CN101495862A - 诊断和监测动脉粥样硬化性心血管疾病的方法和组合物 - Google Patents
诊断和监测动脉粥样硬化性心血管疾病的方法和组合物 Download PDFInfo
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Abstract
本发明鉴定了在动脉粥样硬化中差异性表达的循环蛋白。这些蛋白质,特别是作为一组蛋白质的循环水平能将急性心肌梗塞患者与稳定的劳累性心绞痛患者及无动脉粥样硬化性心血管病史者区分开来。这些蛋白水平还可预测心血管事件、测定治疗效力、确定病程阶段等。例如,这些标记蛋白可用作开发血管特异性药物制剂所需的替代临床表征的生物标记。
Description
相关申请的交叉引用
本申请要求2005年6月24日提交的美国临时申请60/693,756的优先权,该份申请的内容出于所有目的全文纳入本文作为参考。
发明背景
发明领域
本申请涉及生物信息学和动脉粥样硬化性疾病领域。具体地说,本发明涉及用于动脉粥样硬化性疾病的诊断、监测和治疗剂开发的方法和组合物。
相关领域描述
由于我们进行早期和准确诊断然后进行积极治疗的能力有限,动脉粥样硬化性心血管疾病(ASCVD)依旧是全球发病率和死亡率的主要原因。ASCVD患者代表了不均匀的一群个体,其所患疾病以不同的速度和截然不同的模式发展。虽然ASCVD患者明显有适当的治疗方法,但每年的复发率和死亡率依旧有2-4%。由于我们不能准确地鉴定可从积极风险降低(aggressive risk reduction)中获益的那些患者,初级预防(primary prevention)的各种优点还未实现。
虽然某些疾病标记已显示能在群体水平预测治疗的结果和反应,但它们不够灵敏或特异,从而不足以临床应用于个体患者。因此,超过半数的冠状动脉疾病患者的首次临床表现便是心肌梗塞或死亡。
体检和目前的诊断方法不能准确测定个体患ASCVD并发症的风险。已知的风险因素,例如高血压、高脂血症、糖尿病、家族史和吸烟未能确立动脉粥样硬化性疾病的诊断方法。依赖于解剖学数据(例如,冠状动脉造影术、冠状动脉钙化度(coronary calcium score)、CT或MRI血管造影术)的诊断方法缺乏有关该疾病过程的生物学活性的信息,对未来心脏活动(cardiac event)的预测不佳。功能性评估内皮功能可以是非特异性的并且与动脉粥样硬化性疾病过程的存在无关,虽然一些数据证明这些测量值有预后价值。个体生物标记,例如脂质和炎性标记已显示能预测ASCVD患者对治疗的结果和反应,一些标记用作产生动脉粥样硬化性疾病的重要风险因子。然而,迄今为止,没有一种生物标记足够特异从而足以临床应用于诊断个体患者的ASCVD。
动脉粥样硬化性心血管疾病的复杂性质
据信,动脉粥样硬化通常是涉及多种生物学途径的复杂疾病。动脉粥样硬化性疾病过程的自然变迁史以及对风险因素的反应不同和个体的治疗反应变化部分反映了遗传背景和它们与导致该疾病发生和改变的环境因素之间错综复杂的相互作用中的差异。心血管系统本身的复杂性质也影响动脉粥样硬化性疾病,在该系统中,解剖学、功能和生物学均在健康和疾病中发挥至关重要的作用。由于这种复杂性,一种标记或方法不可能产生足够的信息而获取该疾病过程的真实性质。
单一生物标记方法:炎症
ASCVD的各阶段均涉及炎症,据信炎症是动脉粥样硬化的病理生理学基础的主要部分,其提供该疾病过程的潜在标记。在许多流行病学研究中循环炎性生物标记升高已显示能对心血管风险分层次并评估对治疗的反应。目前,虽然炎症的通用标记可能用于对风险分层次,但它们不足以鉴定个体中是否存在CAD,因为许多标记缺乏特异性。出于相似的原因,炎症的通用标记,例如C-反应性蛋白(CRP)和红细胞沉降率(ESR)早已不用作其它炎性疾病,例如狼疮和类风湿性关节炎的特异性诊断标记,虽然它们依旧是临床实践中对风险分层次和(评估)治疗反应的重要标记。
个体对环境风险因素的反应不均匀也可能诱导ASCVD标记浓度高度变化。在这点上,一种炎性蛋白所携带的生物学信息不足以全面代表血管炎性状态,从而不能准确鉴定是否存在疾病或其严重程度。
动脉粥样硬化的病理生理学基础
动脉粥样硬化斑块由累积的胞内和胞外脂质、平滑肌细胞、结缔组织和葡萄糖胺聚糖构成。动脉粥样硬化最早的可检测损伤是由充满脂质的泡沫细胞构成的脂肪纹,这些细胞是作为单核细胞从循环(系统)迁移入内膜的内皮下层中的巨噬细胞,脂肪纹随后演化成由围绕以结缔组织的内膜平滑肌细胞和胞内及胞外脂质构成的纤维斑块。
已有人提出了相关的假设来解释动脉粥样硬化的发病机理。脂质假说假定血浆LDL水平升高会导致LDL透入动脉壁中,造成脂质累积在平滑肌细胞和巨噬细胞中。LDL对生长因子起反应还会促进平滑肌细胞增生以及迁移入内膜下和内膜区域中。在此环境中,LDL得到修饰或氧化,从而更能造成动脉粥样硬化。修饰或氧化的LDL对单核细胞有趋化性,促使它们迁移入内膜,早期出现在脂肪纹中和转化为巨噬细胞并驻留在内膜下隔室中。巨噬细胞表面的清道夫受体促进氧化的LDL进入这些细胞,将它们转化成充满脂质的巨噬细胞和泡沫细胞。氧化的LDL还对内皮细胞有毒性,可导致它们功能障碍或因更严重的损伤而丧失。
慢性内皮损伤假说假定各种机理造成的内皮损伤导致内皮丧失,血小板附着到内皮下膜、血小板凝集、单核细胞和T-细胞淋巴细胞的趋化作用并释放血小板衍生和单核细胞衍生的生长因子,这些生长因子能诱导平滑肌细胞从介质迁移入内膜中并在其中复制、合成结缔组织和蛋白聚糖进而形成纤维斑块。其它细胞,例如巨噬细胞、内皮细胞、动脉平滑肌细胞也产生能促进平滑肌(细胞)增生并胞外基质产生的生长因子。
内皮功能障碍包括提高了内皮对脂蛋白和其它血浆成分的渗透性,附着分子的表达和生长因子的加工从而导致单核细胞、巨噬细胞和T淋巴细胞附着增加。这些细胞可经内皮迁移并将自己定位于内皮下层中。泡沫细胞也释放生长因子和细胞因子,从而能促进平滑肌细胞迁移和刺激血管内膜(neointimal)增殖,基序、、继续累积脂质并支持内皮细胞功能障碍。临床和实验室研究显示炎症在粥样斑的产生、发展和不稳定中起主要作用。
“自身免疫”假说假定炎性免疫学过程是动脉粥样硬化的最早阶段的特征,其由抵御内源性抗原的体液和细胞免疫反应来启动。人Hsp60表达本身是由几种应激因素启动的对损伤的反应,所述应激因素已知是动脉粥样硬化的风险因素,例如高血压。氧化的LDL是动脉粥样硬化自身抗原的另一候选对象。已在动脉粥样硬化患者中检测到oxLDL的抗体,动脉粥样硬化损伤中也发现了它们。从人动脉粥样硬化损伤处分离的T淋巴细胞已显示对oxLDL有反应,其是细胞免疫应答中的主要自身抗原。所提出的与动脉粥样硬化有关的第三种自身抗原是2-糖蛋白I(2GPI),其是用作体外抗凝剂的一种糖蛋白。动脉粥样硬化斑块中发现了2GPI,在易患动脉粥样硬化的转基因小鼠中用2GPI高度免疫或转移2GPI-反应性T细胞增强了脂肪纹形成。
感染可通过诱导炎症和自身免疫力而导致动脉粥样硬化产生。许多研究证明了传染性因子,病毒(巨细胞病毒、单纯疱疹病毒、肠病毒、甲肝病毒)和细菌(肺炎衣原体(C.pneumoniae)、幽门螺杆菌(H.pylori)、牙周病原体)在动脉粥样硬化中的作用。近年来,已有人提出了新的“病原体负荷”假说,提示多种传染性因子可导致了动脉粥样硬化,感染所致的心血管疾病风险与个体所接触的病原体数量有关。对于一种微生物,肺炎衣原体可能与动脉粥样硬化最相关。
这些假说关系密切,不是相互排斥的。修饰的LDL对培养的内皮细胞具有细胞毒性,可诱导内皮损伤,吸引单核细胞和巨噬细胞并刺激平滑肌生长。修饰的LDL还能抑制巨噬细胞活动性,从而使得巨噬细胞一旦在内皮下间隙中转化成泡沫细胞,即被截留。此外,再生的内皮细胞(损伤后)功能受损,其从血浆摄取LDL增加。
动脉粥样硬化的特征在于除非临界狭窄、血栓形成、动脉瘤或栓塞接连发生否则不为人知。首先,症状和体征反映出受影响的组织的血流量不能随需求而增加,例如心绞痛发作、间歇性跛行。症状和体征通常随着粥样斑缓慢侵入血管腔而逐渐发展。然而,当主要的动脉被急性阻塞时,症状和体征可能是惊人的。
如上所述,目前,因为缺乏合适的诊断方法,超过半数的冠状动脉疾病患者的首次临床表现便是心肌梗塞或死亡。预防和治疗的进一步发展取决于开发出将焦点集中在血管壁初级炎性过程上的方案,该过程在动脉粥样硬化性疾病的病因学中是基础性的。没有能准确报道血管壁疾病活性和/或程度的良好替代标记便不可能开发出能完全确定风险、监测风险的作用向原发病缓解降低或开发靶向血管壁的新型治疗剂的方法。
一种有前途的方法是鉴定能反映血管炎症程度和特征的循环蛋白。已鉴定到许多免疫调制蛋白作为替代标记具有一定价值,但这些生物标记尚未显示添加了足够的信息从而能应用于临床。这是因为i)未能同时顾及所检测的多种标记的数据,ii)未能将单个标记数据与调节循环蛋白水平并混淆信息模式的临床数据整合,iii)遗传变异促进了编码这些标记的基因表达水平并混淆了丰度测定,和iv)缺乏在ASCVD中激活的特异性免疫途径的有关信息,而这些信息能用于更好地选择生物标记。最后,现有技术未能提供可利用一组循环蛋白的检测值的有效诊断或预测方法。
未满足的临床与科学需求
因此,将鉴定患血管炎症和动脉粥样硬化性心血管疾病个体的改进工具用于临床医学和生物医学研究的需求未获满足。目前,虽然对动脉粥样硬化的机制和情况的了解在增加,但我们用于鉴定高风险患者并预测预防方案效力的方法依旧不够。因此,需要新方法来更好地诊断风险患者;鉴定动脉粥样硬化性疾病患者可启动急需的治疗从而能改善临床结果。
发明概述
本发明提供检测循环蛋白表达来诊断、监测动脉粥样硬化病症并开发相关治疗剂的方法,所述动脉粥样硬化病症包括但不限于会导致心绞痛、不稳定心绞痛、急性冠状动脉综合征、心肌梗塞和心力衰竭的病症。具体地说,本发明鉴定和描述了在动脉粥样硬化患者中表达有差异的循环蛋白,所述蛋白包括但不限于循环炎性标记。本文鉴定的循环炎性标记包括MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。
检测本文所鉴定蛋白质的循环水平可将患者分类为属于各种动脉粥样硬化情况,包括动脉粥样硬化性疾病、无疾病、心肌梗塞、稳定的心绞痛、接受药物治疗、未治疗等,所述蛋白质是因动脉粥样硬化过程而在血管壁中特异性产生的。还可用这种分类预测心血管活动和对治疗的反应;并用于预测和评估心血管疾病的并发症。
在本发明的一个实施方式中,对于表明动脉粥样硬化各阶段及其临床后遗症的各种情况,评估一组蛋白质的表达情况(expression profile)。这样一组蛋白质所提供的鉴别水平是用单个标记做不到的。在一个实施方式中,通过检测蛋白质浓度或含量来测定表达分布。
分析方法可包括但不限于:利用数据集形成预测模型,将测试样品数据输入这种模型根据动脉粥样硬化分类来分类样品,其中所述分类选自:动脉粥样硬化性疾病分类、健康分类、血管炎症分类、用药分类、不用药分类和冠状动脉钙化度分类,以及根据该方法的输出来分类样品。在一些实施方式中,利用这种预测模型通过获得哺乳动物对象样品相关数据集来分类该样品,其中所述数据集包括至少3种、至少4种或至少5种选自以下的蛋白质标记:MCP1;MCP2;MCP3;MCP4;嗜酸细胞活化趋化因子;IP10;MCSF;IL3;TNFa;Ang2;IL5;IL7;IGF1;IL10;INFγ;VEGF;MIP1a;RANTES;IL6;IL8;ICAM;TIMP1;CCL19;TCA4/6kine/CCL21;CSF3;TRANCE;IL2;IL4;IL13;Il1b;MCP5;CCL9;CXCL1/GRO1;GROα;IL12;和瘦蛋白(leptin)。数据任选包括临床指征(clinicalindicia)的概况;其它蛋白质表达情况;代谢指标;遗传信息等。
本发明的预测模型利用由本文所述一组或多组标记获得的定量数据。在一些实施方式中,预测模型能提供一定水平的分类准确率;即该模型满足了所需的质量阈值(quality threshold)。有意义的质量阈值可提供满足给定阈值的AUC或准确率,这些术语(AUC;准确率)中的一种或两种在本文中可称为质量指标(quality metric)。预测模型可提供一种质量指标,例如分类的准确率或AUC为至少约0.7,至少约0.8、至少约0.9或更高。用这种模型可以正确选择参数,从而能在灵敏度和选择性之间提供所需平衡。
在其它实施方式中,循环蛋白分析被用于筛选生物学活性物质的动脉粥样硬化治疗效力的方法。在这种方法中,将动脉粥样硬化相关细胞,例如血管壁细胞等在培养物中或在体内与候选物质接触,并测定这种接触对一种或多种标记,例如一组标记表达的作用。在另一实施方式中,分析上述循环蛋白的差异表达被用于患者用在遵循一定治疗方案的方法中。当患者曾接受了某种治疗,在单个时间点或一段时期内测定一种或多种标记(例如一组标记)的表达,所述治疗包括药物、多种药物、非药理学干预以及它们的组合等。
在另一方法中,采用3种或更多本文鉴定的动脉粥样硬化相关蛋白的相对量来诊断或监测个体的动脉粥样硬化。本文鉴定的蛋白组还可包括其它临床指征;其它蛋白质表达情况;代谢指标;遗传信息等。
在另一实施方式中,本发明包括通过以下步骤分类哺乳动物对象样品的方法:获得样品相关数据集,其中所述数据集包括至少3种、或至少4种、或至少5种、或至少6种、或至少7种、或至少8种、或至少9种或9种以上选自以下的蛋白质标记的定量数据:MCP1、MCP2、MCP3、MCP4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1;将数据输入利用数据分类样品的分析方法,其中所述分类选自:动脉粥样硬化性疾病分类、健康分类、血管炎症分类、药物接触分类、未接触药物分类和冠状动脉钙化度分类;和根据该方法的输出来分类样品。
在另一实施方式中,本发明包括通过以下步骤分类哺乳动物对象样品的方法:获得样品相关数据集,其中所述数据集包括至少3种、或至少4种、或至少5种、或至少6种蛋白质标记的定量数据,各标记显示了循环蛋白质浓度与动脉粥样硬化血管组织RNA浓度之间的相互关系;将数据输入利用数据分类样品的分析方法,其中所述分类选自:动脉粥样硬化性疾病分类、健康分类、血管炎症分类、药物接触分类、未接触药物分类和冠状动脉钙化度分类;和根据该方法的输出来分类样品。
附图简述
图1.喂食高脂饮食的载脂蛋白(apo)E-缺陷型小鼠中随动脉粥样硬化进展的时间依赖性血清炎性蛋白表达。热图(heat map)是血清浓度水平的图形化显示,其中,x-轴是各血清样品,y-轴是蛋白质标记。数值表示喂食高脂饮食的apoE-缺陷型小鼠在基线(T00;n=5)和10(T10;n=5)、16(T16;n=4)、24(T24;n=5)及40周(T40;n=5)时的血清蛋白表达水平。请注意,对于16周时间点,数值获自另一独立数据集。
图2.apoE-缺陷型小鼠和对照小鼠的循环炎性蛋白表达水平。热图是标准化表达数值表的图形化显示。数值表示喂食高脂饮食的apoE-小鼠平行组在基线(T00)(n=9)和40周(T40)时(n=9),以及喂食高脂饮食的C57Bl/6(n=5)和C3H/HeJ(n=3)小鼠在基线和40周时(n值分别为5,5)的循环蛋白平均表达水平(log2)。喂食高脂饮食的apoE-缺陷型小鼠的炎性标记水平最高,而C3H/HeJ小鼠的水平最低,尽管它也喂食高脂饮食。采用N-向ANOVA鉴定各种情况下的统计学显著差异。在最右边一列中,报道的p-值未考虑饮食、品系和时间之间可能的相互作用。下文讨论了这些因素的影响和它们彼此的相互作用。
图3.小鼠动脉粥样硬化分类血清炎性标记的蛋白质组学签名(proteomicsignature pattern)。A:鉴定动脉粥样硬化分类蛋白质亚组。采用各种分类算法,包括微阵列预测分析(PAM)、递归特征排除(recursive feature elimination)(RFE)、支持向量机(support vector machine)(SVM)和ANOVA,根据准确区分4种不同动脉粥样硬化性疾病阶段(基线时和10、24及40周时喂食高脂饮食的apoE-缺陷型小鼠)小鼠的能力对一亚组的标记进行排名。这些标记中的部分用所有分类算法进行了排名。B:小鼠动脉粥样硬化性疾病的分类准确率(混淆矩阵(confusionmatrix))。为测定小鼠分类蛋白质预测疾病严重程度的准确率,我们使用以前鉴定的优选蛋白质标记(Ccl21、Ccl9、Csf3、Tnfsf11、Vegfa、Ccl11、Ccl2)。用SVM算法交叉验证根据疾病阶段分组的小鼠实验。用1,000-步N-倍交叉验证方法测定分类准确率,25%的实验用作测试组(test group),其余的用作训练组(training group)。结果以表格形式表示,混淆矩阵如“方法”部分所述。标记“真”表示“的确患病”,而“预测的”表示“预计患病”。C:一独立数据集的分类。采用SVM算法,我们能将独立数据集(“测试”)归入最接近原实验组(“已知的”)的时间点组别。已知实验包括获得蛋白分类符(classifier)组的原始分析中的4个时间点。独立实验组获自未包括在原始组中的16-周时间点。热图中显示了一对多比较(one-vs-allcomparison)所得各实验的SVM评分(亲和度)。16-周时的蛋白质分布情况与原始数据集中10-周时是更相关。
图4.优选分类符标记的血清水平和血管基因表达之间的相关性。A:为研究这些血清标记中一个亚组的疾病相关基因表达,我们研究了它们在血清来源小鼠主动脉中的基因时序表达(temporal expression)。采用定量实时RT-PCR(qRT-PCR),我们能使这些标记的时间依赖性血清蛋白质水平与它们的血管壁基因表达相关。测定了血清蛋白质水平的log10-标准化平均表达比与主动脉基因表达值的log10-标准化平均表达比的皮尔逊相关性(Pearson correlation)。将各时间点的蛋白质微阵列除以apoE缺陷型小鼠的基线水平得到蛋白质水平平均比(n=4-9)。将各时间点的重复qRT-PCR反应结果除以apoE-缺陷型小鼠的基线值得到基因表达水平的平均比。请注意,对于16-周时间点,数值获自另一独立数据集。B:皮尔逊相关性数值的相关性矩阵总结表,比较了血清蛋白质水平的标准化平均比值、血管基因表达的标准化平均比值和喂食高脂饮食时间(log10-喂食周数)。显著性水平为0.05(双侧检验(2-tailed))。
图5.对象的临床特征。名义变量(Nominal variable)(*)以计数(%)表示,连续变量(continuous variables)()以中值(四分位数间距((interquartiles range))表示。通过皮尔逊卡方或曼-惠特尼U检验进行适当比较。基于10000次抽样比较,采用蒙特卡洛方法计算显著性。BP(血压);FH(家族史);ACEI(血管紧张素转换酶抑制剂);BB(β阻断剂);CCB(钙通道阻断剂);AB(α阻断剂);ASA(乙酰水杨酸);BMI(体重指数);DBP(舒张压);SBP(收缩压);HR(心率);CRP(C-反应性蛋白)。
图6.就临床特征进行调整前后,冠状动脉疾病患者和健康对照的血清趋化因子分布。所示数据为几何平均数(95% CI)。通过GLM多变量分析进行调节,通过t-检验比较调整后平均数。*模型1,就年龄和腰围进行调整;模型2,如同模型1进行调整,并就治疗(ACE抑制剂、他汀类药物和阿司匹林)调整。
图7.临床变量和病例比对照的两维层次聚类法(hierarchical clustering)。
图8.主成分分析证明趋化因子、胰岛素耐受性情况和一个其它临床变量(例如高血压和高脂血症)亚组可以解释在对象中观察到的差异中的60-70%,其中炎症标记是主要因素。
图9.该表格显示了用于测定排名变量的最佳数量从而能以最低误差率将实验分类成正确组的支持向量机(SVM)和递归特征排除(RFE)。通过1000次重复交叉验证计算最佳误差率或分类误差,其中25%的实验用作测试组,其余实验用作训练组。
图10.ROC曲线。
图11.该表格显示了预测冠状动脉疾病的对数回归模型(Logistic Regressionmodel)。模型:1)逐步前向选择(Stepwise forward selection),缺失数值不估算;2)逐步前向选择,采用条件均值(conditional means)进行缺失数据估算;3)临床变量和趋化因子评分的逐步前向选择。独立变量:年龄、性别、舒张压(DBP)、收缩压(SBP)、心率、血浆胰岛素、C-反应性蛋白和趋化因子(模型1和2:嗜酸细胞活化趋化因子、IP-10、MCP-1、MCP-2、MCP-3、MCP-4和MIP-1α;模型3:趋化因子评分)。
图12.一系列LDA模型的预期AUC数值和S.E.,标记数如图所示依次增多。
图13.一系列对数回归模型的预期AUC数值和S.E.,标记数如图所示依次增多。
图14.LDA模型预测,MCP-1标记不在可用预测标记组之列。该新模型用Ang-2、IGF-1和M-CSF作为另一种标记组合来超越AUC>0.75的阈值。
图15a.采用赤池信息量基准(Akaike Information Criterion)(AIC)选择对数回归模型的标记。
图15b.一系列对数回归模型的预期AUC数值和S.E.,标记数如图所示依次增多(=在标记选择过程中采用AIC标准从完整模型中依次除去标记数的倒序)。
图16.包括临床变量和生物学标记的对数回归模型。
图17.包括临床可变变量和生物学标记的对数回归模型。包括“β阻断剂”(DC512)和“他汀类药物”(DC3005)及MCP-4的模型产生的AUC预计值超过0.85。
图18.以下三组的第一辨别变量(discriminant variate)值分布的箱线图(boxplot):“未治疗的”、“ACE或他汀类药物”和“ACE和他汀类药物”。
发明详述
定义
除非另有表述,权利要求书和说明书中使用的术语如下所述。
术语“改善”指疾病状态,例如动脉粥样硬化性疾病状态的治疗中获得的任何有益的治疗结果,包括预防、严重程度或进展的减缓、缓解或治愈。
本文所用的术语“哺乳动物”包括人和非人,包括但不限于:人、非人灵长类、狗、猫、鼠、牛、马和猪。
述及两条或多条核酸或多肽序列时的术语“相同性”百分比指当比较和排列对比两条或多条序列或子序列的最大一致性时,利用一种下述序列比较算法(例如,BLASTP和BLASTN或技术人员可用的其它算法)或通过目测检测到有一定百分比的核苷酸或氨基酸残基相同。取决于具体应用,“相同性”百分比可以涉及进行比较的序列区域,例如功能性结构域,或者涉及待比较的两条序列的全长。
为了进行序列比较,通常将一条序列用作供测试序列与之相比的参比序列。当使用序列比较算法时,将测试序列和参比序列输入计算机,根据需要设定子序列的坐标,并设定序列算法程序参数。序列比较算法于是根据所设定的程序参数计算一条或多条测试序列相对于参比序列的序列相同性百分比。
可通过以下方法对要比较的序列进行最佳比对排列,例如Smith和Waterman的局部同源算法(Adv.Appl.Math.2:482(1981))、Needleman和Wunsch的同源比对算法(J.Mol.Biol.48:443(1970))、Pearson和Lipman的相似度检索法(Proc.Nat′l.Acad.Sci.USA 85:2444(1988))、计算机执行这些算法(威斯康星遗传学软件包的GAP、BESTFIT、FASTA和TFASTA,遗传学计算机组(Genetics ComputerGroup),575 Science Dr.,麦迪逊,威斯康星州)或目测(通常参见Ausubel,FM等,Current Protocols in Molecular Biology(《最新分子生物学方法》),4,约翰威立父子公司(John Wiley & Sons,Inc.),布鲁克林,纽约,A.1E.1-A.1F.11,1996-2004)。
适合于测定序列相同性百分比和序列相似性百分比的算法的一个实例是Altschul等(J.Mol.Biol.215:403-410(1990))所述的BLAST算法。执行BLAST分析的软件可从生物技术信息国家中心(National Center for BiotechnologyInformation)公开获得(www.ncbi.nlm.nih.gov/)。
术语“足量”表示足以产生所需作用的用量,例如足以改变蛋白质表达特征的用量。
术语“治疗有效量”是能有效缓解疾病症状的用量。治疗有效量可以是“预防有效量”,因为预防可视为治疗。
TP:真阳性
TN:真阴性
FP:假阳性
FN:假阴性
N:阴性样品总数
P:阳性样品总数
A:样品总数
准确率=(TP+TN)/A
平均CV误差=平均分类误差误差=1-平均准确率
灵敏度=TP/P=TP/(TP+FN)
特异性=TN/N=TN/(TN+FP)
本申请所用的缩写包括以下:CAD=冠状动脉疾病;MIP1a=MIP1α;LDA=线性辨别分析;MI=心肌梗塞;ASCVD=动脉粥样硬化性心血管疾病。
必须注意,除非文中另有明确表述,说明书和随附的权利要求书中所用的单数形式“一”、“一个”和“该”包括复数含意。
在本文中,动脉粥样硬化(也称为动脉硬化、动脉粥样化血管疾病、动脉阻塞性疾病)指特征在于血管壁上有斑块累积及血管炎症的心血管疾病。所述斑块由胞内和胞外脂质、平滑肌细胞、结缔组织、炎性细胞和葡萄糖胺聚糖累计而成。炎症与脂质累积常在血管壁中联合发生,血管炎症是动脉粥样硬化性疾病过程的标志。
心肌梗塞是通常由流向心肌部分的冠状动脉血液突然减少导致的缺血性心肌坏死。在绝大多数急性MI患者中,急性血栓(常与斑块破裂有关)阻塞了向受损区域供血的动脉。斑块破裂通常发生在以前被富集于炎性细胞中的动脉粥样硬化斑块所部分阻塞之处。据估计,动脉粥样硬化斑块中内皮机能障碍和血管炎症所诱导的血小板功能改变导致血栓形成。心肌梗塞可分类成ST升高和非ST升高型MI(也称为不稳定心绞痛)。两种心肌梗塞形式中均有心肌坏死。ST升高型心肌梗塞中有透壁心肌损伤,从而导致心电图上ST升高。在非ST升高型心肌梗塞中,损伤在心内膜下,不引起心电图上ST段升高。心肌梗塞(ST升高型和非ST升高型)代表了一种不稳定的动脉粥样硬化性心血管疾病。急性冠状动脉综合征包括各种形式的不稳定冠状动脉疾病。
心绞痛指向心血流不足导致的胸部疼痛或不适。心绞痛可视为动脉粥样硬化性心血管疾病的症状之一。心绞痛可分类为稳定型,其遵循一种规律的慢性症状模式,与不稳定动脉粥样硬化性心血管疾病不同。稳定型动脉粥样硬化性心血管疾病的病理生理学基础也是复杂的,但在生物学上区别于不稳定型。稳定心绞痛一般不是心肌坏死。
心力衰竭可能是心肌梗塞导致的心肌机能障碍所致。
目前方法的几个特征值得注意。动脉粥样硬化和相关的病症是通过评估是否存在一种或一组蛋白质标记的血检来诊断的。所述标记包括MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。已知,这些标记在动脉粥样硬化过程中在血管壁中特异性产生。在一些实施方式中,这种预测模型利用从循环标记获得的定量数据,所述标记包括MCP1;MCP2;MCP3;MCP4;嗜酸细胞活化趋化因子;IP10;MCSF;IL3;TNFa;Ang2;IL5;IL7;IGF1;IL10;INFγ;VEGF;MIP1a;RANTES;IL6;IL8;ICAM;TIMP1;CCL19;TCA4/6kine/CCL21;CSF3;TRANCE;IL2;IL4;IL13;Il1b;MCP5;CCL9;CXCL1/GRO1;GROα;IL12;和瘦蛋白。有用的其它循环标记包括sVCAM;sICAM-1;E-选择蛋白;P-选择蛋白;白介素-6,白介素-18;肌酸激酶;LDL,oxLDL,LDL粒度,脂蛋白(a);肌钙蛋白I,肌钙蛋白T;LPLA2;CRP;HDL,甘油三酯,胰岛素,BNP(脑钠尿肽),神经趋化蛋白(fractalkine),骨桥蛋白,骨保护素,制瘤素-M,髓过氧化物酶,ADMA,PAI-1(纤溶酶原激活物抑制剂),SAA(循环淀粉样蛋白A),t-PA(组织型纤维蛋白溶酶原激活剂),sCD40配体,血纤蛋白原,高半胱氨酸,D-二聚体,白细胞计数;还可包括本文所述的各种其它标记,包括指征,代谢指标,遗传信息和其它循环标记。
在本发明的某些实施方式中,由患者样品获取分类数据集,其中该数据集包括选自以下的至少三种蛋白质标记的定量数据:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。所述至少三种蛋白质标记可包括选自以下的标记组(marker set):MCP-1、IGF-1、TNFa;MCP-1、IGF-1、M-CSF;ANG-2、IGF-1、M-CSF;和MCP-4,IGF-1,M-CSF。当数据集包括至少四种蛋白质标记的定量数据时,所述至少四种蛋白质标记可选自下组:MCP-1,MCP-2,MCP-3,MCP-4,嗜酸细胞活化趋化因子,IP-10,M-CSF,IL-3,TNFa,Ang-2,IL-5,IL-7和IGF-1;MCP-1,IGF-1,TNFa,IL-5;MCP-1,IGF-1,M-CSF,MCP-2;ANG-2,IGF-1,M-CSF,IL-5;MCP-1,IGF-1,TNFa,MCP-2;和MCP-4,IGF-1,M-CSF,IL-5。当数据集包括至少五种标记的定量数据时,所述至少五种标记可包括选自以下的标记组:MCP-1,MCP-2,MCP-3,MCP-4,嗜酸细胞活化趋化因子,IP-10,M-CSF,IL-3,TNFa,Ang-2,IL-5,IL-7和IGF-1;MCP-1,IGF-1,TNFa,IL-5,M-CSF;MCP-1,IGF-1,M-CSF,MCP-2,IP-10;ANG-2,IGF-1,M-CSF,IL-5,TNFa;MCP-1,IGF-1,TNFa,MCP-2,IP-10;MCP-4,IGF-1,M-CSF,IL-5,TNFa;和MCP-4,IGF-1,M-CSF,IL-5,MCP-2。
在本发明的另一实施方式中,至少两种、至少三种、至少四种、至少五种或更多种标记选自:M-CSF、嗜酸细胞活化趋化因子、IP-10、MCP-1、MCP-2、MCP-3、MCP-4、IL-3、IL-5、IL-7、IL-8、MIP1a、TNFa和RANTES。
鉴定动脉粥样硬化相关循环蛋白能提供诊断和预后方法,所述方法能通过检测所鉴定循环蛋白的水平变化来检测病症(例如冠状动脉疾病、动脉粥样硬化等)的发生,特别是这种病症表明有心肌梗塞、心力衰竭等倾向时;或评估个体这种疾病的易发性。这些方法还包括筛选治疗剂和方法的效力;给疾病分阶段和分类;等等。可采用早期检测来测定进程性疾病的发生,从而能用合适的预防性或保护性手段加以干预。
感兴趣的循环蛋白包括表1所列的那些:
除了本申请中以名称、登录号或序列指定的具体生物标记外,本发明还考虑采用与所例举序列有至少90%或至少95%或至少97%相同且目前知导的或将被发现可用于本发明方法的生物标记变体。这些变体可代表多态性、间接变体、突变等。本发明的诊断方法可用各种技术和试剂。在本发明的一个实施方式中,可检验血液样品或衍生自血液的样品,例如血检、循环(蛋白)等中是否存在多肽。通常抽取血液样品,然后检验衍生产物,例如血检或血清。可利用特异性结合成分检测这些多肽。将抗体用于这一目的尤其值得关注。这种试验可采用多种形式,包括抗体阵列;ELISA和RIA;在悬液和/或溶液中进行标记抗体的结合然后通过流式细胞术、质谱法等进行检测等等。检测可利用一种或一组抗体,优选阵列形式的一组抗体。表达签名(expression signature)通常联用检测方法与结果分析来测定是否存在与疾病签名统计学意义上显著的匹配。
在另一实施方式中,采用体内成像来检测心脏组织中是否存在动脉粥样硬化相关蛋白。这些方法可采用,例如这些蛋白质的经标记的特异性抗体或配体。在这些实施方式中,将多肽特异性的以可测方式标记的抗体、配体等物质给予个体(例如,通过注射),采用标准成像技术(包括但不限于磁共振成象、计算机化断层显像扫描等)来定位被标记的细胞。检测可采用一种成像试剂或多种成像试剂的混合物。
在另一实施方式中,分析血管(优选受动脉粥样硬化影响的一条或多条血管)组织的mRNA样品中的动脉粥样硬化指示性遗传学签名(genetic signature)。
所提供的循环蛋白表达模式表现了动脉粥样硬化中的炎性签名的特征,并进一步将特定的免疫相关路径与糖尿病和药物疗法关联起来。虽然目前的数据显示它们在动脉粥样硬化的炎症反应中具有显著的作用,但将血管壁中的免疫路径与疾病的一些关键方面关联起来的直接数据依然很少,所述关键方面包括风险因素影响初级炎性反应(primary inflammatory process)的机制和调节例如高血压和高脂血症等风险因素的药物如何特异性地影响了炎症的机制。本发明鉴定了可用于诊断和分类动脉粥样硬化性心血管疾病的炎症生物标记的表达分布情况。
在诊断患者动脉粥样硬化和相关病症的方法中,获取本文提供的生物标记在血液、血清等中的表达模式,将其与对照值比较来确诊。本发明分析还可包括源于临床变量的输入值。例如,可将患者的血源样品例如血液、血浆、血清等加给一种或一组特异性结合试剂来确定是否存在要找的标记。该项分析一般包括至少一种本文所述的标记,例如M-CSF、嗜酸细胞活化趋化因子、IP-10、MCP-1、MCP-2、MCP-3、MCP-4、IL-3、IL-5、IL-7、IL-8、MIP1a、TNFa、Ang-2、IGF-1和RANTES,通常是至少两种标记,更常见是至少三种标记,还可包括4、5、6、7种或最多所有的标记。优选的标记组包括以下标记中的至少3种:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1,可以包括4、5、6、7、8、9、10、11、12种或所有标记。
该项分析还可包括可能存在于血清或组织样品中的其它蛋白质的表达信息。采用适用于具体标记的方法来获得定量信息。标记包括但不限于:sVCAM;sICAM-1;E-选择蛋白;P-选择蛋白;白介素-6,白介素-18;肌酸激酶;LDL,oxLDL,LDL粒度,脂蛋白(a);肌钙蛋白I,肌钙蛋白T;LPLA2;CRP;Ccl9;Ccl2;Ccl21;Ccl19;IL-5;Tnfsf11;Vegfa;Cxcl1;瘦蛋白,HDL,甘油三酯,胰岛素,BNP(脑钠尿肽(brain naturetic peptide)),神经趋化蛋白,骨桥蛋白,骨保护素,制瘤素-M,髓过氧化物酶,ADMA,PAI-1(纤溶酶原激活物抑制剂),SAA(血清淀粉样蛋白A),t-PA(组织型纤维蛋白溶酶原激活剂),sCD40配体,血纤蛋白原,高半胱氨酸,D-二聚体,白细胞计数等。其它变量包括临床指征,通常是对这些临床指征进行评估后将所得数据与循环标记分析组合用于某算法。这些临床标记包括但不限于:性别;年龄;葡萄糖;胰岛素;体重指数(BMI);心率;腰围;舒张压;收缩压;血脂障碍;吸烟否;等等。其它变量包括用外周血测定的基因表达指标、代谢指标和遗传学信息
本发明方法可用于取定动脉粥样硬化的阶段、动脉粥样硬化预后、评估动脉粥样硬化的进展程度、监测治疗反应等。鉴于本文所述,本领域普通技术人员不难理解如何用本发明实现这些应用。例如,可如下确定动脉粥样硬化阶段:一组数据集与从阶段已知的疾病样品所获得的一份或多份数据集作比较;或者,构建能预测阶段的模型,然后将某数据集输入该模型以获得预测的阶段。可采用类似方法来提供动脉粥样硬化的预后。可通过观察预测模型例如上述模型所得的一种或多种预测值的随时间变化来监测进展。可采用本发明方法并确定已知疾病患者的一种或多种分类结果是否接近或落入常规分类来测定治疗反应。
采用上述方法,如本领域所知,定量测定某测试样品中的标记。然后将如此获得的定量数据应用于分析性分类方法。在这种方法中,根据某算法处理原始数据,其中该算法已用训练组的数据预先确定,参照本文实施例所述。一种算法可用本文提供的训练组的数据,或用本文提供的指导来产生处理另一不同数据组的算法。
分析性分类方法可采用各种统计学分析方法来处理定量数据并提供样品的分类信息。有用方法的实例包括线性辨别分析、递归特征排除、微阵列预测分析、对数回归、CART算法、FlexTree算法、LART算法、随机森林算法(random forestalgorithm)、MART算法、机械学习算法(machine learning algorithm);等等。
采用这些方法中的任一种,用动脉粥样硬化数据集建立预测模型。在建立这种模型的过程中,将包含对照和患病样品的数据集用作训练组。训练组包所有感兴趣标记的数据。本文提供了感兴趣标记的预测模型的实例,例如参见实施例6-10。
本文所示的预测模型利用了多项蛋白质水平测定的结果,提供能以所需准确率将个体分类为属于特定状态的算法,其中状态可以是动脉粥样硬化或非动脉粥样硬化。感兴趣的分类包括但不限于:将样品指定为一种或多种动脉粥样硬化性疾病状态i)动脉粥样硬化状态与非动脉粥样硬化状态,ii)MI状态与心绞痛状态,iii)低钙状态与高钙状态。
可根据预测模型法作出分类,所述方法设定一阈值,据此阈值确定某样品属于某给定类别的概率。该概率优选至少50%、或至少60%或至少70%或至少80%或更高。还可通过确定获得的数据集与参比数据集相比是否有统计学显著的差异来作出分类。如果存在所述差异,则认定获得数据集的来源样品不属于参比数据集代表的类别。相反,如果在统计学上这样的比较与参比数据集的差异不明显,则将获得数据集的来源样品归入参比数据集代表的类别。
可根据某模型提供某具体数值或数值范围的AUC或准确率等质量指标准确率的能力来评估其预测能力。在一些实施方式中,所需的质量阈值是分类某样品的准确率如下所示的预测模型:至少约0.7、至少约0.75、至少约0.8、至少约0.85、至少约0.9、至少约0.95或更高。作为另一指标,所需的质量阈值可以指分类某样品的AUC(曲线下面积)如下所示的预测模型:至少约0.7、至少约0.75、至少约0.8、至少约0.85、至少约0.9、至少约0.95或更高。
本领域已知可以“调谐”预测模型的相对灵敏度和特异性以提高选择性指标或灵敏度指标,这项指标具有反比关系。可根据所进行的测试的具体要求调节上述模型的限度来提供选定的灵敏度或特异性水平。灵敏度或/和特异性可以至少约0.7、至少约0.75、至少约0.8、至少约0.85、至少约0.9或更高。
可通过检测各标记的数值来初步分析原始数据,通常按一式三份或多次一式三份进行。可以处理数据,例如可利用标准曲线转换原始数据,一式三份检测值的平均值可用于计算各患者的平均值和标准偏差。可先转换这些数值,再用于模型中,例如log-转换,Box-Cox转换(参见Box和Cox,(1964)J.Royal Stat.Soc.,B系列,26:211-246)等。然后将数据输入按照状态分类样品的预测模型。可将得到的信息传递给患者或专业医护人员。
为建立动脉粥样硬化状态的预测模型,在训练组中使用包括已知对照样品和对应于感兴趣的动脉粥样硬化分类的样品的强大数据集。采用普遍认可的标准选择取样规模。如上所述,可采用不同的统计学方法获得高度准确的预测模型。实施例5、11和12给出了这种分析的实例。
在一个实施方式中,基于预测模型进行层次聚类法,其中,将皮尔逊相关性用作聚类指标。一种方法是将患者动脉粥样硬化数据集视作“有监督的学习(supervised learning)”中的“学习样品”。CART是一项医药学应用标准(Singer(1999)Recursive Partitioning in the Health Sciences,斯普林格公司(Springer)),该方法可通过以下步骤改进:将任一项定性特征转换成定量特征;根据所得显著性水平对这些特征进行分选,通过样品再用法(sample reuse method)来评估霍特林T2统计量(Hotelling′s T2 statistic);并适当地应用拉索法(lasso method)。预测问题转换成了仍与预测相关联的回归问题,实际上通过在对回归质量的评估中适当运用Gini分类标准。
该方法产生了称为FlexTree的方法(Huang(2004)PNAS 101:10529-10534)。用于模拟和用于SNP和其它形式的数据时,FlexTree效果良好。已开发了自动执行FlexTree的软件。或者可用LARTree或LART。幸运的是,近年来已开发出了称为LARTree(或简单LART)的方法(Turnbull(2005)Classification Treeswith Subset Analysis Selection by the Lasso,斯坦福大学)。拉索该名称反映其为二叉树(binary tree),如CART和FlexTree中那样;拉索法(Lasso),如前所述;通过Efron等所谓的的LARS((2004)Annals of Statistics 32:407-451)执行拉索法。也可参见Huang等,(2004)Tree-structured supervised learning and thegenetics of hypertension.Proc Natl Acad Sci U S A.101(29):10529-34。
可用的其它分析方法包括逻辑回归(logic regression)。一种逻辑回归方法见Ruczinski(2003)Journal of Computational and Graphical Statistics 12:475-512。逻辑回归与CART的相似之处在于其分类符(classifier)可以展示为二叉树。其不同之处在于各节点(node)具有关于特征的布尔语句(Boolean statement),该语句比CART产生的简单“和”语句更全面。
另一种方法是最近收缩形心(nearest shrunken centroid)的方法(Tibshirani(2002)PNAS 99:6567-72)。该技术是k-均值样(k-means-like)的,但优点在于通过收缩聚类中心,可以自动选择特征(如拉索方法一样)从而能将注意力集中于能提供信息的少量特征。该方法可作为PAM软件购得,使用广泛。其它两组算法是随机森林算法(Breiman(2001)Machine Learning 45:5-32)和MART算法(Hastie(2001)The Elements of Statistical Learning,斯普林格公司)。这两种方法早已是“委员会方法(committee method)”。因此,它们包括对结果进行“表决”的预测符。
为提供显著性定级,可以测定错误发现率(false discovery rate)(FDR)。首先,产生不相似度数值的一组零分布(null distribution)。在一个实施方式中,对观察到的分布的数值进行排序,获得了几乎零概率(out of chance)的相关系数分布序列,从而能产生相应的相关系数的零分布(参见,纳入本文作为参考的Tusher等,(2001)PNAS 98,5116-21)。通过以下步骤获得零分布组:对每一种测得分布的数值进行排序;计算所有分布的成对相关系数(pair-wise correlationcoefficients);计算该排序的相关系数的概率密度函数;重复该过程N次,其中N是较大的数值,通常是300。利用该N种分布可以计算出相关系数值相关值(平均值、中值等),这些相关系数的数值大于由给定显著性水平实测相似度数值分布所得的(相似度)数值。
FDR是预计假显著相关的数量(根据随机数据集中大于该选定皮尔逊相关系数的相关数来估算)与经验数据(显著相关)中大于该选定皮尔逊相关系数的相关的数之比。该限界相关值可应用于不同实验分布数据之间的相关性。
利用上述分布,可选择显著性的置信水平。可用该置信水平确定高于随机结果的相关系数最低值。采用该方法可获得正相关、负相关或这二者的阈值。利用所得阈值,用户可过滤成对的相关系数的观测值,排除未超过阈值的那些。此外,还可估算某给定阈值的假阳性率。对于各种“随机相关”分布,可以确定有多少观测值落在阈值范围外。该方法提供了一个数值序列。该序列的平均值和标准偏差显示潜在假阳性的平均数及其标准偏差。
在另一分析方法中,分别将横断分析(cross-sectional analysis)中选择的变量用作预测符。鉴于具体的ASCVD结果,患者观察期的随机长度,蛋白质组学特征和其它特征的选择,分析存活率的参数方法可能优于广泛应用的半-参数Cox模型。存活率的威布尔参数拟合可以使风险率(hazard rate)单调升高、降低或维持恒定,还具有发现比风险比表示(hazards representation)(与Cox模型一样)和加速失效时间表示(failure-time representation)。采用该模型可实现在建立回归系数的近最大似然度估算函数(estimator)时用到的所有统计学标准工具的功能。
此外,还可利用Cox模型,主要是由于拉索方法将共变量(covariate)数量降低至了可操控的规模,这将显著简化分析,使得对存活率的完全非参数评估方法成为可能。这些统计学工具适用于所有格式的蛋白质组学数据。本发明提供了一组易于测定并具有高信息含量的生物标记、临床和遗传学数据,所述信息是检测临床上显著的动脉粥样硬化性冠状动脉血管疾病个体。而且,本发明的算法还提供了关于未来心血管疾病风险的信息。
在预测模型的建立中,可能需要选择一标记亚组,即至少3种、至少4种、至少5种、至少6种直至整组标记。通常,根据定量样品分析所需来选择标记亚组,例如考虑试剂的可得性,定量测定的方便性等,但同时仍应确保不失为高度准确的预测模型。
选择大量高信息含量标记来构建分类模型需要确定性能指标(performancemetric)和用户-定义阈值,用这些指标和阈值来建立能根据该指标提供有用预测信息的模型。例如,性能指标可以是预测的灵敏度和/或特异性、AUC以及预测模型的总准确率。
如实施例5、11和12所述,训练模型中可采用多种方法。选择标记亚组可以是为了进行标记亚组的前向选择或反向选择。可不使用全部标记而选择标记的数量来优化模型性。确定最佳标记数的一种方法是选择能产生具有所需预测能力(例如,AUC>0.75,或相当的灵敏度/特异性指标)的模型的标记数,所需预测能力与各种组合和各种数量经给定算法所得该指标的最高值相差小于一个标准偏差。
试剂和试剂盒
本发明还提供了用于实施一种或多种上述方法的试剂及包含所述实际的试剂盒。所述试剂及其试剂盒可以多种多样。有用的试剂包括专门为用于产生动脉粥样硬化病症相关循环蛋白标记的上述表达分布所用的试剂。
这种试剂的一种类型是能结合感兴趣标记组的抗体阵列或试剂盒。本领域已知多种不同的阵列形式,这些阵列具有多种不同的探针结构、基板组成和连接技术。代表性阵列或试剂盒包含用于定量测定选自以下的至少2种、至少3种、至少4种、至少5种或更多种标记的试剂或由这些试剂构成:M-CSF、嗜酸细胞活化趋化因子、IP-10、MCP-1、MCP-2、MCP-3、MCP-4、IL-3、IL-5、IL-7、IL-8、MIP1a、TNFa和RANTES。
在其它实施方式中,代表性阵列或试剂盒包含用于定量测定选自以下的至少3种蛋白质标记的试剂或由这些试剂构成:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。所述至少3种蛋白质标记可包含选自以下的标记组或由其构成:MCP-1、IGF-1、TNFa;MCP-1、IGF-1、M-CSF;ANG-2、IGF-1、M-CSF;和MCP-4、IGF-1、M-CSF。
在其它实施方式中,代表性阵列或试剂盒包含用于定量测定选自以下的至少4种蛋白质标记的试剂或由这些试剂构成:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。所述至少4种蛋白质标记可包含以下标记(组)或由其构成:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1;MCP-1、IGF-1、TNFa、IL-5;MCP-1、IGF-1、M-CSF、MCP-2;ANG-2、IGF-1、M-CSF、IL-5;MCP-1、IGF-1、TNFa、MCP-2;和MCP-4、IGF-1、M-CSF、IL-5。
在其它实施方式中,代表性阵列或试剂盒包含用于定量测定选自以下的至少5种蛋白质标记的试剂或由这些试剂构成:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。所述至少5种标记可包含选自以下的标记组或由其构成:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1;MCP-1、IGF-1、TNFa、IL-5、M-CSF;MCP-1、IGF-1、M-CSF、MCP-2、IP-10;ANG-2、IGF-1、M-CSF、IL-5、TNFa;MCP-1、IGF-1、TNFa、MCP-2、IP-10;MCP-4、IGF-1、M-CSF、IL-5、TNFa;和MCP-4、IGF-1、M-CSF、IL-5、MCP-2。
这些试剂盒还可装有用于统计学分析一种或多种表型的软件包,还可装有用于计算分类概率的参比数据库。试剂盒可装有用于各种方法的组份,例如抽取和处理血液样品的装置,二期抗体(second stage antibody)、ELISA试剂、试管、离心柱(spin column)等。
除了以上组分,所述试剂盒还可装有实施所述方法的使用说明书。所述试剂盒中的这些使用说明书可采取多种形式,一个试剂盒中可装有一份或多份使用说明书。这些使用说明书可采取的一种形式是试剂盒包装上或包装内附件上的印刷在合适介质或底材上的信息,如印刷了信息的一张或多张纸。另一种方式是记录了信息的计算机可读介质,例如软盘、CD等。还有另一种方式是网址,可经因特网远程获得信息。试剂盒中装有任何适宜的工具。
实施例
以下是实施本发明的具体实施方式的实施例。提供这些实施例只是说明性目的,不是打算以任何方式性质本发明的范围。已努力确保所用数值(例如,用量、温度等)的准确率,但当然应考虑到有一些实验误差及偏差。
实施例1:动物模型中动脉粥样硬化的血清标记
由小鼠蛋白质阵列获得的血清生物标记数据
由于已知多条生物学途径参与人和小鼠血管组织内的转录,设计了一项概念验证研究(proof of concept study)来检验多分析物方法是否能提高动脉粥样硬化进程中各种阶段之间的区分32。该项研究证明定量测定多种疾病相关的生物标记能提供灵敏度和特异性更高的方法来评定小鼠的动脉粥样硬化性疾病,并看望用于人类。该项研究中鉴定的优选血清蛋白质分类符代表了不同的动脉粥样硬化相关生物学过程,包括巨噬细胞趋化反应(chemoattraction)(Ccl9、Ccl2)、T-细胞趋化因子活性(Ccl21和Ccl19)、先天免疫力(IL-5)、血管钙化(Tnfsf11)、血管生成(Vegfa)和高脂诱导的炎症(Cxcl1、瘦蛋白)。从这些标记的同步检测值获得的签名提高了正确确定小鼠动脉粥样硬化性疾病进程阶段所需的特异性。如以下实施例3和4所述,在前瞻性人队列研究中(cohort study)进一步验证了该方法的可靠性。
为鉴定能与疾病进程和血管壁中基因表达都关联的血清蛋白表达模式,我们利用了纵断面实验设计(longitudinal experimental design)和小鼠遗传学模型加饮食的组合,这些组合产生了不同程度的动脉粥样硬化。此处,我们利用蛋白质阵列来鉴定小鼠血清中表达水平不同的一组炎性生物标记,所述水平与疾病程度相关。还通过定量实时逆转录酶聚合酶链式反应(RTPCR)评估这些标记中一亚组的血管壁基因表达。采用分类算法鉴定一组最灵敏的鉴别符(discriminator),我们能证明血管衍生炎性生物标记的独特签名能准确预测小鼠动脉粥样硬化性疾病的不同严重程度。
方法
实验设计、收集血清和制备RNA.所有实验得到了斯坦福动物研究委员会(Stanford Committee on Animal Research)的批准。以前已描述了总体实验设计(45)。3周龄的雌性apoE敲除(C57BL/6JApoetm1 Unc)、C57Bl/6J和C3H/HeJ小鼠购自杰克逊实验室公司(Jackson Laboratory)(巴港,缅因州)。4周龄时,这些小鼠有些继续喂食常规食物,有些喂食包含21%无水乳脂和0.15%胆固醇(Dyets号101511;戴茨公司(Dyets),伯利恒,宾夕法尼亚州)的高脂饮食,最长40周。如前所述,在每个时间点通过眶后法收集5-9只同队列高脂饮食apoE-缺陷型小鼠的血清。为建立饮食和遗传差异的对照,也在基线和40周时收集喂食常规食物的apoE敲除小鼠(C57BL/6J-Apoetm1 Unc)以及分别喂食常规食物和高脂饮食的野生型C57Bl/6J和C3H/HeJ小鼠的血清。如前所述(45),在各条件(品系-饮食组合)的各时间点收集15只小鼠(3组,每组5只)的主动脉来分离RNA,与血清收集时间表平行。如前所述采用改进的两步纯化方法(45,47)分离总RNA。过去曾定量测定(测定整个主动脉中损伤区域的百分比)过该队列小鼠的主动脉动脉粥样硬化斑块,并已记载在现有文献中(45)。为了分类,还采用了高脂饮食2周、apoE-缺陷型、16-周龄的另一独立小鼠队列(4组,每组3-4只)的血清和主动脉。按照现有技术(45-47,49)合并RNA和血清样品来进行微阵列杂交。所有样品加工和蛋白质杂交均同时进行以消除任何潜在的技术变差。
蛋白质生物芯片杂交和数据处理.按照生产商的使用说明书,使用扎奥米克斯1200试验工作站(Zyomyx 1200 Assay station)(扎奥米克斯公司(Zyomyx))将血清样品与扎奥米克斯鼠科细胞因子生物芯片(Zyomyx Murine CytokineBioChips)(扎奥米克斯公司,海达德,加利福尼亚州)杂交。为准确测定测试血清中的蛋白质水平,制作各分析物的9-点校验曲线(各校验曲线请参见附录S4;可通过Physiological Genomics(生理学基因组学)网址获得)。1使用扎奥米克斯100荧光扫描仪(Zyomyx 100 fluorescence scanner)扫描蛋白质生物芯片,使用GenPix Pro和Zyomyx ZDR 4001版软件进行微阵列的网格定位。测定芯片内变率(所有阴性对照特征的标准偏差与那些特征平均强度的比值)和芯片间变率(平均标准偏差与平均中值强度的比值)作为为质量控制指标。根据分析物,蛋白质阵列提供的对照差率范围是3%至约15%,灵敏度为1-1,000pg/ml(参见,各分析物的校验曲线附录,可从http://physiolgenomics.physiology.org/cgi/content/full/00240.2005/DC1获得)(11)。不在校验曲线的线性部分的数值标记为缺失数值。然后将数值形式的原始数据输入专用于微阵列数据分析的奥雷克尔关系型数据库(Oracle relationaldatabase)(CoBi)(基因数据公司(GeneData))。利用热图构建软件(HeatMapBuilder software)(7)制作热图。详细的补充方法可从http://physiolgenomics.physiology.org/cgi/content/full/00240.2005/DC1获得。
蛋白质选择算法和疾病分类.已有关于蛋白质选择和分类算法的记载(45)。简言之,在有监督的分析(supervised analyses)中,,我们使用5.0版的表达者(Expressionist)软件(基因数据公司),该软件采用多种分类算法,根据各基因区分高脂饮食apoE-小鼠的0、10、24和40周时间点的能力对基因进行排名。这些算法包括方差分析(ANOVA)、支持向量机(SVM)(4)和递归特征排除(RFE)(16),该算法是SVM权重的递归算法,其中,反复进行基因排名并且每次除去固定比例的最低分者(35)。我们还使用已知的微阵列预测分析(PAM)作为附加分类算法(48)。然后,用各方法确定能以最低误差率将各实验正确归类的最佳数量的排名基因用它们。通过交叉验证计算最佳误差率或分类误差,其中,25%的实验用作测试组,其余的用作训练组。这一过程对ANOVA、SVM和RFE算法重复1,000次。对于SVM和RFE,我们的分析采用线性核模型(linear kernel);非线性高斯核模型(Gaussian kernel)得到类似的结果。然后,将这一最小分类符基因亚组用于另一独立数据集的交叉验证和分类。详细的方法见http://physiolgenomics.physiology.org/cgi/content/full/00240.2005/DC1。
彼此独立的数据集的交叉验证和分析.为测定用先前鉴定的蛋白质小亚组进行分类的准确率,我们利用SVM算法(线性核模型)和交叉验证产生混淆矩阵,重复地将实验分为75%的训练组、25%的测试组。结果以表格形式表示。如前所述,我们还利用SVM算法对独立的实验组进行了分类(45,50)。在此项分析中,我们将apoE-缺陷型小鼠的4个时间点的数据作为训练组,独立的实验组作为测试组。以热图方式图示各实验根据一对多比较的SVM输出值(参见图3),该值是上述4种SVM分类符各自的标准化边际值(normalized margin value)。SVM输出值使得我们能看出新实验是如何根据四种SVM超平面分类的。详细方法可从http://physiolgenomics.physiology.org/cgi/content/full/00240.2005/DC1获得。
定量实时RT-PCR.用于Taqman分析的10个基因的引物和探针购自请求式应用生物系统试验公司(Applied Biosystems Assays-on-Demand)(表2)。
表2
Zymomyx Mu_ 名称 Mm_符号 Hs_符号 UG群聚 Mm_LLID
芯片
Mu_Eotaxin 嗜酸细胞活化趋化 Ccl11 CCL11 Mm.4686 20292
因子
Mu_MIP-3b MIP-3b Ccl19 CCL19
Mu_MCP-1 MCP-1 Ccl2 CCL2 Mm.290320 20296
Mu_TCA4/6Ckine TCA4/6Ckine Ccl21 CCL21
Mu_MIP-1g MIP-1g Ccl9 CCL9 Mm.2271 20308
Mu_GCSF GCSF Csf3 CSF3 Mm.1238 12985
Mu_MIP-2 MIP-2 Cxcl2 CXCL1 Mm.4979 20310
Mu_IL-6 IL-6 Il6 IL6 Mm.1019 16193
Mu_TRANCE TRANCE Tnfsf11 TNFSF11 Mm.249221 21943
Mu_MCP-5 MCP-5 Ccl12 CCL12 Mm.867 20293
Zymomyx Mu_芯片 UG群聚 Hs_LLID Mm_ABI-Taqman
Mu_嗜酸细胞活化趋化因子 Hs.54460 6356 Mm00441238_m1
Mu_MIP-3b Hs.50002 6363 Mm00839967_g1
Mu_MCP-1 Hs.303649 6347 Mm00441242_m1
Mu_TCA4/6Ckine Hs.57907 6366 Custom Design
Mu_MIP-1g Mm00441260_m1
Mu_GCSF Hs.2233 1440 Mm00438334_m1
Mu_MIP-2 Hs.789 2919 Mm00436450_m1
Mu_IL-6 Mm00446190_m1
Mu_TRANCE Hs.333791 8600 Mm00441908_m1
Mu_MCP-5 定制设计
按照现有技术(45-47),使用从三组主动脉(每组5根)获得的代表性RNA样品一式三份进行反应。
结果
apoE-缺陷型小鼠中动脉粥样硬化过程中蛋白质表达的时序模式.我们已报导(45)了该队列apoE-缺陷型小鼠中动脉粥样硬化的损伤程度。鉴于apoE缺陷型小鼠主动脉以及主动脉瓣膜中广泛存在的动脉粥样硬化损伤,这些研究中未检查其它血管床。为鉴定与动脉粥样硬化损伤程度相关的血清标记,我们使用蛋白质微阵列在疾病发展时程中同时测定了高脂饮食apoE-缺陷型小鼠30个炎性标记的血清水平。我们将喂食常规食物的apoE-缺陷型小鼠以及野生型C57Bl/6J and C3H/HeJ小鼠的两个时间点的数据作为对照。所检测的30种标记中有8种未显示明显的血清表达水平。该队列小鼠中,22个标记显示独特的时间相关表达模式,其中一些与前述主动脉中动脉粥样硬化程度密切相关(图1)(45)。这些标记包括各种趋化因子(Ccl2、Ccl9、Ccl11、Ccl19、Ccl21、Cxcl1和Cxcl2)和几种细胞因子(Il2、Il4、Il5、Il6、Il10和Il12)以及其它炎性蛋白(Csf1、Csf2、Csf3、Ifng、Tnfsf11)和Vegfa。与作为对照的野生型C57Bl/6J和C3H/HeJ小鼠相比,这些标记中的绝大多数在apoE-缺陷型小鼠中表达较高(图2)。如前所述,在相似的条件下,对照小鼠不发生组织学意义上明显的动脉粥样硬化损伤(47);因此,很容易将疾病相关变化与诸如高脂饮食和衰老等其它因素相区开来。
高脂饮食和衰老引起的品系特异性蛋白质表达.为说明高脂饮食、衰老和遗传背景所致的非动脉粥样硬化依赖性血清蛋白质水平变化,我们使用了许多对照,其中包括熟知的具有不同患动脉粥样硬化倾向的两种小鼠品系,使用了两种不同的饮食和纵断面实验设计。已知这些对照小鼠不发生动脉粥样硬化损伤,因此,它们是用来说明这些独立变量以及这些变量之间可能的相互作用的合适对照。结果,我们鉴定到了apoE-缺陷型小鼠中可能与各变量有关的差异表达的蛋白质并区分出了与血管疾病过程专性相关的那些蛋白质。简单ANOVA显示,不同饮食-品系-时间组合之间,至少12种标记表达有差别(图2)。为说明这三种独立变量之间可能的相互作用,我们采用三向ANOVA。三种独立的变量有三种一级相互作用(时间-品系、时间-饮食、品系-饮食)和一种二级相互作用(时间-品系-饮食)。在说明所有这三种因素之间相互作用的过程中,我们鉴定了5种差异表达的蛋白质(3-向ANOVA,P<0.05),包括Ccl9、Ccl21、Ccl11、Csf1和Il12b。
