

(G)_n；

[式2]

(GGGGS)_m；

[式3]

(EAAAK)_p；

[式4]

(XP)_q；

其中所述n、m和p各自独立地为1或更大的整数；

q是5～40的整数；

X是选自A(Ala)、C(Cys)、D(Asp)、E(Glu)、F(Phe)、G(Gly)、H(His)、I(Ile)、K(Lys)、L(Leu)、M(Met)、N(Asn)、O(Pyl)、P(Pro)、Q(Gln)、R(Arg)、S(Ser)、T(Thr)、U(Sec)、V(Val)、W(Trp)和Y(Tyr)中的任意一种氨基酸。

[表5]

SEQ ID NO	序列信息
		SEQ ID NO:11	GS
SEQ ID NO:12	GGG

在本发明中，式1-3中的n、m和q可以是，但不限于，1或更大的整数，优选1～20的整数。

在本发明中，式4中的X可以是A(Ala)，但不限于此。

此外，作为本发明的一个示例，接头可以包括至少一种选自，但不限于，由SEQ IDNO:96表示的肽接头(A(EAAAK)₄ALEA(EAAAK)₄A)、由SEQ ID NO:97表示的肽接头(PAPAP)、由SEQ ID NO:98表示的肽接头(AEAAAKEAAAKA)、由SEQ ID NO:99表示的肽接头(IEGRMD)、和由SEQ ID NO:100表示的肽接头(DIEGRMD)。

在本发明中，在融合蛋白进一步包括肽接头的情况下，可以增加细胞中活性物质的稳定性，同时进一步提高其生产率。

此外，作为本发明中接头的示例，可以采用这样的肽接头，即由位于人白蛋白282～314位的33个氨基酸组成，更优选地由位于292～304位的13个氨基酸组成，所述人白蛋白在血液中含量最高。从三维结构来看，这部分中的大部分暴露于外部，因此在体内诱导免疫反应的可能性最小。然而，本发明不限于此。

此外，在本发明中，在接头和Fc区分别表达然后彼此连接的情况下，接头可以是本领域已知的交联剂。交联剂可以是例如1,1-双(重氮乙酰基)-2-苯基乙烷、戊二醛、N-羟基琥珀酰亚胺酯(如4-叠氮水杨酸)、包括二琥珀酸亚胺酯(如3,3’-二硫代双(琥珀酰亚胺基丙酸酯))的酰亚胺酯、和双官能马来酰亚胺(如双-N-马来酰亚胺-1,8-辛烷)。然而，交联剂不限于此。

包含Lrig-1胞外结构域和免疫球蛋白的融合蛋白

作为本发明提供的融合蛋白的一个示例，融合蛋白包括由SEQ ID NO:1表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；并且可以采用由SEQ ID NO:5表示的人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表6)。下面表6中由SEQ ID NO:13至SEQ ID NO:16表示的融合蛋白可以由下面表7中由SEQ ID NO:17至SEQ ID NO:20表示的核酸序列编码(见下表7)。

[表6]

[表7]

本发明提供的融合蛋白的一个示例是，一种融合蛋白，包括由SEQ ID NO:3表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；可以采用由SEQ ID NO:5表示的人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表8)。下表8中由SEQ ID NO:21至SEQ ID NO:24表示的融合蛋白可以由下表9中由SEQ IDNO:25至SEQ ID NO:28表示的核酸序列编码(见下表9)。

[表8]

[表9]

作为本发明提供的融合蛋白的另一个示例，融合蛋白包括由SEQ ID NO:3表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；和可以采用由SEQ ID NO:6表示的小鼠IgG2衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表10)。下表10中由SEQ ID NO:29至SEQ ID NO:32表示的融合蛋白可以由下表11中由SEQ ID NO:33至SEQ ID NO:36表示的核酸序列编码(见下表11)。

[表10]

[表11]

作为本发明提供的融合蛋白的又一个示例，融合蛋白包括由SEQ ID NO:1表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:11表示的接头；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；并且可以采用由SEQ ID NO:5表示的人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表12)。下表12中由SEQ ID NO:37至SEQ ID NO:40表示的融合蛋白可以由下表13中由SEQ ID NO:41至SEQ ID NO:44表示的核酸序列编码(见下表13)。

[表12]

[表13]

作为本发明提供的融合蛋白的又一个示例，融合蛋白包括由SEQ ID NO:3表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:11表示的接头；由SEQ ID NO:7至SEQ ID NO:710中的任何一个表示的铰链区；并且可以采用由SEQ ID NO:5表示的人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表14)。下面表14中由SEQ ID NO:45至SEQ ID NO:48表示的融合蛋白可以由下面表15中由SEQ ID NO:49至SEQ ID NO:52表示的核酸序列编码(见下表15)。

[表14]

[表15]

作为本发明提供的融合蛋白的又一个示例，融合蛋白包括由SEQ ID NO:3表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:11表示的接头；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；并且可以采用由SEQ ID NO:6表示的小鼠IgG2衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表16)。下面表16中由SEQ ID NO:53至SEQ ID NO:56表示的融合蛋白可以由下表17中由SEQ ID NO:57至SEQ ID NO:60表示的核酸序列编码(见下表17)。

[表16]

[表17]

作为本发明提供的融合蛋白的又一个示例，融合蛋白包括由SEQ ID NO:1表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:12表示的接头；由SEQ ID NO:11表示的接头；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；并且可以采用由SEQ ID NO:5表示的人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表18)。下表18中由SEQ IDNO:61至SEQ ID NO:64表示的融合蛋白可以由表19中由SEQ ID NO:65至SEQ ID NO:68表示的核酸序列编码(见下表19)。

[表18]

[表19]

作为本发明提供的融合蛋白的又一个示例，融合蛋白包括由SEQ ID NO:3表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:12表示的接头；由SEQ ID NO:11表示的接头；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；并且可以采用由SEQ ID NO:5表示的人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表20)。下表20中由SEQ IDNO:69至SEQ ID NO:72表示的融合蛋白可以由下表21中由SEQ ID NO:73至SEQ ID NO:76表示的核酸序列编码(见下表21)。

[表20]

[表21]

作为本发明提供的融合蛋白的又一个示例，融合蛋白包括由SEQ ID NO:3表示的Lrig-1蛋白的胞外结构域；由SEQ ID NO:12表示的接头；由SEQ ID NO:11表示的接头；由SEQ ID NO:7至SEQ ID NO:10中的任何一个表示的铰链区；并且可以采用由SEQ ID NO:6表示的小鼠IgG2衍生的重链恒定区2(CH2)和重链恒定区3(CH3)(见下表22)。下面表22中由SEQ ID NO:77至SEQ ID NO:80表示的融合蛋白可以由下表23中由SEQ ID NO:81至SEQ IDNO:84表示的核酸序列编码(见下表23)。

[表22]

[表23]

2)核酸分子

本发明的组合物包含编码本发明提供的融合蛋白的核酸分子。

本发明的核酸分子包括通过将本发明提供的融合蛋白的氨基酸序列转化为本领域技术人员已知的多核苷酸序列而获得的任何核酸分子。因此，由于开放阅读框(ORF)的原因，可以制备多种多核苷酸序列，所有这些也包括在本发明的核酸分子中。

3)表达载体

本发明的组合物包含表达载体，其中***了本发明提供的分离的核酸分子。

在本发明中，“载体”是能够运输可与其连接的另一种核酸的核酸分子。一种载体是“质粒”，它是指可以连接额外DNA片段的环状双链DNA。另一种载体是噬菌体载体。还有另一种类型的载体是病毒载体，其中额外的DNA片段可以连接到病毒基因组中。某些载体能够在引入它们的宿主细胞中自主复制(例如，细菌载体是具有细菌复制起点的游离哺乳动物载体)。其他载体(例如，非游离哺乳动物载体)在导入宿主细胞后可整合到宿主细胞的基因组中，并因此与宿主基因组一起复制。此外，某些载体能够指导与其有效连接的基因的表达。这种载体在本文中被称为“重组表达载体”或简称为“表达载体”。通常，在重组DNA技术中有用的表达载体通常是质粒的形式。在本说明书中，“质粒”和“载体”可以互换使用，因为质粒是最常用的载体形式。

本发明中表达载体的具体实例可以选自，但不限于，商业上广泛使用的pCDNA载体、F、R1、RP1、Col、pBR322、ToL、Ti载体；粘粒、噬菌体(如λ噬菌体)、λ噬菌体、M13、Mu、p1P22、Qμ、T-偶数(T-even)、T2、T3、T7；植物病毒。本领域技术人员已知的任何可作为表达载体的表达载体都可以用于本发明，并且可以根据目标宿主细胞的性质选择表达载体。可以通过磷酸钙转染、病毒感染、DEAE-葡聚糖介导的转染、脂质体转染或电穿孔将载体引入宿主细胞。然而，本发明不限于此，本领域技术人员可以采用和使用适合于所用表达载体和宿主细胞的导入方法。载体可以优选包含至少一个选择标记。然而，本发明不限于此，并且可以使用不包含选择标记的载体进行选择，这取决于是否产生了产品。根据目标宿主细胞进行选择标记的选择，这是使用本领域技术人员已知的方法完成的，因此本发明对此没有限制。

为了便于纯化本发明的核酸分子，可以将标签序列***并融合到表达载体中。所述标签包括，但不限于，六组氨酸标签、血凝素标签、myc标签或flag标签，并且本领域技术人员已知的有助于纯化的任何标签可用于本发明。

4)宿主细胞

本发明的组合物包含用本发明提供的表达载体转染得到的宿主细胞。

在本发明中，“宿主细胞”包括单个细胞或细胞培养物，它们可能会或已经是用于掺入多肽***物的载体的受体。宿主细胞包括单个宿主细胞的后代，由于自然突变、偶然突变或有意突变，后代可能不一定与原始亲本细胞完全相同(在形态学或基因组DNA互补方面)。宿主细胞包括用本文的多核苷酸进行体内转染得到的细胞。

在本发明中，宿主细胞可以包括哺乳动物、植物、昆虫、真菌或细胞来源的细胞，并且可以是例如细菌细胞，例如大肠杆菌、链霉菌、鼠伤寒沙门氏菌；真菌细胞，如酵母细胞和毕赤酵母；昆虫细胞如果蝇和甜菜夜蛾Sf9细胞；动物细胞如中国仓鼠卵巢(CHO)细胞、SP2/0(小鼠骨髓瘤)、人淋巴母细胞、COS、NSO(小鼠骨髓瘤)、293T、Bowes黑色素瘤细胞、HT-1080、幼仓鼠肾(BHK)细胞、人胚胎肾(HEK)细胞或PERC.6(人视网膜细胞)，或者植物细胞。然而，宿主细胞不限于此，本领域技术人员已知的可用作宿主细胞系的任何细胞都可用作宿主细胞。

5)与T细胞激活的V结构域免疫球蛋白抑制剂(VISTA)的组合

在本发明中，所述组合物可以进一步包含T细胞活化的V结构域Ig抑制剂(VISTA)或其片段。

在本发明中，所述组合物可以进一步包含融合蛋白，所述融合蛋白包括VISTA或其片段和免疫球蛋白Fc区。这里，VISTA或其片段和免疫球蛋白Fc区之间还可以包含接头。

在本发明中，“T细胞活化的V-结构域Ig抑制剂(VISTA)”对应免疫检查点蛋白，其功能是抑制针对T细胞的免疫活性。VISTA相当于一种表面蛋白，它包括一个含有IgG-V结构域的胞外结构域和一个不含ITAM和ITIM的短胞质结构域。VISTA可以在CD11b+髓样树突状细胞(DC)、CD4+和CD8+T细胞、Foxp3+CD4+调节性T细胞中表达，并可用于抑制T细胞活化后细胞因子的分泌和增殖。VISTA缺陷敲除的小鼠由于慢性炎症表现出器官功能的下降，并且表现出多发性硬化症状的速度比正常小鼠快得多。

在本发明的一个示例中，VISTA可以来源于哺乳动物，包括灵长类动物如人类和猴子，啮齿类动物如小鼠和大鼠等。

在本发明的一个示例中，VISTA可能由SEQ ID NO:85表示的氨基酸序列组成，其是人来源的VISTA，或者可以由SEQ ID NO:87表示的核苷酸编码。然而，本发明不限于此。

在本发明的一个示例中，VISTA可由SEQ ID NO:86表示的氨基酸序列组成，其是小鼠衍生的VISTA，或者可由SEQ ID NO:88表示的核苷酸编码。然而，本发明不限于此。

在本发明的一个示例中，VISTA的片段可以是，但不限于，VISTA的胞外结构域。

在本发明的一个示例中，VISTA的胞外结构域可以由，但不限于，SEQ ID NO:89表示的氨基酸序列组成，该氨基酸序列对应于人来源的VISTA的氨基酸33～194的序列。

在本发明的一个示例中，VISTA的胞外结构域可以由，但不限于，SEQ ID NO:90表示的氨基酸序列组成，其对应于小鼠来源的VISTA的氨基酸33～191的序列。

在本发明的一个示例中，VISTA的片段可以是，但不限于，VISTA胞外结构域的片段。

在本发明中，VISTA胞外结构域的片段可以由SEQ ID NO:91至SEQ ID NO:93中任一个表示的氨基酸序列组成，所述氨基酸序列是人来源的VISTA胞外结构域的一些片段。然而，本发明不限于此。

在本发明中，VISTA胞外结构域的片段可以由SEQ ID NO:94或SEQ ID NO:95表示的氨基酸序列组成，该氨基酸序列是小鼠来源的VISTA胞外结构域的片段。然而，本发明不限于此。

在此，免疫球蛋白Fc区和接头的描述与上述内容重叠，因此将被省略以避免说明书过于复杂。

在本发明中，VISTA或其片段或包含其的融合蛋白可以通过在宿主细胞中***表达载体而容易地获得，所述表达载体中***核酸分子，所述核酸分子通过将本发明中提供的氨基酸序列转化为本领域技术人员已知的多核苷酸序列，培养宿主细胞，然后使用色谱法等进行纯化而获得。

这里，核酸分子、表达载体和宿主细胞的描述也与上述内容重叠，因此将被省略以避免说明书过于复杂。

6)免疫相关疾病及组合

免疫相关疾病

在本发明中，“免疫相关疾病”是由各种免疫细胞，例如效应T细胞或细胞毒性T细胞和炎症细胞的过度激活和/或增殖引起的疾病，并且可以包括但不限于自身免疫性疾病、移植物抗宿主病、器官移植排斥病、哮喘、特应性，或者急性或慢性炎症性疾病。

在本发明中，“自身免疫性疾病”可以是选自但不限于类风湿性关节炎、1型糖尿病、***性硬皮病、***性红斑狼疮、特应性皮炎、牛皮癣、斑秃、哮喘、克罗恩病、白塞病、干燥综合征、吉兰-巴雷综合症、慢性甲状腺炎、多发性硬化、多发性肌炎、强直性脊柱炎、纤维肌炎和结节性多动脉炎中的至少一种。

此外，在本发明中，“自身免疫性疾病”可以由活化的T细胞渗透构成神经的细胞从而诱导炎症或凋亡的过程引起，并且可以是例如神经退行性疾病或神经炎症性疾病(参见Neuromolecular Med.2005；7(3):255-64)。

在本发明中，神经退行性疾病或神经炎症性疾病可以选自但不限于中风、痴呆、阿尔茨海默病、帕金森病、亨廷顿病、Niemann-Pick病、朊病毒病、库贾氏病、额颞叶痴呆、路易斯痴呆、肌萎缩性侧索硬化、副癌综合征、皮质基底节变性、多***萎缩、进行性核麻痹、神经***自身免疫性疾病、脊髓小脑性共济失调、炎性和神经性疼痛、脑血管疾病、脊髓损伤和tau蛋白病的至少一种。

在本发明中，与健康对照相比，免疫相关疾病，例如自身免疫性疾病，可由疾病患者中高频率的自身免疫性T细胞(例如效应T细胞或细胞毒性T细胞)的存在或其活性显著增加而引起，这反过来诱导过度的免疫反应或破坏特定器官的细胞(参见Clinical&Experimental Immunology,180:353-360.,Immunity,Vol.17,1-6,July,2002.,Ann RheumDis 2004；63(Suppl II):96-101.,Immunol Res.2013 December；57(0):12-22)。

在本发明中，可以通过干扰对T细胞(例如，效应T细胞或细胞毒性T细胞)的活化和/或增殖至关重要的细胞内信号途径来预防、改善或治疗免疫相关疾病，所述细胞内信号途径优选为自动反应性T细胞(参见Ann Rheum Dis 2004；63(Suppl II):96-101)。具体而言，本发明的融合蛋白可以在效应T细胞中诱导共抑制信号，从而抑制效应T细胞的增殖并调节其活化过程。因此，融合蛋白可用于有效预防、改善或治疗各种免疫相关疾病，这些疾病可能由T细胞(例如，效应T细胞或细胞毒性T细胞)的过度激活和/或增殖引起。

与免疫相关疾病的治疗剂的组合

本发明的组合物可与其它药物联合使用，用于治疗免疫相关疾病。例如，可以用本发明至少一些实施方式的分子，连同(但不限于)免疫抑制剂如皮质类固醇、环孢菌素、环磷酰胺、***、硫唑嘌呤、甲氨蝶呤、雷帕霉素和他克莫司，生物制剂如TNF-α阻断剂或拮抗剂，或任何其它靶向任何炎性细胞因子的生物制剂，非甾体抗炎药/Cox-2抑制剂，羟氯喹，柳氮磺胺吡啶，金盐，依那西普，英夫利昔单抗，霉酚酸酯、巴西利昔单抗、阿他西普、利妥昔单抗、环磷酰胺、干扰素β-1a、干扰素β-1b、醋酸格拉替雷、盐酸米托蒽醌、阿那白滞素和/或其他生物物质和/或静脉注射免疫球蛋白(IVIG)。这种已知治疗剂的非限制性例子包括干扰素，如干扰素-β-1a(

和

)和干扰素-β-1b(

和

)；一种多肽–醋酸格拉替雷

那他珠单抗

和细胞毒剂–米托蒽醌

此外，本发明的组合物可以与任何已知的治疗多发性硬化的治疗剂或方法结合使用。用于治疗多发性硬化症的所述已知治疗剂或方法的非限制性例子包括干扰素，例如干扰素-β-1a(

和

)和干扰素-β-1b(

和

)；一种多肽–醋酸格拉替雷

那他珠单抗

和细胞毒剂–米托蒽醌

氨吡啶

其他药物包括皮质类固醇、甲氨蝶呤、环磷酰胺、硫唑嘌呤和静脉注射免疫球蛋白(IVIG)、肌苷、奥沙利珠单抗(R1594)、米力奈Mylinax(Caldribine)、阿仑单抗(Campath)、达克珠单抗(Zenapax)、Panaclar/富马酸二甲酯(BG-12)、特立氟胺(HMR1726)、芬戈莫德(FTY720)、拉喹莫德(ABR216062)以及造血干细胞移植、Neurovx、利妥昔单抗(Rituxan)、卡介苗、低剂量纳曲酮、驱虫疗法、血管成形术、静脉支架、和替代疗法例如维生素D、多不饱和脂肪和医用***。

此外，本发明的组合物可以与任何已知的治疗类风湿性关节炎的治疗剂或方法结合使用。用于治疗类风湿性关节炎的所述已知治疗剂或方法的非限制性实例包括糖皮质激素、非甾体抗炎药(NSAID)如水杨酸盐或环加氧酶-2抑制剂、布洛芬和萘普生、双氯芬酸、吲哚美辛、依托度酸；改善病情的抗风湿药(DMARDs)-口服DMARDs:醋硫葡金

硫唑嘌呤

环孢菌素(

and

每种都是通用的)、D-青霉胺

羟氯喹

IM硫代苹果酸金钠

金硫代葡萄糖

来氟米特

甲氨蝶呤

米诺环素

葡萄球菌蛋白A免疫吸附(

柱)、柳氮磺吡啶

生物DMARDs:TNF-α阻断剂，包括阿达木单抗

依那西普

英夫利昔单抗

戈利木单抗

赛妥珠单抗

和其他生物DMARDs，阿那白滞素

利妥昔单抗

拖珠单抗

CD28抑制剂，包括阿巴西普

和贝拉西普。

此外，本发明的组合物可以与任何已知的1型糖尿病治疗剂或方法结合使用。用于治疗1型糖尿病的所述已知治疗剂或方法的非限制性实例包括胰岛素、胰岛素类似物、胰岛移植、包括

在内的干细胞疗法、非胰岛素疗法例如IL-1β抑制剂包括阿那白滞素

阿巴西普

diamyd、阿法西普

奥替利单抗、DiaPep277(Hsp60衍生肽)、α1-抗胰蛋白酶、***、硫唑嘌呤、环孢素、E1-INT(一种包含表皮生长因子类似物和胃泌素类似物的可注射胰岛新生疗法)、他汀类药物包括

(二肽酶(DPP-4)抑制剂)、抗CD3单抗(例如替普珠单抗)；CTLA4-Ig(阿巴西普)、抗IL-1β(康纳单抗)、抗CD20单抗(如利妥昔单抗)。

此外，本发明的组合物可以与任何已知的治疗干燥综合征的治疗剂或方法结合使用。用于治疗干燥综合征的所述已知治疗剂或方法的非限制性实例包括环孢菌素、匹鲁卡品

和西维美林

羟氯喹

可的松(***等)和/或硫唑嘌呤

或环磷酰胺

***、沙利度胺、脱氢表雄酮、NGX267、瑞巴派特、FID 114657、依那

贝利单抗、

(利妥昔单抗)，静脉注射免疫球蛋白(IVIG)，同种异体间充质干细胞(AlloMSCs)，通过“Saliwell Crown”自动神经电刺激。

此外，本发明的组合物可以与任何已知的治疗***性红斑狼疮的治疗剂或方法结合使用。用于治疗***性红斑狼疮的所述已知治疗剂或方法的非限制性实例包括皮质类固醇和改善病情的抗风湿药(DMARDs)、通常的抗疟疾药(如羟氯喹)和免疫抑制剂(如氨甲喋呤和硫唑嘌呤)羟氯喹、细胞毒性药(如环磷酰胺和霉酚酸酯)、羟氯喹(HCQ)、贝利司他

