嵌合吞噬受体的表达载体、基因修饰的宿主细胞及其用途

以文本文件形式提供与本申请相关的序列表以替代纸质副本，并且通过引用在此并入本说明书。包含序列表的文本文件命名为200265_406WO_SEQUENCE_LISTING.txt。该文本文件大小为539KB，于2019年3月26日创建，并通过EFS-Web以电子形式提交。

背景技术

将靶向癌症抗原的基因工程改造的受体修饰的T细胞用于血液系统恶性肿瘤中已显示了临床成功(例如，白血病中的CD19特异性嵌合抗原受体疗法)。仅举几个例子，通过利用靶向CEA、GD2、间皮素、IL13Rα、HER2、FAP和L1CAM的工程化受体的过继细胞免疫疗法治疗实体瘤的许多临床试验正在进行中。工程化受体包括嵌合抗原受体(CAR)和亲和性增强的T细胞受体(TCR)。然而，对实体瘤的治疗存在独特的挑战，包括：向肿瘤部位运输、肿瘤微环境的物理障碍、应激的代谢情况和免疫抑制机制(例如，免疫检查点分子的表达、抑制性细胞因子的产生)。针对过继免疫治疗中增加T细胞持久性和活性的努力仍在进行着。

附图说明

图1A-G显示了示例性串联表达盒的载体图。该串联表达盒包含人乳头瘤病毒16(HPV16)E7蛋白特异性TCR，以诱导肿瘤(例如，宫颈)特异性细胞溶解应答，还包含磷脂酰丝氨酸特异性嵌合吞噬受体(CER)，以在细胞溶解诱导的磷脂酰丝氨酸暴露后激发肿瘤特异性吞噬活性。图1A显示了示例性串联表达盒，其包含编码嵌合吞噬受体5(CER5)构建体的多核苷酸和编码HPV16 E7特异性TCR的多核苷酸。CER5位于HPV16 E7特异性TCR的上游。编码CER5和HPV16 E7 TCR的序列可操作地连接至EF-1α启动子，并被T2A肽隔开。CER5包含Tim4结合结构域、Tim4跨膜结构域和TLR4吞噬信号传导结构域。图1B显示了示例性串联表达盒，其包含编码CER19构建体的多核苷酸和编码HPV16 E7特异性TCR的多核苷酸。CER19位于HPV16 E7特异性TCR的上游。编码CER19和HPV16 E7 TCR的序列可操作地连接至EF-1α启动子，并被T2A肽隔开。CER19包含Tim4结合结构域、Tim4跨膜结构域和TLR5信号传导结构域。图1C显示了示例性串联表达盒，其包含编码CER21构建体的多核苷酸和编码HPV16 E7特异性TCR的多核苷酸。CER21位于HPV16 E7特异性TCR的上游。编码CER21和HPV16 E7 TCR的序列可操作地连接到EF-1α启动子，并被T2A肽隔开。CER21包含Tim4结合结构域、Tim4跨膜结构域和TLR8信号传导结构域。图1D显示了示例性串联表达盒，其包含编码CER25构建体的多核苷酸和编码HPV16 E7特异性TCR的多核苷酸。CER25位于HPV16 E7特异性TCR的上游。编码CER25和HPV16 E7 TCR的序列可操作地连接到EF-1α启动子，并被T2A肽隔开。CER25包含Tim4结合结构域、Tim4跨膜结构域和NFAM1信号传导结构域。图1E显示了示例性串联表达盒，其包含编码CER27构建体的多核苷酸和编码HPV16 E7特异性TCR的多核苷酸。CER27位于HPV16 E7特异性TCR的上游。编码CER27和HPV16 E7 TCR的序列可操作地连接到EF-1α启动子，并被T2A肽隔开。CER27包含Tim4结合结构域、Tim4跨膜结构域和TLR2信号传导结构域。图1F显示了示例性串联表达盒，其包含编码CER29构建体的多核苷酸和编码HPV16 E7特异性TCR的多核苷酸。CER29位于HPV16 E7特异性TCR的上游。编码CER29和HPV16 E7 TCR的序列可操作地连接到EF-1α启动子，并被T2A肽隔开。CER29包含Tim4结合结构域、Tim4跨膜结构域和Traf6信号传导结构域。图1G显示了示例性串联表达盒，其包含编码CER31构建体的多核苷酸和编码HPV16 E7特异性TCR的多核苷酸。CER31位于HPV16 E7特异性TCR的上游。编码CER31和HPV16 E7 TCR的序列可操作地连接到EF-1α启动子，并被T2A肽隔开。CER31包含Tim4结合结构域、Tim4跨膜结构域和Traf3信号传导结构域。

图2显示了用包含CER21-HPV16 E7 TCR的串联表达构建体修饰的人原代CD8+ T细胞的细胞毒性。图像显示了在不同时间点(2小时、4小时和6小时)从HPV16 E7+头颈部鳞状细胞癌(SCC152)细胞发出的caspase 3/7荧光指示剂染料。在使用SCC152细胞的定时共培养实验中，将用CER21-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞(上面一行)与仅使用HPV16 E7 TCR转导的CD8+ T细胞(下面一行)进行了比较。串联表达构建体使CD8+ T细胞具有细胞溶解和吞噬活性，并增强杀伤能力。以1:1的比例孵育效应CD8+ T细胞:靶SCC152细胞。

图3是线形图，显示了在与用慢病毒载体(包含被T2A序列隔开的HPV16 E7 TCR和嵌合吞噬受体21(CER21)的串联盒)转导的人原代CD8+ T细胞共培养后，HPV16 E7+SCC152细胞中随着时间的推移Caspase 3/7的诱导。与仅包含HPV16 E7 TCR的宿主CD8+ T细胞相比，编码HPV16 E7 TCR和CER21的串联表达构建体赋予宿主CD8+ T细胞更高的靶细胞杀伤能力。以1:1的比例将效应CD8+ T细胞与靶SCC152细胞一起孵育。对随着时间的推移的总caspase 3/7荧光进行定量。

图4是柱状图，显示了在与用慢病毒载体(包含被T2A序列隔开的HPV16 E7 TCR和CER的串联盒)转导的CD8+ T细胞共培养后，HPV16 E7+SCC152细胞中Caspase 3/7的诱导。将模拟转导的细胞用作阴性对照。使用

图5显示了共培养开始后6小时从HPV+头颈部鳞状细胞癌(SCC152)细胞发出的caspase 3/7荧光指示剂染料的图像。对使用CER-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞的共培养与仅使用HPV16 E7 TCR转导的CD8+ T细胞的共培养(从上面数第二个)进行比较。与对照CD8+ T细胞相比，使用CER-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞显示出更高的caspase诱导作用。

图6是柱状图，显示了在共培养6小时后，使用HPV16 E7 TCR、CER21-HPV16 E7 TCR串联表达盒、CER29-HPV16 E7 TCR串联表达盒或CER31-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞的吞噬作用的定量。通过Keyence BZ-X710成像系统中的混合捕获软件对吞噬作用进行定量，其中通过识别蓝色染色效应细胞中红色荧光靶点(SCC152细胞)的数量(使用CER-HPV16 E7 TCR串联表达盒转导的细胞痕迹紫色标记的CD8+ T细胞-内化的红色#/蓝色#)x 100确定吞噬作用％。

图7是荧光显微照片，显示了正在吞噬SCC152靶细胞(pHrodo Red标记)的CER21-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞(紫色)。将CER21-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞与SCC152靶细胞的1:1混合物共培养6小时，然后成像。箭头指示紫色CD8+T细胞内体区室中SCC152细胞(红色)内化的代表性图像(左图＝亮视野重叠，右图＝荧光重叠)。使用串联盒工程化的CD8+ T细胞明显吞噬了SCC152肿瘤细胞系。

图8显示了用CER21-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞以Rac1依赖的方式吞噬了靶细胞。小GTP-ase Rac1的激活和膜募集触发了吞噬作用。左侧图像显示了用CER21-HPV16 E7 TCR转导的蓝色标记的CD8+细胞内吞噬的pH rodo红标记的靶细胞。将Rac1抑制剂NSC23766(50μM)加入共培养实验中(右侧图像)，并对体外吞噬作用/吞噬进行定量。荧光显微照片显示了小分子对Rac1的抑制作用消除了CER21-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞的体外吞噬(右)。

图9显示了使用CER29-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞以Rac1依赖方式吞噬靶细胞。小GTP-ase Rac1的激活和膜募集触发了吞噬作用。左侧图像显示了用CER29-HPV16 E7 TCR转导的蓝色标记的CD8+细胞内吞噬的pH rodo红标记的靶细胞。将Rac1抑制剂NSC23766(50μM)加入共培养实验中(右侧图像)，并对体外吞噬作用/吞噬进行定量。荧光显微照片显示了小分子对Rac1的抑制作用消除了CER29-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞的体外吞噬(右)。

图10显示了使用CER31-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞以Rac1依赖方式吞噬靶细胞。小GTP-ase Rac1的激活和膜募集触发了吞噬作用。左侧图像显示了用CER31-HPV16 E7 TCR转导的蓝色标记的CD8+细胞内吞噬的pH rodo红标记的靶细胞。将Rac1抑制剂NSC23766(50μM)加入共培养实验中(右侧图像)，并对体外吞噬作用/吞噬进行定量。荧光显微照片显示了小分子对Rac1的抑制作用消除了CER31-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞的体外吞噬(右)。

图11显示了使用包含CER21-HPV16 E7 TCR的串联表达盒转导的CD8+ T细胞具有细胞溶解和吞噬功能。CER21-HPV16 E7 TCR转导的CD8+ T细胞在体外具有吞噬摄取涂覆了磷脂酰丝氨酸的小珠的能力。将链霉亲和素涂覆的乳胶小珠与生物素-磷脂酰丝氨酸结合，并用于吞噬作用测定。孵育30分钟后，CER21-HPV16 E7 TCR转导的CD8+ T细胞显示出摄取磷脂酰丝氨酸涂覆的小珠(白色箭头表示吞噬事件的代表性图像)。

图12显示了CER21-HPV16 E7 TCR转导的CD8+ T细胞的高倍放大图像，其显示了在体外吞噬摄取磷脂酰丝氨酸涂覆的小珠。

图13显示了在孵育后30分钟时，HPV16 E7 TCR转导的CD8+ T细胞与涂覆磷脂酰丝氨酸的乳胶小珠共培养的光学显微照片。仅使用HPV16 E7 TCR转导的CD8+ T细胞未显示出摄取磷脂酰丝氨酸涂覆的乳胶小珠。

图14是3D柱状图，显示了用CER21-HPV16 E7 TCR串联表达盒或单独用HPV16 E7TCR转导并与SCC152靶细胞共培养的CD8+ T细胞的细胞因子分泌模式。为确定细胞因子分泌模式，将CER21-HPV16 E7 TCR修饰的CD8+ T细胞与SCC152靶细胞共培养。抗原特异性细胞因子的分泌是通过使用中等规模的多阵列细胞因子平板测量每种共培养物中的细胞上清液中的细胞因子浓度来确定的。在测定中测量了下述细胞因子：IFNγ、IL-2、TNFα、IL-4、IL-6、IL-12b、IL-13、IL-1b和IL-10。如细胞因子分泌(例如，IFNγ)所示，用CER21-HPV16E7 TCR串联表达盒转导的CD8+ T细胞表现出抗原特异性效应功能。

图15A-15B显示了T细胞的吞噬活性是由CER特异性诱导的。图15A显示了吞噬作用测定的FACS分析。将CellTrace-紫色标记的模拟转导的T细胞、HPV E7-TCR转导的T细胞和HPV E7-TCR/CER29串联表达盒转导的T细胞与pHrodo红标记的头颈部癌细胞共培养。图15B显示了FACS数据的定量，显示了模拟转导的T细胞和E7 TCR转导的T细胞之间的吞噬作用没有差异。在T细胞中共表达CER29和E7 TCR的T细胞显示出吞噬活性。

具体实施方式

在一个方面中，本公开内容提供了串联表达盒，其用于在同一宿主细胞中共表达编码第一过继免疫疗法分子的第一转基因和编码第二过继免疫疗法分子的第二转基因。本文所述的串联表达盒的实施方式包含编码嵌合吞噬受体(CER)的多核苷酸；和编码嵌合抗原受体(CAR)或重组T细胞受体(TCR)的多核苷酸。本公开内容的串联表达盒可用于在同一宿主细胞中赋予串联的细胞溶解和吞噬表型。在某些实施方式中，对第一靶抗原特异的CAR或TCR的细胞毒活性诱导表达第一靶抗原的靶细胞的凋亡，从而暴露第二靶抗原；以及对第二靶抗原具有特异性的共表达的CER诱导表达第二靶抗原的靶细胞或颗粒的吞噬。该相互作用可能与将产生环境/磷脂酰丝氨酸的表达的基因工程化细胞与和特定的肿瘤或肿瘤细胞具有不同的相互作用的相同细胞相分离，其中所述环境/磷脂酰丝氨酸表达与靶细胞的吞噬有关。

另外，提供了经修饰以表达本公开内容的串联表达盒的细胞，以及用于将此类经修饰的细胞递送至需要其的对象的方法和组合物。

在更详细地阐述本公开内容之前，提供在本文中使用的某些术语的定义，可能有助于理解本公开内容。

在本说明书中，除非另有说明，否则应将任何浓度范围、百分比范围、比率范围或整数范围理解为包括所述范围内的任何整数的值，并且在适当时，包括其分数(例如，整数的十分之一和百分之一)。此外，除非另有说明，否则本文所述的与任何物理特征(如聚合物亚单元、尺寸或厚度)相关的任何数值范围均应被理解为包括在所述范围内的任何整数。如在本文中所使用的，除非另有说明，否则本文所使用的术语“约”表示所示范围、值或结构的±20％。应当理解的是，如在本文中所使用的，术语“一个/种”指所列举组分的“一个/种或多个/种”。替代词(例如“或”)的使用应理解为可选项中的之一、两者都或其任意组合。本文中所使用的术语“包括”、“具有”和“包含”可同义地使用，此等术语及其变体旨在被解释为是非限制性的。

除非在本文中明确地进行不同的定义，否则抗体技术领域的技术人员应按本领域中给出的含义理解术语。术语“抗体”以最广义使用，并且包括多克隆和单克隆抗体。“抗体”可以指完整抗体，其包含彼此之间通过二硫键连接的至少两条重链(H)和两条轻链(L)，以及具有或保有与靶分子结合的能力的完整抗体的抗原结合部分(或抗原结合结构域)。抗体可以是天然存在的、重组生产的、基因工程改造的或免疫球蛋白的修饰形式，例如胞内抗体、肽体、纳米抗体、单域抗体、SMIP、多特异性抗体(例如，双特异性抗体、双功能抗体、三功能抗体、四功能抗体、串联的双-scFV、串联的三-scFv、ADAPTIR)。单克隆抗体或其抗原结合部分可以是非人的、嵌合的、人源化的或人的，优选人源化的或人的。在例如Harlow等编著，Antibodies:A Laboratory Manual，第14章(Cold Spring Harbor Laboratory,ColdSpring Harbor,1988)中对免疫球蛋白的结构和功能进行了综述。完整抗体的“抗原结合部分”或“抗原结合结构域”旨在包括这样的“抗体片段”：其表示完整抗体的一部分并且指的是完整抗体的抗原决定可变区或互补决定区。抗体片段的实例包括但不限于Fab、Fab’、F(ab’)

术语抗体中的“可变区”或“可变结构域”是指参与抗体与抗原结合的抗体重链或轻链的结构域。天然抗体重链和轻链(分别为VH和VL)的可变结构域通常具有相似的结构，每个结构域包含四个保守的框架区(FR)和三个互补决定区(CDR)(参见例如，Kindt等，KubyImmunology,第6版,W.H.Freeman和Co.,91页(2007))。单个VH或VL结构域可以足以赋予抗原结合特异性。此外，可以通过使用与特定抗原结合的抗体的VH或VL结构域分别筛选互补性VL或VH结构域的文库，以分离与该抗原结合的抗体。参见例如，Portolano等，J.Immunol.150:880-887(1993)；Clarkson等，Nature 352:624-628(1991)。

本领域已知，与“高变区”或“HVR”同义的术语“互补决定区”和“CDR”是指抗体可变区内不连续的氨基酸序列，其赋予了抗原特异性和/或结合亲和性。通常，在每个重链可变区中有3个CDR(HCDR1、HCDR2、HCDR3)并且在每个轻链可变区中有3个CDR(LCDR1、LCDR2、LCDR3)。

如在本文中所使用的，术语“结合结构域”、“结合区”和“结合部分”指具有特异性地和非共价地结合、缔合、联合(unite)、识别或组合靶分子(例如肿瘤抗原)的能力的分子(如肽、寡肽、多肽或蛋白)。结合结构域包括任何天然存在的、合成的、半合成或重组产生的针对目标生物分子或其他靶点的结合配偶体。在一些实施方式中，结合结构域是抗原结合结构域，如抗体或者其功能性结合结构域或抗原结合部分。示例性结合结构域包括单链抗体可变区(例如，域抗体、sFv、scFv、Fab)、受体胞外域(例如，TNF-α)、配体(例如，细胞因子、趋化因子)或者因具有与生物分子的特异性结合能力而被选择的合成多肽。

“T细胞受体”(TCR)指在存在于T细胞(也称为T淋巴细胞)表面上且通常负责识别与主要组织相容性复合物(MHC)分子结合的抗原的分子。在大多数T细胞中，TCR通常由二硫键连接的高度可变的α和β链的异二聚体组成(也分别称为TCRα和TCRβ)。在一个小的T细胞子集中，TCR由γ和δ链的异二聚体组成(也分别称为TCRγ和TCRδ)。TCR的每条链都是免疫球蛋白超家族的成员，并具有一个N末端免疫球蛋白可变域、一个免疫球蛋白恒定域、跨膜区域和在C末端短的胞质尾(参见Janeway等，Immunobiology:The Immune System inHealth and Disease,3

术语TCRα-链和β-链的“可变区”或“可变结构域”(Vα和Vβ)或γδTCR的Vγ和Vδ参与TCR与抗原的结合。天然TCR的V

“主要组织相容性复合物分子”(MHC分子)是指将肽抗原递送至细胞表面的糖蛋白。MHC I类分子是异源二聚体，其由跨膜的α链(具有三个α域)和非共价结合的β2微球蛋白组成。MHC II类分子由两个跨膜糖蛋白α和β组成，两者都跨膜。每条链具有两个结构域。MHCI类分子将起源于细胞质的肽传递到细胞表面，肽：MHC复合物在该表面被CD8

“嵌合抗原受体”(CAR)是指包含两个或更多个不同结构域的嵌合蛋白，并且当其在细胞表面表达时可以充当受体。CAR通常由胞外域(包含结合靶抗原的结合结构域)、任选地胞外间隔区结构域、跨膜结构域和胞内信号传导结构域(例如，包含基于免疫受体酪氨酸激活基序(ITAM)的T细胞活化基序，以及任选地胞内共刺激结构域)组成。在某些实施方式中，CAR的胞内信号传导结构域具有含有ITAM的T细胞活化结构域(如CD3ζ)和细胞内共刺激结构域(例如，CD28)。在某些实施方式中，CAR被合成为单一多肽链，或由核酸分子编码为单链多肽。

已知有多种测定可用于鉴定本公开的与特定靶点特异性结合的结合结构域，以及确定结合结构域的亲和性，如Western印迹、ELISA、分析性超速离心、光谱学、表面等离子体共振

术语“抗原”和“Ag”指能够诱导免疫应答的分子。所诱导的免疫应答可以参与抗体产生、特异性免疫活性细胞的激活、或者这两者。大分子(包括蛋白、糖蛋白和糖脂)可以作为抗原。抗原可以来自重组的或基因组DNA。如本文所考虑的，抗原(i)不需要仅由基因的全长核苷酸序列编码或者(ii)完全不需要由“基因”编码。可以产生或合成抗原，或者抗原可以来自生物样品。此类生物样品可以包括但不限于组织样品、肿瘤样品、细胞或生物体液。

术语“表位”或“抗原表位”包括抗原内的任何分子、结构、氨基酸序列或蛋白决定簇，其被相关免疫结合分子特异性结合，如抗体或其片段(例如，scFv)、T细胞受体(TCR)、CAR、嵌合吞噬受体或者其他结合分子、结构域或蛋白。表位决定簇通常含有分子的化学活性表面基团，如氨基酸或糖侧链，并且可以具有特定的三维结构特征以及特定的电荷特征。表位可以是线形表位或构象表位。

如在本文中所使用的，“效应结构域”是融合蛋白或嵌合受体的胞内部分，当接受适宜信号时，在表达效应结构域的细胞中其能够直接或间接地促进生物或生理应答。在某些实施方式中，效应结构域是结合时接收信号的蛋白或蛋白复合物的一部分。在其他实施方式中，效应结构域是直接结合靶分子的蛋白或蛋白复合物的一部分，所述靶分子触发来自该效应结构域的信号。例如，针对CER与靶分子的结合，效应结构域可以向宿主细胞的内部传导信号，激发效应功能，例如吞噬、吞噬溶酶体成熟、或分泌抗炎性和/或免疫抑制细胞因子。当效应结构域含有一个或多个信号传导结构域或基序时，其可以直接促进细胞应答。在其他实施方式中，效应结构域将通过与一个或多个直接促进细胞应答的其他蛋白的结合来间接促进细胞应答。

“吞噬信号传导结构域”指胞内效应结构域，其在与由宿主细胞表达的CER胞外域靶向的靶分子(例如，磷脂酰丝氨酸)结合后，激活宿主细胞中的一个或多个信号传导通路，进而导致吞噬(包括在特定的实施方式中宿主细胞的细胞骨架重排和与靶抗原相关的靶细胞或颗粒的内化)。在某些实施方式中，吞噬信号传导结构域激活一个或多个信号传导通路而导致对靶细胞或颗粒的吞噬作用。在进一步的实施方式中，吞噬信号传导结构域包括主要吞噬信号传导结构域和次要吞噬信号传导结构域。

“连接氨基酸”或“连接氨基酸残基”指在多肽的两个相邻基序、区域或结构域之间的一个或多个(例如，约2-20个)氨基酸残基。连接氨基酸可以由嵌合蛋白的构建体设计产生(例如，在构建编码融合蛋白的核酸分子的过程中使用限制性酶位点产生的氨基酸残基)。

“疾病”是一种对象的健康状况，其中对象不能维持稳态，并且其中如果疾病不能得到改善，则对象的健康将继续恶化。相比之下，对象的“紊乱”或“不利病况”是指对象能够维持稳态的健康状况，但此时对象的健康状况不如其没有紊乱或不利病况时的健康状况。如果不进行治疗，紊乱或不利病况不一定必然导致对象健康状况的进一步下降。

“核酸分子”和“多核苷酸”可以是RNA或DNA形式，其包括cDNA、基因组DNA和合成DNA。核酸分子可以由天然存在的核苷酸(如脱氧核糖核苷酸和核糖核苷酸)、天然存在的核苷酸类似物(例如，天然存在的核苷酸的α-对映体形式)或两者的组合组成。修饰的核苷酸可以具有糖部分、或嘧啶或嘌呤碱基部分的修饰或替换。核酸单体可以通过磷酸二酯键或此类连接的类似物连接。磷酸二酯键的类似物包括硫代磷酸酯、二硫代磷酸酯、亚硒代磷酸酯、二硒代磷酸酯、硫代磷酸硫酸酯、苯胺基磷酸酯、氨基磷酸酯等。核酸分子可以是双链的或单链的，如果是单链的，可以是编码链或非编码链(反义链)。编码分子可以具有与本领域已知的编码序列相同的编码序列，或者可以具有不同的编码序列，该不同的编码序列由于遗传密码的冗余性或简并性，或者通过剪接而能够编码相同多肽。

“编码”指特定多核苷酸序列(如DNA、cDNA和mRNA序列)的固有性质，以作为在生物加工过程中合成其他聚合物和大分子的模板，其具有确定的核苷酸序列(即，rRNA、tRNA和mRNA)或确定的氨基酸序列以及由此产生的生物性质。因此，如果对应于该多核苷酸的mRNA的转录和翻译在细胞或其他生物系统中产生蛋白，则该多核苷酸编码蛋白。可以将编码链和非编码链均称为编码蛋白或多核苷酸的其他产物。除非另有说明，否则“编码氨基酸序列的核苷酸序列”包括彼此为简并形式并且编码相同氨基酸序列的所有核苷酸序列。

如在本文中所使用的，术语“内源性的”或“天然的”指在宿主或宿主细胞中正常存在的基因、蛋白、化合物、分子或活性，包括所述基因、蛋白、化合物、分子或活性的天然存在的变体。

如在本文中所使用的，术语“同源的”或“同源物”指来自宿主细胞的分子或活性，其通过祖先与第二基因或活性相关，例如，来自相同的宿主细胞、来自不同的宿主细胞、来自不同的生物体、来自不同品系、来自不同物种。例如，异源分子或编码所述异源分子的异源基因分别对于天然宿主细胞分子或编码所述分子的基因可以是同源的，但是其可以具有改变的结构、序列、表达水平或其组合。

如在本文中所使用的，“异源的”核酸分子、构建体或序列指不是宿主细胞中天然存在的核酸分子或核酸分子的一部分，但是可以与来自宿主细胞的核酸分子或核酸分子的一部分同源。异源核酸分子，构建体或序列的来源可以是来自不同的属或种。在一些实施方式中，异源的核酸分子不是天然存在的。在某些实施方式中，通过例如缀合、转化、转染、转导、电穿孔等将异源核酸分子(即，不是内源的或天然的)添加到宿主细胞或宿主基因组中，其中添加的分子可以整合到宿主细胞基因组中，或以染色体外遗传物质的形式存在(例如，作为质粒或其他形式的自我复制载体)，并且可以以多个拷贝存在。此外，“异源”是指由导入宿主细胞中的非内源性核酸分子编码的非天然酶、蛋白质或其他活性，即使宿主细胞编码同源蛋白或活性也是如此。

如在本文中所使用的，术语“工程化的”、“重组的”、“经修饰的”或“非天然的”指生物体、微生物、细胞、核酸分子或载体已通过引入外源核酸分子进行了修饰，或指细胞或微生物已经过人为干预进行了基因工程改造，即通过引入异源核酸分子进行了修饰，或指细胞或微生物已被改变以使得内源性核酸分子或基因的表达被控制、失调或是组成型的，其中此类改变或修饰可以是通过基因工程改造引入的。人类产生的遗传改变可以包括例如引入编码一种或多种蛋白、嵌合受体或酶的核酸分子(其可以包括表达控制元件，如启动子)的修饰，或者其他核酸分子的添加、缺失、替换，或其他细胞遗传物质功能性破坏或加入。示例性的修饰包括在来自参照或亲本分子的异源或同源多肽的编码区或其功能片段中的修饰。其他示例性的修饰包括例如在非编码调控区的修饰，其中所述修饰改变基因或操纵子的表达。

如本文所使用的，术语“转基因”指编码目的蛋白(例如，CER、CAR、TCR)的基因或多核苷酸，其在宿主细胞中表达是被期待的，并且已通过基因工程技术转移至细胞中。转基因可以编码具有治疗意义的蛋白，也可以是报告子、标签、标志物、自杀蛋白等蛋白。转基因可以是来自天然来源的、天然基因的修饰或者重组或合成的分子。在某些实施方式中，转基因是载体的组分。

术语抗原“过表达的”或“过表达”指在细胞中异常的高水平的抗原表达。过表达的抗原或抗原过表达通常与疾病状态相关，如在恶性血液病和在对象的特定组织或器官内形成实体瘤的细胞中。可以通过本领域已知的标准测定确定由肿瘤抗原过表达来表征的实体瘤或恶性血液病。

如在本文中所使用的，术语“肽”、“多肽”和“蛋白”可以互换使用，其指由通过肽键共价连接的氨基酸残基构成的化合物。蛋白或肽必需含有至少2个氨基酸，并且对可构成蛋白或肽序列的氨基酸的最大数量没有限制。多肽包括任何这样的肽或蛋白：其含有通过肽键彼此连接在一起的两个或多个氨基酸。如在本文中所使用的，该术语既指短链又指更长的链，短链在本领域中通常也称为例如肽、寡肽和寡聚物，更长的链在本领域中通常称为蛋白，其具有多种类型。“多肽”包括例如生物活性片段、基本上同源的多肽、寡肽、同二聚体、异二聚体、多肽的变体、经修饰的多肽、衍生物、类似物、融合蛋白等。多肽包括天然肽、重组肽、合成肽或其组合。

如在本申请中所使用的，术语“成熟多肽”或“成熟蛋白”指分泌或位于细胞膜或某些细胞器(例如，内质网、高尔基体或内含体)内并且不包含N-末端信号肽的蛋白或多肽。

“信号肽”也称为“信号序列”、“前导序列”、“前导肽”、“定位信号”或“定位序列”，是一种位于新合成蛋白的N-末端的且运往分泌通路的短肽(通常的长度为15-30个氨基酸)。信号肽通常包含位于N-末端的一段短的亲水性、带正电的氨基酸、中间5-15个残基的疏水性结构域和具有信号肽酶切割位点的C-末端区域。在真核生物中，信号肽促使新合成的蛋白转位至内质网，在内质网中信号肽被信号肽酶切割，产生成熟的蛋白，随后前往其适宜的目的地。

两条或多条核酸或氨基酸序列之间的“同一性百分比”是序列共有的相同位置数的函数(即，同一性％＝相同位置数/位置总数x 100)，其要考虑为优化两条或多条序列比对而需要引入的空位数以及每个空位的长度。可以使用数学算法，如BLAST和Gapped BLAST程序，以其缺省参数(例如Altschul等，J.Mol.Biol.215:403,1990；亦参见在www.ncbi.nlm.nih.gov/BLAST的BLASTN)来实现序列比对以及确定两条或多条序列之间的同一性百分比。

本领域中认为，“保守性取代”是一种氨基酸取代具有相似性质的另一种氨基酸。示例性的保守性取代是本领域熟知的(参见例如，WO 97/09433，第10页，公开日：1997年3月13日；Lehninger，Biochemistry，第2版；Worth Publishers,Inc.NY:NY(1975),pp.71-77；Lewin,Genes IV,Oxford University Press,NY and Cell Press,Cambridge,MA(1990),p.8)。

术语“嵌合”指非内源性的并且包含结合或连接在一起的序列(在自然界中通常不会结合或连接在一起)的任何核酸分子或蛋白。例如，嵌合核酸分子可以包括编码来自多个不同基因的多个结构域的核酸。在另一个实例中，嵌合核酸分子可以包括来自不同来源的调控序列和编码序列，或者来自相同来源但是以不同于天然存在的方式排列的调控序列和编码序列。

如在本文中所使用的，将术语“启动子”定义为启动多核苷酸序列的特异性转录所需要的、由细胞的合成机制或所引入的合成机制识别的DNA序列。

如在本文中所使用的，术语“启动子/调控序列”指表达与启动子/调控序列可操作地连接的基因产物所需要的核酸序列。在一些情况下，该序列可以是核心启动子序列，在其他情况下，该序列也可以包含增强子序列和基因产物的表达所需要的其他调控元件。启动子/调控序列可以是例如以组织特异性方式表达基因产物的序列。

“组成型”启动子是这样一种核苷酸序列，当其与编码或确定基因产物的多核苷酸序列可操作地连接时，导致在细胞的大多数或所有生理条件下在该细胞中产生所述基因产物。

“诱导型”启动子是这样一种核苷酸序列，当其与编码或确定基因产物的多核苷酸序列可操作地连接时，仅当在细胞中存在与所述启动子对应的诱导物时，才导致在该细胞中充分地产生所述基因产物。

“组织特异性”启动子是这样一种核苷酸序列，当其与编码或由基因确定的多核苷酸可操作地连接时，仅当细胞是与所述启动子对应的组织类型中的细胞时，才导致在该细胞中充分地产生所述基因产物。

如在本文中所使用的，短语“在转录控制下”或“可操作地连接”指启动子相对于多核苷酸处于正确的位置和方向，以控制RNA聚合酶的转录起始和该多核苷酸的表达。

“载体”是能够转运另一核酸的核酸分子。载体可以是例如质粒、粘粒、病毒或噬菌体。还应将该术语解释为包括促进核酸转移至细胞中的非质粒和非病毒化合物。“表达载体”指这样的载体：当其存在于适宜环境中时能够指引由该载体携带的一个或多个基因编码的蛋白表达。

在某些实施方式中，载体是病毒载体。病毒载体的实例包括但不限于腺病毒载体、腺相关病毒载体、逆转录病毒载体、γ逆转录病毒载体和慢病毒载体。“逆转录病毒”是具有RNA基因组的病毒。“γ逆转录病毒”指逆转录病毒科家族的一个属。γ逆转录病毒的实例包括小鼠干细胞病毒、小鼠白血病病毒、猫白血病病毒、猫肉瘤病毒和禽类网状内皮细胞增生病毒。“慢病毒”指能够感染分裂和非分裂细胞的逆转录病毒的一个属。慢病毒的实例包括但不限于HIV(人类免疫缺陷病毒，包括1型HIV和2型HIV)、马感染性贫血病毒、猫免疫缺陷病毒(FIV)、牛免疫缺陷病毒(BIV)和猿猴免疫缺陷病毒(SIV)。

在其他实施方式中，载体是非病毒载体。非病毒载体的实例包括基于脂质的DNA载体、经修饰的mRNA(modRNA)、自扩增mRNA、封闭式线形双链体(CELiD)DNA和转座子介导的基因转移(PiggyBac,Sleeping Beauty)。当使用非病毒递送系统时，递送载剂可以是脂质体。可以使用脂质制剂在体外、离体或体内将核酸引入宿主细胞。核酸可以包封在脂质体内部、散布在脂质体的脂质双层内、通过将脂质体与核酸结合在一起的连接分子附接至脂质体、包含在胶束内或与之复合或者以其他方式与脂质结合。

如在本文中所使用的，术语“表达盒”指载体核酸的独特组分，其包含至少一个转基因和控制其在宿主细胞中表达的调控序列(例如，启动子，3’UTR)。串联表达盒指这样的载体核酸组分：其包含至少两个转基因，所述转基因在为了串联表达转基因的同一组调控序列的控制下。在某些实施方式中，串联表达盒包含在同一启动子控制下的至少两个转基因。在某些实施方式中，第一转基因和第二转基因被内部核糖体进入位点(IRES)、弗林蛋白酶切割位点或自切割病毒2A肽分隔，以使得能够从单一mRNA共表达两种蛋白。

“颗粒”指细胞碎片或直径至少10nm且至多50μm的小物体。颗粒可以来自活细胞或生物体、环境或合成的。颗粒可以是病毒颗粒、朊病毒颗粒、蛋白颗粒、合成颗粒、小矿物质颗粒或细胞碎片。

如在本文中所使用的，术语“吞噬”指受体介导的过程，其中内源性或外源性细胞或直径大于10nm的颗粒被本公开的吞噬细胞或宿主细胞内化。吞噬通常由多个步骤组成：(1)通过吞噬受体直接或间接地(通过桥接分子)与靶细胞或颗粒上的促吞噬标记物或抗原标记物结合以束缚靶细胞或颗粒；以及(2)内化或吞噬整个靶细胞或颗粒或者其部分。在某些实施方式中，可以通过吞噬细胞或宿主细胞的细胞骨架重排以形成吞噬体(含有内化靶对象的膜结合小室)发生内化。吞噬还可以包括吞噬体的成熟，其中吞噬体变得酸性增加并且与溶酶体融合(以形成吞噬溶酶体)，随后吞噬的靶对象被降解(例如，“吞噬作用”)。或者，在吞噬中可能未观察到吞噬体-溶酶体融合。在又一个实施方式中，在完全降解之前，吞噬体可以将其内容物回流或排出到胞外环境中。在一些实施方式中，吞噬指吞噬作用。在一些实施方式中，吞噬包括本公开的宿主细胞的吞噬细胞将靶细胞或颗粒束缚，但不发生内化。在一些实施方式中，吞噬包括本公开的宿主细胞的吞噬细胞束缚靶细胞或颗粒以及内化部分靶细胞或颗粒。

如在本文中所使用的，术语“吞噬作用”指细胞或大颗粒(>0.5μm)的吞噬过程，其中发生束缚靶细胞或颗粒、吞噬所述靶细胞或颗粒以及降解内化靶细胞或颗粒。在某些实施方式中，吞噬作用包括形成吞噬体，其包围内化了的靶细胞或颗粒，以及使吞噬体与溶酶体融合以形成吞噬溶酶体，其中内容物被降解。在某些实施方式中，在吞噬作用期间，在本公开的宿主细胞上表达的CER与由靶细胞或颗粒表达的靶抗原结合后，形成吞噬突触；在吞噬突触上产生富含肌动蛋白的吞噬杯；吞噬臂通过细胞骨架重排在靶细胞或颗粒周围延伸；最后，通过由马达蛋白产生的力将靶细胞或颗粒拉入吞噬细胞或宿主细胞。如在本文中所使用的，“吞噬作用”包括“胞葬”过程，其特别地指以非炎性方式对凋亡或坏死细胞的吞噬作用。