在较晚的时间点,许多炎性标记的血清水平升高,表示高脂饮食还在C57Bl/6野生型小鼠中激发了炎性应答(图2)。在另一方面,C3H/HeJ小鼠的炎性标记水平最低,即使喂食高脂饮食亦是如此。该发现与我们过去的研究结果一致,在过去的研究中我们比较了C3H/HeJ小鼠与C57Bl/6J小鼠的主动脉血管壁基因表达。当时研究的结论是,C57Bl/6J小鼠在动脉粥样硬化过程中表达炎性标记的遗传倾向性较高。
鉴定小鼠血清中的时间特异性蛋白质表达签名.人类癌症的分类方法就肿瘤的临床特征提供了大量信息,包括转移的倾向性、药物反应和长期预后(13、23、33、43)。对动脉粥样硬化来说,分类算法的临床用途在于预测未来事件。在以前的研究中,我们应用分类算法确定了一组基因,这些基因在血管壁中的表达能准确区分小鼠和人动脉粥样硬化血管组织中疾病的严重程度(45)。在本次研究中,我们采用相似的方法来鉴定血清蛋白最小亚组,用该组蛋白按照准确已知的小鼠动脉粥样硬化四阶段将各蛋白质组学实验准确分类(图3)。在此,我们采用几种熟知的分类算法来鉴定最能区分不同疾病状态小鼠的变量。这些算法包括RFE、SVM和ANOVA。我们还用PAM作为附加分类算法。这些算法根据蛋白质在高脂饮食apoE-小鼠中区分0、10、24和40周时间点的能力对这些蛋白质进行排名。我们的结果显示,大多数算法鉴定了一个蛋白质小亚组(Ccl21、Ccl9、Csf3、Tnfsf11、Vegfa、Ccl11、Ccl2)(图3A)。
该组标记签名的预测能力优于任何单一标记,因为单一标记都不能准确区分不同的疾病状态(分析未显示)。为确定这些蛋白质的血清水平按照不同疾病状态对小鼠进行分类的效用,我们采用SVM算法(线性核模型)通过交叉验证(反复的将按75%训练组和25%测试组分组)产生了一个混淆矩阵。该算法显示,这些血清蛋白质表达的签名能以高达100%的准确准确率区分患病和未患病的小鼠组(图3B),并且还能高准确准确率(79.6-100%)地将疾病中期的小鼠与其它阶段的区分开来(图3B)。
独立数据集的交叉验证和分析.一组分类符蛋白质具有效用的重要证明是它们能对来自独立实验的数据进行准确分类。为验证分类符蛋白质的效用,我们研究了它们将准确独立的一组16周龄apoE-缺陷型小鼠准确分类的能力。采用SVM算法,我们能将准确平行进行的各实验准确地归入正确的疾病进展阶段(图3C)。据该独立组小鼠的蛋白质表达与原实验组(10周龄)的蛋白质表达模式之间的最高相关性所示,这些分类符蛋白质将使得验证数据集与训练组中最接近的时间点准确匹配。必需指出的是,在该分析中,训练组(“已知”)中不包括独立数据集(“测试”)。
生物标记血清蛋白质水平与血管壁基因表达水平相关.据估计,循环蛋白水平与血管壁中的分子事件和表达水平相关的那些生物标记可提供最多的血管疾病相关信息。为查明这些相关性并从生物标记数据获得与动脉粥样硬化的病理生理学有关的信息,我们研究了高信息含量生物标记编码基因的血管壁基因表达模式。采用定量实时RT-PCR,我们能确立数种标记的血清蛋白水平与它们的血管RNA表达之间的关联。在被研究的标记中,Ccl21(r=0.91)、Ccl2(r=0.97)、Ccl19(r=0.80)和Ccl11(r=0.67)显示基因表达的时间相关行增加与血清水平之间高度相关(图4)。这些数据虽然还包括这些标记在其它组织中的表达,但它们提示:表达与血管壁动脉粥样硬化特别相关。通过比较血清蛋白质水平、血管基因表达和高脂饮食时间(log10(喂食周数))的标准化平均比值来测定皮尔逊相关值。如果动脉粥样硬化血管壁中的mRNA表达与所编码蛋白质的血清水平之间的相关系数(r)是至少0.6、至少0.7、至少0.8、至少0.9或更高,则将这种相关性视作显著。
讨论
明显需要改进的工具来诊断和治疗临床前动脉粥样硬化。虽然目前对动脉粥样硬化的机制和情况的了解越来越多,但我们鉴定高风险患者和预测冠状动脉疾病预防手段效力的方法依然不够。由于缺乏动脉粥样硬化性疾病的高灵敏性、高特异性生物标记,半数以上此类患者的首次临床表现便是心肌梗塞或死亡(19,20)。曾就动脉粥样硬化研究了小鼠和人的几种炎性标记,结果支持动脉粥样硬化的炎性假说(38)。然而,各项研究仅关注少数几个单用标记上,一些研究没有进行纵断面实验,只有少数研究证明在血管水平上与基因表达直接相关(25,29,34)。
虽然目前已提出用通用炎症标记划分患者动脉粥样硬化疾病风险级别,但不曾用这些标记在无症状患者中就确定准确疾病类别进行筛选,更重要的是未曾用于预测首次心血管病变。例如C-反应性蛋白(CRP)和血纤蛋白原等标记缺乏特异性的原因可能在于它们不是血管衍生蛋白,可作为各种器官中炎症的信号。还可能,由于高危人群之间的异质性,单独一种标记提供的信息不足以准确预测疾病。出于相似的原因,这些通用炎症标记,例如CRP和沉降速率(ESR)早已不被用作其狼疮(SLE)和类风湿性关节炎(RA)等它炎性疾病的特异性诊断标记。
我们曾经采用本发明所用的实验设计对小鼠主动脉组织RNA分布进行研究,证明可以鉴定到少量能够按照疾病严重程度进行分类的基因(45)。显然,由于不易对血管组织直接进行处理,鉴定血清中的蛋白质标记对于开发诊断人冠状动脉疾病的诊断工具来说具有实际意义。在本文报道的工作中,我们研究了炎性血清生物标记丰度模式以及这些生物标记的亚组是否可用于就疾病进展对动物进行分类。在科学上,这两类信息是互补的,明显加强了对疾病详细分子机制的理解,所述机制包括从基因转录到翻译到胞内途径到向血清中分泌递质。如上所述,鉴定某给定疾病状态的血清标记分布能开发可人用的非侵入性诊断方法。因为我们还具有基于微阵列的患病组织转录情况详细全景(transcriptional landscape),我们能用该图估测导致炎性介质表达的途径中的上游组分,这是开发高度靶向性治疗手段的第一步。实际上,然后可用血清试验(例如本文所述)来检验这种治疗手段的最终效果。我们用蛋白质微阵列同时(检测)多种动脉粥样硬化小鼠模型的血清蛋白质表达分布,所述模型具有不同的动脉粥样硬化易感性和严重程度。用与分类癌症进程和类型所用相似的分类算法,我们能证实:这些血管衍生生物标记的独特签名能准确预测不同程度的小鼠动脉粥样硬化。
在以前的研究中(45),我们的分析显示16周时间点获得的独立数据集的微阵列基因表达分布与24周时间点的更相关,而在此次研究中,相近时间点的蛋白质分布与10周时间点的更相关。基于该发现可能产生许有趣的假设。由于目前蛋白质微阵列中的探针数量有限,本发明研究中的蛋白质分类符不同于以前研究中鉴定的基因分类符。血清蛋白质表达的时间相关行增加还可能滞后于血管壁基因表达水平的变化。
由于相同标记的血管基因表达和血清蛋白质水平之间可能因各种因素(例如转录后修饰和蛋白质稳定性)而不直接相关,这些数据的重要验证是证明这些标记中亚组的疾病相关血管基因表达。我们证实这些标记的时间相关性血清水平与它们在血管壁中的基因表达相关。疾病进展与血管基因表达的时间依赖性关联提示标记产生的主要部位是血管壁。然而,如以前的报道所述(22),血管可能不是炎性标记的唯一来源,其它组织,例如肌肉、脾脏、脂肪组织或肝脏可能也影响着这些标记的血清水平。在我们的研究中评估的一种标记是Il6,已知其产生于肌肉和肝脏以及血管壁。制得关注的是,Il6的血清丰度与疾病的时序性发展不相关,与血管壁中的基因表达只有微弱相关性。这些发现提示:其它组织可能也影响着一些标记(例如Il6)的血清水平,但这些标记的水平与所研究的疾病状态不相关,也无助于分类(对象)。
一些全身性炎性标记的血清水平还可能应研究所用不同小鼠之间代谢参数差异而变得复杂。业已证明,高脂饮食激发在肝内炎性应答(22)。这些基因在整个高脂喂食期间维持高水平表达。为了设立关于这些全身性效应的对照,我们在动脉粥样硬化早期和晚期都对高脂饮食的小鼠进行了比较,结果,血清脂质水平不变(14)而动脉粥样硬化程度改变。因此,这些代谢参数与随时间线性增加的标记血清水平之间相关性不佳。因此,血管衍生标记的时序性变化与动脉粥样硬化的程度更相关,与脂质水平则不甚相关。
本项研究所鉴定的这些标记有力地支持了动脉粥样硬化的炎症性质,所鉴定的各标记能提供了了解疾病在小鼠中潜在机制的部分信息。这些标记包括巨噬细胞和T细胞重要特异性趋化因子。Ccl21(原来称为Exodus-2/SLC/6Ckine/TCA4)是至今鉴定的最强T细胞趋化剂,其在T细胞附着和从血管向炎症组织部位转移中发挥着重要作用(30)。在我们的实验中,相关趋化因子Cxcl12和Ccl19也高水平表达,它们通过激活淋巴细胞功能相关的抗原-1(LFA-1)来介导T细胞与内皮强烈结合(6,15)。重要的是,据信,在正常免疫应答期间Ccl21不参与T细胞的效应细胞功能,但在T细胞介导的自身免疫疾病中,它被发现在内皮细胞中高水平地诱导性表达(8)。因此,疾病相关性高水平循环Ccl21这一新发现和以及高度相关的CCL21在患病血管壁中的表达提出了一个问题,即在小鼠中,自身免疫过程是否参与了动脉粥样硬化的发展(44)。人疾病期间的Ccl21水平尚有待测定。Ccl19[巨噬细胞炎性蛋白(MIP)-3b]与Ccl21的功能有些相似。其与相同的受体即Ccr7结合,是T细胞和B细胞的强效趋化剂。但与Ccl21不同,Ccl19似乎还采与正常的T细胞功能。其在动脉粥样硬化性血管中的表达以及血清水平与主动脉基因表达之间的高度相关性均是新发现。
Ccl2(Mcp1或JE)(3)和Ccl11(嗜酸细胞活化趋化因子)(10,17)在动脉粥样硬化中的作用已很清楚,这些证实了我们的发现。我们也记载了:Cxcl2(MIP-2)和Cxcl1(KC)的血清水平在动脉粥样硬化小鼠的血清中均升高,与其它研究者所述的血清水平一致(29)。如其它研究者的研究所述(29),我们发现Cxl12(MIP-2)的可靠性较低。此外,鉴于血清水平与主动脉基因表达的相关性较低,大量的Cxcl2可能是有非血管性组织产生的,这证实了以前的结论(29)。然而,我们发现与Cxcl2血管基因表达的相关性仍优于例如Il6和Csf3等其它标记。尽管Cxcl1(KC)的水平升高,我们发现该标记不是疾病的稳定预测符,这与近年来的研究一致(34)。近年来有报道将Vegfa描述成急性冠状动脉综合征的独立预测符(18,24)。我们的研究在至少三种所用算法中支持Vegfa是合理的分类符,从而证实其可应用于监测人类疾病。我们的另一非常值得关注的发现是Tnfsf11(TRANCE)在动脉粥样硬化中的作用。Tnfsf11是肿瘤坏死因子(TNF)细胞因子家族的一员,并且是骨保护素的配体,是破骨细胞分化和活化中起到关键因子。该蛋白质也称为树突状细胞存活因子(dentritic cell survivorfactor),参与调节T细胞依赖性免疫应答。近年来,骨保护素被认为是进行性人动脉粥样硬化和人心血管疾病的潜在风险因子(21,37)。据推测在动脉粥样硬化中起作用的其它细胞因子包括Il12b(25)和Il5(9)。虽然我们证明了它们的血清水平能预测疾病状态,但我们未能证实Il12b在动脉粥样硬化损伤时的血管特异性表达。
总之,我们鉴定的优选血清蛋白分类符涵概了多种动脉粥样硬化生物学过程,包括巨噬细胞趋化反应(Ccl9,Ccl2)、T细胞趋化因子活性(Ccl21和Ccl19)、先天免疫性(Il5)、血管钙化(Tnfsf11)、血管生成(Vegfa)和高脂诱导的炎症(Cxcl1,可能还有瘦蛋白)。同时检测这些标记获得的签名代表着不同的动脉粥样硬化相关性生物学过程,有望满足诊断动脉粥样硬化性疾病的特异性要求。如实施例3-12所述,通过合适的前瞻性人试验对该方法的进一步验证获得了用于动脉粥样硬化和冠状动脉疾病的改良筛选诊断工具。
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实施例2:蛋白质微阵列分析
为评估不同趋化因子(嗜酸细胞活化趋化因子、IP-10、MCP-1、MCP-2、MCP-3、MCP-4、IL-8、MIP1a和RANTES)的抗体阵列的性能,我们用市售施莱歇尔和舒尔蛋白质微斑点阵列(FastQuant人趋化因子,S&S拜尔森斯公司(S&SBioscences Inc.),基涅,新罕布什尔州,美国)。该阵列平台采与点样在包被了3-D硝基纤维素表面的标准显微镜载玻片上的多种高特异单克隆性抗体。作为人循环(血)样品,我们选择了有病史、运动试验确定阳性(positive exercise test)或接受过冠状动脉导管术的一组11个已知严重冠状动脉病例,和没有病史及运动试验或冠状动脉造影呈阴性的9个对照。收集循环(血)样品,冷冻保存于-80℃,融化后立即用在阵列上。各样品在一式两份的两个阵列上温育。用一次点样(print run)制备的总共8块载玻片(每块载玻片上8个阵列)对11份患者样品和9份对照进行测评。
该项研究中对各样品进行的重复实验显示阵列之间的重现性良好。对于各抗体,将同一阵列上4重复特征扣除了背景信号的信号中值与重复实验中的各个中值作图比较。重复实验的检测值之间相关系数大多为0.99,表明两组阵列数据之间的一致性优良。
在以下分析中,各分析物循环检测值表示一种循环(血)样品的四次检测值的平均值,其中扣除了空白载玻片的相应平均检测值,用差值的log(10)数值进行分析。将对照9份样品组的蛋白质水平与病例组11份样品的蛋白质水平作比较。对于每种蛋白质,采用高斯误差评分法(Gaussian error score)比较病例和对照组的蛋白质水平分布,并制作成热图,所述评分法检测按照各组样品数值拟合的正态分布交叠。高斯分布图显示了两组中MMP-2/TIMP-2复合物的蛋白质水平实际分布。一种蛋白质检测值不能明确分开这些组中的少量个体,高斯图中明显可见重叠的信号分布。虽然本项工作的目的不是鉴定分类算法,但通过将少量优选蛋白组合并用费希尔线性辨别分析来区分病例样品和对照样品是可能的。
我们用标准ELISA夹心试验,用与该阵列所用相同的捕捉抗体和检测抗体验证了该阵列所得的结果。虽然该阵列所用的抗体对是购买的并已由供应商验证适用于ELISA,还是先检查然后将用于阵列以确保它们符合灵敏度要求。采用ELISA方法分析病例和对照人循环样品,将ELISA数据与阵列数据相比较。分析物之一循环瘦蛋白的比较数据显示,无论以10倍还是20-倍样品稀释液进行ELISA,相关性良好。
实施例3:用于准确预测和诊断人冠状动脉疾病的循环炎性标记签名
人血清生物标记的前期试验数据
由于实施例1和2获得的结果令人鼓舞,我们研究了是否可用蛋白质微阵列鉴定血清炎性蛋白质的签名用作人类动脉粥样硬化性疾病的高灵敏度、高特异性标记。为此,我们设计一项病例-对照嵌套研究(nested case-control study),通过以检测动脉粥样硬化风险因素和遗传决定因素为目的的大型临床流行病学研究选择了51位临床明显CAD患者和44位健康对照。用蛋白质微阵列对报名时收集的血清样品进行多种炎性标记的同时检测。有一个亚组的所测分析物在病例受试者中的浓度明显较高。采用这些标记的血清表达分布的分类算法能准确相对于对照将CAD对象准确分级。此外,这些生物标记的独特签名明显提高了CAD其它已知标记的预测能力。在该前期研究中,我们证明:循环炎性标记的特征模式能准确鉴定动脉粥样硬化患者。
引言
动脉粥样硬化性心血管疾病(ASCVD)是发达国家中发病率和死亡率的主要原因1、2。然而,由于缺乏准确的早期诊断标记,超过半数的冠状动脉疾病(CAD)患者的首次临床表现便是心肌梗塞或死亡3、41、 2。炎症在ASCVD的所有阶段均涉及,认为其是动脉粥样硬化的病理生理学基础,从而提供了该疾病过程的潜在标记5、6、 7。
在大型流行病学研究中,血清炎性生物标记升高已显示能区分心血管风险的级别并评估治疗反应89。虽然可能可用于风险定级,目前的炎性标记缺乏足够的疾病特异性,因而不能用作CAD诊断的筛选工具。例如C-反应性蛋白(CRP)和血纤蛋白原等目前的标记缺乏准确性的原因可能在于它们既不是主要衍生自血管壁又不是主要由参与血管炎性过程的细胞产生的,并且可能作为许多不同器官和组织中的炎症信号。此外,还可能,因为高危人群的疾病表型异质性,单独一种标记提供的信息不足以准确评估冠状动脉循环系统中的血管损坏。出于相似的原因,这些通用炎症标记,例如CRP和红细胞沉降率(ESR)早已不被用作例如狼疮(SLE)和类风湿性关节炎(RA)等其它炎性疾病的特异性诊断标记,尽管它们依旧是临床实践中对风险定级和测评治疗反应的工具。
因此,亟需能更准确反映ASCVD活性并能用作鉴定患者的高度灵敏、高特异性试验的生物标记。我们推测,循环炎性蛋白质的独特签名可更好地鉴定CAD。为解决该问题,我们设计了一次嵌套病例-对照研究(nested case-control study),通过从ADVANCE研究(动脉粥样硬化性疾病,血管功能和遗传流行病学(Atherosclerotic Disease,VAscular FuNction,& GenetiC Epidemiology))选择51位最近发生过心肌梗塞(MI)的患者和44位健康对照,所述ADVANCE研究是关于动脉粥样硬化遗传易感性的群体研究。用商品化购得的蛋白质微阵列对报名时收集的血清样品进行9种炎性标记的同时检测。数据分析包括了大量临床变量,例如病史、用药情况、个人和家族史(一级亲属)以及血浆葡萄糖、胰岛素和C-反应性蛋白(CRP)水平。统计学算法鉴定到蛋白质生物标记签名,当所述签名与其它临床变量联用时能准确鉴别CAD患者和对照。
方法
患者选择和临床数据
所有研究方案均经由学院评审委员会评审和批准。从ADVANCE研究队列的两个不同组别中随机选择患者,所述ADVANCE研究是斯坦福心血管部门(Stanford Cardiovascular division)和北加利福尼亚凯撒永久医疗保健项目(Northern California Kaiser Permanente Medical Care Program)研究部合作进行的一项更大规模的遗传流行病学研究,其目的是调查心血管疾病的遗传决定因素。旧金山海湾地区(San Francisco Bay Area)的总共3666人参与了ADVANCE,根据性别和年龄对这些人进行分类以代表北加利福尼亚州人口状况。所有可能参加试验对象书面表示知情并同意参与,研究方案得到斯坦福大学和凯撒研究部门的人类对象委员会(Human Subjects Committees)的批准。ADVANCE研究队列由特征明确的临床组别构成:743位年轻、明显健康的对照(组1);1023位年长的对照(组2);503位年轻的CAD病例(组3);926位年长的新近诊断CAD病例,病历记载在报名时已发生过首次心肌梗塞(MI),首次心肌梗塞时间距离报名时间的中值是3.4个月(组4);和471位年长的稳定心绞痛首次发作病例(组5)。我们通过性别随机取样法从组2和组4中选择了95例高加索受试者、44位MI病例和51位对照。大型ADVANCE研究数据库包括例如病史、用药情况、个人和家族史(一级亲属)以及血浆葡萄糖、胰岛素和C-反应性蛋白(CRP)水平和脂质分布。只在组2中测得了脂质分布。病例受试者包括45-75岁老年男性和55-75岁女性,都是因急性MI首次发现CAD。鉴定这些受试者的标准是:出院主诊断码(primaryhospital discharge diagnosis code)为410.x,并且,住院期间或入院前72小时内心脏酶类升高(肌钙蛋白I水平≥4.0ng/mL,或者,CK-MB≥5.6ng/ml与CK-MB%≥3.3ng/mL至少其一)。导引病变(index event)(中值为3.4个月)后7-20周采集血清。ADVANCE研究委员会审阅了临床文件,确认了诊断结论。对照是不同性别的60-69岁老人,据其主要医师报告并检索凯撒永久数据库(Kaiser PermanenteDatabase)的结果,他们没有任何ASCVD表现或其它重症疾病的临床史。在报名参见ADVANCE后的首次寻访时擦剂临床数据和空腹血清样品。用标准方法检测葡萄糖和胰岛素的血浆浓度。通过高灵敏度ELISA试验测定CRP。
蛋白质微阵列杂交和数据处理
为测定9种不同趋化因子(嗜酸细胞活化趋化因子、IP-10、MCP-1、MCP-2、MCP-3、MCP-4、IL-8、MIP1a和RANTES)的浓度,我们使用市售施莱歇尔和舒尔蛋白质微斑点阵列(FastQuant人趋化因子,S&S拜尔森斯公司,基涅,新罕布什尔州,美国)。该阵列平台采用点样在包被了3-D硝基纤维素表面的标准显微镜载玻片上的多种高特异单克隆性抗体。这些标记的灵敏度和特异性以及与常规ELISA的相关性是已知的。已确定这些标记之间没有交叉反应性。按照生产商的使用说明书使血浆样品与蛋白质微阵列杂交,然后加入生物素化的第二抗体和Cy5-链霉亲和素偶联物。用Axon Genepix 4000B微阵列扫描仪和特征提取软件(Array Vision Fast 8.0,S&S拜尔森斯公司)将扫描图像转化成数字强度,由此测得杂交后荧光强度。根据内标参比值由荧光强度值算得绝对浓度。根据具体分析物,快速定量(FastQuant)蛋白质阵列的对照变率为3%至约15%,灵敏度为1-10pg/ml。快速定量蛋白质阵列的准确率与具有相似线性范围的相应ELISA相当10、11。目前研究的具体的其他方法和质量控制见发行人的在线网址(其他材料可参见Ardigo,Tabibiazar等,“Signature Patterns of CirculatingBiomarkers Accurately Predict Presence of Coronary Artery Disease”),包括阵列重现性和标准曲线。
随后用局部视窗工作站(local Windows workstation)分析原始数值数据并其迁移到专用于微阵列数据分析的奥雷克尔关系型数据库(Oracle relationaldatabase)。出于技术原因,RANTES和IL-8不包括在后续分析中。RANTES标准曲线不是S形,因此不具有计算浓度的线性部分。在病例和对照样品中,大多数IL-8值在标准曲线界限之外。
统计学分析
用曼-惠特尼的U检验(连续变量)和卡方检验(名义变量采)测定两组之间的临床特征差异。用蒙特卡洛方法计算显著性水平。在对U检验和χ检验所示组件分布不均衡的临床变量进行调整之前和之后进行通用线性模型(GLM)多变量分析来鉴定病例和对照之间的趋化因子差异。
用接受器工作特性(ROC)曲线检验趋化因子的诊断性能。采用12对数回归(LR)分析来验证趋化因子数值是否可区分病例和对照。在双变量分析中两组之间差别显著的年龄、性别和临床变量也纳入这些模型作为独立变量。由于两组之间在用药(常规CAD处方药,例如ACE-抑制剂和他汀类药物)方面的差异会在模型中引入假的疾病预测符,我们决定从分析中排成关于药物治疗的所有信息。
构建了三种LR模型应对以下问题:独立变量的数量相对升高,存在缺失值(8位对象中约10个值)和趋化因子浓度之间的共线性。对变量(采纳概率(entryprobability)为0.05;排除概率(removal probability)为0.15)进行两次前向逐步选择:不进行缺失数据估算和采用条件均值进行缺失数据估算。专用于解决共线性问题的第三LR模型包括连同临床变量的趋化因子评分。评分计算包括:在一个1-10级别标度(根据十分位数)上对各趋化因子浓度进行重新编码,然后求得各测得趋化因子的平均级数。关于检验、模型构建和缺失数据估算的详尽描述可在线查阅以作补充。采用基于视窗系统的SPSS统计学软件(12.0版)(SPSS公司(SPSS Inc.),芝加哥,伊利诺斯州)进行U和χ2检验、GLM、ROC和LR。
为总览数据结构,我们进行了两维层次聚类法分析(2D-HC)。利用开源软件Tmev,3.0版(TM4套件,遗传学研究院(The Institute for Genomic Research),罗克维尔,马里兰州)13构建2D-HC。分析中用完全连锁和皮尔逊相关性作为距离指标。为测定我们的数据中最大方差的方向,我们采用依据log2的主成分分析(PCA)。
蛋白质选择算法和疾病状态分类:
曾有关于蛋白质选择和分类算法的记载(Tabibiazar 2005 Physiol Genomics.2005年7月14日;22(2):213-26),纳入作为参考)。简言之,在有监督的分析中,我们用多种分类算法根据基因区分病例和对照的效用对其进行排名。该项分析所用的算法包括支持向量机(SVM)14和递归特征排除(RFE)16,RFE是SVM的递归算法,其中,反复进行变量排名并且每次除去固定比例的最低分者16。用SVM-RFE确定能以最低误差率将各实验正确归类的最佳数量的排名基因。通过1000次递归交叉验证计算最佳出错率或分类误差,其中25%的实验用作测试组,其余的用作训练组。作为SVM结果的内部验证,我们还采用了以下监督分类算法:分类和回归树(CART)、线性辨别分析(LDA)和对数回归(见本章前述)。CART是一种采用一系列“如果-则(if-then)”二叉逻辑条件的的灵活的层次分类系统,该系统允许对结果的个性化(individualization)程度和分类误差的比例成本(proportional cost)进行设定。为获得高准确率的分类,我们设定终端节点(terminal node)仅包含纯粹亚组或不超过5个对象。先验信息(prioriinformation)包括:两种类别大小相等且分类误差成本(misclassification cost)相等。通过多次随机置换10%的对象来交叉验证结果。
结果
对象的临床特征
如图5所示,病例组和对照组在体现已确知为CAD风险因素的诸多重要特征上有差异。病例对象的胰岛素耐受表型更明显,血浆胰岛素浓度更高,BMI略高(虽然不明显),腰围更大和血脂异常比例更高。然而,在两组之间的血液葡萄糖水平和糖尿病比例相仅。患者的血压,不论是收缩压还是舒张压都明显低于对照,尽管有更常见的高血压病史。该事实至少可部分揭示为多用抗高血压药物(96.7%比之43.2%)和次级预防性处方药例如ACE-抑制剂、β阻断剂、他汀类药物和阿司匹林等所致。而且,虽然CAD患者的一级亲属中冠状动脉疾病比例高于对照,但两组间的糖尿病、血脂异常、高血压和中风的家族史没有明显不同。有意思的是,虽然两组在血管和代谢表型上有明显差异,但CRP浓度没有可检测的差异。
病例和对照的循环炎性标记
虽然两组之间的CRP没有差异,但多变量GLM风险显示病例组的其它循环炎性标记高于对照(图6),即使在就临床变量和药物治疗进行调整后亦是如此。
比较病例与对照的无监督数据分析
鉴于CAD患者中炎性标记的水平升高,我们研究了利用这些信息通过无监督分析将患者准确分类的可行性。两维层次聚类法表明:CAD患者和对照患者倾向于形成大型同质集群,虽然有个别病例和对照维持在这些大型集群之外群体外(图7)。对于被测变量,临床参数集中为一组,趋化因子则形成另一组。有意思的是,CRP水平与代谢参数的关联度高于趋化因子水平。
主成分分析发现,在对象中观察到差异有60-70%可解释为趋化因子、胰岛素耐受性和部分其它临床变量(例如高血压和高脂血症)所致,其中,炎症标记是主要因素(图8)。
用趋化因子特征和临床变量进行病例和对照状态的分类
为确定能准确区分病例对象和对照对象的最佳、最小变量组,我们采用了SVM分类算法(Tabibiazar 2005 Physiol Genomics.2005年7月14日;22(2):213-26)。SVM鉴定了能高度准确区分不同程度对象的一组15个变量(分类误差率<10%)(图9)。除了已知的CAD风险因素外,检测循环趋化因子明显加强了疾病预测。为验证我们的发现,我们采用了多种其它分类算法,结果,对于预测CAD:LR(80%灵敏度,88%特异性)、LDA(73%,94%)和CART(80%,88%)表现出了相当的高水平灵敏度和特异性。
检测炎性标记改善了只根据临床变量进行的分类
用ROC曲线进一步评估了单一变量和多个变量区分病例对象和对照对象的分类能力。在趋化因子中,MCP-4看来是最灵敏的,MCP-1是特异性最强的,二者均显示良好的准确率(AUC分别是0.896和0.849)(图10A)。应该注意的是,CRP似乎无助于在流行病学范畴以外鉴定疾病,而血管炎症的特异性标记则更准确。图11显示了三种对数回归分析的结果,其中,趋化因子或者通过分步选择(模型1和2)引入,或着作为组合分值(模型3)引入。在CAD患者中,三种模型中有两种的总准确率超过90%,这支持了这一推测:使用多种标记区分ASCVD患者能提供更多信息。LR模型的分类性能与最佳趋化因子,MCP-1和-4(的曲线)的比较是对该假设的进一步证明(图10B)。显然,采用多标记算法明显能更好地预计是否存在疾病。
讨论
需要诊断和治疗临床前ASCVD的更好的工具。目前,虽然对动脉粥样硬化的机制和情况的了解越来越多,但我们仍缺少用于鉴定高风险患者并预测预防方案之效果的方法。越来越多证据暗示:血管炎症是动脉粥样硬化各阶段中主要的病理生理学过程5,并且,已就炎性标记用于诊断的可能性进行了数项研究17。
虽然目前的炎症通用标记被认为可能可用于评定风险级别,它们不足以在普通人群中鉴定CAD18。这些标记缺乏特异性的原因可能在于它们不是血管衍生标记,并且可能是指示各种器官中的炎症的信号。个体对环境风险因素的反应不一致性也可能导致了ASCVD标记浓度的高度不同。在这点上,一种炎性蛋白所携带的生物学信息可能不足以全面表征血管炎性状态,因而可能无法准确鉴定是疾病的存在及程度。相比之下,采用多种炎性标记特征的多维方法可提供动脉粥样硬化相关血管炎症的病征签名。本发明的研究用实验支持了这一假设并提示:用多种炎性标记可有效鉴定患冠状动脉心脏病的患者。
由于血管炎症是动脉粥样硬化的病理生理学基础,动脉粥样硬化血管中产生的趋化因子是CAD标记的主要候选者。趋化因子是白细胞和内皮细胞被活化时产生的一群可构成网络架构的趋化蛋白质19。它们的主要作用是使白细胞在组织中累积并活化,它们与几种细胞受体的相互作用参与形成炎性渗透的特异性20、21。趋化因子常成组存在,各组的组成不同,这种趋化因子组的生物学效应与单个因子的生物学效应可能极其不同,因此,测定细胞因子和趋化因子表达的总体模式比单一蛋白质试验更可能获得有意义的生物学信息。
我们的数据清楚地显示:临床CAD个体中数种趋化因子血浆浓度的调变不同于健康对照,即使在就已知临床变量进行调整后亦是如此。因此,结合这些标记的多变量模型能准确区分这两组的样品。据假设,采用多种分析物的预测模型远比采用一种炎性蛋白质的模型准确。这些结果得到了多种不同算法多变量统计学分析的验证,不同算法的的结果高度一致。
各模型的一致性以及不同试验所得结果的重现性提示:趋化因子特征提供了血管疾病的强烈信号。尽管队列的规模较小并且患者正接受所有可能的治疗,但这些结果仍然具有非常显著的意义。
在我们的数据中,尽管血管和代谢表型明显不同,但在病例和对照之间未观察到CRP水平有明显不同。这可能是因为样品规模较小,并且,使用降CRP药物(例如他汀类药物和阿司匹林)较多的缘故。然而,虽然经治疗,但有心肌梗塞病史的个体患冠状动脉疾病的风险依旧高于没有CAD病史的人22。而且,CRP的主要临床用途被认为是在经典风险因素不确定时更准确地区分个体,但对该提法依然有争议23。虽然治疗期间CRP水平降低可用作治疗反应指数8 9,但在我们的横断面研究中,CRP提供的信息不比其它临床变量多。
我们的研究存在一些局限性。病例对象的血清样品是在急症之后(7周-20周,中值为3.4个月)采集的。虽然炎性标记通常会在4-8周内回复至基线水平,我们不能排除急症导致炎性标记水平改变的可能性。我们的研究设计也未确认蛋白质组学特征用于区分病例和对照的的预后价值,虽然在我们所鉴定的蛋白质组学特征可能的确具有预测原发(primary)或继发(secondary)事件的预后价值。我们的生物标记组明显不是完全清单。实际上,利用更多分析物的阵列有望提高诊断ASCVD的灵敏度和特异性。然而,本发明的初步研究证明了利用蛋白质微阵列同时监测多种生物标记的可行性。
总之,我们已鉴定了循环血清炎性标记组,它们的独特签名能准确区分CAD患者和对照。后文实施例5报道了验证该方法的大规模研究。
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实施例4:用于准确分类冠状动脉疾病的炎性标记的数据分析
用购得的施莱歇尔和舒尔人趋化因子芯片进行研究。我们使用该阵列评估了选自雷诺兹中心(Reynolds Center)队列的100份样品中的循环趋化因子水平。所检测的趋化因子是:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IL-8、RANTES、MIP-1α和IP-10,虽然IL8和RANTES值落在线性范围之外。通过对雷诺兹队列中选定SNP的重新测序和基因分型对广泛研究了编码MCP-1、MCP-2、MCP-3、嗜酸细胞活化趋化因子、IL-8和RANTES的遗传基因座。循环样品来自有心肌梗塞病史的50位个体和50位年龄匹配的对照(参见前文队列描述)。虽然对照在其它变量上不匹配,但性别和种族及其它变量的联合分布是相似的。阵列与生产商提供的试剂杂交、清洗,并用艾克松(Axon)扫描仪扫描,用S&S公司专有软件(阵列视TM夸特(Array VisionTM Quant))进行特征提取。用该阵列所包括的试剂产生标准曲线,测定各份循环样品的浓度。
分析采用新方法,但延用以下主张的基础前提条件是:临床和基因分型数据的纳入能增加生物标记数据的信息,用于就与疾病状态/活性无关的个体间趋化因子水平差异进行标准化。通过测定具有这些匹配数据的趋化因子丰度、临床数据和各SNP的基因分型信息进行分析。
区分病例和对照以及发现能用于区分的那些变量是双类别(two-class)“分类”的基本问题。虽然单个分类符可能也行,但在它们中进行“公投”(vote)通常更好。实际上,在分类符中进行“公投”的方法十分常见,其中两种是“打包法(bagging)”和“补强法(boosting)”。我们在分析之初只用4种分类符,就每一个受试者在它们中进行简单公投。采用交叉验证的标准方法例如5-倍交叉验证来评估预期性能。因此,将数据组随机分成大小几乎相等的5个亚组。依次地,每一次验证在80%的数据上展开(并进行次间公投),取20%的数据计算结果。然后计算五组结果的平均值。也可使用更完备的样品再用方法来评估预期准确率。对99位对象的初步样品进行了所述分析。变量包括嗜酸细胞活化趋化因子、IP-10、MCP-1、MCP-2、MCP-4、MIP1α、性别、年龄、葡萄糖、胰岛素、CRP和脂肪(FAT)。测定变量FAT作为BMI和腰围(WAIST)的首要组分,以线性方式造成后文两预测符91%的差异。共有51例MI和48位对照。我们用经验值(empirical priors)来预测双类别问题的贝叶斯分类规则;这样,它们几乎是每类0.5。将分类误差成本取作相等。(当然,对于双类别问题,只有先验概率乘积与分类误差成本的比值才是重要的。在这里,该比值约为1。)年龄为60岁-72岁,其中,下端的权重高于上端。平均值是64.7岁,第25、50和75区间百分位数分别是62、64、67;年龄的标准偏差是3.1。在以下实施例中,LDA指费希尔线性辨别分析。下文描述了称为CART、FlexTree和LART的方法。对于LART技术,首先用简单的拉索法减少预测符的数量。如何进行分类的详见下文。FlexTree和LART中的一个重要细节是回归系数的霍特林T2分选量,这对于它们的预测能力很重要。由分类移交的权重用于LART加权拉索(方法)。
表3.经5倍交叉验证的性能
算法 | 分类误差百分比 | 灵敏度 | 特异性 |
对数回归 | 16% | 80% | 88% |
LDA | 17% | 73% | 94% |
CART | 15% | 80% | 88% |
LART | 16% | 78% | 90% |
Vote | 12% | 82% | 90% |
表4.所述方法鉴定的变量
CART | MCP-4、FAT、嗜酸细胞活化趋化因子、MIP1α |
LART | MIP1α、MCP-2、MCP-4、嗜酸细胞活化趋化因子、年龄、FAT、葡萄糖、胰岛素 |
对数回归 | MIP1α、MCP-2、MCP-4、嗜酸细胞活化趋化因子 |
LDA | MCP-4、嗜酸细胞活化趋化因子、MIP1α |
进一步分析结合了所述预测符,还有前述99位对象的SNP基因型信息。分类误差的5-倍交叉验证百分比降低至10%,而灵敏度提高至85%,特异性提高至92%。在该项分析中,采用简单的拉索法来缩小所包括的SNP数目。并且,用某基因内SNP信息的CART来估算所有缺失的SNP值。
总之,这些分析强有力地明显支持了本文所述的发明。尽管只评估了少量分析物和临床变量,但通过多种方法获得了相当好的分类结果。所有方法均对循环趋化因子检测值进行了选择,不同方法之间有重叠,其中,MIP1α、MCP-4和嗜酸细胞活化趋化因子在多种算法中非常突出。这些分析提示基因分型数据可能提供更多的有用信息。目前作为动脉粥样硬化性疾病标准诊断方法的高灵敏度CRP在这些分析中没有用处,这提示:多种疾病相关炎性标记的水平可能提供明显优于现有预测符的改进。
我们通过聚类法(无监督的学习)总结了多项特征和各参数的联合分布。在我们的层次聚类法方法中(图6),列是个体(变量),行是特征。在该算法中,各列各行逐次类聚,目的是产生“相近”的特征组和样品组。看变量的类聚,非常有意思的是,趋化因子MCP-2、MIP1-a、MCP-1、IP-10、嗜酸细胞活化趋化因子和MCP-4紧密群集在一起。空腹胰岛素水平、FAT(BMI和腹围的首要成分)和葡萄糖这些代谢变量也群集在一起,这符合考虑到这些变量在葡萄糖代谢和胰岛素耐受中彼此关联所做的预期。未发现性别和年龄接近任一上述集群,二者保持独立。
令人感兴趣的是,hsCRP未与趋化因子类聚而与代谢变量类聚,表明hsCRP水平与血管炎症的关联度不及多趋化因子签名。如同期望,样品集群在类别成员上是不一致的。这些分析表明,无监督的学习(聚类)不足以进行有监督的学习(分类)。根据迄今所得结果,如果要进行准确分类,必需有这样的分类分案:该分案不仅根据特征而且根据结果(可预示纯以特征为依据对后续观察结果所做的分类)进行组别分类。
实施例5:1330位患者的大型临床试验:准确预测和诊断动脉粥样硬化性 心血管疾病和血管炎症的循环生物标记的签名
验证多标记特征的大型临床试验的血清生物标记数据
受到前期临床试验结果的鼓舞,我们检验了多标记特征是否能在更大的试验中得到验证以及它们是否可用作人类动脉粥样硬化性疾病的高度灵敏、高特异性标记。为此,我们采用包括400例临床显著ASCVD和930位对照的大型临床流行病学研究。该项研究的目标是检验动脉粥样硬化的风险因素和新的其它决定因素。用蛋白质微阵列将报名时收集的血清样品用于同时检测多种炎性标记。此处采用前期研究所用的精确法(exact method)(详见前述实施例)。一亚组分析物的浓度病例中明显较高。用这些标记的血清表达特征,分类算法根据与对照的比较对CAD病例进行了准确的分级。此外,由生物标记形成的签名明显提高了其它已知CAD标记的预测能力。该较大试验不仅验证了我们先前的发现,还为使用多标记方法来准确预测和诊断动脉粥样硬化性心血管疾病及其各种临床后遗症提供了更多实例。
预测动脉粥样硬化性疾病:选择高信息含量的标记
选择多个高信息含量标记来构建分类模型需要限定性能指标和用户定义的阈值,从而能根据该指标构成具有实用预测能力的模型。后文中,我们将目标量值(target quantity)定为“曲线下面积”(AUC),预测的灵敏度和/或特异性以及预测模型的总准确率。
现在开始描述选择构建预测模型的项数的一种方法。在该实施方式中,我们描述了在没有任何临床变量和/或调节因子存在下选择标记的方法。该方法如下所述:我们首先将我们的训练数据随机分成10组,各组包括“健康”或“患病”的对象,各自与它们在全体样品中的数量成正比。各对象用其24种标记的检测值和疾病状态标签(无标签表示“健康”,有标签则为“患病”)。我们选择9组,就24种标记中的每一种(MCP-1、IGF-1、TNFα、IL-5、M-CSF、MCP-2、IP10、MCP-4、IL-3、IFNγ、Ang-2、IL-7、IL-10、嗜酸细胞活化趋化因子、IL-2、IL-4、ICAM-1、IL-6、IL-12p40、MIP1a、IL-5、MCP-3、IL13、IL1b)用给定的算法(例如线性辨别分析、二次方程辨别分析、对数回归等)用9组的所有数据训练模型(即,我们创建了一训练亚组)。然后我们将该模型应用于没有参加训练的第10组,我们对检测误差“e”和或许多上述预测质量指标值(quality measure)进行了估算。我们重复以上过程10次,每次随机取样9组来产生训练样本并用第10组来估算检验误差“e”和预测质量指标值。然后,我们用这10份数据构成的样本估算各质量指标值和/或误差以及我们估算值方差的预期值。已知这些数值后,将能提高模型的平均预测能力的标记选作模型的第一项。我们可改用另一改善指标来替代预测质量指标平均值,例如,我们可改选预期质量指标值与其方差估算值的比值最高的项目。将第一项加入该模型后,我们对在当前选择步骤中未被中选的其余标记重复上述过程。这样,在第二步骤中,我们对其余标记重复上述计算。通过选择最能提高我们的目标预测质量指标值的选项,或用当前模型预期值的某种组合减去新模型的值并就那些指标的误差标准化,来选择第二模型项。
图12显示了将该方法应用于一组1300个对象的结果。我们选择AUC>0.75为阈值作为我们的目标预测质量指标,我们用线性辨别分析模型选择项目。
使用以下标记:MCP-1满足质量阈值。
图13显示了用对数回归模型选择项目的结果,其中,诊断样品(discoverysample)和质量阈值不变。与之前的实施例比较发现,两种模型只有头两项相同(MCP-1、IGF-1),第三项不同(TNFα比之M-CSF)。因此,我们可采用多种标记和多种预测模型的组合,这将超越我们的质量阈值。
为证实我们能替换标记而仍然满足某预测质量指标的要求,我们从用于选择的可用标记组合中除去标记MCP-1并重复以上方法。图14给出使用LDA模型和前述1300位对象所得的结果。新的一组两种标记包括Ang-2、IGF-1,这两种二标记能提供AUC>0.75的模型。
作为不同选择标准的实例,我们提供了采用AIC标准在对数模型框架内获得的结果。该标准通常用于选择对数回归模型的最佳项数。该标准平衡了因除去某项导致的误差增加与自由度降低(失去了原由该相为模型提供的自由度)。减项过程通常始于完整模型,终止于某项的除去导致AIC值升高之时。图15a示出了减项结果与AIC标准的函数关系(所示减项过程超过了最佳点)。图15b显示了一模型随项数增加的AUC预测情况。按照从完整模型即包含所有24种标记的模型中减项(主要按AIC标准选择项目)相反的顺序在上述模型中加入项。后一方法(减项)利用至少一种标记(MCP-1)产生了一个预计AUC>0.75的对数回归模型。
可采用前向选择(本实施例中的第一、第二和第三例)或反向选择(本实施例中的第四例)或前向/反向选择方案完成项目选择。该方案能检验所有在前一步骤中从当前缩减模型中除去的项。
相同的选择方法可拓展为同时包括标记和临床变量。后面的两幅图显示了以下情况的结果:对数回归模型的候选变量在全部16种标记之外还包括“高脂血症”(DC912)和“索引日(index day)之前的160天内使用过降脂药物”(图16)或“使用他汀类药物”、“使用ACE阻断剂”(图17)。这些实施例表明,可用组中的临床变量替换获得AUC>0.75所需的至少3标记组中的标记。高脂血症(DC912)和MCP-4组合所获得模型的AUC预期值约为0.85。
采用上述方法,我们还能选定了无需使用所有标记来优化模型性的标记数目。确定最佳项数的一种方法是选择能获得具有如下所述平均预测能力(以AUC检测,或相当的灵敏度/特异性指标)的模型的项数,所述平均预测能力与各种组合和各种数量的给定算法所得最高值相差不超过1个标准偏差。再看图17,包括以下标记的对数回归模型满足了这些要求:DC512、DC3005、MCP-4、IGF-1、M-CSF、IL-5、MCP-2、IP-10。
实施例6:ACE抑制剂反应预测模型
采用实施例5所述的方法,我们用对数回归或线性辨别分析建立了能根据ACE抑制剂实用情况分类样品的模型。按照对象状态(对照或病例)调整这些模型,因为标记的总水平取决于我们的试验对象是否健康。这些模型可用于多种方法,例如筛选化合物来鉴定可用作ACE抑制剂或作用于会聚性途径(convergent pathway)的其它物质以及监测ACE抑制剂的疗效。在第一个实施例中,将所述化合物给予哺乳动物对象,采集所述对象的一份或多份样品,获得一份或多份样品的数据集。这些数据集经ACE抑制剂反应预测模型处理,用所得结果来分类样品。如果样品分类为来自ACE抑制剂用药者,则该化合物可能是推定ACE抑制剂。在第二个实施例中,获得对象的一份或多份样品,由那些样品所得的数据集经ACE抑制剂反应预测模型处理。如果样品分类为来自ACE抑制剂用药者,则治疗可能有效。如果随时间多次取样显示从该模型获得的预测符值有时间依赖性改变,则药物治疗的疗效可能正在改变,预测符值趋近于用药分类指标还是趋近于非用药分类指标指示着疗效改变的方向。示例性模型所用的蛋白质标记连同模型的性能特征见下表5和6。
表5.ACE抑制剂预测模型1
对数回归
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.365 0.688 0.641 0.632 0.635
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
表6.ACE抑制剂预测模型2
线性辨别分析
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.376 0.689 0.632 0.620 0.624
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
实施例7:ACE抑制剂或他汀类药物使用情况预测模型
采用实施例5所述的方法,我们用对数回归或线性辨别分析建立了能根据ACE抑制剂或他汀类药物实用情况分类样品的模型。按照对象状态(对照或病例)调整这些模型,因为标记的总水平取决于我们的试验对象是否健康。这些模型可用于多种方法,例如筛选化合物来鉴定可用作ACE抑制剂或他汀类药物或作用于收缩途径的其它物质以及监测ACE抑制剂或他汀类药物的疗效。在第一个实施例中,将所述化合物给予哺乳动物对象,采集所述对象的一份或多份样品,获得一份或多份样品的数据集。这些数据集经ACE抑制剂或他汀类药物使用情况预测模型处理,利用所得结果来分类样品。如果样品分类为来自ACE抑制剂或他汀类药物用药者,则化合物可能是推定的ACE抑制剂或他汀类药物。在第二个实施例中,获得对象的一份或多份样品,由那些样品所得的数据集经ACE抑制剂或他汀类药物使用情况预测模型处理。如果样品分类为来自ACE抑制剂或他汀类药物用药者,则治疗可能有效。如果随时间多次取样显示从该模型获得的预测符值有时间依赖性改变,则药物治疗的疗效可能正在改变,预测符值趋近于用药分类指标还是趋近于非用药分类指标指示着疗效改变的方向。示例性模型所用的蛋白质标记连同模型的性能特征见下表7和8。
药物应用反应的生物标记分布
我们的研究表明,标记组可用于监测药物对炎症水平的作用。检查多个标记(IL-2、IL-5、IL-4)的数值分布,我们证明剂量作用是对照接受药物治疗数量的函数(即,无药物治疗比之一种药物治疗或两种药物)。作为该方案的一个实例,我们用3种药物反应性标记作为一组(IL-2、IL-4和IL-5)。为产生单一组合评分(singlecombined score),我们建立了线性辨别分析模型,其中,反应变量取以下值:“未治疗的”、“ACE或他汀类药物”、“ACE和他汀类药物”,并且,我们将第一辨别变量用作组合评分的替代品。图18显示了被认为“健康”(“对照”)的对象的结果,所示为三个“治疗”组各自的箱线图。各箱线图的灰色部分从各类别的数值分布的第一分位数延伸到第三分位数。为有助于目测观察类别之间中值水平的差异,在中值附近加了“凹口”。引线(whisker)的延伸长度为分位数间距(interquantiledistance)的1.5倍。该图中未包括溢出值。组合评分明显随药物数目增加而显示下降趋势。各组的凹口几乎不重叠这一事实表明中值的差异非常显著。生物标记组的表现优于单用一种生物标记。
可采用霍特林T2方法获得多种标记的单一评分,由此进行相似的分析。此时,我们能根据霍特林公式估算未治疗组数据的协方差矩阵,计算各对象的“距离”。这后一方法不仅可用于建立许多标记的“组合距离(combined distance)”来监测药物剂量效应,还可用于对剂量效应作推定性检验。(参见纳入本文作为参考的Hotelling,H.(1947).Multivariate Quality Control.刊于C.Eisenhart,M.W.Hastay和W.A.Wallis编,Techniques of Statistical Analysis.纽约:麦克劳-希尔公司(McGraw-Hill.))。
表7.ACE抑制剂或他汀类药物预测模型1
对数回归
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.318 0.751 0.643 0.723 0.682
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
表8.ACE抑制剂或他汀类药物预测模型2
线性辨别分析
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.320 0.754 0.686 0.673 0.680
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
实施例8:冠状动脉钙化度预测模型
采用实施例5所述的方法,我们用对数回归或线性辨别分析建立了能根据预测的冠状动脉钙化度分类样品的模型。示例性模型所用的蛋白质标记连同模型的性能特征见下表9和10。
表9.冠状动脉钙化度预测模型1
对数回归
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.470 0.536 0.567 0.500 0.530
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
表10.冠状动脉钙化度预测模型2
线性辨别分析
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.461 0.560 0.578 0.505 0.539
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
实施例9:稳定与不稳定动脉粥样硬化性疾病预测模型
采用实施例5所述的方法,我们用对数回归或线性辨别分析建立能将样品分类为稳定(即心绞痛)类或不稳定(即心肌梗塞)类的模型。示例性模型所用的蛋白质标记连同模型的性能特征见下表11和12。
表11.稳定与不稳定疾病预测模型1
对数回归
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.438 0.566 0.563 0.562 0.562
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
表12.稳定与不稳定疾病预测模型2
线性辨别分析
所用的变量: 分类误 AUC 灵敏度 特异性 准确率
差
MCP-1、IGF-1、TNFa、MCP-2、 0.444 0.577 0.583 0.529 0.556
IP10、IL-5、M-CSF、MCP-4、
MCP-3、IL-3、Ang-2、IL-7、
嗜酸细胞活化趋化因子
实施例10:疾病与健康对照预测模型
采用实施例5所述的方法,我们用对数回归或线性辨别分析建立能将样品分类为疾病(即心绞痛或心肌梗塞)类或健康对照类的模型。示例性模型所用的蛋白质标记连同模型的性能特征见下表13和14。表13和14还表明模型的性能如何随标记的组合被取代而改变。
表13.疾病与对照预测模型1
线性辨别分析
分类误
所用的变量: 差 AUC 灵敏度 特异性 准确率
MCP-1、IGF-1、TNFa、MCP-2、IP10、
IL-5、M-CSF、MCP-4、MCP-3、IL-3、
Ang-2、IL-7、嗜酸细胞活化趋化因子 0.158 0.915 0.847 0.840 0.842
MCP-1、IGF-1、TNFa 0.245 0.827 0.804 0.733 0.755
MCP-1、IGF-1、M-CSF 0.235 0.825 0.786 0.756 0.765
Ang-2、IGF-1、M-CSF 0.258 0.798 0.718 0.753 0.742
MCP-4、IGF-1、M-CSF 0.258 0.789 0.721 0.750 0.742
MCP-1、IGF-1、TNFa、IL-5 0.225 0.850 0.817 0.757 0.775
MCP-1、IGF-1、M-CSF、MCP-2 0.227 0.842 0.801 0.760 0.773
Ang-2、IGF-1、M-CSF、IL-5 0.239 0.816 0.754 0.764 0.761
MCP-1、IGF-1、TNFa、MCP-2 0.240 0.842 0.792 0.746 0.760
MCP-1、IGF-1、TNFa、IL-5、M-CSF 0.213 0.867 0.837 0.765 0.787
MCP-1、IGF-1、IP10、MCP-2、M-CSF 0.184 0.874 0.807 0.821 0.816
Ang-2、IGF-1、TNFa、IL-5、M-CSF 0.216 0.855 0.807 0.774 0.784
MCP-1、IGF-1、TNFa、MCP-2、IP10 0.203 0.878 0.784 0.802 0.797
MCP-4、IGF-1、M-CSF、TNFa、IL-5 0.221 0.855 0.812 0.765 0.779
MCP-4、IGF-1、M-CSF、MCP-2、IL-5 0.246 0.807 0.736 0.761 0.754
表14.疾病与对照预测模型2
对数回归
分类误
所用的变量: 差 AUC 灵敏度 特异性 准确率
MCP-1、IGF-1、TNFa、MCP-2、IP10、
IL-5、M-CSF、MCP-4、MCP-3、IL-3、
Ang-2、IL-7、嗜酸细胞活化趋化因子 0.153 0.916 0.859 0.841 0.847
MCP-1、IGF-1、TNFa 0.237 0.835 0.804 0.745 0.763
MCP-1、IGF-1、M-CSF 0.239 0.831 0.789 0.749 0.761
Ang-2、IGF-1、M-CSF 0.257 0.799 0.734 0.747 0.743
MCP-4、IGF-1、M-CSF 0.258 0.792 0.733 0.745 0.742
MCP-1、IGF-1、TNFa、IL-5 0.221 0.856 0.826 0.759 0.779
MCP-1、IGF-1、M-CSF、MCP-2 0.236 0.845 0.794 0.750 0.764
Ang-2、IGF-1、M-CSF、IL-5 0.243 0.813 0.766 0.754 0.757
MCP-1、IGF-1、TNFa、MCP-2 0.235 0.849 0.784 0.757 0.765
MCP-1、IGF-1、TNFa、IL-5、M-CSF 0.212 0.868 0.832 0.769 0.788
MCP-1、IGF-1、IP10、MCP-2、M-CSF 0.187 0.876 0.804 0.816 0.813
Ang-2、IGF-1、TNFa、IL-5、M-CSF 0.220 0.855 0.801 0.771 0.780
MCP-1、IGF-1、TNFa、MCP-2、IP10 0.202 0.881 0.794 0.799 0.798
MCP-4、IGF-1、M-CSF、TNFa、IL-5 0.223 0.857 0.807 0.764 0.777
MCP-4、IGF-1、M-CSF、MCP-2、IL-5 0.258 0.810 0.734 0.746 0.742
实施例11:利用LDA模型的分类
我们根据以下标记的数值将患者分为“对照”或“疾病”:MCP-1、IGF-1和TNFa。两类取相等的分类误差成本。根据LDA方法,如果方程(1)的左侧大于该方程的右侧,则将上述标记的值为x的新对象分入“疾病”类,方程中:
a)指数2对应于“疾病”状态
b)指数1对应于“对照”状态
c)N是训练组的总规模
d)N1、N2是训练组中“对照”和“疾病”对象的数量
e)∑是用训练组估算的协方差矩阵
f)μ1,2 are分别是“对照”和“疾病”样品的均值向量。
为构建用于预测的LDA模型,我们使用包括上述3种标记值的训练组,对象包括398位“对照”和398位“疾病”对象。标记值先转换为log10值,用所得数值估算方程1所需的各项。训练组的协方差矩阵和均值向量等于:
协方差矩阵:
MCP-1 IGF-1 TNFa
MCP-1 0.124155 0.069587 0.06659
IGF-1 0.069587 1.321971 0.664374
TNFa 0.06659 0.664374 0.565535
“对照”和“疾病”状态的均值标记向量:
对照 | 1.891552 | 2.830981 | 0.781913 |
疾病 | 1.223976 | 2.324683 | 0.990313 |
方程1所需的协方差矩阵的逆阵是:
V1 V2 V3
1 8.607599 0.13735 -1.17487
2 0.13735 1.848967 -2.18828
3 -1.17487 -2.18828 4.477304
我们分类具有以下数值(经log10转换)的对象:
对象1:
MCP-1 | IGF-1 | TNFa |
0.716998 | 1.316101 | 0.287882 |
根据这些数值和方程1,方程的左侧等于0.5291794,而方程的右侧等于3.232524。根据左侧小于右侧的事实,该对象分类为“对照”。
我们分类具有以下log10转换后标记数值的第二位对象:
对象2:
MCP-1 | IGF-1 | TNFa |
1.991509 | 1.1113031 | 0.536339 |
根据这些数值和利用方程1,方程的左侧等于4.461167,而方程的右侧依旧是3.232524。根据该比较,该对象分类为“疾病”。
本实施例和以下实施例参考纳入本文作为参考的“The elements ofStatistical Learning.Data Mining,Inference and Prediction”,Hastie,T.,Tibshirani,R.,Friedman,J.,Springer Series in Statistics,2001)。
实施例12:利用对数回归模型分类
我们根据以下标记的数值将患者分为“对照”或“疾病”:MCP-1、IGF-1和M-CSF。两类取相等的分类误差成本。根据对数回归方法,如果k类(=疾病)与K类(=对照)的后验概率(posterior probability)比值的对数大于0,则将上述标记数值为x的新对象归入疾病类,否则其归为对照(方程2)。
为拟合对数回归模型,我们使用的训练组包括398位“对照”和398位“疾病”对象。各对象的三种标记的数值经先转换为log10值。对数回归拟合提供了以下系数:
b0 | b1 | b2 | b3 |
-4.95059 | 3.334 | -1.27675 | 1.279328 |
分类了所述三种标记具有以下数值的新对象:
MCP-1 | IGF-1 | M-CSF | |
对象1 | 1.679931 | 3.493781 | 1.169145 |
以下计算式b0+b1*`MCP-1`+b2*`IGF-1`+b3*`M-CSF`等于-2.031。如上所述,该对象的线性预测符值小于0,分类为“对照”。
根据以下数值分类另一位对象:
MCP-1 | IGF-1 | M-CSF | |
对象2 | 2.108252 | 1.7149 | 0.539566 |
采用相同的系数和公式,线性预测符等于0.5799186,对象2分类为“疾病”。
本说明书引用的各出版物出于所有目的全文纳入本文作为参考。除了在本说明书全文中所列的那些出版物,以下出版物也出于所有目的全文纳入本文作为参考:Tabibiazar R,Wagner RA,Deng A,Tsao PS,Quertermous T.Proteomic profilesof serum inflammatory markers accurately predict atherosclerosis in mice.PhysiolGenomics.2006年4月13日;25(2):194-202。
序列表
<110>R.塔比比亚扎(TABIBIAZAR,RAYMOND)
P.S.曹(TSAO,PHILIP S.)
T.科特莫斯(QUERTERMOUS,THOMAS)
B.K.特尔布尔(TURNBULL,BRIT KATZEN)
R.奥尔森(OLSHEN,RICHARD A.)