(贝利单抗)、非甾体抗炎药、***、麦考酚酸莫酯、他克莫司、阿塞西普、鲁普唑、静脉注射免疫球蛋白(IVIG)、

(霉酚酸酯)、

CTLA4-IgG4m(RG2077)、利妥昔单抗、奥瑞珠单抗、依帕珠单抗、CNTO 136、西法木单抗(MEDI-545)、A-623(以前的AMG 623)、AMG 557、隆利组单抗、帕喹莫德(ABR-215757)、LY2127399、CEP-33457、脱氢表雄酮、左旋甲状腺素、阿贝莫司纳(LJP 394)、美金刚、阿片类、雷帕霉素、肾移植和干细胞移植。

7)术语和组成

在本发明中，“预防”可以包括，但不限于，使用本发明的组合物阻断疾病症状或抑制或延迟症状的任何行为。

在本发明中，“改善”或“治疗”可以包括，但不限于，使用本发明的组合物改善或有益地改变疾病症状的任何行为。

在本发明中，药物组合物可以是胶囊、片剂、颗粒剂、注射剂、药膏、粉剂或饮料的形式，并且药物组合物可以靶向人。

在本发明中，药物组合物可以根据常规方法分别配制成口服制剂的形式，例如粉剂、颗粒剂、胶囊、片剂和水悬浮液、外用制剂、栓剂和无菌注射溶液，并使用。然而，药物组合物不限于此。本发明的药物组合物可以进一步包含药学上可接受的载体。作为药学上可接受的载体，粘合剂、助流剂、崩解剂、赋形剂、增溶剂、分散剂、稳定剂、悬浮剂、颜料、香料等可用于口服给药；缓冲剂、防腐剂、止痛剂、增溶剂、等渗剂、稳定剂等可以混合用于注射；并且碱、赋形剂、润滑剂、防腐剂等可以用于局部给药。本发明药物组合物的制剂可以通过与如上所述的药学上可接受的载体混合以多种方式制备。例如，对于口服给药，药物组合物可以配制成片剂、锭剂、胶囊、酏剂、混悬剂、糖浆、薄饼等形式。对于注射给药，药物组合物可以配制成单位剂量安瓿或多种剂型的形式。或者，药物组合物可以配制成溶液、悬浮液、片剂、胶囊、缓释制剂等。

同时，作为适于制备制剂的载体、赋形剂或稀释剂的示例，可以使用乳糖、葡萄糖、蔗糖、山梨醇、甘露醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、***胶、藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石、硬脂酸镁、矿物油等。此外，可以进一步包含填料、抗凝剂、润滑剂、润湿剂、香料、乳化剂、防腐剂等。

在本发明中，药物组合物的给药途径包括但不限于口服、静脉内、肌内、动脉内、髓内、硬膜内、心内、经皮、皮下、腹膜内、鼻内、肠内、局部、舌下或直肠途径。优选口服或肠胃外给药。

在本发明中，所述“胃肠外”包括皮下、皮内、静脉内、肌内、关节内、囊内、胸骨内、硬膜内、病变内和颅内注射或输注技术。本发明的药物组合物也可以以用于直肠给药的栓剂的形式给药。

本发明的药物组合物可以根据多种因素而有很大变化，包括所使用的某种化合物的活性、患者的年龄、体重、一般健康状况、性别、饮食、给药时间、给药途径、***速率、药物组合以及要预防或治疗的某种疾病的严重程度。药物组合物的剂量可以根据患者的病情、体重、疾病的严重程度、药物形式、给药途径和持续时间而变化，并且可以由本领域技术人员适当选择。药物组合物可以以每天0.0001mg/kg～50mg/kg或0.001mg/kg～50mg/kg的量给药。给药可以一天一次或一天几次。该剂量无意以任何方式限制本发明的范围。本发明的药物组合物可以配制成丸剂、糖衣片、胶囊、液体、凝胶、糖浆、浆液或悬浮液的形式。

在本发明中，所述食品组合物可以制备成各种食品的形式，例如饮料、树胶、茶、维生素复合物、粉末、颗粒、片剂、胶囊、糖果、米糕、面包等。

在本发明中，在食品组合物中含有活性成分的情况下，其添加量可以是，但不限于，食品组合物总重量的0.1％-50％。

在本发明中，在食品组合物以饮料形式制备的情况下，除了饮料含有指定比例的食品组合物之外，没有特别的限制，并且饮料可以含有各种调味剂或天然碳水化合物等作为类似于常规饮料的附加成分。具体地，天然碳水化合物的示例可以包括诸如葡萄糖的单糖、诸如果糖的二糖、诸如蔗糖的多糖、诸如糊精和环糊精的常规糖，以及诸如木糖醇、山梨醇和赤藓糖醇的糖醇。调味剂的示例可以包括天然调味剂(甜菊糖、甜叶菊提取物(如莱鲍迪苷A)、甘草甜素等)和合成调味剂(糖精、阿斯巴甜等)。

在本发明中，食品组合物可进一步包含多种营养物、维生素、矿物质(电解质)、调味剂如合成调味剂和天然调味剂、着色剂、果胶酸及其盐、海藻酸及其盐、有机酸、保护性胶体增稠剂、pH调节剂、稳定剂、防腐剂、甘油、酒精、碳酸饮料中使用的碳化剂等。

在本发明中，上述成分可以单独使用或组合使用。所述添加剂的比例不对应于本发明的关键要素，并且可以选自，但不限于，每100重量份本发明的食品组合物0.1～约50重量份的范围。

在本发明中，化妆品组合物可以制备成皮肤软化剂、营养洗剂、营养香精、按摩霜、美容沐浴水添加剂、身体洗剂、身体乳液、沐浴油、婴儿油、婴儿粉、沐浴露、沐浴霜、日晒洗液、日晒霜、晒霜、皮肤洗剂、皮肤霜、紫外线阻挡化妆品、清洁乳液、毛发去除剂(用于美容目的)、面部和身体乳液、面部和身体乳液、皮肤增白乳液、手部乳液、头发乳液、美容乳液，茉莉油、沐浴皂、液体皂、化妆皂、洗发精、洗手液、药用皂(用于非医疗目的)、霜皂、洗面奶、身体清洁剂、头皮清洁剂、洗发香波、香皂、牙齿美白凝胶、牙膏等。本发明的组合物可进一步包含常规用于制备化妆品组合物的溶剂，或合适的载体、赋形剂或稀释剂。

在本发明中，可以进一步添加到化妆品组合物中的溶剂的类型没有特别限制，溶剂的示例可以包括水、盐水、二甲基亚砜或其组合。此外，载体、赋形剂或稀释剂的示例包括但不限于纯净水、油、蜡、脂肪酸、脂肪酸醇、脂肪酸酯、表面活性剂、湿润剂、增稠剂、抗氧化剂、粘度稳定剂、螯合剂、缓冲剂、低级醇等。此外，如果需要，本发明的化妆品组合物可以包含增白剂、保湿剂、维生素、紫外线阻断剂、芳香剂、染料、抗生素、抗菌剂和抗真菌剂。

在本发明中，油的示例可以包括氢化植物油、蓖麻油、棉籽油、橄榄油、棕榈仁油、荷荷巴油和鳄梨油，蜡的示例可以包括蜂蜡、鲸蜡、巴西棕榈蜡、小烛树蜡、褐煤蜡、地蜡、液体石蜡和羊毛脂。

在本发明中，脂肪酸的示例可以包括硬脂酸、亚油酸、亚麻酸和油酸；脂肪酸醇的示例可以包括十六醇、辛基十二醇、油醇、泛醇、羊毛脂醇、硬脂醇和十六醇；脂肪酸酯的示例可以包括肉豆蔻酸异丙酯、棕榈酸异丙酯和硬脂酸丁酯。表面活性剂的示例可以包括本领域已知的阳离子表面活性剂、阴离子表面活性剂和非离子表面活性剂。在这些表面活性剂中，如果可能的话，优选源自天然产物的表面活性剂。此外，本发明的化妆品组合物可以包含湿润剂、增稠剂、抗氧化剂等，它们在化妆品领域是公知的，并且它们的类型和量是本领域已知的

2.预防、改善或治疗免疫相关疾病的方法

本发明的另一个实施方式提供了一种预防、改善或治疗免疫相关疾病的方法，包括向个体施用本发明的融合蛋白的步骤；编码所述融合蛋白的核酸分子；包含核酸分子的表达载体；或者用表达载体转化得到的宿主细胞；或者包括前述任何一种的组合物。

在本发明中，关于融合蛋白、核酸分子、表达载体、宿主细胞、组合物和免疫相关疾病相关的描述与上述药物组合物的描述重叠，因此将被省略以避免说明书过于复杂。

在本发明中，“个体”是被怀疑患有免疫相关疾病的个体，被怀疑患有免疫相关疾病的个体是指已经患有或可能患有所述疾病的哺乳动物，例如人类、小鼠和家畜。然而，可以用本发明的融合蛋白或包含该融合蛋白的组合物治疗的任何个体都不受限制地包括在其中。

本发明的方法可以包括以药物有效量施用融合蛋白或包含融合蛋白的组合物。主治医师或兽医可在合理的医学判断范围内确定适当的每日总用量，并可一次或多次给药。然而，为了本发明的目的，特定患者的特定治疗有效量优选依据多种因素有区别地应用，所述因素包括要实现的反应的类型和程度，特定组合物包括是否根据具体情况使用其他药剂，患者的年龄、体重、一般健康状况、性别和饮食、给药时间、给药途径、组合物的分泌速率、治疗持续时间、与特定组合物同时或结合使用的药物，以及医学领域中公知的类似因素。

同时，一种预防、改善或治疗免疫相关疾病的方法可以是但不限于联合疗法，其进一步包括施用对一种或多种免疫相关疾病具有治疗活性的化合物或物质。

在本发明中，“组合”应理解为代表同时、单独或顺序给药。在以顺序或单独方式给药的情况下，第二种成分应间隔给药，以使组合的有益效果不会丧失。

在本发明中，融合蛋白的剂量可以是，但不限于，每千克患者体重约0.0001μg至500mg。

有益效果

本发明提供的融合蛋白与活化的T细胞中存在的Lrig-1蛋白的配体相互作用，给活化的T细胞提供共抑制信号，从而诱导活化的T细胞的死亡或抑制的活性，使得有效预防、改善或治疗免疫相关疾病成为可能。

附图说明

图1示出了本发明一个实施方式中的Lrig-1蛋白的结构。

图2示出了本发明一个实施方式中的Lrig-1蛋白的结构。

图3示出了本发明一个实施方式中的Lrig-1蛋白的表达水平。

图4示出了本发明一个实施方式中的Lrig-1mRNA的表达水平。

图5示出了本发明一个实施方式中的Lrig-1mRNA的表达水平。

图6图示性的示出了通过比较本发明的一个实施方式中的Lrig-1、Lrig-2和Lrig-3mRNA的表达水平获得的结果。

图7示出了通过比较本发明的一个实施方式中的调节性T细胞和非调节性T细胞中Lrig-1蛋白的表达水平获得的结果。

图8示出了通过鉴定本发明的一个实施方式中的各种免疫细胞表面上Lrig-1蛋白的表达水平获得的结果。

图9示出了T细胞的亚群，其中存在可由本发明一个实施方式中的融合蛋白识别的配体。

图10示出了在本发明的一个实施方式中，通过使初始T细胞和通过用抗CD3/28抗体活化获得的活化T细胞以各自的浓度用融合蛋白和PD-L1-IgG染色而获得的结果。

图11示出了在本发明的一个实施方式中，通过对活化的T细胞(Act)和Th1细胞(TH1)进行免疫沉淀，然后用抗VISTA抗体进行蛋白质印迹分析而获得的结果。

图12A和12B分别示出了在本发明的一个实施方式中，通过用抗CD3/28抗体激活T细胞，使VISTA抗体结合到细胞表面30分钟，用Lrig-1-IgG对细胞表面进行染色，然后通过流式细胞仪进行分析而获得结果(A)，以及通过使融合蛋白结合到激活的T细胞表面30分钟，用VISTA抗体对细胞表面进行染色，然后通过流式细胞仪进行分析而获得结果(B)。

图13A和13B示出了通过用抗CD3/28抗体活化初始T细胞，每24小时用VISTA抗体对T细胞表面进行染色，然后通过流式细胞仪测量VISTA表达水平的变化而获得的结果(A)，以及通过每24小时收集活化T细胞的培养物，然后用VISTA酶联免疫试剂盒测量VISTA胞外结构域的表达水平从而测量培养物中存在的胞外结构域的量而获得的结果(B)。

图14A和14B图示性的示出了在本发明的一个实施方式中，通过从正常小鼠和已诱发类风湿性关节炎(RA)或炎症性肠病(IBD)的小鼠模型中收集血液，通过离心从其中分离血清，然后使用靶向VISTA胞外结构域的酶联免疫吸附试验测量血清中VISTA胞外结构域的浓度而获得的结果。

图15示出了在本发明的一个实施方式中，通过活化初始T细胞，然后用流式细胞仪分析在细胞表面诱导的表面蛋白CD25的表达水平获得的结果。

图16A、16B、16C和17示出了在本发明的一个实施方式中，通过鉴定本发明的融合蛋白在活化的T细胞中的增殖抑制作用获得的结果。

具体实施方式

根据本发明的一个实施方式，其提供了一种预防、改善或治疗免疫相关疾病的组合物，其包括作为活性成分的：融合蛋白，所述融合蛋白由SEQ ID NO:21表示的氨基酸序列组成；编码所述融合蛋白的核酸分子；包含核酸分子的表达载体；或者用表达载体转化得到的宿主细胞。

根据本发明的另一个实施方式，其提供了一种预防、改善或治疗免疫相关疾病的组合物，其包含作为活性成分的：融合蛋白，所述融合蛋白由SEQ ID NO:25表示的核苷酸序列编码得到；编码所述融合蛋白的核酸分子；包含核酸分子的表达载体；或者用表达载体转化得到的宿主细胞。

在下文中，本发明将通过实施例进行更详细的描述。这些实施例仅用于更详细地描述本发明，并且对于本领域技术人员而言显而易见的是，根据本发明的主旨，本发明的范围不受这些实施例的限制。

实施例

[制备实施例1]T细胞亚型细胞培养

为了确定Lrig-1蛋白是否仅在调节性T细胞(Treg)中表达，制备了T细胞亚群Th0、Th1、Th2、Th17和iTreg。与天然分离的nTreg不同，iTreg是指在具有以下组分的培养基中人工诱导分化的细胞。

通过使用从小鼠脾脏获得的首次分离的初始T细胞诱导T细胞亚群分化为各自的细胞，产生含有10％胎牛血清的RPMI1640(Invitrogen Gibco，Grand Island，NY)营养培养基(FBSHyClone，Logan，UT)，以使其进一步包含下表24的成分，并在37℃，5％CO₂的培养箱中进行72小时的培养。

[表24]

分化的细胞	组成
		Th0	抗-CD3、抗-CD28
Th1	IL-12、抗-IL-4抗体
		Th2	IL-4、抗-IFNβ
Th17	IL-6、TGFβ、抗-IFNβ、抗-IL-4
		iTreg	IL-2、TGFβ

[实施例1]Lrig-1的结构分析

预计Lrig-1蛋白胞外结构域的三维立体结构将产生包含Lrig-1蛋白胞外结构域的融合蛋白，其中所述Lrig-1蛋白是调节性T细胞的表面蛋白。

首先，为了预测表位的碱基序列，使用了工具Uniprot(http://www.uniprot.org)和RCSB蛋白质数据库(http://www.rcsb.org/pdb)来预测Lrig-1蛋白的胞外结构域(ECD)的三维立体结构，以便识别ECD的结构。然后，结果在图1和2中示出。

如图1所示，LRR1至LRR15共有15个富含亮氨酸的区域存在于Lrig-1蛋白胞外结构域的Lrig-LRR结构域(41～494位的氨基酸序列)中。每个LRR结构域由23～27个氨基酸组成，其中存在3～5个亮氨酸。

此外，如图2所示，三个免疫球蛋白样结构域存在于Lrig-1蛋白胞外结构域中Lrig-1蛋白第494～781位的氨基酸序列中。

[实施例2]调节性T细胞中Lrig-1mRNA特异性表达的鉴定

对Lrig-1蛋白是否可以作为调节性T细胞的特异性生物标志物进行了验证。

为了验证，使用磁激活细胞分选术(MACS)将CD4+T细胞通过CD4珠从小鼠脾脏中分离。随后，用荧光激活细胞分选仪(FACS)使用CD25抗体分离调节性T(CD4+CD25+T)细胞和非调节性T(CD4+CD25-T)细胞。对于各个细胞和在制备实施例1中分化的细胞，使用Trizol提取mRNA，然后根据制造商提供的说明使用gDNA提取试剂盒(Qiagen)从基因组RNA中去除gDNA。通过BDsprint cDNA Synthesis Kit(Clonetech)将去除gDNA的mRNA合成为cDNA。

采用实时聚合酶链反应(RTPCR)进行cDNA中Lrig-1mRNA表达水平的定量鉴定。

使用下表25所示的引物，根据制造商提供的说明，使用SYBR Green(分子探针)在40个循环的条件下进行实时聚合酶链反应，所述循环包括95℃3分钟，61℃15秒，72℃30秒，使用ΔCT方法计算相对基因表达水平，并使用HPRT进行标准化。结果如图4～6所示。

[表25]

如图3所示，可以看出调节性T(CD4+CD25+T)细胞中Lrig-1的表达是非调节性T(CD4+CD25-T)细胞的18.1倍。这约是Lag3和Ikzf4的表达水平的10倍，Lag3和Ikzf4是以前已知的调节性T细胞的标记。

此外，如图4和5所示，与其他类型的免疫细胞相比，调节性T细胞中Lrig-1mRNA的表达显著更高，并且特别的，与诱导的调节性T细胞相比，天然分离的调节性T细胞中Lrig-1mRNA的表达显著更高。

此外，如图6所示，在对应于Lrig家族的Lrig-1、Lrig-2和Lrig-3中，Lrig-1的表达水平最高。

从上述结果可以看出，本发明的Lrig-1蛋白在调节性T细胞，特别是天然存在的调节性T细胞中可以进行特异性表达。

[实施例3]调节性T细胞中Lrig-1蛋白特异性表达的鉴定

已经确定从Lrig-1mRNA表达的Lrig-1蛋白是否仅在调节性T细胞中进行特异性表达。

使用FOXP3-RFP敲入小鼠，通过将红色荧光蛋白(RFP)偶联到FOXP3启动子(一种对调节性T细胞特异的转录因子)获得FOXP3-RFP，使用磁激活细胞分选(MACS)通过CD4珠从小鼠脾脏分离CD4+T细胞。随后，使用RFP蛋白，通过荧光激活细胞分选仪(FACS)进行分离，获得调节性T细胞(CD4+RFP+T)和非调节性T细胞(CD4+RFP-T)。用购买的Lrig-1抗体对各自的细胞进行染色，用同种型匹配的对照抗体对阴性对照进行染色，用荧光激活细胞分选仪测量Lrig-1的表达水平。结果如图7所示。

如图7所示，由虚线表示的非调节性T细胞显示出与阴性对照几乎相同的Lrig-1表达水平，而在调节性T细胞中存在大量具有高Lrig-1表达水平的细胞。

从上述结果可以看出，本发明的Lrig-1蛋白在调节性T细胞中可进行特异性表达。

[实施例4]在调节性T细胞表面的Lrig-1蛋白的特异性表达的鉴定

从为了成为细胞治疗的目标这一观点来看，Lrig-1蛋白必须在调节性T细胞的表面表达，鉴定了Lrig-1蛋白是否可在调节性T细胞的表面表达。

用抗CD4-APC和抗Lrig-1-PE抗体对制备实施例1的各个分化的T细胞亚群进行染色，并使用荧光激活细胞分选仪(FACS)在各个细胞表面测量Lrig-1蛋白的表达水平。结果如图8所示。

如图8所示，Lrig-1在活化的T细胞、Th1细胞、Th2细胞、Th17细胞和初始T细胞中以0.77至15.3的量进行表达，而Lrig-1在分化诱导的T细胞(iTreg细胞)中表达量高达83.9。

从上述结果可以看出，本发明的Lrig-1蛋白不仅在调节性T(Treg)细胞中可以进行特异性表达，而且特别是在Treg细胞表面以更高水平进行特异性表达。

[制备实施例]融合蛋白的生产

1.表达载体的构建

为了生产本发明的融合蛋白，合成了如表26所示的编码各融合蛋白的各核酸序列。在核酸序列的5’端和3’端分别加入NheI和EcoRI限制性内切酶序列，并在5’端的限制性内切酶序列后***以下序列：Kozak序列(GCCACC)，蛋白质翻译的起始密码子，以及允许表达蛋白在细胞外分泌的小鼠IgGκ轻链信号肽(ATGGAAACCGATACTCTGCTGCTGTGGGTGCTGCTGCTGTGGGTGCCAGGCTCTACCGGG)。随后，如表26所示，在编码每个融合蛋白的核酸序列后***终止密码子，其中每个融合蛋白包括人源的Lrig-1蛋白或VISTA蛋白的胞外结构域；任选的接头；铰链区；人IgG1衍生的重链恒定区2(CH2)和重链恒定区3(CH3)。编码本发明融合蛋白的核酸序列通过使用两个限制性酶序列NheI和EcoRI克隆到pcDNA3.1(+)表达载体中。