术语“免疫系统细胞”或“免疫细胞”是指源自骨髓造血干细胞的免疫系统中的任何细胞。造血干细胞产生两个主要谱系：髓系祖细胞(产生诸如单核细胞、巨噬细胞、树突状细胞、巨核细胞和粒细胞的髓细胞)和淋巴样祖细胞(产生诸如T细胞、B细胞和自然杀伤(NK)细胞的淋巴样细胞)。示例性免疫系统细胞包括CD4

术语“T细胞”指T细胞谱系的细胞。“T细胞谱系的细胞”指显示有T细胞或者其前体或祖细胞的至少一种表型特征的细胞，其是不同于其他淋巴细胞以及红细胞或髓细胞谱系细胞的细胞。此类表型特征可以包括表达一种或多种T细胞特异性的蛋白(例如，CD3

术语“B细胞”指B细胞谱系的细胞。“B细胞谱系的细胞”指显示有B细胞或者其前体或祖细胞的至少一种表型特征的细胞，其是不同于其他淋巴细胞以及红细胞或髓细胞谱系细胞的细胞。此类表型特征可以包括表达一种或多种B细胞特异性的蛋白(例如，CD19

针对在细胞表面上表达免疫受体(例如，TCR)的细胞(例如，T细胞)，术语“细胞毒性活性”也称为“细胞溶解活性”，是指在抗原特异性信号传导(例如，通过TCR)之后，细胞诱导靶细胞经历凋亡。在一些实施方式中，细胞毒性细胞可通过释放颗粒中的细胞毒素(如穿孔素、颗粒酶和颗粒溶素)来诱导靶细胞凋亡。穿孔素插入靶细胞膜并形成孔，以允许水和盐快速进入靶细胞。颗粒酶是在靶细胞中诱导凋亡的丝氨酸蛋白酶。颗粒溶素也能够在靶细胞膜上形成孔，并且是促炎性分子。在一些实施方式中，细胞毒性细胞可以通过Fas配体的相互作用在靶细胞中诱导凋亡，随着Fas分子在靶细胞上表达，Fas配体在抗原特异性信号传导后在T细胞上上调。Fas是在多种不同细胞表面上的凋亡信号传导受体分子。

“疾病”是一种对象的健康状况，其中对象不能维持稳态，并且其中如果疾病不能得到改善，则对象的健康将继续恶化。相比之下，对象的“紊乱”或“不利病况”是指对象能够维持稳态的健康状况，但此时对象的健康状况不如其没有紊乱或不利病况时的健康状况。如果不进行治疗，紊乱或不利病况不一定必然导致对象健康状况的进一步下降。

将如在本文中所使用的术语“癌症”定义为以异常细胞的快速和失控生长为特征的疾病。异常细胞可以形成实体瘤或构成恶性血液病。癌细胞可以局部扩散或通过血流和淋巴系统扩散到身体的其他部位。各种癌症的实例包括但不限于乳腺癌、前列腺癌、卵巢癌、宫颈癌、皮肤癌、胰腺癌、结肠直肠癌、肾癌、肝癌、脑癌、淋巴瘤、白血病、肺癌等。

术语“对象”、“患者”和“个体”在本文中可以互换使用，并且旨在包括在其中能够激发免疫应答的活生物体(例如，哺乳动物)。对象的实例包括人、灵长类、奶牛、马、绵羊、犬、猫、小鼠、大鼠、兔、豚鼠、猪及其转基因物种。

“过继细胞免疫疗法”或“过继免疫疗法”是指施用天然存在或基因工程改造的疾病抗原特异性免疫细胞(例如，T细胞)。过继细胞免疫疗法可以是自体的(免疫细胞来自受体)，同种异体的(免疫细胞来自相同物种的供体)或同基因的(免疫细胞来自与受体基因上相同的供体)。

“自体的”指移植物(例如，器官、组织、细胞)来源于随后其将被重新引入的相同对象。

“同种异体的”指来自相同物种的不同对象的移植物。

本公开的嵌合蛋白或表达嵌合蛋白的细胞(例如，串联表达盒或表达串联表达盒的细胞)的“治疗有效量”或“有效量”指足以使所治疗的疾病、紊乱或不利病况的一种或多种症状得到改善的蛋白或细胞的量。当涉及单独施用单个活性成分或表达单一活性成分的细胞时，治疗有效剂量指成分或表达单独成分的细胞的有效量。当涉及联用时，治疗有效剂量指产生治疗作用的活性成分、或者辅助活性成分与表达活性成分的细胞联用的量，无论是连续施用还是同时施用。

“治疗(treat)”或“治疗(treatment)”或“改善”指对对象疾病、紊乱或不利病况的医疗管理。通常，以足以激发治疗或预防的益处的量施用包含表达本公开的嵌合蛋白的宿主细胞的适宜剂量或治疗方案。治疗或预防/防止的益处包括改善临床结局；减轻或缓解与疾病、紊乱或不利病况相关的症状；减少症状的发生；改善生活质量；延长无疾病状态；降低疾病、紊乱或不利病况的程度；稳定疾病状态；推迟疾病进展；缓解；存活；延长生存期；或其任意组合。

术语“抗肿瘤效应”指可以表现为缩小肿瘤体积、减少肿瘤细胞数、减少转移数、延长预期寿命或改善与癌症病况相关的各种生理症状的生物学效应。“抗肿瘤效应”还可以表现为防止恶性血液病或肿瘤形成。

其他定义提供于本公开的全文之中。

本公开内容的串联表达盒包含编码嵌合吞噬受体(CER)和嵌合抗原受体(CAR)/或T细胞受体(TCR)的至少两个转基因。本文提供的串联表达盒的某些实施方式包括：(a)编码CER的多核苷酸，所述CER包含：胞外域，其包含与靶抗原结合的结合结构域；吞噬信号传导结构域；和跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；和(b)编码CAR的多核苷酸，所述CAR包含：胞外域，其包含与靶抗原结合的结合结构域；胞内信号传导结构域；和跨膜结构域，其位于胞外域和胞内信号传导结构域之间并连接胞外域和胞内信号传导结构域。本文提供的串联表达盒的其他实施方式包括：(a)编码CER的多核苷酸，所述CER包含：胞外域，其包含与靶抗原结合的结合结构域；吞噬信号传导结构域；和跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；和(b)编码重组TCR结合蛋白的多核苷酸。在某些实施方式中，编码CER的多核苷酸位于编码CAR或TCR的多核苷酸的5’端。在其他实施方式中，编码CER的多核苷酸位于编码CAR或TCR的多核苷酸的3’端。

以下提供了转基因及其编码的细胞免疫疗法分子的其他方面。

本公开内容的串联表达盒包含至少一个编码CER的多核苷酸。嵌合吞噬受体通常包含：(a)胞外域，其包含与靶抗原结合的结合结构域，(b)吞噬信号传导结构域；和(c)跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域。在某些实施方式中，本文描述的嵌合吞噬受体的胞外域任选地包含胞外间隔区结构域，其位于结合结构域和跨膜结构域之间并连接结合结构域和跨膜结构域。

本文所述的嵌合吞噬受体能够将对靶抗原具有特异性的吞噬表型赋予经修饰表达所述嵌合吞噬受体的宿主细胞。在某些实施方式中，如本文所述的CER的表达将吞噬表型赋予自然不具有吞噬表型的宿主细胞。在某些实施方式中，吞噬活性是吞噬细胞活性。本公开的CER可以用于将吞噬特异性重定向至表达靶抗原的靶细胞。

如本文所述，CER包含特异性针对靶抗原的胞外域。在某些实施方式中，胞外域包含特异性结合靶抗原(例如，磷脂酰丝氨酸)的结合结构域。通过结合结构域的靶分子结合可以阻断靶分子(例如，受体或配体)与另一分子之间的相互作用，并且例如干扰、减弱或消除靶分子的某些功能(例如，信号转导)。在一些实施方式中，靶分子的结合可以诱导某些生物学途径或鉴定靶分子或表达所述靶分子的细胞以用于消除。

适于在本公开内容的CER中使用的结合结构域可以是特异性结合目标靶分子(例如，磷脂酰丝氨酸)的任何多肽或肽。结合结构域的来源包括受体的胞外域，细胞表面受体或分子的配体和抗体或抗原结合部分，例如来自各种物种的抗体可变区。例如，结合结构域可以包含sFv、scFv、Fab、基于scFv的grababody、VH结构域、VL结构域、单域骆驼抗体(VHH)或域抗体。结合结构域可以来自人、灵长类动物、啮齿动物、禽类或绵羊。结合结构域的其他来源包括来自其他物种的抗体可变区，如骆驼科(来自骆驼、单峰驼或美洲驼；Ghahroudi等，FEBS Lett.414:521,1997；Vincke等，J.Biol.Chem.284:3273,2009；Hamers-Casterman等，Nature 363:446,1993和Nguyen等，J.Mol.Biol.275:413,1998)、护士鲨(Roux等，Proc.Nat′l.Acad.Sci.(USA)95:11804,1998)、斑点银鲛(Nguyen等，Immunogen.54:39,2002)或七鳃鳗(Herrin等，Proc.Nat′l.Acad.Sci.(USA)105:2040,2008和Alder等，Nat.Immunol.9:319,2008)。这些抗体仅使用重链可变区形成抗原结合区，即这些功能性抗体仅为重链的同源二聚体(称为“重链抗体”)(Jespers等，Nat.Biotechnol.22:1161,2004；Cortez-Retamozo等，Cancer Res.64:2853,2004；Baral等，Nature Med.12:580,2006；和Barthelemy等，J.Biol.Chem.283:3639,2008)。在某些实施方式中，结合结构域是小鼠的、嵌合的、人的或人源化的。

在某些实施方式中，CER结合结构域包含抗体或其抗原结合片段，如单链Fv片段(scFv)，其包含对靶疾病抗原具有特异性的VH和VL区。在某些实施方式中，抗体或抗原结合片段是嵌合的、人的或人源化的。在进一步的实施方式中，V

由本公开的CER的胞外域特异性结合的靶分子可以存在于目标细胞(“靶细胞”)上或与之结合。示例性的靶细胞包括癌细胞、与自身免疫性疾病或紊乱或者与炎性疾病或紊乱相关的细胞以及感染性微生物(例如，细菌、病毒或真菌)或受感染的细胞(例如，病毒感染的细胞)。感染性生物(如哺乳动物的寄生虫)的细胞也被认为是靶细胞。

在某些实施方式中，胞外域结合促吞噬标记物。如在本文中所使用的，促吞噬标记物是在凋亡、坏死、焦亡或感染细胞表面上显示出的分别将其与非凋亡、非坏死、非焦亡、溶瘤或非感染的细胞相区分的部分(例如，蛋白、脂质或多糖)。促吞噬标记物可以是在凋亡或坏死细胞表面暴露的细胞内的部分，在凋亡或坏死细胞上具有改变的糖基化或改变的表面电荷的部分，或者与凋亡、坏死、焦亡或溶瘤细胞结合的血清部分。针对凋亡细胞的促吞噬标记物的实例包括磷脂酰丝氨酸(PtdSer)、ICAM-3、氧化的低密度脂蛋白、钙网蛋白、膜联蛋白I、补体C1q和血小板反应蛋白。坏死、溶瘤和焦亡细胞也在细胞表面上暴露PtdSer促吞噬标记物。吞噬受体可以利用可溶性桥连分子作为结合促吞噬标记物的中间物，直接或间接地检测(或结合)靶细胞(例如，受损、感染、凋亡、坏死、焦亡或溶瘤细胞)上的促吞噬标记物。在某些此类实施方式中，胞外域靶向的促吞噬标记物是磷脂酰丝氨酸(PtdSer)、ICAM-3、氧化的低密度脂蛋白、钙网蛋白、膜联蛋白I、补体C1q或血小板反应蛋白。结合磷脂酰丝氨酸的示例性Tim4结合结构域包括包含SEQ ID NO:91、SEQ ID NO:96、SEQ ID NO:91的氨基酸23-279或SEQ ID NO:96的氨基酸25-314的氨基酸序列。

在某些实施方式中，胞外域结合肿瘤抗原。示例性肿瘤抗原包括CD138、CD38、CD33、CD123、CD72、CD79a、CD79b、间皮素、PSMA、BCMA、ROR1、MUC-16、L1CAM、CD22、CD19、CD20、CD23、CD24、CD37、CD30、CA125、CD56、c-Met、EGFR、GD-3、HPV E6、HPV E7、MUC-1、HER2、叶酸受体α、CD97、CD171、CD179a、CD44v6、WT1、VEGF-α、VEGFR1、IL-13Rα1、IL-13Rα2、IL-11Rα、PSA、FcRH5、NKG2D配体、NY-ESO-1、TAG-72、CEA、肝配蛋白A2、肝配蛋白B2、Lewis A抗原、Lewis Y抗原、MAGE、MAGE-A1、RAGE-1、叶酸受体β、EGFRviii、VEGFR-2、LGR5、SSX2、AKAP-4、FLT3、岩藻糖基GM1、GM3、o-乙酰基GD2和GD2。

在某些实施方式中，胞外域结合病毒抗原、细菌抗原、真菌抗原、原生动物抗原或寄生虫抗原。

在某些实施方式中，胞外域任选地包含胞外、非信号传导间隔区或接头结构域。在包含的情况下，此类间隔区或接头结构域可以使结合结构域的位置远离宿主细胞表面，以进一步实现适宜的细胞与细胞接触、结合和活化。胞外间隔区结构域通常位于CER的胞外结合结构域和跨膜结构域之间。可以根据选择的靶分子、选择的结合表位、结合结构域尺寸和亲和性来改变胞外间隔区的长度，以优化靶分子的结合(参见例如，Guest等，J.Immunother.28:203-11,2005；PCT公开号WO2014/031687)。在某些实施方式中，胞外间隔区结构域是免疫球蛋白铰链区(例如，IgG1、IgG2、IgG3、IgG4、IgA、IgD)。免疫球蛋白铰链区可以是野生型免疫球蛋白铰链区或改变的野生型免疫球蛋白铰链区。改变的IgG

可以在本文所述CER中使用的铰链区的其他实例包括在1型膜蛋白(如，CD8a、CD4、CD28和CD7)的胞外区域中存在的铰链区，其可以是野生型的或其变体。在进一步的实施方式中，胞外间隔区结构域包含选自下组的免疫球蛋白Fc结构域的全部或部分：CH1结构域、CH2结构域、CH3结构域或其组合(参见例如，PCT公开号WO2014/031687，其间隔区的全部内容通过引用并入本文)。在又进一步的实施方式中，胞外间隔区结构域可以包含II型C-凝集素的茎区域(胞外域位于C-型凝集素结构域和跨膜结构域之间)。II型C-凝集素包括CD23、CD69、CD72、CD94、NKG2A和NKG2D。在又进一步的实施方式中，胞外间隔区结构域可以来自toll样受体(TLR)近膜结构域。TLR近膜结构域包含位于富含亮氨酸的重复序列(LRR)和TLR的跨膜结构域之间的酸性氨基酸。在某些实施方式中，TLR近膜结构域是TLR1、TLR2、TLR3、TLR4、TLR5、TLR6、TLR7、TLR8或TLR9近膜结构域。示例性TLR近膜结构域是包含SEQ ID NO:1所示的氨基酸序列的TLR4近膜结构域。

胞外域可以来自任何哺乳动物物种，包括人、灵长类动物、奶牛、马、山羊、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪及其转基因物种。在某些实施方式中，胞外域是小鼠的、嵌合的、人的或人源化的。

CER的吞噬信号传导结构域是胞内效应结构域，并且能够应答CER的胞外域与靶分子的结合，而将功能性信号传递给细胞。吞噬信号传导结构域可以是保留了足够的信号传导活性的吞噬信号传导分子的任何部分。在一些实施方式中，使用吞噬信号传导分子的全长或全长胞内部分。在一些实施方式中，使用吞噬信号传导分子或吞噬信号传导分子的胞内部分的截短部分，条件是该截短部分保留了足够的信号传导活性。在进一步的实施方式中，吞噬信号传导结构域是吞噬信号传导分子的完整或截短部分的变体，条件是该变体保留了足够的信号传导活性(即，功能性变体)。

可以用于CER中的示例性吞噬信号传导结构域包括MRC1信号传导结构域、MERTK信号传导结构域、Tyro3信号传导结构域、Axl信号传导结构域、ELMO信号传导结构域、Traf6信号传导结构域、Syk信号传导结构域、MyD88信号传导结构域、PI3K信号传导结构域、FcR信号传导结构域(例如，FcγR1、FcγR2A、FcγR2C、FcγR2B2、FcγR3A、FcγR2C、FcγR3A、FcεR1或FcαR1信号传导结构域)、B细胞活化因子受体(BAFF-R)信号传导结构域、DAP12(也称为TYRO蛋白酪氨酸激酶结合蛋白(TYROBP))信号传导结构域、具有ITAM基序1的NFAT活化蛋白(NFAM1)信号传导结构域、CD79b信号传导结构域、TLR信号传导结构域(例如，TLR1、TLR2、TLR3、TLR4、TLR5、TLR6、TLR7、TLR8或TLR9信号传导结构域)、Traf2信号传导结构域或Traf3信号传导结构域。

在某些实施方式中，吞噬信号传导结构域包含与如下序列具有至少约75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或100％同一性的序列：含有SEQ ID NO:2所示的氨基酸序列的MRC1信号传导结构域，含有SEQ ID NO:3所示的氨基酸序列的MERTK信号传导结构域，含有SEQ ID NO:5所示的氨基酸序列的Tyro3信号传导结构域，含有SEQ ID NO:6所示的氨基酸序列的Axl信号传导结构域，含有SEQ ID NO:7所示的氨基酸序列的ELMO信号传导结构域，含有SEQ ID NO:8所示的氨基酸序列的Traf6信号传导结构域，含有SEQ ID NO:9所示的氨基酸序列的Syk信号传导结构域，含有SEQ IDNO:10所示的氨基酸序列的MyD88信号传导结构域，含有SEQ ID NO:11所示的氨基酸序列的PI3K信号传导结构域，含有SEQ ID NO:12所示的氨基酸序列的FcεRIγ信号传导结构域，含有SEQ ID NO:13所示的氨基酸序列的FcγR1信号传导结构域，含有SEQ ID NO:14所示的氨基酸序列的FcγR2A信号传导结构域，含有SEQ ID NO:15所示的氨基酸序列的FcγR2C信号传导结构域，含有SEQ ID NO:16所示的氨基酸序列的FcγR3A信号传导结构域，含有SEQ IDNO:17所示的氨基酸序列的BAFF-R信号传导结构域，含有SEQ ID NO:18所示的氨基酸序列的DAP12信号传导结构域，含有SEQ ID NO:19所示的氨基酸序列的NFAM1信号传导结构域，含有SEQ ID NO:21所示的氨基酸序列的CD79b信号传导结构域，含有SEQ ID NO:22所示的氨基酸序列的TLR1信号传导结构域，含有SEQ ID NO:23所示的氨基酸序列的TLR2信号传导结构域，含有SEQ ID NO:24所示的氨基酸序列的TLR3信号传导结构域，含有SEQ ID NO:25所示的氨基酸序列的TLR4信号传导结构域，含有SEQ ID NO:26所示的氨基酸序列的TLR5信号传导结构域，含有SEQ ID NO:27所示的氨基酸序列的TLR6信号传导结构域，含有SEQ IDNO:28所示的氨基酸序列的TLR7信号传导结构域，含有SEQ ID NO:29所示的氨基酸序列的TLR8信号传导结构域，含有SEQ ID NO:30所示的氨基酸序列的TLR9信号传导结构域，含有SEQ ID NO:31所示的氨基酸序列的Traf2信号传导结构域或者含有SEQ ID NO:32所示的氨基酸序列的Traf3信号传导结构域。

在一些实施方式中，吞噬信号传导结构域是包含或由SEQ ID NO:2所示的氨基酸序列组成的MRC1信号传导结构域，包含或由SEQ ID NO:3所示的氨基酸序列组成的MERTK信号传导结构域，包含或由SEQ ID NO:5所示的氨基酸序列组成的Tyro3信号传导结构域，包含或由SEQ ID NO:6所示的氨基酸序列组成的Axl信号传导结构域，或包含或由SEQ ID NO:7所示的氨基酸序列组成的ELMO信号传导结构域，包含或由SEQ ID NO:8所示的氨基酸序列组成的Traf6信号传导结构域，包含或由SEQ ID NO:9所示的氨基酸序列组成的Syk信号传导结构域，包含或由SEQ ID NO:10所示的氨基酸序列组成的MyD88信号传导结构域，包含或由SEQ ID NO:11所示的氨基酸序列组成的PI3K信号传导结构域，包含或由SEQ ID NO:12所示的氨基酸序列组成的FcεRIγ信号传导结构域，包含或由SEQ ID NO:13所示的氨基酸序列组成的FcγR1信号传导结构域，包含或由SEQ ID NO:14所示的氨基酸序列组成的FcγR2A信号传导结构域，包含或由SEQ ID NO:15所示的氨基酸序列组成的FcγR2C信号传导结构域，包含或由SEQ ID NO:16所示的氨基酸序列组成的FcγR3A信号传导结构域，包含或由SEQ ID NO:17所示的氨基酸序列组成的BAFF-R信号传导结构域，包含或由SEQ ID NO:18所示的氨基酸序列组成的DAP-12信号传导结构域，包含或由SEQ ID NO:19所示的氨基酸序列组成的NFAM1信号传导结构域，包含或由SEQ ID NO:21所示的氨基酸序列组成的CD79b信号传导结构域，包含或由SEQ ID NO:22所示的氨基酸序列组成的TLR1信号传导结构域，包含或由SEQ ID NO:23所示的氨基酸序列组成的TLR2信号传导结构域，包含或由SEQ ID NO:24所示的氨基酸序列组成的TLR3信号传导结构域，包含或由SEQ ID NO:25所示的氨基酸序列组成的TLR4信号传导结构域，包含或由SEQ ID NO:26所示的氨基酸序列组成的TLR5信号传导结构域，包含或由SEQ ID NO:27所示的氨基酸序列组成的TLR6信号传导结构域，包含或由SEQ ID NO:28所示的氨基酸序列组成的TLR7信号传导结构域，包含或由SEQ ID NO:29所示的氨基酸序列组成的TLR8信号传导结构域，包含或由SEQ ID NO:30所示的氨基酸序列组成的TLR9信号传导结构域，包含或由SEQ ID NO:31所示的氨基酸序列组成的Traf2信号传导结构域，或包含或由SEQ ID NO:32所示的氨基酸序列组成的Traf3信号传导结构域。

截短的吞噬信号传导结构域可以是在其N末端、其C末端或者在N末端和C末端是截短的。在某些实施方式中，MRC1吞噬信号传导结构域是在其对应于SEQ ID NO:2所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；MERTK吞噬信号传导结构域是在其对应于SEQ ID NO:3所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；Tyro3吞噬信号传导结构域是在其对应于SEQ ID NO:5所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；Axl吞噬信号传导结构域是在其对应于SEQ ID NO:6所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；ELMO吞噬信号传导结构域是在其对应于SEQ ID NO:7所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；Traf6吞噬信号传导结构域是在其对应于SEQ ID NO:8所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；Syk吞噬信号传导结构域是在其对应于SEQ ID NO:9所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；MyD88吞噬信号传导结构域是在其对应于SEQ ID NO:10所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；PI3K吞噬信号传导结构域是在其对应于SEQ ID NO:11所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；FcεRIγ吞噬信号传导结构域是在其对应于SEQ ID NO:12所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；FcγR1吞噬信号传导结构域是在其对应于SEQ ID NO:13所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；FcγR2A吞噬信号传导结构域是在其对应于SEQ ID NO:14所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；FcγR2C吞噬信号传导结构域是在其对应于SEQ ID NO:15所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；FcγR3A吞噬信号传导结构域是在其对应于SEQ ID NO:16所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；BAFF-R吞噬信号传导结构域是在其对应于SEQ ID NO:17所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；DAP-12吞噬信号传导结构域是在其对应于SEQ IDNO:18所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；NFAM1吞噬信号传导结构域是在其对应于SEQ ID NO:19所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；CD79b吞噬信号传导结构域是在其对应于SEQ ID NO:21所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR1吞噬信号传导结构域是在其对应于SEQ ID NO:22所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR2吞噬信号传导结构域是在其对应于SEQ ID NO:23所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR3吞噬信号传导结构域是在其对应于SEQ ID NO:24所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR4吞噬信号传导结构域是在其对应于SEQ ID NO:25所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR5吞噬信号传导结构域是在其对应于SEQ ID NO:26所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR6吞噬信号传导结构域是在其对应于SEQ ID NO:27所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR7吞噬信号传导结构域是在其对应于SEQ ID NO:28所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR8吞噬信号传导结构域是在其对应于SEQ ID NO:29所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；TLR9吞噬信号传导结构域是在其对应于SEQ ID NO:30所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；Traf2吞噬信号传导结构域是在其对应于SEQ ID NO:31所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸；或Traf3吞噬信号传导结构域是在其对应于SEQ ID NO:32所示的氨基酸序列的N末端截短1、2、3、4、5或更多个氨基酸。

在某些实施方式中，MRC1吞噬信号传导结构域是在其对应于SEQ ID NO:2所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；MERTK吞噬信号传导结构域是在其对应于SEQ ID NO:3所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；Tyro3吞噬信号传导结构域是在其对应于SEQ ID NO:5所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；Axl吞噬信号传导结构域是在其对应于SEQ ID NO:6所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；ELMO吞噬信号传导结构域是在其对应于SEQ ID NO:7所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；Traf6吞噬信号传导结构域是在其对应于SEQ ID NO:8所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；Syk吞噬信号传导结构域是在其对应于SEQ ID NO:9所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；MyD88吞噬信号传导结构域是在其对应于SEQ ID NO:10所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；PI3K吞噬信号传导结构域是在其对应于SEQ ID NO:11所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；FcεRIγ吞噬信号传导结构域是在其对应于SEQ ID NO:12所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；FcγR1吞噬信号传导结构域是在其对应于SEQ ID NO:13所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；FcγR2A吞噬信号传导结构域是在其对应于SEQ ID NO:14所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；FcγR2C吞噬信号传导结构域是在其对应于SEQ ID NO:15所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；FcγR3A吞噬信号传导结构域是在其对应于SEQ ID NO:16所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；BAFF-R吞噬信号传导结构域是在其对应于SEQ ID NO:17所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；DAP-12吞噬信号传导结构域是在其对应于SEQID NO:18所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；NFAM1吞噬信号传导结构域是在其对应于SEQ ID NO:19所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；CD79b吞噬信号传导结构域是在其对应于SEQ ID NO:21所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR1吞噬信号传导结构域是在其对应于SEQ ID NO:22所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR2吞噬信号传导结构域是在其对应于SEQ ID NO:23所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR3吞噬信号传导结构域是在其对应于SEQ ID NO:24所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR4吞噬信号传导结构域是在其对应于SEQ ID NO:25所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR5吞噬信号传导结构域是在其对应于SEQ ID NO:26所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR6吞噬信号传导结构域是在其对应于SEQ ID NO:27所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR7吞噬信号传导结构域是在其对应于SEQ ID NO:28所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR8吞噬信号传导结构域是在其对应于SEQ ID NO:29所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；TLR9吞噬信号传导结构域是在其对应于SEQ IDNO:30所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；Traf2吞噬信号传导结构域是在其对应于SEQ ID NO:31所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸；或Traf3吞噬信号传导结构域是在其对应于SEQ ID NO:32所示的氨基酸序列的C末端截短1、2、3、4、5或更多个氨基酸。

在某些实施方式中，截短的MyD88吞噬信号传导结构域域包含死亡结构域，但缺少Toll/白介素1受体(TIR)同源结构域。此类截短的MyD88吞噬信号传导结构域的实例包括SEQ ID NO:33所示的氨基酸序列。在某些实施方式中，截短的MyD88吞噬信号传导结构域包含TIR结构域。截短的MyD88吞噬信号传导结构域的实例包括含有SEQ ID NO:106所示的氨基酸序列的TIR结构域。示例性截短的Traf6信号传导结构域包含SEQ ID NO:34所示的氨基酸序列。示例性截短的NFAM1信号传导结构域包含SEQ ID NO:35所示的氨基酸序列。示例性截短的CD79b信号传导结构域包含SEQ ID NO:20所示的氨基酸序列。

在某些实施方式中，CER包含第一吞噬信号传导结构域和第二吞噬信号传导结构域。在一些实施方式中，CER包含来自同一分子的第一吞噬信号传导结构域和第二吞噬信号传导结构域。在其他实施方式中，第一吞噬信号传导结构域和第二吞噬信号传导结构域来自不同分子。

吞噬信号传导结构域可以来自哺乳动物物种，包括人、灵长类动物、奶牛、马、山羊、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪及其转基因物种。

本公开内容的CER包含跨膜结构域，其连接胞外域和吞噬信号传导结构域并位于胞外域和吞噬信号传导结构域之间。跨膜结构域是横穿宿主细胞膜并将CER锚定在宿主细胞膜中的疏水性α螺旋。跨膜结构域可直接融合至结合结构域或细胞外间隔区结构域(如果存在的话)。在某些实施方式中，跨膜结构域来自完整的膜蛋白(例如，受体、分化簇(CD)分子、酶、转运蛋白、细胞粘附分子等)。跨膜结构域可以选自与胞外域或吞噬信号传导结构域相同的分子(例如，CER包含TLR4吞噬信号传导结构域和TLR4跨膜结构域或者CER包含Tim4结合结构域和Tim4跨膜结构域)。在某些实施方式中，跨膜结构域和胞外域分别选自不同分子。在其他实施方式中，跨膜结构域和吞噬信号传导结构域分别选自不同分子。在另外的其他实施方式中，跨膜结构域、胞外域和吞噬信号传导结构域分别选自不同分子。

在某些实施方式中，跨膜结构域包含Tim1、Tim4、Tim3、FcR(例如，FcγR1、FcγR2A、FcγR2B2、FcγR2C、FcγR3A、FcεR1或FcαR1)、CD8a、CD28、MERTK、Axl、Tyro3、CD4、DAP12、MRC1、TLR1、TLR2、TLR3、TLR4、TLR5、TLR6、TLR7、TLR8或TLR9跨膜结构域。

在某些实施方式中，跨膜结构域包含与以下序列具有至少约75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％、99％、99.5％或100％同一性的序列：包含SEQ ID NO:36所示的氨基酸序列的Tim1跨膜结构域，包含SEQ ID NO:37或38所示的氨基酸序列的Tim4跨膜结构域，包含SEQ ID NO:39所示的氨基酸序列的Tim3跨膜结构域，包含SEQ ID NO:40所示的氨基酸序列的FcγR1跨膜结构域，包含SEQ ID NO:41所示的氨基酸序列的FcγR2A跨膜结构域，包含SEQ ID NO:42所示的氨基酸序列的FcγR2B2跨膜结构域，包含SEQ ID NO:43所示的氨基酸序列的FcγR2C跨膜结构域，包含SEQ ID NO:44所示的氨基酸序列的FcγR3A跨膜结构域，包含SEQ ID NO:45所示的氨基酸序列的FcεR1跨膜结构域，包含SEQ ID NO:46所示的氨基酸序列的FcαR1跨膜结构域，包含SEQ ID NO:47所示的氨基酸序列的CD8a跨膜结构域，包含SEQ ID NO:107所示的氨基酸序列的CD28跨膜结构域，包含SEQ ID NO:48所示的氨基酸序列的MERTK跨膜结构域，包含SEQ ID NO:49所示的氨基酸序列的Axl跨膜结构域，包含SEQ ID NO:50所示的氨基酸序列的Tyro3跨膜结构域，包含SEQID NO:51所示的氨基酸序列的CD4跨膜结构域，包含SEQ ID NO:52所示的氨基酸序列的DAP12跨膜结构域，包含SEQ ID NO:53所示的氨基酸序列的MRC1跨膜结构域，包含SEQ IDNO:54所示的氨基酸序列的TLR1跨膜结构域，包含SEQ ID NO:55所示的氨基酸序列的TLR2跨膜结构域，包含SEQ ID NO:56所示的氨基酸序列的TLR3跨膜结构域，包含SEQ ID NO:57所示的氨基酸序列的TLR4跨膜结构域，包含SEQ ID NO:58所示的氨基酸序列的TLR5跨膜结构域，包含SEQ ID NO:59所示的氨基酸序列的TLR6跨膜结构域，包含SEQ ID NO:60所示的氨基酸序列的TLR7跨膜结构域，包含SEQ ID NO:61所示的氨基酸序列的TLR8跨膜结构域，或包含SEQ ID NO:62所示的氨基酸序列的TLR9跨膜结构域，

在某些实施方式中，跨膜结构域是包含或由SEQ ID NO:36所示的氨基酸序列组成的Tim1跨膜结构域，包含或由SEQ ID NO:37或38所示的氨基酸序列组成的Tim4跨膜结构域，包含或由SEQ ID NO:39所示的氨基酸序列组成的Tim3跨膜结构域，包含或由SEQ IDNO:40所示的氨基酸序列组成的FcγR1跨膜结构域，包含或由SEQ ID NO:41所示的氨基酸序列组成的FcγR2A跨膜结构域，包含或由SEQ ID NO:42所示的氨基酸序列组成的FcγR2B2跨膜结构域，包含或由SEQ ID NO:43所示的氨基酸序列组成的FcγR2C跨膜结构域，包含或由SEQ ID NO:44所示的氨基酸序列组成的FcγR3A跨膜结构域，包含或由SEQ ID NO:45所示的氨基酸序列组成的FcεR1跨膜结构域，包含或由SEQ ID NO:46所示的氨基酸序列组成的FcαR1跨膜结构域，包含或由SEQ ID NO:47所示的氨基酸序列组成的CD8a跨膜结构域，包含或由SEQ ID NO:107所示的氨基酸序列组成的CD28跨膜结构域，包含或由SEQ IDNO:48所示的氨基酸序列组成的MERTK跨膜结构域，包含或由SEQ ID NO:49所示的氨基酸序列组成的Axl跨膜结构域，包含或由SEQ ID NO:50所示的氨基酸序列组成的Tyro3跨膜结构域，包含或由SEQ ID NO:51所示的氨基酸序列组成的CD4跨膜结构域，包含或由SEQ ID NO:52所示的氨基酸序列组成的DAP12跨膜结构域，包含或由SEQ ID NO:53所示的氨基酸序列组成的MRC1跨膜结构域，包含或由SEQ ID NO:54所示的氨基酸序列组成的TLR1跨膜结构域，包含或由SEQ ID NO:55所示的氨基酸序列组成的TLR2跨膜结构域，包含或由SEQ IDNO:56所示的氨基酸序列组成的TLR3跨膜结构域，包含或由SEQ ID NO:57所示的氨基酸序列组成的TLR4跨膜结构域，包含或由SEQ ID NO:58所示的氨基酸序列组成的TLR5跨膜结构域，包含或由SEQ ID NO:59所示的氨基酸序列组成的TLR6跨膜结构域，包含或由SEQ IDNO:60所示的氨基酸序列组成的TLR7跨膜结构域，包含或由SEQ ID NO:61所示的氨基酸序列组成的TLR8跨膜结构域，或包含或由SEQ ID NO:62所示的氨基酸序列组成的TLR9跨膜结构域。

跨膜结构域可以来自任何哺乳动物物种，包括人、灵长类动物、奶牛、马、山羊、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪及其转基因物种。

在某些实施方式中，嵌合吞噬受体包含来自任何哺乳动物物种的多核苷酸序列，包括人、灵长类动物、奶牛、马、山羊、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪、及其转基因物种或其任何组合。在某些实施方式中，嵌合吞噬受体是小鼠的、嵌合的、人的或人源化的。

应当理解的是，本文所述的CER的一个结构域与另一个结构域的直接融合并不排除中间存在连接氨基酸。连接氨基酸可以是天然的或非天然的(例如，嵌合蛋白的构建体设计的结果)。

在表1中提供了在本公开的串联表达盒中使用的CER的实施方式，并且还在PCT申请号PCT/2017/053553和PCT/US2018/52297中进行了描述，其全部内容通过引用整体并入。

表1：示例性嵌合吞噬受体

在某些实施方式中，本公开内容的串联表达盒包含编码嵌合抗原受体(CAR)的转基因。嵌合抗原受体是重组受体，其通常包含：胞外域，其包含与靶抗原结合的结合结构域；胞内信号传导结构域，和跨膜结构域，其位于胞外域和胞内信号传导结构域之间并连接胞外域和胞内信号传导结构域。

适用于本公开内容的CAR的结合结构域包括任何抗原结合多肽。结合结构域可以包含抗体或其抗原结合片段，包括例如，全长重链、Fab片段、Fab’、F(ab’)