E.海托普罗斯(HYTOPOULOS,EVANGELOS)
<120>诊断和监测动脉粥样硬化性心血管疾病的方法和组合物
<130>STAN-410WO
<140>
<141>
<150>60/693,756
<151>2005-06-24
<160>360
<170>PatentIn version 3.3
<210>1
<211>760
<212>DNA
<213>智人(Homo sapiens)
<400>1
gaggaaccga gaggctgaga ctaacccaga aacatccaat tctcaaactg aagctcgcac 60
tctcgcctcc agcatgaaag tctctgccgc ccttctgtgc ctgctgctca tagcagccac 120
cttcattccc caagggctcg ctcagccaga tgcaatcaat gccccagtca cctgctgtta 180
taacttcacc aataggaaga tctcagtgca gaggctcgcg agctatagaa gaatcaccag 240
cagcaagtgt cccaaagaag ctgtgatctt caagaccatt gtggccaagg agatctgtgc 300
tgaccccaag cagaagtggg ttcaggattc catggaccac ctggacaagc aaacccaaac 360
tccgaagact tgaacactca ctccacaacc caagaatctg cagctaactt attttcccct 420
agctttcccc agacaccctg ttttatttta ttataatgaa ttttgtttgt tgatgtgaaa 480
cattatgcct taagtaatgt taattcttat ttaagttatt gatgttttaa gtttatcttt 540
catggtacta gtgtttttta gatacagaga cttggggaaa ttgcttttcc tcttgaacca 600
cagttctacc cctgggatgt tttgagggtc tttgcaagaa tcattaatac aaagaatttt 660
ttttaacatt ccaatgcatt gctaaaatat tattgtggaa atgaatattt tgtaactatt 720
acaccaaata aatatatttt tgtacaaaaa aaaaaaaaaa 760
<210>2
<211>584
<212>DNA
<213>小鼠(Mus musculus)
<400>2
agtgcagaga gccagacggg aggaaggcca gcccagcacc agcaccagcc aactctcact 60
gaagccagct ctctcttcct ccaccaccat gcaggtccct gtcatgcttc tgggcctgct 120
gttcacagtt gccggctgga gcatccacgt gttggctcag ccagatgcag ttaacgcccc 180
actcacctgc tgctactcat tcaccagcaa gatgatccca atgagtaggc tggagagcta 240
caagaggatc accagcagca ggtgtcccaa agaagctgta gtttttgtca ccaagctcaa 300
gagagaggtc tgtgctgacc ccaagaagga atgggtccag acatacatta aaaacctgga 360
tcggaaccaa atgagatcag aacctacaac tttatttaaa actgcatctg ccctaaggtc 420
ttcagcacct ttgaatgtga agttgacccg taaatctgaa gctaatgcat ccactacctt 480
ttccacaacc acctcaagca cttctgtagg agtgaccagt gtgacagtga actagtgtga 540
ctcggactgt gatgccttaa ttaatattaa acttatttaa ctta 584
<210>3
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>3
Met Lys Val Ser Ala Ala Leu Leu Cys Leu Leu Leu Ile Ala Ala Thr
1 5 10 15
Phe Ile Pro Gln Gly Leu Ala Gln Pro Asp Ala Ile Asn Ala Pro Val
20 25 30
Thr Cys Cys Tyr Asn Phe Thr Asn Arg Lys Ile Ser Val Gln Arg Leu
35 40 45
Ala Ser Tyr Arg Arg Ile Thr Ser Ser Lys Cys Pro Lys Glu Ala Val
50 55 60
Ile Phe Lys Thr Ile Val Ala Lys Glu Ile Cys Ala Asp Pro Lys Gln
65 70 75 80
Lys Trp Val Gln Asp Ser Met Asp His Leu Asp Lys Gln Thr Gln Thr
85 90 95
Pro Lys Thr
<210>4
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>4
Met Lys Val Ser Ala Ala Leu Leu Cys Leu Leu Leu Ile Ala Ala Thr
1 5 10 15
Phe Ile Pro Gln Gly Leu Ala Gln Pro Asp Ala Ile Asn Ala Pro Val
20 25 30
Thr Cys Cys Tyr Asn Phe Thr Asn Arg Lys Ile Ser Val Gln Arg Leu
35 40 45
Ala Ser Tyr Arg Arg Ile Thr Ser Ser Lys Cys Pro Lys Glu Ala Val
50 55 60
Ile Phe Lys Thr Ile Val Ala Lys Glu Ile Cys Ala Asp Pro Lys Gln
65 70 75 80
Lys Trp Val Gln Asp Ser Met Asp His Leu Asp Lys Gln Thr Gln Thr
85 90 95
Pro Lys Thr
<210>5
<211>25
<212>PRT
<213>智人(Homo sapiens)
<400>5
Met Lys Val Ser Ala Ala Leu Leu Cys Leu Leu Leu Ile Ala Ala Thr
1 5 10 15
Phe Ile Pro Gln Gly Leu Ala Gln Pro
20 25
<210>6
<211>148
<212>PRT
<213>小鼠(Mus musculus)
<400>6
Met Gln Val Pro Val Met Leu Leu Gly Leu Leu Phe Thr Val Ala Gly
1 5 10 15
Trp Ser Ile His Val Leu Ala Gln Pro Asp Ala Val Asn Ala Pro Leu
20 25 30
Thr Cys Cys Tyr Ser Phe Thr Ser Lys Met Ile Pro Met Ser Arg Leu
35 40 45
Glu Ser Tyr Lys Arg Ile Thr Ser Ser Arg Cys Pro Lys Glu Ala Val
50 55 60
Val Phe Val Thr Lys Leu Lys Arg Glu Val Cys Ala Asp Pro Lys Lys
65 70 75 80
Glu Trp Val Gln Thr Tyr Ile Lys Asn Leu Asp Arg Asn Gln Met Arg
85 90 95
Ser Glu Pro Thr Thr Leu Phe Lys Thr Ala Ser Ala Leu Arg Ser Ser
100 105 110
Ala Pro Leu Asn Val Lys Leu Thr Arg Lys Ser Glu Ala Asn Ala Ser
115 120 125
Thr Thr Phe Ser Thr Thr Thr Ser Ser Thr Ser Val Gly Val Thr Ser
130 135 140
Val Thr Val Asn
145
<210>7
<211>148
<212>PRT
<213>小鼠(Mus musculus)
<400>7
Met Gln Val Pro Val Met Leu Leu Gly Leu Leu Phe Thr Val Ala Gly
1 5 10 15
Trp Ser Ile His Val Leu Ala Gln Pro Asp Ala Val Asn Ala Pro Leu
20 25 30
Thr Cys Cys Tyr Ser Phe Thr Ser Lys Met Ile Pro Met Ser Arg Leu
35 40 45
Glu Ser Tyr Lys Arg Ile Thr Ser Ser Arg Cys Pro Lys Glu Ala Val
50 55 60
Val Phe Val Thr Lys Leu Lys Arg Glu Val Cys Ala Asp Pro Lys Lys
65 70 75 80
Glu Trp Val Gln Thr Tyr Ile Lys Asn Leu Asp Arg Asn Gln Met Arg
85 90 95
Ser Glu Pro Thr Thr Leu Phe Lys Thr Ala Ser Ala Leu Arg Ser Ser
100 105 110
Ala Pro Leu Asn Val Lys Leu Thr Arg Lys Ser Glu Ala Asn Ala Ser
115 120 125
Thr Thr Phe Ser Thr Thr Thr Ser Ser Thr Ser Val Gly Val Thr Ser
130 135 140
Val Thr Val Asn
145
<210>8
<211>148
<212>PRT
<213>小鼠(Mus musculus)
<400>8
Met Gln Val Pro Val Met Leu Leu Gly Leu Leu Phe Thr Val Ala Gly
1 5 10 15
Trp Ser Ile His Val Leu Ala Gln Pro Asp Ala Val Asn Ala Pro Leu
20 25 30
Thr Cys Cys Tyr Ser Phe Thr Ser Lys Met Ile Pro Met Ser Arg Leu
35 40 45
Glu Ser Tyr Lys Arg Ile Thr Ser Ser Arg Cys Pro Lys Glu Ala Val
50 55 60
Val Phe Val Thr Lys Leu Lys Arg Glu Val Cys Ala Asp Pro Lys Lys
65 70 75 80
Glu Trp Val Gln Thr Tyr Ile Lys Asn Leu Asp Arg Asn Gln Met Arg
85 90 95
Ser Glu Pro Thr Thr Leu Phe Lys Thr Ala Ser Ala Leu Arg Ser Ser
100 105 110
Ala Pro Leu Asn Val Lys Leu Thr Arg Lys Ser Glu Ala Asn Ala Ser
115 120 125
Thr Thr Phe Ser Thr Thr Thr Ser Ser Thr Ser Val Gly Val Thr Ser
130 135 140
Val Thr Val Asn
145
<210>9
<211>1351
<212>DNA
<213>智人(Homo sapiens)
<400>9
gtgatggaga gcaccagcaa agccttaggg cccatccctg gcctcctgtt acccacagag 60
gggtaggccc ttggctctct tccactatga cgtcagcttc cattcttcct ttcttataga 120
caattttcca tttcaaggaa atcagagccc ttaatagttc agtgaggtca ctttgctgag 180
cacaatccca tacccttcag cctctgctcc acagagccta agcaaaagat agaaactcac 240
aacttccttg ttttgttatc tggaaattat cccaggatct ggtgcttact cagcatattc 300
aaggaaggtc ttacttcatt cttccttgat tgtgaccatg cccaggctct ctgctcccta 360
taaaaggcag gcagagccac cgaggagcag agaggttgag aacaacccag aaaccttcac 420
ctctcatgct gaagctcaca cccttgccct ccaagatgaa ggtttctgca gcgcttctgt 480
gcctgctgct catggcagcc actttcagcc ctcagggact tgctcagcca gattcagttt 540
ccattccaat cacctgctgc tttaacgtga tcaataggaa aattcctatc cagaggctgg 600
agagctacac aagaatcacc aacatccaat gtcccaagga agctgtgatc ttcaagacca 660
aacggggcaa ggaggtctgt gctgacccca aggagagatg ggtcagggat tccatgaagc 720
atctggacca aatatttcaa aatctgaagc catgagcctt catacatgga ctgagagtca 780
gagcttgaag aaaagcttat ttattttccc caacctcccc caggtgcagt gtgacattat 840
tttattataa catccacaaa gagattattt ttaaataatt taaagcataa tatttcttaa 900
aaagtattta attatattta agttgttgat gttttaactc tatctgtcat acatcctagt 960
gaatgtaaaa tgcaaaatcc tggtgatgtg ttttttgttt ttgttttcct gtgagctcaa 1020
ctaagttcac ggcaaaatgt cattgttctc cctcctacct gtctgtagtg ttgtggggtc 1080
ctcccatgga tcatcaaggt gaaacacttt ggtattcttt ggcaatcagt gctcctgtaa 1140
gtcaaatgtg tgctttgtac tgctgttgtt gaaattgatg ttactgtata taactatgga 1200
attttgaaaa aaaatttcaa aaagaaaaaa atatatataa tttaaaacta aaaaaaaaaa 1260
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1320
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa a 1351
<210>10
<211>516
<212>DNA
<213>小鼠(Mus musculus)
<400>10
gaattcggca cgagggattg agaggacgct agccttcact ccaaaatctt tgccttcaac 60
atgaagatct acgcagtgct tctttgcctg ctgctcatag ctgtccctgt cagcccagag 120
aagctgactg ggccagataa ggctccagtc acctgctgct ttcatgtact aaagctgaag 180
atcccccttc gggtgctgaa aagctacgag agaatcaaca atatccagtg ccccatggaa 240
gctgtggttt tccagaccaa gcagggtatg tctctctgtg tagaccccac acagaagtgg 300
gtcagtgagt acatggagat ccttgaccag aagtctcaaa ttctgcagcc ttgaaccttc 360
acacctgagt taagagacag ccaaagctgg aagttctccc ctaatcttct ccaggcagag 420
agatgttaca agcagatggt gcctgggctg cgtgttttct catccttgtc tgttatatga 480
acaactgaaa taaaagctta cactgatttg caaatt 516
<210>11
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>11
Met Lys Val Ser Ala Ala Leu Leu Cys Leu Leu Leu Met Ala Ala Thr
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gln Pro Asp Ser Val Ser Ile Pro Ile
20 25 30
Thr Cys Cys Phe Asn Val Ile Asn Arg Lys Ile Pro Ile Gln Arg Leu
35 40 45
Glu Ser Tyr Thr Arg Ile Thr Asn Ile Gln Cys Pro Lys Glu Ala Val
50 55 60
Ile Phe Lys Thr Lys Arg Gly Lys Glu Val Cys Ala Asp Pro Lys Glu
65 70 75 80
Arg Trp Val Arg Asp Ser Met Lys His Leu Asp Gln Ile Phe Gln Asn
85 90 95
Leu Lys Pro
<210>12
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>12
Met Lys Val Ser Ala Ala Leu Leu Cys Leu Leu Leu Met Ala Ala Thr
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gln Pro Asp Ser Val Ser Ile Pro Ile
20 25 30
Thr Cys Cys Phe Asn Val Ile Asn Arg Lys Ile Pro Ile Gln Arg Leu
35 40 45
Glu Ser Tyr Thr Arg Ile Thr Asn Ile Gln Cys Pro Lys Glu Ala Val
50 55 60
Ile Phe Lys Thr Lys Arg Gly Lys Glu Val Cys Ala Asp Pro Lys Glu
65 70 75 80
Arg Trp Val Arg Asp Ser Met Lys His Leu Asp Gln Ile Phe Gln Asn
85 90 95
Leu Lys Pro
<210>13
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>13
Met Lys Ile Tyr Ala Val Leu Leu Cys Leu Leu Leu Ile Ala Val Pro
1 5 10 15
Val Ser Pro Glu Lys Leu Thr Gly Pro Asp Lys Ala Pro Val Thr Cys
20 25 30
Cys Phe His Val Leu Lys Leu Lys Ile Pro Leu Arg Val Leu Lys Ser
35 40 45
Tyr Glu Arg Ile Asn Asn Ile Gln Cys Pro Met Glu Ala Val Val Phe
50 55 60
Gln Thr Lys Gln Gly Met Ser Leu Cys Val Asp Pro Thr Gln Lys Trp
65 70 75 80
Val Ser Glu Tyr Met Glu Ile Leu Asp Gln Lys Ser Gln Ile Leu Gln
85 90 95
Pro
<210>14
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>14
Met Lys Ile Tyr Ala Val Leu Leu Cys Leu Leu Leu Ile Ala Val Pro
1 5 10 15
Val Ser Pro Glu Lys Leu Thr Gly Pro Asp Lys Ala Pro Val Thr Cys
20 25 30
Cys Phe His Val Leu Lys Leu Lys Ile Pro Leu Arg Val Leu Lys Ser
35 40 45
Tyr Glu Arg Ile Asn Asn Ile Gln Cys Pro Met Glu Ala Val Val Phe
50 55 60
Gln Thr Lys Gln Gly Met Ser Leu Cys Val Asp Pro Thr Gln Lys Trp
65 70 75 80
Val Ser Glu Tyr Met Glu Ile Leu Asp Gln Lys Ser Gln Ile Leu Gln
85 90 95
Pro
<210>15
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>15
Met Lys Ile Tyr Ala Val Leu Leu Cys Leu Leu Leu Ile Ala Val Pro
1 5 10 15
Val Ser Pro Glu Lys Leu Thr Gly Pro Asp Lys Ala Pro Val Thr Cys
20 25 30
Cys Phe His Val Leu Lys Leu Lys Ile Pro Leu Arg Val Leu Lys Ser
35 40 45
Tyr Glu Arg Ile Asn Asn Ile Gln Cys Pro Met Glu Ala Val Val Phe
50 55 60
Gln Thr Lys Gln Gly Met Ser Leu Cys Val Asp Pro Thr Gln Lys Trp
65 70 75 80
Val Ser Glu Tyr Met Glu Ile Leu Asp Gln Lys Ser Gln Ile Leu Gln
85 90 95
Pro
<210>16
<211>810
<212>DNA
<213>智人(Homo sapiens)
<400>16
agcagagggg ctgagaccaa accagaaacc tccaattctc atgtggaagc ccatgccctc 60
accctccaac atgaaagcct ctgcagcact tctgtgtctg ctgctcacag cagctgcttt 120
cagcccccag gggcttgctc agccagttgg gattaatact tcaactacct gctgctacag 180
atttatcaat aagaaaatcc ctaagcagag gctggagagc tacagaagga ccaccagtag 240
ccactgtccc cgggaagctg taatcttcaa gaccaaactg gacaaggaga tctgtgctga 300
ccccacacag aagtgggtcc aggactttat gaagcacctg gacaagaaaa cccaaactcc 360
aaagctttga acattcatga ctgaactaaa aacaagccat gacttgagaa acaaataatt 420
tgtataccct gtcctttctc agagtggttc tgagattatt ttaatctaat tctaaggaat 480
atgagcttta tgtaataatg tgaatcatgg tttttcttag tagattttaa aagttattaa 540
tattttaatt taatcttcca tggattttgg tgggttttga acataaagcc ttggatgtat 600
atgtcatctc agtgctgtaa aaactgtggg atgctcctcc cttctctacc tcatgggggt 660
attgtataag tccttgcaag aatcagtgca aagatttgct ttaattgtta agatatgatg 720
tccctatgga agcatattgt tattatataa ttacatattt gcatatgtat gactcccaaa 780
ttttcacata aaatagattt ttgtaaaaaa 810
<210>17
<211>911
<212>DNA
<213>小鼠(Mus musculus)
<400>17
agagaagcaa ggccagcaca gagtctgcca gctctcactg aagccagctc tctcactctc 60
tttctccacc atgaggatct ctgccacgct tctgtgcctg ctgctcatag ccgctgcttt 120
cagcatccaa gtgtgggccc aaccagatgg gcccaatgca tccacatgct gctatgtcaa 180
gaaacaaaag atccccaaga ggaatctcaa gagctacaga aggatcacca gtagtcggtg 240
tccctgggaa gctgttatct tcaagacaaa gaagggcatg gaagtctgtg ctgaagccca 300
tcagaagtgg gtcgaggagg ctatagcata cttagacatg aaaaccccaa ctccaaagcc 360
ttgaagaaat gtgcctgaac agaaaccaac ctaggagcca agaagcaaaa attcctcacc 420
gctgttcttt ctgagaactg ttgatgaaat gtgttgatca cggtcctaag ggataggagc 480
tgtctgtagg aatgtgaaac agtcacgcct aaggaatggt ctttaagtta ttaatatttt 540
tatttaatta gccatgtact ttggtgtgat ttgaatgtaa agctctggag acctcatgtc 600
actttaacat tgtgttagct gcagaattct ccccctttcc ccatttttac tttgttcttg 660
tattatgaag ggactttgca agaatcagtg caaagatttt atttaaaaac ttttaggata 720
aaatcataat gttatgatac tgtgtggttt ttaaatgtat gactactgaa gtttcatata 780
aaatgtattt ttgcacaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 840
aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 900
aaaaaaaaaa a 911
<210>18
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>18
Met Lys Ala Ser Ala Ala Leu Leu Cys Leu Leu Leu Thr Ala Ala Ala
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gln Pro Val Gly Ile Asn Thr Ser Thr
20 25 30
Thr Cys Cys Tyr Arg Phe Ile Asn Lys Lys Ile Pro Lys Gln Arg Leu
35 40 45
Glu Ser Tyr Arg Arg Thr Thr Ser Ser His Cys Pro Arg Glu Ala Val
50 55 60
Ile Phe Lys Thr Lys Leu Asp Lys Glu Ile Cys Ala Asp Pro Thr Gln
65 70 75 80
Lys Trp Val Gln Asp Phe Met Lys His Leu Asp Lys Lys Thr Gln Thr
85 90 95
Pro Lys Leu
<210>19
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>19
Met Lys Ala Ser Ala Ala Leu Leu Cys Leu Leu Leu Thr Ala Ala Ala
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gln Pro Val Gly Ile Asn Thr Ser Thr
20 25 30
Thr Cys Cys Tyr Arg Phe Ile Asn Lys Lys Ile Pro Lys Gln Arg Leu
35 40 45
Glu Ser Tyr Arg Arg Thr Thr Ser Ser His Cys Pro Arg Glu Ala Val
50 55 60
Ile Phe Lys Thr Lys Leu Asp Lys Glu Ile Cys Ala Asp Pro Thr Gln
65 70 75 80
Lys Trp Val Gln Asp Phe Met Lys His Leu Asp Lys Lys Thr Gln Thr
85 90 95
Pro Lys Leu
<210>20
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>20
Met Lys Ala Ser Ala Ala Leu Leu Cys Leu Leu Leu Thr Ala Ala Ala
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gln Pro Val Gly Ile Asn Thr Ser Thr
20 25 30
Thr Cys Cys Tyr Arg Phe Ile Asn Lys Lys Ile Pro Lys Gln Arg Leu
35 40 45
Glu Ser Tyr Arg Arg Thr Thr Ser Ser His Cys Pro Arg Glu Ala Val
50 55 60
Ile Phe Lys Thr Lys Leu Asp Lys Glu Ile Cys Ala Asp Pro Thr Gln
65 70 75 80
Lys Trp Val Gln Asp Phe Met Lys His Leu Asp Lys Lys Thr Gln Thr
85 90 95
Pro Lys Leu
<210>21
<211>109
<212>PRT
<213>智人(Homo sapiens)
<400>21
Met Trp Lys Pro Met Pro Ser Pro Ser Asn Met Lys Ala Ser Ala Ala
1 5 10 15
Leu Leu Cys Leu Leu Leu Thr Ala Ala Ala Phe Ser Pro Gln Gly Leu
20 25 30
Ala Gln Pro Val Gly Ile Asn Thr Ser Thr Thr Cys Cys Tyr Arg Phe
35 40 45
Ile Asn Lys Lys Ile Pro Lys Gln Arg Leu Glu Ser Tyr Arg Arg Thr
50 55 60
Thr Ser Ser His Cys Pro Arg Glu Ala Val Ile Phe Lys Thr Lys Leu
65 70 75 80
Asp Lys Glu Ile Cys Ala Asp Pro Thr Gln Lys Trp Val Gln Asp Phe
85 90 95
Met Lys His Leu Asp Lys Lys Thr Gln Thr Pro Lys Leu
100 105
<210>22
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>22
Met Arg Ile Ser Ala Thr Leu Leu Cys Leu Leu Leu Ile Ala Ala Ala
1 5 10 15
Phe Ser Ile Gln Val Trp Ala Gln Pro Asp Gly Pro Asn Ala Ser Thr
20 25 30
Cys Cys Tyr Val Lys Lys Gln Lys Ile Pro Lys Arg Asn Leu Lys Ser
35 40 45
Tyr Arg Arg Ile Thr Ser Ser Arg Cys Pro Trp Glu Ala Val Ile Phe
50 55 60
Lys Thr Lys Lys Gly Met Glu Val Cys Ala Glu Ala His Gln Lys Trp
65 70 75 80
Val Glu Glu Ala Ile Ala Tyr Leu Asp Met Lys Thr Pro Thr Pro Lys
85 90 95
Pro
<210>23
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>23
Met Arg Ile Ser Ala Thr Leu Leu Cys Leu Leu Leu Ile Ala Ala Ala
1 5 10 15
Phe Ser Ile Gln Val Trp Ala Gln Pro Asp Gly Pro Asn Ala Ser Thr
20 25 30
Cys Cys Tyr Val Lys Lys Gln Lys Ile Pro Lys Arg Asn Leu Lys Ser
35 40 45
Tyr Arg Arg Ile Thr Ser Ser Arg Cys Pro Trp Glu Ala Val Ile Phe
50 55 60
Lys Thr Lys Lys Gly Met Glu Val Cys Ala Glu Ala His Gln Lys Trp
65 70 75 80
Val Glu Glu Ala Ile Ala Tyr Leu Asp Met Lys Thr Pro Thr Pro Lys
85 90 95
Pro
<210>24
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>24
Met Arg Ile Ser Ala Thr Leu Leu Cys Leu Leu Leu Ile Ala Ala Ala
1 5 10 15
Phe Ser Ile Gln Val Trp Ala Gln Pro Asp Gly Pro Asn Ala Ser Thr
20 25 30
Cys Cys Tyr Val Lys Lys Gln Lys Ile Pro Lys Arg Asn Leu Lys Ser
35 40 45
Tyr Arg Arg Ile Thr Ser Ser Arg Cys Pro Trp Glu Ala Val Ile Phe
50 55 60
Lys Thr Lys Lys Gly Met Glu Val Cys Ala Glu Ala His Gln Lys Trp
65 70 75 80
Val Glu Glu Ala Ile Ala Tyr Leu Asp Met Lys Thr Pro Thr Pro Lys
85 90 95
Pro
<210>25
<211>861
<212>DNA
<213>智人(Homo sapiens)
<400>25
aaaaggccgg cggaacagcc agaggagcag agaggcaaag aaacattgtg aaatctccaa 60
ctcttaacct tcaacatgaa agtctctgca gtgcttctgt gcctgctgct catgacagca 120
gctttcaacc cccagggact tgctcagcca gatgcactca acgtcccatc tacttgctgc 180
ttcacattta gcagtaagaa gatctccttg cagaggctga agagctatgt gatcaccacc 240
agcaggtgtc cccagaaggc tgtcatcttc agaaccaaac tgggcaagga gatctgtgct 300
gacccaaagg agaagtgggt ccagaattat atgaaacacc tgggccggaa agctcacacc 360
ctgaagactt gaactctgct acccctactg aaatcaagct ggagtacgtg aaatgacttt 420
tccattctcc tctggcctcc tcttctatgc tttggaatac ttctaccata attttcaaat 480
aggatgcatt cggttttgtg attcaaaatg tactatgtgt taagtaatat tggctattat 540
ttgacttgtt gctggtttgg agtttatttg agtattgctg atcttttcta aagcaaggcc 600
ttgagcaagt aggttgctgt ctctaagccc ccttcccttc cactatgagc tgctggcagt 660
gggtttgtat tcggttccca ggggttgaga gcatgcctgt gggagtcatg gacatgaagg 720
gatgctgcaa tgtaggaagg agagctcttt gtgaatgtga ggtgttgcta aatatgttat 780
tgtggaaaga tgaatgcaat agtaggactg ctgacatttt gcagaaaata cattttattt 840
aaaatctcct aaaaaaaaaa a 861
<210>26
<211>999
<212>DNA
<213>小鼠(Mus musculus)
<400>26
agaatctctc tccaagctgt gaccgacact ggcaagatgc aggccctact attccttatg 60
gcacttctct tgccttctgg ggctggagct gaggagatta ttggtggtgt tgagtctaga 120
ccacattctc gcccttacat ggcccatctg gagatcacca ctgagagagg gttcacagct 180
acctgtggtg ggtttctcat aacccgccaa tttgtgatga ctgctgcaca ctgtagtgga 240
agagaaatca ctgtcaccct tggagctcat gatgtgagca agacagaatc cacacagcag 300
aagataaaag tagaaaaaca aatcgttcac ccaaagtaca acttctattc caatctccat 360
gacatcatgt tactgaagct tcaaaagaaa gccaaagaga ctccctctgt gaatgtaatt 420
cctctgcctc gtccttctga ctttatcaag ccggggaaga tgtgccgggc agctggctgg 480
gggcgaactg gagtgacaga acctacctca gatacactga gggaggtgaa actgagaatc 540
atggataaag aggcctgtaa aaactattgg cattatgact ataacctcca ggtctgcgtg 600
ggcagtccca gaaagaaaag atcggcatac aagggagact ctggaggacc tctactgtgt 660
gctggggtgg cccacggtat tgtatcttat ggacgcggag atgcaaagcc ccctgcagtc 720
ttcacccgaa tctcctcata tgtgccctgg attaacagag tcataaaggg cgagtagtga 780
aaagcctgac ctgcgtgcaa tcagagtctt caagccagag ctcttctaat aacccttggg 840
ttcaacaaag catgtgtcca tcctgtcccc tgcctgcccc cagcctgtcc ccagcctgtc 900
cccagcctgc ccccagcctg cccccaagat gatctgaaag atgaattctg tgatgatgga 960
ctgttccctg taatgcacct cagtaaagac ctaacctcc 999
<210>27
<211>98
<212>PRT
<213>智人(Homo sapiens)
<400>27
Met Lys Val Ser Ala Val Leu Leu Cys Leu Leu Leu Met Thr Ala Ala
1 5 10 15
Phe Asn Pro Gln Gly Leu Ala Gln Pro Asp Ala Leu Asn Val Pro Ser
20 25 30
Thr Cys Cys Phe Thr Phe Ser Ser Lys Lys Ile Ser Leu Gln Arg Leu
35 40 45
Lys Ser Tyr Val Ile Thr Thr Ser Arg Cys Pro Gln Lys Ala Val Ile
50 55 60
Phe Arg Thr Lys Leu Gly Lys Glu Ile Cys Ala Asp Pro Lys Glu Lys
65 70 75 80
Trp Val Gln Asn Tyr Met Lys His Leu Gly Arg Lys Ala His Thr Leu
85 90 95
Lys Thr
<210>28
<211>246
<212>PRT
<213>小鼠(Mus musculus)
<400>28
Met Gln Ala Leu Leu Phe Leu Met Ala Leu Leu Leu Pro Ser Gly Ala
1 5 10 15
Gly Ala Glu Glu Ile Ile Gly Gly Val Glu Ser Arg Pro His Ser Arg
20 25 30
Pro Tyr Met Ala His Leu Glu Ile Thr Thr Glu Arg Gly Phe Thr Ala
35 40 45
Thr Cys Gly Gly Phe Leu Ile Thr Arg Gln Phe Val Met Thr Ala Ala
50 55 60
His Cys Ser Gly Arg Glu Ile Thr Val Thr Leu Gly Ala His Asp Val
65 70 75 80
Ser Lys Thr Glu Ser Thr Gln Gln Lys Ile Lys Val Glu Lys Gln Ile
85 90 95
Val His Pro Lys Tyr Asn Phe Tyr Ser Asn Leu His Asp Ile Met Leu
100 105 110
Leu Lys Leu Gln Lys Lys Ala Lys Glu Thr Pro Ser Val Asn Val Ile
115 120 125
Pro Leu Pro Arg Pro Ser Asp Phe Ile Lys Pro Gly Lys Met Cys Arg
130 135 140
Ala Ala Gly Trp Gly Arg Thr Gly Val Thr Glu Pro Thr Ser Asp Thr
145 150 155 160
Leu Arg Glu Val Lys Leu Arg Ile Met Asp Lys Glu Ala Cys Lys Asn
165 170 175
Tyr Trp His Tyr Asp Tyr Asn Leu Gln Val Cys Val Gly Ser Pro Arg
180 185 190
Lys Lys Arg Ser Ala Tyr Lys Gly Asp Ser Gly Gly Pro Leu Leu Cys
195 200 205
Ala Gly Val Ala His Gly Ile Val Ser Tyr Gly Arg Gly Asp Ala Lys
210 215 220
Pro Pro Ala Val Phe Thr Arg Ile Ser Ser Tyr Val Pro Trp Ile Asn
225 230 235 240
Arg Val Ile Lys Gly Glu
245
<210>29
<211>925
<212>DNA
<213>智人(Homo sapiens)
<400>29
atgggcaaag gcttccctgg aatctcccac actgtctgct ccctataaaa ggcaggcaga 60
tgggccagag gagcagagag gctgagacca acccagaaac caccacctct cacgccaaag 120
ctcacacctt cagcctccaa catgaaggtc tccgcagcac ttctgtggct gctgctcata 180
gcagctgcct tcagccccca ggggctcgct gggccagctt ctgtcccaac cacctgctgc 240
tttaacctgg ccaataggaa gatacccctt cagcgactag agagctacag gagaatcacc 300
agtggcaaat gtccccagaa agctgtgatc ttcaagacca aactggccaa ggatatctgt 360
gccgacccca agaagaagtg ggtgcaggat tccatgaagt atctggacca aaaatctcca 420
actccaaagc cataaataat caccattttt gaaaccaaac cagagcctga gtgttgccta 480
atttgttttc ccttcttaca atgcattctg aggtaacctc attatcagtc caaagggcat 540
gggttttatt atatatatat attttttttt ttaaaaaaaa aacgtattgc atttaattta 600
ttgaggcttt aaaacttatc ctccatgaat atcagttatt tttaaactgt aaagctttgt 660
gcagattctt taccccctgg gagccccaat tcgatcccct gtcacgtgtg ggcaatgttc 720
cccctctcct ctcttcctcc ctggaatctt gtaaaggtcc tggcaaagat gatcagtatg 780
aaaatgtcat tgttcttgtg aacccaaagt gtgactcatt aaatggaagt aaatgttgtt 840
ttaggaatac ataaagtatg tgcatatttt attatagtca ctagttgtaa tttttttgtg 900
ggaaatccac actgagctga ggggg 925
<210>30
<211>982
<212>DNA
<213>小鼠(Mus musculus)
<400>30
tgagaggctg agatccaagc agtaacttcc atctgtctcc ctccaccatg cagagctcca 60
cagcgcttct attcctgctg ctcacggtca cttccttcac ctcccaggtg ctggctcacc 120
caggctccat cccaacttcc tgctgcttta tcatgaccag taagaagatc cccaacacac 180
tactgaagag ctacaaaaga atcaccaaca acagatgcac cctgaaagcc atagtcttca 240
agaccaggtt gggcaaagag atctgtgctg accccaagaa gaagtgggtc caggatgcca 300
caaagcacct ggaccaaaaa ctccaaactc caaaaccata aacaacctcc tctcttgaca 360
ctaacccaga gcctaagaac tgcttgattc cttctctttc ctaagacgtg ctctgaggga 420
atatcagcac cagtcgccca aggacttggc ttcatgtagt tccagatggg actggaagtc 480
attatgtttg ctgaaataag tcagactcaa aagattgtgt aatttcttgc atatgcaaca 540
tcttaaaagg ggggcatgaa aggagatgtg ggattattga ggaacacaat gggacgagtt 600
aggagtaact gaggataata gcagcttata cacatatatg aaaatgtcta ttgttttgca 660
cgaattaata tacactaatt aaaattaatt tacactaact aaaatgttaa tatttaaaga 720
catgttacat ttaagaaatt ggagttttaa agcataattt aatgatatca gtcctttttg 780
ttattgtgtt gtttgtttgc ttgcttgttt gaaacaggga ctcactgtat caccctgact 840
gacctgtaac tcactgtgta gaccaggctg acctcaaact cacagaaatt tacctgcctc 900
tgcctttaag tgctaccatg ccaagccaga atgtttttta ttagatatac caatatatat 960
aataaaatat tttactacaa aa 982
<210>31
<211>97
<212>PRT
<213>智人(Homo sapiens)
<400>31
Met Lys Val Ser Ala Ala Leu Leu Trp Leu Leu Leu Ile Ala Ala Ala
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gly Pro Ala Ser Val Pro Thr Thr Cys
20 25 30
Cys Phe Asn Leu Ala Asn Arg Lys Ile Pro Leu Gln Arg Leu Glu Ser
35 40 45
Tyr Arg Arg Ile Thr Ser Gly Lys Cys Pro Gln Lys Ala Val Ile Phe
50 55 60
Lys Thr Lys Leu Ala Lys Asp Ile Cys Ala Asp Pro Lys Lys Lys Trp
65 70 75 80
Val Gln Asp Ser Met Lys Tyr Leu Asp Gln Lys Ser Pro Thr Pro Lys
85 90 95
Pro
<210>32
<211>97
<212>PRT
<213>智人(Homo sapiens)
<400>32
Met Lys Val Ser Ala Ala Leu Leu Trp Leu Leu Leu Ile Ala Ala Ala
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gly Pro Ala Ser Val Pro Thr Thr Cys
20 25 30
Cys Phe Asn Leu Ala Asn Arg Lys Ile Pro Leu Gln Arg Leu Glu Ser
35 40 45
Tyr Arg Arg Ile Thr Ser Gly Lys Cys Pro Gln Lys Ala Val Ile Phe
50 55 60
Lys Thr Lys Leu Ala Lys Asp Ile Cys Ala Asp Pro Lys Lys Lys Trp
65 70 75 80
Val Gln Asp Ser Met Lys Tyr Leu Asp Gln Lys Ser Pro Thr Pro Lys
85 90 95
Pro
<210>33
<211>97
<212>PRT
<213>智人(Homo sapiens)
<400>33
Met Lys Val Ser Ala Ala Leu Leu Trp Leu Leu Leu Ile Ala Ala Ala
1 5 10 15
Phe Ser Pro Gln Gly Leu Ala Gly Pro Ala Ser Val Pro Thr Thr Cys
20 25 30
Cys Phe Asn Leu Ala Asn Arg Lys Ile Pro Leu Gln Arg Leu Glu Ser
35 40 45
Tyr Arg Arg Ile Thr Ser Gly Lys Cys Pro Gln Lys Ala Val Ile Phe
50 55 60
Lys Thr Lys Leu Ala Lys Asp Ile Cys Ala Asp Pro Lys Lys Lys Trp
65 70 75 80
Val Gln Asp Ser Met Lys Tyr Leu Asp Gln Lys Ser Pro Thr Pro Lys
85 90 95
Pro
<210>34
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>34
Met Gln Ser Ser Thr Ala Leu Leu Phe Leu Leu Leu Thr Val Thr Ser
1 5 10 15
Phe Thr Ser Gln Val Leu Ala His Pro Gly Ser Ile Pro Thr Ser Cys
20 25 30
Cys Phe Ile Met Thr Ser Lys Lys Ile Pro Asn Thr Leu Leu Lys Ser
35 40 45
Tyr Lys Arg Ile Thr Asn Asn Arg Cys Thr Leu Lys Ala Ile Val Phe
50 55 60
Lys Thr Arg Leu Gly Lys Glu Ile Cys Ala Asp Pro Lys Lys Lys Trp
65 70 75 80
Val Gln Asp Ala Thr Lys His Leu Asp Gln Lys Leu Gln Thr Pro Lys
85 90 95
Pro
<210>35
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>35
Met Gln Ser Ser Thr Ala Leu Leu Phe Leu Leu Leu Thr Val Thr Ser
1 5 10 15
Phe Thr Ser Gln Val Leu Ala His Pro Gly Ser Ile Pro Thr Ser Cys
20 25 30
Cys Phe Ile Met Thr Ser Lys Lys Ile Pro Asn Thr Leu Leu Lys Ser
35 40 45
Tyr Lys Arg Ile Thr Asn Asn Arg Cys Thr Leu Lys Ala Ile Val Phe
50 55 60
Lys Thr Arg Leu Gly Lys Glu Ile Cys Ala Asp Pro Lys Lys Lys Trp
65 70 75 80
Val Gln Asp Ala Thr Lys His Leu Asp Gln Lys Leu Gln Thr Pro Lys
85 90 95
Pro
<210>36
<211>97
<212>PRT
<213>小鼠(Mus musculus)
<400>36
Met Gln Ser Ser Thr Ala Leu Leu Phe Leu Leu Leu Thr Val Thr Ser
1 5 10 15
Phe Thr Ser Gln Val Leu Ala His Pro Gly Ser Ile Pro Thr Ser Cys
20 25 30
Cys Phe Ile Met Thr Ser Lys Lys Ile Pro Asn Thr Leu Leu Lys Ser
35 40 45
Tyr Lys Arg Ile Thr Asn Asn Arg Cys Thr Leu Lys Ala Ile Val Phe
50 55 60
Lys Thr Arg Leu Gly Lys Glu Ile Cys Ala Asp Pro Lys Lys Lys Trp
65 70 75 80
Val Gln Asp Ala Thr Lys His Leu Asp Gln Lys Leu Gln Thr Pro Lys
85 90 95
Pro
<210>37
<211>1172
<212>DNA
<213>智人(Homo sapiens)
<400>37
gagacattcc tcaattgctt agacatattc tgagcctaca gcagaggaac ctccagtctc 60
agcaccatga atcaaactgc gattctgatt tgctgcctta tctttctgac tctaagtggc 120
attcaaggag tacctctctc tagaaccgta cgctgtacct gcatcagcat tagtaatcaa 180
cctgttaatc caaggtcttt agaaaaactt gaaattattc ctgcaagcca attttgtcca 240
cgtgttgaga tcattgctac aatgaaaaag aagggtgaga agagatgtct gaatccagaa 300
tcgaaggcca tcaagaattt actgaaagca gttagcaagg aaatgtctaa aagatctcct 360
taaaaccaga ggggagcaaa atcgatgcag tgcttccaag gatggaccac acagaggctg 420
cctctcccat cacttcccta catggagtat atgtcaagcc ataattgttc ttagtttgca 480
gttacactaa aaggtgacca atgatggtca ccaaatcagc tgctactact cctgtaggaa 540
ggttaatgtt catcatccta agctattcag taataactct accctggcac tataatgtaa 600
gctctactga ggtgctatgt tcttagtgga tgttctgacc ctgcttcaaa tatttccctc 660
acctttccca tcttccaagg gtactaagga atctttctgc tttggggttt atcagaattc 720
tcagaatctc aaataactaa aaggtatgca atcaaatctg ctttttaaag aatgctcttt 780
acttcatgga cttccactgc catcctccca aggggcccaa attctttcag tggctaccta 840
catacaattc caaacacata caggaaggta gaaatatctg aaaatgtatg tgtaagtatt 900
cttatttaat gaaagactgt acaaagtata agtcttagat gtatatattt cctatattgt 960
tttcagtgta catggaataa catgtaatta agtactatgt atcaatgagt aacaggaaaa 1020
ttttaaaaat acagatagat atatgctctg catgttacat aagataaatg tgctgaatgg 1080
ttttcaaata aaaatgaggt actctcctgg aaatattaag aaagactatc taaatgttga 1140
aagatcaaaa ggttaataaa gtaattataa ct 1172
<210>38
<211>1063
<212>DNA
<213>小鼠(Mus musculus)
<400>38
catcccgagc caaccttccg gaagcctccc catcagcacc atgaacccaa gtgctgccgt 60
cattttctgc ctcatcctgc tgggtctgag tgggactcaa gggatccctc tcgcaaggac 120
ggtccgctgc aactgcatcc atatcgatga cgggccagtg agaatgaggg ccatagggaa 180
gcttgaaatc atccctgcga gcctatcctg cccacgtgtt gagatcattg ccacgatgaa 240
aaagaatgat gagcagagat gtctgaatcc ggaatctaag accatcaaga atttaatgaa 300
agcgtttagc caaaaaaggt ctaaaagggc tccttaactg gagtgaagcc acgcacacac 360
cccggtgctg cgatggatgg acagcagaga gcctctctcc atcactcccc tttacccagt 420
ggatggctag tcctaattgc ccttggtctt ctgaaaggtg accagccgtg gtcacatcag 480
ctgctactcc tcctgcagga tgatggtcaa gccatggtcc tgagacaaaa gtaactgccg 540
aagcaagaat tctttaaggg ctggtctgag tcctcgctca agtggctggg atggctgtcc 600
tagctctgta ctgtaagcta tgtggaggtg cgacgccctt caccatgtgc catgcccagg 660
ctgctcccca caccctcctt gtcctcccta gctcaggctc gtcagttcta agtttacctg 720
agctctttta tttcagatgt aagactacaa atttaagttt gtaagcacga acttaaccac 780
catcttccca aggggttatc aagatactca gaggaacctg aaaatgtatg tgtaaatact 840
atttaatgaa cgactgtaca aagtagaatt cctaatgtat tttttgtatg ctttgcattg 900
tatatggaag aacttgtgtc atcaagtatg tatcaatggg tagttaaagt ttatttttaa 960
aaccgtccaa taccttttgt attatgtaac attcaaaaga caatgtactg tattgaaagt 1020
agtaagagac ccaaaatgta ataaagtaat aataactgac atg 1063
<210>39
<211>98
<212>PRT
<213>智人(Homo sapiens)
<400>39
Met Asn Gln Thr Ala Ile Leu Ile Cys Cys Leu Ile Phe Leu Thr Leu
1 5 10 15
Ser Gly Ile Gln Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys
20 25 30
Ile Ser Ile Ser Asn Gln Pro Val Asn Pro Arg Ser Leu Glu Lys Leu
35 40 45
Glu Ile Ile Pro Ala Ser Gln Phe Cys Pro Arg Val Glu Ile Ile Ala
50 55 60
Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro Glu Ser Lys
65 70 75 80
Ala Ile Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Met Ser Lys Arg
85 90 95
Ser Pro
<210>40
<211>98
<212>PRT
<213>智人(Homo sapiens)
<400>40
Met Asn Gln Thr Ala Ile Leu Ile Cys Cys Leu Ile Phe Leu Thr Leu
1 5 10 15
Ser Gly Ile Gln Gly Val Pro Leu Ser Arg Thr Val Arg Cys Thr Cys
20 25 30
Ile Ser Ile Ser Asn Gln Pro Val Asn Pro Arg Ser Leu Glu Lys Leu
35 40 45
Glu Ile Ile Pro Ala Ser Gln Phe Cys Pro Arg Val Glu Ile Ile Ala
50 55 60
Thr Met Lys Lys Lys Gly Glu Lys Arg Cys Leu Asn Pro Glu Ser Lys
65 70 75 80
Ala Ile Lys Asn Leu Leu Lys Ala Val Ser Lys Glu Arg Ser Lys Arg
85 90 95
Ser Pro
<210>41
<211>98
<212>PRT
<213>小鼠(Mus musculus)
<400>41
Met Asn Pro Ser Ala Ala Val Ile Phe Cys Leu Ile Leu Leu Gly Leu
1 5 10 15
Ser Gly Thr Gln Gly Ile Pro Leu Ala Arg Thr Val Arg Cys Asn Cys
20 25 30
Ile His Ile Asp Asp Gly Pro Val Arg Met Arg Ala Ile Gly Lys Leu
35 40 45
Glu Ile Ile Pro Ala Ser Leu Ser Cys Pro Arg Val Glu Ile Ile Ala
50 55 60
Thr Met Lys Lys Asn Asp Glu Gln Arg Cys Leu Asn Pro Glu Ser Lys
65 70 75 80
Thr Ile Lys Asn Leu Met Lys Ala Phe Ser Gln Lys Arg Ser Lys Arg
85 90 95
Ala Pro
<210>42
<211>98
<212>PRT
<213>小鼠(Mus musculus)
<400>42
Met Asn Pro Ser Ala Ala Val Ile Phe Cys Leu Ile Leu Leu Gly Leu
1 5 10 15
Ser Gly Thr Gln Gly Ile Pro Leu Ala Arg Thr Val Arg Cys Asn Cys
20 25 30
Ile His Ile Asp Asp Gly Pro Val Arg Met Arg Ala Ile Gly Lys Leu
35 40 45
Glu Ile Ile Pro Ala Ser Leu Ser Cys Pro Arg Val Glu Ile Ile Ala
50 55 60
Thr Met Lys Lys Asn Asp Glu Gln Arg Cys Leu Asn Pro Glu Ser Lys
65 70 75 80
Thr Ile Lys Asn Leu Met Lys Ala PheSer Gln Lys ArgSer Lys Arg
85 90 95
Ala Pro
<210>43
<211>98
<212>PRT
<213>小鼠(Mus musculus)
<400>43
Met Asn Pro Ser Ala Ala Val Ile Phe Cys Leu Ile Leu Leu Gly Leu
1 5 10 15
Ser Gly Thr Gln Gly Ile Pro Leu Ala Arg Thr Val Arg Cys Asn Cys
20 25 30
Ile His Ile Asp Asp Gly Pro Val Arg Met Arg Ala Ile Gly Lys Leu
35 40 45
Glu Ile Ile Pro Ala Ser Leu Ser Cys Pro Arg Val Glu Ile Ile Ala
50 55 60
Thr Met Lys Lys Asn Asp Glu Gln Arg Cys Leu Asn Pro Glu Ser Lys
65 70 75 80
Thr Ile Lys Asn Leu Met Lys Ala Phe Ser Gln Lys Arg Ser Lys Arg
85 90 95
Ala Pro
<210>44
<211>2749
<212>DNA
<213>智人(Homo sapiens)
<400>44
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc 60
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc 120
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca 180
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc 240
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag 300
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt 360
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat 420
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg 480
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg 540
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact 600
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag 660
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa 720
tgctccagcc aagatgtggt gaccaagcct gattgcaact gcctgtaccc caaagccatc 780
cctagcagtg acccggcctc tgtctcccct catcagcccc tcgccccctc catggcccct 840
gtggctggct tgacctggga ggactctgag ggaactgagg gcagctccct cttgcctggt 900
gagcagcccc tgcacacagt ggatccaggc agtgccaagc agcggccacc caggagcacc 960
tgccagagct ttgagccgcc agagacccca gttgtcaagg acagcaccat cggtggctca 1020
ccacagcctc gcccctctgt cggggccttc aaccccggga tggaggatat tcttgactct 1080
gcaatgggca ctaattgggt cccagaagaa gcctctggag aggccagtga gattcccgta 1140
ccccaaggga cagagctttc cccctccagg ccaggagggg gcagcatgca gacagagccc 1200
gccagaccca gcaacttcct ctcagcatct tctccactcc ctgcatcagc aaagggccaa 1260
cagccggcag atgtaactgg tacagccttg cccagggtgg gccccgtgag gcccactggc 1320
caggactgga atcacacccc ccagaagaca gaccatccat ctgccctgct cagagacccc 1380
ccggagccag gctctcccag gatctcatca ctgcgccccc agggcctcag caacccctcc 1440
accctctctg ctcagccaca gctttccaga agccactcct cgggcagcgt gctgcccctt 1500
ggggagctgg agggcaggag gagcaccagg gatcggagga gccccgcaga gccagaagga 1560
ggaccagcaa gtgaaggggc agccaggccc ctgccccgtt ttaactccgt tcctttgact 1620
gacacaggcc atgagaggca gtccgaggga tcctccagcc cgcagctcca ggagtctgtc 1680
ttccacctgc tggtgcccag tgtcatcctg gtcttgctgg ccgtcggagg cctcttgttc 1740
tacaggtgga ggcggcggag ccatcaagag cctcagagag cggattctcc cttggagcaa 1800
ccagagggca gccccctgac tcaggatgac agacaggtgg aactgccagt gtagagggaa 1860
ttctaagctg gacgcacaga acagtctctc cgtgggagga gacattatgg ggcgtccacc 1920
accacccctc cctggccatc ctcctggaat gtggtctgcc ctccaccaga gctcctgcct 1980
gccaggactg gaccagagca gccaggctgg ggcccctctg tctcaacccg cagacccttg 2040
actgaatgag agaggccaga ggatgctccc catgctgcca ctatttattg tgagccctgg 2100
aggctcccat gtgcttgagg aaggctggtg agcccggctc aggaccctct tccctcaggg 2160
gctgcaccct cctctcactc ccttccatgc cggaacccag gccagggacc caccggcctg 2220
tggtttgtgg gaaagcaggg tggacgctga ggagtgaaag aaccctgcac ccagagggcc 2280
tgcctggtgc caaggtatcc cagcctggac aggcatggac ctgtctccag agagaggagc 2340
ctgaagttcg tggggcggga cagcgtcggc ctgatttccc gtaaaggtgt gcagcctgag 2400
agacgggaag aggaggcctc tggacctgct ggtctgcact gacagcctga agggtctaca 2460
ccctcggctc acctaagtgc cctgtgctgg ttgccaggcg cagaggggag gccagccctg 2520
ccctcaggac ctgcctgacc tgccagtgat gccaagaggg ggatcaagca ctggcctctg 2580
cccctcctcc ttccagcacc tgccagagct tctccaggag gccaagcaga ggctcccctc 2640
atgaaggaag ccattgcact gtgaacactg tacctgcctg ctgaacagcc tgcccccgtc 2700
catccatgag ccagcatccg tccgtcctcc actctccagc ctctcccca 2749
<210>45
<211>1519
<212>DNA
<213>智人(Homo sapiens)
<400>45
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc 60
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc 120
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca 180
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc 240
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag 300
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt 360
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat 420
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg 480
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg 540
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact 600
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag 660
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa 720
tgctccagcc aagatgtggt gaccaagcct gattgcaact gcctgtaccc caaagccatc 780
cctagcagtg acccggcctc tgtctcccct catcagcccc tcgccccctc catggcccct 840
gtggctggct tgacctggga ggactctgag ggaactgagg gcagctccct cttgcctggt 900
gagcagcccc tgcacacagt ggatccaggc agtgccaagc agcggccacc caggagcacc 960
tgccagagct ttgagccgcc agagacccca gttgtcaagg acagcaccat cggtggctca 1020
ccacagcctc gcccctctgt cggggccttc aaccccggga tggaggatat tcttgactct 1080
gcaatgggca ctaattgggt cccagaagaa gcctctggag aggccagtga gattcccgta 1140
ccccaaggga cagagctttc cccctccagg ccaggagggg gcagcatgca gacagagccc 1200
gccagaccca gcaacttcct ctcagcatct tctccactcc ctgcatcagc aaagggccaa 1260
cagccggcag atgtaactgg ccatgagagg cagtccgagg gatcctccag cccgcagctc 1320
caggagtctg tcttccacct gctggtgccc agtgtcatcc tggtcttgct ggccgtcgga 1380
ggcctcttgt tctacaggtg gaggcggcgg agccatcaag agcctcagag agcggattct 1440
cccttggagc aaccagaggg cagccccctg actcaggatg acagacaggt ggaactgcca 1500
gtgtagaggg aattctaag 1519
<210>46
<211>1855
<212>DNA
<213>智人(Homo sapiens)
<400>46
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc 60
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc 120
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca 180
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc 240
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag 300
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt 360
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat 420
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg 480
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg 540
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact 600
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag 660
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa 720
tgctccagcc aaggccatga gaggcagtcc gagggatcct ccagcccgca gctccaggag 780
tctgtcttcc acctgctggt gcccagtgtc atcctggtct tgctggccgt cggaggcctc 840
ttgttctaca ggtggaggcg gcggagccat caagagcctc agagagcgga ttctcccttg 900
gagcaaccag agggcagccc cctgactcag gatgacagac aggtggaact gccagtgtag 960
agggaattct aagctggacg cacagaacag tctctccgtg ggaggagaca ttatggggcg 1020
tccaccacca cccctccctg gccatcctcc tggaatgtgg tctgccctcc accagagctc 1080
ctgcctgcca ggactggacc agagcagcca ggctggggcc cctctgtctc aacccgcaga 1140
cccttgactg aatgagagag gccagaggat gctccccatg ctgccactat ttattgtgag 1200
ccctggaggc tcccatgtgc ttgaggaagg ctggtgagcc cggctcagga ccctcttccc 1260
tcaggggctg caccctcctc tcactccctt ccatgccgga acccaggcca gggacccacc 1320
ggcctgtggt ttgtgggaaa gcagggtgga cgctgaggag tgaaagaacc ctgcacccag 1380
agggcctgcc tggtgccaag gtatcccagc ctggacaggc atggacctgt ctccagagag 1440
aggagcctga agttcgtggg gcgggacagc gtcggcctga tttcccgtaa aggtgtgcag 1500
cctgagagac gggaagagga ggcctctgga cctgctggtc tgcactgaca gcctgaaggg 1560
tctacaccct cggctcacct aagtgccctg tgctggttgc caggcgcaga ggggaggcca 1620
gccctgccct caggacctgc ctgacctgcc agtgatgcca agagggggat caagcactgg 1680
cctctgcccc tcctccttcc agcacctgcc agagcttctc caggaggcca agcagaggct 1740
cccctcatga aggaagccat tgcactgtga acactgtacc tgcctgctga acagcctgcc 1800
cccgtccatc catgagccag catccgtccg tcctccactc tccagcctct cccca 1855
<210>47
<211>2545
<212>DNA
<213>智人(Homo sapiens)
<400>47
gagggctggc cagtgaggct cggcccgggg aaagtgaaag tttgcctggg tcctctcggc 60
gccagagccg ctctccgcat cccaggacag cggtgcggcc ctcggccggg gcgcccactc 120
cgcagcagcc agcgagcgag cgagcgagcg agggcggccg acgcgcccgg ccgggaccca 180
gctgcccgta tgaccgcgcc gggcgccgcc gggcgctgcc ctcccacgac atggctgggc 240
tccctgctgt tgttggtctg tctcctggcg agcaggagta tcaccgagga ggtgtcggag 300
tactgtagcc acatgattgg gagtggacac ctgcagtctc tgcagcggct gattgacagt 360
cagatggaga cctcgtgcca aattacattt gagtttgtag accaggaaca gttgaaagat 420
ccagtgtgct accttaagaa ggcatttctc ctggtacaag acataatgga ggacaccatg 480
cgcttcagag ataacacccc caatgccatc gccattgtgc agctgcagga actctctttg 540
aggctgaaga gctgcttcac caaggattat gaagagcatg acaaggcctg cgtccgaact 600
ttctatgaga cacctctcca gttgctggag aaggtcaaga atgtctttaa tgaaacaaag 660
aatctccttg acaaggactg gaatattttc agcaagaact gcaacaacag ctttgctgaa 720
tgctccagcc aagatgtggt gaccaagcct gattgcaact gcctgtaccc caaagccatc 780
cctagcagtg acccggcctc tgtctcccct catcagcccc tcgccccctc catggcccct 840
gtggctggct tgacctggga ggactctgag ggaactgagg gcagctccct cttgcctggt 900
gagcagcccc tgcacacagt ggatccaggc agtgccaagc agcggccacc caggagcacc 960
tgccagagct ttgagccgcc agagacccca gttgtcaagg acagcaccat cggtggctca 1020
ccacagcctc gcccctctgt cggggccttc aaccccggga tggaggatat tcttgactct 1080
gcaatgggca ctaattgggt cccagaagaa gcctctggag aggccagtga gattcccgta 1140
ccccaaggga cagagctttc cccctccagg ccaggagggg gcagcatgca gacagagccc 1200
gccagaccca gcaacttcct ctcagcatct tctccactcc ctgcatcagc aaagggccaa 1260
cagccggcag atgtaactgg tacagccttg cccagggtgg gccccgtgag gcccactggc 1320
caggactgga atcacacccc ccagaagaca gaccatccat ctgccctgct cagagacccc 1380
ccggagccag gctctcccag gatctcatca ctgcgccccc agggcctcag caacccctcc 1440
accctctctg ctcagccaca gctttccaga agccactcct cgggcagcgt gctgcccctt 1500
ggggagctgg agggcaggag gagcaccagg gatcggagga gccccgcaga gccagaagga 1560
ggaccagcaa gtgaaggggc agccaggccc ctgccccgtt ttaactccgt tcctttgact 1620
gacacaggcc atgagaggca gtccgaggga tcctccagcc cgcagctcca ggagtctgtc 1680
ttccacctgc tggtgcccag tgtcatcctg gtcttgctgg ccgtcggagg cctcttgttc 1740
tacaggtgga ggcggcggag ccatcaagag cctcagagag cggattctcc cttggagcaa 1800
ccagagggca gccccctgac tcaggatgac agacaggtgg aactgccagt gtagagggaa 1860
ttctaagacc cctcaccatc ctggacacac tcgtttgtca atgtccctct gaaaatgtga 1920
cgcccagccc cggacacagt actccagatg ttgtctgacc agctcagaga gagtacagtg 1980
ggactgttac cttccttgat atggacagta ttcttctatt tgtgcagatt aagattgcat 2040
tagttttttt cttaacaact gcatcatact gttgtcatat gttgagcctg tggttctata 2100
aaacccctag ttccatttcc cataaacttc tgtcaagcca gaccatctct accctgtact 2160
tggacaactt aactttttta accaaagtgc agtttatgtt cacctttgtt aaagccacct 2220
ttgtggtttc tgcccatcac ctgaacctac tgaagttgtg tgaaatccta attctgtcat 2280
ctccgtagcc ctcccagttg tgcctcctgc acattgatga gtgcctgctg ttgtctttgc 2340
ccatgttgtt gatgtagctg tgaccctatt gttcctcacc cctgcccccc gccaacccca 2400
gctggcccac ctcttccccc tcccacccaa gcccacagcc agcccatcag gaagccttcc 2460
tggcttctcc acaaccttct gactgtcttt tcagtcatgc cccctgctct tttgtatttg 2520
gctaatagta tatcaatttg cactt 2545
<210>48
<211>4169
<212>DNA
<213>小鼠(Mus musculus)
<400>48
gacagagcga cggggaagag agctagcggg gacgaccagg cggcccgctt gggggaaggg 60
agtcggcggc tcagtgggcc tctggggtgt agtatgtgtc agtgcctgtg agtgtgtttg 120
tgtgtgtgta tgtctgtgtg tgtctggcgg agagccaggg tgatttccca taaaccacat 180
gccccgccag cccgcccgct taaaaggctg tgccgagggc tggccagcga agctcggcca 240
ggggaaagtg aaagtttgcc tcggtgctct cggtgtcgct gcggctctct gcatcccagg 300
acagcggcgt ggccctcgac cggggcgcgg gctcttcagc cactagcgag caagggagcg 360
agcgaaccag ggcggccaac acgccgtgcc gggacccagc tgcccgtatg accgcgcggg 420
gcgccgcggg gcgctgccct tcttcgacat ggctgggctc ccggctgctg ctggtctgtc 480
tcctcatgag caggagtatt gccaaggagg tgtcagaaca ctgtagccac atgattggga 540
atggacacct gaaggtcctg cagcagttga tcgacagtca aatggagact tcatgccaga 600
ttgcctttga atttgtagac caggaacagc tggatgatcc tgtttgctac ctaaagaagg 660
ccttttttct ggtacaagac ataatagatg agaccatgcg ctttaaagac aacaccccca 720
atgctaacgc caccgagagg ctccaggaac tctccaataa cctgaacagc tgcttcacca 780
aggactatga ggagcagaac aaggcctgtg tccgaacttt ccatgagact cctctccagc 840
tgctggagaa gatcaagaac ttctttaatg aaacaaagaa tctccttgaa aaggactgga 900
acatttttac caagaactgc aacaacagct ttgctaagtg ctctagccga gatgtggtga 960
ccaagcctga ttgcaactgc ctgtacccta aagccacccc tagcagtgac ccggcctctg 1020
cctcccctca ccagcccccc gccccctcca tggcccctct ggctggcttg gcttgggatg 1080
attctcagag gacagagggc agctccctct tgcccagtga gcttcccctt cgcatagagg 1140
acccaggcag tgccaagcag cgaccaccca ggagtacctg ccagaccctc gagtcaacag 1200
agcaaccaaa ccatggggac agactcactg aggactcaca acctcatcct tctgcggggg 1260
ggcccgtccc tggggtggaa gacattcttg aatcttcact gggcactaac tgggtcctag 1320
aagaagcttc tggagaggct agtgagggat ttttgaccca ggaagcaaag ttttccccct 1380
ccacgcctgt agggggcagc atccaggcag agactgacag acccagggcc ctctcagcat 1440
ctccattccc taaatcaaca gaggaccaaa agccagtgga tataacagac aggccgttga 1500
cagaggtgaa ccctatgaga cccattggcc agacacagaa taatactcct gagaagactg 1560
atggtacatc cacgctgcgt gaagaccacc aggagccagg ctctccccat attgcgacac 1620
cgaatcccca acgagtcagc aactcagcca cccccgttgc tcagttactg cttcccaaaa 1680
gccactcttg gggcattgtg ctgccccttg gggagcttga gggcaagaga agtaccaggg 1740
atcgaaggag ccccgcagag ctggaaggag gatcagcaag tgagggggca gccaggcctg 1800
tggcccgttt taattccatt cctttgactg acacaggcca tgtggagcag catgagggat 1860
cctctgaccc ccagatccct gagtctgtct tccacctgct ggtgccgggc atcatcctag 1920
tcttgctgac tgttgggggc ctcctgttct acaagtggaa gtggaggagc catcgaaacc 1980
ctcagacatt ggattcttct gtggggcgac cagaggacag ctccctgacc caggatgagg 2040
acagacaggt ggaactgcca gtatagaaag gattctatgc tgggcacaca ggactatctc 2100
tttatggaag gagacatatg ggaacatcca ccactaccct ctcctaccat cttcctggga 2160
atgtggccta ccactaccag agctcctgcc taccaagact ggatgaaaga agcagctttg 2220
atggggtctt tccatcctca cccttagact ctcaaccaaa gagaaagggc tggaggatgc 2280
cccccacata ctgccactat ttattgtggg ccctggaggc tccctgcatt ggaggaaggg 2340
cagctcagca gctcaggacc ctttccctta ggggctgctt cctcccctca aaaccagaac 2400
ctggcaaggg actcactagc ctggatggcc catgggagac caggtcagat gagaaggagc 2460
agaagagccc tgtgcccaga agacccaact ggtgccaagg aatcccagca tggacaggca 2520
gggacctgtt tcccaagaag agagcctgat attcaaaggg tgggacagca tctgcccgac 2580
ttcccgtaaa ggcataaagg cacgcagccc aaaagacggg aagaggaggc ctttggctgc 2640
ttgtgttgac agcttaaagg ggtctacacc ctcaacttgc ttaagtgccc tctgctgata 2700
gccaggaagg agggagacca gccctgcccc tcaggacctg acctggctca tgatgccaag 2760
aggaagacag agctctagcc tcgtcttctc ctgcccacag cccctgccag agttcttttg 2820
cccagcagag gcacccctca tgaaggaagc cattgcactg tgaatactga acctgcctgc 2880
tgaacagcct gtcccatcca tccctatgag tgaccatccg tccgaatgtt ctcccacttc 2940
cttcagcctc tcctcggctt cttgcactga gctggcctca cgtgttgact gagggagccc 3000
ctgagcccca accttcccct gcctcagcct ttgattgtcc agggtgaagc tgtgggagaa 3060
ccgcctgggc taccagtcag agctggtctt tgggctgtgt tccttgccca ggtttctgca 3120
tcttgcactt tgacattccc aggagggaag tgactagtgg aagggagaga ggaaggggag 3180
gcagagacaa aggccacagg cagagctatg aatgagaatg ggtcttgaaa atatgtgtgc 3240
acccctaagc ttgaaattga tctctatact ctagcccctc agccagcctc cttcctgttg 3300
tctgaaacct ggagctaagc aggttgtcct gtcacaagct ctggggactg agctccatgc 3360
tccaacccca ccctcttctg acctttgttc tccagacctg acccaggtag gcaagggtac 3420
cctcccagtc tcacctacca tactgtgcca tctctagcca agcaagccag gtttagagaa 3480
gggtcaaaaa aaaaaaaaaa aaagggttgt ttacttccaa cttgttctga tgccctctgt 3540
ttcccaggcc aggcttgtct gtggtgacct gggcatgggt gacagggctc tcatttgccc 3600
cttggtctct ttatgctgct gagtccccct ttcctgccct ccctggctac tgggtcaata 3660
atctttcagg ccatgaatct gggaggagag tggtctgtaa gctccatcag ccctgtcctg 3720
agacagcagg ggggaaggac actggagact ttcttgtggg gcttacttag ccttctggtt 3780
acagactatt tccatgctag aaaatacata ttttaaaata gaaggaaaaa cacagaaaca 3840
aaacaaaaca aggcattctc tacccctcca ccttaaacat atattattaa agacagaaga 3900
gaaaatccaa cccattgcaa gaagctcttt gtgggtgcct ggttacatcg gagcagggga 3960
gcctcaaatc cacctttgga gccgcccctg tgtgcattag gaacccttct ctcctctgag 4020
aaagctcaga gggagcactg cctcacaaac tgtgagactg cgttttttat acttggaagt 4080
ggtgaattat tttatataag gtcatttaaa tatctattta aaaaatagga agctgctttt 4140
atatttaata ataaaagaag tgcacaagc 4169
<210>49
<211>554
<212>PRT
<213>智人(Homo sapiens)
<400>49
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His
195 200 205
Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu
210 215 220
Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro
225 230 235 240
Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser
260 265 270
Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn
275 280 285
Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val
290 295 300
Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly
305 310 315 320
Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu
325 330 335
Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala
340 345 350
Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro
355 360 365
Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro
370 375 380
Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro
385 390 395 400
Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro
405 410 415
Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly
420 425 430
Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp
435 440 445
Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala
450 455 460
Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly
465 470 475 480
His Glu Arg Gln Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser
485 490 495
Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val
500 505 510
Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro
515 520 525
Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr
530 535 540
Gln Asp Asp Arg Gln Val Glu Leu Pro Val
545 550
<210>50
<211>438
<212>PRT
<213>智人(Homo sapiens)
<400>50
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His
195 200 205
Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu
210 215 220
Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro
225 230 235 240
Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser
260 265 270
Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn
275 280 285
Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val
290 295 300
Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly
305 310 315 320
Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu
325 330 335
Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala
340 345 350
Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly His Glu Arg Gln
355 360 365
Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser Val Phe His Leu
370 375 380
Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val Gly Gly Leu Leu
385 390 395 400
Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro Gln Arg Ala Asp
405 410 415
Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg
420 425 430
Gln Val Glu Leu Pro Val
435
<210>51
<211>256
<212>PRT
<213>智人(Homo sapiens)
<400>51
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Gly His Glu Arg Gln Ser Glu Gly Ser Ser Ser
180 185 190
Pro Gln Leu Gln Glu Ser Val Phe His Leu Leu Val Pro Ser Val Ile
195 200 205
Leu Val Leu Leu Ala Val Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg
210 215 220
Arg Ser His Gln Glu Pro Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro
225 230 235 240
Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg Gln Val Glu Leu Pro Val
245 250 255
<210>52
<211>554
<212>PRT
<213>智人(Homo sapiens)
<400>52
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His
195 200 205
Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu
210 215 220
Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro
225 230 235 240
Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser
260 265 270
Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn
275 280 285
Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val
290 295 300
Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly
305 310 315 320
Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu
325 330 335
Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala
340 345 350
Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro
355 360 365
Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro
370 375 380
Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro
385 390 395 400
Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro
405 410 415
Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly
420 425 430
Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp
435 440 445
Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala
450 455 460
Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly
465 470 475 480
His Glu Arg Gln Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser
485 490 495
Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val
500 505 510
Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro
515 520 525
Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr
530 535 540
Gln Asp Asp Arg Gln Val Glu Leu Pro Val
545 550
<210>53
<211>554
<212>PRT
<213>智人(Homo sapiens)
<400>53
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His
195 200 205
Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu
210 215 220
Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro
225 230 235 240
Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser
260 265 270
Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn
275 280 285
Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val
290 295 300
Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly
305 310 315 320
Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu
325 330 335
Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala
340 345 350
Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro
355 360 365
Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro
370 375 380
Gln Lys Thr Asp Hi s Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro
385 390 395 400
Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro
405 410 415
Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly
420 425 430
Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp
435 440 445
Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala
450 455 460
Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly
465 470 475 480
His Glu Arg Gln Ser Glu Gly Ser Ser Ser Pro Gln Leu Gln Glu Ser
485 490 495
Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val
500 505 510
Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro
515 520 525
Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr
530 535 540
Gln Asp Asp Arg Gln Val Glu Leu Pro Val
545 550
<210>54
<211>243
<212>PRT
<213>智人(Homo sapiens)
<400>54
Thr Trp Leu Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg
1 5 10 15
Ser Ile Thr Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser
20 25 30
Gly His Leu Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr
35 40 45
Ser Cys Gln Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp
50 55 60
Pro Val Cys Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met
65 70 75 80
Glu Asp Thr Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile
85 90 95
Val Gln Leu Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys
100 105 110
Asp Tyr Glu Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr
115 120 125
Pro Leu Gln Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys
130 135 140
Asn Leu Leu Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn
145 150 155 160
Ser Phe Ala Glu Cys Ser Ser Gln Gly His Glu Arg Gln Ser Glu Gly
165 170 175
Ser Phe Ser Pro Gln Leu Gln Glu Ser Val Phe His Leu Leu Val Pro