[表26]

2.融合蛋白的纯化

用上面编号1中构建的表达载体用聚乙烯亚胺转化293F细胞，然后在37℃和8％CO₂的条件下培养6天。将培养物上清液过滤，通过蛋白A树脂，用1×PBS洗涤。用0.1M甘氨酸溶液在pH 3.5下进行洗脱。然后，向获得的溶液中加入pH 9.0的1M TRIS溶液以中和pH。随后，将该溶液用PBS溶液透析，然后浓缩并使用。

[实施例5]本发明的融合蛋白识别的Lrig-1配体分布的鉴定

为了发现其中存在Lrig-1蛋白配体的免疫细胞，诱导被认为是调节性T细胞标靶的初始T细胞分化为活化的T细胞、Th1细胞、Th2细胞或Th17细胞，然后用制备实施例5中的融合蛋白(初级抗体)和抗人PE抗体(次级抗体)对这些分化的细胞进行染色。使用荧光激活细胞分选仪(FACS)测量制备实施例5中的融合蛋白结合到各自细胞表面的水平。结果如图9所示。

如图9所示，制备实施例5中的融合蛋白几乎不与初始T细胞表面的抗原结合，因此观察到弱染色(0.71％)；并且制备实施例5中的融合蛋白以非常高的水平结合活化的T细胞、Th1细胞、Th2细胞和Th17细胞表面上的抗原，因此观察到96％或更高程度的染色。

根据这些结果，可以发现Lrig-1蛋白的配体是由T细胞受体刺激诱导的表面蛋白。

[实施例6]活化的T细胞中Lrig-1蛋白表达水平的鉴定

为了进行比较，用PD-L1-IgG融合蛋白(产品名称:rmB7-H1/Fc嵌合体，由R&DSystems公司制造，类别号:1019-B7)(以下称为“PD-L1-IgG”)以浓度相关的方式对初始T细胞和活化的T细胞的表面进行染色，所述融合蛋白可以识别PD-1，其先前已知可在活化的T细胞和T细胞亚群中高度表达，或者在制备实施例5中的融合蛋白中高度表达；并且使用细胞分选仪测量结合到各个细胞表面的制备实施例5中的融合蛋白的水平。结果如图10所示。

如图10所示，鉴定出在用制备实施例5中的融合蛋白染色的情况下，与用PD-L1-IgG染色的情况下观察到的比例相比，在活化的T细胞的表面上以浓度相关的方式观察到显著高的融合蛋白表达水平。

根据这些结果，发现与初始T细胞相比，Lrig-1蛋白的配体在活化的T细胞或T细胞亚群的表面上以高表达水平进行表达。

[实施例7]活化的T细胞中Lrig-1蛋白配体的鉴定

在实施例6中，证实了Lrig-1蛋白的配体在活化的T细胞表面高度表达的事实。基于这一事实，为了鉴定在活化的T细胞上表达的配体是哪种分子，用制备实施例5中的融合蛋白对活化的T细胞和Th1细胞的细胞裂解物进行免疫沉淀。使用Lrig-1蛋白候选配体中的各种抗体进行鉴定。因此，蛋白质印迹是通过T细胞活化的V结构域Ig抑制因子(VISTA，一种免疫检查点)的单克隆抗体进行的。结果如图11所示。

如图11所示，发现与制备实施例5中的融合蛋白结合的分子是VISTA。此外，发现在活化的T细胞(Act)和Th1细胞(TH1)中，VISTA都以非常高的水平与制备实施例5中的融合蛋白结合。从这些结果可以看出，Lrig-1蛋白的配体是VISTA。

[实施例8]活化的T细胞中的VISTA和Lrig-1蛋白之间相互作用的鉴定

为了鉴定活化的T细胞表面上存在的VISTA是否直接与Lrig-1蛋白相互作用，VISTA单克隆抗体以浓度相关的方式结合到活化的T细胞表面，然后用制备实施例5中的融合蛋白对活化的T细胞进行染色。然后，用荧光激活细胞分选仪检查染色程度。结果如图12A和12B所示。

如图12A所示，发现在细胞表面仅用制备实施例5中的融合蛋白染色的情况下，融合蛋白显示出约95％的结合率，而在用制备实施例5中的融合蛋白染色前VISTA单克隆抗体以浓度相关性方式结合的情况下，融合蛋白显示出的结合率由于竞争而显著降低。

相反，如图12B所示，发现即使在制备实施例5中的融合蛋白首先结合到活化的T细胞的表面，然后VISTA单克隆抗体结合到其上的情况下，VISTA染色的速率也降低。

从这些结果中，可以发现VISTA在活化的T细胞表面表达，Lrig-1蛋白识别VISTA并与其相互作用。

[实施例9]T细胞表面的VISTA表达模式的鉴定

为了确定VISTA在T细胞表面的表达模式，用抗CD3/28抗体激活小鼠初始T细胞，然后在各自的时间点检查VISTA的表达水平。结果如图13A所示。

如图13A所示，发现VISTA的表达水平逐渐增加，直到激活72小时；然而，经过96小时后，其在表面上的表达水平逐渐降低。

为了确定上述现象的原因，通过识别VISTA胞外结构域的酶联免疫吸附试验，在各自的时间点测量活化T细胞的细胞培养基中存在的VISTA胞外结构域的表达水平。结果如图13B所示。

如图13B所示，发现在激活后经过72小时，在培养基中几乎没有检测到VISTA的胞外结构域；然而，经过96小时后，在培养基中VISTA胞外结构域的表达水平迅速增加(图13B)。也就是说，从VISTA胞外结构域的表达水平显示出与活化T细胞表面上存在的VISTA的表达水平直接相反的模式的观点来看，发现培养基中VISTA的胞外结构域是通过切割活化T细胞表面上存在的VISTA而分泌的。

[实施例10]VISTA胞外结构域分泌与自身免疫性疾病发病之间相关性的鉴定

为了研究VISTA胞外结构域的分泌与自身免疫性疾病发病之间的相关性，从小鼠动物模型制备血清，其中所述小鼠动物模型被诱导患有类风湿性关节炎(RA)或炎性肠病(IBD)的自身免疫性疾病，然后通过使用VISTA特异性抗体的酶联免疫吸附试验分析血清中存在的VISTA胞外结构域的量。结果如图14所示。

如图14所示，发现在诱发类风湿性关节炎或IBD自身免疫性疾病的小鼠血清中，比在正常小鼠血清中检测到更大量的VISTA胞外结构域。

[实施例11]VISTA胞外结构域分泌与自身免疫性疾病发病之间相关性的鉴定

CD4+CD62L+T细胞是初始T细胞，从8周龄C57BL/6小鼠的脾脏中分离，然后使用固定在板上的抗CD3/抗CD28单克隆抗体激活初始T细胞。此后，通过用流式细胞仪分析CD25表面蛋白的表达水平来确定T细胞的活化程度，CD25表面蛋白是通过在T细胞表面诱导表达的。结果如图15所示。如图15所示，对于抑制T细胞活化的对照组，在用环孢菌素(临床实践中使用的免疫抑制剂)处理T细胞的情况下，可以看出T细胞的活化被抑制，导致CD25的表达从43.1％降低到0.33％。

从这些结果可以看出，在用作为VISTA配体的Lrig1-IgG刺激VISTA的情况下，在活化的T细胞中诱导共抑制信号，从而显著抑制T细胞的活化，并且制备实施例5中的融合蛋白显示出比刺激PD-1的PD-L1-IgG更好的抑制T细胞活化的程度。

此外，可以看出，在制备实施例5中的融合蛋白与VISTA的胞外结构域或其片段联合给药的情况下，或包含VISTA胞外结构域或其片段和免疫球蛋白的融合蛋白，可以在T细胞中更有效地诱导共抑制信号，从而更有效地诱导T细胞的活化。

[实施例12]本发明的融合蛋白对免疫相关疾病的治疗效果

CD4+CD62L+T细胞是初始T细胞，从8周龄C57BL/6小鼠的脾脏中分离，然后使用固定在板上的抗CD3/抗CD28单克隆抗体激活初始T细胞。此后，将活化的T细胞分配到96孔板中。然后，用1μg/ml的抗CD3单克隆抗体和制备实施例5中的融合蛋白处理96孔板，所述融合蛋白对应于1μg/ml、5μg/ml或10μg/ml的浓度，然后用CSFE染色。然后，在流式细胞仪观察下分析细胞的增殖程度。结果如图16和17所示。这里，作为对照，使用抗FLAG抗体代替制备实施例5中的融合蛋白。

如图17和18所示，在单独用对照和CD3处理的情况下，活化的T细胞的增殖抑制程度最大为7.87％或9.82％，而在用制备实施例5中的融合蛋白Lrig-1-IgG(mL1-hFc)处理的情况下，活化的T细胞的增殖在5μg/ml的浓度下被抑制18.17％，在10μg/ml的浓度下被抑制47.60％(图17和18)。

从这些结果可以看出，在用本发明的融合蛋白处理活化的T细胞的情况下，可以在活化的T细胞中诱导共抑制信号，从而显著抑制T细胞的活化。因此，本发明的融合蛋白可以非常有效地预防、改善或治疗由活化的T细胞引起的免疫相关疾病。

尽管上面已经详细描述了本发明，但是本发明的范围不限于此。对于本领域技术人员将显而易见的是，在不脱离权利要求中描述的本发明的技术精神的情况下，可以进行各种修改和改变。

工业适用性

本发明提供的融合蛋白可以与活化的T细胞中存在的Lrig-1蛋白的配体相互作用，以向活化的T细胞提供共抑制信号，从而诱导活化的T细胞的死亡或抑制的活性，这使得该融合蛋白能够非常有效地应用于预防、改善或治疗免疫相关疾病的领域。

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Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr

755 760

<210> 4

<211> 2280

<212> DNA

<213> 小鼠(Mus musculus)

<400> 4

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

2280

<210> 5

<211> 206

<212> PRT

<213> 人(Homo sapiens)

<400> 5

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

1 5 10 15

Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val

20 25 30

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

35 40 45

Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val

50 55 60

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

65 70 75 80

Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser

85 90 95

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

100 105 110

Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

115 120 125

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

130 135 140

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

145 150 155 160

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

165 170 175

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

180 185 190

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

195 200 205

<210> 6

<211> 206

<212> PRT

<213> 小鼠(Mus musculus)

<400> 6

Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro

1 5 10 15

Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val

20 25 30

Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr

35 40 45

Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala

50 55 60

Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys

65 70 75 80

Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser

85 90 95

Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro

100 105 110

Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val

115 120 125

Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly

130 135 140

Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp

145 150 155 160

Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp

165 170 175

Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His

180 185 190

Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys

195 200 205

<210> 7

<211> 26

<212> PRT

<213> 人(Homo sapiens)

<400> 7

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala

1 5 10 15

Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

20 25

<210> 8

<211> 27

<212> PRT

<213> 小鼠(Mus musculus)

<400> 8

Glu Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro

1 5 10 15

Ala Pro Asn Leu Leu Gly Gly Pro Ser Val Phe

20 25

<210> 9

<211> 39

<212> PRT

<213> 人(Homo sapiens)

<400> 9

Arg Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys

1 5 10 15

Glu Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro Ser His

20 25 30

Thr Gln Pro Leu Gly Val Phe

35

<210> 10

<211> 26

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 阿巴西普铰链

<400> 10

Glu Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala

1 5 10 15

Pro Glu Leu Leu Gly Gly Ser Ser Val Phe

20 25

<210> 11

<211> 2

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 肽接头

<400> 11

Gly Ser

11

<210> 12

<211> 3

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 肽接头

<400> 12

Gly Gly Gly

1

<210> 13

<211> 994

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 13

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Glu Pro Lys Ser Ser Asp

755 760 765

Lys Thr His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

770 775 780

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

785 790 795 800

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

805 810 815

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

820 825 830

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

835 840 845

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

850 855 860

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

865 870 875 880

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

885 890 895

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

900 905 910

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

915 920 925

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

930 935 940

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

945 950 955 960

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

965 970 975

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

980 985 990

Gly Lys

<210> 14

<211> 995

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 14

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Glu Pro Arg Gly Pro Thr

755 760 765

Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly

770 775 780

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

785 790 795 800

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

805 810 815

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

820 825 830

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

835 840 845

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

850 855 860

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

865 870 875 880

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

885 890 895

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

900 905 910

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

915 920 925

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

930 935 940

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

945 950 955 960

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

965 970 975

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

980 985 990

Pro Gly Lys

995

<210> 15

<211> 1007

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 15

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Arg Asn Thr Gly Arg Gly

755 760 765

Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln Glu Glu Arg

770 775 780

Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro Leu Gly Val

785 790 795 800

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

805 810 815

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu

820 825 830

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

835 840 845

Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser

850 855 860

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

865 870 875 880

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile

885 890 895

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

900 905 910

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

915 920 925

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

930 935 940

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

945 950 955 960

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg

965 970 975

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

980 985 990

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

995 1000 1005

<210> 16

<211> 994

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 16

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Glu Pro Lys Ser Ser Asp

755 760 765

Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu Leu Gly Gly

770 775 780

Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

785 790 795 800

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

805 810 815

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

820 825 830

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

835 840 845

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

850 855 860

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

865 870 875 880

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

885 890 895

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

900 905 910

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

915 920 925

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

930 935 940

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

945 950 955 960

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

965 970 975

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

980 985 990

Gly Lys

<210> 17

<211> 2982

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 17

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcgagc caaagtcctc tgataagaca cacacctctc caccatgccc agcaccagag 2340

ctgctgggag gaccaagcgt gttcctgttt cctccaaagc ccaaggacac actgatgatc 2400

tccaggacac cagaggtgac ctgcgtggtg gtggacgtga gccacgagga ccccgaggtg 2460

aagttcaact ggtacgtgga tggcgtggag gtgcacaatg ccaagaccaa gcccagagag 2520

gagcagtaca actctaccta tagggtggtg agcgtgctga cagtgctgca ccaggactgg 2580

ctgaacggca aggagtataa gtgcaaggtg agcaataagg ccctgcctgc cccaatcgag 2640

aagacaatct ccaaggccaa gggccagcca agagagcccc aggtgtacac cctgccccct 2700

agcagggatg agctgacaaa gaaccaggtg tccctgacct gtctggtgaa gggcttttat 2760

ccctccgaca tcgccgtgga gtgggagtct aatggccagc ctgagaataa ctacaagaca 2820

accccacccg tgctggattc tgacggcagc ttctttctgt attctaagct gaccgtggac 2880

aagagcaggt ggcagcaggg caacgtgttc agctgctccg tgatgcacga agcactgcac 2940

aatcactaca cccagaaatc actgtcactg agccctggca aa 2982

<210> 18

<211> 2985

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 18

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcgagc ctcggggccc taccatcaag ccctgccccc cttgcaagtg ccctgcccct 2340

aatctgctgg gcggaccctc cgtgttcctg tttcctccaa agcccaagga cacactgatg 2400

atctccagga caccagaggt gacctgcgtg gtggtggacg tgagccacga ggaccccgag 2460

gtgaagttca actggtacgt ggatggcgtg gaggtgcaca atgccaagac caagcccaga 2520

gaggagcagt acaactctac ctatagggtg gtgagcgtgc tgacagtgct gcaccaggac 2580

tggctgaacg gcaaggagta taagtgcaag gtgagcaata aggccctgcc tgccccaatc 2640

gagaagacaa tctccaaggc caagggccag ccaagagagc cccaggtgta caccctgccc 2700

cctagcaggg atgagctgac aaagaaccag gtgtccctga cctgtctggt gaagggcttt 2760

tatccctccg acatcgccgt ggagtgggag tctaatggcc agcctgagaa taactacaag 2820

acaaccccac ccgtgctgga ttctgacggc agcttctttc tgtattctaa gctgaccgtg 2880

gacaagagca ggtggcagca gggcaacgtg ttcagctgct ccgtgatgca cgaagcactg 2940

cacaatcact acacccagaa atcactgtca ctgagccctg gcaaa 2985

<210> 19

<211> 3021

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 19

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttccgca acaccggccg cggcggcgag gagaagaaga aggagaagga gaaggaggag 2340

caggaggagc gcgagaccaa gacccccgag tgccccagcc acacccagcc cctgggcgtg 2400

ttcctgtttc ctccaaagcc caaggacaca ctgatgatct ccaggacacc agaggtgacc 2460

tgcgtggtgg tggacgtgag ccacgaggac cccgaggtga agttcaactg gtacgtggat 2520

ggcgtggagg tgcacaatgc caagaccaag cccagagagg agcagtacaa ctctacctat 2580

agggtggtga gcgtgctgac agtgctgcac caggactggc tgaacggcaa ggagtataag 2640

tgcaaggtga gcaataaggc cctgcctgcc ccaatcgaga agacaatctc caaggccaag 2700

ggccagccaa gagagcccca ggtgtacacc ctgcccccta gcagggatga gctgacaaag 2760

aaccaggtgt ccctgacctg tctggtgaag ggcttttatc cctccgacat cgccgtggag 2820

tgggagtcta atggccagcc tgagaataac tacaagacaa ccccacccgt gctggattct 2880

gacggcagct tctttctgta ttctaagctg accgtggaca agagcaggtg gcagcagggc 2940

aacgtgttca gctgctccgt gatgcacgaa gcactgcaca atcactacac ccagaaatca 3000

ctgtcactga gccctggcaa a 3021

<210> 20

<211> 2982

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 20

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcgaac cgaaatcttc tgacaaaacc cacacctctc cgccgtctcc ggctccggaa 2340

ctgctgggtg gttcttctgt tttcctgttt cctccaaagc ccaaggacac actgatgatc 2400

tccaggacac cagaggtgac ctgcgtggtg gtggacgtga gccacgagga ccccgaggtg 2460

aagttcaact ggtacgtgga tggcgtggag gtgcacaatg ccaagaccaa gcccagagag 2520

gagcagtaca actctaccta tagggtggtg agcgtgctga cagtgctgca ccaggactgg 2580

ctgaacggca aggagtataa gtgcaaggtg agcaataagg ccctgcctgc cccaatcgag 2640

aagacaatct ccaaggccaa gggccagcca agagagcccc aggtgtacac cctgccccct 2700

agcagggatg agctgacaaa gaaccaggtg tccctgacct gtctggtgaa gggcttttat 2760

ccctccgaca tcgccgtgga gtgggagtct aatggccagc ctgagaataa ctacaagaca 2820

accccacccg tgctggattc tgacggcagc ttctttctgt attctaagct gaccgtggac 2880

aagagcaggt ggcagcaggg caacgtgttc agctgctccg tgatgcacga agcactgcac 2940

aatcactaca cccagaaatc actgtcactg agccctggca aa 2982

<210> 21

<211> 992

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 21

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Glu Pro Lys Ser Ser Asp Lys Thr

755 760 765

His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

770 775 780

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

785 790 795 800

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

805 810 815

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

820 825 830

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

835 840 845

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

850 855 860

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

865 870 875 880

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

885 890 895

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

900 905 910

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

915 920 925

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

930 935 940

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

945 950 955 960

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

965 970 975

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

980 985 990

<210> 22

<211> 993

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 22

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Glu Pro Arg Gly Pro Thr Ile Lys

755 760 765

Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro

770 775 780

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

785 790 795 800

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

805 810 815

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

820 825 830

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

835 840 845

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

850 855 860

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

865 870 875 880

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

885 890 895

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

900 905 910

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

915 920 925

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

930 935 940

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

945 950 955 960

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

965 970 975

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

980 985 990

Lys

<210> 23

<211> 1005

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 23

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu

755 760 765

Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr

770 775 780

Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro Leu Gly Val Phe Leu

785 790 795 800

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

805 810 815

Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys

820 825 830

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

835 840 845

Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu

850 855 860

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

865 870 875 880

Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys

885 890 895

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

900 905 910

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

915 920 925

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

930 935 940

Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly

945 950 955 960

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

965 970 975

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

980 985 990

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

995 1000 1005

<210> 24

<211> 992

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 24

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Glu Pro Lys Ser Ser Asp Lys Thr