在某些实施方式中，在本公开内容中提供的CAR的胞外域任选地包含胞外、非信号传导间隔区或接头结构域。在包含的情况下，此类间隔区或接头结构域可以使结合结构域的位置远离宿主细胞表面，以进一步实现适宜的细胞与细胞接触、结合和活化。胞外间隔区结构域通常位于CAR的胞外结合结构域和跨膜结构域之间。可以根据选择的靶分子、选择的结合表位、结合结构域尺寸和亲和性来改变胞外间隔区的长度，以优化靶分子的结合(参见例如，Guest等，J.Immunother.28:203-11,2005；PCT公开号WO2014/031687)。在某些实施方式中，胞外间隔区结构域是免疫球蛋白铰链区(例如，IgG1、IgG2、IgG3、IgG4、IgA、IgD)。铰链区可以是野生型免疫球蛋白铰链区或改变的野生型免疫球蛋白铰链区。改变的IgG

可以在本文所述的CAR中使用的铰链区的其他实例包括来自1型膜蛋白(如CD8a、CD4、CD28和CD7)的胞外区域的铰链区，其可以是野生型或其变体。在进一步的实施方式中，胞外间隔区结构域包含选自下组的免疫球蛋白Fc结构域的全部或部分：CH1结构域、CH2结构域、CH3结构域或其组合(参见例如，PCT公开号WO2014/031687，其间隔区的全部内容通过引用并入本文)。在又进一步的实施方式中，胞外间隔区结构域可以包含II型C-凝集素的茎区域(胞外域位于C-型凝集素结构域和跨膜结构域之间)。II型C-凝集素包括CD23、CD69、CD72、CD94、NKG2A和NKG2D。

本公开内容的CAR包含跨膜结构域，其连接胞外域和胞内信号传导结构域并位于胞外域和胞内信号传导结构域之间。跨膜结构域是横穿宿主细胞膜并将CAR锚定在宿主细胞膜中的疏水性α螺旋。跨膜结构域可直接融合至结合结构域或细胞外间隔区结构域(如果存在的话)。在某些实施方式中，跨膜结构域来自完整的膜蛋白(例如，受体、分化簇(CD)分子、酶、转运蛋白、细胞粘附分子等)。跨膜结构域可以选自与胞外域或吞噬信号传导结构域相同的分子(例如，CAR包含CD28共刺激信号传导结构域和CD28跨膜结构域)。在某些实施方式中，跨膜结构域和胞外域分别选自不同分子。在其他实施方式中，跨膜结构域和胞内信号传导结构域分别选自不同分子。在另外的其他实施方式中，跨膜结构域、胞外域和吞噬信号传导结构域分别选自不同分子。

用于本公开内容的CAR的示例性跨膜结构域包括CD28、CD2、CD3ε、CD3δ、CD3ζ、CD25、CD27、CD40、CD79A、CD79B、CD80、CD86、CD95(Fas)、CD134(OX40)、CD137(4-1BB)、CD150(SLAMF1)、CD152(CTLA4)、CD200R、CD223(LAG3)、CD270(HVEM)、CD272(BTLA)、CD273(PD-L2)、CD274(PD-L1)、CD278(ICOS)、CD279(PD-1)、CD300、CD357(GITR)、A2aR、DAP10、FcRα、FcRβ、FcRγ、Fyn、GAL9、KIR、Lck、LAT、LRP、NKG2D、NOTCH1、NOTCH2、NOTCH3、NOTCH4、PTCH2、ROR2、Ryk、Slp76、SIRPα、pTα、TCRα、TCRβ、TIM3、TRIM、LPA5和Zap70。示例性的CD28跨膜结构域包含SEQ ID NO:107所示的氨基酸序列。

CAR的胞内信号传导结构域是胞内效应结构域，并且能够应答CAR的细胞外域与靶分子的结合而将功能性信号传递至细胞。胞内信号传导结构域可以是保留了足够的信号传导活性的胞内信号传导分子的任何部分。在一些实施方式中，使用胞内信号传导分子的全长或全长胞内组分。在一些实施方式中，使用细胞内信号分子的截短部分或细胞内信号分子的胞内组分，条件是截短的部分保留足够的信号转导活性。在进一步的实施方式中，胞内信号传导结构域是胞内信号传导分子的完整或截短部分的变体，条件是该变体保留足够的信号转导活性(即，是功能性变体)。

在某些实施方式中，CAR的胞内信号传导结构域包含含有信号传导结构域的免疫受体酪氨酸激活基序(ITAM)。包含信号传导结构域的ITAM通常包含至少一个(一个、两个、三个、四个或更多个)ITAM，其指YXXL/I-X

CAR胞内信号传导结构域任选地包含共刺激信号传导结构域，当其与主要或经典(例如，ITAM驱动的)活化信号结合而激活时，促进或增强T细胞应答，如T细胞活化、细胞因子产生、增殖、分化、存活、效应功能或其组合。在CAR中使用的共刺激信号传导结构域包括例如CD27、CD28、CD40L、GITR、NKG2C、CARD1、CD2、CD7、CD27、CD30、CD40、CD54(ICAM)、CD83、CD134(OX-40)、CD137(4-1BB)、CD150(SLAMF1)、CD152(CTLA4)、CD223(LAG3)、CD226、CD270(HVEM)、CD273(PD-L2)、CD274(PD-L1)、CD278(ICOS)、DAP10、LAT、LFA-1、LIGHT、NKG2C、SLP76、TRIM、ZAP70或其任何组合。在一个特定的实施方式中，共刺激信号传导结构域包含OX40、CD2、CD27、CD28、ICAM-1、LFA-1(CD11a/CD18)、ICOS(CD278)或4-1BB(CD137)信号传导结构域。可以用于本公开内容的CAR中的示例性CD28共刺激信号传导结构域包含SEQ IDNO:169或170所示的氨基酸序列。示例性4-1BB共刺激信号传导结构域包含SEQ ID NO:168所示的氨基酸序列。在某些实施方式中，CAR包含一个、两个或更多个共刺激信号传导结构域。

在某些实施方式中，嵌合抗原受体包含来自任何哺乳动物物种的多核苷酸序列，包括人、灵长类动物、奶牛、马、山羊、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪、其转基因物种或其任何组合。在某些实施方式中，嵌合抗原受体是小鼠的、嵌合的、人的或人源化的。

在某些实施方式中，CAR是第一代CAR、第二代CAR或第三代CAR。第一代CAR通常具有胞内信号传导结构域，其包含CD3ζ、FcγRI或其他含ITAM的活化结构域的胞内信号传导结构域，以提供T细胞活化信号。第二代CAR还包含共刺激信号传导结构域(例如，来自内源性T细胞共刺激受体的共刺激信号传导结构域，如CD28、4-1BB或ICOS)。第三代CAR包含含有ITAM的活化结构域、第一共刺激信号传导结构域和第二共刺激信号传导结构域。

在某些实施方式中，CAR是基于T细胞受体的嵌合抗原受体(TCR-CAR)。TCR-CAR是通常包含可溶性TCR(包含Vα结构域和Cα结构域的多肽链以及包含Vβ结构域和Cβ结构域的多肽链)的异二聚体融合蛋白，其中VβCβ多肽链连接至跨膜结构域和胞内信号传导组分(例如，含有ITAM的活化结构域和任选地共刺激信号传导结构域)(参见例如，Walseng等，2017Scientific Reports 7:10713)。

本公开内容的CAR可以靶向多种抗原，包括病毒抗原、细菌抗原、真菌抗原、寄生虫抗原、肿瘤抗原、自身免疫性疾病抗原。CAR可以靶向的示例性肿瘤抗原包括CD138、CD38、CD33、CD123、CD72、CD79a、CD79b、间皮素、PSMA、BCMA、ROR1、MUC-16、L1CAM、CD22、CD19、CD20、CD23、CD24、CD37、CD30、CA125、CD56、c-Met、EGFR、GD-3、HPV E6、HPV E7、MUC-1、HER2、叶酸受体α、CD97、CD171、CD179a、CD44v6、WT1、VEGF-α、VEGFR1、IL-13Rα1、IL-13Rα2、IL-11Rα、PSA、FcRH5、NKG2D配体、NY-ESO-1、TAG-72、CEA、肝配蛋白A2、肝配蛋白B2、Lewis A抗原、Lewis Y抗原、MAGE、MAGE-A1、RAGE-1、叶酸受体β、EGFRviii、VEGFR-2、LGR5、SSX2、AKAP-4、FLT3、岩藻糖基GM1、GM3、o-乙酰基GD2和GD2。

在某些实施方式中，本公开内容的串联表达盒包含编码重组TCR结合蛋白的转基因。重组TCR结合蛋白包括由α链多肽和β链多肽的异二聚体或γ链多肽和δ链多肽的异二聚体及其结合片段和融合蛋白组成的“传统”TCR，包括例如：单链TCR、单域TCR、可溶性TCR融合TCR蛋白和TCR融合构建体(TRuC

在某些实施方式中，重组TCR结合蛋白是单链TCR(scTCR)，其包含通过柔性接头与Vβ连接的Vα。在一些实施方式中，scTCR包含Vα-接头-Vβ多肽。在其他实施方式中，scTCR包含Vβ-接头-Vα多肽。

在某些实施方式中，重组TCR结合蛋白是单结构域TCR(例如，Vβ)。

在某些实施方式中，重组TCR结合蛋白是单链TCR(scTCR)融合蛋白。scTCR融合蛋白包含含有scTCR(TCR Vα结构域连接至TCR Vβ结构域)的结合结构域、任选地胞外间隔区、跨膜结构域、和含有含CD3ζITAM激活结构域和任选地共刺激信号传导结构域的胞内信号传导结构域(参见，Aggen等，2012,Gene Ther.19:365-374；Stone等，CancerImmunol.Immunother.2014,63:1163-76)。

在某些实施方式中，重组TCR结合蛋白是TCR融合构建体(TRuC

在某些实施方式中，TCR结合蛋白包含来自任何哺乳动物物种的多核苷酸序列，包括人、灵长类动物、奶牛、马、山羊、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪、其转基因物种或其任何组合。在某些实施方式中，TCR结合蛋白是小鼠的、嵌合的、人的或人源化的。

本公开内容的TCR结合蛋白可以结合多种抗原，包括肿瘤抗原、病毒抗原、细菌抗原、真菌抗原、寄生虫抗原和自身免疫性疾病抗原。重组TCR结合蛋白可以靶向的示例性肿瘤抗原包括WT-1、间皮素、MART-1、NY-ESO-1、MAGE-A3、HPV E7、存活素、α甲胎蛋白和肿瘤特异性新抗原。可以在本公开内容的串联表达盒中使用的示例性HPV16 E7特异性TCR在PCT公开申请号WO2015/184228中提供(通过引用整体并入)。在某些实施方式中，HPV16 E7特异性TCR包含SEQ ID NO:90所示的氨基酸序列。SEQ ID NO:90所示的氨基酸序列在TCRβ链序列和TCRα链序列之间包含P2A自裂解肽，其将在宿主细胞中裂解以形成两条多肽链。因而，在某些实施方式中，以SEQ ID NO:90表示的TCR包含单独的TCRβ和TCRα多肽链，其能够二聚化以形成αβTCR。在某些实施方式中，HPV16 E7特异性TCR包含Vβ，其含有SEQ ID NO:92所示的氨基酸序列。在某些实施方式中，HPV16 E7特异性TCR包含Vα，其含有SEQ ID NO:94所示的氨基酸序列。在进一步的实施方式中，HPV16特异性E7TCR包含含有SEQ ID NO:92所示的氨基酸序列的Vβ和含有SEQ ID NO:94所示的氨基酸序列的Vα。

在某些实施方式中，TCR的Cα结构域、Cβ结构域或两者均包含半胱氨酸取代以在两个恒定结构域半胱氨酸残基之间形成链间二硫键，其在未修饰的TCR中不存在。此类修饰的TCR可以形成更稳定的异二聚体。在特定实施方式中，Cα结构域在野生型蛋白序列的位置48包含Thr→Cys取代，和Cβ结构域在野生型蛋白序列的位置56包含Ser→Cys取代(参见，PCT公开的申请号WO2015/184228)。示例性半胱氨酸修饰的TCR Cβ恒定区包含SEQ ID NO:93所示的氨基酸序列。

在某些实施方式中，TCR包括用疏水性氨基酸取代α和β链之一或两者的恒定区的跨膜结构域中的一个、两个或三个氨基酸，以增加跨膜结构域的疏水性。在某些实施方式中，TCRα链的选自Ser112、Met114和Gly115的一个、两个或三个残基被Gly、Ala、Val、Leu、Ile、Pro、Phe、Met或Trp取代。示例性半胱氨酸修饰的、“LVL”取代的TCR Cα区包含SEQ IDNO:95所示的氨基酸序列。

在某些实施方式中，由串联表达盒编码的CER和CAR/或TCR结合蛋白靶向相同的抗原。在其他实施方式中，由串联表达盒编码的CER和CAR/或TCR结合蛋白分别靶向不同的抗原。

在某些方面中，本公开内容提供了编码本文所述的任何一种或多种受体(例如，CER、CAR和TCR结合蛋白)的核酸分子。核酸可以指单链或双链DNA、cDNA或RNA，并且可以包括彼此互补的核酸的正链和负链，包括反义DNA、cDNA和RNA。核酸可以是天然存在的或合成形式的DNA或RNA。编码所需受体的核酸序列可以使用标准技术使用本领域已知的重组方法来获得或产生，如通过从表达所需序列或其一部分的细胞中筛选文库，通过从已知包含相同序列的载体中获得序列，或通过直接从包含相同序列的细胞或组织中分离序列或其一部分来进行，如在例如Sambrook等(1989和2001版；Molecular Cloning:A LaboratoryManual,Cold Spring Harbor Laboratory Press,NY)和Ausubel等(Current Protocolsin Molecular Biology,2003)中所描述的。或者，目标序列可以合成生产，而不是克隆。

编码本文提供的受体组合物的多核苷酸可以来自任何动物，如人、灵长类动物、奶牛、马、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪或其组合。在某些实施方式中，包含在串联表达盒中的编码至少一个受体或两个受体的多核苷酸来自于与插入该多核苷酸的宿主细胞相同的动物物种。

在某些实施方式中，编码受体的多核苷酸包含在5’末端的编码信号肽的序列(也称为前导肽或信号序列)，其用于将前体蛋白靶向分泌途径。在细胞加工以及受体在宿主细胞膜的定位过程中，任选地将信号肽从细胞外结构域的N-末端切割下来。信号肽序列已被切割或去除的多肽也可以称为成熟多肽。可以在本公开内容的受体中使用的信号肽的实例包括来自内源性分泌蛋白的信号肽，包括例如GM-CSF(SEQ ID NO:64所示的氨基酸序列)或Tim4(SEQ ID NO:65所示的氨基酸序列)。如在本文中所使用的，本文提供的受体多核苷酸或多肽序列(例如，CER、CAR或TCR结合蛋白)可以包括或不包括信号序列。本领域技术人员应当理解的是，对于本文公开的包括信号肽序列的序列，可以用能够将编码的蛋白转运到细胞外膜的另一种信号肽代替该信号肽序列。

在某些实施方式中，对本公开内容中的编码受体的多核苷酸进行密码子优化，以在包含多核苷酸的靶宿主细胞中有效表达(参见例如，Scholten等，Clin.Immunol.119:135-145(2006))。如在本文中所使用的，“密码子优化的”多核苷酸包含异源多核苷酸，该异源多核苷酸具有对应于目标宿主细胞中tRNA的丰度的沉默突变修饰的密码子。

在本公开内容中提供的编码至少两个转基因(例如，CER和CAR、CER和TCR结合蛋白)的多核苷酸可以用于组成串联表达盒。串联表达盒指在为了串联或共表达至少两个转基因的同一组调控序列的控制下或与其有效连接的包含至少两个转基因的载体核酸的组分。可以在本公开内容的串联表达盒中使用的调控序列包括适当的转录起始、终止、启动子和增强子序列；有效的RNA处理信号，如剪接和聚腺苷酸化信号；稳定胞质mRNA的序列；增强翻译效率的序列(即，Kozak共有序列)；增强蛋白稳定性的序列；增强蛋白分泌的序列或其任何组合。

在某些实施方式中，可以构建串联表达盒以优化空间和时间上的控制。例如，串联表达盒可以包含启动子元件，以优化空间和时间上的控制。在一些实施方式中，串联表达盒包含组织特异性启动子或增强子，其能够将串联表达盒特异性导入器官、细胞类型(例如，免疫细胞)或病理微环境，如肿瘤或受感染的组织。“增强子”是附加的启动子元件，其可以协同或独立地起作用以激活转录。在某些实施方式中，串联表达盒包含组成型启动子。用于在本公开内容中使用的串联表达盒的示例性组成型启动子是EF-1α启动子。在某些实施方式中，串联表达盒包含诱导型启动子。在某些实施方式中，串联表达盒包含组织特异性启动子。

串联表达盒中包含的至少两个转基因可以是任何顺序的。例如，包含编码CER的多核苷酸和编码CAR的多核苷酸的串联表达盒从5’至3’可以排列为：CER-CAR或CAR-CER。在另一个实例中，包含编码CER的多核苷酸和编码TCR的多核苷酸的串联表达盒从5’至3’可以排列为：CER-TCR或TCR-CER。

在某些实施方式中，包含两个或更多个结合形成多聚体或复合物的多肽链的受体可以由串联表达构建体中的两个或更多个多核苷酸分子编码。预期在本公开内容的串联表达构建体中表达的示例性多聚体受体包括多链CAR、TCR、TCR-CAR和TRuC

在某些实施方式中，本公开内容的串联表达盒可以包含内部核糖体进入位点(IRES)或肽切割位点，如弗林蛋白酶切割位点或病毒2A肽，其位于在串联表达盒内包含的每个多核苷酸之间，以使得能够从单一mRNA中共表达多种蛋白。例如，IRES、弗林蛋白酶切割位点或病毒2A肽可以位于串联表达盒内编码CER的多核苷酸和编码CAR的多核苷酸之间。在另一个实例中，IRES、弗林蛋白酶切割位点或病毒2A肽可以位于每个编码CER的多核苷酸、编码TCRα链多肽的多核苷酸和编码TCRβ链多肽的多核苷酸之间。在某些实施方式中，病毒2A肽是猪捷申病毒-1(P2A)、Thosea asigna病毒(T2A)、马甲型鼻病毒(E2A)、口蹄疫病毒(F2A)或其变体。示例性T2A肽包含SEQ ID NO:67、68、69和75中任一项所示的氨基酸序列。示例性P2A肽包含SEQ ID NO:70或71所示的氨基酸序列。示例性E2A肽序列包含SEQ ID NO:72所示的氨基酸序列。示例性F2A肽序列包含SEQ ID NO:73所示的氨基酸序列。

本公开内容的串联表达盒的某些实施方式包含编码特异性针对靶抗原(例如，肿瘤抗原)的CAR和/或TCR的多核苷酸和编码与促吞噬标记物(例如，凋亡标记物，如磷脂酰丝氨酸)结合的CER的多核苷酸。在通过CAR/或TCR结合表达靶抗原的靶细胞后，经修饰以表达这种串联表达盒的细胞诱导靶细胞凋亡。凋亡诱导促吞噬标记物(如磷脂酰丝氨酸)在靶细胞上的暴露，然后可靶向受损或凋亡的细胞使其被CER吞噬。

本公开内容的示例性串联表达盒包含：(a)编码CER的多核苷酸，该CER包含：胞外域，所述胞外域包含结合磷脂酰丝氨酸的Tim4结合结构域；TLR4吞噬信号传导结构域；Tim4跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；(b)编码HPV-E7特异性重组T细胞受体(TCR)β链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)β链包含TCRβ可变区和TCRβ恒定区；和(c)编码HPV-E7特异性重组TCRα链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)α链包含TCRα可变区和TCRα恒定区(参见图1A)。在某些实施方式中，串联表达盒包含2A肽序列，其散布在编码CER的多核苷酸、编码TCRβ链的多核苷酸和编码TCRα链的多核苷酸之间。在某些实施方式中，串联表达盒包含与CER和TCR多核苷酸可操作地连接的EF-1α启动子。在某些实施方式中，此类示例性串联表达盒(“CER5-HPV16 E7 TCR”)包含含有SEQ ID NO:97所示的氨基酸序列的CER5和含有SEQ IDNO:90所示的氨基酸序列的HPV16 E7 TCR。

本公开内容的另一示例性串联表达盒包含：(a)编码CER的多核苷酸，该CER包含：胞外域，所述胞外域包含结合磷脂酰丝氨酸的Tim4结合结构域；TLR5吞噬信号传导结构域；Tim4跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；(b)编码HPV-E7特异性重组T细胞受体(TCR)β链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)β链包含TCRβ可变区和TCRβ恒定区；和(c)编码HPV-E7特异性重组TCRα链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)α链包含TCRα可变区和TCRα恒定区(参见图1B)。在某些实施方式中，串联表达盒包含2A肽序列，其散布在编码CER的多核苷酸、编码TCRβ链的多核苷酸和编码TCRα链的多核苷酸之间。在某些实施方式中，串联表达盒包含与CER和TCR多核苷酸可操作地连接的EF-1α启动子。在某些实施方式中，此类示例性串联表达盒(“CER19-HPV16 E7 TCR”)包含含有SEQ ID NO:98所示的氨基酸序列的CER19和含有SEQ ID NO:90所示的氨基酸序列的HPV16 E7 TCR。

本公开内容的另一示例性串联表达盒包含：(a)编码CER的多核苷酸，该CER包含：胞外域，所述胞外域包含结合磷脂酰丝氨酸的Tim4结合结构域；TLR8吞噬信号传导结构域；Tim4跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；(b)编码HPV-E7特异性重组T细胞受体(TCR)β链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)β链包含TCRβ可变区和TCRβ恒定区；和(c)编码HPV-E7特异性重组TCRα链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)α链包含TCRα可变区和TCRα恒定区(参见图1C)。在某些实施方式中，串联表达盒包含2A肽序列，其散布在编码CER的多核苷酸、编码TCRβ链的多核苷酸和编码TCRα链的多核苷酸之间。在某些实施方式中，串联表达盒包含与CER和TCR多核苷酸可操作地连接的EF-1α启动子。在某些实施方式中，此类示例性串联表达盒(“CER21-HPV16 E7 TCR”)包含含有SEQ ID NO:99所示的氨基酸序列的CER21和含有SEQ ID NO:90所示的氨基酸序列的HPV16 E7 TCR。

本公开内容的另一示例性串联表达盒包含：(a)编码CER的多核苷酸，该CER包含：胞外域，所述胞外域包含结合磷脂酰丝氨酸的Tim4结合结构域；NFAM1吞噬信号传导结构域；Tim4跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；(b)编码HPV-E7特异性重组T细胞受体(TCR)β链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)β链包含TCRβ可变区和TCRβ恒定区；和(c)编码HPV-E7特异性重组TCRα链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)α链包含TCRα可变区和TCRα恒定区(参见图1D)。在某些实施方式中，串联表达盒包含2A肽序列，其散布在编码CER的多核苷酸、编码TCRβ链的多核苷酸和编码TCRα链的多核苷酸之间。在某些实施方式中，串联表达盒包含与CER和TCR多核苷酸可操作地连接的EF-1α启动子。在某些实施方式中，此类示例性串联表达盒(“CER25-HPV16 E7 TCR”)包含含有SEQ ID NO:100所示的氨基酸序列的CER25和含有SEQ ID NO:90所示的氨基酸序列的HPV16 E7 TCR。

本公开内容的另一示例性串联表达盒包含：(a)编码CER的多核苷酸，该CER包含：胞外域，所述胞外域包含结合磷脂酰丝氨酸的Tim4结合结构域；TLR2吞噬信号传导结构域；Tim4跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；(b)编码HPV-E7特异性重组T细胞受体(TCR)β链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)β链包含TCRβ可变区和TCRβ恒定区；和(c)编码HPV-E7特异性重组TCRα链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)α链包含TCRα可变区和TCRα恒定区(参见图1E)。在某些实施方式中，串联表达盒包含2A肽序列，其散布在编码CER的多核苷酸、编码TCRβ链的多核苷酸和编码TCRα链的多核苷酸之间。在某些实施方式中，串联表达盒包含与CER和TCR多核苷酸可操作地连接的EF-1α启动子。在某些实施方式中，此类示例性串联表达盒(“CER27-HPV16 E7 TCR”)包含含有SEQ ID NO:101所示的氨基酸序列的CER27和含有SEQ ID NO:90所示的氨基酸序列的HPV16 E7 TCR。

本公开内容的另一示例性串联表达盒包含：(a)编码CER的多核苷酸，该CER包含：胞外域，所述胞外域包含结合磷脂酰丝氨酸的Tim4结合结构域；Traf6吞噬信号传导结构域；Tim4跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；(b)编码HPV-E7特异性重组T细胞受体(TCR)β链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)β链包含TCRβ可变区和TCRβ恒定区；和(c)编码HPV-E7特异性重组TCRα链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)α链包含TCRα可变区和TCRα恒定区(参见图1F)。在某些实施方式中，串联表达盒包含2A肽序列，其散布在编码CER的多核苷酸、编码TCRβ链的多核苷酸和编码TCRα链的多核苷酸之间。在某些实施方式中，串联表达盒包含与CER和TCR多核苷酸可操作地连接的EF-1α启动子。在某些实施方式中，此类示例性串联表达盒(“CER29-HPV16 E7 TCR”)包含含有SEQ ID NO:102所示的氨基酸序列的CER29和含有SEQ ID NO:90所示的氨基酸序列的HPV16 E7 TCR。

本公开内容的又一示例性串联表达盒包含：(a)编码CER的多核苷酸，该CER包含：胞外域，所述胞外域包含结合磷脂酰丝氨酸的Tim4结合结构域；Traf3吞噬信号传导结构域；Tim4跨膜结构域，其位于胞外域和吞噬信号传导结构域之间并连接胞外域和吞噬信号传导结构域；(b)编码HPV-E7特异性重组T细胞受体(TCR)β链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)β链包含TCRβ可变区和TCRβ恒定区；和(c)编码HPV-E7特异性重组TCRα链的多核苷酸，所述HPV-E7特异性重组T细胞受体(TCR)α链包含TCRα可变区和TCRα恒定区(参见图1G)。在某些实施方式中，串联表达盒包含2A肽序列，其散布在编码CER的多核苷酸、编码TCRβ链的多核苷酸和编码TCRα链的多核苷酸之间。在某些实施方式中，串联表达盒包含与CER和TCR多核苷酸可操作地连接的EF-1α启动子。在某些实施方式中，此类示例性串联表达盒(“CER31-HPV16 E7 TCR”)包含含有SEQ ID NO:103所示的氨基酸序列的CER31和含有SEQ ID NO:90所示的氨基酸序列的HPV16 E7 TCR。

可以将编码所需串联表达盒的多核苷酸插入适宜载体中，例如病毒载体、非病毒质粒载体和非病毒载体，如基于脂质的DNA载体、经修饰的mRNA(modRNA)、自我扩增的mRNA、CELiD和转座子介导的基因转移(PiggyBac,Sleeping Beauty)，以导入目的宿主细胞(例如，免疫细胞)。可以将编码本公开内容的串联表达盒的多核苷酸克隆进入任何适宜的载体中，如表达载体、复制载体、探针产生载体或测序载体。在某些实施方式中，将编码CER的多核苷酸和编码CAR或TCR结合蛋白的多核苷酸连接在一起成为单个多核苷酸，然后将其插入载体。在其他实施方式中，可以将编码CER的多核苷酸和编码CAR或TCR结合蛋白的多核苷酸分别插入载体中，以使得表达的氨基酸序列产生功能性CER和CAR/或TCR。在本文中将编码串联表达盒的载体称为“串联表达载体”。

在某些实施方式中，载体包含编码串联表达载体的多核苷酸。在某些实施方式中，载体包含编码CER和CAR/或TCR结合蛋白的串联表达盒。

在某些实施方式中，使用允许串联表达盒长期整合并繁殖到子代细胞的载体。实例包括病毒载体，如腺病毒、腺相关病毒、痘苗病毒、疱疹病毒、巨细胞病毒、痘病毒或逆转录病毒载体，如慢病毒载体。衍生自慢病毒的载体可用于实现长期基因转移，并且与载体相比具有更多优势，包括转导非增殖细胞(如肝细胞)的能力和低免疫原性。

在某些实施方式中，将保持游离的非整合载体用于本公开内容的串联表达盒。非整合病毒载体的实例包括腺病毒载体和已被突变为非整合型的整合型病毒载体，例如非整合型慢病毒载体和非整合型泡沫病毒载体。

在本文中将编码核心病毒的载体称为“病毒载体”。存在大量适用于本公开的组合物的病毒载体，包括经鉴定用于人类基因疗法应用的那些(参见，Pfeifer和Verma，Ann.Rev.Genomics Hum.Genet.2:177,2001)。适宜病毒载体包括基于RNA病毒的载体，如来源于逆转录病毒的载体，例如来源于莫洛尼小鼠白血病病毒(MLV)的载体，以及包括更复杂的来源于逆转录病毒的载体，例如来源于慢病毒的载体。HIV-1-来源的载体属于这一类别。其他实例包括来源于HIV-2、FIV、马传染性贫血病毒、SIV和Maedi-Visna病毒(绵羊慢病毒)的慢病毒载体。使用逆转录病毒和慢病毒载体以及包装细胞用于将含有嵌合受体转基因的病毒颗粒转导入哺乳动物宿主细胞的方法是本领域公知的并且此前已有描述，例如，在美国专利号8,119,772；Walchli等，PLoS One 6:327930,2011；Zhao等，J.Immunol.174:4415,2005；Engels等，Hum.Gene Ther.14:1155,2003；Frecha等，Mol.Ther.18:1748,2010；Verhoeyen等，Methods Mol.Biol.506:97,2009中。逆转录病毒和慢病毒载体构建体以及表达系统也是能够购买得到的。

在某些实施方式中，病毒载体用于向宿主细胞引入编码串联表达盒的非内源性多核酸序列。病毒载体可以是逆转录病毒载体或慢病毒载体。病毒载体还可以包含编码用于转导的标记物的核酸序列。用于病毒载体的转导标记物是本领域已知的，并且包括选择标记物，其可以赋予药物抗性，或可检测标记物，如能够被如流式细胞术等方法检测到的荧光标记物或细胞表面蛋白。在特定实施方式中，病毒载体还包含用于转导的基因标记物，所述基因标记物包含荧光蛋白(例如，绿色、黄色)、人CD2的胞外域或截短的人EGFR(EGFRt或tEGFR；参见Wang等，Blood 118:1255,2011)示例性tEGFR序列包含SEQ ID NO:82所示的氨基酸序列。

还可以将其他病毒载体用于多核苷酸递送，包括DNA病毒载体，包括例如基于腺病毒的载体和基于腺相关病毒(AAV)的载体；来自单纯疱疹病毒(HSV)的载体，包括扩增子载体、复制缺陷HSV和减毒HSV(Krisky等，Gene Ther.5:1517,1998)。

还可以将最近开发用于基因疗法用途的其他病毒载体与本公开的组合物和方法一起使用。此类载体包括来自杆状病毒和α-病毒的那些(Jolly,D J.1999.Emerging ViralVectors.pp 209-40，Friedmann T.编，The Development of Human Gene Therapy.NewYork:Cold Spring Harbor Lab)，或质粒载体(如睡美人或其他转座子载体)。

在需要时间控制的情况下，串联表达载体可以包含能够使得转导细胞诱导性耗竭的元件。例如，此类载体可以包含诱导型自杀基因。自杀基因可以是凋亡基因或赋予试剂(例如，药物)敏感性的基因。示例性的自杀基因包括化学诱导型caspase 9(iCASP9)(美国专利公开号2013/0071414)、化学诱导型Fas或单纯疱疹病毒胸苷激酶(HSV-TK)(赋予对更昔洛韦的敏感性)。在进一步的实施方式中，可以对串联表达载体进行设计以表达已知的细胞表面抗原，其在输注相关抗体后，能够耗竭转导的细胞。可以用于耗竭转导的细胞的细胞表面抗原及其相关抗体的实例包括CD20和利妥昔单抗、RQR8(CD34和CD20表位的组合，能够进行CD34选择和抗-CD20缺失)和利妥昔单抗以及EGFR和西妥昔单抗。

也可以将诱导型载体系统用于串联表达盒的诱导表达，如四环素(Tet)-On载体系统，其用多西环素激活转基因表达(Heinz等，Hum.Gene Ther.2011,22:166-76)。也可以将小分子反应性转录因子用于调控表达。串联表达盒的诱导表达也可以通过使用选择性hock(RUSH)系统来完成，该系统基于通过hook锚定于内质网膜上的链霉亲和素和引入CER和CAR/或TCR结构的链霉亲和素结合蛋白，其中向该系统加入生物素导致CER和CAR/或TCR从内质网释放(Agaugue等，2015,Mol.Ther.23(Suppl.1):S88)。

在某些实施方式中，还可以对串联表达盒修饰的宿主细胞进行修饰以共表达一个或多个小GTPases。Rho GTPases是小的(～21k Da)信号转导G蛋白家族，也是Ras超家族的亚家族，在吞噬作用中可调节各种细胞类型的肌动蛋白细胞骨架组织，并促进伪足扩展和吞噬体关闭(参见例如，Castellano等，2000,J.Cell Sci.113:2955-2961)。吞噬需要将F-肌动蛋白募集到栓系的细胞或颗粒下，并且F-肌动蛋白重排以允许膜延伸导致细胞或颗粒内化。RhoGTPases包括RhoA、Rac1、Rac2、RhoG和CDC42。其他小GTPases(如Rap1)参与补体介导的吞噬作用的调控。小GTPase与编码CER的串联表达盒的共表达可促进或增强宿主细胞对靶细胞或颗粒的内在化和/或吞噬体形成。在一些实施方式中，与含有串联表达盒的载体相比，编码GTPase的重组核酸分子被编码在单独的载体上。在其他实施方式中，编码GTPase的重组核酸分子与串联表达盒编码在相同载体上。GTPase和串联表达盒可以在相同载体上在不同启动子的调控下表达(例如，在不同的多个克隆位点)。或者，串联表达盒和GTPase可以在多顺反子载体中的一个启动子的调控下表达。

可以与串联表达盒共表达的GTPases的实例包括Rac1、Rac2、Rab5(也称为Rab5a)、Rab7、Rap1、RhoA、RhoG、CDC42或其任何组合。在特定实施方式中，GTPase包含或是与SEQ IDNO:83所示的Rac1氨基酸序列、SEQ ID NO:84所示的Rab5氨基酸序列、SEQ ID NO:85所示的Rab7氨基酸序列、SEQ ID NO:86所示的Rap1氨基酸序列、SEQ ID NO:87所示的RhoA氨基酸序列、SEQ ID NO:108所示的CDC42氨基酸序列或其任何组合具有至少90％、至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％、至少99.5％或100％同一性的序列。在某些实施方式中，在宿主细胞中诱导或调节GTPase的表达，以使得经过足够长的时间使串联表达盒编码的CER结合其靶抗原后，GPTase的表达才能开启。在进一步的实施方式中，在足够的时间使CER介导的表达靶抗原的细胞吞噬之后，可以关闭GTPase的表达。

在某些实施方式中，通过引入如本文所述的串联表达盒，可以将从受试者获得的细胞(如免疫细胞)进行基因修饰形成非天然的或重组的细胞(例如，非天然的或重组的免疫细胞)，从而细胞表达位于细胞表面的CER和CAR/或TCR。在某些实施方式中，宿主细胞是免疫细胞，如髓样祖细胞或淋巴样祖细胞。可以进行修饰以包含串联表达盒或包含串联表达盒的载体的示例性免疫细胞包括T细胞、自然杀伤细胞、B细胞、淋巴样前体细胞、抗原呈递细胞、树突状细胞、朗格汉斯细胞、髓样前体细胞、成熟的髓样细胞、单核细胞或巨噬细胞。

在某些实施方式中，B细胞被遗传修饰以表达本公开内容的串联表达盒。B细胞具有对作为宿主细胞可能是有利的某些性质，包括：运输到炎症部位、能够内化和提呈抗原、能够共刺激T细胞、高度增殖和自我更新(持续生存)。在某些实施方式中，串联表达盒修饰的B细胞能够将吞噬的靶细胞或吞噬的靶颗粒消化成更小的肽并通过MHC分子将其提呈至T细胞。串联表达盒修饰的B细胞的抗原提呈可能有助于针对非靶向抗原的免疫应答的抗原扩散。B细胞包括与B细胞谱系相关的祖细胞或前体细胞(例如，前-祖-B细胞、祖-B细胞和前-B细胞)；未成熟和未活化的B细胞；或者成熟的和功能性的或活化的B细胞。在某些实施方式中，B细胞可以是初始B细胞、浆细胞、调节性B细胞、边缘区B细胞、滤泡性B细胞、淋巴浆细胞样细胞、浆母细胞、记忆B细胞或其任意组合。可以根据初始B细胞上缺乏CD27的表达将记忆B细胞与初始B细胞相区分开。在某些实施方式中，B细胞可以是来自人类、小鼠、大鼠或其他哺乳动物的原代细胞或细胞系。B细胞系是本领域技术人员熟知的。如果从哺乳动物获得，B细胞可以从很多来源获得，包括血液、骨髓、脾脏、淋巴结或其他组织或体液。B细胞组分可以是富集的或纯化的。