180 185 190
Ser Val Ile Leu Val Leu Leu Ala Val Gly Gly Leu Leu Phe Tyr Arg
195 200 205
Trp Arg Arg Arg Ser His Gln Glu Pro Gln Arg Ala Asp Ser Pro Leu
210 215 220
Glu Gln Pro Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg Gln Val Glu
225 230 235 240
Leu Pro Val
<210>55
<211>438
<212>PRT
<213>智人(Homo sapiens)
<400>55
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro His
195 200 205
Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu
210 215 220
Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro
225 230 235 240
Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser
260 265 270
Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn
275 280 285
Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val
290 295 300
Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly
305 310 315 320
Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu
325 330 335
Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala
340 345 350
Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly His Glu Arg Gln
355 360 365
Ser Glu Gly Ser Phe Ser Pro Gln Leu Gln Glu Ser Val Phe His Leu
370 375 380
Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val Gly Gly Leu Leu
385 390 395 400
Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro Gln Arg Ala Asp
405 410 415
Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr Gln Asp Asp Arg
420 425 430
Gln Val Glu Leu Pro Val
435
<210>56
<211>554
<212>PRT
<213>智人(Homo sapiens)
<400>56
Met Thr Ala Pro Gly Ala Ala Gly Arg Cys Pro Pro Thr Thr Trp Leu
1 5 10 15
Gly Ser Leu Leu Leu Leu Val Cys Leu Leu Ala Ser Arg Ser Ile Thr
20 25 30
Glu Glu Val Ser Glu Tyr Cys Ser His Met Ile Gly Ser Gly His Leu
35 40 45
Gln Ser Leu Gln Arg Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Thr Phe Glu Phe Val Asp Gln Glu Gln Leu Lys Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Leu Leu Val Gln Asp Ile Met Glu Asp Thr
85 90 95
Met Arg Phe Arg Asp Asn Thr Pro Asn Ala Ile Ala Ile Val Gln Leu
100 105 110
Gln Glu Leu Ser Leu Arg Leu Lys Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu His Asp Lys Ala Cys Val Arg Thr Phe Tyr Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Val Lys Asn Val Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Asp Lys Asp Trp Asn Ile Phe Ser Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Glu Cys Ser Ser Gln Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Ile Pro Ser Ser Asp Pro Ala Ser Val Ser Pro Hi s
195 200 205
Gln Pro Leu Ala Pro Ser Met Ala Pro Val Ala Gly Leu Thr Trp Glu
210 215 220
Asp Ser Glu Gly Thr Glu Gly Ser Ser Leu Leu Pro Gly Glu Gln Pro
225 230 235 240
Leu His Thr Val Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Ser Phe Glu Pro Pro Glu Thr Pro Val Val Lys Asp Ser
260 265 270
Thr Ile Gly Gly Ser Pro Gln Pro Arg Pro Ser Val Gly Ala Phe Asn
275 280 285
Pro Gly Met Glu Asp Ile Leu Asp Ser Ala Met Gly Thr Asn Trp Val
290 295 300
Pro Glu Glu Ala Ser Gly Glu Ala Ser Glu Ile Pro Val Pro Gln Gly
305 310 315 320
Thr Glu Leu Ser Pro Ser Arg Pro Gly Gly Gly Ser Met Gln Thr Glu
325 330 335
Pro Ala Arg Pro Ser Asn Phe Leu Ser Ala Ser Ser Pro Leu Pro Ala
340 345 350
Ser Ala Lys Gly Gln Gln Pro Ala Asp Val Thr Gly Thr Ala Leu Pro
355 360 365
Arg Val Gly Pro Val Arg Pro Thr Gly Gln Asp Trp Asn His Thr Pro
370 375 380
Gln Lys Thr Asp His Pro Ser Ala Leu Leu Arg Asp Pro Pro Glu Pro
385 390 395 400
Gly Ser Pro Arg Ile Ser Ser Leu Arg Pro Gln Gly Leu Ser Asn Pro
405 410 415
Ser Thr Leu Ser Ala Gln Pro Gln Leu Ser Arg Ser His Ser Ser Gly
420 425 430
Ser Val Leu Pro Leu Gly Glu Leu Glu Gly Arg Arg Ser Thr Arg Asp
435 440 445
Arg Arg Ser Pro Ala Glu Pro Glu Gly Gly Pro Ala Ser Glu Gly Ala
450 455 460
Ala Arg Pro Leu Pro Arg Phe Asn Ser Val Pro Leu Thr Asp Thr Gly
465 470 475 480
His Glu Arg Gln Ser Glu Gly Ser Phe Ser Pro Gln Leu Gln Glu Ser
485 490 495
Val Phe His Leu Leu Val Pro Ser Val Ile Leu Val Leu Leu Ala Val
500 505 510
Gly Gly Leu Leu Phe Tyr Arg Trp Arg Arg Arg Ser His Gln Glu Pro
515 520 525
Gln Arg Ala Asp Ser Pro Leu Glu Gln Pro Glu Gly Ser Pro Leu Thr
530 535 540
Gln Asp Asp Arg Gln Val Glu Leu Pro Val
545 550
<210>57
<211>552
<212>PRT
<213>小鼠(Mus musculus)
<400>57
Met Thr Ala Arg Gly Ala Ala Gly Arg Cys Pro Ser Ser Thr Trp Leu
1 5 10 15
Gly Ser Arg Leu Leu Leu Val Cys Leu Leu Met Ser Arg Ser Ile Ala
20 25 30
Lys Glu Val Ser Glu His Cys Ser His Met Ile Gly Asn Gly His Leu
35 40 45
Lys Val Leu Gln Gln Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Ala Phe Glu Phe Val Asp Gln Glu Gln Leu Asp Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Phe Leu Val Gln Asp Ile Ile Asp Glu Thr
85 90 95
Met Arg Phe Lys Asp Asn Thr Pro Asn Ala Asn Ala Thr Glu Arg Leu
100 105 110
Gln Glu Leu Ser Asn Asn Leu Asn Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu Gln Asn Lys Ala Cys Val Arg Thr Phe His Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Ile Lys Asn Phe Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Glu Lys Asp Trp Asn Ile Phe Thr Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Lys Cys Ser Ser Arg Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Thr Pro Ser Ser Asp Pro Ala Ser Ala Ser Pro His
195 200 205
Gln Pro Pro Ala Pro Ser Met Ala Pro Leu Ala Gly Leu Ala Trp Asp
210 215 220
Asp Ser Gln Arg Thr Glu Gly Ser Ser Leu Leu Pro Ser Glu Leu Pro
225 230 235 240
Leu Arg Ile Glu Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Thr Leu Glu Ser Thr Glu Gln Pro Asn His Gly Asp Arg
260 265 270
Leu Thr Glu Asp Ser Gln Pro His Pro Ser Ala Gly Gly Pro Val Pro
275 280 285
Gly Val Glu AspIle Leu Glu Ser Ser Leu Gly Thr Asn Trp Val Leu
290 295 300
Glu Glu Ala Ser Gly Glu Ala Ser Glu Gly Phe Leu Thr Gln Glu Ala
305 310 315 320
Lys Phe Ser Pro Ser Thr Pro Val Gly Gly Ser Ile Gln Ala Glu Thr
325 330 335
Asp Arg Pro Arg Ala Leu Ser Ala Ser Pro Phe Pro Lys Ser Thr Glu
340 345 350
Asp Gln Lys Pro Val Asp Ile Thr Asp Arg Pro Leu Thr Glu Val Asn
355 360 365
Pro Met Arg Pro Ile Gly Gln Thr Gln Asn Asn Thr Pro Glu Lys Thr
370 375 380
Asp Gly Thr Ser Thr Leu Arg Glu Asp His Gln Glu Pro Gly Ser Pro
385 390 395 400
His Ile Ala Thr Pro Asn Pro Gln Arg Val Ser Asn Ser Ala Thr Pro
405 410 415
Val Ala Gln Leu Leu Leu Pro Lys Ser His Ser Trp Gly Ile Val Leu
420 425 430
Pro Leu Gly Glu Leu Glu Gly Lys Arg Ser Thr Arg Asp Arg Arg Ser
435 440 445
Pro Ala Glu Leu Glu Gly Gly Ser Ala Ser Glu Gly Ala Ala Arg Pro
450 455 460
Val Ala Arg Phe Asn Ser Ile Pro Leu Thr Asp Thr Gly His Val Glu
465 470 475 480
Gln His Glu Gly Ser Ser Asp Pro Gln Ile Pro Glu Ser Val Phe His
485 490 495
Leu Leu Val Pro Gly Ile Ile Leu Val Leu Leu Thr Val Gly Gly Leu
500 505 510
Leu Phe Tyr Lys Trp Lys Trp Arg Ser His Arg Asn Pro Gln Thr Leu
515 520 525
Asp Ser Ser Val Gly Arg Pro Glu Asp Ser Ser Leu Thr Gln Asp Glu
530 535 540
Asp Arg Gln Val Glu Leu Pro Val
545 550
<210>58
<211>552
<212>PRT
<213>小鼠(Mus musculus)
<400>58
Met Thr Ala Arg Gly Ala Ala Gly Arg Cys Pro Ser Ser Thr Trp Leu
1 5 10 15
Gly Ser Arg Leu Leu Leu Val Cys Leu Leu Met Ser Arg Ser Ile Ala
20 25 30
Lys Glu Val Ser Glu His Cys Ser His Met Ile Gly Asn Gly His Leu
35 40 45
Lys Val Leu Gln Gln Leu Ile Asp Ser Gln Met Glu Thr Ser Cys Gln
50 55 60
Ile Ala Phe Glu Phe Val Asp Gln Glu Gln Leu Asp Asp Pro Val Cys
65 70 75 80
Tyr Leu Lys Lys Ala Phe Phe Leu Val Gln Asp Ile Ile Asp Glu Thr
85 90 95
Met Arg Phe Lys Asp Asn Thr Pro Asn Ala Asn Ala Thr Glu Arg Leu
100 105 110
Gln Glu Leu Ser Asn Asn Leu Asn Ser Cys Phe Thr Lys Asp Tyr Glu
115 120 125
Glu Gln Asn Lys Ala Cys Val Arg Thr Phe His Glu Thr Pro Leu Gln
130 135 140
Leu Leu Glu Lys Ile Lys Asn Phe Phe Asn Glu Thr Lys Asn Leu Leu
145 150 155 160
Glu Lys Asp Trp Asn Ile Phe Thr Lys Asn Cys Asn Asn Ser Phe Ala
165 170 175
Lys Cys Ser Ser Arg Asp Val Val Thr Lys Pro Asp Cys Asn Cys Leu
180 185 190
Tyr Pro Lys Ala Thr Pro Ser Ser Asp Pro Ala Ser Ala Ser Pro His
195 200 205
Gln Pro Pro Ala Pro Ser Met Ala Pro Leu Ala Gly Leu Ala Trp Asp
210 215 220
Asp Ser Gln Arg Thr Glu Gly Ser Ser Leu Leu Pro Ser Glu Leu Pro
225 230 235 240
Leu Arg Ile Glu Asp Pro Gly Ser Ala Lys Gln Arg Pro Pro Arg Ser
245 250 255
Thr Cys Gln Thr Leu Glu Ser Thr Glu Gln Pro Asn His Gly Asp Arg
260 265 270
Leu Thr Glu Asp Ser Gln Pro His Pro Ser Ala Gly Gly Pro Val Pro
275 280 285
Gly Val Glu Asp Ile Leu Glu Ser Ser Leu Gly Thr Asn Trp Val Leu
290 295 300
Glu Glu Ala Ser Gly Glu Ala Ser Glu Gly Phe Leu Thr Gln Glu Ala
305 310 315 320
Lys Phe Ser Pro Ser Thr Pro Val Gly Gly Ser Ile Gln Ala Glu Thr
325 330 335
Asp Arg Pro Arg Ala Leu Ser Ala Ser Pro Phe Pro Lys Ser Thr Glu
340 345 350
Asp Gln Lys Pro Val Asp Ile Thr Asp Arg Pro Leu Thr Glu Val Asn
355 360 365
Pro Met Arg Pro Ile Gly Gln Thr Gln Asn Asn Thr Pro Glu Lys Thr
370 375 380
Asp Gly Thr Ser Thr Leu Arg Glu Asp His Gln Glu Pro Gly Ser Pro
385 390 395 400
His Ile Ala Thr Pro Asn Pro Gln Arg Val Ser Asn Ser Ala Thr Pro
405 410 415
Val Ala Gln Leu Leu Leu Pro Lys Ser His Ser Trp Gly Ile Val Leu
420 425 430
Pro Leu Gly Glu Leu Glu Gly Lys Arg Ser Thr Arg Asp Arg Arg Ser
435 440 445
Pro Ala Glu Leu Glu Gly Gly Ser Ala Ser Glu Gly Ala Ala Arg Pro
450 455 460
Val Ala Arg Phe Asn Ser Ile Pro Leu Thr Asp Thr Gly His Val Glu
465 470 475 480
Gln His Glu Gly Ser Ser Asp Pro Gln Ile Pro Glu Ser Val Phe His
485 490 495
Leu Leu Val Pro Gly Ile Ile Leu Val Leu Leu Thr Val Gly Gly Leu
500 505 510
Leu Phe Tyr Lys Trp Lys Trp Arg Ser His Arg Asp Pro Gln Thr Leu
515 520 525
Asp Ser Ser Val Gly Arg Pro Glu Asp Ser Ser Leu Thr Gln Asp Glu
530 535 540
Asp Arg Gln Val Glu Leu Pro Val
545 550
<210>59
<211>924
<212>DNA
<213>智人(Homo sapiens)
<400>59
cagagcccca cgaaggacca gaacaagaca gagtgcctcc tgccgatcca aacatgagcc 60
gcctgcccgt cctgctcctg ctccaactcc tggtccgccc cggactccaa gctcccatga 120
cccagacaac gcccttgaag acaagctggg ttaactgctc taacatgatc gatgaaatta 180
taacacactt aaagcagcca cctttgcctt tgctggactt caacaacctc aatggggaag 240
accaagacat tctgatggaa aataaccttc gaaggccaaa cctggaggca ttcaacaggg 300
ctgtcaagag tttacagaac gcatcagcaa ttgagagcat tcttaaaaat ctcctgccat 360
gtctgcccct ggccacggcc gcacccacgc gacatccaat ccatatcaag gacggtgact 420
ggaatgaatt ccggaggaaa ctgacgttct atctgaaaac ccttgagaat gcgcaggctc 480
aacagacgac tttgagcctc gcgatctttt gagtccaacg tccagctcgt tctctgggcc 540
ttctcaccac agagcctcgg gacatcaaaa acagcagaac ttctgaaacc tctgggtcat 600
ctctcacaca ttccaggacc agaagcattt caccttttcc tgcggcatca gatgaattgt 660
taattatcta atttctgaaa tgtgcagctc ccatttggcc ttgtgcggtt gtgttctcat 720
ttttatccca ttgagactat ttatttatgt atgtatgtat ttatttattt attgcctgga 780
gtgtgaactg tatttatttt agcagaggag ccatgtcctg ctgcttctgc aaaaaactca 840
gagtggggtg gggagcatgt tcatttgtac ctcgagtttt aaactggttc ctagggatgt 900
gtgagaataa actagactct gaac 924
<210>60
<211>629
<212>DNA
<213>小鼠(Mus musculus)
<400>60
aaccccttgg aggaccagaa cgagacaatg gttcttgcca gctctaccac cagcatccac 60
accatgctgc tcctgctcct gatgctcttc cacctgggac tccaagcttc aatcagtggc 120
cgggataccc accgtttaac cagaacgttg aattgcagct ctattgtcaa ggagattata 180
gggaagctcc cagaacctga actcaaaact gatgatgaag gaccctctct gaggaataag 240
agctttcgga gagtaaacct gtccaaattc gtggaaagcc aaggagaagt ggatcctgag 300
gacagatacg ttatcaagtc caatcttcag aaacttaact gttgcctgcc tacatctgcg 360
aatgactctg cgctgccagg ggtcttcatt cgagatctgg atgactttcg gaagaaactg 420
agattctaca tggtccacct taacgatctg gagacagtgc taacctctag accacctcag 480
cccgcatctg gctccgtctc tcctaaccgt ggaaccgtgg aatgttaaaa cagcaggcag 540
agcacctaaa gtctgaatgt tcctcatggc ccatggtcaa aaggatttta cattccttta 600
tgccatcaaa tgtcttatca atttatcta 629
<210>61
<211>152
<212>PRT
<213>智人(Homo sapiens)
<400>61
Met Ser Arg Leu Pro Val Leu Leu Leu Leu Gln Leu Leu Val Arg Pro
1 5 10 15
Gly Leu Gln Ala Pro Met Thr Gln Thr Thr Pro Leu Lys Thr Ser Trp
20 25 30
Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln
35 40 45
Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln
50 55 60
Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe
65 70 75 80
Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile
85 90 95
Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr
100 105 110
Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg
115 120 125
Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln
130 135 140
Thr Thr Leu Ser Leu Ala Ile Phe
145 150
<210>62
<211>152
<212>PRT
<213>智人(Homo sapiens)
<400>62
Met Ser Arg Leu Pro Val Leu Leu Leu Leu Gln Leu Leu Val Arg Pro
1 5 10 15
Gly Leu Gln Ala Pro Met Thr Gln Thr Thr Pro Leu Lys Thr Ser Trp
20 25 30
Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln
35 40 45
Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln
50 55 60
Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe
65 70 75 80
Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile
85 90 95
Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr
100 105 110
Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg
115 120 125
Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln
130 135 140
Thr Thr Leu Ser Leu Ala Ile Phe
145 150
<210>63
<211>152
<212>PRT
<213>智人(Homo sapiens)
<400>63
Met Ser Arg Leu Pro Val Leu Leu Leu Leu Gln Leu Leu Val Arg Pro
1 5 10 15
Gly Leu Gln Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp
20 25 30
Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln
35 40 45
Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln
50 55 60
Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe
65 70 75 80
Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile
85 90 95
Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr AlaAla Pro Thr
100 105 110
Arg His Pro Ile Hi s Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg
115 120 125
Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln
130 135 140
Thr Thr Leu Ser Leu Ala Ile Phe
145 150
<210>64
<211>152
<212>PRT
<213>智人(Homo sapiens)
<400>64
Met Ser Arg Leu Pro Val Leu Leu Leu Leu Gln Leu Leu Val Arg Pro
1 5 10 15
Gly Leu Gln Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp
20 25 30
Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr His Leu Lys Gln
35 40 45
Pro Pro Leu Pro Leu Leu Asp Phe Asn Ser Leu Asn Gly Glu Asp Gln
50 55 60
Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe
65 70 75 80
Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile
85 90 95
Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr
100 105 110
Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg
115 120 125
Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln
130 135 140
Thr Thr Leu Ser Leu Ala Ile Phe
145 150
<210>65
<211>152
<212>PRT
<213>智人(Homo sapiens)
<400>65
Met Ser Arg Leu Pro Val Leu Leu Leu Leu Gln Leu Leu Val Arg Pro
1 5 10 15
Gly Leu Gln Ala Pro Met Thr Gln Thr Thr Ser Leu Lys Thr Ser Trp
20 25 30
Val Asn Cys Ser Asn Met Ile Asp Glu Ile Ile Thr Arg Leu Lys Gln
35 40 45
Pro Pro Leu Pro Leu Leu Asp Phe Asn Asn Leu Asn Gly Glu Asp Gln
50 55 60
Asp Ile Leu Met Glu Asn Asn Leu Arg Arg Pro Asn Leu Glu Ala Phe
65 70 75 80
Asn Arg Ala Val Lys Ser Leu Gln Asn Ala Ser Ala Ile Glu Ser Ile
85 90 95
Leu Lys Asn Leu Leu Pro Cys Leu Pro Leu Ala Thr Ala Ala Pro Thr
100 105 110
Arg His Pro Ile His Ile Lys Asp Gly Asp Trp Asn Glu Phe Arg Arg
115 120 125
Lys Leu Thr Phe Tyr Leu Lys Thr Leu Glu Asn Ala Gln Ala Gln Gln
130 135 140
Thr Thr Leu Ser Leu Ala Ile Phe
145 150
<210>66
<211>166
<212>PRT
<213>小鼠(Mus musculus)
<400>66
Met Val Leu Ala Ser Ser Thr Thr Ser Ile His Thr Met Leu Leu Leu
1 5 10 15
Leu Leu Met Leu Phe His Leu Gly Leu Gln Ala Ser Ile Ser Gly Arg
20 25 30
Asp Thr His Arg Leu Thr Arg Thr Leu Asn Cys Ser Ser Ile Val Lys
35 40 45
Glu Ile Ile Gly Lys Leu Pro Glu Pro Glu Leu Lys Thr Asp Asp Glu
50 55 60
Gly Pro Ser Leu Arg Asn Lys Ser Phe Arg Arg Val Asn Leu Ser Lys
65 70 75 80
Phe Val Glu Ser Gln Gly Glu Val Asp Pro Glu Asp Arg Tyr Val Ile
85 90 95
Lys Ser Asn Leu Gln Lys Leu Asn Cys Cys Leu Pro Thr Ser Ala Asn
100 105 110
Asp Ser Ala Leu Pro Gly Val Phe Ile Arg Asp Leu Asp Asp Phe Arg
115 120 125
Lys Lys Leu Arg Phe Tyr Met Val His Leu Asn Asp Leu Glu Thr Val
130 135 140
Leu Thr Ser Arg Pro Pro Gln Pro Ala Ser Gly Ser Val Ser Pro Asn
145 150 155 160
Arg Gly Thr Val Glu Cys
165
<210>67
<211>166
<212>PRT
<213>小鼠(Mus musculus)
<400>67
Met Val Leu Ala Ser Ser Thr Thr Ser Ile His Thr Met Leu Leu Leu
1 5 10 15
Leu Leu Met Leu Phe His Leu Gly Leu Gln Ala Ser Ile Ser Gly Arg
20 25 30
Asp Thr His Arg Leu Thr Arg Thr Leu Asn Cys Ser Ser Ile Val Lys
35 40 45
Glu Ile Ile Gly Lys Leu Pro Glu Pro Glu Leu Lys Thr Asp Asp Glu
50 55 60
Gly Pro Ser Leu Arg Asn Lys Ser Phe Arg Arg Val Asn Leu Ser Lys
65 70 75 80
Phe Val Glu Ser Gln Gly Glu Val Asp Pro Glu Asp Arg Tyr Val Ile
85 90 95
Lys Ser Asn Leu Gln Lys Leu Asn Cys Cys Leu Pro Thr Ser Ala Asn
100 105 110
Asp Ser Ala Leu Pro Gly Val Phe Ile Arg Asp Leu Asp Asp Phe Arg
115 120 125
Lys Lys Leu Arg Phe Tyr Met Val His Leu Asn Asp Leu Glu Thr Val
130 135 140
Leu Thr Ser Arg Pro Pro Gln Pro Ala Ser Gly Ser Val Ser Pro Asn
145 150 155 160
Arg Gly Thr Val Glu Cys
165
<210>68
<211>166
<212>PRT
<213>小鼠(Mus musculus)
<400>68
Met Val Leu Ala Ser Ser Thr Thr Ser Ile His Thr Met Leu Leu Leu
1 5 10 15
Leu Leu Met Leu Phe His Leu Gly Leu Gln Ala Ser Ile Ser Gly Arg
20 25 30
Asp Thr His Arg Leu Thr Arg Thr Leu Asn Cys Ser Ser Ile Val Lys
35 40 45
Glu Ile Ile Gly Lys Leu Pro Glu Pro Glu Leu Lys Thr Asp Asp Glu
50 55 60
Gly Pro Ser Leu Arg Asn Lys Ser Phe Arg Arg Val Asn Leu Ser Lys
65 70 75 80
Phe Val Glu Ser Gln Gly Glu Val Asp Pro Glu AspArg Tyr Val Ile
85 90 95
Lys Ser Asn Leu Gln Lys Leu Asn Cys Cys Leu Pro Thr Ser Ala Asn
100 105 110
Asp Ser Ala Leu Pro Gly Val Phe Ile Arg Asp Leu Asp Asp Phe Arg
115 120 125
Lys Lys Leu Arg Phe Tyr Met Val His Leu Asn Asp Leu Glu Thr Val
130 135 140
Leu Thr Ser Arg Pro Pro Gln Pro Ala Ser Gly Ser Val Ser Pro Asn
145 150 155 160
Arg Gly Thr Val Glu Cys
165
<210>69
<211>1669
<212>DNA
<213>智人(Homo sapiens)
<400>69
ctccctcagc aaggacagca gaggaccagc taagagggag agaagcaact acagaccccc 60
cctgaaaaca accctcagac gccacatccc ctgacaagct gccaggcagg ttctcttcct 120
ctcacatact gacccacggc tccaccctct ctcccctgga aaggacacca tgagcactga 180
aagcatgatc cgggacgtgg agctggccga ggaggcgctc cccaagaaga caggggggcc 240
ccagggctcc aggcggtgct tgttcctcag cctcttctcc ttcctgatcg tggcaggcgc 300
caccacgctc ttctgcctgc tgcactttgg agtgatcggc ccccagaggg aagagttccc 360
cagggacctc tctctaatca gccctctggc ccaggcagtc agatcatctt ctcgaacccc 420
gagtgacaag cctgtagccc atgttgtagc aaaccctcaa gctgaggggc agctccagtg 480
gctgaaccgc cgggccaatg ccctcctggc caatggcgtg gagctgagag ataaccagct 540
ggtggtgcca tcagagggcc tgtacctcat ctactcccag gtcctcttca agggccaagg 600
ctgcccctcc acccatgtgc tcctcaccca caccatcagc cgcatcgccg tctcctacca 660
gaccaaggtc aacctcctct ctgccatcaa gagcccctgc cagagggaga ccccagaggg 720
ggctgaggcc aagccctggt atgagcccat ctatctggga ggggtcttcc agctggagaa 780
gggtgaccga ctcagcgctg agatcaatcg gcccgactat ctcgactttg ccgagtctgg 840
gcaggtctac tttgggatca ttgccctgtg aggaggacga acatccaacc ttcccaaacg 900
cctcccctgc cccaatccct ttattacccc ctccttcaga caccctcaac ctcttctggc 960
tcaaaaagag aattgggggc ttagggtcgg aacccaagct tagaacttta agcaacaaga 1020
ccaccacttc gaaacctggg attcaggaat gtgtggcctg cacagtgaag tgctggcaac 1080
cactaagaat tcaaactggg gcctccagaa ctcactgggg cctacagctt tgatccctga 1140
catctggaat ctggagacca gggagccttt ggttctggcc agaatgctgc aggacttgag 1200
aagacctcac ctagaaattg acacaagtgg accttaggcc ttcctctctc cagatgtttc 1260
cagacttcct tgagacacgg agcccagccc tccccatgga gccagctccc tctatttatg 1320
tttgcacttg tgattattta ttatttattt attatttatt tatttacaga tgaatgtatt 1380
tatttgggag accggggtat cctgggggac ccaatgtagg agctgccttg gctcagacat 1440
gttttccgtg aaaacggagc tgaacaatag gctgttccca tgtagccccc tggcctctgt 1500
gccttctttt gattatgttt tttaaaatat ttatctgatt aagttgtcta aacaatgctg 1560
atttggtgac caactgtcac tcattgctga gcctctgctc cccaggggag ttgtgtctgt 1620
aatcgcccta ctattcagtg gcgagaaata aagtttgctt agaaaagaa 1669
<210>70
<211>1619
<212>DNA
<213>小鼠(Mus musculus)
<400>70
cctcagcgag gacagcaagg gactagccag gagggagaac agaaactcca gaacatcttg 60
gaaatagctc ccagaaaagc aagcagccaa ccaggcaggt tctgtccctt tcactcactg 120
gcccaaggcg ccacatctcc ctccagaaaa gacaccatga gcacagaaag catgatccgc 180
gacgtggaac tggcagaaga ggcactcccc caaaagatgg ggggcttcca gaactccagg 240
cggtgcctat gtctcagcct cttctcattc ctgcttgtgg caggggccac cacgctcttc 300
tgtctactga acttcggggt gatcggtccc caaagggatg agaagttccc aaatggcctc 360
cctctcatca gttctatggc ccagaccctc acactcagat catcttctca aaattcgagt 420
gacaagcctg tagcccacgt cgtagcaaac caccaagtgg aggagcagct ggagtggctg 480
agccagcgcg ccaacgccct cctggccaac ggcatggatc tcaaagacaa ccaactagtg 540
gtgccagccg atgggttgta ccttgtctac tcccaggttc tcttcaaggg acaaggctgc 600
cccgactacg tgctcctcac ccacaccgtc agccgatttg ctatctcata ccaggagaaa 660
gtcaacctcc tctctgccgt caagagcccc tgccccaagg acacccctga gggggctgag 720
ctcaaaccct ggtatgagcc catatacctg ggaggagtct tccagctgga gaagggggac 780
caactcagcg ctgaggtcaa tctgcccaag tacttagact ttgcggagtc cgggcaggtc 840
tactttggag tcattgctct gtgaagggaa tgggtgttca tccattctct acccagcccc 900
cactctgacc cctttactct gaccccttta ttgtctactc ctcagagccc ccagtctgtg 960
tccttctaac ttagaaaggg gattatggct cagagtccaa ctctgtgctc agagctttca 1020
acaactactc agaaacacaa gatgctggga cagtgacctg gactgtgggc ctctcatgca 1080
ccaccatcaa ggactcaaat gggctttccg aattcactgg agcctcgaat gtccattcct 1140
gagttctgca aagggagagt ggtcaggttg cctctgtctc agaatgaggc tggataagat 1200
ctcaggcctt cctaccttca gacctttcca gactcttccc tgaggtgcaa tgcacagcct 1260
tcctcacaga gccagccccc ctctatttat atttgcactt attatttatt atttatttat 1320
tatttattta tttgcttatg aatgtattta tttggaaggc cggggtgtcc tggaggaccc 1380
agtgtgggaa gctgtcttca gacagacatg ttttctgtga aaacggagct gagctgtccc 1440
cacctggcct ctctaccttg ttgcctcctc ttttgcttat gtttaaaaca aaatatttat 1500
ctaacccaat tgtcttaata acgctgattt ggtgaccagg ctgtcgctac atcactgaac 1560
ctctgctccc cacgggagcc gtgactgtaa ttgccctaca gtcaattgag agaaataaa 1619
<210>71
<211>233
<212>PRT
<213>智人(Homo sapiens)
<400>71
Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala
1 5 10 15
Leu Pro Lys Lys Thr Gly Gly Pro Gln Gly Ser Arg Arg Cys Leu Phe
20 25 30
Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe
35 40 45
Cys Leu Leu Hi s Phe Gly Val Ile Gly Pro Gln Arg Glu Glu Phe Pro
50 55 60
Arg Asp Leu Ser Leu Ile Ser Pro Leu Ala Gln Ala Val Arg Ser Ser
65 70 75 80
Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala Asn Pro
85 90 95
Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu
100 105 110
Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val Pro Ser
115 120 125
Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly Gln Gly
130 135 140
Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile Ser Arg Ile Ala
145 150 155 160
Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys Ser Pro
165 170 175
Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Glu
180 185 190
Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp Arg Leu
195 200 205
Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu Ser Gly
210 215 220
Gln Val Tyr Phe Gly Ile Ile Ala Leu
225 230
<210>72
<211>233
<212>PRT
<213>智人(Homo sapiens)
<400>72
Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala
1 5 10 15
Leu Pro Lys Lys Thr Gly Gly Pro Gln Gly Ser Arg Arg Cys Leu Phe
20 25 30
Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe
35 40 45
Cys Leu Leu His Phe Gly Val Ile Gly Pro Gln Arg Glu Glu Phe Pro
50 55 60
Arg Asp Leu Ser Leu Ile Ser Pro Leu Ala Gln Ala Val Arg Ser Ser
65 70 75 80
Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala Asn Pro
85 90 95
Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu
100 105 110
Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val Pro Ser
115 120 125
Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly Gln Gly
130 135 140
Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile Ser Arg Ile Ala
145 150 155 160
Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys Ser Pro
165 170 175
Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Glu
180 185 190
Pro Ile Tyr Leu Gly Gly ValPhe Gln Leu Glu Lys Gly Asp Arg Leu
195 200 205
Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu Ser Gly
210 215 220
Gln Val Tyr Phe Gly Ile Ile Ala Leu
225 230
<210>73
<211>18
<212>PRT
<213>智人(Homo sapiens)
<400>73
Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe
1 5 10 15
Cys Leu
<210>74
<211>233
<212>PRT
<213>智人(Homo sapiens)
<400>74
Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala
1 5 10 15
Leu Pro Lys Lys Thr Gly Gly Pro Gln Gly Ser Arg Arg Cys Leu Phe
20 25 30
Leu Ser Leu Phe Ser Phe Leu Ile Val Ala Gly Ala Thr Thr Leu Phe
35 40 45
Cys Leu Leu His Phe Gly Val Ile Gly Pro Gln Arg Glu Glu Phe Pro
50 55 60
Arg Asp Leu Ser Leu Ile Ser Pro Leu Ala Gln Ala Val Arg Ser Ser
65 70 75 80
Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val Ala Asn Pro
85 90 95
Gln Ala Glu Gly Gln Leu Gln Trp Leu Asn Arg Arg Ala Asn Ala Leu
100 105 110
Leu Ala Asn Gly Val Glu Leu Arg Asp Asn Gln Leu Val Val Pro Ser
115 120 125
Glu Gly Leu Tyr Leu Ile Tyr Ser Gln Val Leu Phe Lys Gly Gln Gly
130 135 140
Cys Pro Ser Thr His Val Leu Leu Thr His Thr Ile Ser Arg Ile Ala
145 150 155 160
Val Ser Tyr Gln Thr Lys Val Asn Leu Leu Ser Ala Ile Lys Ser Pro
165 170 175
Cys Gln Arg Glu Thr Pro Glu Gly Ala Glu Ala Lys Pro Trp Tyr Glu
180 185 190
Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp Arg Leu
195 200 205
Ser Ala Glu Ile Asn Arg Pro Asp Tyr Leu Asp Phe Ala Glu Ser Gly
210 215 220
Gln Val Tyr Phe Gly Ile Ile Ala Leu
225 230
<210>75
<211>15
<212>PRT
<213>智人(Homo sapiens)
<400>75
Ser Ser Ser Arg Thr Pro Ser Asp Lys Pro Val Ala His Val Val
1 5 10 15
<210>76
<211>235
<212>PRT
<213>小鼠(Mus musculus)
<400>76
Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala
1 5 10 15
Leu Pro Gln Lys Met Gly Gly Phe Gln Asn Ser Arg Arg Cys Leu Cys
20 25 30
Leu Ser Leu Phe Ser Phe Leu Leu Val Ala Gly Ala Thr Thr Leu Phe
35 40 45
Cys Leu Leu Asn Phe Gly Val Ile Gly Pro Gln Arg Asp Glu Lys Phe
50 55 60
Pro Asn Gly Leu Pro Leu Ile Ser Ser Met Ala Gln Thr Leu Thr Leu
65 70 75 80
Arg Ser Ser Ser Gln Asn Ser Ser Asp Lys Pro Val Ala His Val Val
85 90 95
Ala Asn His Gln Val Glu Glu Gln Leu Glu Trp Leu Ser Gln Arg Ala
100 105 110
Asn Ala Leu Leu Ala Asn Gly Met Asp Leu Lys Asp Asn Gln Leu Val
115 120 125
Val Pro Ala Asp Gly Leu Tyr Leu Val Tyr Ser Gln Val Leu Phe Lys
130 135 140
Gly Gln Gly Cys Pro Asp Tyr Val Leu Leu Thr His Thr Val Ser Arg
145 150 155 160
Phe Ala Ile Ser Tyr Gln Glu Lys Val Asn Leu Leu Ser Ala Val Lys
165 170 175
Ser Pro Cys Pro Lys Asp Thr Pro Glu Gly Ala Glu Leu Lys Pro Trp
180 185 190
Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp
195 200 205
Gln Leu Ser Ala Glu Val Asn Leu Pro Lys Tyr Leu Asp Phe Ala Glu
210 215 220
Ser Gly Gln Val Tyr Phe Gly Val Ile Ala Leu
225 230 235
<210>77
<211>235
<212>PRT
<213>小鼠(Mus musculus)
<400>77
Met Ser Thr Glu Ser Met Ile Arg Asp Val Glu Leu Ala Glu Glu Ala
1 5 10 15
Leu Pro Gln Lys Met Gly Gly Phe Gln Asn Ser Arg Arg Cys Leu Cys
20 25 30
Leu Ser Leu Phe Ser Phe Leu Leu Val Ala Gly Ala Thr Thr Leu Phe
35 40 45
Cys Leu Leu Asn Phe Gly Val Ile Gly Pro Gln Arg Asp Glu Lys Phe
50 55 60
Pro Asn Gly Leu Pro Leu Ile Ser Ser Met Ala Gln Thr Leu Thr Leu
65 70 75 80
Arg Ser Ser Ser Gln Asn Ser Ser Asp Lys Pro Val Ala His Val Val
85 90 95
Ala Asn His Gln Val Glu Glu Gln Leu Glu Trp Leu Ser Gln Arg Ala
100 105 110
Asn Ala Leu Leu Ala Asn Gly Met Asp Leu Lys Asp Asn Gln Leu Val
115 120 125
Val Pro Ala Asp Gly Leu Tyr Leu Val Tyr Ser Gln Val Leu Phe Lys
130 135 140
Gly Gln Gly Cys Pro Asp Tyr Val Leu Leu Thr His Thr Val Ser Arg
145 150 155 160
Phe Ala Ile Ser Tyr Gln Glu Lys Val Asn Leu Leu Ser Ala Val Lys
165 170 175
Ser Pro Cys Pro Lys Asp Thr Pro Glu Gly Ala Glu Leu Lys Pro Trp
180 185 190
Tyr Glu Pro Ile Tyr Leu Gly Gly Val Phe Gln Leu Glu Lys Gly Asp
195 200 205
Gln Leu Ser Ala Glu Val Asn Leu Pro Lys Tyr Leu Asp Phe Ala Glu
210 215 220
Ser Gly Gln Val Tyr Phe Gly Val Ile Ala Leu
225 230 235
<210>78
<211>2269
<212>DNA
<213>智人(Homo sapiens)
<400>78
tgggttggtg tttatctcct cccagccttg agggagggaa caacactgta ggatctgggg 60
agagaggaac aaaggaccgt gaaagctgct ctgtaaaagc tgacacagcc ctcccaagtg 120
agcaggactg ttcttcccac tgcaatctga cagtttactg catgcctgga gagaacacag 180
cagtaaaaac caggtttgct actggaaaaa gaggaaagag aagactttca ttgacggacc 240
cagccatggc agcgtagcag ccctgcgttt cagacggcag cagctcggga ctctggacgt 300
gtgtttgccc tcaagtttgc taagctgctg gtttattact gaagaaagaa tgtggcagat 360
tgttttcttt actctgagct gtgatcttgt cttggccgca gcctataaca actttcggaa 420
gagcatggac agcataggaa agaagcaata tcaggtccag catgggtcct gcagctacac 480
tttcctcctg ccagagatgg acaactgccg ctcttcctcc agcccctacg tgtccaatgc 540
tgtgcagagg gacgcgccgc tcgaatacga tgactcggtg cagaggctgc aagtgctgga 600
gaacatcatg gaaaacaaca ctcagtggct aatgaagctt gagaattata tccaggacaa 660
catgaagaaa gaaatggtag agatacagca gaatgcagta cagaaccaga cggctgtgat 720
gatagaaata gggacaaacc tgttgaacca aacagctgag caaacgcgga agttaactga 780
tgtggaagcc caagtattaa atcagaccac gagacttgaa cttcagctct tggaacactc 840
cctctcgaca aacaaattgg aaaaacagat tttggaccag accagtgaaa taaacaaatt 900
gcaagataag aacagtttcc tagaaaagaa ggtgctagct atggaagaca agcacatcat 960
ccaactacag tcaataaaag aagagaaaga tcagctacag gtgttagtat ccaagcaaaa 1020
ttccatcatt gaagaactag aaaaaaaaat agtgactgcc acggtgaata attcagttct 1080
tcaaaagcag caacatgatc tcatggagac agttaataac ttactgacta tgatgtccac 1140
atcaaactca gctaaggacc ccactgttgc taaagaagaa caaatcagct tcagagactg 1200
tgctgaagta ttcaaatcag gacacaccac aaatggcatc tacacgttaa cattccctaa 1260
ttctacagaa gagatcaagg cctactgtga catggaagct ggaggaggcg ggtggacaat 1320
tattcagcga cgtgaggatg gcagcgttga ttttcagagg acttggaaag aatataaagt 1380
gggatttggt aacccttcag gagaatattg gctgggaaat gagtttgttt cgcaactgac 1440
taatcagcaa cgctatgtgc ttaaaataca ccttaaagac tgggaaggga atgaggctta 1500
ctcattgtat gaacatttct atctctcaag tgaagaactc aattatagga ttcaccttaa 1560
aggacttaca gggacagccg gcaaaataag cagcatcagc caaccaggaa atgattttag 1620
cacaaaggat ggagacaacg acaaatgtat ttgcaaatgt tcacaaatgc taacaggagg 1680
ctggtggttt gatgcatgtg gtccttccaa cttgaacgga atgtactatc cacagaggca 1740
gaacacaaat aagttcaacg gcattaaatg gtactactgg aaaggctcag gctattcgct 1800
caaggccaca accatgatga tccgaccagc agatttctaa acatcccagt ccacctgagg 1860
aactgtctcg aactattttc aaagacttaa gcccagtgca ctgaaagtca cggctgcgca 1920
ctgtgtcctc ttccaccaca gagggcgtgt gctcggtgct gacgggaccc acatgctcca 1980
gattagagcc tgtaaacttt atcacttaaa cttgcatcac ttaacggacc aaagcaagac 2040
cctaaacatc cataattgtg attagacaga acacctatgc aaagatgaac ccgaggctga 2100
gaatcagact gacagtttac agacgctgct gtcacaacca agaatgttat gtgcaagttt 2160
atcagtaaat aactggaaaa cagaacactt atgttataca atacagatca tcttggaact 2220
gcattcttct gagcactgtt tatacactgt gtaaataccc atatgtcct 2269
<210>79
<211>2475
<212>DNA
<213>小鼠(Mus musculus)
<400>79
gatactgaca ctgtagactc aggggagaaa caaagagtcc gtgcagacct ctggagtgag 60
cagggctgct ccttcctctc aggacagctc cgagtgtgcc ggggagaaga gaagagaaga 120
gacaggcact gggaaagagc ctgctgcggg acggagaagg ctctcactga tggacttatt 180
cacacggcac agccctgtgc cttagacagc agctgagagc tcaggacgca agtttgctga 240
actcacagtt tagaacccaa aaagagagag agaatgtggc agatcatttt cctaactttt 300
ggctgggatc ttgtcttggc ctcagcctac agtaacttta ggaagagcgt ggacagcaca 360
ggcagaaggc agtaccaggt ccagaacgga ccctgcagct acacgttcct gctgccggag 420
accgacagct gccgatcttc ctccagcccc tacatgtcca atgccgtgca gagggatgca 480
cccctcgact acgacgactc agtgcaaagg ctgcaggtgc tggagaacat tctagagaac 540
aacacacagt ggctgatgaa gctggagaat tacattcagg acaacatgaa gaaggagatg 600
gtggagatcc aacagaatgt ggtgcagaac cagacagctg tgatgataga gattggaacc 660
agcttgctga accagacagc agcacaaact cggaaactga ctgatgtgga agcccaagta 720
ctaaaccaga cgacaagact cgagctgcag cttctccaac attctatttc taccaacaaa 780
ttggaaaagc agattttgga tcagaccagt gaaataaaca agctacaaaa taagaacagc 840
ttcctagaac agaaagttct ggacatggag ggcaagcaca gcgagcagct acagtccatg 900
aaggagcaga aggacgagct ccaggtgctg gtgtccaagc agagctctgt cattgacgag 960
ctggagaaga agctggtgac agccacggtc aacaactcgc tccttcagaa gcagcagcat 1020
gacctaatgg agaccgtcaa cagcttgctg accatgatgt catcacccaa ctccaagagc 1080
tcggttgcta tccgtaaaga agagcaaacc accttcagag actgtgcgga aatcttcaag 1140
tcaggactca ccaccagtgg catctacaca ctgaccttcc ccaactccac agaggagatc 1200
aaggcctact gtgacatgga cgtgggtgga ggagggtgga cagtcatcca acaccgagaa 1260
gatggcagtg tggacttcca gaggacgtgg aaagaataca aagagggctt cgggagccct 1320
ctgggagagt actggctggg caatgagttt gtctcccagc tgaccggtca gcaccgctac 1380
gtgcttaaga tccagctgaa ggactgggaa ggcaacgagg cgcattcgct gtatgatcac 1440
ttctacctcg ctggtgaaga gtccaactac aggattcacc ttacaggact cacggggacc 1500
gcgggcaaaa taagtagcat cagccaacca ggaagtgatt ttagcacaaa ggattcggac 1560
aatgacaaat gcatctgcaa gtgttcccag atgctctcag gaggctggtg gtttgacgca 1620
tgtggtcctt ccaacttgaa tggacagtac tacccacaaa aacagaatac aaataagttt 1680
aacggtatca agtggtacta ctggaagggg tccggctact cgctcaaggc cacaaccatg 1740
atgatccggc cagcagattt ctaaatgcct gcctacacta ccagaagaac ttgctgcatc 1800
caaagattaa ctccaaggca ctgagagaca ccaatgcata gcagcccctt tccacatcag 1860
gaagtgctcc tgggggtggg gagggtctgt gtgtaccaga ctgaagcgca tcacttaagc 1920
ctgcaccgct aaccaaccaa aggcactgca gtctggagaa acacttctgg gaaggttgtg 1980
gctgaggatc agaaggacag cgtgcagact ctgtcacagg gaagaatgtt ccgtgggagt 2040
tcagcagtaa ataactggaa aacagaacac ttagatggtg cagataaatc ttgggaccac 2100
attcctctaa gcacggtttc tagagtgaat acattcacag ctcggctgtc acaatgacaa 2160
ggccgtgtcc tcgcactgtg gcagccagta tccagggatt tctaagtggt gggcacaggt 2220
tatcatctgg agaagcacac attcattgtt ttcctcttgg gtgctttaca tgttcatttg 2280
aaaacaacac atttacctat cttgatggct tagtttttaa tggctggcta ctatttacta 2340
tatggcaaaa atgcccacat ctctggaata accaccaaat aagcgccatg ttggtgaatg 2400
cggagactgt actattttgt tttcttcctg gctgttaaat atgaaggtat ttttagtaat 2460
taaatataag ttatt 2475
<210>80
<211>496
<212>PRT
<213>智人(Homo sapiens)
<400>80
Met Trp Gln Ile Val Phe Phe Thr Leu Ser Cys Asp Leu Val Leu Ala
1 5 10 15
Ala Ala Tyr Asn Asn Phe Arg Lys Ser Met Asp Ser Ile Gly Lys Lys
20 25 30
Gln Tyr Gln Val Gln His Gly Ser Cys Ser Tyr Thr Phe Leu Leu Pro
35 40 45
Glu Met Asp Asn Cys Arg Ser Ser Ser Ser Pro Tyr Val Ser Asn Ala
50 55 60
Val Gln Arg Asp Ala Pro Leu Glu Tyr Asp Asp Ser Val Gln Arg Leu
65 70 75 80
Gln Val Leu Glu Asn Ile Met Glu Asn Asn Thr Gln Trp Leu Met Lys
85 90 95
Leu Glu Asn Tyr Ile Gln Asp Asn Met Lys Lys Glu Met Val Glu Ile
100 105 110
Gln Gln Asn Ala Val Gln Asn Gln Thr Ala Val Met Ile Glu Ile Gly
115 120 125
Thr Asn Leu Leu Asn Gln Thr Ala Glu Gln Thr Arg Lys Leu Thr Asp
130 135 140
Val Glu Ala Gln Val Leu Asn Gln Thr Thr Arg Leu Glu Leu Gln Leu
145 150 155 160
Leu Glu His Ser Leu Ser Thr Asn Lys Leu Glu Lys Gln Ile Leu Asp
165 170 175
Gln Thr Ser Glu Ile Asn Lys Leu Gln Asp Lys Asn Ser Phe Leu Glu
180 185 190
Lys Lys Val Leu Ala Met Glu Asp Lys His IleIle Gln Leu Gln Ser
195 200 205
Ile Lys Glu Glu Lys Asp Gln Leu Gln Val Leu Val Ser Lys Gln Asn
210 215 220
Ser Ile Ile Glu Glu Leu Glu Lys Lys Ile Val Thr Ala Thr Val Asn
225 230 235 240
Asn Ser Val Leu Gln Lys Gln Gln His Asp Leu Met Glu Thr Val Asn
245 250 255
Asn Leu Leu Thr Met Met Ser Thr Ser Asn Ser Ala Lys Asp Pro Thr
260 265 270
Val Ala Lys Glu Glu Gln Ile Ser Phe Arg Asp Cys Ala Glu Val Phe
275 280 285
Lys Ser Gly His Thr Thr Asn Gly Ile Tyr Thr Leu Thr Phe Pro Asn
290 295 300
Ser Thr Glu Glu Ile Lys Ala Tyr Cys Asp Met Glu Ala Gly Gly Gly
305 310 315 320
Gly Trp Thr Ile Ile Gln Arg Arg Glu Asp Gly Ser Val Asp Phe Gln
325 330 335
Arg Thr Trp Lys Glu Tyr Lys Val Gly Phe Gly Asn Pro Ser Gly Glu
340 345 350
Tyr Trp Leu Gly Asn Glu Phe Val Ser Gln Leu Thr Asn Gln Gln Arg
355 360 365
Tyr Val Leu Lys Ile His Leu Lys Asp Trp Glu Gly Asn Glu Ala Tyr
370 375 380
Ser Leu Tyr Glu His Phe Tyr Leu Ser Ser Glu Glu Leu Asn Tyr Arg
385 390 395 400
Ile Hi s Leu Lys Gly Leu Thr Gly Thr Ala Gly Lys Ile Ser Ser Ile
405 410 415
Ser Gln Pro Gly Asn Asp Phe Ser Thr Lys Asp Gly Asp Asn Asp Lys
420 425 430
Cys Ile Cys Lys Cys Ser Gln Met Leu Thr Gly Gly Trp Trp Phe Asp
435 440 445
Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Tyr Tyr Pro Gln Arg Gln
450 455 460
Asn Thr Asn Lys Phe Asn Gly Ile Lys Trp Tyr Tyr Trp Lys Gly Ser
465 470 475 480
Gly Tyr Ser Leu Lys Ala Thr Thr Met Met Ile Arg Pro Ala Asp Phe
485 490 495
<210>81
<211>496
<212>PRT
<213>智人(Homo sapiens)
<400>81
Met Trp Gln Ile Val Phe Phe Thr Leu Ser Cys Asp Leu Val Leu Ala
1 5 10 15
Ala Ala Tyr Asn Asn Phe Arg Lys Ser Met Asp Ser Ile Gly Lys Lys
20 25 30
Gln Tyr Gln Val Gln His Gly Ser Cys Ser Tyr Thr Phe Leu Leu Pro
35 40 45
Glu Met Asp Asn Cys Arg Ser Ser Ser Ser Pro Tyr Val Ser Asn Ala
50 55 60
Val Gln Arg Asp Ala Pro Leu Glu Tyr Asp Asp Ser Val Gln Arg Leu
65 70 75 80
Gln Val Leu Glu Asn Ile Met Glu Asn Asn Thr Gln Trp Leu Met Lys
85 90 95
Leu Glu Asn Tyr Ile Gln Asp Asn Met Lys Lys Glu Met Val Glu Ile
100 105 110
Gln Gln Asn Ala Val Gln Asn Gln Thr Ala Val Met Ile Glu Ile Gly
115 120 125
Thr Asn Leu Leu Asn Gln Thr Ala Glu Gln Thr Arg Lys Leu Thr Asp
130 135 140
Val Glu Ala Gln Val Leu Asn Gln Thr Thr Arg Leu Glu Leu Gln Leu
145 150 155 160
Leu Glu His Ser Leu Ser Thr Asn Lys Leu Glu Lys Gln Ile Leu Asp
165 170 175
Gln Thr Ser Glu Ile Asn Lys Leu Gln Asp Lys Asn Ser Phe Leu Glu
180 185 190
Lys Lys Val Leu Ala Met Glu Asp Lys His Ile Ile Gln Leu Gln Ser
195 200 205
Ile Lys Glu Glu Lys Asp Gln Leu Gln Val Leu Val Ser Lys Gln Asn
210 215 220
Ser Ile Ile Glu Glu Leu Glu Lys Lys Ile Val Thr Ala Thr Val Asn
225 230 235 240
Asn Ser Val Leu Gln Lys Gln Gln His Asp Leu Met Glu Thr Val Asn
245 250 255
Asn Leu Leu Thr Met Met Ser Thr Ser Asn Ser Ala Lys Asp Pro Thr
260 265 270
Val Ala Lys Glu Glu Gln Ile Ser Phe Arg Asp Cys Ala Glu Val Phe
275 280 285
Lys Ser Gly His Thr Thr Asn Gly Ile Tyr Thr Leu Thr Phe Pro Asn
290 295 300
Ser Thr Glu Glu Ile Lys Ala Tyr Cys Asp Met Glu Ala Gly Gly Gly
305 310 315 320
Gly Trp Thr Ile Ile Gln Arg Arg Glu Asp Gly Ser Val Asp Phe Gln
325 330 335
Arg Thr Trp Lys Glu Tyr Lys Val Gly Phe Gly Asn Pro Ser Gly Glu
340 345 350
Tyr Trp Leu Gly Asn Glu Phe Val Ser Gln Leu Thr Asn Gln Gln Arg
355 360 365
Tyr Val Leu Lys Ile His Leu Lys Asp Trp Glu Gly Asn Glu Ala Tyr
370 375 380
Ser Leu Tyr Glu His Phe Tyr Leu Ser Ser Glu Glu Leu Asn Tyr Arg
385 390 395 400
Ile Hi s Leu Lys Gly Leu Thr Gly Thr Ala Gly Lys Ile Ser Ser Ile
405 410 415
Ser Gln Pro Gly Asn Asp Phe Ser Thr Lys Asp Gly Asp Asn Asp Lys
420 425 430
Cys Ile Cys Lys Cys Ser Gln Met Leu Thr Gly Gly Trp Trp Phe Asp
435 440 445
Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Tyr Tyr Pro Gln Arg Gln
450 455 460
Asn Thr Asn Lys Phe Asn Gly Ile Lys Trp Tyr Tyr Trp Lys Gly Ser
465 470 475 480
Gly Tyr Ser Leu Lys Ala Thr Thr Met Met Ile Arg Pro Ala Asp Phe
485 490 495
<210>82
<211>96
<212>PRT
<213>智人(Homo sapiens)
<400>82
Met Trp Gln Ile Val Phe Phe Thr Leu Ser Cys Asp Leu Val Leu Ala
1 5 10 15
Ala Ala Tyr Asn Asn Phe Arg Lys Ser Met Asp Ser Ile Gly Lys Lys
20 25 30
Gln Tyr Gln Val Gln His Gly Ser Cys Ser Tyr Thr Phe Leu Leu Pro
35 40 45
Glu Met Asp Asn Cys Arg Ser Ser Ser Ser Pro Tyr Val Ser Asn Ala
50 55 60
Val Gln Arg Asp Ala Pro Leu Glu Tyr Asp Asp Ser Val Gln Arg Leu
65 70 75 80
Gln Val Leu Glu Asn Ile Met Glu Asn Asn Thr Gln Trp Leu Met Lys
85 90 95
<210>83
<211>13
<212>PRT
<213>智人(Homo sapiens)
<400>83
Met Lys Lys Glu Met Val Glu Ile Gln Gln Asn Ala Val
1 5 10
<210>84
<211>244
<212>PRT
<213>智人(Homo sapiens)
<400>84
Met Glu Thr Val Asn Asn Leu Leu Thr Met Met Ser Thr Ser Asn Ser
1 5 10 15
Lys Asp Pro Thr Val Ala Lys Glu Glu Gln Ile Ser Phe Arg Asp Cys
20 25 30
Ala Glu Val Phe Lys Ser Gly His Thr Thr Asn Gly Ile Tyr Thr Leu
35 40 45
Thr Phe Pro Asn Ser Thr Glu Glu Ile Lys Ala Tyr Cys Asp Met Glu
50 55 60
Ala Gly Gly Gly Gly Trp Thr Ile Ile Gln Arg Arg Glu Asp Gly Ser
65 70 75 80
Val AspPhe Gln Arg Thr Trp Lys Glu Tyr Lys Val Gly Phe Gly Asn
85 90 95
Pro Ser Gly Glu Tyr Trp Leu Gly Asn Glu Phe Val Ser Gln Leu Thr
100 105 110
Asn Gln Gln Arg Tyr Val Leu Lys Ile His Leu Lys Asp Trp Glu Gly
115 120 125
Asn Glu Ala Tyr Ser Leu Tyr Glu His Phe Tyr Leu Ser Ser Glu Glu
130 135 140
Leu Asn Tyr Arg Ile His Leu Lys Gly Leu Thr Gly Thr Ala Gly Lys
145 150 155 160
Ile Ser Ser Ile Ser Gln Pro Gly Asn Asp Phe Ser Thr Lys Asp Gly
165 170 175
Asp Asn Asp Lys Cys Ile Cys Lys Cys Ser Gln Met Leu Thr Gly Gly
180 185 190
Trp Trp Phe Asp Ala Cys Gly Pro Ser Asn Leu Asn Gly Met Tyr Tyr
195 200 205
Pro Gln Arg Gln Asn Thr Asn Lys Phe Asn Gly Ile Lys Trp Tyr Tyr
210 215 220
Trp Lys Gly Ser Gly Tyr Ser Leu Lys Ala Thr Thr Met Met Ile Arg
225 230 235 240
Pro Ala Asp Phe
<210>85
<211>496
<212>PRT
<213>小鼠(Mus musculus)
<400>85
Met Trp Gln Ile Ile Phe Leu Thr Phe Gly Trp Asp Leu Val Leu Ala
1 5 10 15
Ser Ala Tyr Ser Asn Phe Arg Lys Ser Val Asp Ser Thr Gly Arg Arg
20 25 30
Gln Tyr Gln Val Gln Asn Gly Pro Cys Ser Tyr Thr Phe Leu Leu Pro
35 40 45
Glu Thr Asp Ser Cys Arg Ser Ser Ser Ser Pro Tyr Met Ser Asn Ala
50 55 60
Val Gln Arg Asp Ala Pro Leu Asp Tyr Asp Asp Ser Val Gln Arg Leu
65 70 75 80
Gln Val Leu Glu Asn Ile Leu Glu Asn Asn Thr Gln Trp Leu Met Lys
85 90 95
Leu Glu Asn Tyr Ile Gln Asp Asn Met Lys Lys Glu Met Val Glu Ile
100 105 110
Gln Gln Asn Val Val Gln Asn Gln Thr Ala Val Met Ile Glu Ile Gly
115 120 125
Thr Ser Leu Leu Asn Gln Thr Ala Ala Gln Thr Arg Lys Leu Thr Asp
130 135 140
Val Glu Ala Gln Val Leu Asn Gln Thr Thr Arg Leu Glu Leu Gln Leu
145 150 155 160
Leu Gln His Ser Ile Ser Thr Asn Lys Leu Glu Lys Gln Ile Leu Asp
165 170 175
Gln Thr Ser Glu Ile Asn Lys Leu Gln Asn Lys Asn Ser Phe Leu Glu
180 185 190
Gln Lys Val Leu Asp Met Glu Gly Lys His Ser Glu Gln Leu Gln Ser
195 200 205
Met Lys Glu Gln Lys Asp Glu Leu Gln Val Leu Val Ser Lys Gln Ser
210 215 220
Ser Val Ile Asp Glu Leu Glu Lys Lys Leu Val Thr Ala Thr Val Asn
225 230 235 240
Asn Ser Leu Leu Gln Lys Gln Gln His Asp Leu Met Glu Thr Val Asn
245 250 255
Ser Leu Leu Thr Met Met Ser Ser Pro Asn Ser Lys Ser Ser Val Ala
260 265 270
Ile Arg Lys Glu Glu Gln Thr Thr Phe Arg Asp Cys Ala Glu Ile Phe
275 280 285
Lys Ser Gly Leu Thr Thr Ser Gly Ile Tyr Thr Leu Thr Phe Pro Asn
290 295 300
Ser Thr Glu Glu Ile Lys Ala Tyr Cys Asp Met Asp Val Gly Gly Gly
305 310 315 320
Gly Trp Thr Val Ile Gln His Arg Glu Asp Gly Ser Val Asp Phe Gln
325 330 335
Arg Thr Trp Lys Glu Tyr Lys Glu Gly Phe Gly Ser Pro Leu Gly Glu
340 345 350
Tyr Trp Leu Gly Asn Glu Phe Val Ser Gln Leu Thr Gly Gln His Arg
355 360 365
Tyr Val Leu Lys Ile Gln Leu Lys Asp Trp Glu Gly Asn Glu Ala His
370 375 380
Ser Leu Tyr Asp Hi s Phe Tyr Leu Ala Gly Glu Glu Ser Asn Tyr Arg
385 390 395 400
Ile His Leu Thr Gly Leu Thr Gly Thr Ala Gly Lys Ile Ser Ser Ile
405 410 415
Ser Gln Pro Gly Ser Asp Phe Ser Thr Lys Asp Ser Asp Asn Asp Lys
420 425 430
Cys Ile Cys Lys Cys Ser Gln Met Leu Ser Gly Gly Trp Trp Phe Asp
435 440 445
Ala Cys Gly Pro Ser Asn Leu Asn Gly Gln Tyr Tyr Pro Gln Lys Gln
450 455 460
Asn Thr Asn Lys Phe Asn Gly Ile Lys Trp Tyr Tyr Trp Lys Gly Ser
465 470 475 480
Gly Tyr Ser Leu Lys Ala Thr Thr Met Met Ile Arg Pro Ala Asp Phe
485 490 495
<210>86
<211>496
<212>PRT
<213>小鼠(Mus musculus)
<400>86
Met Trp Gln Ile Ile Phe Leu Thr Phe Gly Trp Asp Leu Val Leu Ala
1 5 10 15
Ser Ala Tyr Ser Asn Phe Arg Lys Ser Val Asp Ser Thr Gly Arg Arg
20 25 30
Gln Tyr Gln Val Gln Asn Gly Pro Cys Ser Tyr Thr Phe Leu Leu Pro
35 40 45
Glu Thr Asp Ser Cys Arg Ser Ser Ser Ser Pro Tyr Met Ser Asn Ala
50 55 60
Val Gln Arg Asp Ala Pro Leu Asp Tyr Asp Asp Ser Val Gln Arg Leu
65 70 75 80
Gln Val Leu Glu Asn Ile Leu Glu Asn Asn Thr Gln Trp Leu Met Lys
85 90 95
Leu Glu Asn Tyr Ile Gln Asp Asn Met Lys Lys Glu Met Val Glu Ile
100 105 110
Gln Gln Asn Val Val Gln Asn Gln Thr Ala Val Met Ile Glu Ile Gly
115 120 125
Thr Ser Leu Leu Asn Gln Thr Ala Ala Gln Thr Arg Lys Leu Thr Asp
130 135 140
Val Glu Ala Gln Val Leu Asn Gln Thr Thr Arg Leu Glu Leu Gln Leu
145 150 155 160
Leu Gln His Ser Ile Ser Thr Asn Lys Leu Glu Lys Gln Ile Leu Asp
165 170 175
Gln Thr Ser Glu Ile Asn Lys Leu Gln Asn Lys Asn Ser Phe Leu Glu
180 185 190
Gln Lys Val Leu Asp Met Glu Gly Lys His Ser Glu Gln Leu Gln Ser
195 200 205
Met Lys Glu Gln Lys Asp Glu Leu Gln Val Leu Val Ser Lys Gln Ser
210 215 220
Ser Val Ile Asp Glu Leu Glu Lys Lys Leu Val Thr Ala Thr Val Asn
225 230 235 240
Asn Ser Leu Leu Gln Lys Gln Gln His Asp Leu Met Glu Thr Val Asn
245 250 255
Ser Leu Leu Thr Met Met Ser Ser Pro Asn Ser Lys Ser Ser Val Ala
260 265 270
Ile Arg Lys Glu Glu Gln Thr Thr Phe Arg Asp Cys Ala Glu Ile Phe
275 280 285
Lys Ser Gly Leu Thr Thr Ser Gly Ile Tyr Thr Leu Thr Phe Pro Asn
290 295 300
Ser Thr Glu Glu Ile Lys Ala Tyr Cys Asp Met Asp Val Gly Gly Gly
305 310 315 320
Gly Trp Thr Val Ile Gln His Arg Glu Asp Gly Ser Val Asp Phe Gln
325 330 335
Arg Thr Trp Lys Glu Tyr Lys Glu Gly Phe Gly Ser Pro Leu Gly Glu
340 345 350
Tyr Trp Leu Gly Asn Glu Phe Val Ser Gln Leu Thr Gly Gln His Arg
355 360 365
Tyr Val Leu Lys Ile Gln Leu Lys Asp Trp Glu Gly Asn Glu Ala His
370 375 380
Ser Leu Tyr Asp His Phe Tyr Leu Ala Gly Glu Glu Ser Asn Tyr Arg
385 390 395 400
Ile His Leu Thr Gly Leu Thr Gly Thr Ala Gly Lys Ile Ser Ser Ile
405 410 415
Ser Gln Pro Gly Ser Asp Phe Ser Thr Lys Asp Ser Asp Asn Asp Lys
420 425 430
Cys Ile Cys Lys Cys Ser Gln Met Leu Ser Gly Gly Trp Trp Phe Asp
435 440 445
Ala Cys Gly Pro Ser Asn Leu Asn Gly Gln Tyr Tyr Pro Gln Lys Gln
450 455 460
Asn Thr Asn Lys Phe Asn Gly Ile Lys Trp Tyr Tyr Trp Lys Gly Ser
465 470 475 480
Gly Tyr Ser Leu Lys Ala Thr Thr Met Met Ile Arg Pro Ala Asp Phe
485 490 495
<210>87
<211>816
<212>DNA
<213>智人(Homo sapiens)
<400>87
atgcactttc tttgccaaag gcaaacgcag aacgtttcag agccatgagg atgcttctgc 60
atttgagttt gctagctctt ggagctgcct acgtgtatgc catccccaca gaaattccca 120
caagtgcatt ggtgaaagag accttggcac tgctttctac tcatcgaact ctgctgatag 180
ccaatgagac tctgaggatt cctgttcctg tacataaaaa tcaccaactg tgcactgaag 240
aaatctttca gggaataggc acactggaga gtcaaactgt gcaagggggt actgtggaaa 300
gactattcaa aaacttgtcc ttaataaaga aatacattga cggccaaaaa aaaaagtgtg 360
gagaagaaag acggagagta aaccaattcc tagactacct gcaagagttt cttggtgtaa 420
tgaacaccga gtggataata gaaagttgag actaaactgg tttgttgcag ccaaagattt 480
tggaggagaa ggacatttta ctgcagtgag aatgagggcc aagaaagagt caggccttaa 540
ttttcagtat aatttaactt cagagggaaa gtaaatattt caggcatact gacactttgc 600
cagaaagcat aaaattctta aaatatattt cagatatcag aatcattgaa gtattttcct 660
ccaggcaaaa ttgatatact tttttcttat ttaacttaac attctgtaaa atgtctgtta 720
acttaatagt atttatgaaa tggttaagaa tttggtaaat tagtatttat ttaatgttat 780
gttgtgttct aataaaacaa aaatagacaa ctgttc 816
<210>88
<211>1534
<212>DNA
<213>小鼠(Mus musculus)
<400>88
cgctcttcct ttgctgaagg ccagcgctga agacttcaga gtcatgagaa ggatgcttct 60
gcacttgagt gttctgactc tcagctgtgt ctgggccact gccatggaga ttcccatgag 120
cacagtggtg aaagagacct tgacacagct gtccgctcac cgagctctgt tgacaagcaa 180
tgagacgatg aggcttcctg tccctactca taaaaatcac cagctatgca ttggagaaat 240
ctttcagggg ctagacatac tgaagaatca aactgtccgt gggggtactg tggaaatgct 300
attccaaaac ctgtcattaa taaagaaata cattgaccgc caaaaagaga agtgtggcga 360
ggagagacgg aggacgaggc agttcctgga ttacctgcaa gagttccttg gtgtgatgag 420
tacagagtgg gcaatggaag gctgaggctg agctgctcca tggtgacagg acttcacaat 480
ttaagttaaa ttgtcaacag atgcaaaaac cccacaaaac tgtgcaaatg caagggatac 540
catatgctgt ttccatttat atttatgtcc tgtagtcagt taaacctatc tatgtccata 600
tatgcaaagt gtttaacctt tttgtatacg cataaaagaa attcctgtag cgcaggctgg 660
cctcaaactg gtaatgtagc caaggataac cttgaatttc tgatcctcct gcctcctctt 720
cctgaaggct gaggttacag acatgcacca ttgccactag ttcatgaagt gctggagatg 780
gaacccaagg ctttgtgcat gttaccaact gagttatact ccctccccct catcctcttc 840
gttgcatcag ggtctcaagt attccaggct gactttgaac tcagtgtgta gccaagggtg 900
accctgaact cttggtccag atggacgcag gaggatcaca tacccaacct tagcatcctt 960
tctcctagcc cctttagata gatgatactt aatgactctc ttgctgaggg atgccacacc 1020
ggggcttcct gctcctatct aacttcaatt taatacccac tagtcaatct ctcctcaact 1080
ccctgctact ctccccaaac tctagtaagc ccacttctat ttcttgggga gagagaaggt 1140
tgacttttct tatgtcctat gtatgaatca gactgtgcca tgactgtgcc tctgtgcctg 1200
gagcagctgg attttggaaa agaaaaggga catctccttg cagtgtgaat gagagccagc 1260
cacatgctgg gccttacttc tccgtgtaac tgaacttaag aagcaaagta aataccacaa 1320
ccttactacc ccatgccaac agaaagcata aaatggttgg gatgttattc aggtatcagg 1380
gtcactggag aagcctcccc cagtttactc caggaaaaac agatgtatgc ttttatttaa 1440
ttctgtaaga tgttcatatt atttatgatg gattcagtaa gttaatattt attacaacgt 1500
atataatatt ctaataaagc agaagggaca actc 1534
<210>89
<211>134
<212>PRT
<213>智人(Homo sapiens)
<400>89
Met Arg Met Leu Leu His Leu Ser Leu Leu Ala Leu Gly Ala Ala Tyr
1 5 10 15
Val Tyr Ala Ile Pro Thr Glu Ile Pro Thr Ser Ala Leu Val Lys Glu
20 25 30
Thr Leu Ala Leu Leu Ser Thr His Arg Thr Leu Leu Ile Ala Asn Glu
35 40 45
Thr Leu Arg Ile Pro Val Pro Val His Lys Asn His Gln Leu Cys Thr
50 55 60
Glu Glu Ile Phe Gln Gly Ile Gly Thr Leu Glu Ser Gln Thr Val Gln
65 70 75 80
Gly Gly Thr Val Glu Arg Leu Phe Lys Asn Leu Ser Leu Ile Lys Lys
85 90 95
Tyr Ile Asp Gly Gln Lys Lys Lys Cys Gly Glu Glu Arg Arg Arg Val
100 105 110
Asn Gln Phe Leu Asp Tyr Leu Gln Glu Phe Leu Gly Val Met Asn Thr
115 120 125
Glu Trp Ile Ile Glu Ser
130
<210>90
<211>134
<212>PRT
<213>智人(Homo sapiens)
<400>90
Met Arg Met Leu Leu His Leu Ser Leu Leu Ala Leu Gly Ala Ala Tyr
1 5 10 15
Val Tyr Ala Ile Pro Thr Glu Ile Pro Thr Ser Ala Leu Val Lys Glu
20 25 30
Thr Leu Ala Leu Leu Ser Thr His Arg Thr Leu Leu Ile Ala Asn Glu
35 40 45
Thr Leu Arg Ile Pro Val Pro Val His Lys Asn His Gln Leu Cys Thr
50 55 60
Glu Glu Ile Phe Gln Gly Ile Gly Thr Leu Glu Ser Gln Thr Val Gln
65 70 75 80
Gly Gly Thr Val Glu Arg Leu Phe Lys Asn Leu Ser Leu Ile Lys Lys
85 90 95
Tyr Ile Asp Gly Gln Lys Lys Lys Cys Gly Glu Glu Arg Arg Arg Val
100 105 110
Asn Gln Phe Leu Asp Tyr Leu Gln Glu Phe Leu Gly Val Met Asn Thr
115 120 125
Glu Trp Ile Ile Glu Ser
130
<210>91
<211>133
<212>PRT
<213>小鼠(Mus musculus)
<400>91
Met Arg Arg Met Leu Leu His Leu Ser Val Leu Thr Leu Ser Cys Val
1 5 10 15
Trp Ala Thr Ala Met Glu Ile Pro Met Ser Thr Val Val Lys Glu Thr
20 25 30
Leu Thr Gln Leu Ser Ala His Arg Ala Leu Leu Thr Ser Asn Glu Thr
35 40 45
Met Arg Leu Pro Val Pro Thr His Lys Asn His Gln Leu Cys Ile Gly
50 55 60
Glu Ile Phe Gln Gly Leu Asp Ile Leu Lys Asn Gln Thr Val Arg Gly
65 70 75 80
Gly Thr Val Glu Met Leu Phe Gln Asn Leu Ser Leu Ile Lys Lys Tyr
85 90 95
Ile Asp Arg Gln Lys Glu Lys Cys Gly Glu Glu Arg Arg Arg Thr Arg
100 105 110
Gln Phe Leu Asp Tyr Leu Gln Glu Phe Leu Gly Val Met Ser Thr Glu
115 120 125
Trp Ala Met Glu Gly
130
<210>92
<211>133
<212>PRT
<213>小鼠(Mus musculus)
<400>92
Met Arg Arg Met Leu Leu His Leu Ser Val Leu Thr Leu Ser Cys Val
1 5 10 15
Trp Ala Thr Ala Met Glu Ile Pro Met Ser Thr Val Val Lys Glu Thr
20 25 30
Leu Thr Gln Leu Ser Ala His Arg Ala Leu Leu Thr Ser Asn Glu Thr
35 40 45
Met Arg Leu Pro Val Pro Thr His Lys Asn His Gln Leu Cys Ile Gly
50 55 60
Glu Ile Phe Gln Gly Leu Asp Ile Leu Lys Asn Gln Thr Val Arg Gly
65 70 75 80
Gly Thr Val Glu Met Leu Phe Gln Asn Leu Ser Leu Ile Lys Lys Tyr
85 90 95
Ile Asp Arg Gln Lys Glu Lys Cys Gly Glu Glu Arg Arg Arg Thr Arg
100 105 110
Gln Phe Leu Asp Tyr Leu Gln Glu Phe Leu Gly Val Met Ser Thr Glu
115 120 125
Trp Ala Met Glu Gly
130
<210>93
<211>132
<212>PRT
<213>小鼠(Mus musculus)
<400>93
Met Arg Arg Met Leu Leu His Leu Ser Val Leu Thr Leu Ser Cys Val
1 5 10 15
Trp Ala Thr Ala Met Glu Ile Pro Met Ser Thr Val Val Lys Glu Thr
20 25 30
Leu Thr Gln Leu Ser Ala His Arg Ala Leu Leu Thr Ser Asn Glu Thr
35 40 45
Met Arg Leu Pro Val Pro Thr His Lys Asn His Gln Leu Cys Ile Gly
50 55 60
Glu Ile Phe Gln Gly Leu Asp Ile Leu Lys Asn Gln Thr Val Arg Gly
65 70 75 80
Gly Thr Val Glu Met Leu Phe Gln Asn Leu Ser Leu Ile Lys Lys Tyr
85 90 95
Ile Asp Arg Gln Lys Glu Lys Cys Gly Glu Glu Arg Arg Arg Thr Arg
100 105 110
Gln Phe Leu Asp Tyr Leu Gln Glu Phe Leu Gly Val Met Ser Thr Glu
115 120 125
Trp Ala Met Glu
130
<210>94
<211>2116
<212>DNA
<213>智人(Homo sapiens)
<400>94
acatccgcgg caacgcctcc ttggtgtcgt ccgcttccaa taacccagct tgcgtcctgc 60
acacttgtgg cttccgtgca cacattaaca actcatggtt ctagctccca gtcgccaagc 120
gttgccaagg cgttgagaga tcatctggga agtcttttac ccagaattgc tttgattcag 180
gccagctggt ttttcctgcg gtgattcgga aattcgcgaa ttcctctggt cctcatccag 240
gtgcgcggga agcaggtgcc caggagagag gggataatga agattccatg ctgatgatcc 300
caaagattga acctgcagac caagcgcaaa gtagaaactg aaagtacact gctggcggat 360
cctacggaag ttatggaaaa ggcaaagcgc agagccacgc cgtagtgtgt gccgcccccc 420
ttgggatgga tgaaactgca gtcgcggcgt gggtaagagg aaccagctgc agagatcacc 480
ctgcccaaca cagactcggc aactccgcgg aagaccaggg tcctgggagt gactatgggc 540
ggtgagagct tgctcctgct ccagttgcgg tcatcatgac tacgcccgcc tcccgcagac 600
catgttccat gtttctttta ggtatatctt tggacttcct cccctgatcc ttgttctgtt 660
gccagtagca tcatctgatt gtgatattga aggtaaagat ggcaaacaat atgagagtgt 720
tctaatggtc agcatcgatc aattattgga cagcatgaaa gaaattggta gcaattgcct 780
gaataatgaa tttaactttt ttaaaagaca tatctgtgat gctaataagg aaggtatgtt 840
tttattccgt gctgctcgca agttgaggca atttcttaaa atgaatagca ctggtgattt 900
tgatctccac ttattaaaag tttcagaagg cacaacaata ctgttgaact gcactggcca 960
ggttaaagga agaaaaccag ctgccctggg tgaagcccaa ccaacaaaga gtttggaaga 1020
aaataaatct ttaaaggaac agaaaaaact gaatgacttg tgtttcctaa agagactatt 1080
acaagagata aaaacttgtt ggaataaaat tttgatgggc actaaagaac actgaaaaat 1140
atggagtggc aatatagaaa cacgaacttt agctgcatcc tccaagaatc tatctgctta 1200
tgcagttttt cagagtggaa tgcttcctag aagttactga atgcaccatg gtcaaaacgg 1260
attagggcat ttgagaaatg catattgtat tactagaaga tgaatacaaa caatggaaac 1320
tgaatgctcc agtcaacaaa ctatttctta tatatgtgaa catttatcaa tcagtataat 1380
tctgtactga tttttgtaag acaatccatg taaggtatca gttgcaataa tacttctcaa 1440
acctgtttaa atatttcaag acattaaatc tatgaagtat ataatggttt caaagattca 1500
aaattgacat tgctttactg tcaaaataat tttatggctc actatgaatc tattatactg 1560
tattaagagt gaaaattgtc ttcttctgtg ctggagatgt tttagagtta acaatgatat 1620
atggataatg ccggtgagaa taagagagtc ataaacctta agtaagcaac agcataacaa 1680