755 760 765

His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu Leu Gly Gly Ser Ser

770 775 780

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

785 790 795 800

Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro

805 810 815

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

820 825 830

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

835 840 845

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

850 855 860

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

865 870 875 880

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

885 890 895

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

900 905 910

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

915 920 925

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

930 935 940

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

945 950 955 960

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

965 970 975

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

980 985 990

<210> 25

<211> 2976

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 25

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

gagccaaagt cctctgataa gacacacacc tctccaccat gcccagcacc agagctgctg 2340

ggaggaccaa gcgtgttcct gtttcctcca aagcccaagg acacactgat gatctccagg 2400

acaccagagg tgacctgcgt ggtggtggac gtgagccacg aggaccccga ggtgaagttc 2460

aactggtacg tggatggcgt ggaggtgcac aatgccaaga ccaagcccag agaggagcag 2520

tacaactcta cctatagggt ggtgagcgtg ctgacagtgc tgcaccagga ctggctgaac 2580

ggcaaggagt ataagtgcaa ggtgagcaat aaggccctgc ctgccccaat cgagaagaca 2640

atctccaagg ccaagggcca gccaagagag ccccaggtgt acaccctgcc ccctagcagg 2700

gatgagctga caaagaacca ggtgtccctg acctgtctgg tgaagggctt ttatccctcc 2760

gacatcgccg tggagtggga gtctaatggc cagcctgaga ataactacaa gacaacccca 2820

cccgtgctgg attctgacgg cagcttcttt ctgtattcta agctgaccgt ggacaagagc 2880

aggtggcagc agggcaacgt gttcagctgc tccgtgatgc acgaagcact gcacaatcac 2940

tacacccaga aatcactgtc actgagccct ggcaaa 2976

<210> 26

<211> 2979

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 26

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

gagcctcggg gccctaccat caagccctgc cccccttgca agtgccctgc ccctaatctg 2340

ctgggcggac cctccgtgtt cctgtttcct ccaaagccca aggacacact gatgatctcc 2400

aggacaccag aggtgacctg cgtggtggtg gacgtgagcc acgaggaccc cgaggtgaag 2460

ttcaactggt acgtggatgg cgtggaggtg cacaatgcca agaccaagcc cagagaggag 2520

cagtacaact ctacctatag ggtggtgagc gtgctgacag tgctgcacca ggactggctg 2580

aacggcaagg agtataagtg caaggtgagc aataaggccc tgcctgcccc aatcgagaag 2640

acaatctcca aggccaaggg ccagccaaga gagccccagg tgtacaccct gccccctagc 2700

agggatgagc tgacaaagaa ccaggtgtcc ctgacctgtc tggtgaaggg cttttatccc 2760

tccgacatcg ccgtggagtg ggagtctaat ggccagcctg agaataacta caagacaacc 2820

ccacccgtgc tggattctga cggcagcttc tttctgtatt ctaagctgac cgtggacaag 2880

agcaggtggc agcagggcaa cgtgttcagc tgctccgtga tgcacgaagc actgcacaat 2940

cactacaccc agaaatcact gtcactgagc cctggcaaa 2979

<210> 27

<211> 3015

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 27

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

cgcaacaccg gccgcggcgg cgaggagaag aagaaggaga aggagaagga ggagcaggag 2340

gagcgcgaga ccaagacccc cgagtgcccc agccacaccc agcccctggg cgtgttcctg 2400

tttcctccaa agcccaagga cacactgatg atctccagga caccagaggt gacctgcgtg 2460

gtggtggacg tgagccacga ggaccccgag gtgaagttca actggtacgt ggatggcgtg 2520

gaggtgcaca atgccaagac caagcccaga gaggagcagt acaactctac ctatagggtg 2580

gtgagcgtgc tgacagtgct gcaccaggac tggctgaacg gcaaggagta taagtgcaag 2640

gtgagcaata aggccctgcc tgccccaatc gagaagacaa tctccaaggc caagggccag 2700

ccaagagagc cccaggtgta caccctgccc cctagcaggg atgagctgac aaagaaccag 2760

gtgtccctga cctgtctggt gaagggcttt tatccctccg acatcgccgt ggagtgggag 2820

tctaatggcc agcctgagaa taactacaag acaaccccac ccgtgctgga ttctgacggc 2880

agcttctttc tgtattctaa gctgaccgtg gacaagagca ggtggcagca gggcaacgtg 2940

ttcagctgct ccgtgatgca cgaagcactg cacaatcact acacccagaa atcactgtca 3000

ctgagccctg gcaaa 3015

<210> 28

<211> 2976

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 28

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

gaaccgaaat cttctgacaa aacccacacc tctccgccgt ctccggctcc ggaactgctg 2340

ggtggttctt ctgttttcct gtttcctcca aagcccaagg acacactgat gatctccagg 2400

acaccagagg tgacctgcgt ggtggtggac gtgagccacg aggaccccga ggtgaagttc 2460

aactggtacg tggatggcgt ggaggtgcac aatgccaaga ccaagcccag agaggagcag 2520

tacaactcta cctatagggt ggtgagcgtg ctgacagtgc tgcaccagga ctggctgaac 2580

ggcaaggagt ataagtgcaa ggtgagcaat aaggccctgc ctgccccaat cgagaagaca 2640

atctccaagg ccaagggcca gccaagagag ccccaggtgt acaccctgcc ccctagcagg 2700

gatgagctga caaagaacca ggtgtccctg acctgtctgg tgaagggctt ttatccctcc 2760

gacatcgccg tggagtggga gtctaatggc cagcctgaga ataactacaa gacaacccca 2820

cccgtgctgg attctgacgg cagcttcttt ctgtattcta agctgaccgt ggacaagagc 2880

aggtggcagc agggcaacgt gttcagctgc tccgtgatgc acgaagcact gcacaatcac 2940

tacacccaga aatcactgtc actgagccct ggcaaa 2976

<210> 29

<211> 992

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 29

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Glu Pro Lys Ser Ser Asp Lys Thr

755 760 765

His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

770 775 780

Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu

785 790 795 800

Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro

805 810 815

Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala

820 825 830

Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val

835 840 845

Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe

850 855 860

Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr

865 870 875 880

Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu

885 890 895

Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys

900 905 910

Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn

915 920 925

Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp

930 935 940

Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys

945 950 955 960

Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly

965 970 975

Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys

980 985 990

<210> 30

<211> 993

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 30

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Glu Pro Arg Gly Pro Thr Ile Lys

755 760 765

Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly Gly Pro

770 775 780

Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser

785 790 795 800

Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp

805 810 815

Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr

820 825 830

Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val

835 840 845

Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu

850 855 860

Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg

865 870 875 880

Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val

885 890 895

Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr

900 905 910

Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr

915 920 925

Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu

930 935 940

Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys

945 950 955 960

Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu

965 970 975

Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly

980 985 990

Lys

<210> 31

<211> 1005

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 31

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Arg Asn Thr Gly Arg Gly Gly Glu

755 760 765

Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln Glu Glu Arg Glu Thr

770 775 780

Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro Leu Gly Val Phe Ile

785 790 795 800

Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser Pro Ile

805 810 815

Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp Val Gln

820 825 830

Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln Thr Gln

835 840 845

Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser Ala Leu

850 855 860

Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys Cys Lys

865 870 875 880

Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile Ser Lys

885 890 895

Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro Pro Pro

900 905 910

Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met Val Thr

915 920 925

Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn Gly Lys

930 935 940

Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser Asp Gly

945 950 955 960

Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn Trp Val

965 970 975

Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu His Asn

980 985 990

His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys

995 1000 1005

<210> 32

<211> 992

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 32

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Glu Pro Lys Ser Ser Asp Lys Thr

755 760 765

His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu Leu Gly Gly Ser Ser

770 775 780

Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu

785 790 795 800

Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro

805 810 815

Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala

820 825 830

Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val

835 840 845

Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe

850 855 860

Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr

865 870 875 880

Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu

885 890 895

Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys

900 905 910

Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn

915 920 925

Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp

930 935 940

Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys

945 950 955 960

Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly

965 970 975

Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys

980 985 990

<210> 33

<211> 2976

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 33

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

gagccaaagt cctctgataa gacacacacc tctccaccat gcccagcacc agagctgctg 2340

ggaggaccaa gcgtgttcat cttcccaccc aagatcaagg acgtgctgat gatctccctg 2400

tcccccatcg tgacctgcgt ggtggtggac gtgtccgagg acgaccccga cgtgcagatc 2460

agttggttcg tgaacaacgt ggaagtgcac accgcccaga cccagaccca cagagaggac 2520

tacaactcca ccctgcgggt ggtgtccgcc ctgcccatcc agcaccagga ctggatgtcc 2580

ggcaaagaat tcaagtgcaa agtgaacaac aaggacctgc ctgcccccat cgagcggacc 2640

atctccaagc ccaagggctc cgtgcgggct ccccaggtgt acgtgctgcc ccctccagag 2700

gaagagatga ccaagaagca ggtcacactg acctgcatgg tcaccgactt catgcccgag 2760

gacatctacg tggaatggac caacaatggc aagaccgagc tgaactacaa gaacaccgag 2820

cctgtgctgg actccgacgg ctcctacttc atgtactcca agctgcgggt ggaaaagaag 2880

aactgggtcg agcggaactc ctactcctgc tccgtggtgc acgagggcct gcacaaccac 2940

cacaccacca agtccttctc ccggaccccc ggcaaa 2976

<210> 34

<211> 2979

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 34

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

gagcctcggg gccctaccat caagccctgc cccccttgca agtgccctgc ccctaatctg 2340

ctgggcggac cctccgtgtt catcttccca cccaagatca aggacgtgct gatgatctcc 2400

ctgtccccca tcgtgacctg cgtggtggtg gacgtgtccg aggacgaccc cgacgtgcag 2460

atcagttggt tcgtgaacaa cgtggaagtg cacaccgccc agacccagac ccacagagag 2520

gactacaact ccaccctgcg ggtggtgtcc gccctgccca tccagcacca ggactggatg 2580

tccggcaaag aattcaagtg caaagtgaac aacaaggacc tgcctgcccc catcgagcgg 2640

accatctcca agcccaaggg ctccgtgcgg gctccccagg tgtacgtgct gccccctcca 2700

gaggaagaga tgaccaagaa gcaggtcaca ctgacctgca tggtcaccga cttcatgccc 2760

gaggacatct acgtggaatg gaccaacaat ggcaagaccg agctgaacta caagaacacc 2820

gagcctgtgc tggactccga cggctcctac ttcatgtact ccaagctgcg ggtggaaaag 2880

aagaactggg tcgagcggaa ctcctactcc tgctccgtgg tgcacgaggg cctgcacaac 2940

caccacacca ccaagtcctt ctcccggacc cccggcaaa 2979

<210> 35

<211> 3015

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 35

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

cgcaacaccg gccgcggcgg cgaggagaag aagaaggaga aggagaagga ggagcaggag 2340

gagcgcgaga ccaagacccc cgagtgcccc agccacaccc agcccctggg cgtgttcatc 2400

ttcccaccca agatcaagga cgtgctgatg atctccctgt cccccatcgt gacctgcgtg 2460

gtggtggacg tgtccgagga cgaccccgac gtgcagatca gttggttcgt gaacaacgtg 2520

gaagtgcaca ccgcccagac ccagacccac agagaggact acaactccac cctgcgggtg 2580

gtgtccgccc tgcccatcca gcaccaggac tggatgtccg gcaaagaatt caagtgcaaa 2640

gtgaacaaca aggacctgcc tgcccccatc gagcggacca tctccaagcc caagggctcc 2700

gtgcgggctc cccaggtgta cgtgctgccc cctccagagg aagagatgac caagaagcag 2760

gtcacactga cctgcatggt caccgacttc atgcccgagg acatctacgt ggaatggacc 2820

aacaatggca agaccgagct gaactacaag aacaccgagc ctgtgctgga ctccgacggc 2880

tcctacttca tgtactccaa gctgcgggtg gaaaagaaga actgggtcga gcggaactcc 2940

tactcctgct ccgtggtgca cgagggcctg cacaaccacc acaccaccaa gtccttctcc 3000

cggacccccg gcaaa 3015

<210> 36

<211> 2976

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 36

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

gaaccgaaat cttctgacaa aacccacacc tctccgccgt ctccggctcc ggaactgctg 2340

ggtggttctt ctgttttcat cttcccaccc aagatcaagg acgtgctgat gatctccctg 2400

tcccccatcg tgacctgcgt ggtggtggac gtgtccgagg acgaccccga cgtgcagatc 2460

agttggttcg tgaacaacgt ggaagtgcac accgcccaga cccagaccca cagagaggac 2520

tacaactcca ccctgcgggt ggtgtccgcc ctgcccatcc agcaccagga ctggatgtcc 2580

ggcaaagaat tcaagtgcaa agtgaacaac aaggacctgc ctgcccccat cgagcggacc 2640

atctccaagc ccaagggctc cgtgcgggct ccccaggtgt acgtgctgcc ccctccagag 2700

gaagagatga ccaagaagca ggtcacactg acctgcatgg tcaccgactt catgcccgag 2760

gacatctacg tggaatggac caacaatggc aagaccgagc tgaactacaa gaacaccgag 2820

cctgtgctgg actccgacgg ctcctacttc atgtactcca agctgcgggt ggaaaagaag 2880

aactgggtcg agcggaactc ctactcctgc tccgtggtgc acgagggcct gcacaaccac 2940

cacaccacca agtccttctc ccggaccccc ggcaaa 2976

<210> 37

<211> 996

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 37

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Ser Glu Pro Lys Ser

755 760 765

Ser Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu Leu

770 775 780

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

785 790 795 800

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

805 810 815

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

820 825 830

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

835 840 845

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

850 855 860

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

865 870 875 880

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

885 890 895

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

900 905 910

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

915 920 925

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

930 935 940

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

945 950 955 960

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

965 970 975

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

980 985 990

Ser Pro Gly Lys

995

<210> 38

<211> 997

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 38

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Ser Glu Pro Arg Gly

755 760 765

Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu

770 775 780

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

785 790 795 800

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

805 810 815

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

820 825 830

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

835 840 845

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

850 855 860

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

865 870 875 880

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

885 890 895

Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln

900 905 910

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

915 920 925

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

930 935 940

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

945 950 955 960

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

965 970 975

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

980 985 990

Leu Ser Pro Gly Lys

995

<210> 39

<211> 1009

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 39

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Ser Arg Asn Thr Gly

755 760 765

Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln Glu

770 775 780

Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro Leu

785 790 795 800

Gly Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

805 810 815

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

820 825 830

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

835 840 845

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

850 855 860

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

865 870 875 880

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

885 890 895

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

900 905 910

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

915 920 925

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

930 935 940

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

945 950 955 960

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

965 970 975

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

980 985 990

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

995 1000 1005

Lys

<210> 40

<211> 996

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 40

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Ser Glu Pro Lys Ser

755 760 765

Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu Leu

770 775 780

Gly Gly Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

785 790 795 800

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

805 810 815

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

820 825 830

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

835 840 845

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

850 855 860

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

865 870 875 880

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

885 890 895

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

900 905 910

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

915 920 925

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

930 935 940

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

945 950 955 960

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

965 970 975

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

980 985 990

Ser Pro Gly Lys

995

<210> 41

<211> 2988

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 41

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggat ccgagccaaa gtcctctgat aagacacaca cctctccacc atgcccagca 2340

ccagagctgc tgggaggacc aagcgtgttc ctgtttcctc caaagcccaa ggacacactg 2400

atgatctcca ggacaccaga ggtgacctgc gtggtggtgg acgtgagcca cgaggacccc 2460

gaggtgaagt tcaactggta cgtggatggc gtggaggtgc acaatgccaa gaccaagccc 2520

agagaggagc agtacaactc tacctatagg gtggtgagcg tgctgacagt gctgcaccag 2580

gactggctga acggcaagga gtataagtgc aaggtgagca ataaggccct gcctgcccca 2640

atcgagaaga caatctccaa ggccaagggc cagccaagag agccccaggt gtacaccctg 2700

ccccctagca gggatgagct gacaaagaac caggtgtccc tgacctgtct ggtgaagggc 2760

ttttatccct ccgacatcgc cgtggagtgg gagtctaatg gccagcctga gaataactac 2820

aagacaaccc cacccgtgct ggattctgac ggcagcttct ttctgtattc taagctgacc 2880

gtggacaaga gcaggtggca gcagggcaac gtgttcagct gctccgtgat gcacgaagca 2940

ctgcacaatc actacaccca gaaatcactg tcactgagcc ctggcaaa 2988

<210> 42

<211> 2991

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 42

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggat ccgagcctcg gggccctacc atcaagccct gccccccttg caagtgccct 2340

gcccctaatc tgctgggcgg accctccgtg ttcctgtttc ctccaaagcc caaggacaca 2400

ctgatgatct ccaggacacc agaggtgacc tgcgtggtgg tggacgtgag ccacgaggac 2460

cccgaggtga agttcaactg gtacgtggat ggcgtggagg tgcacaatgc caagaccaag 2520

cccagagagg agcagtacaa ctctacctat agggtggtga gcgtgctgac agtgctgcac 2580

caggactggc tgaacggcaa ggagtataag tgcaaggtga gcaataaggc cctgcctgcc 2640

ccaatcgaga agacaatctc caaggccaag ggccagccaa gagagcccca ggtgtacacc 2700

ctgcccccta gcagggatga gctgacaaag aaccaggtgt ccctgacctg tctggtgaag 2760

ggcttttatc cctccgacat cgccgtggag tgggagtcta atggccagcc tgagaataac 2820

tacaagacaa ccccacccgt gctggattct gacggcagct tctttctgta ttctaagctg 2880

accgtggaca agagcaggtg gcagcagggc aacgtgttca gctgctccgt gatgcacgaa 2940

gcactgcaca atcactacac ccagaaatca ctgtcactga gccctggcaa a 2991

<210> 43

<211> 3027

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 43

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggat cccgcaacac cggccgcggc ggcgaggaga agaagaagga gaaggagaag 2340

gaggagcagg aggagcgcga gaccaagacc cccgagtgcc ccagccacac ccagcccctg 2400

ggcgtgttcc tgtttcctcc aaagcccaag gacacactga tgatctccag gacaccagag 2460

gtgacctgcg tggtggtgga cgtgagccac gaggaccccg aggtgaagtt caactggtac 2520

gtggatggcg tggaggtgca caatgccaag accaagccca gagaggagca gtacaactct 2580

acctataggg tggtgagcgt gctgacagtg ctgcaccagg actggctgaa cggcaaggag 2640

tataagtgca aggtgagcaa taaggccctg cctgccccaa tcgagaagac aatctccaag 2700

gccaagggcc agccaagaga gccccaggtg tacaccctgc cccctagcag ggatgagctg 2760

acaaagaacc aggtgtccct gacctgtctg gtgaagggct tttatccctc cgacatcgcc 2820

gtggagtggg agtctaatgg ccagcctgag aataactaca agacaacccc acccgtgctg 2880

gattctgacg gcagcttctt tctgtattct aagctgaccg tggacaagag caggtggcag 2940

cagggcaacg tgttcagctg ctccgtgatg cacgaagcac tgcacaatca ctacacccag 3000

aaatcactgt cactgagccc tggcaaa 3027

<210> 44

<211> 2988

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 44

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggat ccgaaccgaa atcttctgac aaaacccaca cctctccgcc gtctccggct 2340

ccggaactgc tgggtggttc ttctgttttc ctgtttcctc caaagcccaa ggacacactg 2400

atgatctcca ggacaccaga ggtgacctgc gtggtggtgg acgtgagcca cgaggacccc 2460

gaggtgaagt tcaactggta cgtggatggc gtggaggtgc acaatgccaa gaccaagccc 2520

agagaggagc agtacaactc tacctatagg gtggtgagcg tgctgacagt gctgcaccag 2580

gactggctga acggcaagga gtataagtgc aaggtgagca ataaggccct gcctgcccca 2640

atcgagaaga caatctccaa ggccaagggc cagccaagag agccccaggt gtacaccctg 2700

ccccctagca gggatgagct gacaaagaac caggtgtccc tgacctgtct ggtgaagggc 2760

ttttatccct ccgacatcgc cgtggagtgg gagtctaatg gccagcctga gaataactac 2820

aagacaaccc cacccgtgct ggattctgac ggcagcttct ttctgtattc taagctgacc 2880

gtggacaaga gcaggtggca gcagggcaac gtgttcagct gctccgtgat gcacgaagca 2940

ctgcacaatc actacaccca gaaatcactg tcactgagcc ctggcaaa 2988

<210> 45

<211> 994

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 45

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Glu Pro Lys Ser Ser Asp

755 760 765

Lys Thr His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

770 775 780

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

785 790 795 800

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

805 810 815

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

820 825 830

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

835 840 845

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

850 855 860

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

865 870 875 880

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

885 890 895

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

900 905 910

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

915 920 925

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

930 935 940

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

945 950 955 960

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

965 970 975

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

980 985 990

Gly Lys

<210> 46

<211> 995

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 46

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Glu Pro Arg Gly Pro Thr

755 760 765

Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly

770 775 780

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

785 790 795 800

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

805 810 815

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

820 825 830

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

835 840 845

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

850 855 860

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

865 870 875 880

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val

885 890 895

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

900 905 910

Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu

915 920 925

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

930 935 940

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

945 950 955 960

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

965 970 975

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

980 985 990

Pro Gly Lys

995

<210> 47

<211> 1007

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 47

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Arg Asn Thr Gly Arg Gly

755 760 765

Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln Glu Glu Arg

770 775 780

Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro Leu Gly Val

785 790 795 800

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

805 810 815

Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu

820 825 830

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

835 840 845

Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser

850 855 860

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

865 870 875 880

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile

885 890 895

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

900 905 910

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

915 920 925

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

930 935 940

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

945 950 955 960

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg

965 970 975

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

980 985 990

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

995 1000 1005

<210> 48

<211> 994

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 48

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Glu Pro Lys Ser Ser Asp

755 760 765

Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu Leu Gly Gly

770 775 780

Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

785 790 795 800

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

805 810 815

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

820 825 830

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

835 840 845

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

850 855 860

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

865 870 875 880

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

885 890 895

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

900 905 910

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

915 920 925

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

930 935 940

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

945 950 955 960

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

965 970 975

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

980 985 990

Gly Lys

<210> 49

<211> 2982

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 49

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatccgagc caaagtcctc tgataagaca cacacctctc caccatgccc agcaccagag 2340

ctgctgggag gaccaagcgt gttcctgttt cctccaaagc ccaaggacac actgatgatc 2400

tccaggacac cagaggtgac ctgcgtggtg gtggacgtga gccacgagga ccccgaggtg 2460

aagttcaact ggtacgtgga tggcgtggag gtgcacaatg ccaagaccaa gcccagagag 2520

gagcagtaca actctaccta tagggtggtg agcgtgctga cagtgctgca ccaggactgg 2580

ctgaacggca aggagtataa gtgcaaggtg agcaataagg ccctgcctgc cccaatcgag 2640

aagacaatct ccaaggccaa gggccagcca agagagcccc aggtgtacac cctgccccct 2700

agcagggatg agctgacaaa gaaccaggtg tccctgacct gtctggtgaa gggcttttat 2760

ccctccgaca tcgccgtgga gtgggagtct aatggccagc ctgagaataa ctacaagaca 2820

accccacccg tgctggattc tgacggcagc ttctttctgt attctaagct gaccgtggac 2880

aagagcaggt ggcagcaggg caacgtgttc agctgctccg tgatgcacga agcactgcac 2940

aatcactaca cccagaaatc actgtcactg agccctggca aa 2982

<210> 50

<211> 2985

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 50

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatccgagc ctcggggccc taccatcaag ccctgccccc cttgcaagtg ccctgcccct 2340