在某些实施方式中，T细胞被遗传修饰以表达本公开内容的串联表达盒。示例性T细胞包括CD4

在某些实施方式中，表达本公开内容的串联表达盒的宿主细胞不是T细胞或T细胞谱系的细胞，但是是祖细胞、干细胞或已被修饰以表达细胞表面抗CD3的细胞。

在某些实施方式中，将基因编辑方法用于修饰宿主细胞基因组，以包含编码本公开的串联表达盒。基因编辑或基因组编辑是一种基因工程方法，其中使用基因工程核酸内切酶插入、置换或从宿主细胞的基因组中删除DNA。核酸酶在基因组中的靶基因座处形成特异性的双链断裂。然后，宿主细胞的内源性DNA修复途径修复所诱导的一个或多个断裂，例如通过非同源末端连接(NHEJ)和同源重组。在基因编辑中使用的示例性核酸内切酶包括锌指核酸酶(ZFN)、转录激活样效应因子(TALE)核酸酶、成簇的规律间隔短回文重复序列(CRISPR)/Cas核酸酶系统(例如，CRISPR-Cas9)、大范围核酸酶或其组合。使用基因编辑核酸内切酶在包括B细胞和T细胞的免疫细胞中破坏或敲除基因或基因表达的方法是本领域已知的，并且例如在PCT公开号WO 2015/066262；WO 2013/074916；WO 2014/059173；Cheong等，Nat.Comm.2016 7:10934；Chu等，Proc.Natl.Acad.Sci.USA 2016 113:12514-12519中对其进行了描述；来自每份文献的方法的全部内容均通过引用并入本文。

在某些实施方式中，宿主细胞内源性基因的表达被抑制、敲减或敲除。在B细胞中可以被抑制、敲减或敲除的内源性基因的实例包括IGH、IGκ、IGλ或其任何组合。在T细胞中可以被抑制、敲减或敲除的内源性基因的实例包括TCR基因(TRA或TRB)、HLA基因(I类HLA基因或II类HLA基因)、免疫检查点分子(PD-L1、PD-L2、CD80、CD86、B7-H3、B7-H4、HVEM、腺苷、GAL9、VISTA、CEACAM-1、CEACAM-3、CEACAM-5、PVRL2、PD-1、CTLA-4、BTLA、KIR、LAG3、TIM3、A2aR、CD244/2B4、CD160、TIGIT、LAIR-1或PVRIG/CD112R)或其任何组合。可以在基因水平、转录水平、翻译水平或其组合抑制、敲减或敲除内源性基因的表达。可以通过例如RNA干扰剂(例如，siRNA、shRNA、miRNA等)或经工程改造的核酸内切酶(例如，CRISPR/Cas核酸酶系统、锌指核酸酶(ZFN)、转录激活样效应因子核酸酶(TALEN)、大范围核酸酶)或其任意组合实现抑制、敲减或敲除内源性基因的方法。在某些实施方式中，如通过经工程改造的核酸内切酶，将本公开内容的串联表达盒插入内源性B细胞基因的基因座中而敲除内源性B细胞基因(例如，IGH、IGκ或IGλ)。在某些实施方式中，如通过经工程改造的核酸内切酶，将编码本公开内容的串联表达盒的多核苷酸插入内源性T细胞基因的基因座中以敲除内源性T细胞基因(例如，TCR基因、HLA基因或免疫检查点分子基因)。

本公开内容还提供了包含串联表达盒修饰的宿主细胞群的组合物。在某些实施方式中，串联表达盒修饰的宿主细胞群可以是B细胞群、T细胞群、自然杀伤细胞群、淋巴前体细胞群、抗原呈递细胞群、树突状细胞群、朗格汉斯细胞群、骨髓前体细胞群、成熟髓样细胞群或其任何组合。而且，特定细胞类型的串联表达盒修饰的宿主细胞群可以由一种或多种亚型组成。例如，B细胞群可以由串联表达盒修饰的初始B细胞、浆细胞、调节性B细胞、边缘区B细胞、淋巴浆细胞样细胞、成浆细胞、记忆性B细胞或其任何组合组成。在另一个实例中，T细胞群可以由串联表达盒修饰的CD4

在某些实施方式中，宿主细胞群由各自表达相同串联表达盒的细胞组成。在其他实施方式中，宿主细胞群由两个或更多个宿主细胞亚群的混合物组成，其中每个亚群表达不同的串联表达盒。

在某些实施方式中，当制备串联表达盒修饰的宿主细胞(例如，B细胞或T细胞)时，可以将促进宿主细胞(例如，B细胞或T细胞)增殖的一种或多种生长因子细胞因子添加到细胞培养基中。细胞因子可以是人的或非人的。可以用于促进T细胞增殖的示例性生长因子细胞因子包括IL-2、IL-15等。可以用于促进B细胞增殖的示例性生长因子细胞因子包括CD40L、IL-2、IL-4、IL-15、IL-21、BAFF等。

在使用串联表达盒载体对宿主细胞进行基因修饰之前，宿主细胞(例如，T细胞、B细胞、自然杀伤细胞等)的来源是从对象(例如，全血、外周血单核细胞、骨髓、淋巴结组织、脐带血、胸腺组织、来自感染部位的组织、腹水、胸腔积液、脾脏组织)中获得的，使用本领域已知的方法从其中分离宿主细胞。可以根据已知的技术收集特定宿主细胞亚群，并根据已知技术进行富集或耗竭，如与抗体亲和结合、流式细胞术和/或免疫磁性选择。在富集和/或耗竭步骤并引入串联表达盒之后，可以根据已知的技术或对本领域技术人员而言将是显而易见的该技术的变体对所需的经修饰的宿主细胞进行体外扩增。

由串联表达盒编码的受体在宿主细胞上的表达可以根据很多本领域公认的用于测定宿主细胞(例如，T细胞)活性的方法来进行功能表征，包括确定T细胞的结合、活化或诱导，还包括确定抗原特异性的T细胞应答。实例包括确定T细胞增殖、T细胞因子释放、抗原特异性T细胞刺激、CTL活性(例如，通过检测预载靶细胞中

在某些实施方式中，包含CER的串联表达盒修饰的宿主细胞对靶细胞具有约20至约1,500的吞噬指数。“吞噬指数”是对转导的宿主细胞吞噬活性的量度，其通过计数在设定时间段内在培养基中孵育的靶细胞或颗粒和串联表达盒修饰宿主细胞的混悬液中，每个串联表达盒修饰宿主细胞摄入的靶细胞或颗粒数而确定。可以通过乘数[被吞噬的靶细胞总数/计数的串联表达盒修饰细胞的总数(例如，吞噬频率)]x[每个串联表达盒

宿主细胞可以来自动物，如人、灵长类动物、奶牛、马、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠、猪或其组合。在一个优选的实施方式中，动物是人。宿主细胞可以来自健康对象或患有与抗原的表达或过表达相关的疾病的对象。

在一个方面中，本公开内容提供了赋予细胞抗原特异性细胞溶解活性和吞噬活性的方法，其包括将根据本文中任何实施方式所述的串联表达盒引入宿主细胞；和在宿主细胞中表达CER和CAR/或TCR结合蛋白。在某些实施方式中，CER和CAR/或TCR结合蛋白结合至相同靶抗原。在一些实施方式中，CER和CAR/或TCR结合至不同靶抗原。在某些实施方式中，经本公开内容的串联表达盒修饰的宿主细胞能够吞噬靶细胞或靶细胞的一部分。因此，经本公开内容的串联表达盒修饰的细胞可通过多种方式具有靶向细胞杀伤能力：靶细胞的细胞溶解、整个靶细胞的吞噬、靶细胞的一部分的吞噬或其任何组合。

在另一个方面中，本公开内容提供了用于增强细胞抗原特异性细胞毒性活性的方法，其包括将根据本文中任何实施方式所述的串联表达盒引入宿主细胞；和在宿主细胞中表达CER和CAR/或TCR结合蛋白，其中与仅表达CAR/或TCR结合蛋白的宿主细胞相比，串联表达盒的表达增强宿主细胞的细胞毒活性。在某些实施方式中，与仅表达CAR/或TCR的宿主细胞相比，宿主细胞的细胞毒活性增加至少约10％、15％、20％、25％、30％、35％、40％、50％、55％、60％、65％、70％、75％、80％、85％、90％、95％、100％、110％、120％、130％、140％、150％、160％、170％、180％、190％、200％或更多。在进一步的实施方式中，串联表达盒赋予协同细胞毒应答。在一些实施方式中，宿主细胞是T细胞或NK细胞。测量宿主细胞(特别是免疫细胞，如T细胞和NK细胞)细胞毒活性的方法包括铬(

在另一个方面中，可以将根据本文提供的任何实施方式所述的串联表达盒用于治疗患有疾病、紊乱或不利病况的对象的方法中。这些方法的实施方式包括向对象施用治疗有效量的药物组合物，该药物组合物包含根据本说明书所述的一种或多种串联表达盒、编码一种或多种串联表达盒的多核苷酸、包含一种或多种串联表达盒的载体或经基因修饰以表达一种或多种串联表达盒的宿主细胞群。

可以使用表达如本公开所述的表达串联表达盒的细胞治疗的疾病包括癌症、自身免疫性疾病、感染性疾病(病毒、细菌、真菌、原生动物感染)。过继免疫和基因疗法是用于各种类型的癌症(Morgan等，Science 314:126,2006；Schmitt等，Hum.Gene Ther.20:1240,2009；June,J.Clin.Invest.117:1466,2007)和感染性疾病(Kitchen等，PLoS One 4:38208,2009；Rossi等，Nat.Biotechnol.25:1444,2007；Zhang等，PLoS Pathog.6:e1001018,2010；Luo等，J.Mol.Med.89:903,2011)的有希望的疗法。

多种癌症，包括实体瘤和白血病，均适于使用本文提供的串联表达盒组合物来治疗。可以使用本文所述的受体、经修饰的宿主细胞和组合物治疗的示例性癌症包括乳腺、前列腺和结肠腺癌；所有形式的肺支气管肺癌；髓样白血病；黑色素瘤；肝癌；神经母细胞瘤；乳头状瘤；胺前体摄取与脱羧细胞瘤；迷芽瘤；鳃原瘤；恶性类癌综合征；类癌心脏病；和癌(例如，Walker癌、基底细胞癌、基底鳞状细胞癌、Brown-Pearce癌、导管癌、Ehrlich肿瘤、Krebs 2癌、Merkel细胞癌、粘液性癌、非小细胞肺癌、燕麦细胞癌、乳头状癌、硬癌、细支气管癌、支气管癌、磷状细胞癌和过渡细胞癌)。可以使用本文所述的受体、经修饰的宿主细胞和组合物治疗的其他癌症类型包括组织细胞病；恶性组织细胞病；白血病；霍奇金氏病；免疫增生性小肠病；非霍奇金氏淋巴瘤；浆细胞瘤；多发性骨髓瘤；浆细胞瘤；网状内皮组织增殖；黑色素瘤；软骨母细胞瘤；软骨瘤；软骨肉瘤；纤维瘤；纤维肉瘤；巨细胞瘤；组织细胞瘤；脂肪瘤；脂肪肉瘤；间皮瘤；粘液瘤；粘液肉瘤；骨瘤；骨肉瘤；脊索瘤；颅咽管瘤；无性细胞瘤；错构瘤；间质瘤；中肾瘤；肌肉瘤；成釉细胞瘤；牙骨质瘤；牙瘤；畸胎瘤；胸腺瘤；滋养细胞肿瘤。而且，还考虑可以使用本文所述的受体、经修饰的宿主细胞和组合物治疗下述类型的癌症：腺瘤；胆管瘤；胆脂瘤；圆柱瘤；囊腺癌；囊腺瘤；颗粒细胞瘤；两性胚胎细胞瘤；肝癌；汗腺瘤；胰岛细胞瘤；莱迪希细胞瘤；乳头状瘤；支持细胞瘤；卵泡膜细胞瘤；平滑肌瘤；平滑肌肉瘤；成肌细胞瘤；肌瘤；肌肉瘤；横纹肌瘤；横纹肌肉瘤；室管膜瘤；神经节细胞瘤；神经胶质瘤；髓母细胞瘤；脑膜瘤；神经鞘瘤；神经母细胞瘤；神经上皮瘤；神经纤维瘤；神经瘤；副神经节瘤；副神经节瘤非嗜铬细胞瘤。可以治疗的癌症类型还包括血管角化瘤；血管淋巴样增生伴嗜酸性粒细胞增多；血管瘤硬化；血管瘤病；血管球瘤；血管内皮瘤；血管瘤；血管外皮细胞瘤；血管肉瘤；淋巴管瘤；淋巴管肌瘤；淋巴管肉瘤；松果体瘤；癌肉瘤；软骨肉瘤；叶状囊肉瘤；纤维肉瘤；血管肉瘤；平滑肌肉瘤；白血病性肉瘤；脂肪肉瘤；淋巴管肉瘤；肌肉瘤；粘液肉瘤；卵巢癌；横纹肌肉瘤；肉瘤；赘生物；神经纤维瘤病和宫颈非典型增生。

适于使用本文所述的串联表达盒组合物疗法的示例性过度增生性病症是B细胞癌，包括B细胞淋巴瘤(如各种形式的霍奇金氏病、非霍奇金氏淋巴瘤(NHL)或中枢神经系统淋巴瘤)、白血病(如急性淋巴细胞白血病(ALL)、慢性淋巴细胞白血病(CLL)、毛细胞白血病、慢性髓性白血病的B母细胞转化)和骨髓瘤(如多发性骨髓瘤)。其他可以使用本文所述的受体、经修饰的宿主细胞和组合物治疗的B细胞癌症包括小淋巴细胞性淋巴瘤、B细胞前淋巴细胞白血病、淋巴浆细胞性淋巴瘤、脾边缘区淋巴瘤、浆细胞性骨髓瘤、骨单发浆细胞瘤、骨外浆细胞瘤、粘膜相关淋巴组织(MALT)的节外边缘区B细胞淋巴瘤、淋巴结边缘区B细胞淋巴瘤、滤泡性淋巴瘤、套细胞淋巴瘤、弥漫性大B细胞淋巴瘤、纵隔(胸腺)大B细胞淋巴瘤、血管内大B细胞淋巴瘤、原发性积液淋巴瘤、伯基特氏淋巴瘤/白血病、不确定恶性潜能的B细胞增殖、淋巴瘤样肉芽肿病和移植后淋巴组织增生性疾病。

感染性疾病包括与感染剂相关的那些并且包括任意多种细菌(例如，致病性E.coli、S.typhimurium、P.aeruginosa、B.anthracis、C.botulinum、C.difficile、C.perfringens、H.pylori、V.cholerae、Listeria spp.、Rickettsia spp.、Chlamydiaspp.等)、分枝杆菌和寄生虫(包括原生动物任何已知的寄生虫成员)。感染性病毒包括真核病毒，如腺病毒、布尼亚病毒、疱疹病毒、乳多空病毒、乳头瘤病毒(例如，HPV)、副粘病毒、小核糖核酸病毒、弹状病毒(例如，狂犬病病毒)、正粘病毒(例如，流感病毒)、痘病毒(例如，牛痘病毒)、呼肠孤病毒、逆转录病毒、慢病毒(例如HIV)、黄病毒(例如，HCV，HBV)等。在某些实施方式中，将包含根据本公开的串联表达盒的组合物用于治疗会在对象中建立持续感染的微生物的感染。

治疗对象的方法包括施用有效量的串联表达盒修饰的细胞(即，表达串联表达盒的重组细胞)。串联表达盒修饰的细胞对于对象而言可以是异基因的、同基因的、同种异体的或自体的。

包含串联表达盒修饰的细胞的药物组合物可以由医疗领域的技术人员确定以适于所治疗(或预防)的疾病或病症的方式施用。将通过这些因素如患者病况、体格、体重、体表面积、年龄、性别、疾病的类型和严重程度、所施用的特定疗法、活性成分的特定形式、施用的时间和方法以及伴随施用的其他药物来确定组合物施用的适宜剂量、适宜持续时间和频率。本公开提供了药物组合物，所述药物组合物包含串联表达盒修饰的细胞和药学上可接受的载体、稀释剂或赋形剂。适宜的赋形剂包括水、盐水、右旋糖、甘油等及其组合。其他适宜的输注介质可以是任意的等渗介质制剂，包括盐水、Normosol R(Abbott)、Plasma-Lyte A(Baxter)、5％右旋糖水溶液或林格氏乳酸盐。

在药物组合物中细胞的治疗有效量至少是1个细胞(例如，1个串联表达盒修饰的T细胞)或者更通常地是多于10

如本文所述的包含串联表达盒、包含串联表达盒的载体或串联表达盒修饰的细胞的组合物可以静脉内、腹膜内、鼻内、肿瘤内、骨髓内、淋巴结内和/或脑脊髓液内施用。

串联表达盒组合物可以与一种或多种其他治疗剂组合给予对象。可以与根据本说明书所述的串联表达盒组合物联合施用的治疗剂的实例包括放射疗法、基因工程细胞免疫疗法(例如，T细胞、树突状细胞、自然杀伤细胞、巨噬细胞、嵌合抗原受体疗法)、抗体疗法、免疫检查点分子抑制剂疗法、UV光疗法、电脉冲疗法、高强度聚焦超声疗法、溶瘤病毒疗法或药物疗法，如化学治疗剂、治疗性肽、激素、适体、抗生素、抗病毒剂、抗真菌剂、抗炎剂、小分子疗法。

放射疗法包括外部束放射疗法(例如，常规外部束放射疗法、立体定向放射疗法、三维保形放射疗法、强度调制放射疗法、体积调制电弧疗法、粒子疗法、质子疗法和螺旋钻疗法)、近距离放射疗法、全身放射性同位素疗法、术中放射疗法或其任何组合。

与本文所述的串联表达盒组合物结合使用的示例性抗体包括利妥昔单抗、帕妥珠单抗、曲妥珠单抗、阿仑单抗、替伊莫单抗、本妥昔单抗、西妥昔单抗、贝伐单抗、阿昔单抗、阿达木单抗、阿法西普、巴利西单抗、贝利单抗、贝佐洛单抗、卡那基单抗、赛妥珠单抗、达克珠单抗、地诺单抗、依法珠单抗、戈利木单抗、olaratumab、帕利珠单抗、帕尼单抗和托珠单抗。

可以与本文所述的串联表达盒组合物结合使用的示例性免疫检查点分子的抑制剂包括靶向PD-L1、PD-L2、CD80、CD86、B7-H3、B7-H4、HVEM、腺苷、GAL9、VISTA、CEACAM-1、CEACAM-3、CEACAM-5、PVRL2、PD-1、CTLA-4、BTLA、KIR、LAG3、TIM3、A2aR、CD244/2B4、CD160、TIGIT、LAIR-1、PVRIG/CD112R或其任何组合的检查点抑制剂。在某些实施方式中，疫检查点抑制剂可以是抗体、肽、RNAi剂或小分子。对CTLA-4具有特异性的抗体可以是伊匹单抗或曲美母单抗。对PD-1具有特异性的抗体可以是匹利珠单抗(pidilizumab)、纳武单抗或派姆单抗。对PD-L1具体特异性的抗体可以是德瓦鲁单抗(durvalumab)、阿特珠单抗或阿维鲁单抗(avelumab)。

化疗药物包括抑制有丝分裂或细胞分裂的非特异性细胞毒剂，以及通过靶向与肿瘤生长、进展和转移有关的特定分子(例如癌基因)来阻止癌细胞生长和扩散的分子靶向疗法。与本文所述的串联表达盒组合物结合使用的示例性非特异性化疗剂包括烷化剂、基于铂的药剂、细胞毒剂、染色质功能抑制剂、拓扑异构酶抑制剂、微管抑制药、DNA损伤剂、抗代谢物(如叶酸拮抗剂、嘧啶类似物、嘌呤类似物和糖修饰类似物)、DNA合成抑制剂、DNA相互作用剂(如嵌入剂)和DNA修复抑制剂。

被考虑用于本文考虑的联合疗法的化学治疗剂的实例包括维罗非尼、达拉非尼、曲美替尼、考比替尼、阿那曲唑

用于本文考虑的联合疗法的示例性烷化剂包括氮芥、乙烯亚胺衍生物、烷基磺酸盐、亚硝基脲和三氮烯，乌拉莫司汀(Aminouracil

用于本文考虑的联合疗法的示例性的基于铂的药剂包括卡铂、顺铂、奥沙利铂、奈达铂、吡铂、沙铂、菲铂和三铂四硝酸酯。

可以与本文所述的串联表达盒组合物结合使用的示例性分子靶向抑制剂包括靶向与癌细胞生长和存活有关的分子的小分子，包括，例如激素拮抗剂、信号转导抑制剂、基因表达抑制剂(例如，翻译抑制剂)、凋亡诱导剂、血管生成抑制剂(例如，VEGF途径抑制剂)、酪氨酸激酶抑制剂(例如，EGF/EGFR途径抑制剂)、生长因子抑制剂、GTPase抑制剂、丝氨酸/苏氨酸激酶抑制剂、转录因子抑制剂、与癌症相关的驱动突变的抑制剂，B-Raf抑制剂、MEK抑制剂、mTOR抑制剂、腺苷途径抑制剂、EGFR抑制剂、PI3K抑制剂、BCL2抑制剂、VEGFR抑制剂、MET抑制剂、MYC抑制剂、BCR-ABL抑制剂、HER2抑制剂、H-RAS抑制剂、K-RAS抑制剂、PDGFR抑制剂、ALK抑制剂、ROS1抑制剂和BTK抑制剂。在某些实施方式中，分子靶向疗法的使用包括对被鉴定为患有具有分子靶标(例如，驱动癌基因)的肿瘤的对象施用对分子靶标具有特异性的分子靶向疗法。在某些实施方式中，分子靶标具有激活突变。在某些实施方式中，将串联表达盒修饰的细胞与分子靶向抑制剂结合使用，可增加抗肿瘤反应的强度、抗肿瘤反应的持久性或两者。在某些实施方式中，以低于典型剂量的分子靶向疗法与串联表达盒修饰的细胞联合使用。

可以与本文所述的串联表达盒组合物结合使用的示例性血管生成抑制剂包括但不限于A6(Angstrom Pharmaceuticals)，ABT-510(Abbott Laboratories)，ABT-627(阿曲生坦)(Abbott Laboratories/Xinlay)，ABT-869(Abbott Laboratories)，Actimid(CC4047，泊马度胺)(Celgene Corporation)，AdGVPEDF.11D(GenVec)，ADH-1(Exherin)(Adherex Technologies)，AEE788(Novartis)，AG-013736(阿西替尼)(Pfizer)，AG3340(普马司他)(Agouron Pharmaceuticals)，AGX1053(AngioGenex)，AGX51(AngioGenex)，ALN-VSP(ALN-VSP O2)(Alnylam Pharmaceuticals)，AMG 386(Amgen)，AMG706(Amgen)，阿帕替尼(YN968D1)(Jiangsu Hengrui Medicine)，AP23573(地磷莫司/MK8669)(AriadPharmaceuticals)，AQ4N(Novavea)，ARQ 197(ArQule)，ASA404(Novartis/Antisoma)，阿替莫德(Callisto Pharmaceuticals)，ATN-161(Attenuon)，AV-412(AveoPharmaceuticals)，AV-951(Aveo Pharmaceuticals)，阿瓦斯汀(贝伐单抗)(Genentech)，AZD2171(西地尼布/Recentin)(AstraZeneca)，BAY 57-9352(替拉替尼)(Bayer)，BEZ235(Novartis)，BIBF1120(Boehringer Ingelheim Pharmaceuticals)，BIBW 2992(Boehringer Ingelheim Pharmaceuticals)，BMS-275291(Bristol-Myers Squibb)，BMS-582664(布立尼布)(Bristol-Myers Squibb)，BMS-690514(Bristol-Myers Squibb)，骨化三醇，CCI-779(驮瑞塞尔)(Wyeth)，CDP-791(ImClone Systems)，高粗榧碱(高三尖杉酯碱/HHT)(ChemGenex Therapeutics)，西乐葆(塞来昔布)(Pfizer)，CEP-7055(Cephalon/Sanofi)，CHIR-265(Chiron Corporation)，NGR-TNF，COL-3(Metastat)(CollagenexPharmaceuticals)，康普瑞汀(Oxigene)，CP-751,871(Figitumumab)(Pfizer)，CP-547,632(Pfizer)，CS-7017(Daiichi Sankyo Pharma)，CT-322(Angiocept)(Adnexus)，姜黄素，达肝素(法安明)(Pfizer)，双硫仑(安塔布司)，E7820(Eisai Limited)，E7080(EisaiLimited)，EMD 121974(西仑吉肽)(EMD Pharmaceuticals)，ENMD-1198(EntreMed)，ENMD-2076(EntreMed)，恩度(Simcere)，爱比妥(ImClone/Bristol-Myers Squibb)，EZN-2208(Enzon Pharmaceuticals)，EZN-2968(Enzon Pharmaceuticals)，GC1008(Genzyme)，染料木素，GSK1363089(Foretinib)(GlaxoSmithKline)，GW786034(帕唑帕尼)(GlaxoSmithKline)，GT-111(Vascular Biogenics Ltd.)，IMC-1121B(雷莫芦单抗)(ImClone Systems)，IMC-18F1(ImClone Systems)，IMC-3G3(ImClone LLC)，INCB007839(Incyte Corporation)，INGN 241(Introgen Therapeutics)，易瑞沙(ZD1839/吉非替尼)，LBH589(Faridak/Panobinostst)(Novartis)，Lucentis(雷珠单抗)(Genentech/Novartis)，LY317615(Enzastaurin)(Eli Lilly and Company)，Macugen(哌加他尼)(Pfizer)，MEDI522(Abegrin)(MedImmune)，MLN518(坦度替尼)(Millennium)，Neovastat(AE941/倍尼芬)(Aeterna Zentaris)，Nexavar(Bayer/Onyx)，NM-3(GenzymeCorporation)，那可丁(Cougar Biotechnology)，NPI-2358(Nereus Pharmaceuticals)，OSI-930(OSI)，Palomid 529(Paloma Pharmaceuticals，Inc.)，Panzem胶囊剂(2ME2)(EntreMed)，Panzem NCD(2ME2)(EntreMed)，PF-02341066(Pfizer)，PF-04554878(Pfizer)，PI-88(Progen Industries/Medigen Biotechnology)，PKC412(Novartis)，茶多酚E(绿茶提取物)(Polypheno E International，Inc.)，PPI-2458(PraecisPharmaceuticals)，PTC299(PTC Therapeutics)，PTK787(瓦他拉尼)(Novartis)，PXD101(贝利司他)(CuraGen Corporation)，RAD001(依维莫司)(Novartis)，RAF265(Novartis)，瑞格非尼(BAY73-4506)(Bayer)，Revlimid(Celgene)，阿奈可他(Alcon Research)，SN38(脂质体)(Neopharm)，SNS-032(BMS-387032)(Sunesis)，SOM230(帕瑞肽)(Novartis)，角鲨胺(Genaera)，苏拉明，索坦(Pfizer)，特罗凯(Genentech)，TB-403(Thrombogenics)，Tempostatin(Collard Biopharmaceuticals)，四硫钼酸盐(Sigma-Aldrich)，TG100801(TargeGen)，沙利度胺(Celgene Corporation)，亭扎肝素钠，TKI258(Novartis)，TRC093(Tracon Pharmaceuticals Inc.)，VEGF Trap(阿柏西普)(Regeneron Pharmaceuticals)，VEGF Trap-Eye(Regeneron Pharmaceuticals)，Veglin(VasGene Therapeutics)，硼替佐米(Millennium)，XL184(Exelixis)，XL647(Exelixis)，XL784(Exelixis)，XL820(Exelixis)，XL999(Exelixis)，ZD6474(AstraZeneca)，伏立诺他(Merck)和ZSTK474。

可以与本文所述的串联表达盒组合物结合使用的示例性血管内皮生长因子(VEGF)受体抑制剂包括但不限于贝伐单抗

可以与本文所述的串联表达盒组合物结合使用的示例性EGF通路抑制剂包括但不限于酪氨酸磷酸化抑制剂46、EKB-569、厄洛替尼

可以与本文所述的串联表达盒组合物结合使用的示例性的mTOR抑制剂包括但不限于雷帕霉素

可以与本文所述的串联表达盒组合物结合使用的示例性磷酸肌醇3-激酶(PI3K)抑制剂包括但不限于4-[2-(1H-吲唑-4-基)-6-[[4-(甲基磺酰基)哌嗪-1-基]甲基]噻吩并[3,2-d]嘧啶-4-基]吗啉(也称为GDC0941，并在PCT公开号WO 09/036082和WO 09/055730中描述)；2-甲基-2-[4-[3-甲基-2-氧代-8-(喹啉-3-基)-2,3-二氢咪唑并[4,5-c]喹啉-1-基]苯基]丙腈(也称为BEZ 235或NVP-BEZ 235，并在PCT公开号WO 06/122806中描述)；4-(三氟甲基)-5-(2,6-二吗啉嘧啶-4-基)吡啶-2-胺(也称为BKM120或NVP-BKM120，并在PCT公开号WO2007/084786中描述)；陶扎色替(VX680或MK-0457，CAS 639089-54-6)；(5Z)-5-[[4-(4-吡啶基)-6-喹啉基]亚甲基]-2,4-噻唑烷二酮(GSK1059615，CAS958852-01-2)；(1E,4S,4aR,5R,6aS,9aR)-5-(乙酰氧基)-1-[(二-2-丙烯基氨基)亚甲基]-4,4a,5,6,6a,8,9,9a-八氢-11-羟基-4-(甲氧基甲基)-4a,6a-二甲基-环戊[5,6]萘并[1,2-c]吡喃-2,7,10(1H)-三酮(PX866，CAS 502632-66-8)；和8-苯基-2-(吗啉-4-基)-色烯-4-酮(LY294002，CAS 154447-36-6)。示例性的蛋白激酶B(PKB)或AKT抑制剂包括但不限于8-[4-(1-氨基环丁基)苯]-9-苯基-1,2,4-噻唑并[3,4-f][1,6]萘啶-3(2H)-酮(MK-2206，CAS 1032349-93-1)；哌立福辛(KRX0401)；4-十二烷基-N-1,3,4-噻二唑-2-基-苯磺酰胺(PHT-427，CAS1191951-57-1)；4-[2-(4-氨基-1,2,5-噁二唑-3-基)-1-乙基-7-[(3S)-3-哌啶基甲氧基]-1H-咪唑并[4,5-c]吡啶-4-基]-2-甲基-3-丁炔-2-醇(GSK690693，CAS 937174-76-0)；8-(1-羟基乙基)-2-甲氧基-3-[(4-甲氧基苯基)甲氧基]-6H-二苯并[b,d]吡喃-6-酮(palomid 529、P529或SG-00529)；Tricirbine(6-氨基-4-甲基-8-(β-D-呋喃核糖基)-4H,8H-吡咯并[4,3,2-de]嘧啶并[4,5-c]哒嗪)；(αS)-α-[[[5-(3-甲基-1H-吲唑-5-基)-3-吡啶基]氧基]甲基]-苯乙胺(A674563，CAS 552325-73-2)；4-[(4-氯苯基)甲基]-1-(7H-吡咯并[2,3-d]嘧啶-4-基)-4-哌啶胺(CCT128930，CAS 885499-61-6)；4-(4-氯苯基)-4-[4-(1H-吡唑-4-基)苯基]-哌啶(AT7867，CAS 857531-00-1)；和Archexin(RX-0201，CAS663232-27-7)。

在某些实施方式中，与CER修饰的细胞结合使用的酪氨酸激酶抑制剂是间变性淋巴瘤激酶(ALK)抑制剂。示例性的ALK抑制剂包括克唑替尼、色瑞替尼、阿来替尼、布加替尼、dalantercept、恩曲替尼和劳拉替尼。

在串联表达盒修饰的细胞与一种或多种其他疗法组合施用的某些实施方案中，一种或多种另外的疗法可以以单一疗法施用的剂量施用，否则该剂量可能被认为是亚治疗的。在此类实施方式中，串联表达盒可提供累加或协同作用，使得可以以较低剂量施用一种或多种其他疗法。联合疗法包括在其他疗法之前(例如，其他疗法之前1天至30天或更长时间)、与其他疗法同时(在同一天)或在其他疗法之后(例如，其他疗法之后1天至30天或更长时间)施用本文所述的串联表达盒组合物。在某些实施方式中，在一种或多种其他疗法施用之后施用串联表达盒修饰的细胞。在进一步的实施方式中，在一种或多种其他疗法施用后1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30天，施用串联表达载体修饰的细胞。在更进一步的实施方式中，在一种或多种其他疗法施用后4周内、3周内、2周内或1周内施用串联表达盒修饰的细胞。当一种或多种其他疗法涉及多个剂量时，可以在一种或多种其他疗法的初始剂量之后、一种或多种其他疗法的最终剂量之后、或者在一种或多种其他疗法的多个剂量之间施用串联表达盒修饰的细胞。

在某些实施方式中，本公开内容的方法包括耗竭步骤。在治疗获益足够长的时间后，可以进行耗竭步骤，以便从对象中除去串联表达盒修饰的细胞，从而减轻对对象的毒性。在此类实施方式中，包含串联表达盒的载体可以包含诱导型自杀基因，如iCASP9、诱导型Fas或HSV-TK。类似地，可以设计该载体以表达已知的细胞表面抗原，如CD20或截短的EGFR(SEQ ID NO:82)，其通过输注相关的单克隆抗体(mAb)来促进转导细胞的耗竭。例如，针对CD20的利妥昔蛋白或针对EGFR的西妥昔单抗。靶向成熟淋巴细胞表面上存在的CD52的Alemtuzumab也可用于耗竭转导的B细胞、T细胞或自然杀伤细胞。

可以使用本公开内容的组合物和方法治疗的对象包括动物，如人、灵长类动物、奶牛、马、绵羊、犬、猫、小鼠、大鼠、家兔、豚鼠或猪。对象可以是男性或女性，以及可以是任何适宜的年龄，包括婴儿、少年、青少年、成人和老年对象。

实施例

将包含磷脂酰丝氨酸结合蛋白Tim4的胞外域和Tim4跨膜结构域的多核苷酸与TLR4的胞内信号传导结构域融合，以形成编码SEQ ID NO:97所示的氨基酸序列的嵌合吞噬受体“CER5”。将包含磷脂酰丝氨酸结合蛋白Tim4的胞外域和Tim4跨膜结构域的多核苷酸与TLR5的胞内信号传导结构域融合，以形成编码SEQ ID NO:98所示的氨基酸序列的嵌合吞噬受体“CER19”。将包含磷脂酰丝氨酸结合蛋白Tim4的胞外域和Tim4跨膜结构域的多核苷酸与TLR8的胞内信号传导结构域融合，以形成编码SEQ ID NO:99所示的氨基酸序列的嵌合吞噬受体“CER21”。将包含磷脂酰丝氨酸结合蛋白Tim4的胞外域和Tim4跨膜结构域的多核苷酸与NFAM1的胞内信号传导结构域融合，以形成编码SEQ ID NO:100所示的氨基酸序列的嵌合吞噬受体“CER25”。将包含磷脂酰丝氨酸结合蛋白Tim4的胞外域和Tim4跨膜结构域的多核苷酸与TLR2的胞内信号传导结构域融合，以形成编码SEQ ID NO:101所示的氨基酸序列的嵌合吞噬受体“CER27”。将包含磷脂酰丝氨酸结合蛋白Tim4的胞外域和Tim4跨膜结构域的多核苷酸与Traf6的胞内信号传导结构域融合，以形成编码SEQ ID NO:102所示的氨基酸序列的嵌合吞噬受体“CER29”。将包含磷脂酰丝氨酸结合蛋白Tim4的胞外域和Tim4跨膜结构域的多核苷酸与Traf3的胞内信号传导结构域融合，以形成编码SEQ ID NO:103所示的氨基酸序列的嵌合吞噬受体“CER31”。

使用P2A自切割肽的序列，将编码TCRβ链的多核苷酸和编码HPV16 E7特异性TCR的TCRα的多核苷酸(参见PCT公开号WO2015/184228)融合。TCR Vα结构域包含SEQ ID NO:94所示的氨基酸序列，TCR Vβ区包含SEQ ID NO:92所示的氨基酸序列。Cα结构域包含一个半胱氨酸取代和在位置12、14和15上的LVL取代，并且包含SEQ ID NO:95所示的氨基酸序列。Cβ也包含一个半胱氨酸取代，并且包含SEQ ID NO:93所示的氨基酸序列。编码的HPV16 E7特异性TCR包含SEQ ID NO:90所示的氨基酸序列。在表2中提供了在本实施例中描述的串联表达构建体的氨基酸序列。