ggtccaagat acctaaaaga gatttcaaga gatttaatta atcatgaatg tgtaacacag 1740
tgccttcaat aaatggtata gcaaatgttt tgacatgaaa aaaggacaat ttcaaaaaaa 1800
taaaataaaa taaaaataaa ttcacctagt ctaaggatgc taaaccttag tactgagtta 1860
cattgtcatt tatatagatt ataacttgtc taaataagtt tgcaatttgg gagatatatt 1920
tttaagataa taatatatgt ttacctttta attaatgaaa tatctgtatt taattttgac 1980
actatatctg tatataaaat attttcatac agcattacaa attgcttact ttggaataca 2040
tttctccttt gataaaataa atgagctatg tattaacaaa aaaaaaaaaa aaaaaaaaaa 2100
aaaaaaaaaa aaaaaa 2116
<210>95
<211>2478
<212>DNA
<213>小鼠(Mus musculus)
<400>95
gggcagatcc tacggaagtt atggcaaagc cagagcgcct gggtggccgg tgatgcatgc 60
ggcccctctt gggatggatg gaccaggcgt ggcgtgggtg agaggagtca gctgcctgaa 120
ctgccctgcc cagcaccggt ttgcggccac ccggtggatg accggggtcc tgggagtgat 180
tatgggtggt gagagccggc tcctgctgca gtcccagtca tcatgactac acccacctcc 240
cgcagaccat gttccatgtt tcttttagat atatctttgg aattcctcca ctgatccttg 300
ttctgctgcc tgtcacatca tctgagtgcc acattaaaga caaagaaggt aaagcatatg 360
agagtgtact gatgatcagc atcgatgaat tggacaaaat gacaggaact gatagtaatt 420
gcccgaataa tgaaccaaac ttttttagaa aacatgtatg tgatgataca aaggaagctg 480
cttttctaaa tcgtgctgct cgcaagttga agcaatttct taaaatgaat atcagtgaag 540
aattcaatgt ccacttacta acagtatcac aaggcacaca aacactggtg aactgcacaa 600
gtaaggaaga aaaaaacgta aaggaacaga aaaagaatga tgcatgtttc ctaaagagac 660
tactgagaga aataaaaact tgttggaata aaattttgaa gggcagtata taaacaggac 720
atgtagtaac aacctccaag aatctactgg ttcatatact tggagaggtt gaaacccttc 780
cagaagttcc tggatgcctc ctgctcaaat aagccaagca gctgagaaat ctacagtgag 840
gtatgagatg atggacacag aaatgcagct gactgctgcc gtcagcatat acatataaag 900
atatatcaac tatacagatt tttgtaatgc aatcatgtca actgcaatgc ttttaaaacc 960
gttccaaatg tttctaacac tacaaagtct acaaaaagca aggctatgaa gattcagagt 1020
caccactgtt ttcttagcaa aatgatggta tggttaaaca ttcattggtg aaccactggg 1080
ggagtggaac tgtcctgttt tagactggag atactggagg gctcacggtg atggataatg 1140
ctcttgaaaa caagagtcta tcttaaagca gcagcaaaaa gaagcttaag gcacttaagg 1200
catcaacaaa tgtagttaaa tatgaatgta taacacataa cttcagtaaa gagcatagca 1260
gatattttta aataaaagta tttttaaaga tagaaatgca cttattccaa agatactgaa 1320
ccttagtatt cagtcgcttt tgacacttgt gtataataaa gcttatataa ctgaattttc 1380
aatttgaaaa gtatattttt aaaagaataa tatatgctag acttttaatt aatgtatatg 1440
tttaattttg gcattctgtc tgtctctctg tctctctctc tctctctctc tctctctacc 1500
tatctatcta tatatataat tttcatatac taccaattgc gtactttgga tagtgtctct 1560
ttttaaccta aatgaccttt attaacagct gtcaggttcc cttactctcg agagtgttca 1620
ttgctgcact gtcatttgat cccagtttta ttgaacacat atcctttaac acactcacgt 1680
ccagatttag caggagacta ggaccctata actttgttaa gagagaaaac actaatttct 1740
tgttttatag tagggtctta ttcgtatcta aggcaggcta ggattgcaga catgagccaa 1800
tatgcttaat tagaaacatt ctttttatgt taaactcatg tcttttacaa gatgcctaca 1860
tatatcctat gtatatgcct gtttaaatcc ttttttgtaa ggtctgctgt cttccttcag 1920
ttgtaatgga aagaaacact atgttgtgga ggccaaattt ctgaaagtga taagggtttg 1980
cttgtactga attctcattc tccttgcttt ttccagccac gtgagcatct agctatctat 2040
acgctggatg tatttgaccg atgcctgctc cactggcaca ttgcatgtgt ggtagccatg 2100
ccttcttgct tctccttttc cccaacccct ataatgctct actcagtggt acagatagct 2160
gggattatca caattttgag agaaacacca attgtttaaa gtttgtttca taatcaccat 2220
ttgcccagaa aacagttctc tcaacttgtt tgcaacatgt aataatttaa gaaactcaat 2280
tttgttaatg gactttcgat aacttcctta gatatcccac atctcctacg tgtcagtcct 2340
ttgtcctgag gaactggtaa aatgggtaag cccttagcta gcgaactgaa ggcattcgca 2400
tgtgtaagat aatctctata cctgcaaggc tgtctggatg gctccctacc aatattgaac 2460
aatattctga ttttggcg 2478
<210>96
<211>177
<212>PRT
<213>智人(Homo sapiens)
<400>96
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Leu Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Ala Ser Ser Asp Cys Asp Ile Glu Gly Lys
20 25 30
Asp Gly Lys Gln Tyr Glu Ser Val Leu Met Val Ser Ile Asp Gln Leu
35 40 45
Leu Asp Ser Met Lys Glu Ile Gly Ser Asn Cys Leu Asn Asn Glu Phe
50 55 60
Asn Phe Phe Lys Arg His Ile Cys Asp Ala Asn Lys Glu Gly Met Phe
65 70 75 80
Leu Phe Arg Ala Ala Arg Lys Leu Arg Gln Phe Leu Lys Met Asn Ser
85 90 95
Thr Gly Asp Phe Asp Leu His Leu Leu Lys Val Ser Glu Gly Thr Thr
100 105 110
Ile Leu Leu Asn Cys Thr Gly Gln Val Lys Gly Arg Lys Pro Ala Ala
115 120 125
Leu Gly Glu Ala Gln Pro Thr Lys Ser Leu Glu Glu Asn Lys Ser Leu
130 135 140
Lys Glu Gln Lys Lys Leu Asn Asp Leu Cys Phe Leu Lys Arg Leu Leu
145 150 155 160
Gln Glu Ile Lys Thr Cys Trp Asn Lys Ile Leu Met Gly Thr Lys Glu
165 170 175
His
<210>97
<211>177
<212>PRT
<213>智人(Homo sapiens)
<400>97
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Leu Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Ala Ser Ser Asp Cys Asp Ile Glu Gly Lys
20 25 30
Asp Gly Lys Gln Tyr Glu Ser Val Leu Met Val Ser Ile Asp Gln Leu
35 40 45
Leu Asp Ser Met Lys Glu Ile Gly Ser Asn Cys Leu Asn Asn Glu Phe
50 55 60
Asn Phe Phe Lys Arg His Ile Cys Asp Ala Asn Lys Glu Gly Met Phe
65 70 75 80
Leu Phe Arg Ala Ala Arg Lys Leu Arg Gln Phe Leu Lys Met Asn Ser
85 90 95
Thr Gly Asp Phe Asp Leu Hi s Leu Leu Lys Val Ser Glu Gly Thr Thr
100 105 110
Ile Leu Leu Asn Cys Thr Gly Gln Val Lys Gly Arg Lys Pro Ala Ala
115 120 125
Leu Gly Glu Ala Gln Pro Thr Lys Ser Leu Glu Glu Asn Lys Ser Leu
130 135 140
Lys Glu Gln Lys Lys Leu Asn Asp Leu Cys Phe Leu Lys Arg Leu Leu
145 150 155 160
Gln Glu Ile Lys Thr Cys Trp Asn Lys Ile Leu Met Gly Thr Lys Glu
165 170 175
His
<210>98
<211>115
<212>PRT
<213>智人(Homo sapiens)
<400>98
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Leu Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Ala Ser Ser Asp Cys Asp Ile Glu Gly Lys
20 25 30
Asp Gly Lys Gln Tyr Glu Ser Val Leu Met Val Ser Ile Asp Gln Leu
35 40 45
Leu Asp Ser Met Lys Glu Ile Gly Ser Asn Cys Leu Asn Asn Glu Phe
50 55 60
Asn Phe Phe Lys Arg His Ile Cys Asp Ala Asn Lys Glu Glu Asn Lys
65 70 75 80
Ser Leu Lys Glu Gln Lys Lys Leu Asn Asp Leu Cys Phe Leu Lys Arg
85 90 95
Leu Leu Gln Glu Ile Lys Thr Cys Trp Asn Lys Ile Leu Met Gly Thr
100 105 110
Lys Glu His
115
<210>99
<211>64
<212>PRT
<213>智人(Homo sapiens)
<400>99
Met Lys Glu Ile Gly Ser Asn Cys Leu Asn Asn Glu Phe Asn Phe Phe
1 5 10 15
Lys Arg His Ile Cys Asp Ala Asn Lys Glu Glu Asn Lys Ser Leu Lys
20 25 30
Glu Gln Lys Lys Leu Asn Asp Leu Cys Phe Leu Lys Arg Leu Leu Gln
35 40 45
Glu Ile Lys Thr Cys Trp Asn Lys Ile Leu Met Gly Thr Lys Glu His
50 55 60
<210>100
<211>37
<212>PRT
<213>智人(Homo sapiens)
<400>100
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Leu Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Ala Ser Ser Asp Cys Asp Ile Glu Gly Gln
20 25 30
His Glu Arg Asn Trp
35
<210>101
<211>31
<212>PRT
<213>智人(Homo sapiens)
<400>101
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Leu Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Ala Ser Ser Asp Cys Asp Ile Glu Gly
20 25 30
<210>102
<211>133
<212>PRT
<213>智人(Homo sapiens)
<400>102
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Leu Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Ala Ser Ser Asp Cys Asp Ile Glu Gly Lys
20 25 30
Asp Gly Lys Gln Tyr Glu Ser Val Leu Met Val Ser Ile Asp Gln Leu
35 40 45
Leu Asp Ser Met Lys Glu Ile Gly Ser Asn Cys Leu Asn Asn Glu Phe
50 55 60
Asn Phe Phe Lys Arg His Ile Cys Asp Ala Asn Lys Val Lys Gly Arg
65 70 75 80
Lys Pro Ala Ala Leu Gly Glu Ala Gln Pro Thr Lys Ser Leu Glu Glu
85 90 95
Asn Lys Ser Leu Lys Glu Gln Lys Lys Leu Asn Asp Leu Cys Phe Leu
100 105 110
Lys Arg Leu Leu Gln Glu Ile Lys Thr Cys Trp Asn Lys Ile Leu Met
115 120 125
Gly Thr Lys Glu His
130
<210>103
<211>154
<212>PRT
<213>小鼠(Mus musculus)
<400>103
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Ile Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Thr Ser Ser Glu Cys His Ile Lys Asp Lys
20 25 30
Glu Gly Lys Ala Tyr Glu Ser Val Leu Met Ile Ser Ile Asp Glu Leu
35 40 45
Asp Lys Met Thr Gly Thr Asp Ser Asn Cys Pro Asn Asn Glu Pro Asn
50 55 60
Phe Phe Arg Lys His Val Cys Asp Asp Thr Lys Glu Ala Ala Phe Leu
65 70 75 80
Asn Arg Ala Ala Arg Lys Leu Lys Gln Phe Leu Lys Met Asn Ile Ser
85 90 95
Glu Glu Phe Asn Val Hi s Leu Leu Thr Val Ser Gln Gly Thr Gln Thr
100 105 110
Leu Val Asn Cys Thr Ser Lys Glu Glu Lys Asn Val Lys Glu Gln Lys
115 120 125
Lys Asn Asp Ala Cys Phe Leu Lys Arg Leu Leu Arg Glu Ile Lys Thr
130 135 140
Cys Trp Asn Lys Ile Leu Lys Gly Ser Ile
145 150
<210>104
<211>154
<212>PRT
<213>小鼠(Mus musculus)
<400>104
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Ile Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Thr Ser Ser Glu Cys His Ile Lys Asp Lys
20 25 30
Glu Gly Lys Ala Tyr Glu Ser Val Leu Met Ile Ser Ile Asp Glu Leu
35 40 45
Asp Lys Met Thr Gly Thr Asp Ser Asn Cys Pro Asn Asn Glu Pro Asn
50 55 60
Phe Phe Arg Lys His Val Cys Asp Asp Thr Lys Glu Ala Ala Phe Leu
65 70 75 80
Asn Arg Ala Ala Arg Lys Leu Lys Gln Phe Leu Lys Met Asn Ile Ser
85 90 95
Glu Glu Phe Asn Val His Leu Leu Thr Val Ser Gln Gly Thr Gln Thr
100 105 110
Leu Val Asn Cys Thr Ser Lys Glu Glu Lys Asn Val Lys Glu Gln Lys
115 120 125
Lys Asn Asp Ala Cys Phe Leu Lys Arg Leu Leu Arg Glu Ile Lys Thr
130 135 140
Cys Trp Asn Lys Ile Leu Lys Gly Ser Ile
145 150
<210>105
<211>154
<212>PRT
<213>小鼠(Mus musculus)
<400>105
Met Phe His Val Ser Phe Arg Tyr Ile Phe Gly Ile Pro Pro Leu Ile
1 5 10 15
Leu Val Leu Leu Pro Val Thr Ser Ser Glu Cys His Ile Lys Asp Lys
20 25 30
Glu Gly Lys Ala Tyr Glu Ser Val Leu Met Ile Ser Ile Asp Glu Leu
35 40 45
Asp Lys Met Thr Gly Thr Asp Ser Asn Cys Pro Asn Asn Glu Pro Asn
50 55 60
Phe Phe Arg Lys His Val Cys Asp Asp Thr Lys Glu Ala Ala Phe Leu
65 70 75 80
Asn Arg Ala Ala Arg Lys Leu Lys Gln Phe Leu Lys Met Asn Ile Ser
85 90 95
Glu Glu Phe Asn Val His Leu Leu Thr Val Ser Gln Gly Thr Gln Thr
100 105 110
Leu Val Asn Cys Thr Ser Lys Glu Glu Lys Asn Val Lys Glu Gln Lys
115 120 125
Lys Asn Asp Ala Cys Phe Leu Lys Arg Leu Leu Arg Glu Ile Lys Thr
130 135 140
Cys Trp Asn Lys Ile Leu Lys Gly Ser Ile
145 150
<210>106
<211>137
<212>PRT
<213>小鼠(Mus musculus)
<400>106
Val Leu Leu Pro Val Thr Ser Ser Glu Cys His Ile Lys Asp Lys Glu
1 5 10 15
Gly Lys Ala Tyr Glu Ser Val Leu Met Ile Ser Ile Asp Glu Leu Asp
20 25 30
Ile Met Thr Gly Thr Asp Ser Asn Cys Pro Asn Asn Glu Pro Asn Phe
35 40 45
Phe Arg Lys His Val Cys Asp Asp Thr Lys Glu Ala Ala Phe Leu Asn
50 55 60
Arg Ala Ala Arg Lys Leu Lys Gln Phe Leu Lys Met Asn Ile Ser Glu
65 70 75 80
Glu Phe Asn Val His Leu Leu Thr Val Ser Gln Gly Thr Gln Thr Leu
85 90 95
Val Asn Cys Thr Ser Lys Glu Glu Lys Asn Val Lys Glu Gln Lys Lys
100 105 110
Asn Asp Ala Cys Phe Leu Lys Arg Leu Leu Arg Glu Ile Lys Thr Cys
115 120 125
Trp Asn Lys Ile Leu Lys Gly Ser Ile
130 135
<210>107
<211>7260
<212>DNA
<213>智人(Homo sapiens)
<400>107
tcactgtcac tgctaaattc agagcagatt agagcctgcg caatggaata aagtcctcaa 60
aattgaaatg tgacattgct ctcaacatct cccatctctc tggatttcct tttgcttcat 120
tattcctgct aaccaattca ttttcagact ttgtacttca gaagcaatgg gaaaaatcag 180
cagtcttcca acccaattat ttaagtgctg cttttgtgat ttcttgaagg tgaagatgca 240
caccatgtcc tcctcgcatc tcttctacct ggcgctgtgc ctgctcacct tcaccagctc 300
tgccacggct ggaccggaga cgctctgcgg ggctgagctg gtggatgctc ttcagttcgt 360
gtgtggagac aggggctttt atttcaacaa gcccacaggg tatggctcca gcagtcggag 420
ggcgcctcag acaggcatcg tggatgagtg ctgcttccgg agctgtgatc taaggaggct 480
ggagatgtat tgcgcacccc tcaagcctgc caagtcagct cgctctgtcc gtgcccagcg 540
ccacaccgac atgcccaaga cccagaagga agtacatttg aagaacgcaa gtagagggag 600
tgcaggaaac aagaactaca ggatgtagga agaccctcct gaggagtgaa gagtgacatg 660
ccaccgcagg atcctttgct ctgcacgagt tacctgttaa actttggaac acctaccaaa 720
aaataagttt gataacattt aaaagatggg cgtttccccc aatgaaatac acaagtaaac 780
attccaacat tgtctttagg agtgatttgc accttgcaaa aatggtcctg gagttggtag 840
attgctgttg atcttttatc aataatgttc tatagaaaag aaaaaaaaat atatatatat 900
atatatctta gtccctgcct ctcaagagcc acaaatgcat gggtgttgta tagatccagt 960
tgcactaaat tcctctctga atcttggctg ctggagccat tcattcagca accttgtcta 1020
agtggtttat gaattgtttc cttatttgca cttctttcta cacaactcgg gctgtttgtt 1080
ttacagtgtc tgataatctt gttagtctat acccaccacc tcccttcata acctttatat 1140
ttgccgaatt tggcctcctc aaaagcagca gcaagtcgtc aagaagcaca ccaattctaa 1200
cccacaagat tccatctgtg gcatttgtac caaatataag ttggatgcat tttattttag 1260
acacaaagct ttatttttcc acatcatgct tacaaaaaag aataatgcaa atagttgcaa 1320
ctttgaggcc aatcattttt aggcatatgt tttaaacata gaaagtttct tcaactcaaa 1380
agagttcctt caaatgatga gttaatgtgc aacctaatta gtaactttcc tctttttatt 1440
ttttccatat agagcactat gtaaatttag catatcaatt atacaggata tatcaaacag 1500
tatgtaaaac tctgtttttt agtataatgg tgctattttg tagtttgtta tatgaaagag 1560
tctggccaaa acggtaatac gtgaaagcaa aacaataggg gaagcctgga gccaaagatg 1620
acacaagggg aagggtactg aaaacaccat ccatttggga aagaaggcaa agtcccccca 1680
gttatgcctt ccaagaggaa cttcagacac aaaagtccac tgatgcaaat tggactggcg 1740
agtccagaga ggaaactgtg gaatggaaaa agcagaaggc taggaatttt agcagtcctg 1800
gtttcttttt ctcatggaag aaatgaacat ctgccagctg tgtcatggac tcaccactgt 1860
gtgaccttgg gcaagtcact tcacctctct gtgcctcagt ttcctcatct gcaaaatggg 1920
ggcaatatgt catctaccta cctcaaaggg gtggtataag gtttaaaaag ataaagattc 1980
agattttttt accctgggtt gctgtaaggg tgcaacatca gggcgcttga gttgctgaga 2040
tgcaaggaat tctataaata acccattcat agcatagcta gagattggtg aattgaatgc 2100
tcctgacatc tcagttcttg tcagtgaagc tatccaaata actggccaac tagttgttaa 2160
aagctaacag ctcaatctct taaaacactt ttcaaaatat gtgggaagca tttgattttc 2220
aatttgattt tgaattctgc atttggtttt atgaatacaa agataagtga aaagagagaa 2280
aggaaaagaa aaaggagaaa aacaaagaga tttctaccag tgaaagggga attaattact 2340
ctttgttagc actcactgac tcttctatgc agttactaca tatctagtaa aaccttgttt 2400
aatactataa ataatattct attcattttg aaaaacacaa tgattccttc ttttctaggc 2460
aatataagga aagtgatcca aaatttgaaa tattaaaata atatctaata aaaagtcaca 2520
aagttatctt ctttaacaaa ctttactctt attcttagct gtatatacat ttttttaaaa 2580
agtttgttaa aatatgcttg actagagttt cagttgaaag gcaaaaactt ccatcacaac 2640
aagaaatttc ccatgcctgc tcagaagggt agcccctagc tctctgtgaa tgtgttttat 2700
ccattcaact gaaaattggt atcaagaaag tccactggtt agtgtactag tccatcatag 2760
cctagaaaat gatccctatc tgcagatcaa gattttctca ttagaacaat gaattatcca 2820
gcattcagat ctttctagtc accttagaac tttttggtta aaagtaccca ggcttgatta 2880
tttcatgcaa attctatatt ttacattctt ggaaagtcta tatgaaaaac aaaaataaca 2940
tcttcagttt ttctcccact gggtcacctc aaggatcaga ggccaggaaa aaaaaaaaag 3000
actccctgga tctctgaata tatgcaaaaa gaaggcccca tttagtggag ccagcaatcc 3060
tgttcagtca acaagtattt taactctcag tccaacatta tttgaattga gcacctcaag 3120
catgcttagc aatgttctaa tcactatgga cagatgtaaa agaaactata catcattttt 3180
gccctctgcc tgttttccag acatacaggt tctgtggaat aagatactgg actcctcttc 3240
ccaagatggc acttcttttt atttcttgtc cccagtgtgt accttttaaa attattccct 3300
ctcaacaaaa ctttataggc agtcttctgc agacttaaca tgttttctgt catagttaga 3360
tgtgataatt ctaagagtgt ctatgactta tttccttcac ttaattctat ccacagtcaa 3420
aaatccccca aggaggaaag ctgaaagatg caactgccaa tattatcttt cttaactttt 3480
tccaacacat aatcctctcc aactggatta taaataaatt gaaaataact cattatacca 3540
attcactatt ttatttttta atgaattaaa actagaaaac aaattgatgc aaaccctgga 3600
agtcagttga ttactatata ctacagcaga atgactcaga tttcatagaa aggagcaacc 3660
aaaatgtcac aaccaaaact ttacaagctt tgcttcagaa ttagattgct ttataattct 3720
tgaatgaggc aatttcaaga tatttgtaaa agaacagtaa acattggtaa gaatgagctt 3780
tcaactcata ggcttatttc caatttaatt gaccatactg gatacttagg tcaaatttct 3840
gttctctctt gcccaaataa tattaaagta ttatttgaac tttttaagat gaggcagttc 3900
ccctgaaaaa gttaatgcag ctctccatca gaatccactc ttctagggat atgaaaatct 3960
cttaacaccc accctacata cacagacaca cacacacaca cacacacaca cacacacaca 4020
cacacattca ccctaaggat ccaatggaat actgaaaaga aatcacttcc ttgaaaattt 4080
tattaaaaaa caaacaaaca aacaaaaagc ctgtccaccc ttgagaatcc ttcctctcct 4140
tggaacgtca atgtttgtgt agatgaaacc atctcatgct ctgtggctcc agggtttctg 4200
ttactatttt atgcacttgg gagaaggctt agaataaaag atgtagcaca ttttgctttc 4260
ccatttattg tttggccagc tatgccaatg tggtgctatt gtttctttaa gaaagtactt 4320
gactaaaaaa aaaagaaaaa aagaaaaaaa agaaagcata gacatatttt tttaaagtat 4380
aaaaacaaca attctataga tagatggctt aataaaatag cattaggtct atctagccac 4440
caccaccttt caacttttta tcactcacaa gtagtgtact gttcaccaaa ttgtgaattt 4500
gggggtgcag gggcaggagt tggaaatttt ttaaagttag aaggctccat tgttttgttg 4560
gctctcaaac ttagcaaaat tagcaatata ttatccaatc ttctgaactt gatcaagagc 4620
atggagaata aacgcgggaa aaaagatctt ataggcaaat agaagaattt aaaagataag 4680
taagttcctt attgattttt gtgcactctg ctctaaaaca gatattcagc aagtggagaa 4740
aataagaaca aagagaaaaa atacatagat ttacctgcaa aaaatagctt ctgccaaatc 4800
ccccttgggt attctttggc atttactggt ttatagaaga cattctccct tcacccagac 4860
atctcaaaga gcagtagctc tcatgaaaag caatcactga tctcatttgg gaaatgttgg 4920
aaagtatttc cttatgagat gggggttatc tactgataaa gaaagaattt atgagaaatt 4980
gttgaaagag atggctaaca atctgtgaag attttttgtt tcttggtttt gttttttttt 5040
ttttttttac tttatacagt ctttatgaat ttcttaatgt tcaaaatgac ttggttcttt 5100
tcttcttttt tttatatcag aatgaggaat aataagttaa acccacatag actctttaaa 5160
actataggct agatagaaat gtatgtttga cttgttgaag ctataatcag actatttaaa 5220
atgttttgct atttttaatc ttaaaagatt gtgctaattt attagagcag aacctgtttg 5280
gctctcctca gaagaaagaa tctttccatt caaatcacat ggctttccac caatattttc 5340
aaaagataaa tctgatttat gcaatggcat catttatttt aaaacagaag aattgtgaaa 5400
gtttatgccc ctcccttgca aagaccataa agtccagatc tggtaggggg gcaacaacaa 5460
aaggaaaatg ttgttgattc ttggttttgg attttgtttt gttttcaatg ctagtgttta 5520
atcctgtagt acatatttgc ttattgctat tttaatattt tataagacct tcctgttagg 5580
tattagaaag tgatacatag atatcttttt tgtgtaattt ctatttaaaa aagagagaag 5640
actgtcagaa gctttaagtg catatggtac aggataaaga tatcaattta aataaccaat 5700
tcctatctgg aacaatgctt ttgtttttta aagaaacctc tcacagataa gacagaggcc 5760
caggggattt ttgaagctgt ctttattctg cccccatccc aacccagccc ttattatttt 5820
agtatctgcc tcagaatttt atagagggct gaccaagctg aaactctaga attaaaggaa 5880
cctcactgaa aacatatatt tcacgtgttc cctctctttt ttttcctttt tgtgagatgg 5940
ggtctcgcac tgtcccccag gctggagtgc agtggcatga tctcggctca ctgcaacctc 6000
cacctcctgg gtttaagcga ttctcctgcc tcagcctcct gagtagctgg gattacaggc 6060
acccaccact atgcccggct aattttttgg atttttaata gagacggggt tttaccatgt 6120
tggccaggtt ggactcaaac tcctgacctt gtgatttgcc cgcctcagcc tcccaaattg 6180
ctgggattac aggcatgagc caccacaccc tgcccatgtg ttccctctta atgtatgatt 6240
acatggatct taaacatgat ccttctctcc tcattcttca actatctttg atggggtctt 6300
tcaaggggaa aaaaatccaa gcttttttaa agtaaaaaaa aaaaaagaga ggacacaaaa 6360
ccaaatgtta ctgctcaact gaaatatgag ttaagatgga gacagagttt ctcctaataa 6420
ccggagctga attacctttc actttcaaaa acatgacctt ccacaatcct tagaatctgc 6480
ctttttttat attactgagg cctaaaagta aacattactc attttatttt gcccaaaatg 6540
cactgatgta aagtaggaaa aataaaaaca gagctctaaa atccctttca agccacccat 6600
tgaccccact caccaactca tagcaaagtc acttctgtta atcccttaat ctgattttgt 6660
ttggatattt atcttgtacc cgctgctaaa cacactgcag gagggactct gaaacctcaa 6720
gctgtctact tacatctttt atctgtgtct gtgtatcatg aaaatgtcta ttcaaaatat 6780
caaaaccttt caaatatcac gcagcttata ttcagtttac ataaaggccc caaataccat 6840
gtcagatctt tttggtaaaa gagttaatga actatgagaa ttgggattac atcatgtatt 6900
ttgcctcatg tatttttatc acacttatag gccaagtgtg ataaataaac ttacagacac 6960
tgaattaatt tcccctgcta ctttgaaacc agaaaataat gactggccat tcgttacatc 7020
tgtcttagtt gaaaagcata ttttttatta aattaattct gattgtattt gaaattatta 7080
ttcaattcac ttatggcaga ggaatatcaa tcctaatgac ttctaaaaat gtaactaatt 7140
gaatcattat cttacattta ctgtttaata agcatatttt gaaaatgtat ggctagagtg 7200
tcataataaa atggtatatc tttctttagt aattacaaaa aaaaaaaaaa aaaaaaaaaa 7260
<210>108
<211>1536
<212>DNA
<213>小鼠(Mus musculus)
<400>108
gacttcttga agataaagat acacatcatg tcgtcttcac acctcttcta cctggcgctc 60
tgcttgctca ccttcaccag ctccaccaca gctggaccag agaccctttg cggggctgag 120
ctggtggatg ctcttcagtt cgtgtgtgga ccgaggggct tttacttcaa caagcccaca 180
ggctatggct ccagcattcg gagggcacct cagacaggca ttgtggatga gtgttgcttc 240
cggagctgtg atctgaggag actggagatg tactgtgccc cactgaagcc tacaaaagca 300
gcccgctcta tccgtgccca gcgccacact gacatgccca agactcagaa gtccccgtcc 360
ctatcgacaa acaagaaaac gaagctgcaa aggagaagga aaggaagtac atttgaagaa 420
cacaagtaga ggaagtgcag gaaacaagac ctacagaatg taggaggagc ctcccacgga 480
gcagaaaatg ccacatcacc gcaggatcct ttgctgcttg agcaacctgc aaaacatcga 540
aacacctacc aaataacaat aataagtcca ataacattac aaagatgggc atttccccca 600
atgaaatata caagtaaaca ttccaacatc gtctttagga gtgtttgttt aaaaagcttt 660
gcaccttgca aaagtggtcc tggcgtgggt agattgctgt tgatccttta tcaataacat 720
tctatagaga aaaaaatata tatatataac tatatctcct agtccctgcc tctaaagagc 780
cgaaaatgca tggatgttgt agagatccag ttgctctaag tttctctctg aattttggct 840
gctgaagcca ttcatttagc aactgtgtag aggtggttta tgaatggttc ccttatcttc 900
acctcttccc acgtagctca agctgcttgt tttacagagt ctaatcatct tgtctagctc 960
cattagacac accctttcct aacacttgta tttgttgaat ttggcctcct taagagcaat 1020
agcaaataag tagtcaagtg gcctaccaag ttttaacgta cctgactcca tctgtggcat 1080
ttgtaccaaa tataagttga atgcatttat tttagacaca aagctttatt ttttttgaca 1140
ttgtgtttca agaaaaaaaa tagaataaca ataactacaa ctttgaggcc aatcattttt 1200
aggtgtgtgt ttgaagcata gaacgtctct taaactctca atggttcctt caaatgataa 1260
gttagtatgt aacctaagta tagcagtttc tctctttttt atttttttcc atatagagca 1320
ctatgtaaag ttagtatatc aataatacag gaaatatcaa acagtatgta aaactctgtt 1380
gttgttgttt tttagtacaa tggtgctatt ttgtagtttg ttatatgaaa gaatctagtc 1440
aacacagtaa aaggagaaag caaagcaaaa acaacaaacg aaagcctgga gcctaagatg 1500
acaaaacgag gaagggaact gaaaaaaaaa aaaaaa 1536
<210>109
<211>2170
<212>DNA
<213>小鼠(Mus musculus)
<400>109
ggcatattca gaaattttaa acagatacag gctgtgctca gaaagcagga gcttactggc 60
ggctgcttgt ccaacttttc tctttggaag gggactttcg tgactgagct ggggtttgaa 120
ttttggttta aggctctgct cttagactca ccgcgcggcg cggcaaggca aagcctcttt 180
aggtgaatcg gctgctgctt gcccctgctg ctgctgtgct gcctctgtca cttgcctctg 240
gctctgtcgc tcgcccctgc cgctgctgct gctgctgctg ctgctgctgc tgctgctgct 300
gctgccgttt gcccctgccg ctgtctatgt tctgccttct ccttttgatc actggcccta 360
cttcaagttt ccattctcag caaaattata tccttccaga cttgtgtttt ttcaatttgc 420
aagcacttct aagccgctgt caccggctcc ttggaggcag ttgccggagg gcttaattca 480
taaaagatcc cagtcaaaga gtgcagcggg tttttttttt gtgctgcatt caaatgcttc 540
atcgctatga gtttttctta ggcaagtaag tggcttggga cttcgggaga caaccttgtc 600
aagcacctaa ttgtgccgtc ctcgcgctgc cagcaagctt cagccacctt acaggagtga 660
agtcagcgtt catatacgct gtgtggtctg gcagctggga ttgtgtgtcc caaagggatt 720
gtggaatgtt acctcggcag gcatgcattc cacgtttgga aaatcggctc caaatgaact 780
ttctttccct gctgggtctg cagaacattt cagaagcgga gctagcaata cccttcaact 840
tttttcctgt gcttgcagca ggagatggct gaagggagct actgcatgcg tggtggtctt 900
tgaaacatag ctcagggaag agaggtcagc tgcctagagc gattggtaca cacagggcgc 960
ctgctggctt tgtactctga ggctcaaggt atttcccagt gcctgagcca ggggacgatg 1020
ggggaggaag ggaaggagct ggaacttgaa tcactattct ggatagccga gatagatagc 1080
catacaatgg aaatgagtgg cttcccttgg gggaaaaaga cggactccaa ctcccagctg 1140
tgcaatttac tcattgttta aatggacaaa aggcagttta cccaggctca gagcatacct 1200
gcctgggtgt ccaaatgtaa ctagatgctt tcacaaaccc cacccacaaa acaacacctg 1260
ttcttaagtc ctcagttttg tgttcacctc ggcctcatag tacccactct gacctgctgt 1320
gtaaacgacc cggacctacc aaaatgaccg cacctgcaat aaagatacac atcatgtcgt 1380
cttcacacct cttctacctg gcgctctgct tgctcacctt caccagctcc accacagctg 1440
gaccagagac cctttgcggg gctgagctgg tggatgctct tcagttcgtg tgtggaccga 1500
ggggctttta cttcaacaag cccacaggct atggctccag cattcggagg gcacctcaga 1560
caggcattgt ggatgagtgt tgcttccgga gctgtgatct gaggagactg gagatgtact 1620
gtgccccact gaagcctaca aaagcagccc gctctatccg tgcccagcgc cacactgaca 1680
tgcccaagac tcagaagtcc ccgtccctat cgacaaacaa gaaaacgaag ctgcaaagga 1740
gaaggaaagg tgagccaaag acacacccag aaggggaaca ggaggaggta acggaggcaa 1800
ctcggaaaat cagaggtccc agagaaaaaa gactgggcta ggaactgtga gcaagcaggc 1860
aaagagggac atgcgggaac agggatgaag gacgtgcggg aacagggatg aagaaggagc 1920
agacaggagc ccaggaaagc cgcagaggag ctgaagcaag gcagtcctca ctaagctaga 1980
taatgtctgt gacggaagta agaaagtcct cctctgggat acggcactta cacatgggaa 2040
gaatggtacg gggaagtgta acacctcaga aagtgacaag tgaccaggat ggaacatcaa 2100
caacaataac aaccattaaa aacatgccac caagaccttc cctccccttc ttaaaaatat 2160
aaatcagagt 2170
<210>110
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>110
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe
1 5 10 15
Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Glu Val His Leu Lys Asn Ala Ser Arg Gly
130 135 140
Ser Ala Gly Asn Lys Asn Tyr Arg Met
145 150
<210>111
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>111
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe
1 5 10 15
Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Glu Val His Leu Lys Asn Ala Ser Arg Gly
130 135 140
Ser Ala Gly Asn Lys Asn Tyr Arg Met
145 150
<210>112
<211>195
<212>PRT
<213>智人(Homo sapiens)
<400>112
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe
1 5 10 15
Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Tyr Gln Pro Pro Ser Thr Asn Lys Asn Thr
130 135 140
Lys Ser Gln Arg Arg Lys Gly Trp Pro Lys Thr His Pro Gly Gly Glu
145 150 155 160
Gln Lys Glu Gly Thr Glu Ala Ser Leu Gln Ile Arg Gly Lys Lys Lys
165 170 175
Glu Gln Arg Arg Glu Ile Gly Ser Arg Asn Ala Glu Cys Arg Gly Lys
180 185 190
Lys Gly Lys
195
<210>113
<211>139
<212>PRT
<213>智人(Homo sapiens)
<400>113
Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu Phe Tyr Leu
1 5 10 15
Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala Gly Pro Glu
20 25 30
Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe Val Cys Gly
35 40 45
Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly Ser Ser Ser
50 55 60
ArgArg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys Phe Arg Ser
65 70 75 80
Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu Lys Pro Ala
85 90 95
Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp Met Pro Lys
100 105 110
Thr Gln Lys Tyr Gln Pro Pro Ser Thr Asn Lys Asn Thr Lys Ser Gln
115 120 125
Arg Arg Lys Gly Ser Thr Phe Glu Glu Arg Lys
130 135
<210>114
<211>137
<212>PRT
<213>智人(Homo sapiens)
<400>114
Met Ile Thr Pro Thr Val Lys Met His Thr Met Ser Ser Ser His Leu
1 5 10 15
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala
20 25 30
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
35 40 45
Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
50 55 60
Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
65 70 75 80
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
85 90 95
Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp
100 105 110
Met Pro Lys Thr Gln Lys Glu Val His Leu Lys Asn Ala Ser Arg Gly
115 120 125
Ser Ala Gly Asn Lys Asn Tyr Arg Met
130 135
<210>115
<211>184
<212>PRT
<213>智人(Homo sapiens)
<400>115
His Cys Ser Gln His Leu Pro Ser Leu Trp Ile Ser Phe Cys Phe Ile
1 5 10 15
Ile Pro Ala Asn Gln Phe Ile Phe Arg Leu Cys Thr Ser Glu Ala Met
20 25 30
Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe Cys
35 40 45
Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu Phe
50 55 60
Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala Gly
65 70 75 80
Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe Val
85 90 95
Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly Ser
100 105 110
Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys Phe
115 120 125
Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu Lys
130 135 140
Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp Met
145 150 155 160
Pro Lys Thr Gln Lys Glu Val His Leu Lys Asn Ala Ser Arg Gly Ser
165 170 175
Ala Gly Asn Lys Asn Tyr Arg Met
180
<210>116
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>116
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe
1 5 10 15
Cys Asp Phe Leu Lys Val Lys Met His Thr Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Ala Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Ala Lys Ser Ala Arg Ser Val Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Glu Val His Leu Lys Asn Ala Ser Arg Gly
130 135 140
Ser Ala Gly Asn Lys Asn Tyr Arg Met
145 150
<210>117
<211>21
<212>PRT
<213>智人(Homo sapiens)
<400>117
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Cys Cys Phe
1 5 10 15
Cys Asp Phe Leu Lys
20
<210>118
<211>130
<212>PRT
<213>智人(Homo sapiens)
<400>118
Met His Thr Met Ser Ser Ser His Leu Phe Tyr Leu Ala Leu Cys Leu
1 5 10 15
Leu Thr Phe Thr Ser Ser Ala Thr Ala Gly Pro Glu Thr Leu Cys Gly
20 25 30
Ala Glu Leu Val Asp Ala Leu Gln Phe Val Cys Gly Asp Arg Gly Phe
35 40 45
Tyr Phe Asn Lys Pro Thr Gly Tyr Gly Ser Ser Ser Arg Arg Ala Pro
50 55 60
Gln Thr Gly Ile Val Asp Glu Cys Cys Phe Arg Ser Cys Asp Leu Arg
65 70 75 80
Arg Leu Glu Met Tyr Cys Ala Pro Leu Lys Pro Ala Lys Ser Ala Arg
85 90 95
Ser Val Arg Ala Gln Arg His Thr Asp Met Pro Lys Thr Gln Lys Glu
100 105 110
Val His Leu Lys Asn Ala Ser Arg Gly Ser Ala Gly Asn Lys Asn Tyr
115 120 125
Arg Met
130
<210>119
<211>23
<212>PRT
<213>智人(Homo sapiens)
<400>119
Thr Gly Trp Pro Lys Thr His Pro Gly Gly Glu Gln Lys Glu Gly Thr
1 5 10 15
Glu Ala Ser Leu Gln Ile Arg
20
<210>120
<211>133
<212>PRT
<213>小鼠(Mus musculus)
<400>120
Met Ser Ser Ser His Leu Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe
1 5 10 15
Thr Ser Ser Thr Thr Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu
20 25 30
Val Asp Ala Leu Gln Phe Val Cys Gly Pro Arg Gly Phe Tyr Phe Asn
35 40 45
Lys Pro Thr Gly Tyr Gly Ser Ser Ile Arg Arg Ala Pro Gln Thr Gly
50 55 60
Ile Val Asp Glu Cys Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu
65 70 75 80
Met Tyr Cys Ala Pro Leu Lys Pro Thr Lys Ala Ala Arg Ser Ile Arg
85 90 95
Ala Gln Arg His Thr Asp Met Pro Lys Thr Gln Lys Ser Pro Ser Leu
100 105 110
Ser Thr Asn Lys Lys Thr Lys Leu Gln Arg Arg Arg Lys Gly Ser Thr
115 120 125
Phe Glu Glu His Lys
130
<210>121
<211>165
<212>PRT
<213>小鼠(Mus musculus)
<400>121
Met Thr Ala Pro Ala Ile Lys Ile His Ile Met Ser Ser Ser His Leu
1 5 10 15
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Thr Thr Ala
20 25 30
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
35 40 45
Val Cys Gly Pro Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
50 55 60
Ser Ser Ile Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
65 70 75 80
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
85 90 95
Lys Pro Thr Lys Ala Ala Arg Ser Ile Arg Ala Gln Arg His Thr Asp
100 105 110
Met Pro Lys Thr Gln Lys Ser Pro Ser Leu Ser Thr Asn Lys Lys Thr
115 120 125
Lys Leu Gln Arg Arg Arg Lys Gly Glu Pro Lys Thr His Pro Glu Gly
130 135 140
Glu Gln Glu Glu Val Thr Glu Ala Thr Arg Lys Ile Arg Gly Pro Arg
145 150 155 160
Glu Lys Arg Leu Gly
165
<210>122
<211>153
<212>PRT
<213>小鼠(Mus musculus)
<400>122
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Ile Cys Leu
1 5 10 15
Cys Asp Phe Leu Lys Ile Lys Ile His Ile Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Thr Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Pro Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ile Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Thr Lys Ala Ala Arg Ser Ile Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Glu Val His Leu Lys Asn Thr Ser Arg Gly
130 135 140
Ser Ala Gly Asn Lys Thr Tyr Arg Met
145 150
<210>123
<211>159
<212>PRT
<213>小鼠(Mus musculus)
<400>123
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Ile Cys Leu
1 5 10 15
Cys Asp Phe Leu Lys Ile Lys Ile His Ile Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Thr Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Pro Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ile Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Thr Lys Ala Ala Arg Ser Ile Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Ser Pro Ser Leu Ser Thr Asn Lys Lys Thr
130 135 140
Lys Leu Gln Arg Arg Arg Lys Gly Ser Thr Phe Glu Glu His Lys
145 150 155
<210>124
<211>153
<212>PRT
<213>小鼠(Mus musculus)
<400>124
Met Gly Lys Ile Ser Ser Leu Pro Thr Gln Leu Phe Lys Ile Cys Leu
1 5 10 15
Cys Asp Phe Leu Lys Ile Lys Ile His Ile Met Ser Ser Ser His Leu
20 25 30
Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe Thr Ser Ser Thr Thr Ala
35 40 45
Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe
50 55 60
Val Cys Gly Pro Arg Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly
65 70 75 80
Ser Ser Ile Arg Arg Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys
85 90 95
Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu
100 105 110
Lys Pro Thr Lys Ala Ala Arg Ser Ile Arg Ala Gln Arg His Thr Asp
115 120 125
Met Pro Lys Thr Gln Lys Glu Val His Leu Lys Asn Thr Ser Arg Gly
130 135 140
Ser Ala Gly Asn Lys Thr Tyr Arg Met
145 150
<210>125
<211>127
<212>PRT
<213>小鼠(Mus musculus)
<400>125
Met Ser Ser Ser His Leu Phe Tyr Leu Ala Leu Cys Leu Leu Thr Phe
1 5 10 15
Thr Ser Ser Thr Thr Ala Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu
20 25 30
Val Asp Ala Leu Gln Phe Val Cys Gly Pro Arg Gly Phe Tyr Phe Asn
35 40 45
Lys Pro Thr Gly Tyr Gly Ser Ser Ile Arg Arg Ala Pro Gln Thr Gly
50 55 60
Ile Val Asp Glu Cys Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu
65 70 75 80
Met Tyr Cys Ala Pro Leu Lys Pro Thr Lys Ala Ala Arg Ser Ile Arg
85 90 95
Ala Gln Arg His Thr Asp Met Pro Lys Thr Gln Lys Glu Val His Leu
100 105 110
Lys Asn Thr Ser Arg Gly Ser Ala Gly Asn Lys Thr Tyr Arg Met
115 120 125
<210>126
<211>1629
<212>DNA
<213>智人(Homo sapiens)
<400>126
acacatcagg ggcttgctct tgcaaaacca aaccacaaga cagacttgca aaagaaggca 60
tgcacagctc agcactgctc tgttgcctgg tcctcctgac tggggtgagg gccagcccag 120
gccagggcac ccagtctgag aacagctgca cccacttccc aggcaacctg cctaacatgc 180
ttcgagatct ccgagatgcc ttcagcagag tgaagacttt ctttcaaatg aaggatcagc 240
tggacaactt gttgttaaag gagtccttgc tggaggactt taagggttac ctgggttgcc 300
aagccttgtc tgagatgatc cagttttacc tggaggaggt gatgccccaa gctgagaacc 360
aagacccaga catcaaggcg catgtgaact ccctggggga gaacctgaag accctcaggc 420
tgaggctacg gcgctgtcat cgatttcttc cctgtgaaaa caagagcaag gccgtggagc 480
aggtgaagaa tgcctttaat aagctccaag agaaaggcat ctacaaagcc atgagtgagt 540
ttgacatctt catcaactac atagaagcct acatgacaat gaagatacga aactgagaca 600
tcagggtggc gactctatag actctaggac ataaattaga ggtctccaaa atcggatctg 660
gggctctggg atagctgacc cagccccttg agaaacctta ttgtacctct cttatagaat 720
atttattacc tctgatacct caacccccat ttctatttat ttactgagct tctctgtgaa 780
cgatttagaa agaagcccaa tattataatt tttttcaata tttattattt tcacctgttt 840
ttaagctgtt tccatagggt gacacactat ggtatttgag tgttttaaga taaattataa 900
gttacataag ggaggaaaaa aaatgttctt tggggagcca acagaagctt ccattccaag 960
cctgaccacg ctttctagct gttgagctgt tttccctgac ctccctctaa tttatcttgt 1020
ctctgggctt ggggcttcct aactgctaca aatactctta ggaagagaaa ccagggagcc 1080
cctttgatga ttaattcacc ttccagtgtc tcggagggat tcccctaacc tcattcccca 1140
accacttcat tcttgaaagc tgtggccagc ttgttattta taacaaccta aatttggttc 1200
taggccgggc gcggtggctc acgcctgtaa tcccagcact ttgggaggct gaggcgggtg 1260
gatcacttga ggtcaggagt tcctaaccag cctggtcaac atggtgaaac cccgtctcta 1320
ctaaaaatac aaaaattagc cgggcatggt ggcgcgcacc tgtaatccca gctacttggg 1380
aggctgaggc aagagaattg cttgaaccca ggagatggaa gttgcagtga gctgatatca 1440
tgcccctgta ctccagcctg ggtgacagag caagactctg tctcaaaaaa taaaaataaa 1500
aataaatttg gttctaatag aactcagttt taactagaat ttattcaatt cctctgggaa 1560
tgttacattg tttgtctgtc ttcatagcag attttaattt tgaataaata aatgtatctt 1620
attcacatc 1629
<210>127
<211>1314
<212>DNA
<213>小鼠(Mus musculus)
<400>127
gggggggggg atttagagac ttgctcttgc actaccaaag ccacaaagca gccttgcaga 60
aaagagagct ccatcatgcc tggctcagca ctgctatgct gcctgctctt actgactggc 120
atgaggatca gcaggggcca gtacagccgg gaagacaata actgcaccca cttcccagtc 180
ggccagagcc acatgctcct agagctgcgg actgccttca gccaggtgaa gactttcttt 240
caaacaaagg accagctgga caacatactg ctaaccgact ccttaatgca ggactttaag 300
ggttacttgg gttgccaagc cttatcggaa atgatccagt tttacctggt agaagtgatg 360
ccccaggcag agaagcatgg cccagaaatc aaggagcatt tgaattccct gggtgagaag 420
ctgaagaccc tcaggatgcg gctgaggcgc tgtcatcgat ttctcccctg tgaaaataag 480
agcaaggcag tggagcaggt gaagagtgat tttaataagc tccaagacca aggtgtctac 540
aaggccatga atgaatttga catcttcatc aactgcatag aagcatacat gatgatcaaa 600
atgaaaagct aaaacacctg cagtgtgtat tgagtctgct ggactccagg acctagacag 660
agctctctaa atctgatcca gggatcttag ctaacggaaa caactccttg gaaaacctcg 720
tttgtacctc tctccgaaat atttattacc tctgatacct cagttcccat tctatttatt 780
cactgagctt ctctgtgaac tatttagaaa gaagcccaat attataattt tacagtattt 840
attattttta acctgtgttt aagctgtttc cattggggac actttatagt atttaaaggg 900
agattatatt atatgatggg aggggttctt ccttgggaag caattgaagc ttctattcta 960
aggctggcca cacttgagag ctgcagggcc ctttgctatg gtgtcctttc aattgctctc 1020
atccctgagt tcagagctcc taagagagtt gtgaagaaac tcatgggtct tgggaagaga 1080
aaccagggag atcctttgat gatcattcct gcagcagctc agagggttcc cctactgtca 1140
tcccccagcc gcttcatccc tgaaaactgt ggccagtttg ttatttataa ccacctaaaa 1200
ttagttctaa tagaactcat ttttaactag aagtaatgca attcctctgg gaatggtgta 1260
ttgtttgtct gcctttgtag cagcatctaa ttttgaataa atggatctta ttcg 1314
<210>128
<211>178
<212>PRT
<213>智人(Homo sapiens)
<400>128
Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val
1 5 10 15
Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His
20 25 30
Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe
35 40 45
Ser Arg Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu
50 55 60
Leu Leu Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys
65 70 75 80
Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro
85 90 95
Gln Ala Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu
100 105 110
Gly Glu Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg
115 120 125
Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn
130 135 140
Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu
145 150 155 160
Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile
165 170 175
Arg Asn
<210>129
<211>178
<212>PRT
<213>智人(Homo sapiens)
<400>129
Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val
1 5 10 15
Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His
20 25 30
Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe
35 40 45
Ser Arg Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu
50 55 60
Leu Leu Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys
65 70 75 80
Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro
85 90 95
Gln Ala Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu
100 105 110
Gly Glu Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg
115 120 125
Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn
130 135 140
Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu
145 150 155 160
Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile
165 170 175
Arg Asn
<210>130
<211>178
<212>PRT
<213>智人(Homo sapiens)
<400>130
Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val
1 5 10 15
Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His
20 25 30
Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe
35 40 45
Ser Arg Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu
50 55 60
Leu Leu Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys
65 70 75 80
Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro
85 90 95
Gln Ala Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu
100 105 110
Gly Glu Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys Leu Arg
115 120 125
Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn
130 135 140
Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu
145 150 155 160
Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile
165 170 175
Arg Asn
<210>131
<211>178
<212>PRT
<213>智人(Homo sapiens)
<400>131
Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val
1 5 10 15
Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His
20 25 30
Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe
35 40 45
Ser Arg Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu
50 55 60
Leu Leu Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys
65 70 75 80
Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro
85 90 95
Gln Ala Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu
100 105 110
Gly Glu Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg
115 120 125
Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn
130 135 140
Ala Phe Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu
145 150 155 160
Phe Asp Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile
165 170 175
Arg Asn
<210>132
<211>55
<212>PRT
<213>智人(Homo sapiens)
<400>132
Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr Gly Val
1 5 10 15
Arg Ala Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His
20 25 30
Phe Pro Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe
35 40 45
Ser Arg Val Lys Thr Phe Phe
50 55
<210>133
<211>160
<212>PRT
<213>智人(Homo sapiens)
<400>133
Ser Pro Gly Gln Gly Thr Gln Ser Glu Asn Ser Cys Thr His Phe Pro
1 5 10 15
Gly Asn Leu Pro Asn Met Leu Arg Asp Leu Arg Asp Ala Phe Ser Arg
20 25 30
Val Lys Thr Phe Phe Gln Met Lys Asp Gln Leu Asp Asn Leu Leu Leu
35 40 45
Lys Glu Ser Leu Leu Glu Asp Phe Lys Gly Tyr Leu Gly Cys Gln Ala
50 55 60
Leu Ser Glu Met Ile Gln Phe Tyr Leu Glu Glu Val Met Pro Gln Ala
65 70 75 80
Glu Asn Gln Asp Pro Asp Ile Lys Ala His Val Asn Ser Leu Gly Glu
85 90 95
Asn Leu Lys Thr Leu Arg Leu Arg Leu Arg Arg Cys His Arg Phe Leu
100 105 110
Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Asn Ala Phe
115 120 125
Asn Lys Leu Gln Glu Lys Gly Ile Tyr Lys Ala Met Ser Glu Phe Asp
130 135 140
Ile Phe Ile Asn Tyr Ile Glu Ala Tyr Met Thr Met Lys Ile Arg Asn
145 150 155 160
<210>134
<211>14
<212>PRT
<213>智人(Homo sapiens)
<400>134
Met His Ser Ser Ala Leu Leu Cys Cys Leu Val Leu Leu Thr
1 5 10
<210>135
<211>178
<212>PRT
<213>小鼠(Mus musculus)
<400>135
Met Pro Gly Ser Ala Leu Leu Cys Cys Leu Leu Leu Leu Thr Gly Met
1 5 10 15
Arg Ile Ser Arg Gly Gln Tyr Ser Arg Glu Asp Asn Asn Cys Thr His
20 25 30
Phe Pro Val Gly Gln Ser His Met Leu Leu Glu Leu Arg Thr Ala Phe
35 40 45
Ser Gln Val Lys Thr Phe Phe Gln Thr Lys Asp Gln Leu Asp Asn Ile
50 55 60
Leu Leu Thr Asp Ser Leu Met Gln Asp Phe Lys Gly Tyr Leu Gly Cys
65 70 75 80
Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Val Glu Val Met Pro
85 90 95
Gln Ala Glu Lys His Gly Pro Glu Ile Lys Glu His Leu Asn Ser Leu
100 105 110
Gly Glu Lys Leu Lys Thr Leu Arg Met Arg Leu Arg Arg Cys His Arg
115 120 125
Phe Leu Pro Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Ser
130 135 140
Asp Phe Asn Lys Leu Gln Asp Gln Gly Val Tyr Lys Ala Met Asn Glu
145 150 155 160
Phe Asp Ile Phe Ile Asn Cys Ile Glu Ala Tyr Met Met Ile Lys Met
165 170 175
Lys Ser
<210>136
<211>178
<212>PRT
<213>小鼠(Mus musculus)
<400>136
Met Pro Gly Ser Ala Leu Leu Cys Cys Leu Leu Leu Leu Thr Gly Met
1 5 10 15
Arg Ile Ser Arg Gly Gln Tyr Ser Arg Glu Asp Asn Asn Cys Thr His
20 25 30
Phe Pro Val Gly Gln Ser His Met Leu Leu Glu Leu Arg Thr Ala Phe
35 40 45
Ser Gln Val Lys Thr Phe Phe Gln Thr Lys Asp Gln Leu Asp Asn Ile
50 55 60
Leu Leu Thr Asp Ser Leu Met Gln Asp Phe Lys Gly Tyr Leu Gly Cys
65 70 75 80
Gln Ala Leu Ser Glu Met Ile Gln Phe Tyr Leu Val Glu Val Met Pro
85 90 95
Gln Ala Glu Lys His Gly Pro Glu Ile Lys Glu His Leu Asn Ser Leu
100 105 110
Gly Glu Lys Leu Lys Thr Leu Arg Met Arg Leu Arg Arg Cys His Arg
115 120 125
Phe Leu Lys Cys Glu Asn Lys Ser Lys Ala Val Glu Gln Val Lys Ser
130 135 140
Asp Phe Asn Lys Leu Glu Asp Gln Gly Val Tyr Lys Ala Met Asn Glu
145 150 155 160
Phe Asp Ile Phe Ile Asn Cys Ile Glu Ala Tyr Met Met Ile Lys Met
165 170 175
Lys Ser
<210>137
<211>1240
<212>DNA
<213>智人(Homo sapiens)
<400>137
cacattgttc tgatcatctg aagatcagct attagaagag aaagatcagt taagtccttt 60
ggacctgatc agcttgatac aagaactact gatttcaact tctttggctt aattctctcg 120
gaaacgatga aatatacaag ttatatcttg gcttttcagc tctgcatcgt tttgggttct 180
cttggctgtt actgccagga cccatatgta aaagaagcag aaaaccttaa gaaatatttt 240
aatgcaggtc attcagatgt agcggataat ggaactcttt tcttaggcat tttgaagaat 300
tggaaagagg agagtgacag aaaaataatg cagagccaaa ttgtctcctt ttacttcaaa 360
ctttttaaaa actttaaaga tgaccagagc atccaaaaga gtgtggagac catcaaggaa 420
gacatgaatg tcaagttttt caatagcaac aaaaagaaac gagatgactt cgaaaagctg 480
actaattatt cggtaactga cttgaatgtc caacgcaaag caatacatga actcatccaa 540
gtgatggctg aactgtcgcc agcagctaaa acagggaagc gaaaaaggag tcagatgctg 600
tttcgaggtc gaagagcatc ccagtaatgg ttgtcctgcc tgcaatattt gaattttaaa 660
tctaaatcta tttattaata tttaacatta tttatatggg gaatatattt ttagactcat 720
caatcaaata agtatttata atagcaactt ttgtgtaatg aaaatgaata tctattaata 780
tatgtattat ttataattcc tatatcctgt gactgtctca cttaatcctt tgttttctga 840
ctaattaggc aaggctatgt gattacaagg ctttatctca ggggccaact aggcagccaa 900
cctaagcaag atcccatggg ttgtgtgttt atttcacttg atgatacaat gaacacttat 960
aagtgaagtg atactatcca gttactgccg gtttgaaaat atgcctgcaa tctgagccag 1020
tgctttaatg gcatgtcaga cagaacttga atgtgtcagg tgaccctgat gaaaacatag 1080
catctcagga gatttcatgc ctggtgcttc caaatattgt tgacaactgt gactgtaccc 1140
aaatggaaag taactcattt gttaaaatta tcaatatcta atatatatga ataaagtgta 1200
agttcacaac aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 1240
<210>138
<211>1208
<212>DNA
<213>小鼠(Mus musculus)
<400>138
gatagctgcc atcggctgac ctagagaaga cacatcagct gatcctttgg accctctgac 60
ttgagacaga agttctgggc ttctcctcct gcggcctagc tctgagacaa tgaacgctac 120
acactgcatc ttggctttgc agctcttcct catggctgtt tctggctgtt actgccacgg 180
cacagtcatt gaaagcctag aaagtctgaa taactatttt aactcaagtg gcatagatgt 240
ggaagaaaag agtctcttct tggatatctg gaggaactgg caaaaggatg gtgacatgaa 300
aatcctgcag agccagatta tctctttcta cctcagactc tttgaagtct tgaaagacaa 360
tcaggccatc agcaacaaca taagcgtcat tgaatcacac ctgattacta ccttcttcag 420
caacagcaag gcgaaaaagg atgcattcat gagtattgcc aagtttgagg tcaacaaccc 480
acaggtccag cgccaagcat tcaatgagct catccgagtg gtccaccagc tgttgccgga 540
atccagcctc aggaagcgga aaaggagtcg ctgctgattc ggggtgggga agagattgtc 600
ccaataagaa taattctgcc agcactattt gaatttttaa atctaaacct atttattaat 660
atttaaaact atttatatgg agaatctatt ttagatgcat caaccaaaga agtatttata 720
gtaacaactt atatgtgata agagtgaatt cctattaata tatgtgttat ttataatttc 780
tgtctcctca actatttctc tttgaccaat taattattct ttctgactaa ttagccaaga 840
ctgtgattgc ggggttgtat ctgggggtgg gggacagcca agcggctgac tgaactcaga 900
ttgtagcttg tacctttact tcactgacca ataagaaaca ttcagagctg cagtgacccc 960
gggaggtgct gctgatggga ggagatgtct acactccggg ccagcgcttt aacagcaggc 1020
cagacagcac tcgaatgagt caggtagtaa caggctgtcc ctgaaagaaa gcagtgtctc 1080
aagagacttg acacctggtg cttccctata cagctgaaaa ctgtgactac acccgaatga 1140
caaataactc gctcatttat agtttatcac tgtctaattg catatgaata aagtatacct 1200
ttgcaacc 1208
<210>139
<211>166
<212>PRT
<213>智人(Homo sapiens)
<400>139
Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu
1 5 10 15
Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu
20 25 30
Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn
35 40 45
Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp
50 55 60
Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe
65 70 75 80
Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile
85 90 95
Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg
100 105 110
Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val
115 120 125
Gln Arg Lys Ala Ile Hi s Glu Leu Ile Gln Val Met Ala Glu Leu Ser
130 135 140
Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg
145 150 155 160
Gly Arg Arg Ala Ser Gln
165
<210>140
<211>166
<212>PRT
<213>智人(Homo sapiens)
<400>140
Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu
1 5 10 15
Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu
20 25 30
Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn
35 40 45
Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp
50 55 60
Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe
65 70 75 80
Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile
85 90 95
Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg
100 105 110
Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val
115 120 125
Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser
130 135 140
Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg
145 150 155 160
Gly Arg Arg Ala Ser Gln
165
<210>141
<211>144
<212>PRT
<213>智人(Homo sapiens)
<400>141
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly
115 120 125
Lys Arg Lys Arg Ser Gln Met Leu Phe Arg Gly Arg Arg Ala Ser Gln
130 135 140
<210>142
<211>134
<212>PRT
<213>智人(Homo sapiens)
<400>142
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly
115 120 125
Lys Arg Lys Arg Ser Leu
130
<210>143
<211>133
<212>PRT
<213>智人(Homo sapiens)
<400>143
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly
115 120 125
Lys Arg Lys Arg Ser
130
<210>144
<211>133
<212>PRT
<213>智人(Homo sapiens)
<400>144
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly
115 120 125
Lys Arg Lys Arg Leu
130
<210>145
<211>130
<212>PRT
<213>智人(Homo sapiens)
<400>145
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly
115 120 125
Lys Leu
130
<210>146
<211>125
<212>PRT
<213>智人(Homo sapiens)
<400>146
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Leu
115 120 125
<210>147
<211>124
<212>PRT
<213>智人(Homo sapiens)
<400>147
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala
115 120
<210>148
<211>166
<212>PRT
<213>智人(Homo sapiens)
<400>148
Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu
1 5 10 15
Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu
20 25 30
Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn
35 40 45
Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp
50 55 60
Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe
65 70 75 80
Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile
85 90 95
Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg
100 105 110
Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val
115 120 125
Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val MetAla Glu Leu Ser
130 135 140
Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Gln
145 150 155 160
Gly Arg Arg Ala Ser Gln
165
<210>149
<211>144
<212>PRT
<213>智人(Homo sapiens)
<400>149
Met Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
1 5 10 15
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
20 25 30
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
35 40 45
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
50 55 60
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
65 70 75 80
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
85 90 95
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
100 105 110
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly
115 120 125
Lys Arg Thr Arg Ser Gln Met Leu Phe Arg Gly Arg Arg Ala Ser Gln
130 135 140
<210>150
<211>143
<212>PRT
<213>智人(Homo sapiens)
<400>150
Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn
1 5 10 15
Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile
20 25 30
Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln
35 40 45
Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln
50 55 60
Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys
65 70 75 80
Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr
85 90 95
Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu
100 105 110
Leu Ile Gln Val Met Ala Glu Leu Pro Pro Ala Ala Glu Thr Gly Lys
115 120 125
Arg Lys Arg Ser Gln Met Leu Phe Arg Gly Arg Arg Ala Ser Gln
130 135 140
<210>151
<211>155
<212>PRT
<213>小鼠(Mus musculus)
<400>151
Met Asn Ala Thr His Cys Ile Leu Ala Leu Gln Leu Phe Leu Met Ala
1 5 10 15
Val Ser Gly Cys Tyr Cys His Gly Thr Val Ile Glu Ser Leu Glu Ser
20 25 30
Leu Asn Asn Tyr Phe Asn Ser Ser Gly Ile Asp Val Glu Glu Lys Ser
35 40 45
Leu Phe Leu Asp Ile Trp Arg Asn Trp Gln Lys Asp Gly Asp Met Lys
50 55 60
Ile Leu Gln Ser Gln Ile Ile Ser Phe Tyr Leu Arg Leu Phe Glu Val
65 70 75 80
Leu Lys Asp Asn Gln Ala Ile Ser Asn Asn Ile Ser Val Ile Glu Ser
85 90 95
His Leu Ile Thr Thr Phe Phe Ser Asn Ser Lys Ala Lys Lys Asp Ala
100 105 110
Phe Met Ser Ile Ala Lys Phe Glu Val Asn Asn Pro Gln Val Gln Arg
115 120 125
Gln Ala Phe Asn Glu Leu Ile Arg Val Val His Gln Leu Leu Pro Glu
130 135 140
Ser Ser Leu Arg Lys Arg Lys Arg Ser Arg Cys
145 150 155
<210>152
<211>155
<212>PRT
<213>小鼠(Mus musculus)
<400>152
Met Asn Ala Thr His Cys Ile Leu Ala Leu Gln Leu Phe Leu Met Ala
1 5 10 15
Val Ser Gly Cys Tyr Cys His Gly Thr Val Ile Glu Ser Leu Glu Ser
20 25 30
Leu Asn Asn Tyr Phe Asn Ser Ser Gly Ile Asp Val Glu Glu Lys Ser
35 40 45
Leu Phe Leu Asp Ile Trp Arg Asn Trp Gln Lys Asp Gly Asp Met Lys
50 55 60
Ile Leu Gln Ser Gln Ile Ile Ser Phe Tyr Leu Arg Leu Phe Glu Val
65 70 75 80
Leu Lys Asp Asn Gln Ala Ile Ser Asn Asn Ile Ser Val Ile Glu Ser
85 90 95
His Leu Ile Thr Thr Phe Phe Ser Asn Ser Lys Ala Lys Lys Asp Ala
100 105 110
Phe Met Ser Ile Ala Lys Phe Glu Val Asn Asn Pro Gln Val Gln Arg
115 120 125
Gln Ala Phe Asn Glu Leu Ile Arg Val Val His Gln Leu Leu Pro Glu
130 135 140
Ser Ser Leu Arg Lys Arg Lys Arg Ser Arg Cys
145 150 155
<210>153
<211>155
<212>PRT
<213>小鼠(Mus musculus)
<400>153
Met Asn Ala Thr His Cys Ile Leu Ala Leu Gln Leu Phe Leu Met Ala
1 5 10 15
Val Ser Gly Cys Tyr Cys His Gly Thr Val Ile Glu Ser Leu Glu Ser
20 25 30
Leu Asn Asn Tyr Phe Asn Ser Ser Gly Ile Asp Val Glu Glu Lys Ser
35 40 45
Leu Phe Leu Asp Ile Trp Arg Asn Trp Gln Lys Asp Gly Asp Met Lys
50 55 60
Ile Leu Gln Ser Gln Ile Ile Ser Phe Tyr Leu Arg Leu Phe Glu Val
65 70 75 80
Leu Lys Asp Asn Gln Ala Ile Ser Asn Asn Ile Ser Val Ile Glu Ser
85 90 95
His Leu Ile Thr Thr Phe Phe Ser Asn Ser Lys Ala Lys Lys Asp Ala
100 105 110
Phe Met Ser Ile Ala Lys Phe Glu Val Asn Asn Pro Gln Val Gln Arg
115 120 125
Gln Ala Phe Asn Glu Leu Ile Arg Val Val His Gln Leu Leu Pro Glu
130 135 140
Ser Ser Leu Arg Lys Arg Lys Arg Ser Arg Cys
145 150 155
<210>154
<211>3665
<212>DNA
<213>智人(Homo sapiens)
<400>154
ggcttggggc agccgggtag ctcggaggtc gtggcgctgg gggctagcac cagcgctctg 60
tcgggaggcg cagcggttag gtggaccggt cagcggactc accggccagg gcgctcggtg 120
ctggaatttg atattcattg atccgggttt tatccctctt cttttttctt aaacattttt 180
ttttaaaact gtattgtttc tcgttttaat ttatttttgc ttgccattcc ccacttgaat 240
cgggccgacg gcttggggag attgctctac ttccccaaat cactgtggat tttggaaacc 300
agcagaaaga ggaaagaggt agcaagagct ccagagagaa gtcgaggaag agagagacgg 360
ggtcagagag agcgcgcggg cgtgcgagca gcgaaagcga caggggcaaa gtgagtgacc 420
tgcttttggg ggtgaccgcc ggagcgcggc gtgagccctc ccccttggga tcccgcagct 480