aatctgctgg gcggaccctc cgtgttcctg tttcctccaa agcccaagga cacactgatg 2400

atctccagga caccagaggt gacctgcgtg gtggtggacg tgagccacga ggaccccgag 2460

gtgaagttca actggtacgt ggatggcgtg gaggtgcaca atgccaagac caagcccaga 2520

gaggagcagt acaactctac ctatagggtg gtgagcgtgc tgacagtgct gcaccaggac 2580

tggctgaacg gcaaggagta taagtgcaag gtgagcaata aggccctgcc tgccccaatc 2640

gagaagacaa tctccaaggc caagggccag ccaagagagc cccaggtgta caccctgccc 2700

cctagcaggg atgagctgac aaagaaccag gtgtccctga cctgtctggt gaagggcttt 2760

tatccctccg acatcgccgt ggagtgggag tctaatggcc agcctgagaa taactacaag 2820

acaaccccac ccgtgctgga ttctgacggc agcttctttc tgtattctaa gctgaccgtg 2880

gacaagagca ggtggcagca gggcaacgtg ttcagctgct ccgtgatgca cgaagcactg 2940

cacaatcact acacccagaa atcactgtca ctgagccctg gcaaa 2985

<210> 51

<211> 3021

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 51

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatcccgca acaccggccg cggcggcgag gagaagaaga aggagaagga gaaggaggag 2340

caggaggagc gcgagaccaa gacccccgag tgccccagcc acacccagcc cctgggcgtg 2400

ttcctgtttc ctccaaagcc caaggacaca ctgatgatct ccaggacacc agaggtgacc 2460

tgcgtggtgg tggacgtgag ccacgaggac cccgaggtga agttcaactg gtacgtggat 2520

ggcgtggagg tgcacaatgc caagaccaag cccagagagg agcagtacaa ctctacctat 2580

agggtggtga gcgtgctgac agtgctgcac caggactggc tgaacggcaa ggagtataag 2640

tgcaaggtga gcaataaggc cctgcctgcc ccaatcgaga agacaatctc caaggccaag 2700

ggccagccaa gagagcccca ggtgtacacc ctgcccccta gcagggatga gctgacaaag 2760

aaccaggtgt ccctgacctg tctggtgaag ggcttttatc cctccgacat cgccgtggag 2820

tgggagtcta atggccagcc tgagaataac tacaagacaa ccccacccgt gctggattct 2880

gacggcagct tctttctgta ttctaagctg accgtggaca agagcaggtg gcagcagggc 2940

aacgtgttca gctgctccgt gatgcacgaa gcactgcaca atcactacac ccagaaatca 3000

ctgtcactga gccctggcaa a 3021

<210> 52

<211> 2982

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 52

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatccgaac cgaaatcttc tgacaaaacc cacacctctc cgccgtctcc ggctccggaa 2340

ctgctgggtg gttcttctgt tttcctgttt cctccaaagc ccaaggacac actgatgatc 2400

tccaggacac cagaggtgac ctgcgtggtg gtggacgtga gccacgagga ccccgaggtg 2460

aagttcaact ggtacgtgga tggcgtggag gtgcacaatg ccaagaccaa gcccagagag 2520

gagcagtaca actctaccta tagggtggtg agcgtgctga cagtgctgca ccaggactgg 2580

ctgaacggca aggagtataa gtgcaaggtg agcaataagg ccctgcctgc cccaatcgag 2640

aagacaatct ccaaggccaa gggccagcca agagagcccc aggtgtacac cctgccccct 2700

agcagggatg agctgacaaa gaaccaggtg tccctgacct gtctggtgaa gggcttttat 2760

ccctccgaca tcgccgtgga gtgggagtct aatggccagc ctgagaataa ctacaagaca 2820

accccacccg tgctggattc tgacggcagc ttctttctgt attctaagct gaccgtggac 2880

aagagcaggt ggcagcaggg caacgtgttc agctgctccg tgatgcacga agcactgcac 2940

aatcactaca cccagaaatc actgtcactg agccctggca aa 2982

<210> 53

<211> 994

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 53

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Glu Pro Lys Ser Ser Asp

755 760 765

Lys Thr His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

770 775 780

Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile

785 790 795 800

Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp

805 810 815

Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His

820 825 830

Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg

835 840 845

Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys

850 855 860

Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu

865 870 875 880

Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr

885 890 895

Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu

900 905 910

Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp

915 920 925

Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val

930 935 940

Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu

945 950 955 960

Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His

965 970 975

Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro

980 985 990

Gly Lys

<210> 54

<211> 995

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 54

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Glu Pro Arg Gly Pro Thr

755 760 765

Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn Leu Leu Gly

770 775 780

Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met

785 790 795 800

Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu

805 810 815

Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val

820 825 830

His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu

835 840 845

Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly

850 855 860

Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile

865 870 875 880

Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val

885 890 895

Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr

900 905 910

Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu

915 920 925

Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro

930 935 940

Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val

945 950 955 960

Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val

965 970 975

His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr

980 985 990

Pro Gly Lys

995

<210> 55

<211> 1007

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 55

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Arg Asn Thr Gly Arg Gly

755 760 765

Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln Glu Glu Arg

770 775 780

Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro Leu Gly Val

785 790 795 800

Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile Ser Leu Ser

805 810 815

Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp Asp Pro Asp

820 825 830

Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His Thr Ala Gln

835 840 845

Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg Val Val Ser

850 855 860

Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys Glu Phe Lys

865 870 875 880

Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu Arg Thr Ile

885 890 895

Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr Val Leu Pro

900 905 910

Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu Thr Cys Met

915 920 925

Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp Thr Asn Asn

930 935 940

Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val Leu Asp Ser

945 950 955 960

Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu Lys Lys Asn

965 970 975

Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His Glu Gly Leu

980 985 990

His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro Gly Lys

995 1000 1005

<210> 56

<211> 994

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 56

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Ser Glu Pro Lys Ser Ser Asp

755 760 765

Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu Leu Gly Gly

770 775 780

Ser Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile

785 790 795 800

Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp

805 810 815

Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His

820 825 830

Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg

835 840 845

Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys

850 855 860

Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu

865 870 875 880

Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr

885 890 895

Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu

900 905 910

Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp

915 920 925

Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val

930 935 940

Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu

945 950 955 960

Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His

965 970 975

Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro

980 985 990

Gly Lys

<210> 57

<211> 2982

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 57

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatccgagc caaagtcctc tgataagaca cacacctctc caccatgccc agcaccagag 2340

ctgctgggag gaccaagcgt gttcatcttc ccacccaaga tcaaggacgt gctgatgatc 2400

tccctgtccc ccatcgtgac ctgcgtggtg gtggacgtgt ccgaggacga ccccgacgtg 2460

cagatcagtt ggttcgtgaa caacgtggaa gtgcacaccg cccagaccca gacccacaga 2520

gaggactaca actccaccct gcgggtggtg tccgccctgc ccatccagca ccaggactgg 2580

atgtccggca aagaattcaa gtgcaaagtg aacaacaagg acctgcctgc ccccatcgag 2640

cggaccatct ccaagcccaa gggctccgtg cgggctcccc aggtgtacgt gctgccccct 2700

ccagaggaag agatgaccaa gaagcaggtc acactgacct gcatggtcac cgacttcatg 2760

cccgaggaca tctacgtgga atggaccaac aatggcaaga ccgagctgaa ctacaagaac 2820

accgagcctg tgctggactc cgacggctcc tacttcatgt actccaagct gcgggtggaa 2880

aagaagaact gggtcgagcg gaactcctac tcctgctccg tggtgcacga gggcctgcac 2940

aaccaccaca ccaccaagtc cttctcccgg acccccggca aa 2982

<210> 58

<211> 2985

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 58

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatccgagc ctcggggccc taccatcaag ccctgccccc cttgcaagtg ccctgcccct 2340

aatctgctgg gcggaccctc cgtgttcatc ttcccaccca agatcaagga cgtgctgatg 2400

atctccctgt cccccatcgt gacctgcgtg gtggtggacg tgtccgagga cgaccccgac 2460

gtgcagatca gttggttcgt gaacaacgtg gaagtgcaca ccgcccagac ccagacccac 2520

agagaggact acaactccac cctgcgggtg gtgtccgccc tgcccatcca gcaccaggac 2580

tggatgtccg gcaaagaatt caagtgcaaa gtgaacaaca aggacctgcc tgcccccatc 2640

gagcggacca tctccaagcc caagggctcc gtgcgggctc cccaggtgta cgtgctgccc 2700

cctccagagg aagagatgac caagaagcag gtcacactga cctgcatggt caccgacttc 2760

atgcccgagg acatctacgt ggaatggacc aacaatggca agaccgagct gaactacaag 2820

aacaccgagc ctgtgctgga ctccgacggc tcctacttca tgtactccaa gctgcgggtg 2880

gaaaagaaga actgggtcga gcggaactcc tactcctgct ccgtggtgca cgagggcctg 2940

cacaaccacc acaccaccaa gtccttctcc cggacccccg gcaaa 2985

<210> 59

<211> 3021

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 59

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatcccgca acaccggccg cggcggcgag gagaagaaga aggagaagga gaaggaggag 2340

caggaggagc gcgagaccaa gacccccgag tgccccagcc acacccagcc cctgggcgtg 2400

ttcatcttcc cacccaagat caaggacgtg ctgatgatct ccctgtcccc catcgtgacc 2460

tgcgtggtgg tggacgtgtc cgaggacgac cccgacgtgc agatcagttg gttcgtgaac 2520

aacgtggaag tgcacaccgc ccagacccag acccacagag aggactacaa ctccaccctg 2580

cgggtggtgt ccgccctgcc catccagcac caggactgga tgtccggcaa agaattcaag 2640

tgcaaagtga acaacaagga cctgcctgcc cccatcgagc ggaccatctc caagcccaag 2700

ggctccgtgc gggctcccca ggtgtacgtg ctgccccctc cagaggaaga gatgaccaag 2760

aagcaggtca cactgacctg catggtcacc gacttcatgc ccgaggacat ctacgtggaa 2820

tggaccaaca atggcaagac cgagctgaac tacaagaaca ccgagcctgt gctggactcc 2880

gacggctcct acttcatgta ctccaagctg cgggtggaaa agaagaactg ggtcgagcgg 2940

aactcctact cctgctccgt ggtgcacgag ggcctgcaca accaccacac caccaagtcc 3000

ttctcccgga cccccggcaa a 3021

<210> 60

<211> 2982

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 60

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggatccgaac cgaaatcttc tgacaaaacc cacacctctc cgccgtctcc ggctccggaa 2340

ctgctgggtg gttcttctgt tttcatcttc ccacccaaga tcaaggacgt gctgatgatc 2400

tccctgtccc ccatcgtgac ctgcgtggtg gtggacgtgt ccgaggacga ccccgacgtg 2460

cagatcagtt ggttcgtgaa caacgtggaa gtgcacaccg cccagaccca gacccacaga 2520

gaggactaca actccaccct gcgggtggtg tccgccctgc ccatccagca ccaggactgg 2580

atgtccggca aagaattcaa gtgcaaagtg aacaacaagg acctgcctgc ccccatcgag 2640

cggaccatct ccaagcccaa gggctccgtg cgggctcccc aggtgtacgt gctgccccct 2700

ccagaggaag agatgaccaa gaagcaggtc acactgacct gcatggtcac cgacttcatg 2760

cccgaggaca tctacgtgga atggaccaac aatggcaaga ccgagctgaa ctacaagaac 2820

accgagcctg tgctggactc cgacggctcc tacttcatgt actccaagct gcgggtggaa 2880

aagaagaact gggtcgagcg gaactcctac tcctgctccg tggtgcacga gggcctgcac 2940

aaccaccaca ccaccaagtc cttctcccgg acccccggca aa 2982

<210> 61

<211> 999

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 61

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Gly Gly Gly Ser Glu

755 760 765

Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Pro

770 775 780

Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

785 790 795 800

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

805 810 815

Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp

820 825 830

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr

835 840 845

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

850 855 860

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

865 870 875 880

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

885 890 895

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys

900 905 910

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

915 920 925

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

930 935 940

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

945 950 955 960

Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

965 970 975

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

980 985 990

Leu Ser Leu Ser Pro Gly Lys

995

<210> 62

<211> 1000

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 62

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Gly Gly Gly Ser Glu

755 760 765

Pro Arg Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala

770 775 780

Pro Asn Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro

785 790 795 800

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val

805 810 815

Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val

820 825 830

Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln

835 840 845

Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln

850 855 860

Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala

865 870 875 880

Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro

885 890 895

Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr

900 905 910

Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser

915 920 925

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr

930 935 940

Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

945 950 955 960

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe

965 970 975

Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys

980 985 990

Ser Leu Ser Leu Ser Pro Gly Lys

995 1000

<210> 63

<211> 1012

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 63

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Gly Gly Gly Ser Arg

755 760 765

Asn Thr Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu

770 775 780

Glu Gln Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr

785 790 795 800

Gln Pro Leu Gly Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

805 810 815

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

820 825 830

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

835 840 845

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr

850 855 860

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

865 870 875 880

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

885 890 895

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

900 905 910

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

915 920 925

Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val

930 935 940

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

945 950 955 960

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

965 970 975

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

980 985 990

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

995 1000 1005

Ser Pro Gly Lys

1010

<210> 64

<211> 999

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 64

Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala Gly Asp

1 5 10 15

Ser Leu Asp Cys Gly Gly Arg Gly Leu Ala Ala Leu Pro Gly Asp Leu

20 25 30

Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Lys Leu Ser Glu

35 40 45

Ile Asp Pro Ala Gly Phe Glu Asp Leu Pro Asn Leu Gln Glu Val Tyr

50 55 60

Leu Asn Asn Asn Glu Leu Thr Ala Val Pro Ser Leu Gly Ala Ala Ser

65 70 75 80

Ser His Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Arg Ser Val

85 90 95

Glu Gly Ser Gln Leu Lys Ala Tyr Leu Ser Leu Glu Val Leu Asp Leu

100 105 110

Ser Leu Asn Asn Ile Thr Glu Val Arg Asn Thr Cys Phe Pro His Gly

115 120 125

Pro Pro Ile Lys Glu Leu Asn Leu Ala Gly Asn Arg Ile Gly Thr Leu

130 135 140

Glu Leu Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr Leu Arg

145 150 155 160

Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Arg Ala Phe Lys Leu

165 170 175

Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg Leu Ile

180 185 190

Glu Gly Leu Thr Phe Gln Gly Leu Asn Ser Leu Glu Val Leu Lys Leu

195 200 205

Gln Arg Asn Asn Ile Ser Lys Leu Thr Asp Gly Ala Phe Trp Gly Leu

210 215 220

Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val Glu Val

225 230 235 240

Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu His Leu

245 250 255

Ser Asn Asn Ser Ile Ala Arg Ile His Arg Lys Gly Trp Ser Phe Cys

260 265 270

Gln Lys Leu His Glu Leu Val Leu Ser Phe Asn Asn Leu Thr Arg Leu

275 280 285

Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Val Leu Arg Leu

290 295 300

Ser His Asn Ser Ile Ser His Ile Ala Glu Gly Ala Phe Lys Gly Leu

305 310 315 320

Arg Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser Gly Thr

325 330 335

Ile Glu Asp Thr Ser Gly Ala Phe Ser Gly Leu Asp Ser Leu Ser Lys

340 345 350

Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg Ala Phe

355 360 365

Ser Gly Leu Glu Gly Leu Glu His Leu Asn Leu Gly Gly Asn Ala Ile

370 375 380

Arg Ser Val Gln Phe Asp Ala Phe Val Lys Met Lys Asn Leu Lys Glu

385 390 395 400

Leu His Ile Ser Ser Asp Ser Phe Leu Cys Asp Cys Gln Leu Lys Trp

405 410 415

Leu Pro Pro Trp Leu Ile Gly Arg Met Leu Gln Ala Phe Val Thr Ala

420 425 430

Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe Ser Val

435 440 445

Pro Pro Glu Ser Phe Val Cys Asp Asp Phe Leu Lys Pro Gln Ile Ile

450 455 460

Thr Gln Pro Glu Thr Thr Met Ala Met Val Gly Lys Asp Ile Arg Phe

465 470 475 480

Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe Ala Trp

485 490 495

Lys Lys Asp Asn Glu Val Leu Thr Asn Ala Asp Met Glu Asn Phe Val

500 505 510

His Val His Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr Ile Leu

515 520 525

His Leu Arg Gln Val Thr Phe Gly His Glu Gly Arg Tyr Gln Cys Val

530 535 540

Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg Leu Thr

545 550 555 560

Val Asn Val Leu Pro Ser Phe Thr Lys Thr Pro His Asp Ile Thr Ile

565 570 575

Arg Thr Thr Thr Val Ala Arg Leu Glu Cys Ala Ala Thr Gly His Pro

580 585 590

Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe Pro Ala

595 600 605

Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val Phe Phe

610 615 620

Ile Thr Asp Val Lys Ile Asp Asp Ala Gly Val Tyr Ser Cys Thr Ala

625 630 635 640

Gln Asn Ser Ala Gly Ser Ile Ser Ala Asn Ala Thr Leu Thr Val Leu

645 650 655

Glu Thr Pro Ser Leu Val Val Pro Leu Glu Asp Arg Val Val Ser Val

660 665 670

Gly Glu Thr Val Ala Leu Gln Cys Lys Ala Thr Gly Asn Pro Pro Pro

675 680 685

Arg Ile Thr Trp Phe Lys Gly Asp Arg Pro Leu Ser Leu Thr Glu Arg

690 695 700

His His Leu Thr Pro Asp Asn Gln Leu Leu Val Val Gln Asn Val Val

705 710 715 720

Ala Glu Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Thr Leu Gly

725 730 735

Thr Glu Arg Ala His Ser Gln Leu Ser Val Leu Pro Ala Ala Gly Cys

740 745 750

Arg Lys Asp Gly Thr Thr Val Gly Ile Phe Gly Gly Gly Gly Ser Glu

755 760 765

Pro Lys Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro

770 775 780

Glu Leu Leu Gly Gly Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys

785 790 795 800

Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val

805 810 815

Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp

820 825 830

Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr

835 840 845

Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp

850 855 860

Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu

865 870 875 880

Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg

885 890 895

Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys

900 905 910

Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp

915 920 925

Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys

930 935 940

Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser

945 950 955 960

Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser

965 970 975

Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser

980 985 990

Leu Ser Leu Ser Pro Gly Lys

995

<210> 65

<211> 2997

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 65

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggcg gtggcggatc cgagccaaag tcctctgata agacacacac ctctccacca 2340

tgcccagcac cagagctgct gggaggacca agcgtgttcc tgtttcctcc aaagcccaag 2400

gacacactga tgatctccag gacaccagag gtgacctgcg tggtggtgga cgtgagccac 2460

gaggaccccg aggtgaagtt caactggtac gtggatggcg tggaggtgca caatgccaag 2520

accaagccca gagaggagca gtacaactct acctataggg tggtgagcgt gctgacagtg 2580

ctgcaccagg actggctgaa cggcaaggag tataagtgca aggtgagcaa taaggccctg 2640

cctgccccaa tcgagaagac aatctccaag gccaagggcc agccaagaga gccccaggtg 2700

tacaccctgc cccctagcag ggatgagctg acaaagaacc aggtgtccct gacctgtctg 2760

gtgaagggct tttatccctc cgacatcgcc gtggagtggg agtctaatgg ccagcctgag 2820

aataactaca agacaacccc acccgtgctg gattctgacg gcagcttctt tctgtattct 2880

aagctgaccg tggacaagag caggtggcag cagggcaacg tgttcagctg ctccgtgatg 2940

cacgaagcac tgcacaatca ctacacccag aaatcactgt cactgagccc tggcaaa 2997

<210> 66

<211> 3000

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 66

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggcg gtggcggatc cgagcctcgg ggccctacca tcaagccctg ccccccttgc 2340

aagtgccctg cccctaatct gctgggcgga ccctccgtgt tcctgtttcc tccaaagccc 2400

aaggacacac tgatgatctc caggacacca gaggtgacct gcgtggtggt ggacgtgagc 2460

cacgaggacc ccgaggtgaa gttcaactgg tacgtggatg gcgtggaggt gcacaatgcc 2520

aagaccaagc ccagagagga gcagtacaac tctacctata gggtggtgag cgtgctgaca 2580

gtgctgcacc aggactggct gaacggcaag gagtataagt gcaaggtgag caataaggcc 2640

ctgcctgccc caatcgagaa gacaatctcc aaggccaagg gccagccaag agagccccag 2700

gtgtacaccc tgccccctag cagggatgag ctgacaaaga accaggtgtc cctgacctgt 2760

ctggtgaagg gcttttatcc ctccgacatc gccgtggagt gggagtctaa tggccagcct 2820

gagaataact acaagacaac cccacccgtg ctggattctg acggcagctt ctttctgtat 2880

tctaagctga ccgtggacaa gagcaggtgg cagcagggca acgtgttcag ctgctccgtg 2940

atgcacgaag cactgcacaa tcactacacc cagaaatcac tgtcactgag ccctggcaaa 3000

3000

<210> 67

<211> 3036

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 67

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggcg gtggcggatc ccgcaacacc ggccgcggcg gcgaggagaa gaagaaggag 2340