表2：示例性串联表达盒

将所选择的CER多核苷酸和HPV16 E7 TCR多核苷酸插入到同一pLenti慢病毒载体中，其之间具有T2A序列(编码SEQ ID NO:68所示的氨基酸)。(参见图1A-1G)。通过静脉穿刺从人供体中收集外周血，并使用淋巴细胞分离介质通过密度梯度离心分离人外周血单核细胞(PBMC)。使用市售的分离试剂盒从PBMC中富集CD8+ T细胞，并在完全细胞生长培养基中用抗CD3和抗CD28激活。将表达CER-HPV16 E7 TCR组合的50μl病毒载体稀释在0.5ml完全细胞生长培养基中，然后添加到CD8+ T细胞中。随后将转导的CD8+ T细胞在32℃预热的离心机中以270x g rpm离心1小时。将CD8+ T细胞在37℃下孵育24小时。将T细胞在完全细胞生长培养基中再扩增72小时，去除小珠，并使其扩增5天，然后用于功能测定。

使用caspase 3/7凋亡试剂

将串联表达盒转导的CD8+ T细胞与SCC152细胞以1:1的比例共培养6小时，以检测串联表达盒转导的CD8+ T细胞的吞噬活性。使用KEYENCE BZ-X710荧光显微镜，20X物镜和混合捕获软件对吞噬事件进行可视化和量化。用CER21-HPV16 E7 TCR、CER29-HPV16 E7TCR或CER31-HPV16 E7 TCR串联盒转导的CD8+ T细胞能够吞噬SCC152细胞(参见图6和7)。将Rac1抑制剂NSC23766(50μM)也加入共培养实验中，并测量体外吞噬作用。用Rac1抑制剂处理后，发现CER21-HPV16 E7 TCR、CER29-HPV16 E7 TCR或CER31-HPV16 E7 TCR转导的T细胞以Rac1依赖方式吞噬了SCC152细胞(参见图8-10)。图11和图12显示，用CER21-HPV16 E7TCR串联表达盒转导的CD8+ T细胞吞噬了链霉亲和素包被的乳胶小珠，其上包被了生物素偶联的磷脂酰丝氨酸。孵育约30分钟后，在CER21-HPV16 E7 TCR+ T细胞内部可以看到磷脂酰丝氨酸包被的小珠。

在与SCC152细胞共培养实验期间，通过对细胞上清液进行采样，测量了使用CER21-HPV16 E7 TCR串联表达盒转导的CD8+ T细胞的细胞因子应答，并表明如通过IFNγ应答所测量的，CER21-HPV16 E7 TCR+ T细胞显示出抗原特异性效应功能(见图14)。

在共培养测定中评价了CER修饰的T细胞吞噬靶细胞和概括吞噬信号传导事件的能力。用编码HPV E7特异性TCR(包含SEQ ID NO:158的多肽序列)的核酸或编码HPV E7特异性TCR+CER29(包含SEQ ID NO:169的多肽序列)的串联表达盒转导T细胞。将pHrodo-标记的HPV+SCC152头颈癌细胞与模拟转导的T细胞、HPV E7 TCR转导的T细胞或HPV E7 TCR/CER29转导的T细胞共培养。通过FACS分析吞噬作用，结果显示大量细胞痕量紫色标记的E7 TCR/CER29-T细胞被pHrodo阳性双重染色(参见图15A)。对FACS数据的定量显示模拟转导的T细胞与E7 TCR转导的T细胞之间没有差异(见图15B)。

可以将上述各种实施方式组合以提供其他实施方式。本说明书中提及和/或在应用数据表中列出的所有美国专利、美国专利申请公开文件、美国专利申请、外国专利、外国专利申请和非专利出版物，包括但不限于2018年03月28日提交的美国临时专利申请号62/649,499，其整体通过引用并入本文。如果需要采用各种专利、申请和公开文件的概念以提供其他实施方式，可以修改实施方式的各个方面。

可以根据以上的详细描述对实施方式进行这些和其他改变。通常，在权利要求中，所使用的术语不应解释为将权利要求限制为说明书和权利要求中公开的特定实施方式，而应解释为包括所有可能的实施方式以及这些权利要求所享有的等同物的全部范围。因此，权利要求不受公开内容的限制。

序列表

<110> 森罗治疗公司

D·M·科瑞

I·伊巴拉

<120> 嵌合吞噬受体的表达载体、基因修饰的宿主细胞及其用途

<130> 200265.406WO

<140> PCT

<141> 2019-03-27

<150> US 62/649,499

<151> 2018-03-28

<160> 195

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Tyr Lys Lys Arg Arg Val His Leu Pro Gln Glu Gly Ala Phe Glu Asn

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Thr Leu Tyr Phe Asn Ser Gln Ser Ser Pro Gly Thr Ser Asp Met Lys

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Asp Leu Val Gly Asn Ile Glu Gln Asn Glu His Ser Val Ile

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Ser Glu Leu Val Val Asn Tyr Ile Ala Lys Lys Ser Phe Cys Arg Arg

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Ala Ile Glu Leu Thr Leu His Ser Leu Gly Val Ser Glu Glu Leu Gln

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

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Lys Ile Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu

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Lys Gln Glu Asp Gly Thr Ser Leu Lys Val Ala Val Lys Thr Met Lys

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

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Ala Cys Met Lys Asp Phe Ser His Pro Asn Val Ile Arg Leu Leu Gly

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Val Cys Ile Glu Met Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile

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Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Tyr Leu Leu Tyr Ser

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Arg Leu Glu Thr Gly Pro Lys His Ile Pro Leu Gln Thr Leu Leu Lys

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Phe Met Val Asp Ile Ala Leu Gly Met Glu Tyr Leu Ser Asn Arg Asn

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Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp

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

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Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp

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Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp

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Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Met

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Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu

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His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr

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Glu Ile Met Tyr Ser Cys Trp Arg Thr Asp Pro Leu Asp Arg Pro Thr

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Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Leu Glu Ser Leu Pro

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Asp Val Arg Asn Gln Ala Asp Val Ile Tyr Val Asn Thr Gln Leu Leu

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Glu Ser Ser Glu Gly Leu Ala Gln Gly Ser Thr Leu Ala Pro Leu Asp

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

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

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Gly Glu Arg Leu Val Arg Asn Gly Val Ser Trp Ser His Ser Ser Met

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Leu Pro Leu Gly Ser Ser Leu Pro Asp Glu Leu Leu Phe Ala Asp Asp

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Ser Ser Glu Gly Ser Glu Val Leu Met

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Ala Leu Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser

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

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Glu Leu Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu

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Val Leu Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu

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Gly Asn Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys

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Thr Met Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu

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Ser Glu Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg

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Leu Leu Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro

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Met Val Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu

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

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Leu Leu Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser

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Asn Arg Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu

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Arg Asp Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys

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Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro

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Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser

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Lys Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr

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Arg Gly Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp

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Tyr Leu Leu His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp

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Glu Leu Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp

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Arg Pro Thr Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu

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Ser Leu Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr

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Gln Leu Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr

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Gly Leu Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr

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

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Asp Val Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly

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His Ser Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe

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Val Asp Asp Ser Leu Glu Asp Ser Glu Val Leu Met

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

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Val Met Ala Arg Gly Glu Pro Ala Val His Phe Arg Ala Ala Arg Ser

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

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Gly Ile Ser Asp Glu Leu Lys Glu Lys Leu Glu Asp Val Leu Ile Pro

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Glu Gln Gln Phe Thr Leu Gly Arg Met Leu Gly Lys Gly Glu Phe Gly

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Ser Val Arg Glu Ala Gln Leu Lys Gln Glu Asp Gly Ser Phe Val Lys

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Val Ala Val Lys Met Leu Lys Ala Asp Ile Ile Ala Ser Ser Asp Ile

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Glu Glu Phe Leu Arg Glu Ala Ala Cys Met Lys Glu Phe Asp His Pro

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His Val Ala Lys Leu Val Gly Val Ser Leu Arg Ser Arg Ala Lys Gly

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Arg Leu Pro Ile Pro Met Val Ile Leu Pro Phe Met Lys His Gly Asp

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

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Leu Pro Leu Gln Thr Leu Ile Arg Phe Met Val Asp Ile Ala Cys Gly

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Met Glu Tyr Leu Ser Ser Arg Asn Phe Ile His Arg Asp Leu Ala Ala

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Arg Asn Cys Met Leu Ala Glu Asp Met Thr Val Cys Val Ala Asp Phe

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Gly Leu Ser Arg Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Cys

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Ala Ser Lys Leu Pro Val Lys Trp Leu Ala Leu Glu Ser Leu Ala Asp

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Asn Leu Tyr Thr Val Gln Ser Asp Val Trp Ala Phe Gly Val Thr Met

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Trp Glu Ile Met Thr Arg Gly Gln Thr Pro Tyr Ala Gly Ile Glu Asn

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Ala Glu Ile Tyr Asn Tyr Leu Ile Gly Gly Asn Arg Leu Lys Gln Pro

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Pro Glu Cys Met Glu Asp Val Tyr Asp Leu Met Tyr Gln Cys Trp Ser

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Ala Asp Pro Lys Gln Arg Pro Ser Phe Thr Cys Leu Arg Met Glu Leu

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Glu Asn Ile Leu Gly Gln Leu Ser Val Leu Ser Ala Ser Gln Asp Pro

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

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Leu Glu Leu Pro Gly Arg Asp Gln Pro Tyr Ser Gly Ala Gly Asp Gly

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

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Leu Thr Pro Gly Gly Leu Ala Glu Gln Pro Gly Gln Ala Glu His Gln

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

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Gly Leu Leu Pro His Ser Ser Cys

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His Arg Arg Lys Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr

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Val Glu Arg Gly Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr

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

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Glu Leu Lys Glu Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val

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Ala Leu Gly Lys Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu

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

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Met Lys Ile Ala Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser

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Glu Ala Val Cys Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu

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Ile Gly Val Cys Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro

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

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Leu Tyr Ser Arg Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met

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Leu Val Lys Phe Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser

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Thr Lys Arg Phe Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu

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Asn Glu Asn Met Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys

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Ile Tyr Asn Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro

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Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser

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Lys Ser Asp Val Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr

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Arg Gly Gln Thr Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp

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Tyr Leu Arg Gln Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp

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Gly Leu Tyr Ala Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp

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Arg Pro Ser Phe Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys

325 330 335

Ala Leu Pro Pro Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met

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Asp Glu Gly Gly Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala

355 360 365

Asp Pro Pro Thr Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr

370 375 380

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

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Thr Pro Ser Pro Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro

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Gly Gln Glu Asp Gly Ala

420

<210> 7

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<213> 智人

<220>

<223> ELMO 信号传导结构域

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Met Pro Pro Pro Ala Asp Ile Val Lys Val Ala Ile Glu Trp Pro Gly

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Ala Tyr Pro Lys Leu Met Glu Ile Asp Gln Lys Lys Pro Leu Ser Ala

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Ile Ile Lys Glu Val Cys Asp Gly Trp Ser Leu Ala Asn His Glu Tyr

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Phe Ala Leu Gln His Ala Asp Ser Ser Asn Phe Tyr Ile Thr Glu Lys

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Asn Arg Asn Glu Ile Lys Asn Gly Thr Ile Leu Arg Leu Thr Thr Ser

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Pro Ala Gln Asn Ala Gln Gln Leu His Glu Arg Ile Gln Ser Ser Ser

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Met Asp Ala Lys Leu Glu Ala Leu Lys Asp Leu Ala Ser Leu Ser Arg

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

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Leu Thr Gln Met Val Glu Ser Gly Thr Glu Arg Tyr Gln Lys Leu Gln

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Lys Ile Met Lys Pro Cys Phe Gly Asp Met Leu Ser Phe Thr Leu Thr

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Ala Phe Val Glu Leu Met Asp His Gly Ile Val Ser Trp Asp Thr Phe

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Ser Val Ala Phe Ile Lys Lys Ile Ala Ser Phe Val Asn Lys Ser Ala

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Ile Asp Ile Ser Ile Leu Gln Arg Ser Leu Ala Ile Leu Glu Ser Met

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Val Leu Asn Ser His Asp Leu Tyr Gln Lys Val Ala Gln Glu Ile Thr

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Ile Gly Gln Leu Ile Pro His Leu Gln Gly Ser Asp Gln Glu Ile Gln

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Thr Tyr Thr Ile Ala Val Ile Asn Ala Leu Phe Leu Lys Ala Pro Asp

245 250 255

Glu Arg Arg Gln Glu Met Ala Asn Ile Leu Ala Gln Lys Gln Leu Arg

260 265 270

Ser Ile Ile Leu Thr His Val Ile Arg Ala Gln Arg Ala Ile Asn Asn

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Glu Met Ala His Gln Leu Tyr Val Leu Gln Val Leu Thr Phe Asn Leu

290 295 300

Leu Glu Asp Arg Met Met Thr Lys Met Asp Pro Gln Asp Gln Ala Gln

305 310 315 320

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

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Glu Pro Asn Asn Ser Ser Gly Ser Met Glu Lys Arg Lys Ser Met Tyr

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Thr Arg Asp Tyr Lys Lys Leu Gly Phe Ile Asn His Val Asn Pro Ala

355 360 365

Met Asp Phe Thr Gln Thr Pro Pro Gly Met Leu Ala Leu Asp Asn Met

370 375 380

Leu Tyr Phe Ala Lys His His Gln Asp Ala Tyr Ile Arg Ile Val Leu

385 390 395 400

Glu Asn Ser Ser Arg Glu Asp Lys His Glu Cys Pro Phe Gly Arg Ser

405 410 415

Ser Ile Glu Leu Thr Lys Met Leu Cys Glu Ile Leu Lys Val Gly Glu

420 425 430

Leu Pro Ser Glu Thr Cys Asn Asp Phe His Pro Met Phe Phe Thr His

435 440 445

Asp Arg Ser Phe Glu Glu Phe Phe Cys Ile Cys Ile Gln Leu Leu Asn

450 455 460

Lys Thr Trp Lys Glu Met Arg Ala Thr Ser Glu Asp Phe Asn Lys Val

465 470 475 480

Met Gln Val Val Lys Glu Gln Val Met Arg Ala Leu Thr Thr Lys Pro

485 490 495

Ser Ser Leu Asp Gln Phe Lys Ser Lys Leu Gln Asn Leu Ser Tyr Thr

500 505 510

Glu Ile Leu Lys Ile Arg Gln Ser Glu Arg Met Asn Gln Glu Asp Phe

515 520 525

Gln Ser Arg Pro Ile Leu Glu Leu Lys Glu Lys Ile Gln Pro Glu Ile

530 535 540

Leu Glu Leu Ile Lys Gln Gln Arg Leu Asn Arg Leu Val Glu Gly Thr

545 550 555 560

Cys Phe Arg Lys Leu Asn Ala Arg Arg Arg Gln Asp Lys Phe Trp Tyr

565 570 575

Cys Arg Leu Ser Pro Asn His Lys Val Leu His Tyr Gly Asp Leu Glu

580 585 590

Glu Ser Pro Gln Gly Glu Val Pro His Asp Ser Leu Gln Asp Lys Leu

595 600 605

Pro Val Ala Asp Ile Lys Ala Val Val Thr Gly Lys Asp Cys Pro His

610 615 620

Met Lys Glu Lys Gly Ala Leu Lys Gln Asn Lys Glu Val Leu Glu Leu

625 630 635 640

Ala Phe Ser Ile Leu Tyr Asp Ser Asn Cys Gln Leu Asn Phe Ile Ala

645 650 655

Pro Asp Lys His Glu Tyr Cys Ile Trp Thr Asp Gly Leu Asn Ala Leu

660 665 670

Leu Gly Lys Asp Met Met Ser Asp Leu Thr Arg Asn Asp Leu Asp Thr

675 680 685

Leu Leu Ser Met Glu Ile Lys Leu Arg Leu Leu Asp Leu Glu Asn Ile

690 695 700

Gln Ile Pro Asp Ala Pro Pro Pro Ile Pro Lys Glu Pro Ser Asn Tyr

705 710 715 720

Asp Phe Val Tyr Asp Cys Asn

725

<210> 8

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<213> 智人

<220>

<223> Traf6 信号传导结构域 - 全长

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Met Ser Leu Leu Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu

1 5 10 15

Ser Asp Cys Cys Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys

20 25 30

Asp Asp Ser Val Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser

35 40 45

Phe Met Glu Glu Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu

50 55 60

Glu Ser Lys Tyr Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala

65 70 75 80

Val Gln Thr Pro Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys

85 90 95

Ser Ile Arg Asp Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu

100 105 110

Leu Glu Asn Gln Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu

115 120 125

Ser Leu Met Val Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu

130 135 140

Leu Arg His Leu Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met

145 150 155 160

Asp Cys Pro Gln Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile

165 170 175

His Ile Leu Lys Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys

180 185 190

Ala Ala Ser Met Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys

195 200 205

Pro Leu Ala Asn Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg

210 215 220

Glu Gln Met Pro Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile

225 230 235 240

Pro Cys Thr Phe Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn

245 250 255

His Leu Ala Arg His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met

260 265 270

Leu Ala Gln Ala Val His Ser Leu Ser Val Ile Pro Asp Ser Gly Tyr

275 280 285

Ile Ser Glu Val Arg Asn Phe Gln Glu Thr Ile His Gln Leu Glu Gly

290 295 300

Arg Leu Val Arg Gln Asp His Gln Ile Arg Glu Leu Thr Ala Lys Met

305 310 315 320

Glu Thr Gln Ser Met Tyr Val Ser Glu Leu Lys Arg Thr Ile Arg Thr

325 330 335

Leu Glu Asp Lys Val Ala Glu Ile Glu Ala Gln Gln Cys Asn Gly Ile

340 345 350

Tyr Ile Trp Lys Ile Gly Asn Phe Gly Met His Leu Lys Cys Gln Glu

355 360 365

Glu Glu Lys Pro Val Val Ile His Ser Pro Gly Phe Tyr Thr Gly Lys

370 375 380

Pro Gly Tyr Lys Leu Cys Met Arg Leu His Leu Gln Leu Pro Thr Ala

385 390 395 400

Gln Arg Cys Ala Asn Tyr Ile Ser Leu Phe Val His Thr Met Gln Gly

405 410 415

Glu Tyr Asp Ser His Leu Pro Trp Pro Phe Gln Gly Thr Ile Arg Leu

420 425 430

Thr Ile Leu Asp Gln Ser Glu Ala Pro Val Arg Gln Asn His Glu Glu

435 440 445

Ile Met Asp Ala Lys Pro Glu Leu Leu Ala Phe Gln Arg Pro Thr Ile

450 455 460

Pro Arg Asn Pro Lys Gly Phe Gly Tyr Val Thr Phe Met His Leu Glu

465 470 475 480

Ala Leu Arg Gln Arg Thr Phe Ile Lys Asp Asp Thr Leu Leu Val Arg

485 490 495

Cys Glu Val Ser Thr Arg Phe Asp Met Gly Ser Leu Arg Arg Glu Gly

500 505 510

Phe Gln Pro Arg Ser Thr Asp Ala Gly Val

515 520

<210> 9

<211> 261

<212> PRT

<213> 智人

<220>

<223> Syk 信号传导结构域

<400> 9

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

1 5 10 15

Lys Gly Tyr Tyr Gln Met Lys Lys Val Val Lys Thr Val Ala Val Lys

20 25 30

Ile Leu Lys Asn Glu Ala Asn Asp Pro Ala Leu Lys Asp Glu Leu Leu

35 40 45

Ala Glu Ala Asn Val Met Gln Gln Leu Asp Asn Pro Tyr Ile Val Arg

50 55 60

Met Ile Gly Ile Cys Glu Ala Glu Ser Trp Met Leu Val Met Glu Met

65 70 75 80

Ala Glu Leu Gly Pro Leu Asn Lys Tyr Leu Gln Gln Asn Arg His Val

85 90 95

Lys Asp Lys Asn Ile Ile Glu Leu Val His Gln Val Ser Met Gly Met

100 105 110

Lys Tyr Leu Glu Glu Ser Asn Phe Val His Arg Asp Leu Ala Ala Arg

115 120 125

Asn Val Leu Leu Val Thr Gln His Tyr Ala Lys Ile Ser Asp Phe Gly

130 135 140

Leu Ser Lys Ala Leu Arg Ala Asp Glu Asn Tyr Tyr Lys Ala Gln Thr

145 150 155 160

His Gly Lys Trp Pro Val Lys Trp Tyr Ala Pro Glu Cys Ile Asn Tyr

165 170 175

Tyr Lys Phe Ser Ser Lys Ser Asp Val Trp Ser Phe Gly Val Leu Met

180 185 190

Trp Glu Ala Phe Ser Tyr Gly Gln Lys Pro Tyr Arg Gly Met Lys Gly

195 200 205

Ser Glu Val Thr Ala Met Leu Glu Lys Gly Glu Arg Met Gly Cys Pro

210 215 220

Ala Gly Cys Pro Arg Glu Met Tyr Asp Leu Met Asn Leu Cys Trp Thr

225 230 235 240

Tyr Asp Val Glu Asn Arg Pro Gly Phe Ala Ala Val Glu Leu Arg Leu

245 250 255

Arg Asn Tyr Tyr Tyr

260

<210> 10

<211> 296

<212> PRT

<213> 智人

<220>

<223> MyD88 信号传导结构域

<400> 10

Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser

1 5 10 15

Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg

20 25 30

Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr

35 40 45

Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu

50 55 60

Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly

65 70 75 80

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

85 90 95

Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp

100 105 110

Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro

115 120 125

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

130 135 140

Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly His Met Pro Glu Arg

145 150 155 160

Phe Asp Ala Phe Ile Cys Tyr Cys Pro Ser Asp Ile Gln Phe Val Gln

165 170 175

Glu Met Ile Arg Gln Leu Glu Gln Thr Asn Tyr Arg Leu Lys Leu Cys

180 185 190

Val Ser Asp Arg Asp Val Leu Pro Gly Thr Cys Val Trp Ser Ile Ala

195 200 205

Ser Glu Leu Ile Glu Lys Arg Cys Arg Arg Met Val Val Val Val Ser

210 215 220

Asp Asp Tyr Leu Gln Ser Lys Glu Cys Asp Phe Gln Thr Lys Phe Ala

225 230 235 240

Leu Ser Leu Ser Pro Gly Ala His Gln Lys Arg Leu Ile Pro Ile Lys

245 250 255

Tyr Lys Ala Met Lys Lys Glu Phe Pro Ser Ile Leu Arg Phe Ile Thr

260 265 270

Val Cys Asp Tyr Thr Asn Pro Cys Thr Lys Ser Trp Phe Trp Thr Arg

275 280 285

Leu Ala Lys Ala Leu Ser Leu Pro

290 295

<210> 11

<400> 11

000

<210> 12

<211> 42

<212> PRT

<213> 智人

<220>

<223> FcεR1γ 信号传导结构域

<400> 12

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

1 5 10 15

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

20 25 30

Glu Thr Leu Lys His Glu Lys Pro Pro Gln

35 40

<210> 13

<211> 61

<212> PRT

<213> 智人

<220>

<223> FcγR1 信号传导结构域

<400> 13

Arg Lys Glu Leu Lys Arg Lys Lys Lys Trp Asp Leu Glu Ile Ser Leu

1 5 10 15

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

20 25 30

His Leu Glu Glu Glu Leu Lys Cys Gln Glu Gln Lys Glu Glu Gln Leu

35 40 45

Gln Glu Gly Val His Arg Lys Glu Pro Gln Gly Ala Thr

50 55 60

<210> 14

<211> 77

<212> PRT

<213> 智人

<220>

<223> FcγR2A 信号传导结构域

<400> 14

Cys Arg Lys Lys Arg Ile Ser Ala Asn Ser Thr Asp Pro Val Lys Ala

1 5 10 15

Ala Gln Phe Glu Pro Pro Gly Arg Gln Met Ile Ala Ile Arg Lys Arg

20 25 30

Gln Leu Glu Glu Thr Asn Asn Asp Tyr Glu Thr Ala Asp Gly Gly Tyr

35 40 45

Met Thr Leu Asn Pro Arg Ala Pro Thr Asp Asp Asp Lys Asn Ile Tyr

50 55 60

Leu Thr Leu Pro Pro Asn Asp His Val Asn Ser Asn Asn

65 70 75

<210> 15

<211> 77

<212> PRT

<213> 智人

<220>

<223> FcγR2c 信号传导结构域

<400> 15

Cys Arg Lys Lys Arg Ile Ser Ala Asn Ser Thr Asp Pro Val Lys Ala

1 5 10 15

Ala Gln Phe Glu Pro Pro Gly Arg Gln Met Ile Ala Ile Arg Lys Arg

20 25 30

Gln Pro Glu Glu Thr Asn Asn Asp Tyr Glu Thr Ala Asp Gly Gly Tyr

35 40 45

Met Thr Leu Asn Pro Arg Ala Pro Thr Asp Asp Asp Lys Asn Ile Tyr

50 55 60

Leu Thr Leu Pro Pro Asn Asp His Val Asn Ser Asn Asn

65 70 75

<210> 16

<211> 25

<212> PRT

<213> 智人

<220>

<223> FcγR3A 信号传导结构域

<400> 16

Lys Thr Asn Ile Arg Ser Ser Thr Arg Asp Trp Lys Asp His Lys Phe

1 5 10 15

Lys Trp Arg Lys Asp Pro Gln Asp Lys

20 25

<210> 17

<211> 85

<212> PRT

<213> 智人

<220>

<223> BAFF-R 信号传导结构域

<400> 17

Ser Trp Arg Arg Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu

1 5 10 15

Ala Pro Asp Gly Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile

20 25 30

Ile Leu Ser Pro Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro

35 40 45

Pro Gly Glu Asp Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val

50 55 60

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

65 70 75 80

Gly Pro Glu Gln Gln

85

<210> 18

<211> 52

<212> PRT

<213> 智人

<220>

<223> DAP12 信号传导结构域

<400> 18

Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala

1 5 10 15

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

20 25 30

Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg

35 40 45

Pro Tyr Tyr Lys

50

<210> 19

<211> 86

<212> PRT

<213> 智人

<220>

<223> NFAM1 信号传导结构域

<400> 19

Leu Trp Asn Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg

1 5 10 15

Lys Cys Pro Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser

20 25 30

Glu Ser Val Tyr Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala

35 40 45

Cys Ile Glu Asn Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro

50 55 60

Leu Ser Gln Glu Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn

65 70 75 80

Leu Val Tyr Glu Asn Leu

85

<210> 20

<211> 29

<212> PRT

<213> 智人

<220>

<223> CD79b 信号传导结构域 (氨基酸185-229)

<400> 20

Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly Leu Asp

1 5 10 15

Ile Asp Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu

20 25

<210> 21

<211> 45

<212> PRT

<213> 智人

<220>

<223> CD79b 信号传导结构域 (氨基酸185-213)