gaccagtcgc gctgacggac agacagacag acaccgcccc cagccccagc taccacctcc 540
tccccggccg gcggcggaca gtggacgcgg cggcgagccg cgggcagggg ccggagcccg 600
cgcccggagg cggggtggag ggggtcgggg ctcgcggcgt cgcactgaaa cttttcgtcc 660
aacttctggg ctgttctcgc ttcggaggag ccgtggtccg cgcgggggaa gccgagccga 720
gcggagccgc gagaagtgct agctcgggcc gggaggagcc gcagccggag gagggggagg 780
aggaagaaga gaaggaagag gagagggggc cgcagtggcg actcggcgct cggaagccgg 840
gctcatggac gggtgaggcg gcggtgtgcg cagacagtgc tccagccgcg cgcgctcccc 900
aggccctggc ccgggcctcg ggccggggag gaagagtagc tcgccgaggc gccgaggaga 960
gcgggccgcc ccacagcccg agccggagag ggagcgcgag ccgcgccggc cccggtcggg 1020
cctccgaaac catgaacttt ctgctgtctt gggtgcattg gagccttgcc ttgctgctct 1080
acctccacca tgccaagtgg tcccaggctg cacccatggc agaaggagga gggcagaatc 1140
atcacgaagt ggtgaagttc atggatgtct atcagcgcag ctactgccat ccaatcgaga 1200
ccctggtgga catcttccag gagtaccctg atgagatcga gtacatcttc aagccatcct 1260
gtgtgcccct gatgcgatgc gggggctgct gcaatgacga gggcctggag tgtgtgccca 1320
ctgaggagtc caacatcacc atgcagatta tgcggatcaa acctcaccaa ggccagcaca 1380
taggagagat gagcttccta cagcacaaca aatgtgaatg cagaccaaag aaagatagag 1440
caagacaaga aaaaaaatca gttcgaggaa agggaaaggg gcaaaaacga aagcgcaaga 1500
aatcccggta taagtcctgg agcgtgtacg ttggtgcccg ctgctgtcta atgccctgga 1560
gcctccctgg cccccatccc tgtgggcctt gctcagagcg gagaaagcat ttgtttgtac 1620
aagatccgca gacgtgtaaa tgttcctgca aaaacacaga ctcgcgttgc aaggcgaggc 1680
agcttgagtt aaacgaacgt acttgcagat gtgacaagcc gaggcggtga gccgggcagg 1740
aggaaggagc ctccctcagg gtttcgggaa ccagatctct caccaggaaa gactgataca 1800
gaacgatcga tacagaaacc acgctgccgc caccacacca tcaccatcga cagaacagtc 1860
cttaatccag aaacctgaaa tgaaggaaga ggagactctg cgcagagcac tttgggtccg 1920
gagggcgaga ctccggcgga agcattcccg ggcgggtgac ccagcacggt ccctcttgga 1980
attggattcg ccattttatt tttcttgctg ctaaatcacc gagcccggaa gattagagag 2040
ttttatttct gggattcctg tagacacacc cacccacata catacattta tatatatata 2100
tattatatat atataaaaat aaatatctct attttatata tataaaatat atatattctt 2160
tttttaaatt aacagtgcta atgttattgg tgtcttcact ggatgtattt gactgctgtg 2220
gacttgagtt gggaggggaa tgttcccact cagatcctga cagggaagag gaggagatga 2280
gagactctgg catgatcttt tttttgtccc acttggtggg gccagggtcc tctcccctgc 2340
ccaggaatgt gcaaggccag ggcatggggg caaatatgac ccagttttgg gaacaccgac 2400
aaacccagcc ctggcgctga gcctctctac cccaggtcag acggacagaa agacagatca 2460
caggtacagg gatgaggaca ccggctctga ccaggagttt ggggagcttc aggacattgc 2520
tgtgctttgg ggattccctc cacatgctgc acgcgcatct cgcccccagg ggcactgcct 2580
ggaagattca ggagcctggg cggccttcgc ttactctcac ctgcttctga gttgcccagg 2640
agaccactgg cagatgtccc ggcgaagaga agagacacat tgttggaaga agcagcccat 2700
gacagctccc cttcctggga ctcgccctca tcctcttcct gctccccttc ctggggtgca 2760
gcctaaaagg acctatgtcc tcacaccatt gaaaccacta gttctgtccc cccaggagac 2820
ctggttgtgt gtgtgtgagt ggttgacctt cctccatccc ctggtccttc ccttcccttc 2880
ccgaggcaca gagagacagg gcaggatcca cgtgcccatt gtggaggcag agaaaagaga 2940
aagtgtttta tatacggtac ttatttaata tcccttttta attagaaatt aaaacagtta 3000
atttaattaa agagtagggt tttttttcag tattcttggt taatatttaa tttcaactat 3060
ttatgagatg tatcttttgc tctctcttgc tctcttattt gtaccggttt ttgtatataa 3120
aattcatgtt tccaatctct ctctccctga tcggtgacag tcactagctt atcttgaaca 3180
gatatttaat tttgctaaca ctcagctctg ccctccccga tcccctggct ccccagcaca 3240
cattcctttg aaataaggtt tcaatataca tctacatact atatatatat ttggcaactt 3300
gtatttgtgt gtatatatat atatatatgt ttatgtatat atgtgattct gataaaatag 3360
acattgctat tctgtttttt atatgtaaaa acaaaacaag aaaaaataga gaattctaca 3420
tactaaatct ctctcctttt ttaattttaa tatttgttat catttattta ttggtgctac 3480
tgtttatccg taataattgt ggggaaaaga tattaacatc acgtctttgt ctctagtgca 3540
gtttttcgag atattccgta gtacatattt atttttaaac aacgacaaag aaatacagat 3600
atatcttaaa aaaaaaaaag cattttgtat taaagaattt aattctgatc tcaaaaaaaa 3660
aaaaa 3665
<210>155
<211>3596
<212>DNA
<213>智人(Homo sapiens)
<400>155
ggcttggggc agccgggtag ctcggaggtc gtggcgctgg gggctagcac cagcgctctg 60
tcgggaggcg cagcggttag gtggaccggt cagcggactc accggccagg gcgctcggtg 120
ctggaatttg atattcattg atccgggttt tatccctctt cttttttctt aaacattttt 180
ttttaaaact gtattgtttc tcgttttaat ttatttttgc ttgccattcc ccacttgaat 240
cgggccgacg gcttggggag attgctctac ttccccaaat cactgtggat tttggaaacc 300
agcagaaaga ggaaagaggt agcaagagct ccagagagaa gtcgaggaag agagagacgg 360
ggtcagagag agcgcgcggg cgtgcgagca gcgaaagcga caggggcaaa gtgagtgacc 420
tgcttttggg ggtgaccgcc ggagcgcggc gtgagccctc ccccttggga tcccgcagct 480
gaccagtcgc gctgacggac agacagacag acaccgcccc cagccccagc taccacctcc 540
tccccggccg gcggcggaca gtggacgcgg cggcgagccg cgggcagggg ccggagcccg 600
cgcccggagg cggggtggag ggggtcgggg ctcgcggcgt cgcactgaaa cttttcgtcc 660
aacttctggg ctgttctcgc ttcggaggag ccgtggtccg cgcgggggaa gccgagccga 720
gcggagccgc gagaagtgct agctcgggcc gggaggagcc gcagccggag gagggggagg 780
aggaagaaga gaaggaagag gagagggggc cgcagtggcg actcggcgct cggaagccgg 840
gctcatggac gggtgaggcg gcggtgtgcg cagacagtgc tccagccgcg cgcgctcccc 900
aggccctggc ccgggcctcg ggccggggag gaagagtagc tcgccgaggc gccgaggaga 960
gcgggccgcc ccacagcccg agccggagag ggagcgcgag ccgcgccggc cccggtcggg 1020
cctccgaaac catgaacttt ctgctgtctt gggtgcattg gagccttgcc ttgctgctct 1080
acctccacca tgccaagtgg tcccaggctg cacccatggc agaaggagga gggcagaatc 1140
atcacgaagt ggtgaagttc atggatgtct atcagcgcag ctactgccat ccaatcgaga 1200
ccctggtgga catcttccag gagtaccctg atgagatcga gtacatcttc aagccatcct 1260
gtgtgcccct gatgcgatgc gggggctgct gcaatgacga gggcctggag tgtgtgccca 1320
ctgaggagtc caacatcacc atgcagatta tgcggatcaa acctcaccaa ggccagcaca 1380
taggagagat gagcttccta cagcacaaca aatgtgaatg cagaccaaag aaagatagag 1440
caagacaaga aaaaaaatca gttcgaggaa agggaaaggg gcaaaaacga aagcgcaaga 1500
aatcccgtcc ctgtgggcct tgctcagagc ggagaaagca tttgtttgta caagatccgc 1560
agacgtgtaa atgttcctgc aaaaacacag actcgcgttg caaggcgagg cagcttgagt 1620
taaacgaacg tacttgcaga tgtgacaagc cgaggcggtg agccgggcag gaggaaggag 1680
cctccctcag ggtttcggga accagatctc tcaccaggaa agactgatac agaacgatcg 1740
atacagaaac cacgctgccg ccaccacacc atcaccatcg acagaacagt ccttaatcca 1800
gaaacctgaa atgaaggaag aggagactct gcgcagagca ctttgggtcc ggagggcgag 1860
actccggcgg aagcattccc gggcgggtga cccagcacgg tccctcttgg aattggattc 1920
gccattttat ttttcttgct gctaaatcac cgagcccgga agattagaga gttttatttc 1980
tgggattcct gtagacacac ccacccacat acatacattt atatatatat atattatata 2040
tatataaaaa taaatatctc tattttatat atataaaata tatatattct ttttttaaat 2100
taacagtgct aatgttattg gtgtcttcac tggatgtatt tgactgctgt ggacttgagt 2160
tgggagggga atgttcccac tcagatcctg acagggaaga ggaggagatg agagactctg 2220
gcatgatctt ttttttgtcc cacttggtgg ggccagggtc ctctcccctg cccaggaatg 2280
tgcaaggcca gggcatgggg gcaaatatga cccagttttg ggaacaccga caaacccagc 2340
cctggcgctg agcctctcta ccccaggtca gacggacaga aagacagatc acaggtacag 2400
ggatgaggac accggctctg accaggagtt tggggagctt caggacattg ctgtgctttg 2460
gggattccct ccacatgctg cacgcgcatc tcgcccccag gggcactgcc tggaagattc 2520
aggagcctgg gcggccttcg cttactctca cctgcttctg agttgcccag gagaccactg 2580
gcagatgtcc cggcgaagag aagagacaca ttgttggaag aagcagccca tgacagctcc 2640
ccttcctggg actcgccctc atcctcttcc tgctcccctt cctggggtgc agcctaaaag 2700
gacctatgtc ctcacaccat tgaaaccact agttctgtcc ccccaggaga cctggttgtg 2760
tgtgtgtgag tggttgacct tcctccatcc cctggtcctt cccttccctt cccgaggcac 2820
agagagacag ggcaggatcc acgtgcccat tgtggaggca gagaaaagag aaagtgtttt 2880
atatacggta cttatttaat atcccttttt aattagaaat taaaacagtt aatttaatta 2940
aagagtaggg ttttttttca gtattcttgg ttaatattta atttcaacta tttatgagat 3000
gtatcttttg ctctctcttg ctctcttatt tgtaccggtt tttgtatata aaattcatgt 3060
ttccaatctc tctctccctg atcggtgaca gtcactagct tatcttgaac agatatttaa 3120
ttttgctaac actcagctct gccctccccg atcccctggc tccccagcac acattccttt 3180
gaaataaggt ttcaatatac atctacatac tatatatata tttggcaact tgtatttgtg 3240
tgtatatata tatatatatg tttatgtata tatgtgattc tgataaaata gacattgcta 3300
ttctgttttt tatatgtaaa aacaaaacaa gaaaaaatag agaattctac atactaaatc 3360
tctctccttt tttaatttta atatttgtta tcatttattt attggtgcta ctgtttatcc 3420
gtaataattg tggggaaaag atattaacat cacgtctttg tctctagtgc agtttttcga 3480
gatattccgt agtacatatt tatttttaaa caacgacaaa gaaatacaga tatatcttaa 3540
aaaaaaaaaa gcattttgta ttaaagaatt taattctgat ctcaaaaaaa aaaaaa 3596
<210>156
<211>3542
<212>DNA
<213>智人(Homo sapiens)
<400>156
ggcttggggc agccgggtag ctcggaggtc gtggcgctgg gggctagcac cagcgctctg 60
tcgggaggcg cagcggttag gtggaccggt cagcggactc accggccagg gcgctcggtg 120
ctggaatttg atattcattg atccgggttt tatccctctt cttttttctt aaacattttt 180
ttttaaaact gtattgtttc tcgttttaat ttatttttgc ttgccattcc ccacttgaat 240
cgggccgacg gcttggggag attgctctac ttccccaaat cactgtggat tttggaaacc 300
agcagaaaga ggaaagaggt agcaagagct ccagagagaa gtcgaggaag agagagacgg 360
ggtcagagag agcgcgcggg cgtgcgagca gcgaaagcga caggggcaaa gtgagtgacc 420
tgcttttggg ggtgaccgcc ggagcgcggc gtgagccctc ccccttggga tcccgcagct 480
gaccagtcgc gctgacggac agacagacag acaccgcccc cagccccagc taccacctcc 540
tccccggccg gcggcggaca gtggacgcgg cggcgagccg cgggcagggg ccggagcccg 600
cgcccggagg cggggtggag ggggtcgggg ctcgcggcgt cgcactgaaa cttttcgtcc 660
aacttctggg ctgttctcgc ttcggaggag ccgtggtccg cgcgggggaa gccgagccga 720
gcggagccgc gagaagtgct agctcgggcc gggaggagcc gcagccggag gagggggagg 780
aggaagaaga gaaggaagag gagagggggc cgcagtggcg actcggcgct cggaagccgg 840
gctcatggac gggtgaggcg gcggtgtgcg cagacagtgc tccagccgcg cgcgctcccc 900
aggccctggc ccgggcctcg ggccggggag gaagagtagc tcgccgaggc gccgaggaga 960
gcgggccgcc ccacagcccg agccggagag ggagcgcgag ccgcgccggc cccggtcggg 1020
cctccgaaac catgaacttt ctgctgtctt gggtgcattg gagccttgcc ttgctgctct 1080
acctccacca tgccaagtgg tcccaggctg cacccatggc agaaggagga gggcagaatc 1140
atcacgaagt ggtgaagttc atggatgtct atcagcgcag ctactgccat ccaatcgaga 1200
ccctggtgga catcttccag gagtaccctg atgagatcga gtacatcttc aagccatcct 1260
gtgtgcccct gatgcgatgc gggggctgct gcaatgacga gggcctggag tgtgtgccca 1320
ctgaggagtc caacatcacc atgcagatta tgcggatcaa acctcaccaa ggccagcaca 1380
taggagagat gagcttccta cagcacaaca aatgtgaatg cagaccaaag aaagatagag 1440
caagacaaga aaatccctgt gggccttgct cagagcggag aaagcatttg tttgtacaag 1500
atccgcagac gtgtaaatgt tcctgcaaaa acacagactc gcgttgcaag gcgaggcagc 1560
ttgagttaaa cgaacgtact tgcagatgtg acaagccgag gcggtgagcc gggcaggagg 1620
aaggagcctc cctcagggtt tcgggaacca gatctctcac caggaaagac tgatacagaa 1680
cgatcgatac agaaaccacg ctgccgccac cacaccatca ccatcgacag aacagtcctt 1740
aatccagaaa cctgaaatga aggaagagga gactctgcgc agagcacttt gggtccggag 1800
ggcgagactc cggcggaagc attcccgggc gggtgaccca gcacggtccc tcttggaatt 1860
ggattcgcca ttttattttt cttgctgcta aatcaccgag cccggaagat tagagagttt 1920
tatttctggg attcctgtag acacacccac ccacatacat acatttatat atatatatat 1980
tatatatata taaaaataaa tatctctatt ttatatatat aaaatatata tattcttttt 2040
ttaaattaac agtgctaatg ttattggtgt cttcactgga tgtatttgac tgctgtggac 2100
ttgagttggg aggggaatgt tcccactcag atcctgacag ggaagaggag gagatgagag 2160
actctggcat gatctttttt ttgtcccact tggtggggcc agggtcctct cccctgccca 2220
ggaatgtgca aggccagggc atgggggcaa atatgaccca gttttgggaa caccgacaaa 2280
cccagccctg gcgctgagcc tctctacccc aggtcagacg gacagaaaga cagatcacag 2340
gtacagggat gaggacaccg gctctgacca ggagtttggg gagcttcagg acattgctgt 2400
gctttgggga ttccctccac atgctgcacg cgcatctcgc ccccaggggc actgcctgga 2460
agattcagga gcctgggcgg ccttcgctta ctctcacctg cttctgagtt gcccaggaga 2520
ccactggcag atgtcccggc gaagagaaga gacacattgt tggaagaagc agcccatgac 2580
agctcccctt cctgggactc gccctcatcc tcttcctgct ccccttcctg gggtgcagcc 2640
taaaaggacc tatgtcctca caccattgaa accactagtt ctgtcccccc aggagacctg 2700
gttgtgtgtg tgtgagtggt tgaccttcct ccatcccctg gtccttccct tcccttcccg 2760
aggcacagag agacagggca ggatccacgt gcccattgtg gaggcagaga aaagagaaag 2820
tgttttatat acggtactta tttaatatcc ctttttaatt agaaattaaa acagttaatt 2880
taattaaaga gtagggtttt ttttcagtat tcttggttaa tatttaattt caactattta 2940
tgagatgtat cttttgctct ctcttgctct cttatttgta ccggtttttg tatataaaat 3000
tcatgtttcc aatctctctc tccctgatcg gtgacagtca ctagcttatc ttgaacagat 3060
atttaatttt gctaacactc agctctgccc tccccgatcc cctggctccc cagcacacat 3120
tcctttgaaa taaggtttca atatacatct acatactata tatatatttg gcaacttgta 3180
tttgtgtgta tatatatata tatatgttta tgtatatatg tgattctgat aaaatagaca 3240
ttgctattct gttttttata tgtaaaaaca aaacaagaaa aaatagagaa ttctacatac 3300
taaatctctc tcctttttta attttaatat ttgttatcat ttatttattg gtgctactgt 3360
ttatccgtaa taattgtggg gaaaagatat taacatcacg tctttgtctc tagtgcagtt 3420
tttcgagata ttccgtagta catatttatt tttaaacaac gacaaagaaa tacagatata 3480
tcttaaaaaa aaaaaagcat tttgtattaa agaatttaat tctgatctca aaaaaaaaaa 3540
aa 3542
<210>157
<211>3507
<212>DNA
<213>智人(Homo sapiens)
<400>157
ggcttggggc agccgggtag ctcggaggtc gtggcgctgg gggctagcac cagcgctctg 60
tcgggaggcg cagcggttag gtggaccggt cagcggactc accggccagg gcgctcggtg 120
ctggaatttg atattcattg atccgggttt tatccctctt cttttttctt aaacattttt 180
ttttaaaact gtattgtttc tcgttttaat ttatttttgc ttgccattcc ccacttgaat 240
cgggccgacg gcttggggag attgctctac ttccccaaat cactgtggat tttggaaacc 300
agcagaaaga ggaaagaggt agcaagagct ccagagagaa gtcgaggaag agagagacgg 360
ggtcagagag agcgcgcggg cgtgcgagca gcgaaagcga caggggcaaa gtgagtgacc 420
tgcttttggg ggtgaccgcc ggagcgcggc gtgagccctc ccccttggga tcccgcagct 480
gaccagtcgc gctgacggac agacagacag acaccgcccc cagccccagc taccacctcc 540
tccccggccg gcggcggaca gtggacgcgg cggcgagccg cgggcagggg ccggagcccg 600
cgcccggagg cggggtggag ggggtcgggg ctcgcggcgt cgcactgaaa cttttcgtcc 660
aacttctggg ctgttctcgc ttcggaggag ccgtggtccg cgcgggggaa gccgagccga 720
gcggagccgc gagaagtgct agctcgggcc gggaggagcc gcagccggag gagggggagg 780
aggaagaaga gaaggaagag gagagggggc cgcagtggcg actcggcgct cggaagccgg 840
gctcatggac gggtgaggcg gcggtgtgcg cagacagtgc tccagccgcg cgcgctcccc 900
aggccctggc ccgggcctcg ggccggggag gaagagtagc tcgccgaggc gccgaggaga 960
gcgggccgcc ccacagcccg agccggagag ggagcgcgag ccgcgccggc cccggtcggg 1020
cctccgaaac catgaacttt ctgctgtctt gggtgcattg gagccttgcc ttgctgctct 1080
acctccacca tgccaagtgg tcccaggctg cacccatggc agaaggagga gggcagaatc 1140
atcacgaagt ggtgaagttc atggatgtct atcagcgcag ctactgccat ccaatcgaga 1200
ccctggtgga catcttccag gagtaccctg atgagatcga gtacatcttc aagccatcct 1260
gtgtgcccct gatgcgatgc gggggctgct gcaatgacga gggcctggag tgtgtgccca 1320
ctgaggagtc caacatcacc atgcagatta tgcggatcaa acctcaccaa ggccagcaca 1380
taggagagat gagcttccta cagcacaaca aatgtgaatg cagaccaaag aaagatagag 1440
caagacaaga aaatccctgt gggccttgct cagagcggag aaagcatttg tttgtacaag 1500
atccgcagac gtgtaaatgt tcctgcaaaa acacagactc gcgttgcaag atgtgacaag 1560
ccgaggcggt gagccgggca ggaggaagga gcctccctca gggtttcggg aaccagatct 1620
ctcaccagga aagactgata cagaacgatc gatacagaaa ccacgctgcc gccaccacac 1680
catcaccatc gacagaacag tccttaatcc agaaacctga aatgaaggaa gaggagactc 1740
tgcgcagagc actttgggtc cggagggcga gactccggcg gaagcattcc cgggcgggtg 1800
acccagcacg gtccctcttg gaattggatt cgccatttta tttttcttgc tgctaaatca 1860
ccgagcccgg aagattagag agttttattt ctgggattcc tgtagacaca cccacccaca 1920
tacatacatt tatatatata tatattatat atatataaaa ataaatatct ctattttata 1980
tatataaaat atatatattc tttttttaaa ttaacagtgc taatgttatt ggtgtcttca 2040
ctggatgtat ttgactgctg tggacttgag ttgggagggg aatgttccca ctcagatcct 2100
gacagggaag aggaggagat gagagactct ggcatgatct tttttttgtc ccacttggtg 2160
gggccagggt cctctcccct gcccaggaat gtgcaaggcc agggcatggg ggcaaatatg 2220
acccagtttt gggaacaccg acaaacccag ccctggcgct gagcctctct accccaggtc 2280
agacggacag aaagacagat cacaggtaca gggatgagga caccggctct gaccaggagt 2340
ttggggagct tcaggacatt gctgtgcttt ggggattccc tccacatgct gcacgcgcat 2400
ctcgccccca ggggcactgc ctggaagatt caggagcctg ggcggccttc gcttactctc 2460
acctgcttct gagttgccca ggagaccact ggcagatgtc ccggcgaaga gaagagacac 2520
attgttggaa gaagcagccc atgacagctc cccttcctgg gactcgccct catcctcttc 2580
ctgctcccct tcctggggtg cagcctaaaa ggacctatgt cctcacacca ttgaaaccac 2640
tagttctgtc cccccaggag acctggttgt gtgtgtgtga gtggttgacc ttcctccatc 2700
ccctggtcct tcccttccct tcccgaggca cagagagaca gggcaggatc cacgtgccca 2760
ttgtggaggc agagaaaaga gaaagtgttt tatatacggt acttatttaa tatccctttt 2820
taattagaaa ttaaaacagt taatttaatt aaagagtagg gttttttttc agtattcttg 2880
gttaatattt aatttcaact atttatgaga tgtatctttt gctctctctt gctctcttat 2940
ttgtaccggt ttttgtatat aaaattcatg tttccaatct ctctctccct gatcggtgac 3000
agtcactagc ttatcttgaa cagatattta attttgctaa cactcagctc tgccctcccc 3060
gatcccctgg ctccccagca cacattcctt tgaaataagg tttcaatata catctacata 3120
ctatatatat atttggcaac ttgtatttgt gtgtatatat atatatatat gtttatgtat 3180
atatgtgatt ctgataaaat agacattgct attctgtttt ttatatgtaa aaacaaaaca 3240
agaaaaaata gagaattcta catactaaat ctctctcctt ttttaatttt aatatttgtt 3300
atcatttatt tattggtgct actgtttatc cgtaataatt gtggggaaaa gatattaaca 3360
tcacgtcttt gtctctagtg cagtttttcg agatattccg tagtacatat ttatttttaa 3420
acaacgacaa agaaatacag atatatctta aaaaaaaaaa agcattttgt attaaagaat 3480
ttaattctga tctcaaaaaa aaaaaaa 3507
<210>158
<211>3410
<212>DNA
<213>智人(Homo sapiens)
<400>158
ggcttggggc agccgggtag ctcggaggtc gtggcgctgg gggctagcac cagcgctctg 60
tcgggaggcg cagcggttag gtggaccggt cagcggactc accggccagg gcgctcggtg 120
ctggaatttg atattcattg atccgggttt tatccctctt cttttttctt aaacattttt 180
ttttaaaact gtattgtttc tcgttttaat ttatttttgc ttgccattcc ccacttgaat 240
cgggccgacg gcttggggag attgctctac ttccccaaat cactgtggat tttggaaacc 300
agcagaaaga ggaaagaggt agcaagagct ccagagagaa gtcgaggaag agagagacgg 360
ggtcagagag agcgcgcggg cgtgcgagca gcgaaagcga caggggcaaa gtgagtgacc 420
tgcttttggg ggtgaccgcc ggagcgcggc gtgagccctc ccccttggga tcccgcagct 480
gaccagtcgc gctgacggac agacagacag acaccgcccc cagccccagc taccacctcc 540
tccccggccg gcggcggaca gtggacgcgg cggcgagccg cgggcagggg ccggagcccg 600
cgcccggagg cggggtggag ggggtcgggg ctcgcggcgt cgcactgaaa cttttcgtcc 660
aacttctggg ctgttctcgc ttcggaggag ccgtggtccg cgcgggggaa gccgagccga 720
gcggagccgc gagaagtgct agctcgggcc gggaggagcc gcagccggag gagggggagg 780
aggaagaaga gaaggaagag gagagggggc cgcagtggcg actcggcgct cggaagccgg 840
gctcatggac gggtgaggcg gcggtgtgcg cagacagtgc tccagccgcg cgcgctcccc 900
aggccctggc ccgggcctcg ggccggggag gaagagtagc tcgccgaggc gccgaggaga 960
gcgggccgcc ccacagcccg agccggagag ggagcgcgag ccgcgccggc cccggtcggg 1020
cctccgaaac catgaacttt ctgctgtctt gggtgcattg gagccttgcc ttgctgctct 1080
acctccacca tgccaagtgg tcccaggctg cacccatggc agaaggagga gggcagaatc 1140
atcacgaagt ggtgaagttc atggatgtct atcagcgcag ctactgccat ccaatcgaga 1200
ccctggtgga catcttccag gagtaccctg atgagatcga gtacatcttc aagccatcct 1260
gtgtgcccct gatgcgatgc gggggctgct gcaatgacga gggcctggag tgtgtgccca 1320
ctgaggagtc caacatcacc atgcagatta tgcggatcaa acctcaccaa ggccagcaca 1380
taggagagat gagcttccta cagcacaaca aatgtgaatg cagaccaaag aaagatagag 1440
caagacaaga aaaatgtgac aagccgaggc ggtgagccgg gcaggaggaa ggagcctccc 1500
tcagggtttc gggaaccaga tctctcacca ggaaagactg atacagaacg atcgatacag 1560
aaaccacgct gccgccacca caccatcacc atcgacagaa cagtccttaa tccagaaacc 1620
tgaaatgaag gaagaggaga ctctgcgcag agcactttgg gtccggaggg cgagactccg 1680
gcggaagcat tcccgggcgg gtgacccagc acggtccctc ttggaattgg attcgccatt 1740
ttatttttct tgctgctaaa tcaccgagcc cggaagatta gagagtttta tttctgggat 1800
tcctgtagac acacccaccc acatacatac atttatatat atatatatta tatatatata 1860
aaaataaata tctctatttt atatatataa aatatatata ttcttttttt aaattaacag 1920
tgctaatgtt attggtgtct tcactggatg tatttgactg ctgtggactt gagttgggag 1980
gggaatgttc ccactcagat cctgacaggg aagaggagga gatgagagac tctggcatga 2040
tctttttttt gtcccacttg gtggggccag ggtcctctcc cctgcccagg aatgtgcaag 2100
gccagggcat gggggcaaat atgacccagt tttgggaaca ccgacaaacc cagccctggc 2160
gctgagcctc tctaccccag gtcagacgga cagaaagaca gatcacaggt acagggatga 2220
ggacaccggc tctgaccagg agtttgggga gcttcaggac attgctgtgc tttggggatt 2280
ccctccacat gctgcacgcg catctcgccc ccaggggcac tgcctggaag attcaggagc 2340
ctgggcggcc ttcgcttact ctcacctgct tctgagttgc ccaggagacc actggcagat 2400
gtcccggcga agagaagaga cacattgttg gaagaagcag cccatgacag ctccccttcc 2460
tgggactcgc cctcatcctc ttcctgctcc ccttcctggg gtgcagccta aaaggaccta 2520
tgtcctcaca ccattgaaac cactagttct gtccccccag gagacctggt tgtgtgtgtg 2580
tgagtggttg accttcctcc atcccctggt ccttcccttc ccttcccgag gcacagagag 2640
acagggcagg atccacgtgc ccattgtgga ggcagagaaa agagaaagtg ttttatatac 2700
ggtacttatt taatatccct ttttaattag aaattaaaac agttaattta attaaagagt 2760
agggtttttt ttcagtattc ttggttaata tttaatttca actatttatg agatgtatct 2820
tttgctctct cttgctctct tatttgtacc ggtttttgta tataaaattc atgtttccaa 2880
tctctctctc cctgatcggt gacagtcact agcttatctt gaacagatat ttaattttgc 2940
taacactcag ctctgccctc cccgatcccc tggctcccca gcacacattc ctttgaaata 3000
aggtttcaat atacatctac atactatata tatatttggc aacttgtatt tgtgtgtata 3060
tatatatata tatgtttatg tatatatgtg attctgataa aatagacatt gctattctgt 3120
tttttatatg taaaaacaaa acaagaaaaa atagagaatt ctacatacta aatctctctc 3180
cttttttaat tttaatattt gttatcattt atttattggt gctactgttt atccgtaata 3240
attgtgggga aaagatatta acatcacgtc tttgtctcta gtgcagtttt tcgagatatt 3300
ccgtagtaca tatttatttt taaacaacga caaagaaata cagatatatc ttaaaaaaaa 3360
aaaagcattt tgtattaaag aatttaattc tgatctcaaa aaaaaaaaaa 3410
<210>159
<211>3476
<212>DNA
<213>智人(Homo sapiens)
<400>159
ggcttggggc agccgggtag ctcggaggtc gtggcgctgg gggctagcac cagcgctctg 60
tcgggaggcg cagcggttag gtggaccggt cagcggactc accggccagg gcgctcggtg 120
ctggaatttg atattcattg atccgggttt tatccctctt cttttttctt aaacattttt 180
ttttaaaact gtattgtttc tcgttttaat ttatttttgc ttgccattcc ccacttgaat 240
cgggccgacg gcttggggag attgctctac ttccccaaat cactgtggat tttggaaacc 300
agcagaaaga ggaaagaggt agcaagagct ccagagagaa gtcgaggaag agagagacgg 360
ggtcagagag agcgcgcggg cgtgcgagca gcgaaagcga caggggcaaa gtgagtgacc 420
tgcttttggg ggtgaccgcc ggagcgcggc gtgagccctc ccccttggga tcccgcagct 480
gaccagtcgc gctgacggac agacagacag acaccgcccc cagccccagc taccacctcc 540
tccccggccg gcggcggaca gtggacgcgg cggcgagccg cgggcagggg ccggagcccg 600
cgcccggagg cggggtggag ggggtcgggg ctcgcggcgt cgcactgaaa cttttcgtcc 660
aacttctggg ctgttctcgc ttcggaggag ccgtggtccg cgcgggggaa gccgagccga 720
gcggagccgc gagaagtgct agctcgggcc gggaggagcc gcagccggag gagggggagg 780
aggaagaaga gaaggaagag gagagggggc cgcagtggcg actcggcgct cggaagccgg 840
gctcatggac gggtgaggcg gcggtgtgcg cagacagtgc tccagccgcg cgcgctcccc 900
aggccctggc ccgggcctcg ggccggggag gaagagtagc tcgccgaggc gccgaggaga 960
gcgggccgcc ccacagcccg agccggagag ggagcgcgag ccgcgccggc cccggtcggg 1020
cctccgaaac catgaacttt ctgctgtctt gggtgcattg gagccttgcc ttgctgctct 1080
acctccacca tgccaagtgg tcccaggctg cacccatggc agaaggagga gggcagaatc 1140
atcacgaagt ggtgaagttc atggatgtct atcagcgcag ctactgccat ccaatcgaga 1200
ccctggtgga catcttccag gagtaccctg atgagatcga gtacatcttc aagccatcct 1260
gtgtgcccct gatgcgatgc gggggctgct gcaatgacga gggcctggag tgtgtgccca 1320
ctgaggagtc caacatcacc atgcagatta tgcggatcaa acctcaccaa ggccagcaca 1380
taggagagat gagcttccta cagcacaaca aatgtgaatg cagaccaaag aaagatagag 1440
caagacaaga aaatccctgt gggccttgct cagagcggag aaagcatttg tttgtacaag 1500
atccgcagac gtgtaaatgt tcctgcaaaa acacagactc gcgttgcaag gcgaggcagc 1560
ttgagttaaa cgaacgtact tgcagatctc tcaccaggaa agactgatac agaacgatcg 1620
atacagaaac cacgctgccg ccaccacacc atcaccatcg acagaacagt ccttaatcca 1680
gaaacctgaa atgaaggaag aggagactct gcgcagagca ctttgggtcc ggagggcgag 1740
actccggcgg aagcattccc gggcgggtga cccagcacgg tccctcttgg aattggattc 1800
gccattttat ttttcttgct gctaaatcac cgagcccgga agattagaga gttttatttc 1860
tgggattcct gtagacacac ccacccacat acatacattt atatatatat atattatata 1920
tatataaaaa taaatatctc tattttatat atataaaata tatatattct ttttttaaat 1980
taacagtgct aatgttattg gtgtcttcac tggatgtatt tgactgctgt ggacttgagt 2040
tgggagggga atgttcccac tcagatcctg acagggaaga ggaggagatg agagactctg 2100
gcatgatctt ttttttgtcc cacttggtgg ggccagggtc ctctcccctg cccaggaatg 2160
tgcaaggcca gggcatgggg gcaaatatga cccagttttg ggaacaccga caaacccagc 2220
cctggcgctg agcctctcta ccccaggtca gacggacaga aagacagatc acaggtacag 2280
ggatgaggac accggctctg accaggagtt tggggagctt caggacattg ctgtgctttg 2340
gggattccct ccacatgctg cacgcgcatc tcgcccccag gggcactgcc tggaagattc 2400
aggagcctgg gcggccttcg cttactctca cctgcttctg agttgcccag gagaccactg 2460
gcagatgtcc cggcgaagag aagagacaca ttgttggaag aagcagccca tgacagctcc 2520
ccttcctggg actcgccctc atcctcttcc tgctcccctt cctggggtgc agcctaaaag 2580
gacctatgtc ctcacaccat tgaaaccact agttctgtcc ccccaggaga cctggttgtg 2640
tgtgtgtgag tggttgacct tcctccatcc cctggtcctt cccttccctt cccgaggcac 2700
agagagacag ggcaggatcc acgtgcccat tgtggaggca gagaaaagag aaagtgtttt 2760
atatacggta cttatttaat atcccttttt aattagaaat taaaacagtt aatttaatta 2820
aagagtaggg ttttttttca gtattcttgg ttaatattta atttcaacta tttatgagat 2880
gtatcttttg ctctctcttg ctctcttatt tgtaccggtt tttgtatata aaattcatgt 2940
ttccaatctc tctctccctg atcggtgaca gtcactagct tatcttgaac agatatttaa 3000
ttttgctaac actcagctct gccctccccg atcccctggc tccccagcac acattccttt 3060
gaaataaggt ttcaatatac atctacatac tatatatata tttggcaact tgtatttgtg 3120
tgtatatata tatatatatg tttatgtata tatgtgattc tgataaaata gacattgcta 3180
ttctgttttt tatatgtaaa aacaaaacaa gaaaaaatag agaattctac atactaaatc 3240
tctctccttt tttaatttta atatttgtta tcatttattt attggtgcta ctgtttatcc 3300
gtaataattg tggggaaaag atattaacat cacgtctttg tctctagtgc agtttttcga 3360
gatattccgt agtacatatt tatttttaaa caacgacaaa gaaatacaga tatatcttaa 3420
aaaaaaaaaa gcattttgta ttaaagaatt taattctgat ctcaaaaaaa aaaaaa 3476
<210>160
<211>3614
<212>DNA
<213>智人(Homo sapiens)
<400>160
ggcttggggc agccgggtag ctcggaggtc gtggcgctgg gggctagcac cagcgctctg 60
tcgggaggcg cagcggttag gtggaccggt cagcggactc accggccagg gcgctcggtg 120
ctggaatttg atattcattg atccgggttt tatccctctt cttttttctt aaacattttt 180
ttttaaaact gtattgtttc tcgttttaat ttatttttgc ttgccattcc ccacttgaat 240
cgggccgacg gcttggggag attgctctac ttccccaaat cactgtggat tttggaaacc 300
agcagaaaga ggaaagaggt agcaagagct ccagagagaa gtcgaggaag agagagacgg 360
ggtcagagag agcgcgcggg cgtgcgagca gcgaaagcga caggggcaaa gtgagtgacc 420
tgcttttggg ggtgaccgcc ggagcgcggc gtgagccctc ccccttggga tcccgcagct 480
gaccagtcgc gctgacggac agacagacag acaccgcccc cagccccagc taccacctcc 540
tccccggccg gcggcggaca gtggacgcgg cggcgagccg cgggcagggg ccggagcccg 600
cgcccggagg cggggtggag ggggtcgggg ctcgcggcgt cgcactgaaa cttttcgtcc 660
aacttctggg ctgttctcgc ttcggaggag ccgtggtccg cgcgggggaa gccgagccga 720
gcggagccgc gagaagtgct agctcgggcc gggaggagcc gcagccggag gagggggagg 780
aggaagaaga gaaggaagag gagagggggc cgcagtggcg actcggcgct cggaagccgg 840
gctcatggac gggtgaggcg gcggtgtgcg cagacagtgc tccagccgcg cgcgctcccc 900
aggccctggc ccgggcctcg ggccggggag gaagagtagc tcgccgaggc gccgaggaga 960
gcgggccgcc ccacagcccg agccggagag ggagcgcgag ccgcgccggc cccggtcggg 1020
cctccgaaac catgaacttt ctgctgtctt gggtgcattg gagccttgcc ttgctgctct 1080
acctccacca tgccaagtgg tcccaggctg cacccatggc agaaggagga gggcagaatc 1140
atcacgaagt ggtgaagttc atggatgtct atcagcgcag ctactgccat ccaatcgaga 1200
ccctggtgga catcttccag gagtaccctg atgagatcga gtacatcttc aagccatcct 1260
gtgtgcccct gatgcgatgc gggggctgct gcaatgacga gggcctggag tgtgtgccca 1320
ctgaggagtc caacatcacc atgcagatta tgcggatcaa acctcaccaa ggccagcaca 1380
taggagagat gagcttccta cagcacaaca aatgtgaatg cagaccaaag aaagatagag 1440
caagacaaga aaaaaaatca gttcgaggaa agggaaaggg gcaaaaacga aagcgcaaga 1500
aatcccggta taagtcctgg agcgttccct gtgggccttg ctcagagcgg agaaagcatt 1560
tgtttgtaca agatccgcag acgtgtaaat gttcctgcaa aaacacagac tcgcgttgca 1620
aggcgaggca gcttgagtta aacgaacgta cttgcagatg tgacaagccg aggcggtgag 1680
ccgggcagga ggaaggagcc tccctcaggg tttcgggaac cagatctctc accaggaaag 1740
actgatacag aacgatcgat acagaaacca cgctgccgcc accacaccat caccatcgac 1800
agaacagtcc ttaatccaga aacctgaaat gaaggaagag gagactctgc gcagagcact 1860
ttgggtccgg agggcgagac tccggcggaa gcattcccgg gcgggtgacc cagcacggtc 1920
cctcttggaa ttggattcgc cattttattt ttcttgctgc taaatcaccg agcccggaag 1980
attagagagt tttatttctg ggattcctgt agacacaccc acccacatac atacatttat 2040
atatatatat attatatata tataaaaata aatatctcta ttttatatat ataaaatata 2100
tatattcttt ttttaaatta acagtgctaa tgttattggt gtcttcactg gatgtatttg 2160
actgctgtgg acttgagttg ggaggggaat gttcccactc agatcctgac agggaagagg 2220
aggagatgag agactctggc atgatctttt ttttgtccca cttggtgggg ccagggtcct 2280
ctcccctgcc caggaatgtg caaggccagg gcatgggggc aaatatgacc cagttttggg 2340
aacaccgaca aacccagccc tggcgctgag cctctctacc ccaggtcaga cggacagaaa 2400
gacagatcac aggtacaggg atgaggacac cggctctgac caggagtttg gggagcttca 2460
ggacattgct gtgctttggg gattccctcc acatgctgca cgcgcatctc gcccccaggg 2520
gcactgcctg gaagattcag gagcctgggc ggccttcgct tactctcacc tgcttctgag 2580
ttgcccagga gaccactggc agatgtcccg gcgaagagaa gagacacatt gttggaagaa 2640
gcagcccatg acagctcccc ttcctgggac tcgccctcat cctcttcctg ctccccttcc 2700
tggggtgcag cctaaaagga cctatgtcct cacaccattg aaaccactag ttctgtcccc 2760
ccaggagacc tggttgtgtg tgtgtgagtg gttgaccttc ctccatcccc tggtccttcc 2820
cttcccttcc cgaggcacag agagacaggg caggatccac gtgcccattg tggaggcaga 2880
gaaaagagaa agtgttttat atacggtact tatttaatat ccctttttaa ttagaaatta 2940
aaacagttaa tttaattaaa gagtagggtt ttttttcagt attcttggtt aatatttaat 3000
ttcaactatt tatgagatgt atcttttgct ctctcttgct ctcttatttg taccggtttt 3060
tgtatataaa attcatgttt ccaatctctc tctccctgat cggtgacagt cactagctta 3120
tcttgaacag atatttaatt ttgctaacac tcagctctgc cctccccgat cccctggctc 3180
cccagcacac attcctttga aataaggttt caatatacat ctacatacta tatatatatt 3240
tggcaacttg tatttgtgtg tatatatata tatatatgtt tatgtatata tgtgattctg 3300
ataaaataga cattgctatt ctgtttttta tatgtaaaaa caaaacaaga aaaaatagag 3360
aattctacat actaaatctc tctccttttt taattttaat atttgttatc atttatttat 3420
tggtgctact gtttatccgt aataattgtg gggaaaagat attaacatca cgtctttgtc 3480
tctagtgcag tttttcgaga tattccgtag tacatattta tttttaaaca acgacaaaga 3540
aatacagata tatcttaaaa aaaaaaaagc attttgtatt aaagaattta attctgatct 3600
caaaaaaaaa aaaa 3614
<210>161
<211>2920
<212>DNA
<213>小鼠(Mus musculus)
<400>161
cgggattgca cggaaacttt tcgtccaact tctgggctct tctcgctccg tagtagccgt 60
ggtctgcgcc gcaggagaca aaccgatcgg agctgggaga agtgctagct cgggcctgga 120
gaagccgggg cccgagaaga gaggggagga agagaaggaa gaggagaggg ggccgcagtg 180
ggcgctcggc tctcaggagc cgagctcatg gacgggtgag gcggccgtgt gcgcagacag 240
tgctccagcc gcgcgcgcgc cccaggcccc ggcccgggcc tcggttccag aagggagagg 300
agcccgccaa ggcgcgcaag agagcgggct gcctcgcagt ccgagccgga gagggagcgc 360
gagccgcgcc ggccccggac gggcctccga aaccatgaac tttctgctct cttgggtgca 420
ctggaccctg gctttactgc tgtacctcca ccatgccaag tggtcccagg ctgcacccac 480
gacagaagga gagcagaagt cccatgaagt gatcaagttc atggatgtct accagcgaag 540
ctactgccgt ccgattgaga ccctggtgga catcttccag gagtaccccg acgagataga 600
gtacatcttc aagccgtcct gtgtgccgct gatgcgctgt gcaggctgct gtaacgatga 660
agccctggag tgcgtgccca cgtcagagag caacatcacc atgcagatca tgcggatcaa 720
acctcaccaa agccagcaca taggagagat gagcttccta cagcacagca gatgtgaatg 780
cagaccaaag aaagacagaa caaagccaga aaaaaaatca gttcgaggaa agggaaaggg 840
tcaaaaacga aagcgcaaga aatcccggtt taaatcctgg agcgttcact gtgagccttg 900
ttcagagcgg agaaagcatt tgtttgtcca agatccgcag acgtgtaaat gttcctgcaa 960
aaacacagac tcgcgttgca aggcgaggca gcttgagtta aacgaacgta cttgcagatg 1020
tgacaagcca aggcggtgag ccaggctgca ggaaggagcc tccctcaggg tttcgggaac 1080
cagacctctc accggaaaga ccgattaacc atgtcaccac cacgccatca tcgtcaccgt 1140
tgacagaaca gtccttaatc cagaaagcct gacatgaagg aagaggagac tcttcgagga 1200
gcactttggg tccggagggc gagactccgg cagacgcatt cccgggcagg tgaccaagca 1260
cggtccctcg tgggactgga ttcgccattt tcttatatct gctgctaaat cgccaagccc 1320
ggaagattag ggttgtttct gggattcctg tagacacacc cacccacata cacacatata 1380
tatatattat atatataaat aaatatatat gttttatata taaaatatat atatattctt 1440
ttttttaaat taactctgct aatgttattg gtgtcttcac tggatatgtt tgactgctgt 1500
ggacttgtgt tgggaggagg atgtcctcac tcggatgccg acacgggaga caatgggatg 1560
aaaggcttca gtgtggtctg agagaggccg aagtcctttt gcctgccggg gagcaagcaa 1620
ggccagggca cgggggcaca tttgctcact tccagaaaca cgacaaaccc attcctggcc 1680
ctgagtcaag aggacagaga gacagatgat gacagagaaa gagataaaga tgccggttcc 1740
aaccagaagt ttggggagcc tcaggacatg gcatgctttg tggatcccca tgatagtcta 1800
caaaagcacc ccgcccctct gggcactgcc tggaagaatc gggagcctgg ccagccttca 1860
gctcgctcct ccacttctga ggggcctagg aggcctccca caggtgtccc ggcaagagaa 1920
gacacggtgg tggaagaaga ggcctggtaa tggcccctcc tcctgggacc ccttcgtcct 1980
ctccttaccc cacctcctgg gtacagccca ggaggacctt gtgtgatcag accattgaaa 2040
ccactaattc tgtccccagg agacttggct gtgtgtgtga gtggcttacc cttcctcatc 2100
ttcccttccc aaggcacaga gcaatggggc aggacccgca agcccctcac ggaggcagag 2160
aaaagagaaa gtgttttata tacggtactt atttaatagc cctttttaat tagaaattaa 2220
aacagttaat ttaattaaag agtagggttt ttttcagtat tcttggttaa tatttaattt 2280
caactattta tgagatgtat ctctcgctct ctcttatttg tacttgtgtg tgtgtgtgtg 2340
tgtgtgtgtg tgtgtgtgtg tgtgtgtgta tgaaatctgt gtttccaatc tctctctccc 2400
agatcggtga cagtcactag cttgtcctga gaagatattt aattttgcta acactcagct 2460
ctgccctccc ttgtccccac cacacattcc tttgaaataa ggtttcaata tacatttaca 2520
tactatatat atatttggca acttgtgttt gtatataaat atatatatat atatatatgt 2580
ttatgtatat atgtgattct gataaaatag acattgctat tctgtttttt atatgtaaaa 2640
acaaaacaag aaaaatagag aattctacat actaaatctc tctccttttt taattttaat 2700
atttgttatc atttatttat tggtgctact gtttatccgt aataattgtg ggggaaaaag 2760
atattaacat cacgtctttg tctctagagc agttttccga gatattccgt agtacatatt 2820
tatttttaaa cagcaacaaa gaaatacaga tatatcttaa aaaaaaaagc attttgtatt 2880
aaagaattga attctgatct caaaaaaaaa aaaaaaaaaa 2920
<210>162
<211>2716
<212>DNA
<213>小鼠(Mus musculus)
<400>162
cgggattgca cggaaacttt tcgtccaact tctgggctct tctcgctccg tagtagccgt 60
ggtctgcgcc gcaggagaca aaccgatcgg agctgggaga agtgctagct cgggcctgga 120
gaagccgggg cccgagaaga gaggggagga agagaaggaa gaggagaggg ggccgcagtg 180
ggcgctcggc tctcaggagc cgagctcatg gacgggtgag gcggccgtgt gcgcagacag 240
tgctccagcc gcgcgcgcgc cccaggcccc ggcccgggcc tcggttccag aagggagagg 300
agcccgccaa ggcgcgcaag agagcgggct gcctcgcagt ccgagccgga gagggagcgc 360
gagccgcgcc ggccccggac gggcctccga aaccatgaac tttctgctct cttgggtgca 420
ctggaccctg gctttactgc tgtacctcca ccatgccaag tggtcccagg ctgcacccac 480
gacagaagga gagcagaagt cccatgaagt gatcaagttc atggatgtct accagcgaag 540
ctactgccgt ccgattgaga ccctggtgga catcttccag gagtaccccg acgagataga 600
gtacatcttc aagccgtcct gtgtgccgct gatgcgctgt gcaggctgct gtaacgatga 660
agccctggag tgcgtgccca cgtcagagag caacatcacc atgcagatca tgcggatcaa 720
acctcaccaa agccagcaca taggagagat gagcttccta cagcacagca gatgtgaatg 780
cagaccaaag aaagacagaa caaagccaga aaaatgtgac aagccaaggc ggtgagccag 840
gctgcaggaa ggagcctccc tcagggtttc gggaaccaga cctctcaccg gaaagaccga 900
ttaaccatgt caccaccacg ccatcatcgt caccgttgac agaacagtcc ttaatccaga 960
aagcctgaca tgaaggaaga ggagactctt cgaggagcac tttgggtccg gagggcgaga 1020
ctccggcaga cgcattcccg ggcaggtgac caagcacggt ccctcgtggg actggattcg 1080
ccattttctt atatctgctg ctaaatcgcc aagcccggaa gattagggtt gtttctggga 1140
ttcctgtaga cacacccacc cacatacaca catatatata tattatatat ataaataaat 1200
atatatgttt tatatataaa atatatatat attctttttt ttaaattaac tctgctaatg 1260
ttattggtgt cttcactgga tatgtttgac tgctgtggac ttgtgttggg aggaggatgt 1320
cctcactcgg atgccgacac gggagacaat gggatgaaag gcttcagtgt ggtctgagag 1380
aggccgaagt ccttttgcct gccggggagc aagcaaggcc agggcacggg ggcacatttg 1440
ctcacttcca gaaacacgac aaacccattc ctggccctga gtcaagagga cagagagaca 1500
gatgatgaca gagaaagaga taaagatgcc ggttccaacc agaagtttgg ggagcctcag 1560
gacatggcat gctttgtgga tccccatgat agtctacaaa agcaccccgc ccctctgggc 1620
actgcctgga agaatcggga gcctggccag ccttcagctc gctcctccac ttctgagggg 1680
cctaggaggc ctcccacagg tgtcccggca agagaagaca cggtggtgga agaagaggcc 1740
tggtaatggc ccctcctcct gggacccctt cgtcctctcc ttaccccacc tcctgggtac 1800
agcccaggag gaccttgtgt gatcagacca ttgaaaccac taattctgtc cccaggagac 1860
ttggctgtgt gtgtgagtgg cttacccttc ctcatcttcc cttcccaagg cacagagcaa 1920
tggggcagga cccgcaagcc cctcacggag gcagagaaaa gagaaagtgt tttatatacg 1980
gtacttattt aatagccctt tttaattaga aattaaaaca gttaatttaa ttaaagagta 2040
gggttttttt cagtattctt ggttaatatt taatttcaac tatttatgag atgtatctct 2100
cgctctctct tatttgtact tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg tgtgtgtgtg 2160
tgtgtatgaa atctgtgttt ccaatctctc tctcccagat cggtgacagt cactagcttg 2220
tcctgagaag atatttaatt ttgctaacac tcagctctgc cctcccttgt ccccaccaca 2280
cattcctttg aaataaggtt tcaatataca tttacatact atatatatat ttggcaactt 2340
gtgtttgtat ataaatatat atatatatat atatgtttat gtatatatgt gattctgata 2400
aaatagacat tgctattctg ttttttatat gtaaaaacaa aacaagaaaa atagagaatt 2460
ctacatacta aatctctctc cttttttaat tttaatattt gttatcattt atttattggt 2520
gctactgttt atccgtaata attgtggggg aaaaagatat taacatcacg tctttgtctc 2580
tagagcagtt ttccgagata ttccgtagta catatttatt tttaaacagc aacaaagaaa 2640
tacagatata tcttaaaaaa aaaagcattt tgtattaaag aattgaattc tgatctcaaa 2700
aaaaaaaaaa aaaaaa 2716
<210>163
<211>2848
<212>DNA
<213>小鼠(Mus musculus)
<400>163
cgggattgca cggaaacttt tcgtccaact tctgggctct tctcgctccg tagtagccgt 60
ggtctgcgcc gcaggagaca aaccgatcgg agctgggaga agtgctagct cgggcctgga 120
gaagccgggg cccgagaaga gaggggagga agagaaggaa gaggagaggg ggccgcagtg 180
ggcgctcggc tctcaggagc cgagctcatg gacgggtgag gcggccgtgt gcgcagacag 240
tgctccagcc gcgcgcgcgc cccaggcccc ggcccgggcc tcggttccag aagggagagg 300
agcccgccaa ggcgcgcaag agagcgggct gcctcgcagt ccgagccgga gagggagcgc 360
gagccgcgcc ggccccggac gggcctccga aaccatgaac tttctgctct cttgggtgca 420
ctggaccctg gctttactgc tgtacctcca ccatgccaag tggtcccagg ctgcacccac 480
gacagaagga gagcagaagt cccatgaagt gatcaagttc atggatgtct accagcgaag 540
ctactgccgt ccgattgaga ccctggtgga catcttccag gagtaccccg acgagataga 600
gtacatcttc aagccgtcct gtgtgccgct gatgcgctgt gcaggctgct gtaacgatga 660
agccctggag tgcgtgccca cgtcagagag caacatcacc atgcagatca tgcggatcaa 720
acctcaccaa agccagcaca taggagagat gagcttccta cagcacagca gatgtgaatg 780
cagaccaaag aaagacagaa caaagccaga aaatcactgt gagccttgtt cagagcggag 840
aaagcatttg tttgtccaag atccgcagac gtgtaaatgt tcctgcaaaa acacagactc 900
gcgttgcaag gcgaggcagc ttgagttaaa cgaacgtact tgcagatgtg acaagccaag 960
gcggtgagcc aggctgcagg aaggagcctc cctcagggtt tcgggaacca gacctctcac 1020
cggaaagacc gattaaccat gtcaccacca cgccatcatc gtcaccgttg acagaacagt 1080
ccttaatcca gaaagcctga catgaaggaa gaggagactc ttcgaggagc actttgggtc 1140
cggagggcga gactccggca gacgcattcc cgggcaggtg accaagcacg gtccctcgtg 1200
ggactggatt cgccattttc ttatatctgc tgctaaatcg ccaagcccgg aagattaggg 1260
ttgtttctgg gattcctgta gacacaccca cccacataca cacatatata tatattatat 1320
atataaataa atatatatgt tttatatata aaatatatat atattctttt ttttaaatta 1380
actctgctaa tgttattggt gtcttcactg gatatgtttg actgctgtgg acttgtgttg 1440
ggaggaggat gtcctcactc ggatgccgac acgggagaca atgggatgaa aggcttcagt 1500
gtggtctgag agaggccgaa gtccttttgc ctgccgggga gcaagcaagg ccagggcacg 1560
ggggcacatt tgctcacttc cagaaacacg acaaacccat tcctggccct gagtcaagag 1620
gacagagaga cagatgatga cagagaaaga gataaagatg ccggttccaa ccagaagttt 1680
ggggagcctc aggacatggc atgctttgtg gatccccatg atagtctaca aaagcacccc 1740
gcccctctgg gcactgcctg gaagaatcgg gagcctggcc agccttcagc tcgctcctcc 1800
acttctgagg ggcctaggag gcctcccaca ggtgtcccgg caagagaaga cacggtggtg 1860
gaagaagagg cctggtaatg gcccctcctc ctgggacccc ttcgtcctct ccttacccca 1920
cctcctgggt acagcccagg aggaccttgt gtgatcagac cattgaaacc actaattctg 1980
tccccaggag acttggctgt gtgtgtgagt ggcttaccct tcctcatctt cccttcccaa 2040
ggcacagagc aatggggcag gacccgcaag cccctcacgg aggcagagaa aagagaaagt 2100
gttttatata cggtacttat ttaatagccc tttttaatta gaaattaaaa cagttaattt 2160
aattaaagag tagggttttt ttcagtattc ttggttaata tttaatttca actatttatg 2220
agatgtatct ctcgctctct cttatttgta cttgtgtgtg tgtgtgtgtg tgtgtgtgtg 2280
tgtgtgtgtg tgtgtgtatg aaatctgtgt ttccaatctc tctctcccag atcggtgaca 2340
gtcactagct tgtcctgaga agatatttaa ttttgctaac actcagctct gccctccctt 2400
gtccccacca cacattcctt tgaaataagg tttcaatata catttacata ctatatatat 2460
atttggcaac ttgtgtttgt atataaatat atatatatat atatatgttt atgtatatat 2520
gtgattctga taaaatagac attgctattc tgttttttat atgtaaaaac aaaacaagaa 2580
aaatagagaa ttctacatac taaatctctc tcctttttta attttaatat ttgttatcat 2640
ttatttattg gtgctactgt ttatccgtaa taattgtggg ggaaaaagat attaacatca 2700
cgtctttgtc tctagagcag ttttccgaga tattccgtag tacatattta tttttaaaca 2760
gcaacaaaga aatacagata tatcttaaaa aaaaaagcat tttgtattaa agaattgaat 2820
tctgatctca aaaaaaaaaa aaaaaaaa 2848
<210>164
<211>395
<212>PRT
<213>智人(Homo sapiens)
<400>164
Met Thr Asp Arg Gln Thr Asp Thr Ala Pro Ser Pro Ser Tyr His Leu
1 5 10 15
Leu Pro Gly Arg Arg Arg Thr Val Asp Ala Ala Ala Ser Arg Gly Gln
20 25 30
Gly Pro Glu Pro Ala Pro Gly Gly Gly Val Glu Gly Val Gly Ala Arg
35 40 45
Gly Val Ala Leu Lys Leu Phe Val Gln Leu Leu Gly Cys Ser Arg Phe
50 55 60
Gly Gly Ala Val Val Arg Ala Gly Glu Ala Glu Pro Ser Gly Ala Ala
65 70 75 80
Arg Ser Ala Ser Ser Gly Arg Glu Glu Pro Gln Pro Glu Glu Gly Glu
85 90 95
Glu Glu Glu Glu Lys Glu Glu Glu Arg Gly Pro Gln Trp Arg Leu Gly
100 105 110
Ala Arg Lys Pro Gly Ser Trp Thr Gly Glu Ala Ala Val Cys Ala Asp
115 120 125
Ser Ala Pro Ala Ala Arg Ala Pro Gln Ala Leu Ala Arg Ala Ser Gly
130 135 140
Arg Gly Gly Arg Val Ala Arg Arg Gly Ala Glu Glu Ser Gly Pro Pro
145 150 155 160
His Ser Pro Ser Arg Arg Gly Ser Ala Ser Arg Ala Gly Pro Gly Arg
165 170 175
Ala Ser Glu Thr Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu
180 185 190
Ala Leu Leu Leu Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro
195 200 205
Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys Phe Met
210 215 220
Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp
225 230 235 240
Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser
245 250 255
Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu
260 265 270
Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg
275 280 285
Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln
290 295 300
His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu
305 310 315 320
Lys Lys Ser Val Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys
325 330 335
Lys Ser Arg Tyr Lys Ser Trp Ser Val Pro Cys Gly Pro Cys Ser Glu
340 345 350
Arg Arg Lys His Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser
355 360 365
Cys Lys Asn Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn
370 375 380
Glu Arg Thr Cys Arg Cys Asp Lys Pro Arg Arg
385 390 395
<210>165
<211>412
<212>PRT
<213>智人(Homo sapiens)
<400>165
Met Thr Asp Arg Gln Thr Asp Thr Ala Pro Ser Pro Ser Tyr His Leu
1 5 10 15
Leu Pro Gly Arg Arg Arg Thr Val Asp Ala Ala Ala Ser Arg Gly Gln
20 25 30
Gly Pro Glu Pro Ala Pro Gly Gly Gly Val Glu Gly Val Gly Ala Arg
35 40 45
Gly Val Ala Leu Lys Leu Phe Val Gln Leu Leu Gly Cys Ser Arg Phe
50 55 60
Gly Gly Ala Val Val Arg Ala Gly Glu Ala Glu Pro Ser Gly Ala Ala
65 70 75 80
Arg Ser Ala Ser Ser Gly Arg Glu Glu Pro Gln Pro Glu Glu Gly Glu
85 90 95
Glu Glu Glu Glu Lys Glu Glu Glu Arg Gly Pro Gln Trp Arg Leu Gly
100 105 110
Ala Arg Lys Pro Gly Ser Trp Thr Gly Glu Ala Ala Val Cys Ala Asp
115 120 125
Ser Ala Pro Ala Ala Arg Ala Pro Gln Ala Leu Ala Arg Ala Ser Gly
130 135 140
Arg Gly Gly Arg Val Ala Arg Arg Gly Ala Glu Glu Ser Gly Pro Pro
145 150 155 160
His Ser Pro Ser Arg Arg Gly Ser Ala Ser Arg Ala Gly Pro Gly Arg
165 170 175
Ala Ser Glu Thr Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu
180 185 190
Ala Leu Leu Leu Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro
195 200 205
Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys Phe Met
210 215 220
Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp
225 230 235 240
Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser
245 250 255
Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu
260 265 270
Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg
275 280 285
Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln
290 295 300
His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu
305 310 315 320
Lys Lys Ser Val Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys
325 330 335
Lys Ser Arg Tyr Lys Ser Trp Ser Val Tyr Val Gly Ala Arg Cys Cys
340 345 350
Leu Met Pro Trp Ser Leu Pro Gly Pro His Pro Cys Gly Pro Cys Ser
355 360 365
Glu Arg Arg Lys His Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys
370 375 380
Ser Cys Lys Asn Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu
385 390 395 400
Asn Glu Arg Thr Cys Arg Cys Asp Lys Pro Arg Arg
405 410
<210>166
<211>389
<212>PRT
<213>智人(Homo sapiens)
<400>166
Met Thr Asp Arg Gln Thr Asp Thr Ala Pro Ser Pro Ser Tyr His Leu
1 5 10 15
Leu Pro Gly Arg Arg Arg Thr Val Asp Ala Ala Ala Ser Arg Gly Gln
20 25 30
Gly Pro Glu Pro Ala Pro Gly Gly Gly Val Glu Gly Val Gly Ala Arg
35 40 45
Gly Val Ala Leu Lys Leu Phe Val Gln Leu Leu Gly Cys Ser Arg Phe
50 55 60
Gly Gly Ala Val Val Arg Ala Gly Glu Ala Glu Pro Ser Gly Ala Ala
65 70 75 80
Arg Ser Ala Ser Ser Gly Arg Glu Glu Pro Gln Pro Glu Glu Gly Glu
85 90 95
Glu Glu Glu Glu Lys Glu Glu Glu Arg Gly Pro Gln Trp Arg Leu Gly
100 105 110
Ala Arg Lys Pro Gly Ser Trp Thr Gly Glu Ala Ala Val Cys Ala Asp
115 120 125
Ser Ala Pro Ala Ala Arg Ala Pro Gln Ala Leu Ala Arg Ala Ser Gly
130 135 140
Arg Gly Gly Arg Val Ala Arg Arg Gly Ala Glu Glu Ser Gly Pro Pro
145 150 155 160
His Ser Pro Ser Arg Arg Gly Ser Ala Ser Arg Ala Gly Pro Gly Arg
165 170 175
Ala Ser Glu Thr Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu
180 185 190
Ala Leu Leu Leu Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro
195 200 205
Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys Phe Met
210 215 220
Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp
225 230 235 240
Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser
245 250 255
Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu
260 265 270
Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg
275 280 285
Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln
290 295 300
His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu
305 310 315 320
Lys Lys Ser Val Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys
325 330 335
Lys Ser Arg Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys His Leu Phe
340 345 350
Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp Ser
355 360 365
Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg Cys
370 375 380
Asp Lys Pro Arg Arg
385
<210>167
<211>371
<212>PRT
<213>智人(Homo sapiens)
<400>167
Met Thr Asp Arg Gln Thr Asp Thr Ala Pro Ser Pro Ser Tyr His Leu
1 5 10 15
Leu Pro Gly Arg Arg Arg Thr Val Asp Ala Ala Ala Ser Arg Gly Gln
20 25 30
Gly Pro Glu Pro Ala Pro Gly Gly Gly Val Glu Gly Val Gly Ala Arg
35 40 45
Gly Val Ala Leu Lys Leu Phe Val Gln Leu Leu Gly Cys Ser Arg Phe
50 55 60
Gly Gly Ala Val Val Arg Ala Gly Glu Ala Glu Pro Ser Gly Ala Ala
65 70 75 80
Arg Ser Ala Ser Ser Gly Arg Glu Glu Pro Gln Pro Glu Glu Gly Glu
85 90 95
Glu Glu Glu Glu Lys Glu Glu Glu Arg Gly Pro Gln Trp Arg Leu Gly
100 105 110
Ala Arg Lys Pro Gly Ser Trp Thr Gly Glu Ala Ala Val Cys Ala Asp
115 120 125
Ser Ala Pro Ala Ala Arg Ala Pro Gln Ala Leu Ala Arg Ala Ser Gly
130 135 140
Arg Gly Gly Arg Val Ala Arg Arg Gly Ala Glu Glu Ser Gly Pro Pro
145 150 155 160
His Ser Pro Ser Arg Arg Gly Ser Ala Ser Arg Ala Gly Pro Gly Arg
165 170 175
Ala Ser Glu Thr Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu
180 185 190
Ala Leu Leu Leu Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro
195 200 205
Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys Phe Met
210 215 220
Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp
225 230 235 240
Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser
245 250 255
Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu
260 265 270
Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg
275 280 285
Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln
290 295 300
His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu
305 310 315 320
Asn Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys His Leu Phe Val Gln
325 330 335
Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp Ser Arg Cys
340 345 350
Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg Cys Asp Lys
355 360 365
Pro Arg Arg
370
<210>168
<211>354
<212>PRT
<213>智人(Homo sapiens)
<400>168
Met Thr Asp Arg Gln Thr Asp Thr Ala Pro Ser Pro Ser Tyr His Leu
1 5 10 15
Leu Pro Gly Arg Arg Arg Thr Val Asp Ala Ala Ala Ser Arg Gly Gln
20 25 30
Gly Pro Glu Pro Ala Pro Gly Gly Gly Val Glu Gly Val Gly Ala Arg
35 40 45
Gly Val Ala Leu Lys Leu Phe Val Gln Leu Leu Gly Cys Ser Arg Phe
50 55 60
Gly Gly Ala Val Val Arg Ala Gly Glu Ala Glu Pro Ser Gly Ala Ala
65 70 75 80
Arg Ser Ala Ser Ser Gly Arg Glu Glu Pro Gln Pro Glu Glu Gly Glu
85 90 95
Glu Glu Glu Glu Lys Glu Glu Glu Arg Gly Pro Gln Trp Arg Leu Gly
100 105 110
Ala Arg Lys Pro Gly Ser Trp Thr Gly Glu Ala Ala Val Cys Ala Asp
115 120 125
Ser Ala Pro Ala Ala Arg Ala Pro Gln Ala Leu Ala Arg Ala Ser Gly
130 135 140
Arg Gly Gly Arg Val Ala Arg Arg Gly Ala Glu Glu Ser Gly Pro Pro
145 150 155 160
His Ser Pro Ser Arg Arg Gly Ser Ala Ser Arg Ala Gly Pro Gly Arg
165 170 175
Ala Ser Glu Thr Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu
180 185 190
Ala Leu Leu Leu Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro
195 200 205
Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys Phe Met
210 215 220
Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp
225 230 235 240
Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser
245 250 255
Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu
260 265 270
Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg
275 280 285
Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln
290 295 300
His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu
305 310 315 320
Asn Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys His Leu Phe Val Gln
325 330 335
Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp Ser Arg Cys
340 345 350
Lys Met
<210>169
<211>327
<212>PRT
<213>智人(Homo sapiens)
<400>169
Met Thr Asp Arg Gln Thr Asp Thr Ala Pro Ser Pro Ser Tyr His Leu
1 5 10 15
Leu Pro Gly Arg Arg Arg Thr Val Asp Ala Ala Ala Ser Arg Gly Gln
20 25 30
Gly Pro Glu Pro Ala Pro Gly Gly Gly Val Glu Gly Val Gly Ala Arg
35 40 45
Gly Val Ala Leu Lys Leu Phe Val Gln Leu Leu Gly Cys Ser Arg Phe
50 55 60
Gly Gly Ala Val Val Arg Ala Gly Glu Ala Glu Pro Ser Gly Ala Ala
65 70 75 80
Arg Ser Ala Ser Ser Gly Arg Glu Glu Pro Gln Pro Glu Glu Gly Glu
85 90 95
Glu Glu Glu Glu Lys Glu Glu Glu Arg Gly Pro Gln Trp Arg Leu Gly
100 105 110
Ala Arg Lys Pro Gly Ser Trp Thr Gly Glu Ala Ala Val Cys Ala Asp
115 120 125
Ser Ala Pro Ala Ala Arg Ala Pro Gln Ala Leu Ala Arg Ala Ser Gly
130 135 140
Arg Gly Gly Arg Val Ala Arg Arg Gly Ala Glu Glu Ser Gly Pro Pro
145 150 155 160
His Ser Pro Ser Arg Arg Gly Ser Ala Ser Arg Ala Gly Pro Gly Arg
165 170 175
Ala Ser Glu Thr Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu
180 185 190
Ala Leu Leu Leu Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro
195 200 205
Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys Phe Met
210 215 220
Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp
225 230 235 240
Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser
245 250 255
Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu
260 265 270
Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg
275 280 285
Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln
290 295 300
His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu
305 310 315 320
Lys Cys Asp Lys Pro Arg Arg
325
<210>170
<211>371
<212>PRT
<213>智人(Homo sapiens)
<400>170
Met Thr Asp Arg Gln Thr Asp Thr Ala Pro Ser Pro Ser Tyr His Leu
1 5 10 15
Leu Pro Gly Arg Arg Arg Thr Val Asp Ala Ala Ala Ser Arg Gly Gln
20 25 30
Gly Pro Glu Pro Ala Pro Gly Gly Gly Val Glu Gly Val Gly Ala Arg
35 40 45
Gly Val Ala Leu Lys Leu Phe Val Gln Leu Leu Gly Cys Ser Arg Phe
50 55 60
Gly Gly Ala Val Val Arg Ala Gly Glu Ala Glu Pro Ser Gly Ala Ala
65 70 75 80
Arg Ser Ala Ser Ser Gly Arg Glu Glu Pro Gln Pro Glu Glu Gly Glu
85 90 95
Glu Glu Glu Glu Lys Glu Glu Glu Arg Gly Pro Gln Trp Arg Leu Gly
100 105 110
Ala Arg Lys Pro Gly Ser Trp Thr Gly Glu Ala Ala Val Cys Ala Asp
115 120 125
Ser Ala Pro Ala Ala Arg Ala Pro Gln Ala Leu Ala Arg Ala Ser Gly
130 135 140
Arg Gly Gly Arg Val Ala Arg Arg Gly Ala Glu Glu Ser Gly Pro Pro
145 150 155 160
His Ser Pro Ser Arg Arg Gly Ser Ala Ser Arg Ala Gly Pro Gly Arg
165 170 175
Ala Ser Glu Thr Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu
180 185 190
Ala Leu Leu Leu Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro
195 200 205
Met Ala Glu Gly Gly Gly Gln Asn His His Glu Val Val Lys Phe Met
210 215 220
Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp
225 230 235 240
Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser
245 250 255
Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu
260 265 270
Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg
275 280 285
Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln
290 295 300
His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu
305 310 315 320
Asn Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys His Leu Phe Val Gln
325 330 335
Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp Ser Arg Cys
340 345 350
Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg Ser Leu Thr
355 360 365
Arg Lys Asp
370
<210>171
<211>232
<212>PRT
<213>智人(Homo sapiens)
<400>171
Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Met Ala Glu Gly
20 25 30
Gly Gly Gln Asn His His Glu Val Val Lys Phe Met Asp Val Tyr Gln
35 40 45
Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu
50 55 60
Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu
65 70 75 80
Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu Glu Cys Val Pro
85 90 95
Thr Glu Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His
100 105 110
Gln Gly Gln His Ile Gly Glu Met Ser Phe Leu Gln His Asn Lys Cys
115 120 125
Glu Cys Arg Pro Lys Lys Asp Arg Ala Arg Gln Glu Lys Lys Ser Val
130 135 140
Arg Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Tyr
145 150 155 160
Lys Ser Trp Ser Val Tyr Val Gly Ala Arg Cys Cys Leu Met Pro Trp
165 170 175
Ser Leu Pro Gly Pro His Pro Cys Gly Pro Cys Ser Glu Arg Arg Lys
180 185 190
His Leu Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn
195 200 205
Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr
210 215 220
Cys Arg Cys Asp Lys Pro Arg Arg