aaggagaagg aggagcagga ggagcgcgag accaagaccc ccgagtgccc cagccacacc 2400

cagcccctgg gcgtgttcct gtttcctcca aagcccaagg acacactgat gatctccagg 2460

acaccagagg tgacctgcgt ggtggtggac gtgagccacg aggaccccga ggtgaagttc 2520

aactggtacg tggatggcgt ggaggtgcac aatgccaaga ccaagcccag agaggagcag 2580

tacaactcta cctatagggt ggtgagcgtg ctgacagtgc tgcaccagga ctggctgaac 2640

ggcaaggagt ataagtgcaa ggtgagcaat aaggccctgc ctgccccaat cgagaagaca 2700

atctccaagg ccaagggcca gccaagagag ccccaggtgt acaccctgcc ccctagcagg 2760

gatgagctga caaagaacca ggtgtccctg acctgtctgg tgaagggctt ttatccctcc 2820

gacatcgccg tggagtggga gtctaatggc cagcctgaga ataactacaa gacaacccca 2880

cccgtgctgg attctgacgg cagcttcttt ctgtattcta agctgaccgt ggacaagagc 2940

aggtggcagc agggcaacgt gttcagctgc tccgtgatgc acgaagcact gcacaatcac 3000

tacacccaga aatcactgtc actgagccct ggcaaa 3036

<210> 68

<211> 2997

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 68

gctgggcctc gggctccttg tgctgccgcc tgcacatgtg caggcgattc cctggactgc 60

ggcggcagag gcctggccgc cctgcctggc gatctgccat cctggacccg gagcctgaac 120

ctgagctaca acaagctgag cgagatcgat cccgccggct ttgaggacct gcctaacctg 180

caggaggtgt atctgaacaa taacgagctg accgcggtac catccctggg cgctgcttca 240

tcacatgtcg tctctctctt tctgcagcac aacaagattc gcagcgtgga ggggagccag 300

ctgaaggcct acctttcctt agaagtgtta gatctgagtt tgaacaacat cacggaagtg 360

cggaacacct gctttccaca cggaccgcct ataaaggagc tcaacctggc aggcaatcgg 420

attggcaccc tggagttggg agcatttgat ggtctgtcac ggtcgctgct aactcttcgc 480

ctgagcaaaa acaggatcac ccagcttcct gtaagagcat tcaagctacc caggctgaca 540

caactggacc tcaatcggaa caggattcgg ctgatagagg gcctcacctt ccaggggctc 600

aacagcttgg aggtgctgaa gcttcagcga aacaacatca gcaaactgac agatggggcc 660

ttctggggac tgtccaagat gcatgtgctg cacctggagt acaacagcct ggtagaagtg 720

aacagcggct cgctctacgg cctcacggcc ctgcatcagc tccacctcag caacaattcc 780

atcgctcgca ttcaccgcaa gggctggagc ttctgccaga agctgcatga gttggtcctg 840

tccttcaaca acctgacacg gctggacgag gagagcctgg ccgagctgag cagcctgagt 900

gtcctgcgtc tcagccacaa ttccatcagc cacattgcgg agggtgcctt caagggactc 960

aggagcctgc gagtcttgga tctggaccat aacgagattt cgggcacaat agaggacacg 1020

agcggcgcct tctcagggct cgacagcctc agcaagctga ctctgtttgg aaacaagatc 1080

aagtctgtgg ctaagagagc attctcgggg ctggaaggcc tggagcacct gaaccttgga 1140

gggaatgcga tcagatctgt ccagtttgat gcctttgtga agatgaagaa tcttaaagag 1200

ctccatatca gcagcgacag cttcctgtgt gactgccagc tgaagtggct gcccccgtgg 1260

ctaattggca ggatgctgca ggcctttgtg acagccacct gtgcccaccc agaatcactg 1320

aagggtcaga gcattttctc tgtgccacca gagagtttcg tgtgcgatga cttcctgaag 1380

ccacagatca tcacccagcc agaaaccacc atggctatgg tgggcaagga catccggttt 1440

acatgctcag cagccagcag cagcagctcc cccatgacct ttgcctggaa gaaagacaat 1500

gaagtcctga ccaatgcaga catggagaac tttgtccacg tccacgcgca ggacggggaa 1560

gtgatggagt acaccaccat cctgcacctc cgtcaggtca ctttcgggca cgagggccgc 1620

taccaatgtg tcatcaccaa ccactttggc tccacctatt cacataaggc caggctcacc 1680

gtgaatgtgt tgccatcatt caccaaaacg ccccacgaca taaccatccg gaccaccacc 1740

gtggcccgcc tcgaatgtgc tgccacaggt cacccaaacc ctcagattgc ctggcagaag 1800

gatggaggca cggatttccc cgctgcccgt gagcgacgca tgcatgtcat gccggatgac 1860

gacgtgtttt tcatcactga tgtgaaaata gatgacgcag gggtttacag ctgtactgct 1920

cagaactcag ccggttctat ttcagctaat gccaccctga ctgtcctaga gaccccatcc 1980

ttggtggtcc ccttggaaga ccgtgtggta tctgtgggag aaacagtggc cctccaatgc 2040

aaagccacgg ggaaccctcc gccccgcatc acctggttca agggggaccg cccgctgagc 2100

ctcactgagc ggcaccacct gacccctgac aaccagctcc tggtggttca gaacgtggtg 2160

gcagaggatg cgggccgata tacctgtgag atgtccaaca ccctgggcac ggagcgagct 2220

cacagccagc tgagcgtcct gcccgcagca ggctgcagga aggatgggac cacggtaggc 2280

atcttcggcg gtggcggatc cgaaccgaaa tcttctgaca aaacccacac ctctccgccg 2340

tctccggctc cggaactgct gggtggttct tctgttttcc tgtttcctcc aaagcccaag 2400

gacacactga tgatctccag gacaccagag gtgacctgcg tggtggtgga cgtgagccac 2460

gaggaccccg aggtgaagtt caactggtac gtggatggcg tggaggtgca caatgccaag 2520

accaagccca gagaggagca gtacaactct acctataggg tggtgagcgt gctgacagtg 2580

ctgcaccagg actggctgaa cggcaaggag tataagtgca aggtgagcaa taaggccctg 2640

cctgccccaa tcgagaagac aatctccaag gccaagggcc agccaagaga gccccaggtg 2700

tacaccctgc cccctagcag ggatgagctg acaaagaacc aggtgtccct gacctgtctg 2760

gtgaagggct tttatccctc cgacatcgcc gtggagtggg agtctaatgg ccagcctgag 2820

aataactaca agacaacccc acccgtgctg gattctgacg gcagcttctt tctgtattct 2880

aagctgaccg tggacaagag caggtggcag cagggcaacg tgttcagctg ctccgtgatg 2940

cacgaagcac tgcacaatca ctacacccag aaatcactgt cactgagccc tggcaaa 2997

<210> 69

<211> 997

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 69

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Glu Pro Lys

755 760 765

Ser Ser Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu

770 775 780

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

785 790 795 800

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

805 810 815

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

820 825 830

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

835 840 845

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

850 855 860

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

865 870 875 880

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

885 890 895

Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln

900 905 910

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

915 920 925

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

930 935 940

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

945 950 955 960

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

965 970 975

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

980 985 990

Leu Ser Pro Gly Lys

995

<210> 70

<211> 998

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 70

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Glu Pro Arg

755 760 765

Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn

770 775 780

Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp

785 790 795 800

Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp

805 810 815

Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly

820 825 830

Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn

835 840 845

Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp

850 855 860

Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro

865 870 875 880

Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu

885 890 895

Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn

900 905 910

Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile

915 920 925

Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr

930 935 940

Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys

945 950 955 960

Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys

965 970 975

Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu

980 985 990

Ser Leu Ser Pro Gly Lys

995

<210> 71

<211> 1010

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 71

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Arg Asn Thr

755 760 765

Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln

770 775 780

Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro

785 790 795 800

Leu Gly Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

805 810 815

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

820 825 830

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

835 840 845

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

850 855 860

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

865 870 875 880

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

885 890 895

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

900 905 910

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

915 920 925

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

930 935 940

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

945 950 955 960

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

965 970 975

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

980 985 990

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

995 1000 1005

Gly Lys

1010

<210> 72

<211> 997

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 72

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Glu Pro Lys

755 760 765

Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu

770 775 780

Leu Gly Gly Ser Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

785 790 795 800

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

805 810 815

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

820 825 830

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

835 840 845

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

850 855 860

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

865 870 875 880

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

885 890 895

Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln

900 905 910

Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala

915 920 925

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

930 935 940

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

945 950 955 960

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

965 970 975

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

980 985 990

Leu Ser Pro Gly Lys

995

<210> 73

<211> 2991

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 73

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatccgagcc aaagtcctct gataagacac acacctctcc accatgccca 2340

gcaccagagc tgctgggagg accaagcgtg ttcctgtttc ctccaaagcc caaggacaca 2400

ctgatgatct ccaggacacc agaggtgacc tgcgtggtgg tggacgtgag ccacgaggac 2460

cccgaggtga agttcaactg gtacgtggat ggcgtggagg tgcacaatgc caagaccaag 2520

cccagagagg agcagtacaa ctctacctat agggtggtga gcgtgctgac agtgctgcac 2580

caggactggc tgaacggcaa ggagtataag tgcaaggtga gcaataaggc cctgcctgcc 2640

ccaatcgaga agacaatctc caaggccaag ggccagccaa gagagcccca ggtgtacacc 2700

ctgcccccta gcagggatga gctgacaaag aaccaggtgt ccctgacctg tctggtgaag 2760

ggcttttatc cctccgacat cgccgtggag tgggagtcta atggccagcc tgagaataac 2820

tacaagacaa ccccacccgt gctggattct gacggcagct tctttctgta ttctaagctg 2880

accgtggaca agagcaggtg gcagcagggc aacgtgttca gctgctccgt gatgcacgaa 2940

gcactgcaca atcactacac ccagaaatca ctgtcactga gccctggcaa a 2991

<210> 74

<211> 2994

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 74

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatccgagcc tcggggccct accatcaagc cctgcccccc ttgcaagtgc 2340

cctgccccta atctgctggg cggaccctcc gtgttcctgt ttcctccaaa gcccaaggac 2400

acactgatga tctccaggac accagaggtg acctgcgtgg tggtggacgt gagccacgag 2460

gaccccgagg tgaagttcaa ctggtacgtg gatggcgtgg aggtgcacaa tgccaagacc 2520

aagcccagag aggagcagta caactctacc tatagggtgg tgagcgtgct gacagtgctg 2580

caccaggact ggctgaacgg caaggagtat aagtgcaagg tgagcaataa ggccctgcct 2640

gccccaatcg agaagacaat ctccaaggcc aagggccagc caagagagcc ccaggtgtac 2700

accctgcccc ctagcaggga tgagctgaca aagaaccagg tgtccctgac ctgtctggtg 2760

aagggctttt atccctccga catcgccgtg gagtgggagt ctaatggcca gcctgagaat 2820

aactacaaga caaccccacc cgtgctggat tctgacggca gcttctttct gtattctaag 2880

ctgaccgtgg acaagagcag gtggcagcag ggcaacgtgt tcagctgctc cgtgatgcac 2940

gaagcactgc acaatcacta cacccagaaa tcactgtcac tgagccctgg caaa 2994

<210> 75

<211> 3030

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 75

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatcccgcaa caccggccgc ggcggcgagg agaagaagaa ggagaaggag 2340

aaggaggagc aggaggagcg cgagaccaag acccccgagt gccccagcca cacccagccc 2400

ctgggcgtgt tcctgtttcc tccaaagccc aaggacacac tgatgatctc caggacacca 2460

gaggtgacct gcgtggtggt ggacgtgagc cacgaggacc ccgaggtgaa gttcaactgg 2520

tacgtggatg gcgtggaggt gcacaatgcc aagaccaagc ccagagagga gcagtacaac 2580

tctacctata gggtggtgag cgtgctgaca gtgctgcacc aggactggct gaacggcaag 2640

gagtataagt gcaaggtgag caataaggcc ctgcctgccc caatcgagaa gacaatctcc 2700

aaggccaagg gccagccaag agagccccag gtgtacaccc tgccccctag cagggatgag 2760

ctgacaaaga accaggtgtc cctgacctgt ctggtgaagg gcttttatcc ctccgacatc 2820

gccgtggagt gggagtctaa tggccagcct gagaataact acaagacaac cccacccgtg 2880

ctggattctg acggcagctt ctttctgtat tctaagctga ccgtggacaa gagcaggtgg 2940

cagcagggca acgtgttcag ctgctccgtg atgcacgaag cactgcacaa tcactacacc 3000

cagaaatcac tgtcactgag ccctggcaaa 3030

<210> 76

<211> 2991

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 76

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatccgaacc gaaatcttct gacaaaaccc acacctctcc gccgtctccg 2340

gctccggaac tgctgggtgg ttcttctgtt ttcctgtttc ctccaaagcc caaggacaca 2400

ctgatgatct ccaggacacc agaggtgacc tgcgtggtgg tggacgtgag ccacgaggac 2460

cccgaggtga agttcaactg gtacgtggat ggcgtggagg tgcacaatgc caagaccaag 2520

cccagagagg agcagtacaa ctctacctat agggtggtga gcgtgctgac agtgctgcac 2580

caggactggc tgaacggcaa ggagtataag tgcaaggtga gcaataaggc cctgcctgcc 2640

ccaatcgaga agacaatctc caaggccaag ggccagccaa gagagcccca ggtgtacacc 2700

ctgcccccta gcagggatga gctgacaaag aaccaggtgt ccctgacctg tctggtgaag 2760

ggcttttatc cctccgacat cgccgtggag tgggagtcta atggccagcc tgagaataac 2820

tacaagacaa ccccacccgt gctggattct gacggcagct tctttctgta ttctaagctg 2880

accgtggaca agagcaggtg gcagcagggc aacgtgttca gctgctccgt gatgcacgaa 2940

gcactgcaca atcactacac ccagaaatca ctgtcactga gccctggcaa a 2991

<210> 77

<211> 997

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 77

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Glu Pro Lys

755 760 765

Ser Ser Asp Lys Thr His Thr Ser Pro Pro Cys Pro Ala Pro Glu Leu

770 775 780

Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val

785 790 795 800

Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val

805 810 815

Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val

820 825 830

Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser

835 840 845

Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met

850 855 860

Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala

865 870 875 880

Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro

885 890 895

Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln

900 905 910

Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr

915 920 925

Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr

930 935 940

Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu

945 950 955 960

Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser

965 970 975

Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser

980 985 990

Arg Thr Pro Gly Lys

995

<210> 78

<211> 998

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 78

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Glu Pro Arg

755 760 765

Gly Pro Thr Ile Lys Pro Cys Pro Pro Cys Lys Cys Pro Ala Pro Asn

770 775 780

Leu Leu Gly Gly Pro Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp

785 790 795 800

Val Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp

805 810 815

Val Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn

820 825 830

Val Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn

835 840 845

Ser Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp

850 855 860

Met Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro

865 870 875 880

Ala Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala

885 890 895

Pro Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys

900 905 910

Gln Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile

915 920 925

Tyr Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn

930 935 940

Thr Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys

945 950 955 960

Leu Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys

965 970 975

Ser Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe

980 985 990

Ser Arg Thr Pro Gly Lys

995

<210> 79

<211> 1010

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 79

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Arg Asn Thr

755 760 765

Gly Arg Gly Gly Glu Glu Lys Lys Lys Glu Lys Glu Lys Glu Glu Gln

770 775 780

Glu Glu Arg Glu Thr Lys Thr Pro Glu Cys Pro Ser His Thr Gln Pro

785 790 795 800

Leu Gly Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val Leu Met Ile

805 810 815

Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val Ser Glu Asp

820 825 830

Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val Glu Val His

835 840 845

Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser Thr Leu Arg

850 855 860

Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met Ser Gly Lys

865 870 875 880

Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala Pro Ile Glu

885 890 895

Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro Gln Val Tyr

900 905 910

Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln Val Thr Leu

915 920 925

Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr Val Glu Trp

930 935 940

Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr Glu Pro Val

945 950 955 960

Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu Arg Val Glu

965 970 975

Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser Val Val His

980 985 990

Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser Arg Thr Pro

995 1000 1005

Gly Lys

1010

<210> 80

<211> 997

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 80

Ala Gln Ala Gly Pro Arg Ala Pro Cys Ala Ala Ala Cys Thr Cys Ala

1 5 10 15

Gly Asp Ser Leu Asp Cys Ser Gly Arg Gly Leu Ala Thr Leu Pro Arg

20 25 30

Asp Leu Pro Ser Trp Thr Arg Ser Leu Asn Leu Ser Tyr Asn Arg Leu

35 40 45

Ser Glu Ile Asp Ser Ala Ala Phe Glu Asp Leu Thr Asn Leu Gln Glu

50 55 60

Val Tyr Leu Asn Ser Asn Glu Leu Thr Ala Ile Pro Ser Leu Gly Ala

65 70 75 80

Ala Ser Ile Gly Val Val Ser Leu Phe Leu Gln His Asn Lys Ile Leu

85 90 95

Ser Val Asp Gly Ser Gln Leu Lys Ser Tyr Leu Ser Leu Glu Val Leu

100 105 110

Asp Leu Ser Ser Asn Asn Ile Thr Glu Ile Arg Ser Ser Cys Phe Pro

115 120 125

Asn Gly Leu Arg Ile Arg Glu Leu Asn Leu Ala Ser Asn Arg Ile Ser

130 135 140

Ile Leu Glu Ser Gly Ala Phe Asp Gly Leu Ser Arg Ser Leu Leu Thr

145 150 155 160

Leu Arg Leu Ser Lys Asn Arg Ile Thr Gln Leu Pro Val Lys Ala Phe

165 170 175

Lys Leu Pro Arg Leu Thr Gln Leu Asp Leu Asn Arg Asn Arg Ile Arg

180 185 190

Leu Ile Glu Gly Leu Thr Phe Gln Gly Leu Asp Ser Leu Glu Val Leu

195 200 205

Arg Leu Gln Arg Asn Asn Ile Ser Arg Leu Thr Asp Gly Ala Phe Trp

210 215 220

Gly Leu Ser Lys Met His Val Leu His Leu Glu Tyr Asn Ser Leu Val

225 230 235 240

Glu Val Asn Ser Gly Ser Leu Tyr Gly Leu Thr Ala Leu His Gln Leu

245 250 255

His Leu Ser Asn Asn Ser Ile Ser Arg Ile Gln Arg Asp Gly Trp Ser

260 265 270

Phe Cys Gln Lys Leu His Glu Leu Ile Leu Ser Phe Asn Asn Leu Thr

275 280 285

Arg Leu Asp Glu Glu Ser Leu Ala Glu Leu Ser Ser Leu Ser Ile Leu

290 295 300

Arg Leu Ser His Asn Ala Ile Ser His Ile Ala Glu Gly Ala Phe Lys

305 310 315 320

Gly Leu Lys Ser Leu Arg Val Leu Asp Leu Asp His Asn Glu Ile Ser

325 330 335

Gly Thr Ile Glu Asp Thr Ser Gly Ala Phe Thr Gly Leu Asp Asn Leu

340 345 350

Ser Lys Leu Thr Leu Phe Gly Asn Lys Ile Lys Ser Val Ala Lys Arg

355 360 365

Ala Phe Ser Gly Leu Glu Ser Leu Glu His Leu Asn Leu Gly Glu Asn

370 375 380

Ala Ile Arg Ser Val Gln Phe Asp Ala Phe Ala Lys Met Lys Asn Leu

385 390 395 400

Lys Glu Leu Tyr Ile Ser Ser Glu Ser Phe Leu Cys Asp Cys Gln Leu

405 410 415

Lys Trp Leu Pro Pro Trp Leu Met Gly Arg Met Leu Gln Ala Phe Val

420 425 430

Thr Ala Thr Cys Ala His Pro Glu Ser Leu Lys Gly Gln Ser Ile Phe

435 440 445

Ser Val Leu Pro Asp Ser Phe Val Cys Asp Asp Phe Pro Lys Pro Gln

450 455 460

Ile Ile Thr Gln Pro Glu Thr Thr Met Ala Val Val Gly Lys Asp Ile

465 470 475 480

Arg Phe Thr Cys Ser Ala Ala Ser Ser Ser Ser Ser Pro Met Thr Phe

485 490 495

Ala Trp Lys Lys Asp Asn Glu Val Leu Ala Asn Ala Asp Met Glu Asn

500 505 510

Phe Ala His Val Arg Ala Gln Asp Gly Glu Val Met Glu Tyr Thr Thr

515 520 525

Ile Leu His Leu Arg His Val Thr Phe Gly His Glu Gly Arg Tyr Gln

530 535 540

Cys Ile Ile Thr Asn His Phe Gly Ser Thr Tyr Ser His Lys Ala Arg

545 550 555 560

Leu Thr Val Asn Val Leu Pro Ser Phe Thr Lys Ile Pro His Asp Ile

565 570 575

Ala Ile Arg Thr Gly Thr Thr Ala Arg Leu Glu Cys Ala Ala Thr Gly

580 585 590

His Pro Asn Pro Gln Ile Ala Trp Gln Lys Asp Gly Gly Thr Asp Phe

595 600 605

Pro Ala Ala Arg Glu Arg Arg Met His Val Met Pro Asp Asp Asp Val

610 615 620

Phe Phe Ile Thr Asp Val Lys Ile Asp Asp Met Gly Val Tyr Ser Cys

625 630 635 640

Thr Ala Gln Asn Ser Ala Gly Ser Val Ser Ala Asn Ala Thr Leu Thr

645 650 655

Val Leu Glu Thr Pro Ser Leu Ala Val Pro Leu Glu Asp Arg Val Val

660 665 670

Thr Val Gly Glu Thr Val Ala Phe Gln Cys Lys Ala Thr Gly Ser Pro

675 680 685

Thr Pro Arg Ile Thr Trp Leu Lys Gly Gly Arg Pro Leu Ser Leu Thr

690 695 700

Glu Arg His His Phe Thr Pro Gly Asn Gln Leu Leu Val Val Gln Asn

705 710 715 720

Val Met Ile Asp Asp Ala Gly Arg Tyr Thr Cys Glu Met Ser Asn Pro

725 730 735

Leu Gly Thr Glu Arg Ala His Ser Gln Leu Ser Ile Leu Pro Thr Pro

740 745 750

Gly Cys Arg Lys Asp Gly Thr Thr Gly Gly Gly Gly Ser Glu Pro Lys

755 760 765

Ser Ser Asp Lys Thr His Thr Ser Pro Pro Ser Pro Ala Pro Glu Leu

770 775 780

Leu Gly Gly Ser Ser Val Phe Ile Phe Pro Pro Lys Ile Lys Asp Val

785 790 795 800

Leu Met Ile Ser Leu Ser Pro Ile Val Thr Cys Val Val Val Asp Val

805 810 815

Ser Glu Asp Asp Pro Asp Val Gln Ile Ser Trp Phe Val Asn Asn Val

820 825 830

Glu Val His Thr Ala Gln Thr Gln Thr His Arg Glu Asp Tyr Asn Ser

835 840 845

Thr Leu Arg Val Val Ser Ala Leu Pro Ile Gln His Gln Asp Trp Met

850 855 860

Ser Gly Lys Glu Phe Lys Cys Lys Val Asn Asn Lys Asp Leu Pro Ala

865 870 875 880

Pro Ile Glu Arg Thr Ile Ser Lys Pro Lys Gly Ser Val Arg Ala Pro

885 890 895

Gln Val Tyr Val Leu Pro Pro Pro Glu Glu Glu Met Thr Lys Lys Gln

900 905 910

Val Thr Leu Thr Cys Met Val Thr Asp Phe Met Pro Glu Asp Ile Tyr

915 920 925

Val Glu Trp Thr Asn Asn Gly Lys Thr Glu Leu Asn Tyr Lys Asn Thr

930 935 940

Glu Pro Val Leu Asp Ser Asp Gly Ser Tyr Phe Met Tyr Ser Lys Leu

945 950 955 960

Arg Val Glu Lys Lys Asn Trp Val Glu Arg Asn Ser Tyr Ser Cys Ser

965 970 975

Val Val His Glu Gly Leu His Asn His His Thr Thr Lys Ser Phe Ser

980 985 990

Arg Thr Pro Gly Lys

995

<210> 81

<211> 2991

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 81

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatccgagcc aaagtcctct gataagacac acacctctcc accatgccca 2340