<400> 21

Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly Leu Asp

1 5 10 15

Ile Asp Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu Arg Thr Gly

20 25 30

Glu Val Lys Trp Ser Val Gly Glu His Pro Gly Gln Glu

35 40 45

<210> 22

<211> 185

<212> PRT

<213> 智人

<220>

<223> TLR1 信号传导结构域

<400> 22

Ser Tyr Leu Asp Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr

1 5 10 15

Gln Thr Arg Arg Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg

20 25 30

Asn Leu Gln Phe His Ala Phe Ile Ser Tyr Ser Gly His Asp Ser Phe

35 40 45

Trp Val Lys Asn Glu Leu Leu Pro Asn Leu Glu Lys Glu Gly Met Gln

50 55 60

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

65 70 75 80

Asn Ile Ile Thr Cys Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu

85 90 95

Ser Pro Asn Phe Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe

100 105 110

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

115 120 125

Leu Leu Glu Pro Ile Pro Gln Tyr Ser Ile Pro Ser Ser Tyr His Lys

130 135 140

Leu Lys Ser Leu Met Ala Arg Arg Thr Tyr Leu Glu Trp Pro Lys Glu

145 150 155 160

Lys Ser Lys Arg Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Ile Asn

165 170 175

Ile Lys Leu Thr Glu Gln Ala Lys Lys

180 185

<210> 23

<211> 175

<212> PRT

<213> 智人

<220>

<223> TLR2 信号传导结构域

<400> 23

His Arg Phe His Gly Leu Trp Tyr Met Lys Met Met Trp Ala Trp Leu

1 5 10 15

Gln Ala Lys Arg Lys Pro Arg Lys Ala Pro Ser Arg Asn Ile Cys Tyr

20 25 30

Asp Ala Phe Val Ser Tyr Ser Glu Arg Asp Ala Tyr Trp Val Glu Asn

35 40 45

Leu Met Val Gln Glu Leu Glu Asn Phe Asn Pro Pro Phe Lys Leu Cys

50 55 60

Leu His Lys Arg Asp Phe Ile Pro Gly Lys Trp Ile Ile Asp Asn Ile

65 70 75 80

Ile Asp Ser Ile Glu Lys Ser His Lys Thr Val Phe Val Leu Ser Glu

85 90 95

Asn Phe Val Lys Ser Glu Trp Cys Lys Tyr Glu Leu Asp Phe Ser His

100 105 110

Phe Arg Leu Phe Asp Glu Asn Asn Asp Ala Ala Ile Leu Ile Leu Leu

115 120 125

Glu Pro Ile Glu Lys Lys Ala Ile Pro Gln Arg Phe Cys Lys Leu Arg

130 135 140

Lys Ile Met Asn Thr Lys Thr Tyr Leu Glu Trp Pro Met Asp Glu Ala

145 150 155 160

Gln Arg Glu Gly Phe Trp Val Asn Leu Arg Ala Ala Ile Lys Ser

165 170 175

<210> 24

<211> 179

<212> PRT

<213> 智人

<220>

<223> TLR3 信号传导结构域

<400> 24

Glu Gly Trp Arg Ile Ser Phe Tyr Trp Asn Val Ser Val His Arg Val

1 5 10 15

Leu Gly Phe Lys Glu Ile Asp Arg Gln Thr Glu Gln Phe Glu Tyr Ala

20 25 30

Ala Tyr Ile Ile His Ala Tyr Lys Asp Lys Asp Trp Val Trp Glu His

35 40 45

Phe Ser Ser Met Glu Lys Glu Asp Gln Ser Leu Lys Phe Cys Leu Glu

50 55 60

Glu Arg Asp Phe Glu Ala Gly Val Phe Glu Leu Glu Ala Ile Val Asn

65 70 75 80

Ser Ile Lys Arg Ser Arg Lys Ile Ile Phe Val Ile Thr His His Leu

85 90 95

Leu Lys Asp Pro Leu Cys Lys Arg Phe Lys Val His His Ala Val Gln

100 105 110

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

115 120 125

Glu Ile Pro Asp Tyr Lys Leu Asn His Ala Leu Cys Leu Arg Arg Gly

130 135 140

Met Phe Lys Ser His Cys Ile Leu Asn Trp Pro Val Gln Lys Glu Arg

145 150 155 160

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

165 170 175

Ser Val His

<210> 25

<211> 187

<212> PRT

<213> 智人

<220>

<223> TLR4 信号传导结构域

<400> 25

Lys Phe Tyr Phe His Leu Met Leu Leu Ala Gly Cys Ile Lys Tyr Gly

1 5 10 15

Arg Gly Glu Asn Ile Tyr Asp Ala Phe Val Ile Tyr Ser Ser Gln Asp

20 25 30

Glu Asp Trp Val Arg Asn Glu Leu Val Lys Asn Leu Glu Glu Gly Val

35 40 45

Pro Pro Phe Gln Leu Cys Leu His Tyr Arg Asp Phe Ile Pro Gly Val

50 55 60

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

65 70 75 80

Val Ile Val Val Val Ser Gln His Phe Ile Gln Ser Arg Trp Cys Ile

85 90 95

Phe Glu Tyr Glu Ile Ala Gln Thr Trp Gln Phe Leu Ser Ser Arg Ala

100 105 110

Gly Ile Ile Phe Ile Val Leu Gln Lys Val Glu Lys Thr Leu Leu Arg

115 120 125

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

130 135 140

Trp Glu Asp Ser Val Leu Gly Arg His Ile Phe Trp Arg Arg Leu Arg

145 150 155 160

Lys Ala Leu Leu Asp Gly Lys Ser Trp Asn Pro Glu Gly Thr Val Gly

165 170 175

Thr Gly Cys Asn Trp Gln Glu Ala Thr Ser Ile

180 185

<210> 26

<211> 198

<212> PRT

<213> 智人

<220>

<223> TLR5 信号传导结构域

<400> 26

Thr Lys Phe Arg Gly Phe Cys Phe Ile Cys Tyr Lys Thr Ala Gln Arg

1 5 10 15

Leu Val Phe Lys Asp His Pro Gln Gly Thr Glu Pro Asp Met Tyr Lys

20 25 30

Tyr Asp Ala Tyr Leu Cys Phe Ser Ser Lys Asp Phe Thr Trp Val Gln

35 40 45

Asn Ala Leu Leu Lys His Leu Asp Thr Gln Tyr Ser Asp Gln Asn Arg

50 55 60

Phe Asn Leu Cys Phe Glu Glu Arg Asp Phe Val Pro Gly Glu Asn Arg

65 70 75 80

Ile Ala Asn Ile Gln Asp Ala Ile Trp Asn Ser Arg Lys Ile Val Cys

85 90 95

Leu Val Ser Arg His Phe Leu Arg Asp Gly Trp Cys Leu Glu Ala Phe

100 105 110

Ser Tyr Ala Gln Gly Arg Cys Leu Ser Asp Leu Asn Ser Ala Leu Ile

115 120 125

Met Val Val Val Gly Ser Leu Ser Gln Tyr Gln Leu Met Lys His Gln

130 135 140

Ser Ile Arg Gly Phe Val Gln Lys Gln Gln Tyr Leu Arg Trp Pro Glu

145 150 155 160

Asp Phe Gln Asp Val Gly Trp Phe Leu His Lys Leu Ser Gln Gln Ile

165 170 175

Leu Lys Lys Glu Lys Glu Lys Lys Lys Asp Asn Asn Ile Pro Leu Gln

180 185 190

Thr Val Ala Thr Ile Ser

195

<210> 27

<211> 189

<212> PRT

<213> 智人

<220>

<223> TLR6 信号传导结构域

<400> 27

Tyr Leu Asp Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr Gln

1 5 10 15

Thr Arg Arg Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn

20 25 30

Leu Gln Phe His Ala Phe Ile Ser Tyr Ser Glu His Asp Ser Ala Trp

35 40 45

Val Lys Ser Glu Leu Val Pro Tyr Leu Glu Lys Glu Asp Ile Gln Ile

50 55 60

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

65 70 75 80

Ile Ile Asn Cys Ile Glu Lys Ser Tyr Lys Ser Ile Phe Val Leu Ser

85 90 95

Pro Asn Phe Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala

100 105 110

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

115 120 125

Leu Glu Pro Ile Pro Gln Asn Ser Ile Pro Asn Lys Tyr His Lys Leu

130 135 140

Lys Ala Leu Met Thr Gln Arg Thr Tyr Leu Gln Trp Pro Lys Glu Lys

145 150 155 160

Ser Lys Arg Gly Leu Phe Trp Ala Asn Ile Arg Ala Ala Phe Asn Met

165 170 175

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

180 185

<210> 28

<211> 189

<212> PRT

<213> 智人

<220>

<223> TLR7 信号传导结构域

<400> 28

His Leu Tyr Phe Trp Asp Val Trp Tyr Ile Tyr His Phe Cys Lys Ala

1 5 10 15

Lys Ile Lys Gly Tyr Gln Arg Leu Ile Ser Pro Asp Cys Cys Tyr Asp

20 25 30

Ala Phe Ile Val Tyr Asp Thr Lys Asp Pro Ala Val Thr Glu Trp Val

35 40 45

Leu Ala Glu Leu Val Ala Lys Leu Glu Asp Pro Arg Glu Lys His Phe

50 55 60

Asn Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Gln Pro Val Leu

65 70 75 80

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

85 90 95

Met Thr Asp Lys Tyr Ala Lys Thr Glu Asn Phe Lys Ile Ala Phe Tyr

100 105 110

Leu Ser His Gln Arg Leu Met Asp Glu Lys Val Asp Val Ile Ile Leu

115 120 125

Ile Phe Leu Glu Lys Pro Phe Gln Lys Ser Lys Phe Leu Gln Leu Arg

130 135 140

Lys Arg Leu Cys Gly Ser Ser Val Leu Glu Trp Pro Thr Asn Pro Gln

145 150 155 160

Ala His Pro Tyr Phe Trp Gln Cys Leu Lys Asn Ala Leu Ala Thr Asp

165 170 175

Asn His Val Ala Tyr Ser Gln Val Phe Lys Glu Thr Val

180 185

<210> 29

<211> 193

<212> PRT

<213> 智人

<220>

<223> TLR8 信号传导结构域

<400> 29

His His Leu Phe Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu

1 5 10 15

Ala Lys Val Lys Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr

20 25 30

Asp Ala Tyr Ile Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp

35 40 45

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

50 55 60

Val Leu Leu Cys Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile

65 70 75 80

Ile Asp Asn Leu Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe

85 90 95

Val Leu Thr Lys Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe

100 105 110

Tyr Leu Ala Leu Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile

115 120 125

Phe Ile Leu Leu Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu

130 135 140

Arg Gln Arg Ile Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro

145 150 155 160

Lys Ala Glu Gly Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr

165 170 175

Glu Asn Asp Ser Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln

180 185 190

Tyr

<210> 30

<211> 193

<212> PRT

<213> 智人

<220>

<223> TLR9 信号传导结构域

<400> 30

Gly Trp Asp Leu Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro

1 5 10 15

Trp Arg Gly Arg Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp

20 25 30

Ala Phe Val Val Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val

35 40 45

Tyr Asn Glu Leu Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala

50 55 60

Leu Arg Leu Cys Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu

65 70 75 80

Phe Glu Asn Leu Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe

85 90 95

Val Leu Ala His Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe

100 105 110

Leu Leu Ala Gln Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val

115 120 125

Leu Val Ile Leu Ser Pro Asp Gly Arg Arg Ser Arg Tyr Val Arg Leu

130 135 140

Arg Gln Arg Leu Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro

145 150 155 160

Ser Gly Gln Arg Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg

165 170 175

Asp Asn His His Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala

180 185 190

Glu

<210> 31

<211> 303

<212> PRT

<213> 智人

<220>

<223> TRAF2 信号传导结构域

<400> 31

Met Ala Ala Ala Ser Val Thr Pro Pro Gly Ser Leu Glu Leu Leu Gln

1 5 10 15

Pro Gly Phe Ser Lys Thr Leu Leu Gly Thr Lys Leu Glu Ala Lys Tyr

20 25 30

Leu Cys Ser Ala Cys Arg Asn Val Leu Arg Arg Pro Phe Gln Ala Gln

35 40 45

Cys Gly His Arg Tyr Cys Ser Phe Cys Leu Ala Ser Ile Leu Ser Ser

50 55 60

Gly Pro Gln Asn Cys Ala Ala Cys Val His Glu Gly Ile Tyr Glu Glu

65 70 75 80

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

85 90 95

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

100 105 110

Thr Trp Lys Gly Thr Leu Lys Glu Tyr Glu Ser Cys His Glu Gly Arg

115 120 125

Cys Pro Leu Met Leu Thr Glu Cys Pro Ala Cys Lys Gly Leu Val Arg

130 135 140

Leu Gly Glu Lys Glu Arg His Leu Glu His Glu Cys Pro Glu Arg Ser

145 150 155 160

Leu Ser Cys Arg His Cys Arg Ala Pro Cys Cys Gly Ala Asp Val Lys

165 170 175

Ala His His Glu Val Cys Pro Lys Phe Pro Leu Thr Cys Asp Gly Cys

180 185 190

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

195 200 205

Cys Gly Lys Cys Arg Val Pro Cys Arg Phe His Ala Ile Gly Cys Leu

210 215 220

Glu Thr Val Glu Gly Glu Lys Gln Gln Glu His Glu Val Gln Trp Leu

225 230 235 240

Arg Glu His Leu Ala Met Leu Leu Ser Ser Val Leu Glu Ala Lys Pro

245 250 255

Leu Leu Gly Asp Gln Ser His Ala Gly Ser Glu Leu Leu Gln Arg Cys

260 265 270

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

275 280 285

Leu Asn Arg Glu Val Glu Arg Val Ala Met Thr Ala Glu Ala Cys

290 295 300

<210> 32

<211> 274

<212> PRT

<213> 智人

<220>

<223> TRAF3 信号传导结构域

<400> 32

Met Glu Ser Ser Lys Lys Met Asp Ser Pro Gly Ala Leu Gln Thr Asn

1 5 10 15

Pro Pro Leu Lys Leu His Thr Asp Arg Ser Ala Gly Thr Pro Val Phe

20 25 30

Val Pro Glu Gln Gly Gly Tyr Lys Glu Lys Phe Val Lys Thr Val Glu

35 40 45

Asp Lys Tyr Lys Cys Glu Lys Cys His Leu Val Leu Cys Ser Pro Lys

50 55 60

Gln Thr Glu Cys Gly His Arg Phe Cys Glu Ser Cys Met Ala Ala Leu

65 70 75 80

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

85 90 95

Lys Asp Lys Val Phe Lys Asp Asn Cys Cys Lys Arg Glu Ile Leu Ala

100 105 110

Leu Gln Ile Tyr Cys Arg Asn Glu Ser Arg Gly Cys Ala Glu Gln Leu

115 120 125

Met Leu Gly His Leu Leu Val His Leu Lys Asn Asp Cys His Phe Glu

130 135 140

Glu Leu Pro Cys Val Arg Pro Asp Cys Lys Glu Lys Val Leu Arg Lys

145 150 155 160

Asp Leu Arg Asp His Val Glu Lys Ala Cys Lys Tyr Arg Glu Ala Thr

165 170 175

Cys Ser His Cys Lys Ser Gln Val Pro Met Ile Ala Leu Gln Lys His

180 185 190

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

195 200 205

Ser Val Gln Thr Leu Leu Arg Ser Glu Leu Ser Ala His Leu Ser Glu

210 215 220

Cys Val Asn Ala Pro Ser Thr Cys Ser Phe Lys Arg Tyr Gly Cys Val

225 230 235 240

Phe Gln Gly Thr Asn Gln Gln Ile Lys Ala His Glu Ala Ser Ser Ala

245 250 255

Val Gln His Val Asn Leu Leu Lys Glu Trp Ser Asn Ser Leu Glu Lys

260 265 270

Lys Val

<210> 33

<211> 155

<212> PRT

<213> 智人

<220>

<223> 截短的MyD88信号传导结构域，无TIR

结构域

<400> 33

Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser

1 5 10 15

Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg

20 25 30

Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr

35 40 45

Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu

50 55 60

Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly

65 70 75 80

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

85 90 95

Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp

100 105 110

Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro

115 120 125

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

130 135 140

Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly

145 150 155

<210> 34

<211> 274

<212> PRT

<213> 智人

<220>

<223> 截短的TRAF6信号传导结构域

<400> 34

Met Ser Leu Leu Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu

1 5 10 15

Ser Asp Cys Cys Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys

20 25 30

Asp Asp Ser Val Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser

35 40 45

Phe Met Glu Glu Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu

50 55 60

Glu Ser Lys Tyr Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala

65 70 75 80

Val Gln Thr Pro Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys

85 90 95

Ser Ile Arg Asp Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu

100 105 110

Leu Glu Asn Gln Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu

115 120 125

Ser Leu Met Val Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu

130 135 140

Leu Arg His Leu Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met

145 150 155 160

Asp Cys Pro Gln Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile

165 170 175

His Ile Leu Lys Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys

180 185 190

Ala Ala Ser Met Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys

195 200 205

Pro Leu Ala Asn Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg

210 215 220

Glu Gln Met Pro Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile

225 230 235 240

Pro Cys Thr Phe Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn

245 250 255

His Leu Ala Arg His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met

260 265 270

Leu Ala

<210> 35

<211> 29

<212> PRT

<213> 智人

<220>

<223> 截短的NFAM1信号传导结构域

<400> 35

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

1 5 10 15

Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn Glu

20 25

<210> 36

<211> 21

<212> PRT

<213> 智人

<220>

<223> Tim1 跨膜结构域

<400> 36

Ile Tyr Ala Gly Val Cys Ile Ser Val Leu Val Leu Leu Ala Leu Leu

1 5 10 15

Gly Val Ile Ile Ala

20

<210> 37

<211> 21

<212> PRT

<213> 智人

<220>

<223> Tim4 跨膜结构域

<400> 37

Leu Leu Met Ile Ile Ala Pro Ser Leu Gly Phe Val Leu Phe Ala Leu

1 5 10 15

Phe Val Ala Phe Leu

20

<210> 38

<211> 21

<212> PRT

<213> 小家鼠

<220>

<223> Tim4 跨膜结构域

<400> 38

Ile Leu Ile Ile Ala Cys Cys Val Gly Phe Val Leu Met Val Leu Leu

1 5 10 15

Phe Leu Ala Phe Leu

20

<210> 39

<211> 21

<212> PRT

<213> 智人

<220>

<223> Tim3 跨膜结构域

<400> 39

Ile Tyr Ile Gly Ala Gly Ile Cys Ala Gly Leu Ala Leu Ala Leu Ile

1 5 10 15

Phe Gly Ala Leu Ile

20

<210> 40

<211> 21

<212> PRT

<213> 智人

<220>

<223> FcγR1 跨膜结构域

<400> 40

Val Leu Phe Tyr Leu Ala Val Gly Ile Met Phe Leu Val Asn Thr Val

1 5 10 15

Leu Trp Val Thr Ile

20

<210> 41

<211> 23

<212> PRT

<213> 智人

<220>

<223> FcγR2A 跨膜结构域

<400> 41

Ile Ile Val Ala Val Val Ile Ala Thr Ala Val Ala Ala Ile Val Ala

1 5 10 15

Ala Val Val Ala Leu Ile Tyr

20

<210> 42

<211> 23

<212> PRT

<213> 智人

<220>

<223> FcγR2B2 跨膜结构域

<400> 42

Ser Ser Ser Pro Met Gly Ile Ile Val Ala Val Val Thr Gly Ile Ala

1 5 10 15

Val Ala Ala Ile Val Ala Ala

20

<210> 43

<211> 23

<212> PRT

<213> 智人

<220>

<223> FcγR2C 跨膜结构域

<400> 43

Ile Ile Val Ala Val Val Thr Gly Ile Ala Val Ala Ala Ile Val Ala

1 5 10 15

Ala Val Val Ala Leu Ile Tyr

20

<210> 44

<211> 21

<212> PRT

<213> 智人

<220>

<223> FcγR3A 跨膜结构域

<400> 44

Val Ser Phe Cys Leu Val Met Val Leu Leu Phe Ala Val Asp Thr Gly

1 5 10 15

Leu Tyr Phe Ser Val

20

<210> 45

<211> 21

<212> PRT

<213> 智人

<220>

<223> FcεR1 跨膜结构域

<400> 45

Leu Cys Tyr Ile Leu Asp Ala Ile Leu Phe Leu Tyr Gly Ile Val Leu

1 5 10 15

Thr Leu Leu Tyr Cys

20

<210> 46

<211> 19

<212> PRT

<213> 智人

<220>

<223> FcαR1 跨膜结构域

<400> 46

Leu Ile Arg Met Ala Val Ala Gly Leu Val Leu Val Ala Leu Leu Ala

1 5 10 15

Ile Leu Val

<210> 47

<211> 21

<212> PRT

<213> 智人

<220>

<223> CD8 跨膜结构域

<400> 47

Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu

1 5 10 15

Ser Leu Val Ile Thr

20

<210> 48

<211> 21

<212> PRT

<213> 智人

<220>

<223> MERTK 跨膜结构域

<400> 48

Phe Gly Cys Phe Cys Gly Phe Ile Leu Ile Gly Leu Ile Leu Tyr Ile

1 5 10 15

Ser Leu Ala Ile Arg

20

<210> 49

<211> 21

<212> PRT

<213> 智人

<220>

<223> Axl 跨膜结构域

<400> 49

Tyr Val Leu Leu Gly Ala Val Val Ala Ala Ala Cys Val Leu Ile Leu

1 5 10 15

Ala Leu Phe Leu Val

20

<210> 50

<211> 21

<212> PRT

<213> 智人

<220>

<223> Tyro3 跨膜结构域

<400> 50

Val Pro Val Val Leu Gly Val Leu Thr Ala Leu Val Thr Ala Ala Ala

1 5 10 15

Leu Ala Leu Ile Leu

20

<210> 51

<211> 22

<212> PRT

<213> 智人

<220>

<223> CD4 跨膜结构域

<400> 51

Met Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile

1 5 10 15

Gly Leu Gly Ile Phe Phe

20

<210> 52

<211> 21

<212> PRT

<213> 智人

<220>

<223> DAP12 跨膜结构域

<400> 52

Gly Val Leu Ala Gly Ile Val Met Gly Asp Leu Val Leu Thr Val Leu

1 5 10 15

Ile Ala Leu Ala Val

20

<210> 53

<211> 21

<212> PRT

<213> 智人

<220>

<223> MRC1 跨膜结构域

<400> 53

Gly Val Val Ile Ile Val Ile Leu Leu Ile Leu Thr Gly Ala Gly Leu

1 5 10 15

Ala Ala Tyr Phe Phe

20

<210> 54

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR1 跨膜结构域

<400> 54

Leu Leu Ile Val Thr Ile Val Ala Thr Met Leu Val Leu Ala Val Thr

1 5 10 15

Val Thr Ser Leu Cys

20

<210> 55

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR2 跨膜结构域

<400> 55

Ala Leu Val Ser Gly Met Cys Cys Ala Leu Phe Leu Leu Ile Leu Leu

1 5 10 15

Thr Gly Val Leu Cys

20

<210> 56

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR3 跨膜结构域

<400> 56

Phe Phe Met Ile Asn Thr Ser Ile Leu Leu Ile Phe Ile Phe Ile Val

1 5 10 15

Leu Leu Ile His Phe

20

<210> 57

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR4 跨膜结构域

<400> 57

Thr Ile Ile Gly Val Ser Val Leu Ser Val Leu Val Val Ser Val Val

1 5 10 15

Ala Val Leu Val Tyr

20

<210> 58

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR5 跨膜结构域

<400> 58

Phe Ser Leu Phe Ile Val Cys Thr Val Thr Leu Thr Leu Phe Leu Met

1 5 10 15

Thr Ile Leu Thr Val

20

<210> 59

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR6 跨膜结构域

<400> 59

Ala Leu Val Ser Gly Met Cys Cys Ala Leu Phe Leu Leu Ile Leu Leu

1 5 10 15

Thr Gly Val Leu Cys

20

<210> 60

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR7 跨膜结构域

<400> 60

Leu Ile Leu Phe Ser Leu Ser Ile Ser Val Ser Leu Phe Leu Met Val

1 5 10 15

Met Met Thr Ala Ser

20

<210> 61

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR8 跨膜结构域

<400> 61

Ala Val Ile Leu Phe Phe Phe Thr Phe Phe Ile Thr Thr Met Val Met

1 5 10 15

Leu Ala Ala Leu Ala

20

<210> 62

<211> 21

<212> PRT

<213> 智人

<220>

<223> TLR9 跨膜结构域

<400> 62

Phe Ala Leu Ser Leu Leu Ala Val Ala Leu Gly Leu Gly Val Pro Met

1 5 10 15

Leu His His Leu Cys

20

<210> 63

<211> 12

<212> PRT

<213> 人工序列

<220>

<223> 修饰的IgG4铰链

<400> 63

Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro

1 5 10

<210> 64

<211> 22

<212> PRT

<213> 智人

<220>

<223> GM-CSF 信号肽

<400> 64

Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro

1 5 10 15

Ala Phe Leu Leu Ile Pro

20

<210> 65

<211> 24

<212> PRT

<213> 智人

<220>

<223> Tim4 信号肽

<400> 65

Met Ser Lys Glu Pro Leu Ile Leu Trp Leu Met Ile Glu Phe Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Val Thr Ser

20

<210> 66

<211> 22

<212> PRT

<213> 小家鼠

<220>

<223> Tim4 信号肽

<400> 66

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala

20

<210> 67

<211> 18

<212> PRT

<213> 人工序列

<220>

<223> T2A 自切割肽

<400> 67

Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro

1 5 10 15

Gly Pro

<210> 68

<211> 23

<212> PRT

<213> 人工序列

<220>

<223> T2A 自切割肽变体

<400> 68

Leu Glu Gly Gly Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp

1 5 10 15

Val Glu Glu Asn Pro Gly Pro

20

<210> 69

<211> 19

<212> PRT

<213> 人工序列

<220>

<223> T2A 自切割肽变体

<400> 69

Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro

1 5 10 15

Gly Pro Arg

<210> 70

<211> 19

<212> PRT

<213> 人工序列

<220>

<223> P2A 自切割肽

<400> 70

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

1 5 10 15

Pro Gly Pro

<210> 71

<211> 27

<212> PRT

<213> 人工序列

<220>

<223> P2A 自切割肽变体

<400> 71

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

1 5 10 15

Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro

20 25

<210> 72

<211> 20

<212> PRT

<213> 人工序列

<220>

<223> E2A 自切割肽

<400> 72

Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser

1 5 10 15

Asn Pro Gly Pro

20

<210> 73

<211> 22

<212> PRT

<213> 人工序列

<220>

<223> F2A 自切割肽

<400> 73

Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val

1 5 10 15

Glu Ser Asn Pro Gly Pro

20

<210> 74

<400> 74

000

<210> 75

<211> 24

<212> PRT

<213> 人工序列

<220>

<223> T2A 自切割肽变体

<400> 75

Leu Glu Gly Gly Gly Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp

1 5 10 15

Val Glu Glu Asn Pro Gly Pro Arg

20

<210> 76

<400> 76

000

<210> 77

<400> 77

000

<210> 78

<400> 78

000

<210> 79

<400> 79

000

<210> 80

<400> 80

000

<210> 81

<400> 81

000

<210> 82

<211> 285

<212> PRT

<213> 智人

<220>

<223> 截短的EGFR

<400> 82

Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu

1 5 10 15

Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile

20 25 30

Ser Gly Asp Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe

35 40 45

Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr

50 55 60

Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn

65 70 75 80

Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg

85 90 95

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

100 105 110

Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val

115 120 125

Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp

130 135 140

Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn

145 150 155 160

Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu

165 170 175

Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser

180 185 190

Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu

195 200 205

Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln

210 215 220

Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly

225 230 235 240

Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro

245 250 255

His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr

260 265 270

Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His

275 280 285

<210> 83

<211> 192

<212> PRT

<213> 智人

<220>

<223> Rac1

<400> 83

Met Gln Ala Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys

1 5 10 15

Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Ala Phe Pro Gly Glu Tyr

20 25 30

Ile Pro Thr Val Phe Asp Asn Tyr Ser Ala Asn Val Met Val Asp Gly

35 40 45

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

50 55 60

Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Asp Val Phe Leu Ile

65 70 75 80

Cys Phe Ser Leu Val Ser Pro Ala Ser Phe Glu Asn Val Arg Ala Lys

85 90 95

Trp Tyr Pro Glu Val Arg His His Cys Pro Asn Thr Pro Ile Ile Leu

100 105 110

Val Gly Thr Lys Leu Asp Leu Arg Asp Asp Lys Asp Thr Ile Glu Lys

115 120 125

Leu Lys Glu Lys Lys Leu Thr Pro Ile Thr Tyr Pro Gln Gly Leu Ala

130 135 140

Met Ala Lys Glu Ile Gly Ala Val Lys Tyr Leu Glu Cys Ser Ala Leu

145 150 155 160

Thr Gln Arg Gly Leu Lys Thr Val Phe Asp Glu Ala Ile Arg Ala Val

165 170 175

Leu Cys Pro Pro Pro Val Lys Lys Arg Lys Arg Lys Cys Leu Leu Leu

180 185 190

<210> 84

<211> 215

<212> PRT

<213> 智人

<220>

<223> Rab5

<400> 84

Met Ala Ser Arg Gly Ala Thr Arg Pro Asn Gly Pro Asn Thr Gly Asn

1 5 10 15

Lys Ile Cys Gln Phe Lys Leu Val Leu Leu Gly Glu Ser Ala Val Gly

20 25 30

Lys Ser Ser Leu Val Leu Arg Phe Val Lys Gly Gln Phe His Glu Phe

35 40 45

Gln Glu Ser Thr Ile Gly Ala Ala Phe Leu Thr Gln Thr Val Cys Leu

50 55 60

Asp Asp Thr Thr Val Lys Phe Glu Ile Trp Asp Thr Ala Gly Gln Glu

65 70 75 80

Arg Tyr His Ser Leu Ala Pro Met Tyr Tyr Arg Gly Ala Gln Ala Ala

85 90 95

Ile Val Val Tyr Asp Ile Thr Asn Glu Glu Ser Phe Ala Arg Ala Lys

100 105 110

Asn Trp Val Lys Glu Leu Gln Arg Gln Ala Ser Pro Asn Ile Val Ile

115 120 125

Ala Leu Ser Gly Asn Lys Ala Asp Leu Ala Asn Lys Arg Ala Val Asp

130 135 140

Phe Gln Glu Ala Gln Ser Tyr Ala Asp Asp Asn Ser Leu Leu Phe Met

145 150 155 160

Glu Thr Ser Ala Lys Thr Ser Met Asn Val Asn Glu Ile Phe Met Ala

165 170 175

Ile Ala Lys Lys Leu Pro Lys Asn Glu Pro Gln Asn Pro Gly Ala Asn

180 185 190

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

195 200 205

Arg Asn Gln Cys Cys Ser Asn

210 215

<210> 85

<211> 207

<212> PRT

<213> 智人

<220>

<223> Rab7

<400> 85

Met Thr Ser Arg Lys Lys Val Leu Leu Lys Val Ile Ile Leu Gly Asp

1 5 10 15

Ser Gly Val Gly Lys Thr Ser Leu Met Asn Gln Tyr Val Asn Lys Lys

20 25 30

Phe Ser Asn Gln Tyr Lys Ala Thr Ile Gly Ala Asp Phe Leu Thr Lys

35 40 45

Glu Val Met Val Asp Asp Arg Leu Val Thr Met Gln Ile Trp Asp Thr

50 55 60

Ala Gly Gln Glu Arg Phe Gln Ser Leu Gly Val Ala Phe Tyr Arg Gly

65 70 75 80

Ala Asp Cys Cys Val Leu Val Phe Asp Val Thr Ala Pro Asn Thr Phe

85 90 95

Lys Thr Leu Asp Ser Trp Arg Asp Glu Phe Leu Ile Gln Ala Ser Pro

100 105 110

Arg Asp Pro Glu Asn Phe Pro Phe Val Val Leu Gly Asn Lys Ile Asp

115 120 125

Leu Glu Asn Arg Gln Val Ala Thr Lys Arg Ala Gln Ala Trp Cys Tyr

130 135 140

Ser Lys Asn Asn Ile Pro Tyr Phe Glu Thr Ser Ala Lys Glu Ala Ile

145 150 155 160

Asn Val Glu Gln Ala Phe Gln Thr Ile Ala Arg Asn Ala Leu Lys Gln

165 170 175

Glu Thr Glu Val Glu Leu Tyr Asn Glu Phe Pro Glu Pro Ile Lys Leu

180 185 190

Asp Lys Asn Asp Arg Ala Lys Ala Ser Ala Glu Ser Cys Ser Cys

195 200 205

<210> 86

<211> 184

<212> PRT

<213> 智人

<220>

<223> Rap1

<400> 86

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

1 5 10 15

Ser Ala Leu Thr Val Gln Phe Val Gln Gly Ile Phe Val Glu Lys Tyr

20 25 30

Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Glu Val Asp Cys

35 40 45

Gln Gln Cys Met Leu Glu Ile Leu Asp Thr Ala Gly Thr Glu Gln Phe

50 55 60

Thr Ala Met Arg Asp Leu Tyr Met Lys Asn Gly Gln Gly Phe Ala Leu

65 70 75 80

Val Tyr Ser Ile Thr Ala Gln Ser Thr Phe Asn Asp Leu Gln Asp Leu

85 90 95

Arg Glu Gln Ile Leu Arg Val Lys Asp Thr Glu Asp Val Pro Met Ile

100 105 110

Leu Val Gly Asn Lys Cys Asp Leu Glu Asp Glu Arg Val Val Gly Lys

115 120 125

Glu Gln Gly Gln Asn Leu Ala Arg Gln Trp Cys Asn Cys Ala Phe Leu

130 135 140

Glu Ser Ser Ala Lys Ser Lys Ile Asn Val Asn Glu Ile Phe Tyr Asp

145 150 155 160

Leu Val Arg Gln Ile Asn Arg Lys Thr Pro Val Glu Lys Lys Lys Pro

165 170 175

Lys Lys Lys Ser Cys Leu Leu Leu

180

<210> 87

<211> 193

<212> PRT

<213> 智人

<220>

<223> RhoA

<400> 87

Met Ala Ala Ile Arg Lys Lys Leu Val Ile Val Gly Asp Gly Ala Cys

1 5 10 15

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

20 25 30

Val Tyr Val Pro Thr Val Phe Glu Asn Tyr Val Ala Asp Ile Glu Val

35 40 45

Asp Gly Lys Gln Val Glu Leu Ala Leu Trp Asp Thr Ala Gly Gln Glu

50 55 60

Asp Tyr Asp Arg Leu Arg Pro Leu Ser Tyr Pro Asp Thr Asp Val Ile

65 70 75 80

Leu Met Cys Phe Ser Ile Asp Ser Pro Asp Ser Leu Glu Asn Ile Pro

85 90 95

Glu Lys Trp Thr Pro Glu Val Lys His Phe Cys Pro Asn Val Pro Ile

100 105 110

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

115 120 125

Arg Glu Leu Ala Lys Met Lys Gln Glu Pro Val Lys Pro Glu Glu Gly

130 135 140

Arg Asp Met Ala Asn Arg Ile Gly Ala Phe Gly Tyr Met Glu Cys Ser

145 150 155 160

Ala Lys Thr Lys Asp Gly Val Arg Glu Val Phe Glu Met Ala Thr Arg

165 170 175

Ala Ala Leu Gln Ala Arg Arg Gly Lys Lys Lys Ser Gly Cys Leu Val

180 185 190

Leu

<210> 88

<400> 88

000

<210> 89

<400> 89

000

<210> 90

<211> 598

<212> PRT

<213> 人工序列

<220>

<223> HPV16 E7 TCRβ链-P2A-TCRα链

<400> 90

Met Ala Pro Gly Leu Leu Cys Trp Ala Leu Leu Cys Leu Leu Gly Ala

1 5 10 15

Gly Leu Val Asp Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys

20 25 30

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

35 40 45

Asp Thr Val Ser Trp Tyr Gln Gln Ala Leu Gly Gln Gly Pro Gln Phe

50 55 60

Ile Phe Gln Tyr Tyr Glu Glu Glu Glu Arg Gln Arg Gly Asn Phe Pro

65 70 75 80

Asp Arg Phe Ser Gly His Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn

85 90 95

Val Asn Ala Leu Leu Leu Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser

100 105 110

Ser Leu Gly Trp Arg Gly Gly Arg Tyr Asn Glu Gln Phe Phe Gly Pro

115 120 125

Gly Thr Arg Leu Thr Val Leu Glu Asp Leu Arg Asn Val Thr Pro Pro

130 135 140

Lys Val Ser Leu Phe Glu Pro Ser Lys Ala Glu Ile Ala Asn Lys Gln

145 150 155 160

Lys Ala Thr Leu Val Cys Leu Ala Arg Gly Phe Phe Pro Asp His Val

165 170 175

Glu Leu Ser Trp Trp Val Asn Gly Lys Glu Val His Ser Gly Val Cys

180 185 190

Thr Asp Pro Gln Ala Tyr Lys Glu Ser Asn Tyr Ser Tyr Cys Leu Ser

195 200 205

Ser Arg Leu Arg Val Ser Ala Thr Phe Trp His Asn Pro Arg Asn His

210 215 220

Phe Arg Cys Gln Val Gln Phe His Gly Leu Ser Glu Glu Asp Lys Trp

225 230 235 240

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

245 250 255

Trp Gly Arg Ala Asp Cys Gly Ile Thr Ser Ala Ser Tyr Gln Gln Gly

260 265 270

Val Leu Ser Ala Thr Ile Leu Tyr Glu Ile Leu Leu Gly Lys Ala Thr

275 280 285

Leu Tyr Ala Val Leu Val Ser Thr Leu Val Val Met Ala Met Val Lys

290 295 300

Arg Lys Asn Ser Arg Ala Lys Arg Ser Gly Ser Gly Ala Thr Asn Phe

305 310 315 320

Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met

325 330 335

Trp Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr Thr

340 345 350

Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly Ala

355 360 365

Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly Leu

370 375 380

Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser Tyr

385 390 395 400

Asn Val Leu Asp Gly Leu Glu Glu Lys Gly Arg Phe Ser Ser Phe Leu

405 410 415

Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln Met

420 425 430

Lys Asp Ser Ala Ser Tyr Leu Cys Ala Ser Val Asp Gly Asn Asn Arg

435 440 445

Leu Ala Phe Gly Lys Gly Asn Gln Val Val Val Ile Pro Asn Ile Gln

450 455 460

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

465 470 475 480

Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile Asn Val Pro

485 490 495

Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys Val Leu Asp

500 505 510

Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala Trp Ser Asn

515 520 525

Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr Asn Ala Thr

530 535 540

Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr Glu Lys Ser

545 550 555 560

Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu Val Ile Val

565 570 575

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

580 585 590

Leu Arg Leu Trp Ser Ser

595

<210> 91

<211> 279

<212> PRT

<213> 小家鼠

<220>

<223> Tim4 结合结构域, 氨基酸1-22是信号肽

<400> 91

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

Gln Ile Asn Ser Arg Gln Thr

275

<210> 92

<211> 135

<212> PRT

<213> 人工序列

<220>

<223> TCR Vβ区

<400> 92

Met Ala Pro Gly Leu Leu Cys Trp Ala Leu Leu Cys Leu Leu Gly Ala

1 5 10 15

Gly Leu Val Asp Ala Gly Val Thr Gln Ser Pro Thr His Leu Ile Lys

20 25 30

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

35 40 45

Asp Thr Val Ser Trp Tyr Gln Gln Ala Leu Gly Gln Gly Pro Gln Phe

50 55 60

Ile Phe Gln Tyr Tyr Glu Glu Glu Glu Arg Gln Arg Gly Asn Phe Pro

65 70 75 80

Asp Arg Phe Ser Gly His Gln Phe Pro Asn Tyr Ser Ser Glu Leu Asn

85 90 95

Val Asn Ala Leu Leu Leu Gly Asp Ser Ala Leu Tyr Leu Cys Ala Ser

100 105 110

Ser Leu Gly Trp Arg Gly Gly Arg Tyr Asn Glu Gln Phe Phe Gly Pro

115 120 125

Gly Thr Arg Leu Thr Val Leu

130 135

<210> 93

<211> 173

<212> PRT

<213> 人工序列

<220>

<223> TCR Cβ区, Cys-取代

<400> 93

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

1 5 10 15

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

20 25 30

Ala Arg Gly Phe Phe Pro Asp His Val Glu Leu Ser Trp Trp Val Asn

35 40 45

Gly Lys Glu Val His Ser Gly Val Cys Thr Asp Pro Gln Ala Tyr Lys

50 55 60

Glu Ser Asn Tyr Ser Tyr Cys Leu Ser Ser Arg Leu Arg Val Ser Ala

65 70 75 80

Thr Phe Trp His Asn Pro Arg Asn His Phe Arg Cys Gln Val Gln Phe

85 90 95

His Gly Leu Ser Glu Glu Asp Lys Trp Pro Glu Gly Ser Pro Lys Pro

100 105 110

Val Thr Gln Asn Ile Ser Ala Glu Ala Trp Gly Arg Ala Asp Cys Gly

115 120 125

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

130 135 140

Tyr Glu Ile Leu Leu Gly Lys Ala Thr Leu Tyr Ala Val Leu Val Ser

145 150 155 160

Thr Leu Val Val Met Ala Met Val Lys Arg Lys Asn Ser

165 170

<210> 94

<211> 126

<212> PRT

<213> 人工序列

<220>

<223> TCR Vα区

<400> 94

Met Trp Gly Val Phe Leu Leu Tyr Val Ser Met Lys Met Gly Gly Thr

1 5 10 15

Thr Gly Gln Asn Ile Asp Gln Pro Thr Glu Met Thr Ala Thr Glu Gly

20 25 30

Ala Ile Val Gln Ile Asn Cys Thr Tyr Gln Thr Ser Gly Phe Asn Gly

35 40 45

Leu Phe Trp Tyr Gln Gln His Ala Gly Glu Ala Pro Thr Phe Leu Ser

50 55 60

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

65 70 75 80

Leu Ser Arg Ser Lys Gly Tyr Ser Tyr Leu Leu Leu Lys Glu Leu Gln

85 90 95

Met Lys Asp Ser Ala Ser Tyr Leu Cys Ala Ser Val Asp Gly Asn Asn

100 105 110

Arg Leu Ala Phe Gly Lys Gly Asn Gln Val Val Val Ile Pro

115 120 125

<210> 95

<211> 137

<212> PRT

<213> 人工序列

<220>

<223> TCR Cα区, Cys-取代, LVL

取代

<400> 95

Asn Ile Gln Asn Pro Glu Pro Ala Val Tyr Gln Leu Lys Asp Pro Arg

1 5 10 15

Ser Gln Asp Ser Thr Leu Cys Leu Phe Thr Asp Phe Asp Ser Gln Ile

20 25 30

Asn Val Pro Lys Thr Met Glu Ser Gly Thr Phe Ile Thr Asp Lys Cys

35 40 45

Val Leu Asp Met Lys Ala Met Asp Ser Lys Ser Asn Gly Ala Ile Ala

50 55 60

Trp Ser Asn Gln Thr Ser Phe Thr Cys Gln Asp Ile Phe Lys Glu Thr

65 70 75 80

Asn Ala Thr Tyr Pro Ser Ser Asp Val Pro Cys Asp Ala Thr Leu Thr

85 90 95

Glu Lys Ser Phe Glu Thr Asp Met Asn Leu Asn Phe Gln Asn Leu Leu

100 105 110

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

115 120 125

Leu Met Thr Leu Arg Leu Trp Ser Ser

130 135

<210> 96

<211> 314

<212> PRT

<213> 智人

<220>

<223> Tim4 结合结构域, 氨基酸1-24信号肽

<400> 96

Met Ser Lys Glu Pro Leu Ile Leu Trp Leu Met Ile Glu Phe Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Val Thr Ser Glu Thr Val Val Thr Glu Val Leu

20 25 30

Gly His Arg Val Thr Leu Pro Cys Leu Tyr Ser Ser Trp Ser His Asn

35 40 45

Ser Asn Ser Met Cys Trp Gly Lys Asp Gln Cys Pro Tyr Ser Gly Cys

50 55 60

Lys Glu Ala Leu Ile Arg Thr Asp Gly Met Arg Val Thr Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Leu Asn Pro Ser Glu Ser Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Ile Asn Val Arg