225 230
<210>172
<211>148
<212>PRT
<213>智人(Homo sapiens)
<400>172
Glu Gly Leu Thr Leu Asp Phe Gly Arg Thr Cys Leu Ile Gln Lys Leu
1 5 10 15
Gln Arg Val Ala Leu Gln Ser Trp Val Glu Arg Gly Ala Ser His Leu
20 25 30
Leu Cys Arg Pro Pro Gly Ser Cys Val Ile Ala Ser His Ala Val Val
35 40 45
Lys Phe Met Asp Val Tyr Gln Arg Ser Tyr Cys His Pro Ile Glu Thr
50 55 60
Leu Val Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe
65 70 75 80
Lys Pro Ser Cys Val Pro Leu Met Arg Cys Gly Gly Cys Cys Asn Asp
85 90 95
Glu Gly Leu Glu Cys Val Pro Thr Glu Glu Ser Asn Ile Thr Met Gln
100 105 110
Ile Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser
115 120 125
Phe Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Ala
130 135 140
Arg Gln Glu Lys
145
<210>173
<211>143
<212>PRT
<213>智人(Homo sapiens)
<400>173
Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Met Ala Glu Gly
20 25 30
Gly Gly Gln Asn His His Glu Val Val Lys Phe Met Asp Val Tyr Gln
35 40 45
Arg Ser Tyr Cys His Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu
50 55 60
Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu
65 70 75 80
Met Arg Cys Gly Gly Cys Cys Asn Asp Glu Gly Leu Glu Cys Val Pro
85 90 95
Thr Glu Glu Ser Asn Ile Thr Met Gln Val Gly Ile Phe Gly Lys Trp
100 105 110
Gly Lys Gly Gly Ile Gly Arg Gly Val Thr Leu Trp Glu Gln Val Val
115 120 125
Pro Gly Arg Phe Leu Ala Arg Phe Ala Leu Ser Gly Ser Cys Pro
130 135 140
<210>174
<211>41
<212>PRT
<213>智人(Homo sapiens)
<400>174
Met Arg Ile Lys Pro His Gln Gly Gln His Ile Gly Glu Met Ser Phe
1 5 10 15
Leu Gln His Asn Lys Cys Glu Cys Arg Pro Lys Lys Asp Arg Pro Arg
20 25 30
Gln Glu Lys Cys Asp Lys Pro Arg Arg
35 40
<210>175
<211>73
<212>PRT
<213>智人(Homo sapiens)
<400>175
Gln Pro Gln Leu Pro Pro Pro Pro Arg Pro Ala Ala Asp Ser Gly Arg
1 5 10 15
Gly Gly Glu Pro Arg Ala Gly Ala Gly Ala Arg Ala Arg Arg Arg Gly
20 25 30
Gly Gly Gly Arg Gly Ser Arg Arg Arg Thr Glu Thr Phe Arg Pro Thr
35 40 45
Ser Gly Leu Phe Ser Leu Arg Arg Ser Arg Gly Pro Arg Gly Gly Ser
50 55 60
Arg Ala Glu Arg Ser Arg Glu Lys Cys
65 70
<210>176
<211>22
<212>PRT
<213>智人(Homo sapiens)
<400>176
Met Asn Phe Leu Leu Ser Trp Val His Trp Ser Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys
20
<210>177
<211>214
<212>PRT
<213>小鼠(Mus musculus)
<400>177
Met Asn Phe Leu Leu Ser Trp Val His Trp Thr Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Thr Thr Glu Gly
20 25 30
Glu Gln Lys Ser His Glu Val Ile Lys Phe Met Asp Val Tyr Gln Arg
35 40 45
Ser Tyr Cys Arg Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu Tyr
50 55 60
Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu Met
65 70 75 80
Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala Leu Glu Cys Val Pro Thr
85 90 95
Ser Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His Gln
100 105 110
Ser Gln His Ile Gly Glu Met Ser Phe Leu Gln His Ser Arg Cys Glu
115 120 125
Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro Glu Lys Lys Ser Val Arg
130 135 140
Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Phe Lys
145 150 155 160
Ser Trp Ser Val His Cys Glu Pro Cys Ser Glu Arg Arg Lys His Leu
165 170 175
Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp
180 185 190
Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg
195 200 205
Cys Asp Lys Pro Arg Arg
210
<210>178
<211>146
<212>PRT
<213>小鼠(Mus musculus)
<400>178
Met Asn Phe Leu Leu Ser Trp Val His Trp Thr Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Thr Thr Glu Gly
20 25 30
Glu Gln Lys Ser His Glu Val Ile Lys Phe Met Asp Val Tyr Gln Arg
35 40 45
Ser Tyr Cys Arg Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu Tyr
50 55 60
Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu Met
65 70 75 80
Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala Leu Glu Cys Val Pro Thr
85 90 95
Ser Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His Gln
100 105 110
Ser Gln His Ile Gly Glu Met Ser Phe Leu Gln His Ser Arg Cys Glu
115 120 125
Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro Glu Lys Cys Asp Lys Pro
130 135 140
Arg Arg
145
<210>179
<211>190
<212>PRT
<213>小鼠(Mus musculus)
<400>179
Met Asn Phe Leu Leu Ser Trp Val His Trp Thr Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Thr Thr Glu Gly
20 25 30
Glu Gln Lys Ser His Glu Val Ile Lys Phe Met Asp Val Tyr Gln Arg
35 40 45
Ser Tyr Cys Arg Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu Tyr
50 55 60
Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu Met
65 70 75 80
Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala Leu Glu Cys Val Pro Thr
85 90 95
Ser Glu Ser Asn Ile Thr Met Gln lle Met Arg Ile Lys Pro His Gln
100 105 110
Ser Gln His Ile Gly Glu Met Ser Phe Leu Gln His Ser Arg Cys Glu
115 120 125
Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro Glu Asn His Cys Glu Pro
130 135 140
Cys Ser Glu Arg Arg Lys His Leu Phe Val Gln Asp Pro Gln Thr Cys
145 150 155 160
Lys Cys Ser Cys Lys Asn Thr Asp Ser Arg Cys Lys Ala Arg Gln Leu
165 170 175
Glu Leu Asn Glu Arg Thr Cys Arg Cys Asp Lys Pro Arg Arg
180 185 190
<210>180
<211>214
<212>PRT
<213>小鼠(Mus musculus)
<400>180
Met Asn Phe Leu Leu Ser Trp Val His Trp Thr Leu Ala Leu Leu Leu
1 5 10 15
Tyr Leu His His Ala Lys Trp Ser Gln Ala Ala Pro Thr Thr Glu Gly
20 25 30
Glu Gln Lys Ser His Glu Val Ile Lys Phe Met Asp Val Tyr Gln Arg
35 40 45
Ser Tyr Cys Arg Pro Ile Glu Thr Leu Val Asp Ile Phe Gln Glu Tyr
50 55 60
Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro Ser Cys Val Pro Leu Met
65 70 75 80
Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala Leu Glu Cys Val Pro Thr
85 90 95
Ser Glu Ser Asn Ile Thr Met Gln Ile Met Arg Ile Lys Pro His Gln
100 105 110
Ser Gln His Ile Gly Glu Met Ser Phe Leu Gln His Ser Arg Cys Glu
115 120 125
Cys Arg Pro Lys Lys Asp Arg Thr Lys Pro Glu Lys Lys Ser Val Arg
130 135 140
Gly Lys Gly Lys Gly Gln Lys Arg Lys Arg Lys Lys Ser Arg Phe Lys
145 150 155 160
Ser Trp Ser Val His Cys Glu Pro Cys Ser Glu Arg Arg Lys His Leu
165 170 175
Phe Val Gln Asp Pro Gln Thr Cys Lys Cys Ser Cys Lys Asn Thr Asp
180 185 190
Ser Arg Cys Lys Ala Arg Gln Leu Glu Leu Asn Glu Arg Thr Cys Arg
195 200 205
Cys Asp Lys Pro Arg Arg
210
<210>181
<211>81
<212>PRT
<213>小鼠(Mus musculus)
<400>181
Met Asp Val Tyr Gln Arg Ser Tyr Cys Arg Pro Ile Glu Thr Leu Val
1 5 10 15
Asp Ile Phe Gln Glu Tyr Pro Asp Glu Ile Glu Tyr Ile Phe Lys Pro
20 25 30
Ser Cys Val Pro Leu Met Arg Cys Ala Gly Cys Cys Asn Asp Glu Ala
35 40 45
Leu Glu Cys Val Pro Thr Ser Glu Ser Asn Ile Thr Met Gln Ile Met
50 55 60
Arg Ile Lys Pro His Gln Ser Gln His Ile Gly Glu Met Ser Phe Leu
65 70 75 80
Gln
<210>182
<211>776
<212>DNA
<213>智人(Homo sapiens)
<400>182
aaggacacgg gcagcagaca gtggtcagtc ctttcttggc tctgctgaca ctcgagccca 60
cattccgtca cctgctcaga atcatgcagg tctccactgc tgcccttgct gtcctcctct 120
gcaccatggc tctctgcaac cagttctctg catcacttgc tgctgacacg ccgaccgcct 180
gctgcttcag ctacacctcc cggcagattc cacagaattt catagctgac tactttgaga 240
cgagcagcca gtgctccaag cccggtgtca tcttcctaac caagcgaagc cggcaggtct 300
gtgctgaccc cagtgaggag tgggtccaga aatatgtcag cgacctagag ctgagtgcct 360
gaggggtcca gaagcttcga ggcccagcga cctcggtggg ccagtgggga ggagcaggag 420
cctgagcctt gggaaacatg cgtgtgacct ccacagctac ctcttctatg gactggttgt 480
tgccaaacag ccacactgtg ggactcttct taacttaaat tttaatttat ttatactatt 540
tagtttttgt aatttatttt cgatttcaca gtgtgtttgt gattgtttgc tctgagagtt 600
cccctgtccc ctcccccttc cctcacaccg cgtctggtga caaccgagtg gctgtcatca 660
gcctgtgtag gcagtcatgg caccaaagcc accagactga caaatgtgta tcggatgctt 720
ttgttcaggg ctgtgatcgg cctggggaaa taataaagca cgctctttta aaaggt 776
<210>183
<211>764
<212>DNA
<213>小鼠(Mus musculus)
<400>183
agaaggatac aagcagcagc gagtaccagt cccttttctg ttctgctgac aagctcaccc 60
tctgtcacct gctcaacatc atgaaggtct ccaccactgc ccttgctgtt cttctctgta 120
ccatgacact ctgcaaccaa gtcttctcag cgccatatgg agctgacacc ccgactgcct 180
gctgcttctc ctacagccgg aagattccac gccaattcat cgttgactat tttgaaacca 240
gcagcctttg ctcccagcca ggtgtcattt tcctgactaa gagaaaccgg cagatctgcg 300
ctgactccaa agagacctgg gtccaagaat acatcactga cctggaactg aatgcctgag 360
agtcttggag gcagcgagga accccccaaa cctccatggg tcccctgtag agcaggggct 420
tgagccgaac attcctgcca cctgcatagc tccatctcct ataagctgtt tgctgccaag 480
tagccacatc gagggactct tcacttgaaa ttttatttaa tttaatccta ttggtttaat 540
actatttaat tttgtaattt attttattgt catacttgta tttgtgacta tttattctga 600
aagacttcag gacacgttcc tcaaccccca tctccctccc agttgttcac actgtttggt 660
gacagctatt ctaggtagac atgatgacaa agtcatgaac tgacaaatgt acaatagatg 720
ctttgtttat accagagaag taataaatat gccctttaac aagt 764
<210>184
<211>92
<212>PRT
<213>智人(Homo sapiens)
<400>184
Met Gln Val Ser Thr Ala Ala Leu Ala Val Leu Leu Cys Thr Met Ala
1 5 10 15
Leu Cys Asn Gln Phe Ser Ala Ser Leu Ala Ala Asp Thr Pro Thr Ala
20 25 30
Cys Cys Phe Ser Tyr Thr Ser Arg Gln Ile Pro Gln Asn Phe Ile Ala
35 40 45
Asp Tyr Phe Glu Thr Ser Ser Gln Cys Ser Lys Pro Gly Val Ile Phe
50 55 60
Leu Thr Lys Arg Ser Arg Gln Val Cys Ala Asp Pro Ser Glu Glu Trp
65 70 75 80
Val Gln Lys Tyr Val Ser Asp Leu Glu Leu Ser Ala
85 90
<210>185
<211>92
<212>PRT
<213>智人(Homo sapiens)
<400>185
Met Gln Val Ser Thr Ala Ala Leu Ala Val Leu Leu Cys Thr Met Ala
1 5 10 15
Leu Cys Asn Gln Phe Ser Ala Ser Leu Ala Ala Asp Thr Pro Thr Ala
20 25 30
Cys Cys Phe Ser Tyr Thr Ser Arg Gln Ile Pro Gln Asn Phe Ile Ala
35 40 45
Asp Tyr Phe Glu Thr Ser Ser Gln Cys Ser Lys Pro Gly Val Ile Phe
50 55 60
Leu Thr Lys Arg Ser Arg Gln Val Cys Ala Asp Pro Ser Glu Glu Trp
65 70 75 80
Val Gln Lys Tyr Val Ser Asp Leu Glu Leu Ser Ala
85 90
<210>186
<211>80
<212>PRT
<213>智人(Homo sapiens)
<400>186
Ala Leu Ala Val Leu Leu Cys Thr Met Ala Leu Cys Asn Gln Phe Ser
1 5 10 15
Ala Ser Leu Ala Ala Asp Thr Pro Thr Ala Cys Cys Phe Ser Tyr Thr
20 25 30
Ser Arg Gln Ile Pro Gln Asn Phe Met Ala Asp Tyr Phe Glu Thr Ser
35 40 45
Ser Gln Cys Ser Lys Pro Ser Val Ile Phe Leu Thr Lys Arg Gly Arg
50 55 60
Gln Val Cys Ala Asp Pro Ser Glu Glu Trp Val Gln Lys Tyr Val Ser
65 70 75 80
<210>187
<211>92
<212>PRT
<213>小鼠(Mus musculus)
<400>187
Met Lys Val Ser Thr Thr Ala Leu Ala Val Leu Leu Cys Thr Met Thr
1 5 10 15
Leu Cys Asn Gln Val Phe Ser Ala Pro Tyr Gly Ala Asp Thr Pro Thr
20 25 30
Ala Cys Cys Phe Ser Tyr Ser Arg Lys Ile Pro Arg Gln Phe Ile Val
35 40 45
Asp Tyr Phe Glu Thr Ser Ser Leu Cys Ser Gln Pro Gly Val Ile Phe
50 55 60
Leu Thr Lys Arg Asn Arg Gln Ile Cys Ala Asp Ser Lys Glu Thr Trp
65 70 75 80
Val Gln Glu Tyr Ile Thr Asp Leu Glu Leu Asn Ala
85 90
<210>188
<211>92
<212>PRT
<213>小鼠(Mus musculus)
<400>188
Met Lys Val Ser Thr Thr Ala Leu Ala Val Leu Leu Cys Thr Met Thr
1 5 10 15
Leu Cys Asn Gln Val Phe Ser Ala Pro Tyr Gly Ala Asp Thr Pro Thr
20 25 30
Ala Cys Cys Phe Ser Tyr Ser Arg Lys Ile Pro Arg Gln Phe Ile Val
35 40 45
Asp Tyr Phe Glu Thr Ser Ser Leu Cys Ser Gln Pro Gly Val Ile Phe
50 55 60
Leu Thr Lys Arg Asn Arg Gln Ile Cys Ala Asp Ser Lys Glu Thr Trp
65 70 75 80
Val Gln Glu Tyr Ile Thr Asp Leu Glu Leu Asn Ala
85 90
<210>189
<211>92
<212>PRT
<213>小鼠(Mus musculus)
<400>189
Met Lys Val Ser Thr Thr Ala Leu Ala Val Leu Leu Cys Thr Met Thr
1 5 10 15
Leu Cys Asn Gln Val Phe Ser Ala Pro Tyr Gly Ala Asp Thr Pro Thr
20 25 30
Ala Cys Cys Phe Ser Tyr Ser Arg Lys Ile Pro Arg Gln Phe Ile Val
35 40 45
Asp Tyr Phe Glu Thr Ser Ser Leu Cys Ser Gln Pro Gly Val Ile Phe
50 55 60
Leu Thr Lys Arg Asn Arg Gln Ile Cys Ala Asp Ser Lys Glu Thr Trp
65 70 75 80
Val Gln Glu Tyr Ile Thr Asp Leu Glu Leu Asn Ala
85 90
<210>190
<211>1237
<212>DNA
<213>智人(Homo sapiens)
<400>190
gctgcagagg attcctgcag aggatcaaga cagcacgtgg acctcgcaca gcctctccca 60
caggtaccat gaaggtctcc gcggcagccc tcgctgtcat cctcattgct actgccctct 120
gcgctcctgc atctgcctcc ccatattcct cggacaccac accctgctgc tttgcctaca 180
ttgcccgccc actgccccgt gcccacatca aggagtattt ctacaccagt ggcaagtgct 240
ccaacccagc agtcgtcttt gtcacccgaa agaaccgcca agtgtgtgcc aacccagaga 300
agaaatgggt tcgggagtac atcaactctt tggagatgag ctaggatgga gagtccttga 360
acctgaactt acacaaattt gcctgtttct gcttgctctt gtcctagctt gggaggcttc 420
ccctcactat cctaccccac ccgctccttg aagggcccag attctaccac acagcagcag 480
ttacaaaaac cttccccagg ctggacgtgg tggctcacgc ctgtaatccc agcactttgg 540
gaggccaagg tgggtggatc acttgaggtc aggagttcga gaccagcctg gccaacatga 600
tgaaacccca tctctactaa aaatacaaaa aattagccgg gcgtggtagc gggcgcctgt 660
agtcccagct actcgggagg ctgaggcagg agaatggcgt gaacccggga ggcggagctt 720
gcagtgagcc gagatcgcgc cactgcactc cagcctgggc gacagagcga gactccgtct 780
caaaaaaaaa aaaaaaaaaa aaaatacaaa aattagccgg gcgtggtggc ccacgcctgt 840
aatcccagct actcgggagg ctaaggcagg aaaattgttt gaacccagga ggtggaggct 900
gcagtgagct gagattgtgc cacttcactc cagcctgggt gacaaagtga gactccgtca 960
caacaacaac aacaaaaagc ttccccaact aaagcctaga agagcttctg aggcgctgct 1020
ttgtcaaaag gaagtctcta ggttctgagc tctggctttg ccttggcttt gccagggctc 1080
tgtgaccagg aaggaagtca gcatgcctct agaggcaagg aggggaggaa cactgcactc 1140
ttaagcttcc gccgtctcaa cccctcacag gagcttactg gcaaacatga aaaatcggct 1200
taccattaaa gttctcaatg caaccataaa aaaaaaa 1237
<210>191
<211>523
<212>DNA
<213>小鼠(Mus musculus)
<400>191
ggcacgagtc gatctcccac agcctctgcc gcgggtacca tgaagatctc tgcagctgcc 60
ctcaccatca tcctcactgc agccgccctc tgcaccccgg cacctgcctc accatatggc 120
tcggacacca ctccctgctg ctttgcctac ctctccctag agctgcctcg tgcccacgtc 180
aaggagtatt tctacaccag cagcaagtgc tccaatcttg cagtcgtgtt tgtcactcga 240
aggaaccgcc aagtgtgtgc caacccagag aagaagtggg ttcaagaata catcaactat 300
ttggagatga gctaggatag agggtttctt gattctgacc ctgtatacgc ttccctgtca 360
tcgcttgctc tagtcctagc cagcttgggg atgccactcc agtaatcccc tactcccact 420
ccggtcctgg gaaaatcggc atctccatcc gctccgaccg gctctcgacc acgaaaccca 480
agaaatcagc atttcattaa aatttccatg atgcaacgga caa 523
<210>192
<211>91
<212>PRT
<213>智人(Homo sapiens)
<400>192
Met Lys Val Ser Ala Ala Ala Leu Ala Val Ile Leu Ile Ala Thr Ala
1 5 10 15
Leu Cys Ala Pro Ala Ser Ala Ser Pro Tyr Ser Ser Asp Thr Thr Pro
20 25 30
Cys Cys Phe Ala Tyr Ile Ala Arg Pro Leu Pro Arg Ala His Ile Lys
35 40 45
Glu Tyr Phe Tyr Thr Ser Gly Lys Cys Ser Asn Pro Ala Val Val Phe
50 55 60
Val Thr Arg Lys Asn Arg Gln Val Cys Ala Asn Pro Glu Lys Lys Trp
65 70 75 80
Val Arg Glu Tyr Ile Asn Ser Leu Glu Met Ser
85 90
<210>193
<211>91
<212>PRT
<213>智人(Homo sapiens)
<400>193
Met Lys Val Ser Ala Ala Ala Leu Ala Val Ile Leu Ile Ala Thr Ala
1 5 10 15
Leu Cys Ala Pro Ala Ser Ala Ser Pro Tyr Ser Ser Asp Thr Thr Pro
20 25 30
Cys Cys Phe Ala Tyr lle Ala Arg Pro Leu Pro Arg Ala His Ile Lys
35 40 45
Glu Tyr Phe Tyr Thr Ser Gly Lys Cys Ser Asn Pro Ala Val Val Phe
50 55 60
Val Thr Arg Lys Asn Arg Gln Val Cys Ala Asn Pro Glu Lys Lys Trp
65 70 75 80
Val Arg Glu Tyr Ile Asn Ser Leu Glu Met Ser
85 90
<210>194
<211>19
<212>PRT
<213>智人(Homo sapiens)
<400>194
Met Lys Val Ser Ala Ala Ala Leu Ala Val Ile Leu Ile Ala Thr Ala
1 5 10 15
Leu Cys Ala
<210>195
<211>91
<212>PRT
<213>小鼠(Mus musculus)
<400>195
Met Lys Ile Ser Ala Ala Ala Leu Thr Ile Ile Leu Thr Ala Ala Ala
1 5 10 15
Leu Cys Thr Pro Ala Pro Ala Ser Pro Tyr Gly Ser Asp Thr Thr Pro
20 25 30
Cys Cys Phe Ala Tyr Leu Ser Leu Glu Leu Pro Arg Ala His Val Lys
35 40 45
Glu Tyr Phe Tyr Thr Ser Ser Lys Cys Ser Asn Leu Ala Val Val Phe
50 55 60
Val Thr Arg Arg Asn Arg Gln Val Cys Ala Asn Pro Glu Lys Lys Trp
65 70 75 80
Val Gln Glu Tyr Ile Asn Tyr Leu Glu Met Ser
85 90
<210>196
<211>91
<212>PRT
<213>小鼠(Mus musculus)
<400>196
Met Lys Ile Ser Ala Ala Ala Leu Thr Ile Ile Leu Thr Ala Ala Ala
1 5 10 15
Leu Cys Thr Pro Ala Pro Ala Ser Pro Tyr Gly Ser Asp Thr Thr Pro
20 25 30
Cys Cys Phe Ala Tyr Leu Ser Leu Ala Leu Pro Arg Ala His Val Lys
35 40 45
Glu Tyr Phe Tyr Thr Ser Ser Lys Cys Ser Asn Leu Ala Val Val Phe
50 55 60
Val Thr Arg Arg Asn Arg Gln Val Cys Ala Asn Pro Glu Lys Lys Trp
65 70 75 80
Val Gln Glu Tyr Ile Asn Tyr Leu Glu Met Ser
85 90
<210>197
<211>91
<212>PRT
<213>小鼠(Mus musculus)
<400>197
Met Lys Ile Ser Ala Ala Ala Leu Thr Ile Ile Leu Thr Ala Ala Ala
1 5 10 15
Leu Cys Thr Pro Ala Pro Ala Ser Pro Tyr Gly Ser Asp Thr Thr Pro
20 25 30
Cys Cys Phe Ala Tyr Leu Ser Leu Ala Leu Pro Arg Ala His Val Lys
35 40 45
Glu Tyr Phe Tyr Thr Ser Ser Lys Cys Ser Asn Leu Ala Val Val Phe
50 55 60
Val Thr Arg Arg Asn Arg Gln Val Cys Ala Asn Pro Glu Lys Lys Trp
65 70 75 80
Val Gln Glu Tyr Ile Asn Tyr Leu Glu Met Ser
85 90
<210>198
<211>1125
<212>DNA
<213>智人(Homo sapiens)
<400>198
ttctgccctc gagcccaccg ggaacgaaag agaagctcta tctcgcctcc aggagcccag 60
ctatgaactc cttctccaca agcgccttcg gtccagttgc cttctccctg gggctgctcc 120
tggtgttgcc tgctgccttc cctgccccag tacccccagg agaagattcc aaagatgtag 180
ccgccccaca cagacagcca ctcacctctt cagaacgaat tgacaaacaa attcggtaca 240
tcctcgacgg catctcagcc ctgagaaagg agacatgtaa caagagtaac atgtgtgaaa 300
gcagcaaaga ggcactggca gaaaacaacc tgaaccttcc aaagatggct gaaaaagatg 360
gatgcttcca atctggattc aatgaggaga cttgcctggt gaaaatcatc actggtcttt 420
tggagtttga ggtataccta gagtacctcc agaacagatt tgagagtagt gaggaacaag 480
ccagagctgt gcagatgagt acaaaagtcc tgatccagtt cctgcagaaa aaggcaaaga 540
atctagatgc aataaccacc cctgacccaa ccacaaatgc cagcctgctg acgaagctgc 600
aggcacagaa ccagtggctg caggacatga caactcatct cattctgcgc agctttaagg 660
agttcctgca gtccagcctg agggctcttc ggcaaatgta gcatgggcac ctcagattgt 720
tgttgttaat gggcattcct tcttctggtc agaaacctgt ccactgggca cagaacttat 780
gttgttctct atggagaact aaaagtatga gcgttaggac actattttaa ttatttttaa 840
tttattaata tttaaatatg tgaagctgag ttaatttatg taagtcatat ttatattttt 900
aagaagtacc acttgaaaca ttttatgtat tagttttgaa ataataatgg aaagtggcta 960
tgcagtttga atatcctttg tttcagagcc agatcatttc ttggaaagtg taggcttacc 1020
tcaaataaat ggctaactta tacatatttt taaagaaata tttatattgt atttatataa 1080
tgtataaatg gtttttatac caataaatgg cattttaaaa aattc 1125
<210>199
<211>1087
<212>DNA
<213>小鼠(Mus musculus)
<400>199
ccaagaacga tagtcaattc cagaaaccgc tatgaagttc ctctctgcaa gagacttcca 60
tccagttgcc ttcttgggac tgatgctggt gacaaccacg gccttcccta cttcacaagt 120
ccggagagga gacttcacag aggataccac tcccaacaga cctgtctata ccacttcaca 180
agtcggaggc ttaattacac atgttctctg ggaaatcgtg gaaatgagaa aagagttgtg 240
caatggcaat tctgattgta tgaacaacga tgatgcactt gcagaaaaca atctgaaact 300
tccagagata caaagaaatg atggatgcta ccaaactgga tataatcagg aaatttgcct 360
attgaaaatt tcctctggtc ttctggagta ccatagctac ctggagtaca tgaagaacaa 420
cttaaaagat aacaagaaag acaaagccag agtccttcag agagatacag aaactctaat 480
tcatatcttc aaccaagagg taaaagattt acataaaata gtccttccta ccccaatttc 540
caatgctctc ctaacagata agctggagtc acagaaggag tggctaagga ccaagaccat 600
ccaattcatc ttgaaatcae ttgaagaatt tctaaaagtc actttgagat ctactcggca 660
aacctagtgc gttatgccta agcatatcag tttgtggaca ttcctcactg tggtcagaaa 720
atatatcctg ttgtcaggta tctgacttat gttgttctct acgaagaact gacaatatga 780
atgttgggac actattttaa ttatttttaa tttattgata atttaaataa gtaaacttta 840
agttaattta tgattgatat ttattatttt tatgaagtgt cacttgaaat gttatatgtt 900
atagttttga aatgataacc taaaaatcta tttgatataa atattctgtt acctagccag 960
atggtttctt ggaatgtata agtttacctc aatgaattgc taatttaaat atgtttttaa 1020
agaaatcttt gtgatgtatt tttataatgt ttagactgtc ttcaaacaaa taaattatat 1080
tatattt 1087
<210>200
<211>212
<212>PRT
<213>智人(Homo sapiens)
<400>200
Met Asn Ser Phe Ser Thr Ser Ala Phe Gly Pro Val Ala Phe Ser Leu
1 5 10 15
Gly Leu Leu Leu Val Leu Pro Ala Ala Phe Pro Ala Pro Val Pro Pro
20 25 30
Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu Thr
35 40 45
Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp Gly Ile
50 55 60
Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn Met Cys Glu Ser
65 70 75 80
Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu Pro Lys Met Ala
85 90 95
Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu
100 105 110
Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr
115 120 125
Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln
130 135 140
Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn
145 150 155 160
Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu Leu
165 170 175
Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr Thr His
180 185 190
Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser Leu Arg Ala
195 200 205
Leu Arg Gln Met
210
<210>201
<211>212
<212>PRT
<213>智人(Homo sapiens)
<400>201
Met Asn Ser Phe Ser Thr Ser Ala Phe Gly Pro Val Ala Phe Ser Leu
1 5 10 15
Gly Leu Leu Leu Val Leu Pro Ala Ala Phe Pro Ala Pro Val Pro Pro
20 25 30
Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu Thr
35 40 45
Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp Gly Ile
50 55 60
Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn Met Cys Glu Ser
65 70 75 80
Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu Pro Lys Met Ala
85 90 95
Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu
100 105 110
Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr
115 120 125
Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln
130 135 140
Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn
145 150 155 160
Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu Leu
165 170 175
Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr Thr His
180 185 190
Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser Leu Arg Ala
195 200 205
Leu Arg Gln Met
210
<210>202
<211>212
<212>PRT
<213>智人(Homo sapiens)
<400>202
Met Asn Ser Phe Ser Thr Ser Ala Phe Gly Pro Val Ala Phe Ser Leu
1 5 10 15
Gly Leu Leu Leu Val Leu Pro Ala Ala Phe Pro Ala Pro Val Pro Pro
20 25 30
Gly Glu Asp Ser Lys Asp Val Ala Ala Pro His Arg Gln Pro Leu Thr
35 40 45
Ser Ser Glu Arg Ile Asp Lys Gln Ile Arg Tyr Ile Leu Asp Gly Ile
50 55 60
Ser Ala Leu Arg Lys Glu Thr Cys Asn Lys Ser Asn Met Cys Glu Ser
65 70 75 80
Ser Lys Glu Ala Leu Ala Glu Asn Asn Leu Asn Leu Pro Lys Met Ala
85 90 95
Glu Lys Asp Gly Cys Phe Gln Ser Gly Phe Asn Glu Glu Thr Cys Leu
100 105 110
Val Lys Ile Ile Thr Gly Leu Leu Glu Phe Glu Val Tyr Leu Glu Tyr
115 120 125
Leu Gln Asn Arg Phe Glu Ser Ser Glu Glu Gln Ala Arg Ala Val Gln
130 135 140
Met Ser Thr Lys Val Leu Ile Gln Phe Leu Gln Lys Lys Ala Lys Asn
145 150 155 160
Leu Asp Ala Ile Thr Thr Pro Asp Pro Thr Thr Asn Ala Ser Leu Leu
165 170 175
Thr Lys Leu Gln Ala Gln Asn Gln Trp Leu Gln Asp Met Thr Thr His
180 185 190
Leu Ile Leu Arg Ser Phe Lys Glu Phe Leu Gln Ser Ser Leu Arg Ala
195 200 205
Leu Arg Gln Met
210
<210>203
<21l>51
<212>PRT
<213>智人(Homo sapiens)
<400>203
Met Gly Pro Arg Ser Pro Gly Ala Leu Lys Leu Leu Lys Pro Thr Trp
1 5 10 15
Phe Arg Ala Glu Arg Gly Arg Ile Leu Leu Thr Ser Leu Leu Gly Met
20 25 30
Ser Lys Glu Asp Leu Val Ala Ser Cys Arg Val Cys Val Tyr Arg Ser
35 40 45
Leu Ser Leu
50
<210>204
<211>211
<212>PRT
<213>小鼠(Mus musculus)
<400>204
Met Lys Phe Leu Ser Ala Arg Asp Phe His Pro Val Ala Phe Leu Gly
1 5 10 15
Leu Met Leu Val Thr Thr Thr Ala Phe Pro Thr Ser Gln Val Arg Arg
20 25 30
Gly Asp Phe Thr Glu Asp Thr Thr Pro Asn Arg Pro Val Tyr Thr Thr
35 40 45
Ser Gln Val Gly Gly Leu Ile Thr His Val Leu Trp Glu Ile Val Glu
50 55 60
Met Arg Lys Glu Leu Cys Asn Gly Asn Ser Asp Cys Met Asn Asn Asp
65 70 75 80
Asp Ala Leu Ala Glu Asn Asn Leu Lys Leu Pro Glu Ile Gln Arg Asn
85 90 95
Asp Gly Cys Tyr Gln Thr Gly Tyr Asn Gln Glu Ile Cys Leu Leu Lys
100 105 110
Ile Ser Ser Gly Leu Leu Glu Tyr His Ser Tyr Leu Glu Tyr Met Lys
115 120 125
Asn Asn Leu Lys Asp Asn Lys Lys Asp Lys Ala Arg Val Leu Gln Arg
130 135 140
Asp Thr Glu Thr Leu Ile His Ile Phe Asn Gln Glu Val Lys Asp Leu
145 150 155 160
His Lys Ile Val Leu Pro Thr Pro Ile Ser Asn Ala Leu Leu Thr Asp
165 170 175
Lys Leu Glu Ser Gln Lys Glu Trp Leu Arg Thr Lys Thr Ile Gln Phe
180 185 190
Ile Leu Lys Ser Leu Glu Glu Phe Leu Lys Val Thr Leu Arg Ser Thr
195 200 205
Arg Gln Thr
210
<210>205
<211>211
<212>PRT
<213>小鼠(Mus musculus)
<400>205
Met Lys Phe Leu Ser Ala Arg Asp Phe His Pro Val Ala Phe Leu Gly
1 5 10 15
Leu Met Leu Val Thr Thr Thr Ala Phe Pro Thr Ser Gln Val Arg Arg
20 25 30
Gly Asp Phe Thr Glu Asp Thr Thr Pro Asn Arg Pro Val Tyr Thr Thr
35 40 45
Ser Gln Val Gly Gly Leu Ile Thr His Val Leu Trp Glu Ile Val Glu
50 55 60
Met Arg Lys Glu Leu Cys Asn Gly Asn Ser Asp Cys Met Asn Asn Asp
65 70 75 80
Asp Ala Leu Ala Glu Asn Asn Leu Lys Leu Pro Glu Ile Gln Arg Asn
85 90 95
Asp Gly Cys Tyr Gln Thr Gly Tyr Asn Gln Glu Ile Cys Leu Leu Lys
100 105 110
Ile Ser Ser Gly Leu Leu Glu Tyr His Ser Tyr Leu Glu Tyr Met Lys
115 120 125
Asn Asn Leu Lys Asp Asn Lys Lys Asp Lys Ala Arg Val Leu Gln Arg
130 135 140
Asp Thr Glu Thr Leu Ile His Ile Phe Asn Gln Glu Val Lys Asp Leu
145 150 155 160
His Lys Ile Val Leu Pro Thr Pro Ile Ser Asn Ala Leu Leu Thr Asp
165 170 175
Lys Leu Glu Ser Gln Lys Glu Trp Leu Arg Thr Lys Thr Ile Gln Phe
180 185 190
Ile Leu Lys Ser Leu Glu Glu Phe Leu Lys Val Thr Leu Arg Ser Thr
195 200 205
Arg Gln Thr
210
<210>206
<211>1666
<212>DNA
<213>智人(Homo sapiens)
<400>206
ctccataagg cacaaacttt cagagacagc agagcacaca agcttctagg acaagagcca 60
ggaagaaacc accggaagga accatctcac tgtgtgtaaa catgacttcc aagctggccg 120
tggctctctt ggcagccttc ctgatttctg cagctctgtg tgaaggtgca gttttgccaa 180
ggagtgctaa agaacttaga tgtcagtgca taaagacata ctccaaacct ttccacccca 240
aatttatcaa agaactgaga gtgattgaga gtggaccaca ctgcgccaac acagaaatta 300
ttgtaaagct ttctgatgga agagagctct gtctggaccc caaggaaaac tgggtgcaga 360
gggttgtgga gaagtttttg aagagggctg agaattcata aaaaaattca ttctctgtgg 420
tatccaagaa tcagtgaaga tgccagtgaa acttcaagca aatctacttc aacacttcat 480
gtattgtgtg ggtctgttgt agggttgcca gatgcaatac aagattcctg gttaaatttg 540
aatttcagta aacaatgaat agtttttcat tgtaccatga aatatccaga acatacttat 600
atgtaaagta ttatttattt gaatctacaa aaaacaacaa ataattttta aatataagga 660
ttttcctaga tattgcacgg gagaatatac aaatagcaaa attgaggcca agggccaaga 720
gaatatccga actttaattt caggaattga atgggtttgc tagaatgtga tatttgaagc 780
atcacataaa aatgatggga caataaattt tgccataaag tcaaatttag ctggaaatcc 840
tggatttttt tctgttaaat ctggcaaccc tagtctgcta gccaggatcc acaagtcctt 900
gttccactgt gccttggttt ctcctttatt tctaagtgga aaaagtatta gccaccatet 960
tacctcacag tgatgttgtg aggacatgtg gaagcacttt aagttttttc atcataacat 1020
aaattatttt caagtgtaac ttattaacct atttattatt tatgtattta tttaagcatc 1080
aaatatttgt gcaagaattt ggaaaaatag aagatgaatc attgattgaa tagttataaa 1140
gatgttatag taaatttatt ttattttaga tattaaatga tgttttatta gataaatttc 1200
aatcagggtt tttagattaa acaaacaaac aattgggtac ccagttaaat tttcatttca 1260
gataaacaac aaataatttt ttagtataag tacattattg tttatctgaa attttaattg 1320
aactaacaat cctagtttga tactcccagt cttgtcattg ccagctgtgt tggtagtgct 1380
gtgttgaatt acggaataat gagttagaac tattaaaaca gccaaaactc cacagtcaat 1440
attagtaatt tcttgctggt tgaaacttgt ttattatgta caaatagatt cttataatat 1500
tatttaaatg actgcatttt taaatacaag gctttatatt tttaacttta agatgttttt 1560
atgtgctctc caaatttttt ttactgtttc tgattgtatg gaaatataaa agtaaatatg 1620
aaacatttaa aatataattt gttgtcaaag taaaaaaaaa aaaaaa 1666
<210>207
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>207
Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser
1 5 10 15
Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu
20 25 30
Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe
35 40 45
Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr
50 55 60
Glu Ile Ile Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro
65 70 75 80
Lys Glu Asn Trp Val Gln Arg Val Val Glu Lys Phe Leu Lys Arg Ala
85 90 95
Glu Asn Ser
<210>208
<211>99
<212>PRT
<213>智人(Homo sapiens)
<400>208
Met Thr Ser Lys Leu Ala Val Ala Leu Leu Ala Ala Phe Leu Ile Ser
1 5 10 15
Ala Ala Leu Cys Glu Gly Ala Val Leu Pro Arg Ser Ala Lys Glu Leu
20 25 30
Arg Cys Gln Cys Ile Lys Thr Tyr Ser Lys Pro Phe His Pro Lys Phe
35 40 45
Ile Lys Glu Leu Arg Val Ile Glu Ser Gly Pro His Cys Ala Asn Thr
50 55 60
Glu Ile Ile Val Lys Leu Ser Asp Gly Arg Glu Leu Cys Leu Asp Pro
65 70 75 80
Lys Glu Asn Trp Val Gln Arg Val Val Glu Lys Phe Leu Lys Arg Ala
85 90 95
Glu Asn Ser
<210>209
<211>2986
<212>DNA
<213>智人(Homo sapiens)
<400>209
gcgccccagt cgacgctgag ctcctctgct actcagagtt gcaacctcag cctcgctatg 60
gctcccagca gcccccggcc cgcgctgccc gcactcctgg tcctgctcgg ggctctgttc 120
ccaggacctg gcaatgccca gacatctgtg tccccctcaa aagtcatcct gccccgggga 180
ggctccgtgc tggtgacatg cagcacctcc tgtgaccagc ccaagttgtt gggcatagag 240
accccgttgc ctaaaaagga gttgctcctg cctgggaaca accggaaggt gtatgaactg 300
agcaatgtgc aagaagatag ccaaccaatg tgctattcaa actgccctga tgggcagtca 360
acagctaaaa ccttcctcac cgtgtactgg actccagaac gggtggaact ggcacccctc 420
ccctcttggc agccagtggg caagaacctt accctacgct gccaggtgga gggtggggca 480
ccccgggcca acctcaccgt ggtgctgctc cgtggggaga aggagctgaa acgggagcca 540
gctgtggggg agcccgctga ggtcacgacc acggtgctgg tgaggagaga tcaccatgga 600
gccaatttct cgtgccgcac tgaactggac ctgcggcccc aagggctgga gctgtttgag 660
aacacctcgg ccccctacca gctccagacc tttgtcctgc cagcgactcc cccacaactt 720
gtcagccccc gggtcctaga ggtggacacg caggggaccg tggtctgttc cctggacggg 780
ctgttcccag tctcggaggc ccaggtccac ctggcactgg gggaccagag gttgaacccc 840
acagtcacct atggcaacga ctccttctcg gccaaggcct cagtcagtgt gaccgcagag 900
gacgagggca cccagcggct gacgtgtgca gtaatactgg ggaaccagag ccaggagaca 960
ctgcagacag tgaccatcta cagctttccg gcgcccaacg tgattctgac gaagccagag 1020
gtctcagaag ggaccgaggt gacagtgaag tgtgaggccc accctagagc caaggtgacg 1080
ctgaatgggg ttccagccca gccactgggc ccgagggccc agctcctgct gaaggccacc 1140
ccagaggaca acgggcgcag cttctcctgc tctgcaaccc tggaggtggc cggccagctt 1200
atacacaaga accagacccg ggagcttcgt gtcctgtatg gcccccgact ggacgagagg 1260
gattgtccgg gaaactggac gtggccagaa aattcccagc agactccaat gtgccaggct 1320
tgggggaacc cattgcccga gctcaagtgt ctaaaggatg gcactttccc actgcccatc 1380
ggggaatcag tgactgtcac tcgagatctt gagggcacct acctctgtcg ggccaggagc 1440
actcaagggg aggtcacccg cgaggtgacc gtgaatgtgc tctccccccg gtatgagatt 1500
gtcatcatca ctgtggtagc agccgcagtc ataatgggca ctgcaggcct cagcacgtac 1560
ctctataacc gccagcggaa gatcaagaaa tacagactac aacaggccca aaaagggacc 1620
cccatgaaac cgaacacaca agccacgcct ccctgaacct atcccgggac agggcctctt 1680
cctcggcctt cccatattgg tggcagtggt gccacactga acagagtgga agacatatgc 1740
catgcagcta cacctaccgg ccctgggacg ccggaggaca gggcattgtc ctcagtcaga 1800
tacaacagca tttggggcca tggtacctgc acacctaaaa cactaggcca cgcatctgat 1860
ctgtagtcac atgactaagc caagaggaag gagcaagact caagacatga ttgatggatg 1920
ttaaagtcta gcctgatgag aggggaagtg gtgggggaga catagcccca ccatgaggac 1980
atacaactgg gaaatactga aacttgctgc ctattgggta tgctgaggcc cacagactta 2040
cagaagaagt ggccctccat agacatgtgt agcatcaaaa cacaaaggcc cacacttcct 2100
gacggatgcc agcttgggca ctgctgtcta ctgaccccaa cccttgatga tatgtattta 2160
ttcatttgtt attttaccag ctatttattg agtgtctttt atgtaggcta aatgaacata 2220
ggtctctggc ctcacggagc tcccagtcca tgtcacattc aaggtcacca ggtacagttg 2280
tacaggttgt acactgcagg agagtgcctg gcaaaaagat caaatggggc tgggacttct 2340
cattggccaa cctgcctttc cccagaagga gtgatttttc tatcggcaca aaagcactat 2400
atggactggt aatggttcac aggttcagag attacccagt gaggccttat tcctcccttc 2460
cccccaaaac tgacaccttt gttagccacc tccccaccca catacatttc tgccagtgtt 2520
cacaatgaca ctcagcggtc atgtctggac atgagtgccc agggaatatg cccaagctat 2580
gccttgtcct cttgtcctgt ttgcatttca ctgggagctt gcactattgc agctccagtt 2640
tcctgcagtg atcagggtcc tgcaagcagt ggggaagggg gccaaggtat tggaggactc 2700
cctcccagct ttggaagggt catccgcgtg tgtgtgtgtg tgtatgtgta gacaagctct 2760
cgctctgtca cccaggctgg agtgcagtgg tgcaatcatg gttcactgca gtcttgacct 2820
tttgggctca agtgatcctc ccacctcagc ctcctgagta gctgggacca taggctcaca 2880
acaccacacc tggcaaattt gatttttttt ttttttttca gagacggggt ctcgcaacat 2940
tgcccagact tcctttgtgt tagttaataa agctttctca actgcc 2986
<210>210
<211>2540
<212>DNA
<213>小鼠(Mus musculus)
<400>210
gcgccgcccg cctcagtctg cacccagtgc tagtgctgag ctccgctgct acctgcactt 60
tgccctggcc ctgcaatggc ttcaacccgt gccaagccca cgctacctct gctcctggcc 120
ctggtcaccg ttgtgatccc tgggcctggt gatgctcagg tatccatcca tcccagagaa 180
gccttcctgc cccagggtgg gtccgtgcag gtgaactgtt cttcctcatg caaggaggac 240
ctcagcctgg gcttggagac tcagtggctg aaagatgagc tcgagagtgg acccaactgg 300
aagctgtttg agctgagcga gatcggggag gacagcagtc cgctgtgctt tgagaactgt 360
ggcaccgtgc agtcgtccgc ttccgctacc atcaccgtgt attcgtttcc ggagagtgtg 420
gagctgagac ctctgccagc ctggcagcaa gtaggcaagg acctcaccct gcgctgccac 480
gtggatggtg gagcaccgcg gacccagctc tcagcagtgc tgctccgtgg ggaggagata 540
ctgagccgcc agccagtggg tgggcacccc aaggacccca aggagatcac attcacggtg 600
ctggctagca gaggggacca cggagccaat ttctcatgcc gcacagaact ggatctcagg 660
ccgcaagggc tggcattgtt ctctaatgtc tccgaggcca ggagcctccg gactttcgat 720
cttccagcta ccatcccaaa gctcgacacc cctgacctcc tggaggtggg cacccagcag 780
aagttgtttt gctccctgga aggcctgttt cctgcctctg aagctcggat atacctggag 840
ctgggaggcc agatgccgac ccaggagagc acaaacagca gtgactctgt gtcagccact 900
gccttggtag aggtgactga ggagttcgac agaaccctgc cgctgcgctg cgttttggag 960
ctagcggacc agatcctgga gacgcagagg accttaacag tctacaactt ttcagctccg 1020
gtcctgaccc tgagccagct ggaggtctcg gaagggagcc aagtaactgt gaagtgtgaa 1080
gcccacagtg ggtcgaaggt ggttcttctg agcggcgtcg agcctaggcc acccaccccg 1140
caggtccaat tcacactgaa tgccagctcg gaggatcaca aacgaagctt cttttgctct 1200
gccgctctgg aggtggcggg aaagttcctg tttaaaaacc agaccctgga actgcacgtg 1260
ctgtatggtc ctcggctgga cgagacggac tgcttgggga actggacctg gcaagagggg 1320
tctcagcaga ctctgaaatg ccaggcctgg gggaacccat ctcctaagat gacctgcaga 1380
cggaaggcag atggtgccct gctgcccatc ggggtggtga agtctgtcaa acaggagatg 1440
aatggtacat acgtgtgcca tgcctttagc tcccatggga atgtcaccag gaatgtgtac 1500
ctgacagtac tgtaccactc tcaaaataac tggactataa tcattctggt gccagtactg 1560
ctggtcattg tgggcctcgt gatggcagcc tcttatgttt ataaccgcca gagaaagatc 1620
aggatataca agttacagaa ggctcaggag gaggccataa aactcaaggg acaagcccca 1680
cctccctgag cctgctggat gagactcctg cctggacccc ctgcagggca acagctgctg 1740
ctgcttttga acagaatggt agacagcatt taccctcagc cacttcctct ggctgtcaca 1800
gaacaggatg gtggcctggg ggatgcacac ttgtagcctc agagctaaga ggactcggtg 1860
gatggagcaa gactgtgaac acgtgtgacc cggacccacc tacagcccgg tggaccttca 1920
gccaagaaac gctgacttca ttctctattg cccctgctga ggggctcctg cctaaggaag 1980
acatgatatc cagtagacac aagcaagaag accacacttc cccccgacac aggaaagctg 2040
agacattgtc cccaactctt cttgatgtat ttattaattt agagttttac cagctattta 2100
ttgagtaccc tgtatatagt agatcagtga ggaggtgaat gtataagtta tggcctggac 2160
cctgctgcag atgctgtgag agtctgggga aagatcacat gggtcgaggg tttctctact 2220
ggtcaggatg cttttctcat aagggtcgac ttttttcacc agtcacataa acactatgtg 2280
gactggcagt ggttctctgc tcctccacat cctggagcgt cccagcacct ccccacctac 2340
ttttgttccc aatgtcagcc accatgcctt agcagctgaa caatcgagcc tcatgctcat 2400
gaaatcatgg tcccaggcgg ctccacctca aagagaaagc ctggaaggaa atgttccaac 2460
tccttagaag ggtcgtgcaa gctgctgtgg gagggtaagc acccctccca gcacagaaac 2520
ctttcctttg aatcaataaa 2540
<210>211
<211>532
<212>PRT
<213>智人(Homo sapiens)
<400>211
Met Ala Pro Ser Ser Pro Arg Pro Ala Leu Pro Ala Leu Leu Val Leu
1 5 10 15
Leu Gly Ala Leu Phe Pro Gly Pro Gly Asn Ala Gln Thr Ser Val Ser
20 25 30
Pro Ser Lys Val Ile Leu Pro Arg Gly Gly Ser Val Leu Val Thr Cys
35 40 45
Ser Thr Ser Cys Asp Gln Pro Lys Leu Leu Gly Ile Glu Thr Pro Leu
50 55 60
Pro Lys Lys Glu Leu Leu Leu Pro Gly Asn Asn Arg Lys Val Tyr Glu
65 70 75 80
Leu Ser Asn Val Gln Glu Asp Ser Gln Pro Met Cys Tyr Ser Asn Cys
85 90 95
Pro Asp Gly Gln Ser Thr Ala Lys Thr Phe Leu Thr Val Tyr Trp Thr
100 105 110
Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Ser Trp Gln Pro Val Gly
115 120 125
Lys Asn Leu Thr Leu Arg Cys Gln Val Glu Gly Gly Ala Pro Arg Ala
130 135 140
Asn Leu Thr Val Val Leu Leu Arg Gly Glu Lys Glu Leu Lys Arg Glu
145 150 155 160
Pro Ala Val Gly Glu Pro Ala Glu Val Thr Thr Thr Val Leu Val Arg
165 170 175
Arg Asp His His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu Asp Leu
180 185 190
Arg Pro Gln Gly Leu Glu Leu Phe Glu Asn Thr Ser Ala Pro Tyr Gln
195 200 205
Leu Gln Thr Phe Val Leu Pro Ala Thr Pro Pro Gln Leu Val Ser Pro
210 215 220
Arg Val Leu Glu Val Asp Thr Gln Gly Thr Val Val Cys Ser Leu Asp
225 230 235 240
Gly Leu Phe Pro Val Ser Glu Ala Gln Val His Leu Ala Leu Gly Asp
245 250 255
Gln Arg Leu Asn Pro Thr Val Thr Tyr Gly Asn Asp Ser Phe Ser Ala
260 265 270
Lys Ala Ser Val Ser Val Thr Ala Glu Asp Glu Gly Thr Gln Arg Leu
275 280 285
Thr Cys Ala Val Ile Leu Gly Asn Gln Ser Gln Glu Thr Leu Gln Thr
290 295 300
Val Thr Ile Tyr Ser Phe Pro Ala Pro Asn Val Ile Leu Thr Lys Pro
305 310 315 320
Glu Val Ser Glu Gly Thr Glu Val Thr Val Lys Cys Glu Ala His Pro
325 330 335
Arg Ala Lys Val Thr Leu Asn Gly Val Pro Ala Gln Pro Leu Gly Pro
340 345 350
Arg Ala Gln Leu Leu Leu Lys Ala Thr Pro Glu Asp Asn Gly Arg Ser
355 360 365
Phe Ser Cys Ser Ala Thr Leu Glu Val Ala Gly Gln Leu Ile His Lys
370 375 380
Asn Gln Thr Arg Glu Leu Arg Val Leu Tyr Gly Pro Arg Leu Asp Glu
385 390 395 400
Arg Asp Cys Pro Gly Asn Trp Thr Trp Pro Glu Asn Ser Gln Gln Thr
405 410 415
Pro Met Cys Gln Ala Trp Gly Asn Pro Leu Pro Glu Leu Lys Cys Leu
420 425 430
Lys Asp Gly Thr Phe Pro Leu Pro Ile Gly Glu Ser Val Thr Val Thr
435 440 445
Arg Asp Leu Glu Gly Thr Tyr Leu Cys Arg Ala Arg Ser Thr Gln Gly
450 455 460
Glu Val Thr Arg Glu Val Thr Val Asn Val Leu Ser Pro Arg Tyr Glu
465 470 475 480
Ile Val Ile Ile Thr Val Val Ala Ala Ala Val Ile Met Gly Thr Ala
485 490 495
Gly Leu Ser Thr Tyr Leu Tyr Asn Arg Gln Arg Lys Ile Lys Lys Tyr
500 505 510
Arg Leu Gln Gln Ala Gln Lys Gly Thr Pro Met Lys Pro Asn Thr Gln
515 520 525
Ala Thr Pro Pro
530
<210>212
<211>89
<212>PRT
<213>智人(Homo sapiens)
<400>212
Gly Pro Gly Asn Ala Gln Thr Ser Val Ser Pro Ser Lys Val Ile Leu
1 5 10 15
Pro Arg Gly Gly Ser Val Leu Val Thr Cys Ser Thr Ser Cys Asp Gln
20 25 30
Pro Met Leu Leu Gly Ile Glu Thr Pro Leu Pro Lys Lys Glu Leu Leu
35 40 45
Leu Pro Gly Asn Asn Arg Lys Val Tyr Glu Leu Ser Asn Val Gln Glu
50 55 60
Asp Ser Gln Pro Met Cys Tyr Ser Asn Cys Pro Asp Gly Gln Ser Thr
65 70 75 80
Ala Lys Thr Phe Leu Thr Val Tyr Trp
85
<210>213
<211>532
<212>PRT
<213>智人(Homo sapiens)
<400>213
Met Ala Pro Ser Ser Pro Arg Pro Ala Leu Pro Ala Leu Leu Val Leu
1 5 10 15
Leu Gly Ala Leu Phe Pro Gly Pro Gly Asn Ala Gln Thr Ser Val Ser
20 25 30
Pro Ser Lys Val Ile Leu Pro Arg Gly Gly Ser Val Leu Val Thr Cys
35 40 45
Ser Thr Ser Cys Asp Gln Pro Lys Leu Leu Gly Ile Glu Thr Pro Leu
50 55 60
Pro Lys Lys Glu Leu Leu Leu Pro Gly Asn Asn Arg Lys Val Tyr Glu
65 70 75 80
Leu Ser Asn Val Gln Glu Asp Ser Gln Pro Met Cys Tyr Ser Asn Cys
85 90 95
Pro Asp Gly Gln Ser Thr Ala Lys Thr Phe Leu Thr Val Tyr Trp Thr
100 105 110
Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Ser Trp Gln Pro Val Gly
115 120 125
Lys Asn Leu Thr Leu Arg Cys Gln Val Glu Gly Gly Ala Pro Arg Ala
130 135 140
Asn Leu Thr Val Val Leu Leu Arg Gly Glu Lys Glu Leu Lys Arg Glu
145 150 155 160
Pro Ala Val Gly Glu Pro Ala Glu Val Thr Thr Thr Val Leu Val Arg
165 170 175
Arg Asp His His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu Asp Leu
180 185 190
Arg Pro Gln Gly Leu Glu Leu Phe Glu Asn Thr Ser Ala Pro Tyr Gln
195 200 205
Leu Gln Thr Phe Val Leu Pro Ala Thr Pro Pro Gln Leu Val Ser Pro
210 215 220
Arg Val Leu Glu Val Asp Thr Gln Gly Thr Val Val Cys Ser Leu Asp
225 230 235 240
Gly Leu Phe Pro Val Ser Glu Ala Gln Val His Leu Ala Leu Gly Asp
245 250 255
Gln Arg Leu Asn Pro Thr Val Thr Tyr Gly Asn Asp Ser Phe Ser Ala
260 265 270
Lys Ala Ser Val Ser Val Thr Ala Glu Asp Glu Gly Thr Gln Arg Leu
275 280 285
Thr Cys Ala Val Ile Leu Gly Asn Gln Ser Gln Glu Thr Leu Gln Thr
290 295 300
Val Thr Ile Tyr Ser Phe Pro Ala Pro Asn Val Ile Leu Thr Lys Pro
305 310 315 320
Glu Val Ser Glu Gly Thr Glu Val Thr Val Lys Cys Glu Ala His Pro
325 330 335
Arg Ala Lys Val Thr Leu Asn Gly Val Pro Ala Gln Pro Leu Gly Pro
340 345 350
Arg Ala Gln Leu Leu Leu Lys Ala Thr Pro Glu Asp Asn Gly Arg Ser
355 360 365
Phe Ser Cys Ser Ala Thr Leu Glu Val Ala Gly Gln Leu Ile His Lys
370 375 380
Asn Gln Thr Arg Glu Leu Arg Val Leu Tyr Gly Pro Arg Leu Asp Glu
385 390 395 400
Arg Asp Cys Pro Gly Asn Trp Thr Trp Pro Glu Asn Ser Gln Gln Thr
405 410 415
Pro Met Cys Gln Ala Trp Gly Asn Pro Leu Pro Glu Leu Lys Cys Leu
420 425 430
Lys Asp Gly Thr Phe Pro Leu Pro Ile Gly Glu Ser Val Thr Val Thr
435 440 445
Arg Asp Leu Glu Gly Thr Tyr Leu Cys Arg Ala Arg Ser Thr Gln Gly
450 455 460
Glu Val Thr Arg Lys Val Thr Val Asn Val Leu Ser Pro Arg Tyr Glu
465 470 475 480
Ile Val Ile Ile Thr Val Val Ala Ala Ala Val Ile Met Gly Thr Ala
485 490 495
Gly Leu Ser Thr Tyr Leu Tyr Asn Arg Gln Arg Lys Ile Lys Lys Tyr
500 505 510
Arg Leu Gln Gln Ala Gln Lys Gly Thr Pro Met Lys Pro Asn Thr Gln
515 520 525
Ala Thr Pro Pro
530
<210>214
<211>43
<212>PRT
<213>智人(Homo sapiens)
<400>214
Met Ala Pro Ser Ser Pro Arg Pro Ala Leu Pro Ala Leu Leu Val Leu
1 5 10 15
Leu Gly Ala Leu Phe Pro Gly Glu Ser Gly Trp Gly Leu Pro Ser Gly
20 25 30
Gln Phe Ser Glu Ala Arg Glu Asp Arg Leu Pro
35 40
<210>215
<211>276
<212>PRT
<213>智人(Homo sapiens)
<220>
<221>MOD_RES
<222>(97)..(98)
<223>Variable amino acid
<220>
<221>MOD_RES
<222>(108)
<223>Variable amino acid
<220>
<221>MOD_RES
<222>(111)
<223>Variable amino acid
<400>215
Gln Arg Leu Asn Pro Thr Val Thr Tyr Gly Asn Asp Ser Phe Ser Ala
1 5 10 15
Lys Ala Ser Val Ser Val Thr Ala Glu Asp Glu Gly Thr Gln Arg Leu
20 25 30
Thr Cys Ala Val Ile Leu Gly Asn Gln Ser Gln Glu Thr Leu Gln Thr
35 40 45
Val Thr Ile Tyr Ser Phe Pro Ala Pro Asn Val Ile Leu Thr Lys Pro
50 55 60
Glu Val Ser Glu Gly Thr Glu Val Thr Val Lys Cys Glu Ala His Pro
65 70 75 80
Arg Ala Lys Val Thr Leu Asn Gly Val Pro Ala Gln Pro Leu Gly Pro
85 90 95
Xaa Xaa Gln Leu Leu Leu Lys Ala Thr Pro Glu Xaa Asn Gly Xaa Ser
100 105 110
Phe Ser Cys Ser Ala Thr Leu Glu Val Ala Gly Gln Leu Ile His Lys
115 120 125
Asn Gln Thr Arg Glu Leu Arg Val Leu Tyr Gly Pro Arg Leu Asp Glu
130 135 140
Arg Asp Cys Pro Gly Asn Trp Thr Trp Pro Glu Asn Ser Gln Gln Thr
145 150 155 160
Pro Met Cys Gln Ala Trp Gly Asn Pro Leu Pro Glu Leu Lys Cys Leu
165 170 175
Lys Asp Gly Thr Phe Pro Leu Pro Ile Gly Glu Ser Val Thr Val Thr
180 185 190
Arg Asp Leu Glu Gly Thr Tyr Leu Cys Arg Ala Arg Ser Thr Gln Gly
195 200 205
Glu Val Thr Arg Glu Val Thr Val Asn Val Leu Ser Pro Arg Tyr Glu
210 215 220
Ile Val Ile Ile Thr Val Val Ala Ala Ala Val Ile Met Gly Thr Ala
225 230 235 240
Gly Leu Ser Thr Tyr Leu Tyr Asn Arg Gln Arg Lys Ile Lys Lys Tyr
245 250 255
Arg Leu Gln Gln Ala Gln Lys Gly Thr Pro Met Lys Pro Asn Thr Gln
260 265 270
Ala Thr Pro Pro
275
<210>216
<211>528
<212>PRT
<213>智人(Homo sapiens)
<400>216
Ser Pro Arg Pro Ala Leu Pro Ala Leu Leu Val Leu Phe Gly Ala Leu
1 5 10 15
Phe Pro Gly Pro Gly Asn Val Gln Thr Ser Val Ser Pro Ser Lys Val
20 25 30
Ile Leu Pro Arg Gly Gly Ser Val Leu Val Thr Cys Ser Thr Ser Cys
35 40 45
Asp Gln Pro Lys Leu Leu Gly Ile Glu Thr Pro Leu Pro Lys Lys Glu
50 55 60
Leu Leu Leu Pro Gly Asn Asn Arg Lys Val Tyr Glu Leu Ser Asn Val
65 70 75 80
Gln Glu Asp Ser Gln Pro Met Cys Tyr Ser Asn Cys Pro Asp Gly Gln
85 90 95
Ser Thr Ala Lys Thr Phe Leu Thr Val Tyr Trp Thr Pro Glu Arg Val
100 105 110
Glu Leu Ala Pro Leu Pro Ser Trp Gln Pro Val Gly Lys Asn Leu Thr
115 120 125
Leu Arg Cys Gln Val Glu Gly Gly Ala Pro Arg Ala Asn Leu Thr Val
130 135 140
Val Leu Leu Arg Gly Glu Lys Glu Leu Lys Arg Glu Pro Ala Val Gly
145 150 155 160
Glu Pro Ala Glu Val Thr Thr Thr Val Leu Val Arg Arg Asp His His
165 170 175
Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu Asp Leu Arg Pro Gln Gly
180 185 190
Leu Glu Leu Phe Glu Asn Thr Ser Ala Pro Tyr Gln Leu Gln Thr Phe
195 200 205
Val Leu Pro Ala Thr Pro Pro Gln Leu Val Ser Pro Arg Val Leu Glu
210 215 220
Val Asp Thr Gln Gly Thr Val Val Cys Ser Leu Asp Gly Leu Phe Pro
225 230 235 240
Val Ser Glu Ala Gln Val His Leu Ala Leu Gly Asp Gln Arg Leu Asn
245 250 255
Pro Thr Val Thr Tyr Gly Asn Asp Ser Phe Ser Ala Lys Ala Ser Val
260 265 270
Ser Val Thr Ala Glu Asp Glu Gly Thr Gln Arg Leu Thr Cys Ala Val
275 280 285
Ile Leu Gly Asn Gln Ser Gln Glu Thr Leu Gln Thr Val Thr Ile Tyr
290 295 300
Ser Phe Pro Ala Pro Asn Val Ile Leu Thr Lys Pro Glu Val Ser Glu
305 310 315 320
Gly Thr Glu Val Thr Val Lys Cys Glu Ala His Pro Arg Ala Lys Val
325 330 335
Thr Leu Asn Gly Val Pro Ala Gln Pro Leu Gly Pro Arg Ala Gln Leu
340 345 350
Leu Leu Lys Ala Thr Pro Glu Asp Asn Gly Arg Ser Phe Ser Cys Ser
355 360 365
Ala Thr Leu Glu Val Ala Gly Gln Leu Ile His Lys Asn Gln Thr Arg
370 375 380
Glu Leu Arg Val Leu Tyr Gly Pro Arg Leu Asp Glu Arg Asp Cys Pro
385 390 395 400
Gly Asn Trp Thr Trp Pro Glu Asn Ser Gln Gln Thr Pro Met Cys Gln
405 410 415
Ala Trp Gly Asn Pro Leu Pro Glu Leu Lys Cys Leu Lys Asp Gly Thr
420 425 430
Phe Pro Leu Pro Ile Gly Glu Ser Val Thr Val Thr Arg Asp Leu Glu
435 440 445
Gly Thr Tyr Leu Cys Arg Ala Arg Ser Thr Gln Gly Glu Val Thr Arg
450 455 460
Glu Val Thr Val Asn Val Leu Ser Pro Arg Tyr Glu Ile Val Ile Ile
465 470 475 480
Thr Val Val Ala Ala Ala Val Ile Met Gly Thr Ala Gly Leu Ser Thr
485 490 495
Tyr Leu Tyr Asn Arg Gln Arg Lys Ile Lys Lys Tyr Arg Leu Gln Gln
500 505 510
Ala Gln Lys Gly Thr Pro Met Lys Pro Asn Thr Gln Ala Thr Pro Pro
515 520 525
<210>217
<211>532
<212>PRT
<213>智人(Homo sapiens)
<220>
<221>MOD_RES
<222>(241)
<223>Variable amino acid
<400>217
Met Ala Pro Ser Ser Pro Arg Pro Ala Leu Pro Ala Leu Leu Val Leu
1 5 10 15
Leu Gly Ala Leu Phe Pro Gly Pro Gly Asn Ala Gln Thr Ser Val Ser
20 25 30
Pro Ser Lys Val Ile Leu Pro Arg Gly Gly Ser Val Leu Val Thr Cys
35 40 45
Ser Thr Ser Cys Asp Gln Pro Lys Leu Leu Gly Ile Glu Thr Pro Leu
50 55 60
Pro Lys Lys Glu Leu Leu Leu Pro Gly Asn Asn Arg Lys Val Tyr Glu
65 70 75 80
Leu Ser Asn Val Gln Glu Asp Ser Gln Pro Met Cys Tyr Ser Asn Cys
85 90 95
Pro Asp Gly Gln Ser Thr Ala Lys Thr Phe Leu Thr Val Tyr Trp Thr
100 105 110
Pro Glu Arg Val Glu Leu Ala Pro Leu Pro Ser Trp Gln Pro Val Gly
115 120 125
Lys Asn Leu Thr Leu Arg Cys Gln Val Glu Gly Gly Ala Pro Arg Ala
130 135 140
Asn Leu Thr Val Val Leu Leu Arg Gly Glu Lys Glu Leu Lys Arg Glu
145 150 155 160
Pro Ala Val Gly Glu Pro Ala Glu Val Thr Thr Thr Val Leu Val Arg
165 170 175
Arg Asp His His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu Asp Leu
180 185 190
Arg Pro Gln Gly Leu Glu Leu Phe Glu Asn Thr Ser Ala Pro Tyr Gln
195 200 205
Leu Gln Thr Phe Val Leu Pro Ala Thr Pro Pro Gln Leu Val Ser Pro
210 215 220
Arg Val Leu Glu Val Asp Thr Gln Gly Thr Val Val Cys Ser Leu Asp
225 230 235 240
Xaa Leu Phe Pro Val Ser Glu Ala Gln Val His Leu Ala Leu Gly Asp
245 250 255
Gln Arg Leu Asn Pro Thr Val Thr Tyr Gly Asn Asp Ser Phe Ser Ala
260 265 270
Lys Ala Ser Val Ser Val Thr Ala Glu Asp Glu Gly Thr Gln Arg Leu
275 280 285
Thr Cys Ala Val Ile Leu Gly Asn Gln Ser Gln Glu Thr Leu Gln Thr
290 295 300
Val Thr Ile Tyr Ser Phe Pro Ala Pro Asn Val Ile Leu Thr Lys Pro
305 310 315 320
Glu Val Ser Glu Gly Thr Glu Val Thr Val Lys Cys Glu Ala His Pro
325 330 335
Arg Ala Lys Val Thr Leu Asn Gly Val Pro Ala Gln Pro Leu Gly Pro
340 345 350
Arg Ala Gln Leu Leu Leu Lys Ala Thr Pro Glu Asp Asn Gly Arg Ser
355 360 365
Phe Ser Cys Ser Ala Thr Leu Glu Val Ala Gly Gln Leu Ile His Lys
370 375 380
Asn Gln Thr Arg Glu Leu Arg Val Leu Tyr Gly Pro Arg Leu Asp Glu
385 390 395 400
Arg Asp Cys Pro Gly Asn Trp Thr Trp Pro Glu Asn Ser Gln Gln Thr
405 410 415
Pro Met Cys Gln Ala Trp Gly Asn Pro Leu Pro Glu Leu Lys Cys Leu
420 425 430
Lys Asp Gly Thr Phe Pro Leu Pro Ile Gly Glu Ser Val Thr Val Thr
435 440 445
Arg Asp Leu Glu Gly Thr Tyr Leu Cys Arg Ala Arg Ser Thr Gln Gly
450 455 460
Glu Val Thr Arg Glu Val Thr Val Asn Val Leu Ser Pro Arg Tyr Glu
465 470 475 480
Ile Val Ile Ile Thr Val Val Ala Ala Ala Val Ile Met Gly Thr Ala
485 490 495
Gly Leu Ser Thr Tyr Leu Tyr Asn Arg Gln Arg Lys Ile Lys Lys Tyr
500 505 510
Arg Leu Gln Gln Ala Gln Lys Gly Thr Pro Met Lys Pro Asn Thr Gln
515 520 525
Ala Thr Pro Pro
530
<210>218
<211>38
<212>PRT
<213>智人(Homo sapiens)
<400>218
Glu Ser Val Thr Val Thr Arg Asp Leu Glu Gly Thr Tyr Leu Cys Arg
1 5 10 15
Ala Arg Ser Thr Gln Gly Glu Val Thr Arg Glu Pro Pro Gly Met Arg
20 25 30
Leu Ser Ser Ser Leu Trp
35
<210>219
<211>537
<212>PRT
<213>小鼠(Mus musculus)
<400>219
Met Ala Ser Thr Arg Ala Lys Pro Thr Leu Pro Leu Leu Leu Ala Leu
1 5 10 15
Val Thr Val Val Ile Pro Gly Pro Gly Asp Ala Gln Val Ser Ile His
20 25 30
Pro Arg Glu Ala Phe Leu Pro Gln Gly Gly Ser Val Gln Val Asn Cys
35 40 45
Ser Ser Ser Cys Lys Glu Asp Leu Ser Leu Gly Leu Glu Thr Gln Trp
50 55 60
Leu Lys Asp Glu Leu Glu Ser Gly Pro Asn Trp Lys Leu Phe Glu Leu
65 70 75 80
Ser Glu Ile Gly Glu Asp Ser Ser Pro Leu Cys Phe Glu Asn Cys Gly
85 90 95
Thr Val Gln Ser Ser Ala Ser Ala Thr Ile Thr Val Tyr Ser Phe Pro
100 105 110
Glu Ser Val Glu Leu Arg Pro Leu Pro Ala Trp Gln Gln Val Gly Lys
115 120 125
Asp Leu Thr Leu Arg Cys His Val Asp Gly Gly Ala Pro Arg Thr Gln
130 135 140
Leu Ser Ala Val Leu Leu Arg Gly Glu Glu Ile Leu Ser Arg Gln Pro
145 150 155 160
Val Gly Gly His Pro Lys Asp Pro Lys Glu Ile Thr Phe Thr Val Leu
165 170 175
Ala Ser Arg Gly Asp His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu
180 185 190
Asp Leu Arg Pro Gln Gly Leu Ala Leu Phe Ser Asn Val Ser Glu Ala
195 200 205
Arg Ser Leu Arg Thr Phe Asp Leu Pro Ala Thr Ile Pro Lys Leu Asp
210 215 220
Thr Pro Asp Leu Leu Glu Val Gly Thr Gln Gln Lys Leu Phe Cys Ser
225 230 235 240
Leu Glu Gly Leu Phe Pro Ala Ser Glu Ala Arg Ile Tyr Leu Glu Leu
245 250 255
Gly Gly Gln Met Pro Thr Gln Glu Ser Thr Asn Ser Ser Asp Ser Val
260 265 270
Ser Ala Thr Ala Leu Val Glu Val Thr Glu Glu Phe Asp Arg Thr Leu
275 280 285
Pro Leu Arg Cys Val Leu Glu Leu Ala Asp Gln Ile Leu Glu Thr Gln
290 295 300
Arg Thr Leu Thr Val Tyr Asn Phe Ser Ala Pro Val Leu Thr Leu Ser
305 310 315 320
Gln Leu Glu Val Ser Glu Gly Ser Gln Val Thr Val Lys Cys Glu Ala
325 330 335
His Ser Gly Ser Lys Val Val Leu Leu Ser Gly Val Glu Pro Arg Pro
340 345 350
Pro Thr Pro Gln Val Gln Phe Thr Leu Asn Ala Ser Ser Glu Asp His
355 360 365
Lys Arg Ser Phe Phe Cys Ser Ala Ala Leu Glu Val Ala Gly Lys Phe
370 375 380
Leu Phe Lys Asn Gln Thr Leu Glu Leu His Val Leu Tyr Gly Pro Arg
385 390 395 400
Leu Asp Glu Thr Asp Cys Leu Gly Asn Trp Thr Trp Gln Glu Gly Ser
405 410 415
Gln Gln Thr Leu Lys Cys Gln Ala Trp Gly Asn Pro Ser Pro Lys Met
420 425 430
Thr Cys Arg Arg Lys Ala Asp Gly Ala Leu Leu Pro Ile Gly Val Val
435 440 445
Lys Ser Val Lys Gln Glu Met Asn Gly Thr Tyr Val Cys His Ala Phe
450 455 460
Ser Ser His Gly Asn Val Thr Arg Asn Val Tyr Leu Thr Val Leu Tyr
465 470 475 480
His Ser Gln Asn Asn Trp Thr Ile Ile Ile Leu Val Pro Val Leu Leu
485 490 495
Val Ile Val Gly Leu Val Met Ala Ala Ser Tyr Val Tyr Asn Arg Gln
500 505 510
Arg Lys Ile Arg Ile Tyr Lys Leu Gln Lys Ala Gln Glu Glu Ala Ile
515 520 525
Lys Leu Lys Gly Gln Ala Pro Pro Pro
530 535
<210>220
<211>360
<212>PRT
<213>小鼠(Mus musculus)
<400>220
Met Ala Ser Thr Arg Ala Lys Pro Thr Leu Pro Leu Leu Leu Ala Leu
1 5 10 15
Val Thr Val Val Ile Pro Gly Pro Gly Asp Ala Gln Val Ser Ile His
20 25 30
Pro Arg Glu Ala Phe Leu Pro Gln Gly Gly Ser Val Gln Val Asn Cys
35 40 45
Ser Ser Ser Cys Lys Glu Asp Leu Ser Leu Gly Leu Glu Thr Gln Trp
50 55 60
Leu Lys Asp Glu Leu Glu Ser Gly Pro Asn Trp Lys Leu Phe Glu Leu
65 70 75 80
Ser Glu Ile Gly Glu Asp Ser Ser Pro Leu Cys Phe Glu Asn Cys Gly
85 90 95
Thr Val Gln Ser Ser Ala Ser Ala Thr Ile Thr Val Tyr Ser Phe Pro
100 105 110
Glu Ser Val Glu Leu Arg Pro Leu Pro Ala Trp Gln Gln Val Gly Lys
115 120 125
Asp Leu Thr Leu Arg Cys His Val Asp Gly Gly Ala Pro Arg Thr Gln
130 135 140
Leu Ser Ala Val Leu Leu Arg Gly Glu Glu Ile Leu Ser Arg Gln Pro
145 150 155 160
Val Gly Gly His Pro Lys Asp Pro Lys Glu Ile Thr Phe Thr Val Leu
165 170 175
Ala Ser Arg Gly Asp His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu
180 185 190
Asp Leu Arg Pro Gln Gly Leu Ala Leu Phe Ser Asn Val Ser Glu Ala
195 200 205
Arg Ser Leu Arg Thr Phe Asp Leu Pro Ala Thr Ile Pro Lys Leu Asp
210 2l5 220
Thr Pro Asp Leu Leu Glu Val Gly Thr Gln Gln Lys Leu Phe Cys Ser
225 230 235 240
Leu Glu Gly Leu Phe Pro Ala Ser Glu Ala Arg Ile Tyr Leu Glu Leu
245 250 255
Gly Gly Gln Met Pro Thr Gln Glu Ser Thr Asn Ser Ser Asp Ser Val
260 265 270
Ser Ala Thr Ala Leu Val Glu Val Thr Glu Glu Phe Asp Arg Thr Leu
275 280 285
Pro Leu Arg Cys Val Leu Glu Leu Ala Asp Gln Ile Leu Glu Thr Gln
290 295 300
Arg Thr Leu Thr Val Tyr Asn Phe Ser Ala Pro Val Leu Thr Leu Ser
305 310 315 320
Gln Leu Glu Val Ser Glu Gly Ser Gln Val Thr Val Lys Cys Glu Ala
325 330 335
His Ser Gly Ser Lys Val Val Leu Leu Ser Gly Val Glu Pro Arg Pro
340 345 350
Pro Thr Pro Gln Val Gln Phe Thr
355 360
<210>221
<211>537
<212>PRT
<213>小鼠(Mus musculus)
<400>221
Met Ala Ser Thr Arg Ala Lys Pro Thr Leu Pro Leu Leu Leu Ala Leu
1 5 10 15
Val Thr Val Val Ile Pro Gly Pro Gly Asp Ala Gln Val Ser Ile His
20 25 30
Pro Arg Glu Ala Phe Leu Pro Gln Gly Gly Ser Val Gln Val Asn Cys
35 40 45
Ser Ser Ser Cys Lys Glu Asp Leu Ser Leu Gly Leu Glu Thr Gln Trp
50 55 60
Leu Lys Asp Glu Leu Glu Ser Gly Pro Asn Trp Lys Leu Phe Glu Leu
65 70 75 80
Ser Glu Ile Gly Glu Asp Ser Ser Pro Leu Cys Phe Glu Asn Cys Gly
85 90 95
Thr Val Gln Ser Ser Ala Ser Ala Thr Ile Thr Val Tyr Ser Phe Pro
100 105 110
Glu Ser Val Glu Leu Arg Pro Leu Pro Ala Trp Gln Gln Val Gly Lys
115 120 125
Asp Leu Thr Leu Arg Cys His Val Asp Gly Gly Ala Pro Arg Thr Gln
130 135 140
Leu Ser Ala Val Leu Leu Arg Gly Glu Glu Ile Leu Ser Arg Gln Pro
145 150 155 160
Val Gly Gly His Pro Lys Asp Pro Lys Glu Ile Thr Phe Thr Val Leu
165 170 175
Ala Ser Arg Gly Asp His Gly Ala Asn Phe Ser Cys Arg Thr Glu Leu
180 185 190
Asp Leu Arg Pro Gln Gly Leu Ala Leu Phe Ser Asn Val Ser Glu Ala
195 200 205
Arg Ser Leu Arg Thr Phe Asp Leu Pro Ala Thr Ile Pro Lys Leu Asp
210 215 220
Thr Pro Asp Leu Leu Glu Val Gly Thr Gln Gln Lys Leu Phe Cys Ser
225 230 235 240
Leu Glu Gly Leu Phe Pro Ala Ser Glu Ala Arg Ile Tyr Leu Glu Leu
245 250 255
Gly Gly Gln Met Pro Thr Gln Glu Ser Thr Asn Ser Ser Asp Ser Val
260 265 270
Ser Ala Thr Ala Leu Val Glu Val Thr Glu Glu Phe Asp Arg Thr Leu
275 280 285
Pro Leu Arg Cys Val Leu Glu Leu Ala Asp Gln Ile Leu Glu Thr Gln
290 295 300
Arg Thr Leu Thr Val Tyr Asn Phe Ser Ala Pro Val Leu Thr Leu Ser
305 310 315 320
Gln Leu Glu Val Ser Glu Gly Ser Gln Val Thr Val Lys Cys Glu Ala
325 330 335
His Ser Gly Ser Lys Val Val Leu Leu Ser Gly Val Glu Pro Arg Pro
340 345 350
Pro Thr Pro Gln Val Gln Phe Thr Leu Asn Ala Ser Ser Glu Asp His