gcaccagagc tgctgggagg accaagcgtg ttcatcttcc cacccaagat caaggacgtg 2400

ctgatgatct ccctgtcccc catcgtgacc tgcgtggtgg tggacgtgtc cgaggacgac 2460

cccgacgtgc agatcagttg gttcgtgaac aacgtggaag tgcacaccgc ccagacccag 2520

acccacagag aggactacaa ctccaccctg cgggtggtgt ccgccctgcc catccagcac 2580

caggactgga tgtccggcaa agaattcaag tgcaaagtga acaacaagga cctgcctgcc 2640

cccatcgagc ggaccatctc caagcccaag ggctccgtgc gggctcccca ggtgtacgtg 2700

ctgccccctc cagaggaaga gatgaccaag aagcaggtca cactgacctg catggtcacc 2760

gacttcatgc ccgaggacat ctacgtggaa tggaccaaca atggcaagac cgagctgaac 2820

tacaagaaca ccgagcctgt gctggactcc gacggctcct acttcatgta ctccaagctg 2880

cgggtggaaa agaagaactg ggtcgagcgg aactcctact cctgctccgt ggtgcacgag 2940

ggcctgcaca accaccacac caccaagtcc ttctcccgga cccccggcaa a 2991

<210> 82

<211> 2994

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 82

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatccgagcc tcggggccct accatcaagc cctgcccccc ttgcaagtgc 2340

cctgccccta atctgctggg cggaccctcc gtgttcatct tcccacccaa gatcaaggac 2400

gtgctgatga tctccctgtc ccccatcgtg acctgcgtgg tggtggacgt gtccgaggac 2460

gaccccgacg tgcagatcag ttggttcgtg aacaacgtgg aagtgcacac cgcccagacc 2520

cagacccaca gagaggacta caactccacc ctgcgggtgg tgtccgccct gcccatccag 2580

caccaggact ggatgtccgg caaagaattc aagtgcaaag tgaacaacaa ggacctgcct 2640

gcccccatcg agcggaccat ctccaagccc aagggctccg tgcgggctcc ccaggtgtac 2700

gtgctgcccc ctccagagga agagatgacc aagaagcagg tcacactgac ctgcatggtc 2760

accgacttca tgcccgagga catctacgtg gaatggacca acaatggcaa gaccgagctg 2820

aactacaaga acaccgagcc tgtgctggac tccgacggct cctacttcat gtactccaag 2880

ctgcgggtgg aaaagaagaa ctgggtcgag cggaactcct actcctgctc cgtggtgcac 2940

gagggcctgc acaaccacca caccaccaag tccttctccc ggacccccgg caaa 2994

<210> 83

<211> 3030

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 83

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatcccgcaa caccggccgc ggcggcgagg agaagaagaa ggagaaggag 2340

aaggaggagc aggaggagcg cgagaccaag acccccgagt gccccagcca cacccagccc 2400

ctgggcgtgt tcatcttccc acccaagatc aaggacgtgc tgatgatctc cctgtccccc 2460

atcgtgacct gcgtggtggt ggacgtgtcc gaggacgacc ccgacgtgca gatcagttgg 2520

ttcgtgaaca acgtggaagt gcacaccgcc cagacccaga cccacagaga ggactacaac 2580

tccaccctgc gggtggtgtc cgccctgccc atccagcacc aggactggat gtccggcaaa 2640

gaattcaagt gcaaagtgaa caacaaggac ctgcctgccc ccatcgagcg gaccatctcc 2700

aagcccaagg gctccgtgcg ggctccccag gtgtacgtgc tgccccctcc agaggaagag 2760

atgaccaaga agcaggtcac actgacctgc atggtcaccg acttcatgcc cgaggacatc 2820

tacgtggaat ggaccaacaa tggcaagacc gagctgaact acaagaacac cgagcctgtg 2880

ctggactccg acggctccta cttcatgtac tccaagctgc gggtggaaaa gaagaactgg 2940

gtcgagcgga actcctactc ctgctccgtg gtgcacgagg gcctgcacaa ccaccacacc 3000

accaagtcct tctcccggac ccccggcaaa 3030

<210> 84

<211> 2991

<212> DNA

<213> 人工序列(Artificial Sequence)

<220>

<223> 融合蛋白

<400> 84

gctcaggctg gacctagggc tccttgcgct gccgcctgca cctgtgcagg cgattctctg 60

gactgcagcg gccggggcct ggccacactg cccagggacc tgccttcctg gaccagatct 120

ctgaacctga gctacaatcg gctgtccgag atcgattctg ccgcctttga ggacctgaca 180

aatctgcagg aggtgtatct gaacagcaat gagctgaccg caatcccctc cctgggagca 240

gcctctatcg gcgtggtgag cctgttcctg cagcacaaca agatcctgag cgtggatggc 300

tcccagctga agagctacct gtctctggag gtgctggacc tgagctccaa caatatcacc 360

gagatcagat ctagctgttt tcctaatggc ctgcggatca gagagctgaa cctggcctct 420

aatcggatca gcatcctgga gtccggcgcc ttcgatggcc tgagcagatc cctgctgaca 480

ctgcgcctgt ccaagaaccg gatcacccag ctgcccgtga aggcctttaa gctgcctagg 540

ctgacacagc tggacctgaa ccggaataga atcaggctga tcgagggcct gaccttccag 600

ggcctggata gcctggaggt gctgcgcctg cagcggaaca atatctcccg cctgacagac 660

ggagcatttt ggggcctgtc taagatgcac gtgctgcacc tggagtacaa tagcctggtg 720

gaggtgaact ctggcagcct gtatggcctg accgccctgc accagctgca cctgtccaac 780

aatagcatca gcagaatcca gagggatggc tggtccttct gccagaagct gcacgagctg 840

atcctgtctt ttaacaatct gaccaggctg gacgaggaga gcctggcaga gctgtcctct 900

ctgtccatcc tgcgcctgtc tcacaatgcc atcagccaca tcgccgaggg cgcctttaag 960

ggcctgaaga gcctgagggt gctggatctg gaccacaacg agatctctgg caccatcgag 1020

gatacaagcg gcgccttcac aggcctggac aatctgtcca agctgaccct gtttggcaac 1080

aagatcaagt ctgtggccaa gcgggccttc tctggcctgg agagcctgga gcacctgaac 1140

ctgggcgaga atgccatcag atccgtgcag ttcgatgcct ttgccaagat gaagaatctg 1200

aaggagctgt acatcagctc cgagagcttc ctgtgcgact gtcagctgaa gtggctgcca 1260

ccttggctga tgggaaggat gctgcaggcc tttgtgaccg ccacatgcgc ccacccagag 1320

agcctgaagg gccagagcat cttctccgtg ctgcccgata gcttcgtgtg cgacgatttt 1380

cctaagccac agatcatcac ccagccagag acaacaatgg ccgtggtggg caaggacatc 1440

cggtttacat gttccgccgc ctctagctcc tctagcccca tgaccttcgc ctggaagaag 1500

gataacgagg tgctggccaa tgccgacatg gagaacttcg cccacgtgag agcccaggat 1560

ggcgaagtga tggagtatac cacaatcctg cacctgcggc acgtgacctt tggccacgag 1620

ggcagatacc agtgcatcat cacaaatcac ttcggctcta cctatagcca caaggccagg 1680

ctgacagtga acgtgctgcc tagctttacc aagatcccac acgacatcgc catcagaaca 1740

ggcaccacag caaggctgga gtgtgcagca accggacacc caaaccctca gatcgcatgg 1800

cagaaggatg gaggcacaga cttccctgca gcccgcgaga ggagaatgca cgtgatgcca 1860

gacgatgacg tgttctttat cacagatgtg aagatcgatg acatgggcgt gtactcctgc 1920

accgcacaga acagcgccgg cagcgtgtcc gccaacgcca ccctgaccgt gctggagaca 1980

ccatccctgg ccgtgcccct ggaggacagg gtggtgaccg tgggcgagac agtggccttt 2040

cagtgtaagg ccaccggctc tccaacacca aggatcacct ggctgaaggg cggcaggccc 2100

ctgagcctga cagagcgcca ccacttcacc cctggcaatc agctgctggt ggtgcagaac 2160

gtgatgatcg atgacgccgg caggtataca tgcgagatga gcaatcctct gggcaccgag 2220

agggcacact cccagctgtc tatcctgcct accccaggct gccggaagga tggcaccaca 2280

ggcggtggcg gatccgaacc gaaatcttct gacaaaaccc acacctctcc gccgtctccg 2340

gctccggaac tgctgggtgg ttcttctgtt ttcatcttcc cacccaagat caaggacgtg 2400

ctgatgatct ccctgtcccc catcgtgacc tgcgtggtgg tggacgtgtc cgaggacgac 2460

cccgacgtgc agatcagttg gttcgtgaac aacgtggaag tgcacaccgc ccagacccag 2520

acccacagag aggactacaa ctccaccctg cgggtggtgt ccgccctgcc catccagcac 2580

caggactgga tgtccggcaa agaattcaag tgcaaagtga acaacaagga cctgcctgcc 2640

cccatcgagc ggaccatctc caagcccaag ggctccgtgc gggctcccca ggtgtacgtg 2700

ctgccccctc cagaggaaga gatgaccaag aagcaggtca cactgacctg catggtcacc 2760

gacttcatgc ccgaggacat ctacgtggaa tggaccaaca atggcaagac cgagctgaac 2820

tacaagaaca ccgagcctgt gctggactcc gacggctcct acttcatgta ctccaagctg 2880

cgggtggaaa agaagaactg ggtcgagcgg aactcctact cctgctccgt ggtgcacgag 2940

ggcctgcaca accaccacac caccaagtcc ttctcccgga cccccggcaa a 2991

<210> 85

<211> 311

<212> PRT

<213> 人(Homo sapiens)

<400> 85

Met Gly Val Pro Thr Ala Leu Glu Ala Gly Ser Trp Arg Trp Gly Ser

1 5 10 15

Leu Leu Phe Ala Leu Phe Leu Ala Ala Ser Leu Gly Pro Val Ala Ala

20 25 30

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

50 55 60

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Thr Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

85 90 95

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

100 105 110

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn

115 120 125

Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr

130 135 140

Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val

145 150 155 160

His Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser

165 170 175

Asn Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn Ile Thr

180 185 190

Ala Ala Ala Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu

195 200 205

Pro Leu Ile Leu Leu Leu Val Tyr Lys Gln Arg Gln Ala Ala Ser Asn

210 215 220

Arg Arg Ala Gln Glu Leu Val Arg Met Asp Ser Asn Ile Gln Gly Ile

225 230 235 240

Glu Asn Pro Gly Phe Glu Ala Ser Pro Pro Ala Gln Gly Ile Pro Glu

245 250 255

Ala Lys Val Arg His Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser

260 265 270

Glu Ser Gly Arg His Leu Leu Ser Glu Pro Ser Thr Pro Leu Ser Pro

275 280 285

Pro Gly Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp

290 295 300

Ser Pro Asn Phe Glu Val Ile

305 310

<210> 86

<211> 309

<212> PRT

<213> 小鼠(Mus musculus)

<400> 86

Met Gly Val Pro Ala Val Pro Glu Ala Ser Ser Pro Arg Trp Gly Thr

1 5 10 15

Leu Leu Leu Ala Ile Phe Leu Ala Ala Ser Arg Gly Leu Val Ala Ala

20 25 30

Phe Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

35 40 45

Asn Ala Thr Leu Thr Cys Arg Ile Leu Gly Pro Val Ser Lys Gly His

50 55 60

Asp Val Thr Ile Tyr Lys Thr Trp Tyr Leu Ser Ser Arg Gly Glu Val

65 70 75 80

Gln Met Cys Lys Glu His Arg Pro Ile Arg Asn Phe Thr Leu Gln His

85 90 95

Leu Gln His His Gly Ser His Leu Lys Ala Asn Ala Ser His Asp Gln

100 105 110

Pro Gln Lys His Gly Leu Glu Leu Ala Ser Asp His His Gly Asn Phe

115 120 125

Ser Ile Thr Leu Arg Asn Val Thr Pro Arg Asp Ser Gly Leu Tyr Cys

130 135 140

Cys Leu Val Ile Glu Leu Lys Asn His His Pro Glu Gln Arg Phe Tyr

145 150 155 160

Gly Ser Met Glu Leu Gln Val Gln Ala Gly Lys Gly Ser Gly Ser Thr

165 170 175

Cys Met Ala Ser Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala Ala Ala

180 185 190

Leu Ala Thr Gly Ala Cys Ile Val Gly Ile Leu Cys Leu Pro Leu Ile

195 200 205

Leu Leu Leu Val Tyr Lys Gln Arg Gln Val Ala Ser His Arg Arg Ala

210 215 220

Gln Glu Leu Val Arg Met Asp Ser Ser Asn Thr Gln Gly Ile Glu Asn

225 230 235 240

Pro Gly Phe Glu Thr Thr Pro Pro Phe Gln Gly Met Pro Glu Ala Lys

245 250 255

Thr Arg Pro Pro Leu Ser Tyr Val Ala Gln Arg Gln Pro Ser Glu Ser

260 265 270

Gly Arg Tyr Leu Leu Ser Asp Pro Ser Thr Pro Leu Ser Pro Pro Gly

275 280 285

Pro Gly Asp Val Phe Phe Pro Ser Leu Asp Pro Val Pro Asp Ser Pro

290 295 300

Asn Ser Glu Ala Ile

305

<210> 87

<211> 4714

<212> DNA

<213> 人(Homo sapiens)

<400> 87

gggggcgggt gcctggagca cggcgctggg gccgcccgca gcgctcactc gctcgcactc 60

agtcgcggga ggcttccccg cgccggccgc gtcccgcccg ctccccggca ccagaagttc 120

ctctgcgcgt ccgacggcga catgggcgtc cccacggccc tggaggccgg cagctggcgc 180

tggggatccc tgctcttcgc tctcttcctg gctgcgtccc taggtccggt ggcagccttc 240

aaggtcgcca cgccgtattc cctgtatgtc tgtcccgagg ggcagaacgt caccctcacc 300

tgcaggctct tgggccctgt ggacaaaggg cacgatgtga ccttctacaa gacgtggtac 360

cgcagctcga ggggcgaggt gcagacctgc tcagagcgcc ggcccatccg caacctcacg 420

ttccaggacc ttcacctgca ccatggaggc caccaggctg ccaacaccag ccacgacctg 480

gctcagcgcc acgggctgga gtcggcctcc gaccaccatg gcaacttctc catcaccatg 540

cgcaacctga ccctgctgga tagcggcctc tactgctgcc tggtggtgga gatcaggcac 600

caccactcgg agcacagggt ccatggtgcc atgagctgtc aggtgcagac aggcaaagat 660

gcaccatcca actgtgtggt gtacccatcc tcctcccagg atagtgaaaa catcacggct 720

gcagccctgg ctacgggtgc ctgcatcgta ggaatcctct gcctccccct catcctgctc 780

ctggtctaca agcaaaggca ggcagcctcc aaccgccgtg cccaggagct ggtgcggatg 840

gacagcaaca ttcaagggat tgaaaacccc ggctttgaag cctcaccacc tgcccagggg 900

atacccgagg ccaaagtcag gcaccccctg tcctatgtgg cccagcggca gccttctgag 960

tctgggcggc atctgctttc ggagcccagc acccccctgt ctcctccagg ccccggagac 1020

gtcttcttcc catccctgga ccctgtccct gactctccaa actttgaggt catctagccc 1080

agctggggga cagtgggctg ttgtggctgg gtctggggca ggtgcatttg agccagggct 1140

ggctctgtga gtggcctcct tggcctcggc cctggttccc tccctcctgc tctgggctca 1200

gatactgtga catcccagaa gcccagcccc tcaacccctc tggatgctac atggggatgc 1260

tggacggctc agcccctgtt ccaaggattt tggggtgctg agattctccc ctagagacct 1320

gaaattcacc agctacagat gccaaatgac ttacatctta agaagtctca gaacgtccag 1380

cccttcagca gctctcgttc tgagacatga gccttgggat gtggcagcat cagtgggaca 1440

agatggacac tgggccaccc tcccaggcac cagacacagg gcacggtgga gagacttctc 1500

ccccgtggcc gccttggctc ccccgttttg cccgaggctg ctcttctgtc agacttcctc 1560

tttgtaccac agtggctctg gggccaggcc tgcctgccca ctggccatcg ccaccttccc 1620

cagctgcctc ctaccagcag tttctctgaa gatctgtcaa caggttaagt caatctgggg 1680

cttccactgc ctgcattcca gtccccagag cttggtggtc ccgaaacggg aagtacatat 1740

tggggcatgg tggcctccgt gagcaaatgg tgtcttgggc aatctgaggc caggacagat 1800

gttgccccac ccactggaga tggtgctgag ggaggtgggt ggggccttct gggaaggtga 1860

gtggagaggg gcacctgccc cccgccctcc ccatccccta ctcccactgc tcagcgcggg 1920

ccattgcaag ggtgccacac aatgtcttgt ccaccctggg acacttctga gtatgaagcg 1980

ggatgctatt aaaaactaca tggggaaaca ggtgcaaacc ctggagatgg attgtaagag 2040

ccagtttaaa tctgcactct gctgctcctc ccccaccccc accttccact ccatacaatc 2100

tgggcctggt ggagtcttcg cttcagagcc attcggccag gtgcgggtga tgttcccatc 2160

tcctgcttgt gggcatgccc tggctttgtt tttatacaca taggcaaggt gagtcctctg 2220

tggaattgtg attgaaggat tttaaagcag gggaggagag tagggggcat ctctgtacac 2280

tctgggggta aaacagggaa ggcagtgcct gagcatgggg acaggtgagg tggggctggg 2340

cagaccccct gtagcgttta gcaggatggg ggccccaggt actgtggaga gcatagtcca 2400

gcctgggcat ttgtctccta gcagcctaca ctggctctgc tgagctgggc ctgggtgctg 2460

aaagccagga tttggggcta ggcgggaaga tgttcgccca attgcttggg gggttggggg 2520

gatggaaaag gggagcacct ctaggctgcc tggcagcagt gagccctggg cctgtggcta 2580

cagccaggga accccacctg gacacatggc cctgcttcta agccccccag ttaggcccaa 2640

aggaatggtc cactgagggc ctcctgctct gcctgggctg ggccaggggc tttgaggaga 2700

gggtaaacat aggcccggag atggggctga cacctcgagt ggccagaata tgcccaaacc 2760

ccggcttctc ccttgtccct aggcagaggg gggtcccttc ttttgttccc tctggtcacc 2820

acaatgcttg atgccagctg ccataggaag agggtgctgg ctggccatgg tggcacacac 2880

ctgtcctccc agcactttgc agggctgagg tggaaggacc gcttaagccc aggtgttcaa 2940

ggctgctgtg agctgtgttc gagccactac actccagcct ggggacggag caaaactttg 3000

cctcaaaaca aattttaaaa agaaagaaag aaggaaagag ggtatgtttt tcacaattca 3060

tgggggcctg catggcagga gtggggacag gacacctgct gttcctggag tcgaaggaca 3120

agcccacagc ccagattccg gttctcccaa ctcaggaaga gcatgccctg ccctctgggg 3180

aggctggcct ggccccagcc ctcagctgct gaccttgagg cagagacaac ttctaagaat 3240

ttggctgcca gaccccaggc ctggctgctg ctgtgtggag agggaggcgg cccgcagcag 3300

aacagccacc gcacttcctc ctcagcttcc tctggtgcgg ccctgccctc tcttctctgg 3360

acccttttac aactgaacgc atctgggctt cgtggtttcc tgttttcagc gaaatttact 3420

ctgagctccc agttccatct tcatccatgg ccacaggccc tgcctacaac gcactaggga 3480

cgtccctccc tgctgctgct ggggaggggc aggctgctgg agccgccctc tgagttgccc 3540

tgggtgcgag aacatggcgc ctccaggggg cgggaggagc actaggggct ggggcaggag 3600

gctcctggag cgctggattc ctggcacagt ctgaggccct gagagggaaa tccatgcttt 3660

taagaactaa ttcattgtta ggagatcaat caggaattag gggccatctt acctatctcc 3720

tgacattcac agtttaatag agacttcctg cctttattcc ctcccaggga gaggctgaag 3780

gaatggaatt gaaagcacca tttggagggt tttgctgaca cagcggggac tgctcagcac 3840

tccctaaaaa cacaccatgg aggccactgg tgactgctgg tgggcaggct ggccctgcct 3900

gggggagtcc gtggcgatgg gcgctggggt ggaggtgcag gagccccagg acctgctttt 3960

caaaagactt ctgcctgacc agagctccca ctacatgcag tggcccaggg cagaggggct 4020

gatacatggc ctttttcagg gggtgctcct cgcggggtgg acttgggagt gtgcagtggg 4080

acagggggct gcaggggtcc tgccaccacc gagcaccaac ttggcccctg gggtcctgcc 4140

tcatgaatga ggccttcccc agggctggcc tgactgtgct gggggctggg ttaacgtttt 4200

ctcagggaac cacaatgcac gaaagaggaa ctggggttgc taaccaggat gctgggaaca 4260

aaggcctctt gaagcccagc cacagcccag ctgagcatga ggcccagccc atagacggca 4320

caggccacct ggcccattcc ctgggcattc cctgctttgc attgctgctt ctcttcaccc 4380

catggaggct atgtcaccct aactatcctg gaatgtgttg agagggattc tgaatgatca 4440

atatagcttg gtgagacagt gccgagatag atagccatgt ctgccttggg cacgggagag 4500

ggaagtggca gcatgcatgc tgtttcttgg ccttttctgt tagaatactt ggtgctttcc 4560

aacacacttt cacatgtgtt gtaacttgtt tgatccaccc ccttccctga aaatcctggg 4620

aggttttatt gctgccattt aacacagagg gcaatagagg ttctgaaagg tctgtgtctt 4680

gtcaaaacaa gtaaacggtg gaactacgac taaa 4714

<210> 88

<211> 4795

<212> DNA

<213> 小鼠(Mus musculus)