115 120 125

Leu Asn Leu Gln Arg Ala Ser Thr Thr Thr His Arg Thr Ala Thr Thr

130 135 140

Thr Thr Arg Arg Thr Thr Thr Thr Ser Pro Thr Thr Thr Arg Gln Met

145 150 155 160

Thr Thr Thr Pro Ala Ala Leu Pro Thr Thr Val Val Thr Thr Pro Asp

165 170 175

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

180 185 190

Thr Ala Asn Thr Cys Leu Ser Leu Thr Pro Ser Thr Leu Pro Glu Glu

195 200 205

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

210 215 220

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

225 230 235 240

Glu Ser Thr Ser Ala Asp Thr Val Leu Leu Thr Ser Lys Glu Ser Lys

245 250 255

Val Trp Asp Leu Pro Ser Thr Ser His Val Ser Met Trp Lys Thr Ser

260 265 270

Asp Ser Val Ser Ser Pro Gln Pro Gly Ala Ser Asp Thr Ala Val Pro

275 280 285

Glu Gln Asn Lys Thr Thr Lys Thr Gly Gln Met Asp Gly Ile Pro Met

290 295 300

Ser Met Lys Asn Glu Met Pro Ile Ser Gln

305 310

<210> 97

<211> 487

<212> PRT

<213> 人工序列

<220>

<223> CER5, 氨基酸1-22是信号肽

<400> 97

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Lys Phe Tyr Phe

290 295 300

His Leu Met Leu Leu Ala Gly Cys Ile Lys Tyr Gly Arg Gly Glu Asn

305 310 315 320

Ile Tyr Asp Ala Phe Val Ile Tyr Ser Ser Gln Asp Glu Asp Trp Val

325 330 335

Arg Asn Glu Leu Val Lys Asn Leu Glu Glu Gly Val Pro Pro Phe Gln

340 345 350

Leu Cys Leu His Tyr Arg Asp Phe Ile Pro Gly Val Ala Ile Ala Ala

355 360 365

Asn Ile Ile His Glu Gly Phe His Lys Ser Arg Lys Val Ile Val Val

370 375 380

Val Ser Gln His Phe Ile Gln Ser Arg Trp Cys Ile Phe Glu Tyr Glu

385 390 395 400

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

405 410 415

Ile Val Leu Gln Lys Val Glu Lys Thr Leu Leu Arg Gln Gln Val Glu

420 425 430

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

435 440 445

Val Leu Gly Arg His Ile Phe Trp Arg Arg Leu Arg Lys Ala Leu Leu

450 455 460

Asp Gly Lys Ser Trp Asn Pro Glu Gly Thr Val Gly Thr Gly Cys Asn

465 470 475 480

Trp Gln Glu Ala Thr Ser Ile

485

<210> 98

<211> 498

<212> PRT

<213> 人工序列

<220>

<223> CER19, 氨基酸1-22是信号肽

<400> 98

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Thr Lys Phe Arg

290 295 300

Gly Phe Cys Phe Ile Cys Tyr Lys Thr Ala Gln Arg Leu Val Phe Lys

305 310 315 320

Asp His Pro Gln Gly Thr Glu Pro Asp Met Tyr Lys Tyr Asp Ala Tyr

325 330 335

Leu Cys Phe Ser Ser Lys Asp Phe Thr Trp Val Gln Asn Ala Leu Leu

340 345 350

Lys His Leu Asp Thr Gln Tyr Ser Asp Gln Asn Arg Phe Asn Leu Cys

355 360 365

Phe Glu Glu Arg Asp Phe Val Pro Gly Glu Asn Arg Ile Ala Asn Ile

370 375 380

Gln Asp Ala Ile Trp Asn Ser Arg Lys Ile Val Cys Leu Val Ser Arg

385 390 395 400

His Phe Leu Arg Asp Gly Trp Cys Leu Glu Ala Phe Ser Tyr Ala Gln

405 410 415

Gly Arg Cys Leu Ser Asp Leu Asn Ser Ala Leu Ile Met Val Val Val

420 425 430

Gly Ser Leu Ser Gln Tyr Gln Leu Met Lys His Gln Ser Ile Arg Gly

435 440 445

Phe Val Gln Lys Gln Gln Tyr Leu Arg Trp Pro Glu Asp Phe Gln Asp

450 455 460

Val Gly Trp Phe Leu His Lys Leu Ser Gln Gln Ile Leu Lys Lys Glu

465 470 475 480

Lys Glu Lys Lys Lys Asp Asn Asn Ile Pro Leu Gln Thr Val Ala Thr

485 490 495

Ile Ser

<210> 99

<211> 493

<212> PRT

<213> 人工序列

<220>

<223> CER21, 氨基酸1-22是信号肽

<400> 99

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr

485 490

<210> 100

<211> 386

<212> PRT

<213> 人工序列

<220>

<223> CER25; 氨基酸1-22是信号肽

<400> 100

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Leu Trp Asn Lys

290 295 300

Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp

305 310 315 320

Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr

325 330 335

Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn

340 345 350

Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu

355 360 365

Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu

370 375 380

Asn Leu

385

<210> 101

<211> 475

<212> PRT

<213> 人工序列

<220>

<223> CER27, 氨基酸1-22是信号肽

<400> 101

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Phe His

290 295 300

Gly Leu Trp Tyr Met Lys Met Met Trp Ala Trp Leu Gln Ala Lys Arg

305 310 315 320

Lys Pro Arg Lys Ala Pro Ser Arg Asn Ile Cys Tyr Asp Ala Phe Val

325 330 335

Ser Tyr Ser Glu Arg Asp Ala Tyr Trp Val Glu Asn Leu Met Val Gln

340 345 350

Glu Leu Glu Asn Phe Asn Pro Pro Phe Lys Leu Cys Leu His Lys Arg

355 360 365

Asp Phe Ile Pro Gly Lys Trp Ile Ile Asp Asn Ile Ile Asp Ser Ile

370 375 380

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

385 390 395 400

Ser Glu Trp Cys Lys Tyr Glu Leu Asp Phe Ser His Phe Arg Leu Phe

405 410 415

Asp Glu Asn Asn Asp Ala Ala Ile Leu Ile Leu Leu Glu Pro Ile Glu

420 425 430

Lys Lys Ala Ile Pro Gln Arg Phe Cys Lys Leu Arg Lys Ile Met Asn

435 440 445

Thr Lys Thr Tyr Leu Glu Trp Pro Met Asp Glu Ala Gln Arg Glu Gly

450 455 460

Phe Trp Val Asn Leu Arg Ala Ala Ile Lys Ser

465 470 475

<210> 102

<211> 574

<212> PRT

<213> 人工序列

<220>

<223> CER29, 氨基酸1-22是信号肽

<400> 102

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala

565 570

<210> 103

<211> 574

<212> PRT

<213> 人工序列

<220>

<223> CER31, 氨基酸1-22是信号肽

<400> 103

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Glu Ser Ser

290 295 300

Lys Lys Met Asp Ser Pro Gly Ala Leu Gln Thr Asn Pro Pro Leu Lys

305 310 315 320

Leu His Thr Asp Arg Ser Ala Gly Thr Pro Val Phe Val Pro Glu Gln

325 330 335

Gly Gly Tyr Lys Glu Lys Phe Val Lys Thr Val Glu Asp Lys Tyr Lys

340 345 350

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

355 360 365

Gly His Arg Phe Cys Glu Ser Cys Met Ala Ala Leu Leu Ser Ser Ser

370 375 380

Ser Pro Lys Cys Thr Ala Cys Gln Glu Ser Ile Val Lys Asp Lys Val

385 390 395 400

Phe Lys Asp Asn Cys Cys Lys Arg Glu Ile Leu Ala Leu Gln Ile Tyr

405 410 415

Cys Arg Asn Glu Ser Arg Gly Cys Ala Glu Gln Leu Met Leu Gly His

420 425 430

Leu Leu Val His Leu Lys Asn Asp Cys His Phe Glu Glu Leu Pro Cys

435 440 445

Val Arg Pro Asp Cys Lys Glu Lys Val Leu Arg Lys Asp Leu Arg Asp

450 455 460

His Val Glu Lys Ala Cys Lys Tyr Arg Glu Ala Thr Cys Ser His Cys

465 470 475 480

Lys Ser Gln Val Pro Met Ile Ala Leu Gln Lys His Glu Asp Thr Asp

485 490 495

Cys Pro Cys Val Val Val Ser Cys Pro His Lys Cys Ser Val Gln Thr

500 505 510

Leu Leu Arg Ser Glu Leu Ser Ala His Leu Ser Glu Cys Val Asn Ala

515 520 525

Pro Ser Thr Cys Ser Phe Lys Arg Tyr Gly Cys Val Phe Gln Gly Thr

530 535 540

Asn Gln Gln Ile Lys Ala His Glu Ala Ser Ser Ala Val Gln His Val

545 550 555 560

Asn Leu Leu Lys Glu Trp Ser Asn Ser Leu Glu Lys Lys Val

565 570

<210> 104

<211> 70

<212> PRT

<213> 智人

<220>

<223> FcγR2B2 信号传导结构域

<400> 104

Val Val Ala Leu Ile Tyr Cys Arg Lys Lys Arg Ile Ser Ala Leu Pro

1 5 10 15

Gly Tyr Pro Glu Cys Arg Glu Met Gly Glu Thr Leu Pro Glu Lys Pro

20 25 30

Ala Asn Pro Thr Asn Pro Asp Glu Ala Asp Lys Val Gly Ala Glu Asn

35 40 45

Thr Ile Thr Tyr Ser Leu Leu Met His Pro Asp Ala Leu Glu Glu Pro

50 55 60

Asp Asp Gln Asn Arg Ile

65 70

<210> 105

<211> 41

<212> PRT

<213> 智人

<220>

<223> FcαR1 信号传导结构域

<400> 105

Glu Asn Trp His Ser His Thr Ala Leu Asn Lys Glu Ala Ser Ala Asp

1 5 10 15

Val Ala Glu Pro Ser Trp Ser Gln Gln Met Cys Gln Pro Gly Leu Thr

20 25 30

Phe Ala Arg Thr Pro Ser Val Cys Lys

35 40

<210> 106

<211> 141

<212> PRT

<213> 智人

<220>

<223> MyD88 TIR结构域

<400> 106

His Met Pro Glu Arg Phe Asp Ala Phe Ile Cys Tyr Cys Pro Ser Asp

1 5 10 15

Ile Gln Phe Val Gln Glu Met Ile Arg Gln Leu Glu Gln Thr Asn Tyr

20 25 30

Arg Leu Lys Leu Cys Val Ser Asp Arg Asp Val Leu Pro Gly Thr Cys

35 40 45

Val Trp Ser Ile Ala Ser Glu Leu Ile Glu Lys Arg Cys Arg Arg Met

50 55 60

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

65 70 75 80

Gln Thr Lys Phe Ala Leu Ser Leu Ser Pro Gly Ala His Gln Lys Arg

85 90 95

Leu Ile Pro Ile Lys Tyr Lys Ala Met Lys Lys Glu Phe Pro Ser Ile

100 105 110

Leu Arg Phe Ile Thr Val Cys Asp Tyr Thr Asn Pro Cys Thr Lys Ser

115 120 125

Trp Phe Trp Thr Arg Leu Ala Lys Ala Leu Ser Leu Pro

130 135 140

<210> 107

<211> 27

<212> PRT

<213> 智人

<220>

<223> CD28 跨膜结构域

<400> 107

Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu

1 5 10 15

Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val

20 25

<210> 108

<211> 191

<212> PRT

<213> 智人

<220>

<223> CDC42

<400> 108

Met Gln Thr Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys

1 5 10 15

Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Lys Phe Pro Ser Glu Tyr

20 25 30

Val Pro Thr Val Phe Asp Asn Tyr Ala Val Thr Val Met Ile Gly Gly

35 40 45

Glu Pro Tyr Thr Leu Gly Leu Phe Asp Thr Ala Gly Gln Glu Asp Tyr

50 55 60

Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Asp Val Phe Leu Val

65 70 75 80

Cys Phe Ser Val Val Ser Pro Ser Ser Phe Glu Asn Val Lys Glu Lys

85 90 95

Trp Val Pro Glu Ile Thr His His Cys Pro Lys Thr Pro Phe Leu Leu

100 105 110

Val Gly Thr Gln Ile Asp Leu Arg Asp Asp Pro Ser Thr Ile Glu Lys

115 120 125

Leu Ala Lys Asn Lys Gln Lys Pro Ile Thr Pro Glu Thr Ala Glu Lys

130 135 140

Leu Ala Arg Asp Leu Lys Ala Val Lys Tyr Val Glu Cys Ser Ala Leu

145 150 155 160

Thr Gln Lys Gly Leu Lys Asn Val Phe Asp Glu Ala Ile Leu Ala Ala

165 170 175

Leu Glu Pro Pro Glu Pro Lys Lys Ser Arg Arg Cys Val Leu Leu

180 185 190

<210> 109

<211> 776

<212> PRT

<213> 人工序列

<220>

<223> CER1, 氨基酸1-22是信号肽

<400> 109

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg

290 295 300

Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser

305 310 315 320

Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala

325 330 335

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

340 345 350

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

355 360 365

Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

370 375 380

Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu

385 390 395 400

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

405 410 415

Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val

420 425 430

Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu

435 440 445

Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe

465 470 475 480

Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe

485 490 495

Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met

500 505 510

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

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr

565 570 575

Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His

580 585 590

Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp

595 600 605

Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe

610 615 620

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

625 630 635 640

Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu

645 650 655

Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met

660 665 670

Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala

675 680 685

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu

690 695 700

Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser

705 710 715 720

Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu

725 730 735

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

740 745 750

Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser

755 760 765

Leu Glu Asp Ser Glu Val Leu Met

770 775

<210> 110

<211> 487

<212> PRT

<213> 人工序列

<220>

<223> CER6, 氨基酸1-22是信号肽

<400> 110

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Val Leu Val Val Ser Val Val Ala Val Leu Val Tyr Lys Phe Tyr Phe

290 295 300

His Leu Met Leu Leu Ala Gly Cys Ile Lys Tyr Gly Arg Gly Glu Asn

305 310 315 320

Ile Tyr Asp Ala Phe Val Ile Tyr Ser Ser Gln Asp Glu Asp Trp Val

325 330 335

Arg Asn Glu Leu Val Lys Asn Leu Glu Glu Gly Val Pro Pro Phe Gln

340 345 350

Leu Cys Leu His Tyr Arg Asp Phe Ile Pro Gly Val Ala Ile Ala Ala

355 360 365

Asn Ile Ile His Glu Gly Phe His Lys Ser Arg Lys Val Ile Val Val

370 375 380

Val Ser Gln His Phe Ile Gln Ser Arg Trp Cys Ile Phe Glu Tyr Glu

385 390 395 400

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

405 410 415

Ile Val Leu Gln Lys Val Glu Lys Thr Leu Leu Arg Gln Gln Val Glu

420 425 430

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

435 440 445

Val Leu Gly Arg His Ile Phe Trp Arg Arg Leu Arg Lys Ala Leu Leu

450 455 460

Asp Gly Lys Ser Trp Asn Pro Glu Gly Thr Val Gly Thr Gly Cys Asn

465 470 475 480

Trp Gln Glu Ala Thr Ser Ile

485

<210> 111

<211> 500

<212> PRT

<213> 人工序列

<220>

<223> CER7, 氨基酸1-22是信号肽

<400> 111

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

Gln Ile Asn Ser Arg Gln Thr Pro Val Leu Ser Leu Asn Ile Thr Cys

275 280 285

Gln Met Asn Lys Thr Ile Ile Gly Val Ser Val Leu Ser Val Leu Val

290 295 300

Val Ser Val Val Ala Val Leu Val Tyr Lys Phe Tyr Phe His Leu Met

305 310 315 320

Leu Leu Ala Gly Cys Ile Lys Tyr Gly Arg Gly Glu Asn Ile Tyr Asp

325 330 335

Ala Phe Val Ile Tyr Ser Ser Gln Asp Glu Asp Trp Val Arg Asn Glu

340 345 350

Leu Val Lys Asn Leu Glu Glu Gly Val Pro Pro Phe Gln Leu Cys Leu

355 360 365

His Tyr Arg Asp Phe Ile Pro Gly Val Ala Ile Ala Ala Asn Ile Ile

370 375 380

His Glu Gly Phe His Lys Ser Arg Lys Val Ile Val Val Val Ser Gln

385 390 395 400

His Phe Ile Gln Ser Arg Trp Cys Ile Phe Glu Tyr Glu Ile Ala Gln

405 410 415

Thr Trp Gln Phe Leu Ser Ser Arg Ala Gly Ile Ile Phe Ile Val Leu

420 425 430

Gln Lys Val Glu Lys Thr Leu Leu Arg Gln Gln Val Glu Leu Tyr Arg

435 440 445

Leu Leu Ser Arg Asn Thr Tyr Leu Glu Trp Glu Asp Ser Val Leu Gly

450 455 460

Arg His Ile Phe Trp Arg Arg Leu Arg Lys Ala Leu Leu Asp Gly Lys

465 470 475 480

Ser Trp Asn Pro Glu Gly Thr Val Gly Thr Gly Cys Asn Trp Gln Glu

485 490 495

Ala Thr Ser Ile

500

<210> 112

<211> 740

<212> PRT

<213> 人工序列

<220>

<223> CER8, 氨基酸1-22是信号肽

<400> 112

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Leu Arg Lys Arg

290 295 300

Arg Lys Glu Thr Arg Phe Gly Gln Ala Phe Asp Ser Val Met Ala Arg

305 310 315 320

Gly Glu Pro Ala Val His Phe Arg Ala Ala Arg Ser Phe Asn Arg Glu

325 330 335

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

340 345 350

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

355 360 365

Thr Leu Gly Arg Met Leu Gly Lys Gly Glu Phe Gly Ser Val Arg Glu

370 375 380

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

385 390 395 400

Met Leu Lys Ala Asp Ile Ile Ala Ser Ser Asp Ile Glu Glu Phe Leu

405 410 415

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

420 425 430

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

435 440 445

Pro Met Val Ile Leu Pro Phe Met Lys His Gly Asp Leu His Ala Phe

450 455 460

Leu Leu Ala Ser Arg Ile Gly Glu Asn Pro Phe Asn Leu Pro Leu Gln

465 470 475 480

Thr Leu Ile Arg Phe Met Val Asp Ile Ala Cys Gly Met Glu Tyr Leu

485 490 495

Ser Ser Arg Asn Phe Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met

500 505 510

Leu Ala Glu Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Arg

515 520 525

Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Cys Ala Ser Lys Leu

530 535 540

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

545 550 555 560

Val Gln Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Met

565 570 575

Thr Arg Gly Gln Thr Pro Tyr Ala Gly Ile Glu Asn Ala Glu Ile Tyr

580 585 590

Asn Tyr Leu Ile Gly Gly Asn Arg Leu Lys Gln Pro Pro Glu Cys Met

595 600 605

Glu Asp Val Tyr Asp Leu Met Tyr Gln Cys Trp Ser Ala Asp Pro Lys

610 615 620

Gln Arg Pro Ser Phe Thr Cys Leu Arg Met Glu Leu Glu Asn Ile Leu

625 630 635 640

Gly Gln Leu Ser Val Leu Ser Ala Ser Gln Asp Pro Leu Tyr Ile Asn

645 650 655

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

660 665 670

Gly Arg Asp Gln Pro Tyr Ser Gly Ala Gly Asp Gly Ser Gly Met Gly

675 680 685

Ala Val Gly Gly Thr Pro Ser Asp Cys Arg Tyr Ile Leu Thr Pro Gly

690 695 700

Gly Leu Ala Glu Gln Pro Gly Gln Ala Glu His Gln Pro Glu Ser Pro

705 710 715 720

Leu Asn Glu Thr Gln Arg Leu Leu Leu Leu Gln Gln Gly Leu Leu Pro

725 730 735

His Ser Ser Cys

740

<210> 113

<211> 352

<212> PRT

<213> 人工序列

<220>

<223> CER9, 氨基酸1-22是信号肽

<400> 113

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Tyr Phe Leu Gly

290 295 300

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

305 310 315 320

Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln

325 330 335

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

340 345 350

<210> 114

<211> 352

<212> PRT

<213> 人工序列

<220>

<223> CER10, 氨基酸1-22是信号肽

<400> 114

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Asp Leu Val Leu Thr Val Leu Ile Ala Leu Ala Val Tyr Phe Leu Gly

290 295 300

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

305 310 315 320

Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln

325 330 335

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

340 345 350

<210> 115

<211> 722

<212> PRT

<213> 人工序列

<220>

<223> CER11, 氨基酸1-22是信号肽

<400> 115

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys

290 295 300

Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly

305 310 315 320

Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr

325 330 335

Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu

340 345 350

Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys

355 360 365

Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn

370 375 380

Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala

385 390 395 400

Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys

405 410 415

Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys

420 425 430

Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu

435 440 445

Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe

465 470 475 480

Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe

485 490 495

Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met

500 505 510

Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr

565 570 575

Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln

580 585 590

Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala

595 600 605

Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe

610 615 620

Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro

625 630 635 640

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

645 650 655

Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr

660 665 670

Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val

675 680 685

His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro

690 695 700

Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp

705 710 715 720

Gly Ala

<210> 116

<211> 342

<212> PRT

<213> 人工序列

<220>

<223> CER12, 氨基酸1-22是信号肽

<400> 116

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Arg Leu Lys Ile

290 295 300

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

305 310 315 320

Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr Glu Thr Leu Lys

325 330 335

His Glu Lys Pro Pro Gln

340

<210> 117

<211> 342

<212> PRT

<213> 人工序列

<220>

<223> CER13, 氨基酸1-22是信号肽

<400> 117

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

Gln Ile Asn Ser Arg Gln Thr Leu Cys Tyr Ile Leu Asp Ala Ile Leu

275 280 285

Phe Leu Tyr Gly Ile Val Leu Thr Leu Leu Tyr Cys Arg Leu Lys Ile

290 295 300

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

305 310 315 320

Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr Glu Thr Leu Lys

325 330 335

His Glu Lys Pro Pro Gln

340

<210> 118

<211> 455

<212> PRT

<213> 人工序列

<220>

<223> CER15, 氨基酸1-22是信号肽

<400> 118

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly

290 295 300

Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu

305 310 315 320

Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe

325 330 335

Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu

340 345 350

Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala

355 360 365

Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala

370 375 380

Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp

385 390 395 400

Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr

405 410 415

Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala

420 425 430

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

435 440 445

Thr Leu Asp Asp Pro Leu Gly

450 455

<210> 119

<211> 441

<212> PRT

<213> 人工序列

<220>

<223> CER16, 氨基酸1-22是信号肽

<400> 119

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Met Pro Glu

290 295 300

Arg Phe Asp Ala Phe Ile Cys Tyr Cys Pro Ser Asp Ile Gln Phe Val

305 310 315 320

Gln Glu Met Ile Arg Gln Leu Glu Gln Thr Asn Tyr Arg Leu Lys Leu

325 330 335

Cys Val Ser Asp Arg Asp Val Leu Pro Gly Thr Cys Val Trp Ser Ile

340 345 350

Ala Ser Glu Leu Ile Glu Lys Arg Cys Arg Arg Met Val Val Val Val

355 360 365

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

370 375 380

Ala Leu Ser Leu Ser Pro Gly Ala His Gln Lys Arg Leu Ile Pro Ile

385 390 395 400

Lys Tyr Lys Ala Met Lys Lys Glu Phe Pro Ser Ile Leu Arg Phe Ile

405 410 415

Thr Val Cys Asp Tyr Thr Asn Pro Cys Thr Lys Ser Trp Phe Trp Thr

420 425 430

Arg Leu Ala Lys Ala Leu Ser Leu Pro

435 440

<210> 120

<211> 479

<212> PRT

<213> 人工序列

<220>

<223> CER17, 氨基酸1-22是信号肽

<400> 120

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Glu Gly Trp Arg

290 295 300

Ile Ser Phe Tyr Trp Asn Val Ser Val His Arg Val Leu Gly Phe Lys

305 310 315 320

Glu Ile Asp Arg Gln Thr Glu Gln Phe Glu Tyr Ala Ala Tyr Ile Ile

325 330 335

His Ala Tyr Lys Asp Lys Asp Trp Val Trp Glu His Phe Ser Ser Met

340 345 350

Glu Lys Glu Asp Gln Ser Leu Lys Phe Cys Leu Glu Glu Arg Asp Phe

355 360 365

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

370 375 380

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

385 390 395 400

Leu Cys Lys Arg Phe Lys Val His His Ala Val Gln Gln Ala Ile Glu

405 410 415

Gln Asn Leu Asp Ser Ile Ile Leu Val Phe Leu Glu Glu Ile Pro Asp

420 425 430

Tyr Lys Leu Asn His Ala Leu Cys Leu Arg Arg Gly Met Phe Lys Ser

435 440 445

His Cys Ile Leu Asn Trp Pro Val Gln Lys Glu Arg Ile Gly Ala Phe

450 455 460

Arg His Lys Leu Gln Val Ala Leu Gly Ser Lys Asn Ser Val His

465 470 475

<210> 121

<211> 479

<212> PRT

<213> 人工序列

<220>

<223> CER18, 氨基酸1-22是信号肽

<400> 121

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

Gln Ile Asn Ser Arg Gln Thr Phe Phe Met Ile Asn Thr Ser Ile Leu

275 280 285

Leu Ile Phe Ile Phe Ile Val Leu Leu Ile His Phe Glu Gly Trp Arg

290 295 300

Ile Ser Phe Tyr Trp Asn Val Ser Val His Arg Val Leu Gly Phe Lys

305 310 315 320

Glu Ile Asp Arg Gln Thr Glu Gln Phe Glu Tyr Ala Ala Tyr Ile Ile

325 330 335

His Ala Tyr Lys Asp Lys Asp Trp Val Trp Glu His Phe Ser Ser Met

340 345 350

Glu Lys Glu Asp Gln Ser Leu Lys Phe Cys Leu Glu Glu Arg Asp Phe

355 360 365

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

370 375 380

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

385 390 395 400

Leu Cys Lys Arg Phe Lys Val His His Ala Val Gln Gln Ala Ile Glu

405 410 415

Gln Asn Leu Asp Ser Ile Ile Leu Val Phe Leu Glu Glu Ile Pro Asp

420 425 430

Tyr Lys Leu Asn His Ala Leu Cys Leu Arg Arg Gly Met Phe Lys Ser

435 440 445

His Cys Ile Leu Asn Trp Pro Val Gln Lys Glu Arg Ile Gly Ala Phe

450 455 460

Arg His Lys Leu Gln Val Ala Leu Gly Ser Lys Asn Ser Val His

465 470 475

<210> 122

<211> 498

<212> PRT

<213> 人工序列

<220>

<223> CER20, 氨基酸1-22是信号肽

<400> 122

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

Gln Ile Asn Ser Arg Gln Thr Phe Ser Leu Phe Ile Val Cys Thr Val

275 280 285

Thr Leu Thr Leu Phe Leu Met Thr Ile Leu Thr Val Thr Lys Phe Arg

290 295 300

Gly Phe Cys Phe Ile Cys Tyr Lys Thr Ala Gln Arg Leu Val Phe Lys

305 310 315 320

Asp His Pro Gln Gly Thr Glu Pro Asp Met Tyr Lys Tyr Asp Ala Tyr

325 330 335

Leu Cys Phe Ser Ser Lys Asp Phe Thr Trp Val Gln Asn Ala Leu Leu

340 345 350

Lys His Leu Asp Thr Gln Tyr Ser Asp Gln Asn Arg Phe Asn Leu Cys

355 360 365

Phe Glu Glu Arg Asp Phe Val Pro Gly Glu Asn Arg Ile Ala Asn Ile

370 375 380

Gln Asp Ala Ile Trp Asn Ser Arg Lys Ile Val Cys Leu Val Ser Arg

385 390 395 400

His Phe Leu Arg Asp Gly Trp Cys Leu Glu Ala Phe Ser Tyr Ala Gln

405 410 415

Gly Arg Cys Leu Ser Asp Leu Asn Ser Ala Leu Ile Met Val Val Val

420 425 430

Gly Ser Leu Ser Gln Tyr Gln Leu Met Lys His Gln Ser Ile Arg Gly

435 440 445

Phe Val Gln Lys Gln Gln Tyr Leu Arg Trp Pro Glu Asp Phe Gln Asp

450 455 460

Val Gly Trp Phe Leu His Lys Leu Ser Gln Gln Ile Leu Lys Lys Glu

465 470 475 480

Lys Glu Lys Lys Lys Asp Asn Asn Ile Pro Leu Gln Thr Val Ala Thr

485 490 495

Ile Ser

<210> 123

<211> 493

<212> PRT

<213> 人工序列

<220>

<223> CER22, 氨基酸1-22是信号肽

<400> 123

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Ile Thr Thr Met Val Met Leu Ala Ala Leu Ala His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr

485 490

<210> 124

<211> 493

<212> PRT

<213> 人工序列

<220>

<223> CER23, 氨基酸1-22是信号肽

<400> 124

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Gly Trp Asp Leu

290 295 300

Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp Arg Gly Arg

305 310 315 320

Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala Phe Val Val

325 330 335

Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr Asn Glu Leu

340 345 350

Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu Arg Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe Glu Asn Leu

370 375 380

Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val Leu Ala His

385 390 395 400

Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu Leu Ala Gln

405 410 415

Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu Val Ile Leu

420 425 430

Ser Pro Asp Gly Arg Arg Ser Arg Tyr Val Arg Leu Arg Gln Arg Leu

435 440 445

Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser Gly Gln Arg

450 455 460

Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp Asn His His

465 470 475 480

Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu

485 490

<210> 125

<211> 493

<212> PRT

<213> 人工序列

<220>

<223> CER24, 氨基酸1-22是信号肽

<400> 125

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Leu Gly Leu Gly Val Pro Met Leu His His Leu Cys Gly Trp Asp Leu

290 295 300

Trp Tyr Cys Phe His Leu Cys Leu Ala Trp Leu Pro Trp Arg Gly Arg

305 310 315 320

Gln Ser Gly Arg Asp Glu Asp Ala Leu Pro Tyr Asp Ala Phe Val Val

325 330 335

Phe Asp Lys Thr Gln Ser Ala Val Ala Asp Trp Val Tyr Asn Glu Leu

340 345 350

Arg Gly Gln Leu Glu Glu Cys Arg Gly Arg Trp Ala Leu Arg Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Leu Pro Gly Lys Thr Leu Phe Glu Asn Leu