<400> 88

gagcattcac tctagcgagc gagcggcgtg tacagccggc tccctgggct cctggagtcc 60

cgcttgctcc aagcgcactc cagcagtctc tttctgctct tgcccggctc gacggcgaca 120

tgggtgtccc cgcggtccca gaggccagca gcccgcgctg gggaaccctg ctccttgcta 180

ttttcctggc tgcatccaga ggtctggtag cagccttcaa ggtcaccact ccatattctc 240

tctatgtgtg tcccgaggga cagaatgcca ccctcacctg caggattctg ggccccgtgt 300

ccaaagggca cgatgtgacc atctacaaga cgtggtacct cagctcacga ggcgaggtcc 360

agatgtgcaa agaacaccgg cccatacgca acttcacatt gcagcacctt cagcaccacg 420

gaagccacct gaaagccaac gccagccatg accagcccca gaagcatggg ctagagctag 480

cttctgacca ccacggtaac ttctctatca ccctgcgcaa tgtgacccca agggacagcg 540

gcctctactg ctgtctagtg atagaattaa aaaaccacca cccagaacaa cggttctacg 600

ggtccatgga gctacaggta caggcaggca aaggctcggg gtccacatgc atggcgtcta 660

atgagcagga cagtgacagc atcacggctg cggccctggc caccggcgcc tgcatcgtgg 720

gaatcctctg cctccccctt atcctgctgc tggtctataa gcagagacag gtggcctctc 780

accgccgtgc ccaggagttg gtgaggatgg acagcagcaa cacccaagga atcgaaaacc 840

caggcttcga gaccactcca cccttccagg ggatgcctga ggccaagacc aggccgccac 900

tgtcctatgt ggcccagcgg caaccttcgg agtcaggacg gtacctgctc tctgacccca 960

gcacacctct gtcgcctcca ggccctgggg acgtcttttt cccatcccta gatccagtcc 1020

ctgactcccc taactctgaa gccatctaaa ccagctgggg aaccatgaac catggtacct 1080

gggtcaggga tatgtgcact tgatctatgg ctggcccttg gacagtcttt taggcactga 1140

ctccagcttc cttgctcctg ctctgagcct agactctgct tttacaagat gcacagaccc 1200

tcccctatct ctttcagacg ctacttgggg ggcagggaga agatgttgga ttgctcatgg 1260

ctgttctcaa gatcttggga tgctgagttc tccctagaga cttgacttcg acagccacag 1320

atgtcagatg acctgcatcc tatgaacgtc cggcttggca agagcctttc ttcatggaaa 1380

ccagtagccc ggaggggatg aggtaggcac cttgccaccc tcccgggaga gagacacaag 1440

atgtgagaga ctcctgctca ctgtgggggt gtggctggcc tgcttgtttg cctgaggatg 1500

ctcctctgtt ggactgactc tatccccctg gattctggag cttggctggc ctatgtccca 1560

ccagaggagc atctcagcag ccttccacca gcaacctgag ggcctgccag cttcgtggct 1620

ctgggctctc attacctgta tggccgtcca cagagctcag tggccagagg ctttgaaaca 1680

ggaagtacat gtcaggttca ggaaccactg tgagctcatt agtgtcttga gcaatgtgag 1740

gcctggacca gtggacacgg agggagggtg gcgagaggat gatggggatg atgaggggaa 1800

cacgctccct tcctgtcctt gtcatccacc actaccacta ttcagtgtgg agcagtggca 1860

aaggtgaccg acctccacaa tgtcctagtg atgctggacc atttctaagt gtgaaagaga 1920

tgctattaaa aacagtatgt ggcaatggct gccaacagct gagtggactg gaggcactgg 1980

ctttaaggcc ctggaggtgc agggcccggt atggggatag ggatgggagt ttcagtgagg 2040

gcctagggat cactccgctt ctgaccactc ttcttctgag cctcacctca gggtgacctt 2100

caggcacaca gaagagcttg cccctggtcc gatactactc ttggctctca tctccagggt 2160

ttggcatgac ctgggcacac agggggagtc ttcagaaagg attttaaagc atgaaaagaa 2220

agggtagttc ttgtgaggta gggatgggca gctgatgttt gagagtgagg agggatacgg 2280

ctgggcagat cactctccag tctctagagg gaaagtagct ctaagtctgg gagagcagca 2340

gcccagtggt accatatgtc ttcttgcagc ttccactggc tgggctgaac tgggcatggg 2400

taggaaagct cctgttctgg gcctgcagcc agggagaacc ccattcattc cctgaggaca 2460

gatgggtggg gagagaagag agagtttcag gccgggaagc agcaataagc tatctgctgg 2520

ggacccagac aagttgtctg atgaggtcca agatgtggga tgccagttat acctggggct 2580

tggggatcct tagaggcttt gtatcatcat cataggagtg tcggggtggc cagggcatca 2640

aagccatgac ccctgtttta tcctcagggt ccactcttct gcaccatcca ttgctctaga 2700

tctatgcagt tactatagac agaatgtgtt gttctgtttg gctttgggga taatggcctg 2760

gcgaactgcc agctgttcag tggcagggct gtgaggccag tcaaagacta gaacccacag 2820

accagctgaa cgatgagtat agcctgtccc ctgggggagc ctgacctgtc tccagcccta 2880

agcttcagac ctcaccactc agatgacttc taagaatttg cctgtgggga cccctgcatg 2940

gctgcagctc cgtggaaagg agaggaggcc cccagcagaa gaaccactcg cttcctgccc 3000

agcttcctcc tgtagggctc taagtctctt cttcttggga ccctgcaagc aaaggcatgt 3060

cagcttggtg gtttcctgtt ttgggtgaag ttttgtgtgg tccgggttct gtctacatcc 3120

atgaacttgg ggtgctacca ccttgctgct gctgtagaga cagctgcagg atcttagggt 3180

ggaaaatgga ggtgccctga ggtgctagcc cttggggcaa aagatggggt ggcaatgaga 3240

cacagtgggg aactgagttc cccaagagga gggaggagcc ctgtagcctc aagggccata 3300

ttgggttcct ggtaccagca aaagcctaga gagcgaagtc tgtattttga ggaggtaatt 3360

gatccttacg gaatccatca gaaatttgga gcgggtgctt tatctatctc tggagggtct 3420

ctacctatct ccgatgaagc tctccctggg cctgggatgg gagaaaccag gaggaaaggt 3480

gtctgataaa gcaggggctt cttgacaagc caaagggcca ctggtagctg ttgtggaccg 3540

agctgaccct gctgaagtat tgtagtgtgc cttggaccaa cttctcaaaa gagcaacccc 3600

ggggctaccc tacttctgcc aggaagaggc ggagaagggg ctgagaggcc tggaaggggc 3660

tagctccttc tttgagaact gctccccgga ggacttggag gaggcggcta ggctacgggc 3720

tgctgagggc cctttgtctt tcctaacctg ggcactgtta ggatgctccc tcctggaaaa 3780

ggctttcctg ggtgtgagct agagcagtgt ccatgccagc gctgaacctg ccatggtggg 3840

agctgaacta aaaatttctc agggaactaa aataggcaaa agaggaactg ggggaggagg 3900

gtgccaggca ggatgggggg aagggagggc agtgcaaaag tctcttgaaa cacagacagc 3960

ccagctgagt gccagtccca gatcacagag aatacggctc atctggctca tgttctgcat 4020

gcttgctgct ttaccctggc actttccttc tccaccatga gtgcgagtcc tgggagtcct 4080

gggagggtga ggattaatgc cagcctgggg agcagatagc tgacagagtc cttgggtaac 4140

tggcttgaac caggacctca ggattccact ctggggatct agctttgtct gggccagtga 4200

agatctctat aatggcatta ttgccagggg ataaacattt cactgggttc tgatctgttg 4260

ggtgtggctt cctggaaaat atggtgagag gaattctgct aaggatacag ttgataagaa 4320

agttctgaga ttgattagta atgcctgcct tggactcagg aagggaagtg gcagtatgaa 4380

tgccatgtct taatcatttt ggttaaaata tgcttcccaa aagatttcca cgtgtgttct 4440

tgtttatttg acatctgtct ccatatcagt cttgaaagcc tttctgtgtg tatatatatg 4500

atgtttgcgt gtatatatgt ttttgtgtgt gcatatggaa gtcagaaatc actgggtgtc 4560

ttcctccatt cctttgcaat gtatgttttt ttttttttta cgatttattt actatatgaa 4620

tgttttgcct gaatacatgc ataggtgtca cgtacatgcc tgctggaacg cttggaactg 4680

gagttacagg tggctatgag ctacagtgtg agcactggga atcaaacctg ggtcttctgc 4740

aagagcaaca aattaaaagt cagctcttaa ctacttgagc tatttttcca actcc 4795

<210> 89

<211> 162

<212> PRT

<213> 人(Homo sapiens)

<400> 89

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

1 5 10 15

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

20 25 30

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

35 40 45

Gln Thr Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

50 55 60

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

65 70 75 80

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn

85 90 95

Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr

100 105 110

Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val

115 120 125

His Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser

130 135 140

Asn Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn Ile Thr

145 150 155 160

Ala Ala

<210> 90

<211> 159

<212> PRT

<213> 小鼠(Mus musculus)

<400> 90

Phe Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

1 5 10 15

Asn Ala Thr Leu Thr Cys Arg Ile Leu Gly Pro Val Ser Lys Gly His

20 25 30

Asp Val Thr Ile Tyr Lys Thr Trp Tyr Leu Ser Ser Arg Gly Glu Val

35 40 45

Gln Met Cys Lys Glu His Arg Pro Ile Arg Asn Phe Thr Leu Gln His

50 55 60

Leu Gln His His Gly Ser His Leu Lys Ala Asn Ala Ser His Asp Gln

65 70 75 80

Pro Gln Lys His Gly Leu Glu Leu Ala Ser Asp His His Gly Asn Phe

85 90 95

Ser Ile Thr Leu Arg Asn Val Thr Pro Arg Asp Ser Gly Leu Tyr Cys

100 105 110

Cys Leu Val Ile Glu Leu Lys Asn His His Pro Glu Gln Arg Phe Tyr

115 120 125

Gly Ser Met Glu Leu Gln Val Gln Ala Gly Lys Gly Ser Gly Ser Thr

130 135 140

Cys Met Ala Ser Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala Ala

145 150 155

<210> 91

<211> 95

<212> PRT

<213> 人(Homo sapiens)

<400> 91

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

1 5 10 15

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

20 25 30

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

35 40 45

Gln Thr Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

50 55 60

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

65 70 75 80

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly

85 90 95

<210> 92

<211> 158

<212> PRT

<213> 人(Homo sapiens)

<400> 92

Phe Lys Val Ala Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

1 5 10 15

Asn Val Thr Leu Thr Cys Arg Leu Leu Gly Pro Val Asp Lys Gly His

20 25 30

Asp Val Thr Phe Tyr Lys Thr Trp Tyr Arg Ser Ser Arg Gly Glu Val

35 40 45

Gln Thr Cys Ser Glu Arg Arg Pro Ile Arg Asn Leu Thr Phe Gln Asp

50 55 60

Leu His Leu His His Gly Gly His Gln Ala Ala Asn Thr Ser His Asp

65 70 75 80

Leu Ala Gln Arg His Gly Leu Glu Ser Ala Ser Asp His His Gly Asn

85 90 95

Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu Tyr

100 105 110

Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg Val

115 120 125

His Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro Ser

130 135 140

Asn Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn

145 150 155

<210> 93

<211> 63

<212> PRT

<213> 人(Homo sapiens)

<400> 93

Asn Phe Ser Ile Thr Met Arg Asn Leu Thr Leu Leu Asp Ser Gly Leu

1 5 10 15

Tyr Cys Cys Leu Val Val Glu Ile Arg His His His Ser Glu His Arg

20 25 30

Val His Gly Ala Met Glu Leu Gln Val Gln Thr Gly Lys Asp Ala Pro

35 40 45

Ser Asn Cys Val Val Tyr Pro Ser Ser Ser Gln Asp Ser Glu Asn

50 55 60

<210> 94

<211> 94

<212> PRT

<213> 小鼠(Mus musculus)

<400> 94

Phe Lys Val Thr Thr Pro Tyr Ser Leu Tyr Val Cys Pro Glu Gly Gln

1 5 10 15

Asn Ala Thr Leu Thr Cys Arg Ile Leu Gly Pro Val Ser Lys Gly His

20 25 30

Asp Val Thr Ile Tyr Lys Thr Trp Tyr Leu Ser Ser Arg Gly Glu Val

35 40 45

Gln Met Cys Lys Glu His Arg Pro Ile Arg Asn Phe Thr Leu Gln His

50 55 60

Leu Gln His His Gly Ser His Leu Lys Ala Asn Ala Ser His Asp Gln

65 70 75 80

Pro Gln Lys His Gly Leu Glu Leu Ala Ser Asp His His Gly

85 90

<210> 95

<211> 65

<212> PRT

<213> 小鼠(Mus musculus)

<400> 95

Asn Phe Ser Ile Thr Leu Arg Asn Val Thr Pro Arg Asp Ser Gly Leu

1 5 10 15

Tyr Cys Cys Leu Val Ile Glu Leu Lys Asn His His Pro Glu Gln Arg

20 25 30

Phe Tyr Gly Ser Met Glu Leu Gln Val Gln Ala Gly Lys Gly Ser Gly

35 40 45

Ser Thr Cys Met Ala Ser Asn Glu Gln Asp Ser Asp Ser Ile Thr Ala

50 55 60

Ala

65

<210> 96

<211> 46

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 肽接头

<400> 96

Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys

1 5 10 15

Glu Ala Ala Ala Lys Ala Leu Glu Ala Glu Ala Ala Ala Lys Glu Ala

20 25 30

Ala Ala Lys Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala

35 40 45

<210> 97

<211> 5

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 肽接头

<400> 97

Pro Ala Pro Ala Pro

1 5

<210> 98

<211> 12

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 肽接头

<400> 98

Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala

1 5 10

<210> 99

<211> 6

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 肽接头

<400> 99

Ile Glu Gly Arg Met Asp

1 5

<210> 100

<211> 7

<212> PRT

<213> 人工序列(Artificial Sequence)

<220>

<223> 肽接头

<400> 100

Asp Ile Glu Gly Arg Met Asp

1 5

Claims

1.一种预防和治疗免疫相关疾病的药物组合物，包括作为活性成分的：

融合蛋白，所述融合蛋白包含富含亮氨酸和免疫球蛋白样结构域-1(Lrig-1)蛋白的胞外结构域和免疫球蛋白Fc区；

编码融合蛋白的核酸分子；

包含核酸分子的表达载体；或者

用表达载体转化的宿主细胞。

2.根据权利要求1所述的药物组合物，其中所述Lrig-1蛋白的胞外结构域由SEQ IDNO:1或SEQ ID NO:3表示的氨基酸序列组成。

3.根据权利要求1的药物组合物，其中所述免疫球蛋白Fc区包括选自CH1、CH2、CH3和CH4结构域中的一种或几种。

4.根据权利要求1所述的药物组合物，其中所述免疫球蛋白Fc区是IgG-，IgA-，IgD-，IgE-或IgM-衍生的Fc区、重链恒定区2(CH2)、重链恒定区3(CH3)、铰链区及其片段，或其组合，或包括该组合的杂化Fc区。

5.根据权利要求1所述的药物组合物，其中所述免疫球蛋白Fc区包括IgG-、IgA-、IgD-、IgE-或IgM衍生的CH2和CH3结构域。

6.根据权利要求1所述的药物组合物，其中所述免疫球蛋白Fc区包括IgG1-、IgG2-、IgG3-或IgG4-衍生的CH2和CH3结构域。

7.根据权利要求1所述的融合蛋白，其中所述免疫球蛋白Fc区包括铰链区。

8.根据权利要求7所述的药物组合物，其中所述免疫球蛋白Fc区包括IgG-、IgA-、IgM-、IgD-、IgE-或Abatacept-衍生的铰链区。

9.根据权利要求7所述的药物组合物，其中所述铰链区包括IgG1-、IgG2-、IgG3-、IgG4-、IgD-或Abatacept-衍生的铰链区。

10.根据权利要求1所述的药物组合物，其中所述免疫球蛋白Fc区包括由SEQ ID NO:5或SEQ ID NO:6表示的CH2和CH3结构域。

11.根据权利要求1所述的药物组合物，其中所述免疫球蛋白Fc区包括由SEQ ID NO:7至SEQ ID NO:10中任意一个表示的铰链区。

12.根据权利要求1所述的药物组合物，其中所述Lrig-1蛋白的胞外结构域直接连接到免疫球蛋白Fc区的氮末端或碳末端。

13.根据权利要求1所述的药物组合物，其中所述Lrig-1蛋白的胞外结构域通过接头连接到免疫球蛋白Fc区的氮末端或碳末端。

14.根据权利要求13所述的药物组合物，其中所述接头是由SEQ ID NO:11和SEQ IDNO:12表示的肽接头中的至少一种。

15.根据权利要求13所述的药物组合物，其中所述接头选自包含肽接头的组中的至少一种，每个肽接头包含由式1至式4任一项表示的核苷酸序列：

[式1]

(G)_n；

[式2]

(GGGGS)_m；

[式3]

(EAAAK)_p；

[式4]

(XP)_q；

其中所述n、m和p各自独立地为1或更大的整数；

q是5～40的整数；和

16.根据权利要求13所述的药物组合物，其中所述接头是选自由SEQ ID NO:96至SEQID NO:100表示的肽接头中的至少一种。

17.根据权利要求1所述的药物组合物，进一步包括：

T细胞活化的V结构域Ig抑制剂(VISTA)或其片段；或者

包含VISTA或其片段和免疫球蛋白Fc区的融合蛋白。

18.根据权利要求1所述的药物组合物，其中所述所述免疫相关疾病选自自身免疫性疾病、移植物抗宿主病、器官移植排斥病、哮喘、特应性，或急性或慢性炎症性疾病。

19.根据权利要求18所述的药物组合物，其中所述自身免疫性疾病选自类风湿性关节炎、1型糖尿病、***性硬皮病、***性红斑狼疮、***性红斑狼疮、特应性皮炎、牛皮癣、斑秃、哮喘、克罗恩病、白塞病、干燥综合征、吉兰-巴雷综合症、慢性甲状腺炎、多发性硬化、多发性肌炎、强直性脊柱炎、纤维肌炎和结节性多动脉炎中的至少一种。

20.根据权利要求18所述的药物组合物，其中所述自身免疫性疾病是神经退行性疾病或神经炎症性疾病。

21.根据权利要求20的药物组合物，其中所述神经退行性疾病或神经炎症性疾病选自中风、痴呆、阿尔茨海默病、帕金森病、亨廷顿病、Niemann-Pick病、朊病毒病、库贾氏病、额颞叶痴呆、路易斯痴呆、肌萎缩性侧索硬化、副癌综合征、皮质基底节变性、多***萎缩、进行性核麻痹、神经***自身免疫性疾病、脊髓小脑性共济失调、炎性和神经性疼痛、脑血管疾病、脊髓损伤和tau蛋白病中的至少一种。

22.一种预防、改善或治疗免疫相关疾病的方法，包括：

将以下的向个体施用步骤：融合蛋白，所述融合蛋白包括富含亮氨酸和免疫球蛋白样结构域-1(Lrig-1)蛋白的胞外结构域和免疫球蛋白Fc区；编码融合蛋白的核酸分子；包含核酸分子的表达载体；或者用表达载体转化的宿主细胞；或者包含前述任一项的组合物。