370 375 380

Trp Ala Ser Val Tyr Gly Ser Arg Lys Thr Leu Phe Val Leu Ala His

385 390 395 400

Thr Asp Arg Val Ser Gly Leu Leu Arg Ala Ser Phe Leu Leu Ala Gln

405 410 415

Gln Arg Leu Leu Glu Asp Arg Lys Asp Val Val Val Leu Val Ile Leu

420 425 430

Ser Pro Asp Gly Arg Arg Ser Arg Tyr Val Arg Leu Arg Gln Arg Leu

435 440 445

Cys Arg Gln Ser Val Leu Leu Trp Pro His Gln Pro Ser Gly Gln Arg

450 455 460

Ser Phe Trp Ala Gln Leu Gly Met Ala Leu Thr Arg Asp Asn His His

465 470 475 480

Phe Tyr Asn Arg Asn Phe Cys Gln Gly Pro Thr Ala Glu

485 490

<210> 126

<211> 485

<212> PRT

<213> 人工序列

<220>

<223> CER26, 氨基酸1-22是信号肽

<400> 126

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Tyr Leu Asp

290 295 300

Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr Arg Arg

305 310 315 320

Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe

325 330 335

His Ala Phe Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn

340 345 350

Glu Leu Leu Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His

355 360 365

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

370 375 380

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

385 390 395 400

Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn

405 410 415

Leu Phe His Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro

420 425 430

Ile Pro Gln Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu

435 440 445

Met Ala Arg Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg

450 455 460

Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr

465 470 475 480

Glu Gln Ala Lys Lys

485

<210> 127

<211> 489

<212> PRT

<213> 人工序列

<220>

<223> CER28, 氨基酸1-22是信号肽

<400> 127

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Leu Tyr Phe

290 295 300

Trp Asp Val Trp Tyr Ile Tyr His Phe Cys Lys Ala Lys Ile Lys Gly

305 310 315 320

Tyr Gln Arg Leu Ile Ser Pro Asp Cys Cys Tyr Asp Ala Phe Ile Val

325 330 335

Tyr Asp Thr Lys Asp Pro Ala Val Thr Glu Trp Val Leu Ala Glu Leu

340 345 350

Val Ala Lys Leu Glu Asp Pro Arg Glu Lys His Phe Asn Leu Cys Leu

355 360 365

Glu Glu Arg Asp Trp Leu Pro Gly Gln Pro Val Leu Glu Asn Leu Ser

370 375 380

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

385 390 395 400

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

405 410 415

Arg Leu Met Asp Glu Lys Val Asp Val Ile Ile Leu Ile Phe Leu Glu

420 425 430

Lys Pro Phe Gln Lys Ser Lys Phe Leu Gln Leu Arg Lys Arg Leu Cys

435 440 445

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

450 455 460

Phe Trp Gln Cys Leu Lys Asn Ala Leu Ala Thr Asp Asn His Val Ala

465 470 475 480

Tyr Ser Gln Val Phe Lys Glu Thr Val

485

<210> 128

<211> 603

<212> PRT

<213> 人工序列

<220>

<223> CER30, 氨基酸1-22是信号肽

<400> 128

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Ala

290 295 300

Ser Val Thr Pro Pro Gly Ser Leu Glu Leu Leu Gln Pro Gly Phe Ser

305 310 315 320

Lys Thr Leu Leu Gly Thr Lys Leu Glu Ala Lys Tyr Leu Cys Ser Ala

325 330 335

Cys Arg Asn Val Leu Arg Arg Pro Phe Gln Ala Gln Cys Gly His Arg

340 345 350

Tyr Cys Ser Phe Cys Leu Ala Ser Ile Leu Ser Ser Gly Pro Gln Asn

355 360 365

Cys Ala Ala Cys Val His Glu Gly Ile Tyr Glu Glu Gly Ile Ser Ile

370 375 380

Leu Glu Ser Ser Ser Ala Phe Pro Asp Asn Ala Ala Arg Arg Glu Val

385 390 395 400

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

405 410 415

Thr Leu Lys Glu Tyr Glu Ser Cys His Glu Gly Arg Cys Pro Leu Met

420 425 430

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

435 440 445

Glu Arg His Leu Glu His Glu Cys Pro Glu Arg Ser Leu Ser Cys Arg

450 455 460

His Cys Arg Ala Pro Cys Cys Gly Ala Asp Val Lys Ala His His Glu

465 470 475 480

Val Cys Pro Lys Phe Pro Leu Thr Cys Asp Gly Cys Gly Lys Lys Lys

485 490 495

Ile Pro Arg Glu Lys Phe Gln Asp His Val Lys Thr Cys Gly Lys Cys

500 505 510

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

515 520 525

Gly Glu Lys Gln Gln Glu His Glu Val Gln Trp Leu Arg Glu His Leu

530 535 540

Ala Met Leu Leu Ser Ser Val Leu Glu Ala Lys Pro Leu Leu Gly Asp

545 550 555 560

Gln Ser His Ala Gly Ser Glu Leu Leu Gln Arg Cys Glu Ser Leu Glu

565 570 575

Lys Lys Thr Ala Thr Phe Glu Asn Ile Val Cys Val Leu Asn Arg Glu

580 585 590

Val Glu Arg Val Ala Met Thr Ala Glu Ala Cys

595 600

<210> 129

<211> 540

<212> PRT

<213> 人工序列

<220>

<223> CER85, 氨基酸1-22是信号肽

<400> 129

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly

290 295 300

Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu

305 310 315 320

Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe

325 330 335

Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu

340 345 350

Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala

355 360 365

Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala

370 375 380

Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp

385 390 395 400

Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr

405 410 415

Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala

420 425 430

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

435 440 445

Thr Leu Asp Asp Pro Leu Gly Ser Trp Arg Arg Arg Gln Arg Arg Leu

450 455 460

Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly Asp Lys Asp Ala Pro

465 470 475 480

Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro Gly Ile Ser Asp Ala

485 490 495

Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp Pro Gly Thr Thr Pro

500 505 510

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

515 520 525

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

530 535 540

<210> 130

<211> 507

<212> PRT

<213> 人工序列

<220>

<223> CER86, 氨基酸1-22是信号肽

<400> 130

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly

290 295 300

Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu

305 310 315 320

Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe

325 330 335

Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu

340 345 350

Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala

355 360 365

Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala

370 375 380

Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp

385 390 395 400

Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr

405 410 415

Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala

420 425 430

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

435 440 445

Thr Leu Asp Asp Pro Leu Gly Tyr Phe Leu Gly Arg Leu Val Pro Arg

450 455 460

Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu

465 470 475 480

Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr

485 490 495

Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys

500 505

<210> 131

<211> 540

<212> PRT

<213> 人工序列

<220>

<223> CER87, 氨基酸1-22是信号肽

<400> 131

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Trp Arg Arg

290 295 300

Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly

305 310 315 320

Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro

325 330 335

Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp

340 345 350

Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val Pro Ala Thr Glu

355 360 365

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

370 375 380

Gln Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser

385 390 395 400

Ser Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg

405 410 415

Arg Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp

420 425 430

Thr Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln

435 440 445

Leu Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln

450 455 460

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

465 470 475 480

Leu Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu

485 490 495

Asp Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys

500 505 510

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

515 520 525

Leu Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly

530 535 540

<210> 132

<211> 507

<212> PRT

<213> 人工序列

<220>

<223> CER88, 氨基酸1-22是信号肽

<400> 132

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Tyr Phe Leu Gly

290 295 300

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

305 310 315 320

Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln

325 330 335

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

340 345 350

Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser

355 360 365

Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg

370 375 380

Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr

385 390 395 400

Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu

405 410 415

Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly

420 425 430

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

435 440 445

Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp

450 455 460

Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro

465 470 475 480

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

485 490 495

Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly

500 505

<210> 133

<211> 500

<212> PRT

<213> 人工序列

<220>

<223> CER89, 氨基酸1-22是信号肽

<400> 133

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly

290 295 300

Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu

305 310 315 320

Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe

325 330 335

Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu

340 345 350

Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala

355 360 365

Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala

370 375 380

Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp

385 390 395 400

Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr

405 410 415

Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala

420 425 430

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

435 440 445

Thr Leu Asp Asp Pro Leu Gly Asp Ser Lys Ala Gly Met Glu Glu Asp

450 455 460

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

465 470 475 480

Ile Val Thr Leu Arg Thr Gly Glu Val Lys Trp Ser Val Gly Glu His

485 490 495

Pro Gly Gln Glu

500

<210> 134

<211> 541

<212> PRT

<213> 人工序列

<220>

<223> CER90, 氨基酸1-22是信号肽

<400> 134

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly

290 295 300

Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu

305 310 315 320

Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe

325 330 335

Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu

340 345 350

Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala

355 360 365

Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala

370 375 380

Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp

385 390 395 400

Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr

405 410 415

Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala

420 425 430

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

435 440 445

Thr Leu Asp Asp Pro Leu Gly Leu Trp Asn Lys Lys Arg Met Arg Gly

450 455 460

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

465 470 475 480

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

485 490 495

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

500 505 510

Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu Arg Pro His Arg Phe

515 520 525

Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu Asn Leu

530 535 540

<210> 135

<211> 692

<212> PRT

<213> 人工序列

<220>

<223> CER91, 氨基酸1-22是信号肽

<400> 135

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly

290 295 300

Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu

305 310 315 320

Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe

325 330 335

Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu

340 345 350

Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala

355 360 365

Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala

370 375 380

Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp

385 390 395 400

Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr

405 410 415

Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala

420 425 430

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

435 440 445

Thr Leu Asp Asp Pro Leu Gly Gly Ser Gly Ala Thr Asn Phe Ser Leu

450 455 460

Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Ala Ser

465 470 475 480

Arg Gly Ala Thr Arg Pro Asn Gly Pro Asn Thr Gly Asn Lys Ile Cys

485 490 495

Gln Phe Lys Leu Val Leu Leu Gly Glu Ser Ala Val Gly Lys Ser Ser

500 505 510

Leu Val Leu Arg Phe Val Lys Gly Gln Phe His Glu Phe Gln Glu Ser

515 520 525

Thr Ile Gly Ala Ala Phe Leu Thr Gln Thr Val Cys Leu Asp Asp Thr

530 535 540

Thr Val Lys Phe Glu Ile Trp Asp Thr Ala Gly Gln Glu Arg Tyr His

545 550 555 560

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

565 570 575

Tyr Asp Ile Thr Asn Glu Glu Ser Phe Ala Arg Ala Lys Asn Trp Val

580 585 590

Lys Glu Leu Gln Arg Gln Ala Ser Pro Asn Ile Val Ile Ala Leu Ser

595 600 605

Gly Asn Lys Ala Asp Leu Ala Asn Lys Arg Ala Val Asp Phe Gln Glu

610 615 620

Ala Gln Ser Tyr Ala Asp Asp Asn Ser Leu Leu Phe Met Glu Thr Ser

625 630 635 640

Ala Lys Thr Ser Met Asn Val Asn Glu Ile Phe Met Ala Ile Ala Lys

645 650 655

Lys Leu Pro Lys Asn Glu Pro Gln Asn Pro Gly Ala Asn Ser Ala Arg

660 665 670

Gly Arg Gly Val Asp Leu Thr Glu Pro Thr Gln Pro Thr Arg Asn Gln

675 680 685

Cys Cys Ser Asn

690

<210> 136

<211> 931

<212> PRT

<213> 人工序列

<220>

<223> CER92, 氨基酸1-22是信号肽

<400> 136

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg

290 295 300

Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser

305 310 315 320

Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala

325 330 335

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

340 345 350

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

355 360 365

Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

370 375 380

Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu

385 390 395 400

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

405 410 415

Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val

420 425 430

Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu

435 440 445

Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe

465 470 475 480

Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe

485 490 495

Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met

500 505 510

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

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr

565 570 575

Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His

580 585 590

Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp

595 600 605

Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe

610 615 620

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

625 630 635 640

Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu

645 650 655

Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met

660 665 670

Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala

675 680 685

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu

690 695 700

Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser

705 710 715 720

Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu

725 730 735

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

740 745 750

Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser

755 760 765

Leu Glu Asp Ser Glu Val Leu Met Met Ala Ala Gly Gly Pro Gly Ala

770 775 780

Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu Pro Leu Ala Ala

785 790 795 800

Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe Leu Asn Val Arg

805 810 815

Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu Glu Met Asp Phe

820 825 830

Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala Asp Pro Thr Gly

835 840 845

Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala Ser Val Gly Arg

850 855 860

Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp Val Leu Leu Glu

865 870 875 880

Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr Ile Leu Lys Gln

885 890 895

Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala Ala Val Asp Ser

900 905 910

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

915 920 925

Pro Leu Gly

930

<210> 137

<211> 861

<212> PRT

<213> 人工序列

<220>

<223> CER93, 氨基酸1-22是信号肽

<400> 137

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg

290 295 300

Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser

305 310 315 320

Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala

325 330 335

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

340 345 350

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

355 360 365

Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

370 375 380

Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu

385 390 395 400

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

405 410 415

Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val

420 425 430

Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu

435 440 445

Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe

465 470 475 480

Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe

485 490 495

Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met

500 505 510

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

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr

565 570 575

Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His

580 585 590

Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp

595 600 605

Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe

610 615 620

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

625 630 635 640

Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu

645 650 655

Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met

660 665 670

Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala

675 680 685

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu

690 695 700

Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser

705 710 715 720

Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu

725 730 735

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

740 745 750

Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser

755 760 765

Leu Glu Asp Ser Glu Val Leu Met Ser Trp Arg Arg Arg Gln Arg Arg

770 775 780

Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly Asp Lys Asp Ala

785 790 795 800

Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro Gly Ile Ser Asp

805 810 815

Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp Pro Gly Thr Thr

820 825 830

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

835 840 845

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

850 855 860

<210> 138

<211> 828

<212> PRT

<213> 人工序列

<220>

<223> CER94, 氨基酸1-22是信号肽

<400> 138

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg

290 295 300

Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser

305 310 315 320

Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala

325 330 335

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

340 345 350

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

355 360 365

Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

370 375 380

Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu

385 390 395 400

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

405 410 415

Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val

420 425 430

Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu

435 440 445

Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe

465 470 475 480

Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe

485 490 495

Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met

500 505 510

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

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr

565 570 575

Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His

580 585 590

Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp

595 600 605

Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe

610 615 620

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

625 630 635 640

Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu

645 650 655

Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met

660 665 670

Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala

675 680 685

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu

690 695 700

Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser

705 710 715 720

Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu

725 730 735

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

740 745 750

Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser

755 760 765

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

770 775 780

Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr

785 790 795 800

Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val

805 810 815

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

820 825

<210> 139

<211> 821

<212> PRT

<213> 人工序列

<220>

<223> CER95, 氨基酸1-22是信号肽

<400> 139

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg

290 295 300

Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser

305 310 315 320

Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala

325 330 335

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

340 345 350

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

355 360 365

Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

370 375 380

Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu

385 390 395 400

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

405 410 415

Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val

420 425 430

Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu

435 440 445

Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe

465 470 475 480

Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe

485 490 495

Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met

500 505 510

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

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr

565 570 575

Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His

580 585 590

Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp

595 600 605

Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe

610 615 620

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

625 630 635 640

Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu

645 650 655

Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met

660 665 670

Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala

675 680 685

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu

690 695 700

Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser

705 710 715 720

Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu

725 730 735

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

740 745 750

Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser

755 760 765

Leu Glu Asp Ser Glu Val Leu Met Asp Ser Lys Ala Gly Met Glu Glu

770 775 780

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

785 790 795 800

Asp Ile Val Thr Leu Arg Thr Gly Glu Val Lys Trp Ser Val Gly Glu

805 810 815

His Pro Gly Gln Glu

820

<210> 140

<211> 862

<212> PRT

<213> 人工序列

<220>

<223> CER96, 氨基酸1-22是信号肽

<400> 140

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg

290 295 300

Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser

305 310 315 320

Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala

325 330 335

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

340 345 350

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

355 360 365

Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

370 375 380

Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu

385 390 395 400

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

405 410 415

Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val

420 425 430

Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu

435 440 445

Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe

465 470 475 480

Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe

485 490 495

Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met

500 505 510

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

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr

565 570 575

Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His

580 585 590

Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp

595 600 605

Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe

610 615 620

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

625 630 635 640

Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu

645 650 655

Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met

660 665 670

Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala

675 680 685

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu

690 695 700

Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser

705 710 715 720

Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu

725 730 735

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

740 745 750

Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser

755 760 765

Leu Glu Asp Ser Glu Val Leu Met Leu Trp Asn Lys Lys Arg Met Arg

770 775 780

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

785 790 795 800

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

805 810 815

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

820 825 830

Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu Arg Pro His Arg

835 840 845

Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu Asn Leu

850 855 860

<210> 141

<211> 774

<212> PRT

<213> 人工序列

<220>

<223> CER97, 氨基酸1-22是信号肽

<400> 141

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys

290 295 300

Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly

305 310 315 320

Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr

325 330 335

Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu

340 345 350

Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys

355 360 365

Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn

370 375 380

Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala

385 390 395 400

Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys

405 410 415

Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys

420 425 430

Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu

435 440 445

Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe

465 470 475 480

Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe

485 490 495

Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met

500 505 510

Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr

565 570 575

Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln

580 585 590

Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala

595 600 605

Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe

610 615 620

Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro

625 630 635 640

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

645 650 655

Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr

660 665 670

Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val

675 680 685

His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro

690 695 700

Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp

705 710 715 720

Gly Ala Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala

725 730 735

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

740 745 750

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

755 760 765

Gln Arg Pro Tyr Tyr Lys

770

<210> 142

<211> 767

<212> PRT

<213> 人工序列

<220>

<223> CER98, 氨基酸1-22是信号肽

<400> 142

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys

290 295 300

Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly

305 310 315 320

Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr

325 330 335

Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu

340 345 350

Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys

355 360 365

Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn

370 375 380

Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala

385 390 395 400

Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys

405 410 415

Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys

420 425 430

Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu

435 440 445

Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe

465 470 475 480

Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe

485 490 495

Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met

500 505 510

Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr

565 570 575

Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln

580 585 590

Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala

595 600 605

Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe

610 615 620

Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro

625 630 635 640

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

645 650 655

Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr

660 665 670

Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val

675 680 685

His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro

690 695 700

Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp

705 710 715 720

Gly Ala Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly

725 730 735

Leu Asp Ile Asp Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu Arg

740 745 750

Thr Gly Glu Val Lys Trp Ser Val Gly Glu His Pro Gly Gln Glu

755 760 765

<210> 143

<211> 808

<212> PRT

<213> 人工序列

<220>

<223> CER99, 氨基酸1-22是信号肽

<400> 143

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys

290 295 300

Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly

305 310 315 320

Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr

325 330 335

Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu

340 345 350

Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys

355 360 365

Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn

370 375 380

Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala

385 390 395 400

Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys

405 410 415

Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys

420 425 430

Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu

435 440 445

Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe

465 470 475 480

Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe

485 490 495

Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met

500 505 510

Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr

565 570 575

Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln

580 585 590

Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala

595 600 605

Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe

610 615 620

Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro

625 630 635 640

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

645 650 655

Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr

660 665 670

Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val

675 680 685

His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro

690 695 700

Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp

705 710 715 720

Gly Ala Leu Trp Asn Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro

725 730 735

Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His

740 745 750

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

755 760 765

Tyr Ala Cys Ile Glu Asn Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln

770 775 780

Ser Pro Leu Ser Gln Glu Arg Pro His Arg Phe Glu Asp Asp Gly Glu

785 790 795 800

Leu Asn Leu Val Tyr Glu Asn Leu

805

<210> 144

<211> 579

<212> PRT

<213> 人工序列

<220>

<223> CER102, 氨基酸1-22是信号肽

<400> 144

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr Leu Trp Asn

485 490 495

Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro

500 505 510

Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val

515 520 525

Tyr Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu

530 535 540

Asn Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln

545 550 555 560

Glu Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr

565 570 575

Glu Asn Leu

<210> 145

<211> 538

<212> PRT

<213> 人工序列

<220>

<223> CER103A, 氨基酸1-22是信号肽

<400> 145

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr Asp Ser Lys

485 490 495

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

500 505 510

Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu Arg Thr Gly Glu Val Lys

515 520 525

Trp Ser Val Gly Glu His Pro Gly Gln Glu

530 535

<210> 146

<211> 522

<212> PRT

<213> 人工序列

<220>

<223> CER103B, 氨基酸1-22是信号肽

<400> 146

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr Asp Ser Lys

485 490 495

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

500 505 510

Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu

515 520

<210> 147

<211> 545

<212> PRT

<213> 人工序列

<220>

<223> CER104, 氨基酸1-22是信号肽

<400> 147

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

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

485 490 495

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

500 505 510

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

515 520 525

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

530 535 540

Lys

545

<210> 148

<211> 578

<212> PRT

<213> 人工序列

<220>

<223> CER105, 氨基酸1-22是信号肽

<400> 148

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr Ser Trp Arg

485 490 495

Arg Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp

500 505 510

Gly Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser

515 520 525

Pro Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu

530 535 540

Asp Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val Pro Ala Thr

545 550 555 560

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

565 570 575

Gln Gln

<210> 149

<211> 579

<212> PRT

<213> 人工序列

<220>

<223> CER106, 氨基酸1-22是信号肽

<400> 149

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Leu Trp Asn Lys

290 295 300

Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp

305 310 315 320

Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr

325 330 335

Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn

340 345 350

Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu

355 360 365

Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu

370 375 380

Asn Leu His His Leu Phe Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val

385 390 395 400

Cys Leu Ala Lys Val Lys Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr

405 410 415

Phe Tyr Asp Ala Tyr Ile Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr

420 425 430

Asp Trp Val Ile Asn Glu Leu Arg Tyr His Leu Glu Glu Ser Arg Asp

435 440 445

Lys Asn Val Leu Leu Cys Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu

450 455 460

Ala Ile Ile Asp Asn Leu Met Gln Ser Ile Asn Gln Ser Lys Lys Thr

465 470 475 480

Val Phe Val Leu Thr Lys Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr

485 490 495

Ala Phe Tyr Leu Ala Leu Gln Arg Leu Met Asp Glu Asn Met Asp Val

500 505 510

Ile Ile Phe Ile Leu Leu Glu Pro Val Leu Gln His Ser Gln Tyr Leu

515 520 525

Arg Leu Arg Gln Arg Ile Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp

530 535 540

Asn Pro Lys Ala Glu Gly Leu Phe Trp Gln Thr Leu Arg Asn Val Val

545 550 555 560

Leu Thr Glu Asn Asp Ser Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile

565 570 575

Lys Gln Tyr

<210> 150

<211> 522

<212> PRT

<213> 人工序列

<220>

<223> CER107, 氨基酸1-22是信号肽

<400> 150

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Asp Ser Lys Ala

290 295 300

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

305 310 315 320

Ala Thr Tyr Glu Asp Ile Val Thr Leu His His Leu Phe Tyr Trp Asp

325 330 335

Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys Gly Tyr Arg

340 345 350

Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile Ser Tyr Asp

355 360 365

Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu Leu Arg Tyr

370 375 380

His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys Leu Glu Glu

385 390 395 400

Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu Met Gln Ser

405 410 415

Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys Lys Tyr Ala

420 425 430

Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu Gln Arg Leu

435 440 445

Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu Glu Pro Val

450 455 460

Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile Cys Lys Ser

465 470 475 480

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

485 490 495

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

500 505 510

Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr

515 520

<210> 151

<211> 545

<212> PRT

<213> 人工序列

<220>

<223> CER108, 氨基酸1-22是信号肽

<400> 151

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Tyr Phe Leu Gly

290 295 300

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

305 310 315 320

Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln

325 330 335

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

340 345 350

His His Leu Phe Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu

355 360 365

Ala Lys Val Lys Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr

370 375 380

Asp Ala Tyr Ile Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp

385 390 395 400

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

405 410 415

Val Leu Leu Cys Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile

420 425 430

Ile Asp Asn Leu Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe

435 440 445

Val Leu Thr Lys Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe

450 455 460

Tyr Leu Ala Leu Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile

465 470 475 480

Phe Ile Leu Leu Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu

485 490 495

Arg Gln Arg Ile Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro

500 505 510

Lys Ala Glu Gly Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr

515 520 525

Glu Asn Asp Ser Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln

530 535 540

Tyr

545

<210> 152

<211> 578

<212> PRT

<213> 人工序列

<220>

<223> CER109, 氨基酸1-22是信号肽

<400> 152

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Trp Arg Arg

290 295 300

Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly

305 310 315 320

Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro

325 330 335

Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp

340 345 350

Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val Pro Ala Thr Glu

355 360 365

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

370 375 380

Gln His His Leu Phe Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys

385 390 395 400

Leu Ala Lys Val Lys Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe

405 410 415

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

420 425 430

Trp Val Ile Asn Glu Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys

435 440 445

Asn Val Leu Leu Cys Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala

450 455 460

Ile Ile Asp Asn Leu Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val

465 470 475 480

Phe Val Leu Thr Lys Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala

485 490 495

Phe Tyr Leu Ala Leu Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile

500 505 510

Ile Phe Ile Leu Leu Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg

515 520 525

Leu Arg Gln Arg Ile Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn

530 535 540

Pro Lys Ala Glu Gly Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu

545 550 555 560

Thr Glu Asn Asp Ser Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys

565 570 575

Gln Tyr

<210> 153

<211> 626

<212> PRT

<213> 人工序列

<220>

<223> CER110, 氨基酸1-22是信号肽

<400> 153

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala Tyr Phe

565 570 575

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

580 585 590

Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln

595 600 605

Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr

610 615 620

Tyr Lys

625

<210> 154

<211> 619

<212> PRT

<213> 人工序列

<220>

<223> CER111A, 氨基酸1-22是信号肽

<400> 154

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala Asp Ser

565 570 575

Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly Leu Asp Ile Asp

580 585 590

Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu Arg Thr Gly Glu Val

595 600 605

Lys Trp Ser Val Gly Glu His Pro Gly Gln Glu

610 615

<210> 155

<211> 603

<212> PRT

<213> 人工序列

<220>

<223> CER111B, 氨基酸1-22是信号肽

<400> 155

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala Asp Ser

565 570 575

Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly Leu Asp Ile Asp

580 585 590

Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu

595 600

<210> 156

<211> 660

<212> PRT

<213> 人工序列

<220>

<223> CER112, 氨基酸1-22是信号肽

<400> 156

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala Leu Trp

565 570 575

Asn Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys

580 585 590

Pro Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser Glu Ser

595 600 605

Val Tyr Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile

610 615 620

Glu Asn Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser

625 630 635 640

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

645 650 655

Tyr Glu Asn Leu

660

<210> 157

<211> 659

<212> PRT

<213> 人工序列

<220>

<223> CER113, 氨基酸1-22是信号肽

<400> 157

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala Ser Trp

565 570 575

Arg Arg Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro

580 585 590

Asp Gly Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile Ile Leu

595 600 605

Ser Pro Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly

610 615 620

Glu Asp Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val Pro Ala

625 630 635 640

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

645 650 655

Glu Gln Gln

<210> 158

<211> 1050

<212> PRT

<213> 人工序列

<220>

<223> CER114, 氨基酸1-22是信号肽

<400> 158

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala Ala Leu

565 570 575

Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu

580 585 590

Asp Ser Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg

595 600 605

Arg Ala Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu

610 615 620

Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu

625 630 635 640

Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn

645 650 655

Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met

660 665 670

Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu

675 680 685

Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu

690 695 700

Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val

705 710 715 720

Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr

725 730 735

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

740 745 750

Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg

755 760 765

Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp

770 775 780

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

785 790 795 800

Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys

805 810 815

Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser

820 825 830

Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly

835 840 845

Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu

850 855 860

Leu His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu

865 870 875 880

Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro

885 890 895

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

900 905 910

Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu

915 920 925

Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu

930 935 940

Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly

945 950 955 960

Ala Ala Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg

965 970 975

Glu Glu Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val

980 985 990

Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu

995 1000 1005

Pro Glu Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser

1010 1015 1020

Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp

1025 1030 1035 1040

Asp Ser Leu Glu Asp Ser Glu Val Leu Met

1045 1050

<210> 159

<211> 1050

<212> PRT

<213> 人工序列

<220>

<223> CER115, 氨基酸1-22是信号肽

<400> 159

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg

290 295 300

Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser

305 310 315 320

Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala

325 330 335

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

340 345 350

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

355 360 365

Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

370 375 380

Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu

385 390 395 400

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

405 410 415

Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val

420 425 430

Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu

435 440 445

Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg

450 455 460

Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe

465 470 475 480

Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe

485 490 495

Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met

500 505 510

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

515 520 525

Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile

530 535 540

Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val

545 550 555 560

Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr

565 570 575

Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His

580 585 590

Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp

595 600 605

Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe

610 615 620

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

625 630 635 640

Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu

645 650 655

Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met

660 665 670

Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala

675 680 685

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu

690 695 700

Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser

705 710 715 720

Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu

725 730 735

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

740 745 750

Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser

755 760 765

Leu Glu Asp Ser Glu Val Leu Met Met Ser Leu Leu Asn Cys Glu Asn

770 775 780

Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys Val Ala Met Ala

785 790 795 800

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

805 810 815

Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu Ile Gln Gly Tyr

820 825 830

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

835 840 845

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

850 855 860

Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp Ala Gly His Lys

865 870 875 880

Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln Leu Phe Pro Asp

885 890 895

Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val Lys Cys Pro Asn

900 905 910

Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu Glu Asp His Gln

915 920 925

Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln Cys Gln Arg Pro

930 935 940

Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys Asp Cys Pro Arg

945 950 955 960

Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met Ala Phe Glu Asp

965 970 975

Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn Val Ile Cys Glu

980 985 990

Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro Asn His Tyr Asp

995 1000 1005

Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe Ser Thr Phe Gly

1010 1015 1020

Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg His Leu Gln Glu

1025 1030 1035 1040

Asn Thr Gln Ser His Met Arg Met Leu Ala

1045 1050

<210> 160

<211> 767

<212> PRT

<213> 人工序列

<220>

<223> CER116, 氨基酸1-22是信号肽

<400> 160

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ser Leu Leu

290 295 300

Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys

305 310 315 320

Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val

325 330 335

Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu Glu

340 345 350

Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys Tyr

355 360 365

Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro

370 375 380

Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp

385 390 395 400

Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln

405 410 415

Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val

420 425 430

Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu

435 440 445

Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln

450 455 460

Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys

465 470 475 480

Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met

485 490 495

Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn

500 505 510

Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro

515 520 525

Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe

530 535 540

Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg

545 550 555 560

His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala His His

565 570 575

Leu Phe Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys

580 585 590

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

595 600 605

Tyr Ile Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile

610 615 620

Asn Glu Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu

625 630 635 640

Leu Cys Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp

645 650 655

Asn Leu Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu

660 665 670

Thr Lys Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu

675 680 685

Ala Leu Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile

690 695 700

Leu Leu Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln

705 710 715 720

Arg Ile Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala

725 730 735

Glu Gly Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn

740 745 750

Asp Ser Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr

755 760 765

<210> 161

<211> 767

<212> PRT

<213> 人工序列

<220>

<223> CER117, 氨基酸1-22是信号肽

<400> 161

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His His Leu Phe

290 295 300

Tyr Trp Asp Val Trp Phe Ile Tyr Asn Val Cys Leu Ala Lys Val Lys

305 310 315 320

Gly Tyr Arg Ser Leu Ser Thr Ser Gln Thr Phe Tyr Asp Ala Tyr Ile

325 330 335

Ser Tyr Asp Thr Lys Asp Ala Ser Val Thr Asp Trp Val Ile Asn Glu

340 345 350

Leu Arg Tyr His Leu Glu Glu Ser Arg Asp Lys Asn Val Leu Leu Cys

355 360 365

Leu Glu Glu Arg Asp Trp Asp Pro Gly Leu Ala Ile Ile Asp Asn Leu

370 375 380

Met Gln Ser Ile Asn Gln Ser Lys Lys Thr Val Phe Val Leu Thr Lys

385 390 395 400

Lys Tyr Ala Lys Ser Trp Asn Phe Lys Thr Ala Phe Tyr Leu Ala Leu

405 410 415

Gln Arg Leu Met Asp Glu Asn Met Asp Val Ile Ile Phe Ile Leu Leu

420 425 430

Glu Pro Val Leu Gln His Ser Gln Tyr Leu Arg Leu Arg Gln Arg Ile

435 440 445

Cys Lys Ser Ser Ile Leu Gln Trp Pro Asp Asn Pro Lys Ala Glu Gly

450 455 460

Leu Phe Trp Gln Thr Leu Arg Asn Val Val Leu Thr Glu Asn Asp Ser

465 470 475 480

Arg Tyr Asn Asn Met Tyr Val Asp Ser Ile Lys Gln Tyr Met Ser Leu

485 490 495

Leu Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys

500 505 510

Cys Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser

515 520 525

Val Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser Phe Met Glu

530 535 540

Glu Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu Glu Ser Lys

545 550 555 560

Tyr Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr

565 570 575

Pro Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg

580 585 590

Asp Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn

595 600 605

Gln Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met

610 615 620

Val Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His

625 630 635 640

Leu Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro

645 650 655

Gln Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu

660 665 670

Lys Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser

675 680 685

Met Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala

690 695 700

Asn Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met

705 710 715 720

Pro Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr

725 730 735

Phe Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala

740 745 750

Arg His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala

755 760 765

<210> 162

<211> 571

<212> PRT

<213> 人工序列

<220>

<223> CER118, 氨基酸1-22是信号肽

<400> 162

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Tyr Leu Asp

290 295 300

Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr Arg Arg

305 310 315 320

Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe

325 330 335

His Ala Phe Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn

340 345 350

Glu Leu Leu Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His

355 360 365

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

370 375 380

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

385 390 395 400

Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn

405 410 415

Leu Phe His Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro

420 425 430

Ile Pro Gln Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu

435 440 445

Met Ala Arg Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg

450 455 460

Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr

465 470 475 480

Glu Gln Ala Lys Lys Leu Trp Asn Lys Lys Arg Met Arg Gly Pro Gly

485 490 495

Lys Asp Pro Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala Ser Ser Pro

500 505 510

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

515 520 525

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

530 535 540

Ala Lys Gln Ser Pro Leu Ser Gln Glu Arg Pro His Arg Phe Glu Asp

545 550 555 560

Asp Gly Glu Leu Asn Leu Val Tyr Glu Asn Leu

565 570

<210> 163

<211> 514

<212> PRT

<213> 人工序列

<220>

<223> CER119B, 氨基酸1-22是信号肽

<400> 163

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Tyr Leu Asp

290 295 300

Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr Arg Arg

305 310 315 320

Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe

325 330 335

His Ala Phe Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn

340 345 350

Glu Leu Leu Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His

355 360 365

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

370 375 380

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

385 390 395 400

Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn

405 410 415

Leu Phe His Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro

420 425 430

Ile Pro Gln Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu

435 440 445

Met Ala Arg Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg

450 455 460

Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr

465 470 475 480

Glu Gln Ala Lys Lys Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr

485 490 495

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

500 505 510

Thr Leu

<210> 164

<211> 537

<212> PRT

<213> 人工序列

<220>

<223> CER120, 氨基酸1-22是信号肽

<400> 164

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Tyr Leu Asp

290 295 300

Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr Arg Arg

305 310 315 320

Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe

325 330 335

His Ala Phe Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn

340 345 350

Glu Leu Leu Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His

355 360 365

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

370 375 380

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

385 390 395 400

Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn

405 410 415

Leu Phe His Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro

420 425 430

Ile Pro Gln Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu

435 440 445

Met Ala Arg Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg

450 455 460

Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr

465 470 475 480

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

485 490 495

Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu

500 505 510

Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp

515 520 525

Leu Asn Thr Gln Arg Pro Tyr Tyr Lys

530 535

<210> 165

<211> 759

<212> PRT

<213> 人工序列

<220>

<223> CER121, 氨基酸1-22是信号肽

<400> 165

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Tyr Leu Asp

290 295 300

Leu Pro Trp Tyr Leu Arg Met Val Cys Gln Trp Thr Gln Thr Arg Arg

305 310 315 320

Arg Ala Arg Asn Ile Pro Leu Glu Glu Leu Gln Arg Asn Leu Gln Phe

325 330 335

His Ala Phe Ile Ser Tyr Ser Gly His Asp Ser Phe Trp Val Lys Asn

340 345 350

Glu Leu Leu Pro Asn Leu Glu Lys Glu Gly Met Gln Ile Cys Leu His

355 360 365

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

370 375 380

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

385 390 395 400

Val Gln Ser Glu Trp Cys His Tyr Glu Leu Tyr Phe Ala His His Asn

405 410 415

Leu Phe His Glu Gly Ser Asn Ser Leu Ile Leu Ile Leu Leu Glu Pro

420 425 430

Ile Pro Gln Tyr Ser Ile Pro Ser Ser Tyr His Lys Leu Lys Ser Leu

435 440 445

Met Ala Arg Arg Thr Tyr Leu Glu Trp Pro Lys Glu Lys Ser Lys Arg

450 455 460

Gly Leu Phe Trp Ala Asn Leu Arg Ala Ala Ile Asn Ile Lys Leu Thr

465 470 475 480

Glu Gln Ala Lys Lys Met Ser Leu Leu Asn Cys Glu Asn Ser Cys Gly

485 490 495

Ser Ser Gln Ser Glu Ser Asp Cys Cys Val Ala Met Ala Ser Ser Cys

500 505 510

Ser Ala Val Thr Lys Asp Asp Ser Val Gly Gly Thr Ala Ser Thr Gly

515 520 525

Asn Leu Ser Ser Ser Phe Met Glu Glu Ile Gln Gly Tyr Asp Val Glu

530 535 540

Phe Asp Pro Pro Leu Glu Ser Lys Tyr Glu Cys Pro Ile Cys Leu Met

545 550 555 560

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

565 570 575

Ala Cys Ile Ile Lys Ser Ile Arg Asp Ala Gly His Lys Cys Pro Val

580 585 590

Asp Asn Glu Ile Leu Leu Glu Asn Gln Leu Phe Pro Asp Asn Phe Ala

595 600 605

Lys Arg Glu Ile Leu Ser Leu Met Val Lys Cys Pro Asn Glu Gly Cys

610 615 620

Leu His Lys Met Glu Leu Arg His Leu Glu Asp His Gln Ala His Cys

625 630 635 640

Glu Phe Ala Leu Met Asp Cys Pro Gln Cys Gln Arg Pro Phe Gln Lys

645 650 655

Phe His Ile Asn Ile His Ile Leu Lys Asp Cys Pro Arg Arg Gln Val

660 665 670

Ser Cys Asp Asn Cys Ala Ala Ser Met Ala Phe Glu Asp Lys Glu Ile

675 680 685

His Asp Gln Asn Cys Pro Leu Ala Asn Val Ile Cys Glu Tyr Cys Asn

690 695 700

Thr Ile Leu Ile Arg Glu Gln Met Pro Asn His Tyr Asp Leu Asp Cys

705 710 715 720

Pro Thr Ala Pro Ile Pro Cys Thr Phe Ser Thr Phe Gly Cys His Glu

725 730 735

Lys Met Gln Arg Asn His Leu Ala Arg His Leu Gln Glu Asn Thr Gln

740 745 750

Ser His Met Arg Met Leu Ala

755

<210> 166

<211> 113

<212> PRT

<213> 智人

<220>

<223> 野生型CD3ζ信号传导结构域

<400> 166

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

1 5 10 15

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

20 25 30

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

35 40 45

Pro Gln Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln

50 55 60

Lys Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu

65 70 75 80

Arg Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr

85 90 95

Ala Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro

100 105 110

Arg

<210> 167

<211> 112

<212> PRT

<213> 智人

<220>

<223>变体CD3ζ信号传导结构域

<400> 167

Arg Val Lys Phe Ser Arg Ser Ala Asp Ala Pro Ala Tyr Gln Gln Gly

1 5 10 15

Gln Asn Gln Leu Tyr Asn Glu Leu Asn Leu Gly Arg Arg Glu Glu Tyr

20 25 30

Asp Val Leu Asp Lys Arg Arg Gly Arg Asp Pro Glu Met Gly Gly Lys

35 40 45

Pro Arg Arg Lys Asn Pro Gln Glu Gly Leu Tyr Asn Glu Leu Gln Lys

50 55 60

Asp Lys Met Ala Glu Ala Tyr Ser Glu Ile Gly Met Lys Gly Glu Arg

65 70 75 80

Arg Arg Gly Lys Gly His Asp Gly Leu Tyr Gln Gly Leu Ser Thr Ala

85 90 95

Thr Lys Asp Thr Tyr Asp Ala Leu His Met Gln Ala Leu Pro Pro Arg

100 105 110

<210> 168

<211> 42

<212> PRT

<213> 智人

<220>

<223> 4-1BB 共刺激信号传导结构域

<400> 168

Lys Arg Gly Arg Lys Lys Leu Leu Tyr Ile Phe Lys Gln Pro Phe Met

1 5 10 15

Arg Pro Val Gln Thr Thr Gln Glu Glu Asp Gly Cys Ser Cys Arg Phe

20 25 30

Pro Glu Glu Glu Glu Gly Gly Cys Glu Leu

35 40

<210> 169

<211> 41

<212> PRT

<213> 智人

<220>

<223> CD28 共刺激信号传导结构域变体,

在全长蛋白的位置L186G/L187G取代

<400> 169

Arg Ser Lys Arg Ser Arg Gly Gly His Ser Asp Tyr Met Asn Met Thr

1 5 10 15

Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro

20 25 30

Pro Arg Asp Phe Ala Ala Tyr Arg Ser

35 40

<210> 170

<211> 41

<212> PRT

<213> 智人

<220>

<223> 野生型CD28共刺激信号传导结构域

<400> 170

Arg Ser Lys Arg Ser Arg Leu Leu His Ser Asp Tyr Met Asn Met Thr

1 5 10 15

Pro Arg Arg Pro Gly Pro Thr Arg Lys His Tyr Gln Pro Tyr Ala Pro

20 25 30

Pro Arg Asp Phe Ala Ala Tyr Arg Ser

35 40

<210> 171

<211> 527

<212> PRT

<213> 人工序列

<220>

<223> CER122, 氨基酸1-22是信号肽

<400> 171

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Phe His

290 295 300

Gly Leu Trp Tyr Met Lys Met Met Trp Ala Trp Leu Gln Ala Lys Arg

305 310 315 320

Lys Pro Arg Lys Ala Pro Ser Arg Asn Ile Cys Tyr Asp Ala Phe Val

325 330 335

Ser Tyr Ser Glu Arg Asp Ala Tyr Trp Val Glu Asn Leu Met Val Gln

340 345 350

Glu Leu Glu Asn Phe Asn Pro Pro Phe Lys Leu Cys Leu His Lys Arg

355 360 365

Asp Phe Ile Pro Gly Lys Trp Ile Ile Asp Asn Ile Ile Asp Ser Ile

370 375 380

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

385 390 395 400

Ser Glu Trp Cys Lys Tyr Glu Leu Asp Phe Ser His Phe Arg Leu Phe

405 410 415

Asp Glu Asn Asn Asp Ala Ala Ile Leu Ile Leu Leu Glu Pro Ile Glu

420 425 430

Lys Lys Ala Ile Pro Gln Arg Phe Cys Lys Leu Arg Lys Ile Met Asn

435 440 445

Thr Lys Thr Tyr Leu Glu Trp Pro Met Asp Glu Ala Gln Arg Glu Gly

450 455 460

Phe Trp Val Asn Leu Arg Ala Ala Ile Lys Ser Tyr Phe Leu Gly Arg

465 470 475 480

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

485 490 495

Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg

500 505 510

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

515 520 525

<210> 172

<211> 749

<212> PRT

<213> 人工序列

<220>

<223> CER123, 氨基酸1-22是信号肽

<400> 172

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190

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

195 200 205

Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg

210 215 220

Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly

225 230 235 240

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys

245 250 255

Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His

260 265 270

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

275 280 285

Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Phe His

290 295 300

Gly Leu Trp Tyr Met Lys Met Met Trp Ala Trp Leu Gln Ala Lys Arg

305 310 315 320

Lys Pro Arg Lys Ala Pro Ser Arg Asn Ile Cys Tyr Asp Ala Phe Val

325 330 335

Ser Tyr Ser Glu Arg Asp Ala Tyr Trp Val Glu Asn Leu Met Val Gln

340 345 350

Glu Leu Glu Asn Phe Asn Pro Pro Phe Lys Leu Cys Leu His Lys Arg

355 360 365

Asp Phe Ile Pro Gly Lys Trp Ile Ile Asp Asn Ile Ile Asp Ser Ile

370 375 380

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

385 390 395 400

Ser Glu Trp Cys Lys Tyr Glu Leu Asp Phe Ser His Phe Arg Leu Phe

405 410 415

Asp Glu Asn Asn Asp Ala Ala Ile Leu Ile Leu Leu Glu Pro Ile Glu

420 425 430

Lys Lys Ala Ile Pro Gln Arg Phe Cys Lys Leu Arg Lys Ile Met Asn

435 440 445

Thr Lys Thr Tyr Leu Glu Trp Pro Met Asp Glu Ala Gln Arg Glu Gly

450 455 460

Phe Trp Val Asn Leu Arg Ala Ala Ile Lys Ser Met Ser Leu Leu Asn

465 470 475 480

Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu Ser Asp Cys Cys Val

485 490 495

Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys Asp Asp Ser Val Gly

500 505 510

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

515 520 525

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

530 535 540

Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala Val Gln Thr Pro Cys

545 550 555 560

Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys Ser Ile Arg Asp Ala

565 570 575

Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu Leu Glu Asn Gln Leu

580 585 590

Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu Ser Leu Met Val Lys

595 600 605

Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu Leu Arg His Leu Glu

610 615 620

Asp His Gln Ala His Cys Glu Phe Ala Leu Met Asp Cys Pro Gln Cys

625 630 635 640

Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile His Ile Leu Lys Asp

645 650 655

Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys Ala Ala Ser Met Ala

660 665 670

Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys Pro Leu Ala Asn Val

675 680 685

Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg Glu Gln Met Pro Asn

690 695 700

His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile Pro Cys Thr Phe Ser

705 710 715 720

Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn His Leu Ala Arg His

725 730 735

Leu Gln Glu Asn Thr Gln Ser His Met Arg Met Leu Ala

740 745

<210> 173

<211> 561

<212> PRT

<213> 人工序列

<220>

<223> CER124, 氨基酸1-22是信号肽

<400> 173

Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp

1 5 10 15

Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu

20 25 30

Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser

35 40 45

Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

50 55 60

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys

65 70 75 80

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

85 90 95

Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys

100 105 110

Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg

115 120 125

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr

130 135 140

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu

145 150 155 160

Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro

165 170 175

Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro

180 185 190