355 360 365
Lys Arg Ser Phe Phe Cys Ser Ala Ala Leu Glu Val Ala Gly Lys Phe
370 375 380
Leu Phe Lys Asn Gln Thr Leu Glu Leu His Val Leu Tyr Gly Pro Arg
385 390 395 400
Leu Asp Glu Thr Asp Cys Leu Gly Asn Trp Thr Trp Gln Glu Gly Ser
405 410 415
Gln Gln Thr Leu Lys Cys Gln Ala Trp Gly Asn Pro Ser Pro Lys Met
420 425 430
Thr Cys Arg Arg Lys Ala Asp Gly Ala Leu Leu Pro Ile Gly Val Val
435 440 445
Lys Ser Val Lys Gln Glu Met Asn Gly Thr Tyr Val Cys His Ala Phe
450 455 460
Ser Ser His Gly Asn Val Thr Arg Asn Val Tyr Leu Thr Val Leu Tyr
465 470 475 480
His Ser Gln Asn Asn Trp Thr Ile Ile Ile Leu Val Pro Val Leu Leu
485 490 495
Val Ile Val Gly Leu Val Met Ala Ala Ser Tyr Val Tyr Asn Arg Gln
500 505 510
Arg Lys Ile Arg Ile Tyr Lys Leu Gln Lys Ala Gln Glu Glu Ala Ile
515 520 525
Lys Leu Lys Gly Gln Ala Pro Pro Pro
530 535
<210>222
<211>931
<212>DNA
<213>智人(Homo sapiens)
<400>222
tttcgtcggc ccgccccttg gcttctgcac tgatggtggg tggatgagta atgcatccag 60
gaagcctgga ggcctgtggt ttccgcaccc gctgccacce ccgcccctag cgtggacatt 120
tatcctctag cgctcaggcc ctgccgccat cgccgcagat ccagcgccca gagagacacc 180
agagaaccca ccatggcccc ctttgagccc ctggcttctg gcatcctgtt gttgctgtgg 240
ctgatagccc ccagcagggc ctgcacctgt gtcccacccc acccacagac ggccttctgc 300
aattccgacc tcgtcatcag ggccaagttc gtggggacac cagaagtcaa ccagaccacc 360
ttataccagc gttatgagat caagatgacc aagatgtata aagggttcca agccttaggg 420
gatgccgctg acatccggtt cgtctacacc cccgccatgg agagtgtctg cggatacttc 480
cacaggtccc acaaccgcag cgaggagttt ctcattgctg gaaaactgca ggatggactc 540
ttgcacatca ctacctgcag ttttgtggct ccctggaaca gcctgagctt agctcagcgc 600
cggggcttca ccaagaccta cactgttggc tgtgaggaat gcacagtgtt tccctgttta 660
tccatcccct gcaaactgca gagtggcact cattgcttgt ggacggacca gctcctccaa 720
ggctctgaaa agggcttcca gtcccgtcac cttgcctgcc tgcctcggga gccagggctg 780
tgcacctggc agtccctgcg gtcccagata gcctgaatcc tgcccggagt ggaagctgaa 840
gcctgcacag tgtccaccct gttcccactc ccatctttct tccggacaat gaaataaaga 900
gttaccaccc agcagaaaaa aaaaaaaaaa a 931
<210>223
<211>624
<212>DNA
<213>小鼠(Mus musculus)
<400>223
atgatggccc cctttgcatc tctggcatct ggcatcctct tgttgctatc actgatagct 60
tccagtaagg cctgtagctg tgceccaccc cacccacaga cagccttctg caactcggac 120
ctggtcataa gggctaaatt catgggttcc ccacgaatca acgagaccac cttataccag 180
cgttataaga tcaagatgat gactaagatg ctaaaaggat tcaaggctgt gggaaatgcc 240
gcagatatcc ggtacgccta caccccagtc atggaaagcc tctgtggata tgcccacaag 300
tcccagaacc gcagtgaaga gtttctcatc acgggccgcc taaggaacgg gaaatttcac 360
atcaatgcct gcagcttctt ggttccctgg cgtactctga gccctgctca gcaaagagtt 420
ttctcaaaaa agaactatag tgctggctgt ggggtgtgca cagtgtttcc ctgtttatct 480
atcccttgca aactggagag tgacactcac tgtttgtgga cggatcaggt cctcgtgggc 540
tctgaggact accagagccg tcactttgct tgcctgccac ggaatctagg cttgtgcact 600
tggagatccc ttggggcccg atga 624
<210>224
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>224
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Ile Lys
50 55 60
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
65 70 75 80
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
85 90 95
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
100 105 110
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
115 120 125
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
130 135 140
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
145 150 155 160
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
165 170 175
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
180 185 190
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
195 200 205
<210>225
<21l>188
<212>PRT
<213>智人(Homo sapiens)
<400>225
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Ser Lys
50 55 60
Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp Ile Arg Phe
65 70 75 80
Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe His Arg Ser
85 90 95
His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu Gln Asp Gly
100 105 110
Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp Asn Ser Leu
115 120 125
Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr Val Gly Cys
130 135 140
Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys Lys Leu Gln
145 150 155 160
Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln Gly Ser Glu
165 170 175
Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Gly
180 185
<210>226
<211>143
<212>PRT
<213>智人(Homo sapiens)
<400>226
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
1 5 10 15
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
20 25 30
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
35 40 45
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
50 55 60
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
65 70 75 80
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
85 90 95
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
100 105 110
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
115 120 125
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
130 135 140
<210>227
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>227
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Ile Lys
50 55 60
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
65 70 75 80
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
85 90 95
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
100 105 110
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
115 120 125
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
130 135 140
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
145 150 155 160
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
165 170 175
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
180 185 190
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
195 200 205
<210>228
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>228
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Ile Lys
50 55 60
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
65 70 75 80
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
85 90 95
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
100 105 110
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
115 120 125
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
130 135 140
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
145 150 155 160
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
165 170 175
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
180 185 190
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
195 200 205
<210>229
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>229
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Ile Lys
50 55 60
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
65 70 75 80
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
85 90 95
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
100 105 110
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
115 120 125
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
130 135 140
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
145 150 155 160
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
165 170 175
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
180 185 190
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
195 200 205
<210>230
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>230
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Ile Lys
50 55 60
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
65 70 75 80
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
85 90 95
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
100 105 110
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
115 120 125
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
130 135 140
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
145 150 155 160
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
165 170 175
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
180 185 190
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
195 200 205
<210>231
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>231
Met Ala Pro Phe Glu Pro Leu Ala Ser Gly Ile Leu Leu Leu Leu Trp
1 5 10 15
Leu Ile Ala Pro Ser Arg Ala Cys Thr Cys Val Pro Pro His Pro Gln
20 25 30
Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Val Gly
35 40 45
Thr Pro Glu Val Asn Gln Thr Thr Leu Tyr Gln Arg Tyr Glu Tle Lys
50 55 60
Met Thr Lys Met Tyr Lys Gly Phe Gln Ala Leu Gly Asp Ala Ala Asp
65 70 75 80
Ile Arg Phe Val Tyr Thr Pro Ala Met Glu Ser Val Cys Gly Tyr Phe
85 90 95
His Arg Ser His Asn Arg Ser Glu Glu Phe Leu Ile Ala Gly Lys Leu
100 105 110
Gln Asp Gly Leu Leu His Ile Thr Thr Cys Ser Phe Val Ala Pro Trp
115 120 125
Asn Ser Leu Ser Leu Ala Gln Arg Arg Gly Phe Thr Lys Thr Tyr Thr
130 135 140
Val Gly Cys Glu Glu Cys Thr Val Phe Pro Cys Leu Ser Ile Pro Cys
145 150 155 160
Lys Leu Gln Ser Gly Thr His Cys Leu Trp Thr Asp Gln Leu Leu Gln
165 170 175
Gly Ser Glu Lys Gly Phe Gln Ser Arg His Leu Ala Cys Leu Pro Arg
180 185 190
Glu Pro Gly Leu Cys Thr Trp Gln Ser Leu Arg Ser Gln Ile Ala
195 200 205
<210>232
<211>207
<212>PRT
<213>小鼠(Mus musculus)
<400>232
Met Met Ala Pro Phe Ala Ser Leu Ala Ser Gly Ile Leu Leu Leu Leu
1 5 10 15
Ser Leu Ile Ala Ser Ser Lys Ala Cys Ser Cys Ala Pro Pro His Pro
20 25 30
Gln Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Met
35 40 45
Gly Ser Pro Arg Ile Asn Glu Thr Thr Leu Tyr Gln Arg Tyr Lys Ile
50 55 60
Lys Met Met Thr Lys Met Leu Lys Gly Phe Lys Ala Val Gly Asn Ala
65 70 75 80
Ala Asp Ile Arg Tyr Ala Tyr Thr Pro Val Met Glu Ser Leu Cys Gly
85 90 95
Tyr Ala His Lys Ser Gln Asn Arg Ser Glu Glu Phe Leu Ile Thr Gly
100 105 110
Arg Leu Arg Asn Gly Lys Phe His Ile Asn Ala Cys Ser Phe Leu Val
115 120 125
Pro Trp Arg Thr Leu Ser Pro Ala Gln Gln Arg Val Phe Ser Lys Lys
130 135 140
Asn Tyr Ser Ala Gly Cys Gly Val Cys Thr Val Phe Pro Cys Leu Ser
145 150 155 160
Ile Pro Cys Lys Leu Glu Ser Asp Thr His Cys Leu Trp Thr Asp Gln
165 170 175
Val Leu Val Gly Ser Glu Asp Tyr Gln Ser Arg His Phe Ala Cys Leu
180 185 190
Pro Arg Asn Leu Gly Leu Cys Thr Trp Arg Ser Leu Gly Ala Arg
195 200 205
<210>233
<211>205
<212>PRT
<213>小鼠(Mus musculus)
<400>233
Met Met Ala Pro Phe Ala Ser Leu Ala Ser Gly Ile Leu Leu Leu Leu
1 5 10 15
Ser Leu Ile Ala Ser Ser Lys Ala Cys Ser Cys Ala Pro Pro His Pro
20 25 30
Gln Thr Ala Phe Cys Asn Ser Asp Leu Val Ile Arg Ala Lys Phe Met
35 40 45
Gly Ser Pro Glu Ile Asn Glu Thr Thr Leu Tyr Gln Arg Tyr Lys Ile
50 55 60
Lys Met Thr Lys Met Leu Lys Gly Phe Lys Ala Val Gly Asn Ala Ala
65 70 75 80
Asp Ile Arg Tyr Ala Tyr Thr Pro Val Met Glu Ser Leu Cys Gly Tyr
85 90 95
Ala His Lys Ser Gln Asn Arg Ser Glu Glu Phe Leu Ile Thr Gly Arg
100 105 110
Leu Arg Asn Gly Asn Leu His Ile Ser Ala Cys Ser Phe Leu Val Pro
115 120 125
Trp Arg Thr Leu Ser Pro Ala Gln Gln Arg Ala Phe Ser Lys Thr Tyr
130 135 140
Ser Ala Gly Cys Gly Val Cys Thr Val Phe Pro Cys Leu Ser Ile Pro
145 150 155 160
Cys Lys Leu Glu Ser Asp Thr His Cys Leu Trp Thr Asp Gln Val Leu
165 170 175
Val Gly Ser Glu Asp Tyr Gln Ser Arg His Phe Ala Cys Leu Pro Arg
180 185 190
Asn Pro Gly Leu Cys Thr Trp Arg Ser Leu Gly Ala Arg
195 200 205
<210>234
<211>48
<212>PRT
<213>小鼠(Mus musculus)
<400>234
Met Asp Ile Tyr Ser Pro Leu Cys Ser Pro Cys Arg His His Arg Arg
1 5 10 15
Ser Gly Leu Leu Glu Thr His Gln Arg Tyr His Asp Gly Pro Leu Cys
20 25 30
Ile Ser Gly Ile Trp His Pro Leu Val Ala Ile Thr Asp Ser Phe Gln
35 40 45
<210>235
<211>684
<212>DNA
<213>智人(Homo sapiens)
<400>235
cattcccagc ctcacatcac tcacaccttg catttcaccc ctgcatccca gtcgccctgc 60
agcctcacac agatcctgca cacacccaga cagctggcgc tcacacattc accgttggcc 120
tgcctctgtt caccctccat ggccctgcta ctggccctca gcctgctggt tctctggact 180
tccccagccc caactctgag tggcaccaat gatgctgaag actgctgcct gtctgtgacc 240
cagaaaccca tccctgggta catcgtgagg aacttccact accttctcat caaggatggc 300
tgcagggtgc ctgctgtagt gttcaccaca ctgaggggcc gccagctctg tgcaccccca 360
gaccagccct gggtagaacg catcatccag agactgcaga ggacctcagc caagatgaag 420
cgccgcagca gttaacctat gaccgtgcag agggagcccg gagtccgagt caagcattgt 480
gaattattac ctaacctggg gaaccgagga ccagaaggaa ggaccaggct tccagctcct 540
ctgcaccaga cctgaccagc caggacaggg cctggggtgt gtgtgagtgt gagtgtgagc 600
gagagggtga gtgtggtcag agtaaagctg ctccaccccc agattgcaat gctaccaata 660
aagccgcctg gtgtttacaa ctaa 684
<210>236
<211>720
<212>DNA
<213>小鼠(Mus musculus)
<400>236
gcgggctcac tggggcacac acaagctcac ttgcacttgg ctcctgaacc ccttcacgcc 60
acaggaggac atctgagcga ttccagtcac tcccctgtga acccgtcgga gcctcggcct 120
ctcagattct tgcgcacaca gtctctcagg ctcactcact ctctgtggcc tgcctcagat 180
tatctgccat ggccccccgt gtgaccccac tcctggcctt cagcctgctg gttctctgga 240
ccttcccagc cccaactctg gggggtgcta atgatgcgga agactgctgc ctgtctgtga 300
cccagcgccc catccctggg aacatcgtga aagccttccg ctaccttctt aatgaagatg 360
gctgcagggt gcctgctgtt gtgttcacca cactaagggg ctatcagctc tgtgcacctc 420
cagaccagcc ctgggtggat cgcatcatcc gaagactgaa gaagtcttct gccaagaaca 480
aaggcaacag caccagaagg agccctgtgt cttgagtaaa gagatgtgaa tcactctggc 540
ccaggaaacc aaggaccaga agagaggacc aggcctcctg atgctctgtc ccagacctaa 600
cccagccaag tctgtgccta gagagtcgat gtgagtgtgg acaagagagt ttgtgtggct 660
agaacaccat ctctctgtgg ctagactgca gagcttccaa taaagccgct tggtaccgtg 720
<210>237
<211>98
<212>PRT
<213>智人(Homo sapiens)
<400>237
Met Ala Leu Leu Leu Ala Leu Ser Leu Leu Val Leu Trp Thr Ser Pro
1 5 10 15
Ala Pro Thr Leu Ser Gly Thr Asn Asp Ala Glu Asp Cys Cys Leu Ser
20 25 30
Val Thr Gln Lys Pro Ile Pro Gly Tyr Ile Val Arg Asn Phe His Tyr
35 40 45
Leu Leu Ile Lys Asp Gly Cys Arg Val Pro Ala Val Val Phe Thr Thr
50 55 60
Leu Arg Gly Arg Gln Leu Cys Ala Pro Pro Asp Gln Pro Trp Val Glu
65 70 75 80
Arg Ile Ile Gln Arg Leu Gln Arg Thr Ser Ala Lys Met Lys Arg Arg
85 90 95
Ser Ser
<210>238
<211>98
<212>PRT
<213>智人(Homo sapiens)
<400>238
Met Ala Leu Leu Leu Ala Leu Ser Leu Leu Val Leu Trp Thr Ser Pro
1 5 10 15
Ala Pro Thr Leu Ser Gly Thr Asn Asp Ala Glu Asp Cys Cys Leu Ser
20 25 30
Val Thr Gln Lys Pro Ile Pro Gly Tyr Ile Val Arg Asn Phe His Tyr
35 40 45
Leu Leu Ile Lys Asp Gly Cys Arg Val Pro Ala Val Val Phe Thr Thr
50 55 60
Leu Arg Gly Arg Gln Leu Cys Ala Pro Pro Asp Gln Pro Trp Val Glu
65 70 75 80
Arg Ile Ile Gln Arg Leu Gln Arg Thr Ser Ala Lys Met Lys Arg Arg
85 90 95
Ser Ser
<210>239
<211>98
<212>PRT
<213>智人(Homo sapiens)
<400>239
Met Ala Leu Leu Leu Ala Leu Ser Leu Leu Val Leu Trp Thr Ser Pro
1 5 10 15
Ala Pro Thr Leu Ser Gly Thr Asn Asp Ala Glu Asp Cys Cys Leu Ser
20 25 30
Val Thr Gln Lys Pro Ile Pro Gly Tyr Ile Val Arg Asn Phe His Tyr
35 40 45
Leu Leu Ile Lys Asp Gly Cys Arg Val Pro Ala Val Val Phe Thr Thr
50 55 60
Leu Arg Gly Arg Gln Leu Cys Ala Pro Pro Asp Gln Pro Trp Val Glu
65 70 75 80
Arg Ile Ile Gln Arg Leu Gln Arg Thr Ser Ala Lys Met Lys Arg Arg
85 90 95
Ser Ser
<210>240
<211>108
<212>PRT
<213>小鼠(Mus musculus)
<400>240
Met Ala Pro Arg Val Thr Pro Leu Leu Ala Phe Ser Leu Leu Val Leu
1 5 10 15
Trp Thr Phe Pro Ala Pro Thr Leu Gly Gly Ala Asn Asp Ala Glu Asp
20 25 30
Cys Cys Leu Ser Val Thr Gln Arg Pro Ile Pro Gly Asn Ile Val Lys
35 40 45
Ala Phe Arg Tyr Leu Leu Asn Glu Asp Gly Cys Arg Val Pro Ala Val
50 55 60
Val Phe Thr Thr Leu Arg Gly Tyr Gln Leu Cys Ala Pro Pro Asp Gln
65 70 75 80
Pro Trp Val Asp Arg Ile Ile Arg Arg Leu Lys Lys Ser Ser Ala Lys
85 90 95
Asn Lys Gly Asn Ser Thr Arg Arg Ser Pro Val Ser
100 105
<210>241
<211>146
<212>PRT
<213>小鼠(Mus museulus)
<400>241
Val His Leu Ser Ser Glu Glu Lys Gly Leu Ile Thr Ser Leu Trp Gly
1 5 10 15
Lys Ile Asp Ile Glu Gln Thr Gly Gly Glu Ala Leu Gly Arg Leu Leu
20 25 30
Ile Val Tyr Pro Trp Thr Ser Arg Phe Phe Asp His Phe Gly Asp Leu
35 40 45
Ser Ser Ala Lys Ala Val Leu Gly Asn Ala Lys Val Leu Ala His Gly
50 55 60
Ala Lys Val Leu Val Ser Phe Gly Asp Ala Ile Lys Asn Leu Asp Asn
65 70 75 80
Leu Lys Gly Thr Phe Ala Lys Leu Ser Glu Leu His Cys Asp Lys Leu
85 90 95
His Val Asp Pro Glu Asn Phe Lys Leu Leu Gly Asn Val Leu Val Ile
100 105 110
Cys Leu Ala Glu His Phe Gly Lys Asp Phe Thr Ile Asp Ala Gln Val
115 120 125
Ala Trp Gln Lys Leu Val Ala Gly Val Ala Asn Ala Leu Ala His Lys
130 135 140
Tyr His
145
<210>242
<211>108
<212>PRT
<213>小鼠(Mus musculus)
<400>242
Met Ala Pro Arg Val Thr Pro Leu Leu Ala Phe Ser Leu Leu Val Leu
1 5 10 15
Trp Thr Phe Pro Ala Pro Thr Leu Gly Gly Ala Asn Asp Ala Glu Asp
20 25 30
Cys Cys Leu Ser Val Thr Gln Arg Pro Ile Pro Gly Asn Ile Val Lys
35 40 45
Ala Phe Arg Tyr Leu Leu Asn Glu Asp Gly Cys Arg Val Pro Ala Val
50 55 60
Val Phe Thr Thr Leu Arg Gly Tyr Gln Leu Cys Ala Pro Pro Asp Gln
65 70 75 80
Pro Trp Val Asp Arg Ile Ile Arg Arg Leu Lys Lys Ser Ser Ala Lys
85 90 95
Asn Lys Gly Asn Ser Thr Arg Arg Ser Pro Val Ser
100 105
<210>243
<211>878
<212>DNA
<213>智人(Homo sapiens)
<400>243
atcccagccc acgcacagac ccccaacttg cagctgccca cctcaccctc agctctggcc 60
tcttactcac cctctaccac agacatggct cagtcactgg ctctgagcct ccttatcctg 120
gttctggcct ttggcatccc caggacccaa ggcagtgatg gaggggctca ggactgttgc 180
ctcaagtaca gccaaaggaa gattcccgcc aaggttgtcc gcagctaccg gaagcaggaa 240
ccaagcttag gctgctccat cccagctatc ctgttcttgc cccgcaagcg ctctcaggca 300
gagctatgtg cagacccaaa ggagctctgg gtgcagcagc tgatgcagca tctggacaag 360
acaccatccc cacagaaacc agcccagggc tgcaggaagg acaggggggc ctccaagact 420
ggcaagaaag gaaagggctc caaaggctgc aagaggactg agcggtcaca gacccctaaa 480
gggccatagc ccagtgagca gcctggagcc ctggagaccc caccagcctc accagcgctt 540
gaagcctgaa cccaagatgc aagaaggagg ctatgctcag gggccctgga gcagccaccc 600
catgctggcc ttgccacact ctttctcctg ctttaaccac cccatctgca ttcccagctc 660
taccctgcat ggctgagctg cccacagcag gccaggtcca gagagaccga ggagggagag 720
tctcccaggg agcatgagag gaggcagcag gactgtcccc ttgaaggaga atcatcagga 780
ccctggacct gatacggctc cccagtacac cccacctctt ccttgtaaat atgatttata 840
cctaactgaa taaaaagctg ttctgtcttc ccacccaa 878
<210>244
<211>831
<212>DNA
<213>小鼠(Mus musculus)
<400>244
tacagctctg gtctcatcct caactcaacc acaatcatgg ctcagatgat gactctgagc 60
ctccttagcc tggtcctggc tctctgcatc ccctggaccc aaggcagtga tggaggggga 120
caggactgct gccttaagta cagccagaag aaaattccct acagtattgt ccgaggctat 180
aggaagcaag aaccaagttt aggctgtccc atcccggcaa tcctgttctt accccggaag 240
cactctaagc ctgagctatg tgcaaaccct gaggaaggct gggtgcagaa cctgatgcgc 300
cgcctggacc agcctccagc cccagggaaa caaagccccg gctgcaggaa gaaccgggga 360
acctctaagt ctggaaagaa aggaaagggc tccaagggct gcaagagaac tgaacagaca 420
cagccctcaa gaggatagcc cagtagcccg cctggagccc aggagatccc ccacgaactt 480
caagctgggt ggttcacggt ccaactcaca ggcaaagagg gagctagaaa acagactcag 540
gagcccaaag cagccacctc atgctggctt ccgtccacac ccttgccctg cttcaaccat 600
tagatctgca cggccatccc tttcttacct ggcggagctg ccttccctgg ggtagaccaa 660
gagagtcaga agaaagagtg tctcccaggg aatgaggaag gagacagcag gactgtcccc 720
tctaggaggt cactcaggtc ccaagacctg aacctgctct ccatggcgcc ctccccttgt 780
ccttgcacct atgatttata cctaactgaa taaaaaagtg atccagcctc a 831
<210>245
<211>134
<212>PRT
<213>智人(Homo sapiens)
<400>245
Met Ala Gln Ser Leu Ala Leu Ser Leu Leu Ile Leu Val Leu Ala Phe
1 5 10 15
Gly Ile Pro Arg Thr Gln Gly Ser Asp Gly Gly Ala Gln Asp Cys Cys
20 25 30
Leu Lys Tyr Ser Gln Arg Lys Ile Pro Ala Lys Val Val Arg Ser Tyr
35 40 45
Arg Lys Gln Glu Pro Ser Leu Gly Cys Ser Ile Pro Ala Ile Leu Phe
50 55 60
Leu Pro Arg Lys Arg Ser Gln Ala Glu Leu Cys Ala Asp Pro Lys Glu
65 70 75 80
Leu Trp Val Gln Gln Leu Met Gln His Leu Asp Lys Thr Pro Ser Pro
85 90 95
Gln Lys Pro Ala Gln Gly Cys Arg Lys Asp Arg Gly Ala Ser Lys Thr
100 105 110
Gly Lys Lys Gly Lys Gly Ser Lys Gly Cys Lys Arg Thr Glu Arg Ser
115 120 125
Gln Thr Pro Lys Gly Pro
130
<210>246
<211>134
<212>PRT
<213>智人(Homo sapiens)
<400>246
Met Ala Gln Ser Leu Ala Leu Ser Leu Leu Ile Leu Val Leu Ala Phe
1 5 10 15
Gly Ile Pro Arg Thr Gln Gly Ser Asp Gly Gly Ala Gln Asp Cys Cys
20 25 30
Leu Lys Tyr Ser Gln Arg Lys Ile Pro Ala Lys Val Val Arg Ser Tyr
35 40 45
Arg Lys Gln Glu Pro Ser Leu Gly Cys Ser Ile Pro Ala Ile Leu Phe
50 55 60
Leu Pro Arg Lys Arg Ser Gln Ala Glu Leu Cys Ala Asp Pro Lys Glu
65 70 75 80
Leu Trp Val Gln Gln Leu Met Gln His Leu Asp Lys Thr Pro Ser Pro
85 90 95
Gln Lys Pro Ala Gln Gly Cys Arg Lys Asp Arg Gly Ala Ser Lys Thr
100 105 110
Gly Lys Lys Gly Lys Gly Ser Lys Gly Cys Lys Arg Thr Glu Arg Ser
115 120 125
Gln Thr Pro Lys Gly Pro
130
<210>247
<211>124
<212>PRT
<213>智人(Homo sapiens)
<400>247
Met Ala Gln Ser Leu Ala Leu Ser Leu Leu Ile Leu Val Leu Ala Phe
1 5 10 15
Gly Ile Pro Arg Thr Gln Gly Ser Asp Gly Gly Ala Gln Asp Cys Cys
20 25 30
Leu Lys Tyr Ser Gln Arg Lys Ile Pro Ala Lys Val Val Arg Ser Tyr
35 40 45
Arg Lys Gln Glu Pro Ser Leu Gly Cys Ser Ile Pro Ala Ile Leu Phe
50 55 60
Leu Pro Arg Lys Arg Ser Gln Ala Glu Leu Cys Ala Asp Pro Lys Glu
65 70 75 80
Leu Trp Val Gln Gln Leu Met Gln His Leu Asp Lys Thr Pro Ser Pro
85 90 95
Gln Lys Pro Ala Gln Gly Cys Arg Lys Asp Arg Gly Ala Ser Lys Thr
100 105 110
Gly Lys Lys Gly Lys Gly Ser Lys Gly Cys Lys Arg
115 120
<210>248
<211>134
<212>PRT
<213>智人(Homo sapiens)
<400>248
Met Ala Gln Ser Leu Ala Leu Ser Leu Leu Ile Leu Val Leu Ala Phe
1 5 10 15
Gly Ile Pro Arg Thr Gln Gly Ser Asp Gly Gly Ala Gln Asp Cys Cys
20 25 30
Leu Lys Tyr Ser Gln Arg Lys Ile Pro Ala Lys Val Val Arg Ser Tyr
35 40 45
Arg Lys Gln Glu Pro Ser Leu Gly Cys Ser Ile Pro Ala Ile Leu Phe
50 55 60
Leu Pro Arg Lys Arg Ser Gln Ala Glu Leu Cys Ala Asp Pro Lys Glu
65 70 75 80
Leu Trp Val Gln Gln Leu Met Gln His Leu Asp Lys Thr Pro Ser Pro
85 90 95
Gln Lys Pro Ala Gln Gly Cys Arg Lys Asp Arg Gly Ala Ser Lys Thr
100 105 110
Gly Lys Lys Gly Lys Gly Ser Lys Gly Cys Lys Arg Thr Glu Arg Ser
115 120 125
Gln Thr Pro Lys Gly Pro
130
<210>249
<211>133
<212>PRT
<213>小鼠(Mus musculus)
<400>249
Met Ala Gln Met Met Thr Leu Ser Leu Leu Ser Leu Val Leu Ala Leu
1 5 10 15
Cys Ile Pro Trp Thr Gln Gly Ser Asp Gly Gly Gly Gln Asp Cys Cys
20 25 30
Leu Lys Tyr Ser Gln Lys Lys Ile Pro Tyr Ser Ile Val Arg Gly Tyr
35 40 45
Arg Lys Gln Glu Pro Ser Leu Gly Cys Pro Ile Pro Ala Ile Leu Phe
50 55 60
Leu Pro Arg Lys His Ser Lys Pro Glu Leu Cys Ala Asn Pro Glu Glu
65 70 75 80
Gly Trp Val Gln Asn Leu Met Arg Arg Leu Asp Gln Pro Pro Ala Pro
85 90 95
Gly Lys Gln Ser Pro Gly Cys Arg Lys Asn Arg Gly Thr Ser Lys Ser
100 105 110
Gly Lys Lys Gly Lys Gly Ser Lys Gly Cys Lys Arg Thr Glu Gln Thr
115 120 125
Gln Pro Ser Arg Gly
130
<210>250
<211>1518
<212>DNA
<213>智人(Homo sapiens)
<400>250
aaaacagccc ggagcctgca gcccagcccc acccagaccc atggctggac ctgccaccca 60
gagccccatg aagctgatgg ccctgcagct gctgctgtgg cacagtgcac tctggacagt 120
gcaggaagcc acccccctgg gccctgccag ctccctgccc cagagcttcc tgctcaagtg 180
cttagagcaa gtgaggaaga tccagggcga tggcgcagcg ctccaggaga agctggtgag 240
tgagtgtgcc acctacaagc tgtgccaccc cgaggagctg gtgctgctcg gacactctct 300
gggcatcccc tgggctcccc tgagcagctg ccccagccag gccctgcagc tggcaggctg 360
cttgagccaa ctccatagcg gccttttcct ctaccagggg ctcctgcagg ecctggaagg 420
gatctccccc gagttgggtc ccaccttgga cacactgcag ctggacgtcg ccgactttgc 480
caccaccatc tggcagcaga tggaagaact gggaatggcc cctgccctgc agcccaccca 540
gggtgccatg ccggccttcg cctctgcttt ccagcgccgg gcaggagggg tcctggttgc 600
ctcccatctg cagagcttcc tggaggtgtc gtaccgcgtt ctacgccacc ttgcccagcc 660
ctgagccaag ccctccccat cccatgtatt tatctctatt taatatttat gtctatttaa 720
gcctcatatt taaagacagg gaagagcaga acggagcccc aggcctctgt gtccttccct 780
gcatttctga gtttcattct cctgcctgta gcagtgagaa aaagctcctg tcctcccatc 840
ccctggactg ggaggtagat aggtaaatac caagtattta ttactatgac tgctccccag 900
ccctggctct gcaatgggca ctgggatgag ccgctgtgag cccctggtcc tgagggtccc 960
cacctgggac ccttgagagt atcaggtctc ccacgtggga gacaagaaat ccctgtttaa 1020
tatttaaaca gcagtgttcc ccatctgggt ccttgcaccc ctcactctgg cctcagccga 1080
ctgcacagcg gcccctgcat ccccttggct gtgaggcccc tggacaagca gaggtggcca 1140
gagctgggag gcatggccct ggggtcccac gaatttgctg gggaatctcg tttttcttct 1200
taagactttt gggacatggt ttgactcccg aacatcaccg acgtgtctcc tgtttttctg 1260
ggtggcetcg ggacacctgc cctgccccca cgagggtcag gactgtgact ctttttaggg 1320
ccaggcaggt gcctggacat ttgccttgct ggacggggac tggggatgtg ggagggagca 1380
gacaggagga atcatgtcag gcctgtgtgt gaaaggaagc tccactgtca ccctccacet 1440
cttcaccccc cactcaccag tgtcccctcc actgtcacat tgtaactgaa cttcaggata 1500
ataaagtgtt tgcctcca 1518
<210>251
<211>1509
<212>DNA
<213>智人(Homo sapiens)
<400>251
aaaacagccc ggagcctgca gcccagcccc acccagaccc atggctggac ctgccaccca 60
gagccccatg aagctgatgg ccctgcagct gctgctgtgg cacagtgcac tctggacagt 120
gcaggaagcc acccccctgg gccctgccag ctccctgccc cagagcttcc tgctcaagtg 180
cttagagcaa gtgaggaaga tccagggcga tggcgcagcg ctccaggaga agctgtgtgc 240
cacctacaag ctgtgccacc ccgaggagct ggtgctgctc ggacactctc tgggcatccc 300
ctgggctccc ctgagcagct gccccagcca ggccctgcag ctggcaggct gcttgagcca 360
actccatagc ggccttttcc tctaccaggg gctcctgcag gccctggaag ggatctcccc 420
cgagttgggt cccaccttgg acacactgca gctggacgtc gccgactttg ccaccaccat 480
ctggcagcag atggaagaac tgggaatggc ccctgccctg cagcccaccc agggtgccat 540
gccggccttc gcctctgctt tccagcgccg ggcaggaggg gtcctggttg cctcccatct 600
gcagagcttc ctggaggtgt cgtaccgcgt tctacgccac cttgcccagc cctgagccaa 660
gccctcccca tcccatgtat ttatctctat ttaatattta tgtctattta agcctcatat 720
ttaaagacag ggaagagcag aacggagccc caggcctctg tgtccttccc tgcatttctg 780
agtttcattc tcctgcctgt agcagtgaga aaaagctcct gtcctcccat cccctggact 840
gggaggtaga taggtaaata ccaagtattt attactatga ctgctcccca gccctggctc 900
tgcaatgggc actgggatga gccgctgtga gcccctggtc ctgagggtcc ccacctggga 960
cccttgagag tatcaggtct cccacgtggg agacaagaaa tccctgttta atatttaaac 1020
agcagtgttc cccatctggg tccttgcacc cctcactctg gcctcagccg actgcacagc 1080
ggcccctgca tccccttggc tgtgaggccc ctggacaagc agaggtggcc agagctggga 1140
ggcatggccc tggggtccca cgaatttgct ggggaatctc gtttttcttc ttaagacttt 1200
tgggacatgg tttgactccc gaacatcacc gacgtgtctc ctgtttttct gggtggcctc 1260
gggacacctg ccctgccccc acgagggtca ggactgtgac tctttttagg gccaggcagg 1320
tgcctggaca tttgccttgc tggacgggga ctggggatgt gggagggagc agacaggagg 1380
aatcatgtca ggcctgtgtg tgaaaggaag ctccactgtc accctccacc tcttcacccc 1440
ccactcacca gtgtcccctc cactgtcaca ttgtaactga acttcaggat aataaagtgt 1500
ttgcctcca 1509
<210>252
<211>1703
<212>DNA
<213>智人(Homo sapiens)
<400>252
aaaacagccc ggagcctgca gcccagcccc acccagaccc atggctggac ctgccaccca 60
gagccccatg aagctgatgg gtgagtgtct tggcccagga tgggagagcc gcctgccctg 120
gcatgggagg gaggctggtg tgacagaggg gctggggatc cccgttctgg gaatggggat 180
taaaggcacc cagtgtcccc gagagggcct caggtggtag ggaacagcat gtctcctgag 240
cccgctctgt ccccagccct gcagctgctg ctgtggcaca gtgcactctg gacagtgcag 300
gaagccaccc ccctgggccc tgccagctcc ctgccccaga gcttcctgct caagtgctta 360
gagcaagtga ggaagatcca gggcgatggc gcagcgctcc aggagaagct gtgtgccacc 420
tacaagetgt gccaccccga ggagctggtg ctgctcggac actctctggg catcccctgg 480
getcccetga gcagctgccc cagccaggcc ctgcagctgg caggctgctt gagccaactc 540
catagcggcc ttttcctcta ccaggggctc ctgcaggccc tggaagggat ctcccccgag 600
ttgggtccca ccttggacac actgcagctg gacgtcgecg actttgccac caccatctgg 660
cagcagatgg aagaactggg aatggcccct gccctgcagc ccacccaggg tgccatgccg 720
gccttcgcct ctgctttcca gcgccgggca ggaggggtcc tggttgcctc ccatctgcag 780
agcttcctgg aggtgtcgta ccgcgttcta cgccaccttg cccagccctg agccaagccc 840
tccccatccc atgtatttat ctctatttaa tatttatgtc tatttaagcc tcatatttaa 900
agacagggaa gagcagaacg gagccccagg cctctgtgtc cttccctgca tttctgagtt 960
tcattctcct gcctgtagca gtgagaaaaa gctcctgtcc tcccatcccc tggactggga 1020
ggtagatagg taaataccaa gtatttatta ctatgactgc tccccagccc tggctctgca 1080
atgggcactg ggatgagccg ctgtgagccc ctggtcctga gggtccccac ctgggaccct 1140
tgagagtatc aggtctccca cgtgggagac aagaaatccc tgtttaatat ttaaacagca 1200
gtgttcccca tctgggtcct tgcacccctc actctggcct cagccgactg cacagcggcc 1260
cctgcatccc cttggctgtg aggcccctgg acaagcagag gtggccagag ctgggaggca 1320
tggccctggg gtcccacgaa tttgctgggg aatctcgttt ttcttcttaa gacttttggg 1380
acatggtttg actcccgaac atcaccgacg tgtctcctgt ttttctgggt ggcctcggga 1440
cacctgccct gcccccacga gggtcaggac tgtgactctt tttagggcca ggcaggtgcc 1500
tggacatttg ccttgctgga cggggactgg ggatgtggga gggagcagac aggaggaatc 1560
atgtcaggcc tgtgtgtgaa aggaagctcc actgtcaccc tccacctctt caccccccac 1620
tcaccagtgt cccctccact gtcacattgt aactgaactt caggataata aagtgtttgc 1680
ctccaaaaaa aaaaaaaaaa aaa 1703
<210>253
<211>1363
<212>DNA
<213>小鼠(Mus musculus)
<400>253
gtataaaggc cccctggagc tgggccctgg cagagcccag agctgcagcc cagatcaccc 60
agaatccatg gctcaacttt ctgcccagag gcgcatgaag ctaatggccc tgcagctgct 120
gctgtggcaa agtgcactat ggtcaggacg agaggccgtt cccctggtca ctgtcagcgc 180
tctgccacca tccctgcctc tgccccgaag cttcctgctt aagtccctgg agcaagtgag 240
gaagatccag gccagcggct cggtgctgct ggagcagttg tgtgccacct acaagctgtg 300
tcaccccgag gagctggtgt tgctgggcca ctctctgggg atcccgaagg cttccctgag 360
tggctgctct agccaggccc tgcagcagac acagtgccta agccagctcc acagtgggct 420
ctgcctctac caaggtctcc tgcaggctct atcgggtatt tcccctgccc tggcccccac 480
cttggacttg cttcagctgg atgttgccaa ctttgccacc accatctggc agcagatgga 540
aaacctaggg gtggccccta ctgtgcagcc cacacagagc gccatgccag ccttcacttc 600
tgccttccag cgccgggcag gaggtgtcct ggccatttcg tacctgcagg gcttcctgga 660
gacggctcgc cttgctctgc accacttggc ctagacctga gcagaaagcc ctttccagat 720
agtttattta tctctattta atatttatgc atatttaagc ctactattta aagacaaaga 780
cgagaaaatg gagctctaag cttctagatc attctctcca cttccgagtt ttgttctcct 840
gcttagagca gagagagaag gctcttgtgt cctcctgtgg aggccaggga aggagatggg 900
taaataccaa gtattgattc ctgctgctgc tccaggcacc cagttctgtg gcagtacccc 960
caaaaaatca gtgagccctg ccgtgctgag gcaccatctc aggggggccc aggcagcatc 1020
tggtctccct tccgggggac aagacatccc tgtttaatat ttaaacagca gtgttcccaa 1080
actgggttct tatatccctt gctctggtca accaggttgc agggtttcct gtcctcacag 1140
gaacgaagtc cctaaagaaa cagtggcagc caggtttagc cccggaattg actggattcc 1200
ttttttaggg ccctgctggc ctggaagttg gagtgggggg cagaggaggc aggaggaagc 1260
ctgggggggg ggttggcatg gagggaggcc ttcccatcca ccctcaccct ccaccccacc 1320
tgtcactata gccaagcttg cggataataa agtgtggtgt tcc 1363
<210>254
<211>200
<212>PRT
<213>智人(Homo sapiens)
<400>254
Met Ser Pro Glu Pro Ala Leu Ser Pro Ala Leu Gln Leu Leu Leu Trp
1 5 10 15
His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro Leu Gly Pro Ala
20 25 30
Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg
35 40 45
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr
50 55 60
Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu
65 70 75 80
Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln
85 90 95
Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu Phe Leu Tyr Gln
100 105 110
Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
115 120 125
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp
130 135 140
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln
145 150 155 160
Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly
165 170 175
Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
180 185 190
Val Leu Arg His Leu Ala Gln Pro
195 200
<210>255
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>255
Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln
1 5 10 15
Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro
20 25 30
Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu
35 40 45
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
50 55 60
Leu Val Ser Glu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu
65 70 75 80
Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
85 90 95
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
100 105 110
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile
115 120 125
Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala
130 135 140
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala
145 150 155 160
Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala
165 170 175
Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser
180 185 190
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
195 200 205
<210>256
<211>204
<212>PRT
<213>智人(Homo sapiens)
<400>256
Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln
1 5 10 15
Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro
20 25 30
Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu
35 40 45
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
50 55 60
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu
65 70 75 80
Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
85 90 95
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
100 105 110
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu
115 120 125
Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala
130 135 140
Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
145 150 155 160
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg
165 170 175
Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
180 185 190
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
195 200
<210>257
<211>207
<212>PRT
<213>智人(Homo sapiens)
<400>257
Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln
1 5 10 15
Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro
20 25 30
Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu
35 40 45
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
50 55 60
Leu Val Ser Glu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu
65 70 75 80
Val Leu Leu Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser
85 90 95
Cys Pro Ser Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His
100 105 110
Ser Gly Leu Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile
115 120 125
Ser Pro Glu Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala
130 135 140
Asp Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala
145 150 155 160
Pro Ala Leu Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala
165 170 175
Phe Gln Arg Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser
180 185 190
Phe Leu Glu Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
195 200 205
<210>258
<211>204
<212>PRT
<213>智人(Homo sapiens)
<400>258
Met Ala Gly Pro Ala Thr Gln Ser Pro Met Lys Leu Met Ala Leu Gln
1 5 10 15
Leu Leu Leu Trp His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro
20 25 30
Leu Gly Pro Ala Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu
35 40 45
Glu Gln Val Arg Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys
50 55 60
Leu Cys Ala Thr Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu
65 70 75 80
Gly His Ser Leu Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser
85 90 95
Gln Ala Leu Gln Leu Ala Gly Cys Leu Ser Gln Leu His Ser Gly Leu
100 105 110
Phe Leu Tyr Gln Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu
115 120 125
Leu Gly Pro Thr Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala
130 135 140
Thr Thr Ile Trp Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu
145 150 155 160
Gln Pro Thr Gln Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg
165 170 175
Arg Ala Gly Gly Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu
180 185 190
Val Ser Tyr Arg Val Leu Arg His Leu Ala Gln Pro
195 200
<210>259
<211>200
<212>PRT
<213>智人(Homo sapiens)
<400>259
Met Ser Pro Glu Pro Ala Leu Ser Pro Ala Leu Gln Leu Leu Leu Trp
1 5 10 15
His Ser Ala Leu Trp Thr Val Gln Glu Ala Thr Pro Leu Gly Pro Ala
20 25 30
Ser Ser Leu Pro Gln Ser Phe Leu Leu Lys Cys Leu Glu Gln Val Arg
35 40 45
Lys Ile Gln Gly Asp Gly Ala Ala Leu Gln Glu Lys Leu Cys Ala Thr
50 55 60
Tyr Lys Leu Cys His Pro Glu Glu Leu Val Leu Leu Gly His Ser Leu
65 70 75 80
Gly Ile Pro Trp Ala Pro Leu Ser Ser Cys Pro Ser Gln Ala Leu Gln
85 90 95
Leu Ala Gly Cys Leu Ser Gln Leu His Ser GIy Leu Phe Leu Tyr Gln
100 105 110
Gly Leu Leu Gln Ala Leu Glu Gly Ile Ser Pro Glu Leu Gly Pro Thr
115 120 125
Leu Asp Thr Leu Gln Leu Asp Val Ala Asp Phe Ala Thr Thr Ile Trp
130 135 140
Gln Gln Met Glu Glu Leu Gly Met Ala Pro Ala Leu Gln Pro Thr Gln
145 150 155 160
Gly Ala Met Pro Ala Phe Ala Ser Ala Phe Gln Arg Arg Ala Gly Gly
165 170 175
Val Leu Val Ala Ser His Leu Gln Ser Phe Leu Glu Val Ser Tyr Arg
180 185 190
Val Leu Arg His Leu Ala Gln Pro
195 200
<210>260
<211>208
<212>PRT
<213>小鼠(Mus musculus)
<400>260
Met Ala Gln Leu Ser Ala Gln Arg Arg Met Lys Leu Met Ala Leu Gln
1 5 10 15
Leu Leu Leu Trp Gln Ser Ala Leu Trp Ser Gly Arg Glu Ala Val Pro
20 25 30
Leu Val Thr Val Ser Ala Leu Pro Pro Ser Leu Pro Leu Pro Arg Ser
35 40 45
Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Ala Ser Gly
50 55 60
Ser Val Leu Leu Glu Gln Leu Cys Ala Thr Tyr Lys Leu Cys His Pro
65 70 75 80
Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Lys Ala Ser
85 90 95
Leu Ser Gly Cys Ser Ser Gln Ala Leu Gln Gln Thr Gln Cys Leu Ser
100 105 110
Gln Leu His Ser Gly Leu Cys Leu Tyr Gln Gly Leu Leu Gln Ala Leu
115 120 125
Ser Gly Ile Ser Pro Ala Leu Ala Pro Thr Leu Asp Leu Leu Gln Leu
130 135 140
Asp Val Ala Asn Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Asn Leu
145 150 155 160
Gly Val Ala Pro Thr Val Gln Pro Thr Gln Ser Ala Met Pro Ala Phe
165 170 175
Thr Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Ala Ile Ser Tyr
180 185 190
Leu Gln Gly Phe Leu Glu Thr Ala Arg Leu Ala Leu His His Leu Ala
195 200 205
<210>261
<211>208
<212>PRT
<213>小鼠(Mus musculus)
<400>261
Met Ala Gln Leu Ser Ala Gln Arg Arg Met Lys Leu Met Ala Leu Gln
1 5 10 15
Leu Leu Leu Trp Gln Ser Ala Leu Trp Ser Gly Arg Glu Ala Val Pro
20 25 30
Leu Val Thr Val Ser Ala Leu Pro Pro Ser Leu Pro Leu Pro Arg Ser
35 40 45
Phe Leu Leu Lys Ser Leu Glu Gln Val Arg Lys Ile Gln Ala Ser Gly
50 55 60
Ser Val Leu Leu Glu Gln Leu Cys Ala Thr Tyr Lys Leu Cys His Pro
65 70 75 80
Glu Glu Leu Val Leu Leu Gly His Ser Leu Gly Ile Pro Lys Ala Ser
85 90 95
Leu Ser Gly Cys Ser Ser Gln Ala Leu Gln Gln Thr Gln Cys Leu Ser
100 105 110
Gln Leu His Ser Gly Leu Cys Leu Tyr Gln Gly Leu Leu Gln Ala Leu
115 120 125
Ser Gly Ile Ser Pro Ala Leu Ala Pro Thr Leu Asp Leu Leu Gln Leu
130 135 140
Asp Val Ala Asn Phe Ala Thr Thr Ile Trp Gln Gln Met Glu Asn Leu
145 150 155 160
Gly Val Ala Pro Thr Val Gln Pro Thr Gln Ser Ala Met Pro Ala Phe
165 170 175
Thr Ser Ala Phe Gln Arg Arg Ala Gly Gly Val Leu Ala Ile Ser Tyr
180 185 190
Leu Gln Gly Phe Leu Glu Thr Ala Arg Leu Ala Leu His His Leu Ala
195 200 205
<210>262
<211>2226
<212>DNA
<213>智人(Homo sapiens)
<400>262
ctcgacccac gcgtccgcgc gccccaggag ccaaagccgg gctccaagtc ggcgccccac 60
gtcgaggctc cgccgcagcc tccggagttg gccgcagaca agaaggggag ggagcgggag 120
agggaggaga gctccgaagc gagagggccg agcgccatgc gccgcgccag cagagactac 180
accaagtacc tgcgtggctc ggaggagatg ggcggcggcc ccggagcccc gcacgagggc 240
cccctgcacg ccccgccgcc gcctgcgccg caccagcccc ccgccgcctc ccgctccatg 300
ttcgtggccc tcctggggct ggggctgggc caggttgtct gcagcgtcgc cctgttcttc 360
tatttcagag cgcagatgga tcctaataga atatcagaag atggcactca ctgcatttat 420
agaattttga gactccatga aaatgcagat tttcaagaca caactctgga gagtcaagat 480
acaaaattaa tacctgattc atgtaggaga attaaacagg cctttcaagg agctgtgcaa 540
aaggaattac aacatatcgt tggatcacag cacatcagag cagagaaagc gatggtggat 600
ggctcatggt tagatctggc caagaggagc aagcttgaag ctcagccttt tgctcatctc 660
actattaatg ccaccgacat cccatctggt tcccataaag tgagtctgtc ctcttggtac 720
catgatcggg gttgggccaa gatctccaac atgactttta gcaatggaaa actaatagtt 780
aatcaggatg gcttttatta cctgtatgcc aacatttgct ttcgacatca tgaaacttca 840
ggagacctag ctacagagta tcttcaacta atggtgtacg tcactaaaac cagcatcaaa 900
atcccaagtt ctcataccct gatgaaagga ggaagcacca agtattggtc agggaattct 960
gaattccatt tttattccat aaacgttggt ggatttttta agttacggtc tggagaggaa 1020
atcagcatcg aggtctccaa cccctcctta ctggatccgg atcaggatgc aacatacttt 1080
ggggctttta aagttcgaga tatagattga gccccagttt ttggagtgtt atgtatttcc 1140
tggatgtttg gaaacatttt ttaaaacaag ccaagaaaga tgtatatagg tgtgtgagac 1200
tactaagagg catggcccca acggtacacg actcagtatc catgctcttg accttgtaga 1260
gaacacgcgt atttacagcc agtgggagat gttagactca tggtgtgtta cacaatggtt 1320
tttaaatttt gtaatgaatt cctagaatta aaccagattg gagcaattac gggttgacct 1380
tatgagaaac tgcatgtggg ctatgggagg ggttggtccc tggtcatgtg ccccttcgca 1440
gctgaagtgg agagggtgtc atctagcgca attgaaggat catctgaagg ggcaaattct 1500
tttgaattgt tacatcatgc tggaacctgc aaaaaatact ttttctaatg aggagagaaa 1560
atatatgtat ttttatataa tatctaaagt tatatttcag atgtaatgtt ttctttgcaa 1620
agtattgtaa attatatttg tgctatagta tttgattcaa aatatttaaa aatgtcttgc 1680
tgttgacata tttaatgttt taaatgtaca gacatattta actggtgcac tttgtaaatt 1740
ccctggggaa aacttgcagc taaggagggg aaaaaaatgt tgtttcctaa tatcaaatgc 1800
agtatatttc ttcgttcttt ttaagttaat agattttttc agacttgtca agcctgtgca 1860
aaaaaattaa aatggatgcc ttgaataata agcaggatgt tggccaccag gtgcctttca 1920
aatttagaaa ctaattgact ttagaaagct gacattgcca aaaaggatac ataatgggcc 1980
actgaaatct gtcaagagta gttatataat tgttgaacag gtgtttttcc acaagtgccg 2040
caaattgtac cttttttttt ttttcaaaat agaaaagtta ttagtggttt atcagcaaaa 2100
aagtccaatt ttaatttagt aaatgttatc ttatactgta caataaaaac attgcctttg 2160
aatgttaatt ttttggtaca aaaataaatt tatatgaaaa cctgaaaaaa aaaacaaaaa 2220
aaaaaa 2226
<210>263
<211>1931
<212>DNA
<213>智人(Homo sapiens)
<400>263
gcgcctggcc tattgaaggt ttttaatctt cagagtttcg actttatcaa caacacttag 60
aagccaccaa agaattgcag atggatccta atagaatatc agaagatggc actcactgca 120
tttatagaat tttgagactc catgaaaatg cagattttca agacacaact ctggagagte 180
aagatacaaa attaatacct gattcatgta ggagaattaa acaggccttt caaggagctg 240
tgcaaaagga attacaacat atcgttggat cacagcacat cagagcagag aaagcgatgg 300
tggatggctc atggttagat ctggccaaga ggagcaagct tgaagctcag ccttttgctc 360
atctcactat taatgccaec gacatcecat ctggttccca taaagtgagt ctgtcctctt 420
ggtaccatga tcggggttgg gccaagatct ccaacatgac ttttagcaat ggaaaactaa 480
tagttaatca ggatggcttt tattacctgt atgccaacat ttgctttcga catcatgaaa 540
cttcaggaga cctagctaca gagtatcttc aactaatggt gtacgtcact aaaaccagca 600
tcaaaatccc aagttctcat accctgatga aaggaggaag caccaagtat tggtcaggga 660
attctgaatt ccatttttat tccataaacg ttggtggatt ttttaagtta cggtctggag 720
aggaaatcag catcgaggtc tccaacccct ccttactgga tccggatcag gatgcaacat 780
actttggggc ttttaaagtt cgagatatag attgagcccc agtttttgga gtgttatgta 840
tttcctggat gtttggaaac attttttaaa acaagccaag aaagatgtat ataggtgtgt 900
gagactacta agaggcatgg ccccaacggt acacgactca gtatccatgc tcttgacctt 960
gtagagaaca cgcgtattta cagccagtgg gagatgttag actcatggtg tgttacacaa 1020
tggtttttaa attttgtaat gaattcctag aattaaacca gattggagca attacgggtt 1080
gaccttatga gaaactgcat gtgggctatg ggaggggttg gtccctggtc atgtgcccct 1140
tcgcagctga agtggagagg gtgtcatcta gcgcaattga aggatcatct gaaggggcaa 1200
attcttttga attgttacat catgctggaa cctgcaaaaa atactttttc taatgaggag 1260
agaaaatata tgtattttta tataatatct aaagttatat ttcagatgta atgttttctt 1320
tgcaaagtat tgtaaattat atttgtgcta tagtatttga ttcaaaatat ttaaaaatgt 1380
cttgctgttg acatatttaa tgttttaaat gtacagacat atttaactgg tgcactttgt 1440
aaattccctg gggaaaactt gcagctaagg aggggaaaaa aatgttgttt cctaatatca 1500
aatgcagtat atttcttcgt tctttttaag ttaatagatt ttttcagact tgtcaagcct 1560
gtgcaaaaaa attaaaatgg atgccttgaa taataagcag gatgttggcc accaggtgcc 1620
tttcaaattt agaaactaat tgactttaga aagctgacat tgccaaaaag gatacataat 1680
gggccactga aatctgtcaa gagtagttat ataattgttg aacaggtgtt tttccacaag 1740
tgccgcaaat tgtacctttt ttgttttttc aaaatagaaa agttattagt ggtttatcag 1800
caaaaaagtc caattttaat ttagtaaatg ttatcttata ctgtacaata aaaacattgc 1860
ctttgaatgt taattttttg gtacaaaaat aaatttatat gaaaacctga aaaaaaaaaa 1920
aaaaaaaaaa a 1931
<210>264
<211>2299
<212>DNA
<213>小鼠(Mus musculus)
<400>264
gagctcggat ccactactcg acccacgcgt ccgcccacgc gtccggccag gacctctgtg 60
aaccggtcgg ggcgggggcc gcctggccgg gagtctgctc ggcggtgggt ggccgaggaa 120
gggagagaac gatcgcggag cagggcgccc gaactccggg cgccgcgcca tgcgccgggc 180
cagccgagac tacggcaagt acctgcgcag ctcggaggag atgggcagcg gccccggcgt 240
cccacacgag ggtccgctgc accccgcgcc ttctgcaccg gctccggcgc cgccacccgc 300
cgcctcccgc tccatgttcc tggccctcct ggggctggga ctgggccagg tggtctgcag 360
catcgctctg ttcctgtact ttcgagcgca gatggatcct aacagaatat cagaagacag 420
cactcactgc ttttatagaa tcctgagact ccatgaaaac gcaggtttgc aggactcgac 480
tctggagagt gaagacacac tacctgactc ctgcaggagg atgaaacaag cctttcaggg 540
ggccgtgcag aaggaactgc aacacattgt ggggccacag cgcttctcag gagctccagc 600
tatgatggaa ggctcatggt tggatgtggc ccagcgaggc aagcctgagg cccagccatt 660
tgcacacctc accatcaatg ctgccagcat cccatcgggt tcccataaag tcactctgtc 720
ctcttggtac cacgatcgag gctgggccaa gatctctaac atgacgttaa gcaacggaaa 780
actaagggtt aaccaagatg gcttctatta cctgtacgcc aacatttgct ttcggcatca 840
tgaaacatcg ggaagcgtac ctacagacta tcttcagctg atggtgtatg tcgttaaaac 900
cagcatcaaa atcccaagtt ctcataacct gatgaaagga gggagcacga aaaactggtc 960
gggcaattct gaattccact tttattccat aaatgttggg ggatttttca agctccgagc 1020
tggtgaagaa attagcattc aggtgtccaa cccttccctg ctggatccgg atcaagatgc 1080
gacgtacttt ggggctttca aagttcagga catagactga gactcatttc gtggaacatt 1140
agcatggatg tcctagatgt ttggaaactt cttaaaaaat ggatgatgtc tatacatgtg 1200
taagactact aagagacatg gcccacggtg tatgaaactc acagccctct ctcttgagcc 1260
tgtacaggtt gtgtatatgt aaagtccata ggtgatgtta gattcatggt gattacacaa 1320
cggttttaca attttgtaat gatttcctag aattgaacca gattgggaga ggtattccga 1380
tgcttatgaa aaacttacac gtgagctatg gaagggggtc acagtctctg ggtctaaccc 1440
ctggacatgt gccactgaga accttgaaat taagaggatg ccatgtcatt gcaaagaaat 1500
gatagtgtga agggttaagt tcttttgaat tgttacattg cgctgggacc tgcaaataag 1560
ttcttttttt ctaatgagga gagaaaaata tatgtatttt tatataatgt ctaaagttat 1620
atttcaggtg taatgttttc tgtgcaaagt tttgtaaatt atatttgtgc tatagtattt 1680
gattcaaaat atttaaaaat gtctcactgt tgacatattt aatgttttaa atgtacagat 1740
gtatttaact ggtgcacttt gtaattcccc tgaaggtact cgtagctaag ggggcagaat 1800
actgtttctg gtgaccacat gtagtttatt tctttattct ttttaactta atagagtctt 1860
cagacttgtc aaaactatgc aagcaaaata aataaataaa aataaaatga ataccttgaa 1920
taataagtag gatgttggtc accaggtgcc tttcaaattt agaagctaat tgactttagg 1980
agctgacata gccaaaaagg atacataata ggctactgaa atctgtcagg agtatttatg 2040
caattattga acaggtgtct ttttttacaa gagctacaaa ttgtaaattt tgtttctttt 2100
ttttcccata gaaaatgtac tatagtttat cagccaaaaa acaatccact ttttaattta 2160
gtgaaagtta ttttattata ctgtacaata aaagcattgt ctctgaatgt taattttttg 2220
gtacaaaaaa taaatttgta cgaaaacctg aaaaaaaaaa aaaaaaaggg cggccgctct 2280
agagggccct attctatag 2299
<210>265
<211>244
<212>PRT
<213>智人(Homo sapiens)
<400>265
Met Asp Pro Asn Arg Ile Ser Glu Asp Gly Thr His Cys Ile Tyr Arg
1 5 10 15
Ile Leu Arg Leu His Glu Asn Ala Asp Phe Gln Asp Thr Thr Leu Glu
20 25 30
Ser Gln Asp Thr Lys Leu Ile Pro Asp Ser Cys Arg Arg Ile Lys Gln
35 40 45
Ala Phe Gln Gly Ala Val Gln Lys Glu Leu Gln His Ile Val Gly Ser
50 55 60
Gln His Ile Arg Ala Glu Lys Ala Met Val Asp Gly Ser Trp Leu Asp
65 70 75 80
Leu Ala Lys Arg Ser Lys Leu Glu Ala Gln Pro Phe Ala His Leu Thr
85 90 95
Ile Asn Ala Thr Asp Ile Pro Ser Gly Ser His Lys Val Ser Leu Ser
100 105 110
Ser Trp Tyr His Asp Arg Gly Trp Ala Lys Ile Ser Asn Met Thr Phe
115 120 125
Ser Asn Gly Lys Leu Ile Val Asn Gln Asp Gly Phe Tyr Tyr Leu Tyr
130 135 140
Ala Asn Ile Cys Phe Arg His His Glu Thr Ser Gly Asp Leu Ala Thr
145 150 155 160
Glu Tyr Leu Gln Leu Met Val Tyr Val Thr Lys Thr Ser Ile Lys Ile
165 170 175
Pro Ser Ser His Thr Leu Met Lys Gly Gly Ser Thr Lys Tyr Trp Ser
180 185 190
Gly Asn Ser Glu Phe His Phe Tyr Ser Ile Asn Val Gly Gly Phe Phe
195 200 205
Lys Leu Arg Ser Gly Glu Glu Ile Ser Ile Glu Val Ser Asn Pro Ser
210 215 220
Leu Leu Asp Pro Asp Gln Asp Ala Thr Tyr Phe Gly Ala Phe Lys Val
225 230 235 240
Arg Asp Ile Asp
<210>266
<211>317
<212>PRT
<213>智人(Homo sapiens)
<400>266
Met Arg Arg Ala Ser Arg Asp Tyr Thr Lys Tyr Leu Arg Gly Ser Glu
1 5 10 15
Glu Met Gly Gly Gly Pro Gly Ala Pro His Glu Gly Pro Leu His Ala
20 25 30
Pro Pro Pro Pro Ala Pro His Gln Pro Pro Ala Ala Ser Arg Ser Met
35 40 45
Phe Val Ala Leu Leu Gly Leu Gly Leu Gly Gln Val Val Cys Ser Val
50 55 60
Ala Leu Phe Phe Tyr Phe Arg Ala Gln Met Asp Pro Asn Arg Ile Ser
65 70 75 80
Glu Asp Gly Thr His Cys Ile Tyr Arg Ile Leu Arg Leu His Glu Asn
85 90 95
Ala Asp Phe Gln Asp Thr Thr Leu Glu Ser Gln Asp Thr Lys Leu Ile
100 105 110
Pro Asp Ser Cys Arg Arg Ile Lys Gln Ala Phe Gln Gly Ala Val Gln
115 120 125
Lys Glu Leu Gln His Ile Val Gly Ser Gln His Ile Arg Ala Glu Lys
130 135 140
Ala Met Val Asp Gly Ser Trp Leu Asp Leu Ala Lys Arg Ser Lys Leu
145 150 155 160
Glu Ala Gln Pro Phe Ala His Leu Thr Ile Asn Ala Thr Asp Ile Pro
165 170 175
Ser Gly Ser His Lys Val Ser Leu Ser Ser Trp Tyr His Asp Arg Gly
180 185 190
Trp Ala Lys Ile Ser Asn Met Thr Phe Ser Asn Gly Lys Leu Ile Val
195 200 205
Asn Gln Asp Gly Phe Tyr Tyr Leu Tyr Ala Asn Ile Cys Phe Arg His
210 215 220
His Glu Thr Ser Gly Asp Leu Ala Thr Glu Tyr Leu Gln Leu Met Val
225 230 235 240
Tyr Val Thr Lys Thr Ser Ile Lys Ile Pro Ser Ser His Thr Leu Met
245 250 255
Lys Gly Gly Ser Thr Lys Tyr Trp Ser Gly Asn Ser Glu Phe His Phe
260 265 270
Tyr Ser Ile Asn Val Gly Gly Phe Phe Lys Leu Arg Ser Gly Glu Glu
275 280 285
Ile Ser lle Glu Val Ser Asn Pro Ser Leu Leu Asp Pro Asp Gln Asp
290 295 300
Ala Thr Tyr Phe Gly Ala Phe Lys Val Arg Asp Ile Asp
305 310 315
<210>267
<211>317
<212>PRT
<213>智人(Homo sapiens)
<400>267
Met Arg Arg Ala Ser Arg Asp Tyr Thr Lys Tyr Leu Arg Gly Ser Glu
1 5 10 15
Glu Met Gly Gly Gly Pro Gly Ala Pro His Glu Gly Pro Leu His Ala
20 25 30
Pro Pro Pro Pro Ala Pro His Gln Pro Pro Ala Ala Ser Arg Ser Met
35 40 45
Phe Val Ala Leu Leu Gly Leu Gly Leu Gly Gln Val Val Cys Ser Val
50 55 60
Ala Leu Phe Phe Tyr Phe Arg Ala Gln Met Asp Pro Asn Arg Ile Ser
65 70 75 80
Glu Asp Gly Thr His Cys Ile Tyr Arg Ile Leu Arg Leu His Glu Asn
85 90 95
Ala Asp Phe Gln Asp Thr Thr Leu Glu Ser Gln Asp Thr Lys Leu Ile
100 105 110
Pro Asp Ser Cys Arg Arg Ile Lys Gln Ala Phe Gln Gly Ala Val Gln
115 120 125
Lys Glu Leu Gln His Ile Val Gly Ser Gln His Ile Arg Ala Glu Lys
130 135 140
Ala Met Val Asp Gly Ser Trp Leu Asp Leu Ala Lys Arg Ser Lys Leu
145 150 155 160
Glu Ala Gln Pro Phe Ala His Leu Thr Ile Asn Ala Thr Asp Ile Pro
165 170 175
Ser Gly Ser His Lys Val Ser Leu Ser Ser Trp Tyr His Asp Arg Gly
180 185 190
Trp Ala Lys Ile Ser Asn Met Thr Phe Ser Asn Gly Lys Leu Ile Val
195 200 205
Asn Gln Asp Gly Phe Tyr Tyr Leu Tyr Ala Asn Ile Cys Phe Arg His
210 215 220
His Glu Thr Ser Gly Asp Leu Ala Thr Glu Tyr Leu Gln Leu Met Val
225 230 235 240
Tyr Val Thr Lys Thr Ser Ile Lys Ile Pro Ser Ser His Thr Leu Met
245 250 255
Lys Gly Gly Ser Thr Lys Tyr Trp Ser Gly Asn Ser Glu Phe His Phe
260 265 270
Tyr Ser Ile Asn Val Gly Gly Phe Phe Lys Leu Arg Ser Gly Glu Glu
275 280 285
Ile Ser Ile Glu Val Ser Asn Pro Ser Leu Leu Asp Pro Asp Gln Asp
290 295 300
Ala Thr Tyr Phe Gly Ala Phe Lys Val Arg Asp Ile Asp
305 310 315
<210>268
<211>244
<212>PRT
<213>智人(Homo sapiens)
<400>268
Met Asp Pro Asn Arg Ile Ser Glu Asp Gly Thr His Cys Ile Tyr Arg
1 5 10 15
Ile Leu Arg Leu His Glu Asn Ala Asp Phe Gln Asp Thr Thr Leu Glu
20 25 30
Ser Gln Asp Thr Lys Leu Ile Pro Asp Ser Cys Arg Arg Ile Lys Gln
35 40 45
Ala Phe Gln Gly Ala Val Gln Lys Glu Leu Gln His Ile Val Gly Ser
50 55 60
Gln His Ile Arg Ala Glu Lys Ala Met Val Asp Gly Ser Trp Leu Asp
65 70 75 80
Leu Ala Lys Arg Ser Lys Leu Glu Ala Gln Pro Phe Ala His Leu Thr
85 90 95
Ile Asn Ala Thr Asp Ile Pro Ser Gly Ser His Lys Val Ser Leu Ser
100 105 110
Ser Trp Tyr His Asp Arg Gly Trp Ala Lys Ile Ser Asn Met Thr Phe
115 120 125
Ser Asn Gly Lys Leu Ile Val Asn Gln Asp Gly Phe Tyr Tyr Leu Tyr
130 135 140
Ala Asn Ile Cys Phe Arg His His Glu Thr Ser Gly Asp Leu Ala Thr
145 150 155 160
Glu Tyr Leu Gln Leu Met Val Tyr Val Thr Lys Thr Ser Ile Lys Ile
165 170 175
Pro Ser Ser His Thr Leu Met Lys Gly Gly Ser Thr Lys Tyr Trp Ser
180 185 190
Gly Asn Ser Glu Phe His Phe Tyr Ser Ile Asn Val Gly Gly Phe Phe
195 200 205
Lys Leu Arg Ser Gly Glu Glu Ile Ser Ile Glu Val Ser Asn Pro Ser
210 215 220
Leu Leu Asp Pro Asp Gln Asp Ala Thr Tyr Phe Gly Ala Phe Lys Val
225 230 235 240
Arg Asp Ile Asp
<210>269
<21l>317
<212>PRT
<213>智人(Homo sapiens)
<400>269
Met Arg Arg Ala Ser Arg Asp Tyr Thr Lys Tyr Leu Arg Gly Ser Glu
1 5 10 15
Glu Met Gly Gly Gly Pro Gly Ala Pro His Glu Gly Pro Leu His Ala
20 25 30
Pro Pro Pro Pro Ala Pro His Gln Pro Pro Ala Ala Ser Arg Ser Met
35 40 45
Phe Val Ala Leu Leu Gly Leu Gly Leu Gly Gln Val Val Cys Ser Val
50 55 60
Ala Leu Phe Phe Tyr Phe Arg Ala Gln Met Asp Pro Asn Arg Ile Ser
65 70 75 80
Glu Asp Gly Thr His Cys Ile Tyr Arg Ile Leu Arg Leu His Glu Asn
85 90 95
Ala Asp Phe Gln Asp Thr Thr Leu Glu Ser Gln Asp Thr Lys Leu Ile
100 105 110
Pro Asp Ser Cys Arg Arg Ile Lys Gln Ala Phe Gln Gly Ala Val Gln
115 120 125
Lys Glu Leu Gln His Ile Val Gly Ser Gln His Ile Arg Ala Glu Lys
130 135 140
Ala Met Val Asp Gly Ser Trp Leu Asp Leu Ala Lys Arg Ser Lys Leu
145 150 155 160
Glu Ala Gln Pro Phe Ala His Leu Thr Ile Asn Ala Thr Asp Ile Pro
165 170 175
Ser Gly Ser His Lys Val Ser Leu Ser Ser Trp Tyr His Asp Arg Gly
180 185 190
Trp Ala Lys Ile Ser Asn Met Thr Phe Ser Asn Gly Lys Leu Ile Val
195 200 205
Asn Gln Asp Gly Phe Tyr Tyr Leu Tyr Ala Asn Ile Cys Phe Arg His
210 215 220
His Glu Thr Ser Gly Asp Leu Ala Thr Glu Tyr Leu Gln Leu Met Val
225 230 235 240
Tyr Val Thr Lys Thr Ser Ile Lys Ile Pro Ser Ser His Thr Leu Met
245 250 255
Lys Gly Gly Ser Thr Lys Tyr Trp Ser Gly Asn Ser Glu Phe His Phe
260 265 270
Tyr Ser Ile Asn Val Gly Gly Phe Phe Lys Leu Arg Ser Gly Glu Glu
275 280 285
Ile Ser Ile Glu Val Ser Asn Pro Ser Leu Leu Asp Pro Asp Gln Asp
290 295 300
Ala Thr Tyr Phe Gly Ala Phe Lys Val Arg Asp Ile Asp
305 310 315
<210>270
<211>316
<212>PRT
<213>小鼠(Mus musculus)
<400>270
Met Arg Arg Ala Ser Arg Asp Tyr Gly Lys Tyr Leu Arg Ser Ser Glu
1 5 10 15
Glu Met Gly Ser Gly Pro Gly Val Pro His Glu Gly Pro Leu His Pro
20 25 30
Ala Pro Ser Ala Pro Ala Pro Ala Pro Pro Pro Ala Ala Ser Arg Ser
35 40 45
Met Phe Leu Ala Leu Leu Gly Leu Gly Leu Gly Gln Val Val Cys Ser
50 55 60
Ile Ala Leu Phe Leu Tyr Phe Arg Ala Gln Met Asp Pro Asn Arg Ile
65 70 75 80
Ser Glu Asp Ser Thr His Cys Phe Tyr Arg Ile Leu Arg Leu His Glu
85 90 95
Asn Ala Gly Leu Gln Asp Ser Thr Leu Glu Ser Glu Asp Thr Leu Pro
100 105 110
Asp Ser Cys Arg Arg Met Lys Gln Ala Phe Gln Gly Ala Val Gln Lys
115 120 125
Glu Leu Gln His Ile Val Gly Pro Gln Arg Phe Ser Gly Ala Pro Ala
130 135 140
Met Met Glu Gly Ser Trp Leu Asp Val Ala Gln Arg Gly Lys Pro Glu
145 150 155 160
Ala Gln Pro Phe Ala His Leu Thr Ile Asn Ala Ala Ser Ile Pro Ser
165 170 175
Gly Ser His Lys Val Thr Leu Ser Ser Trp Tyr His Asp Arg Gly Trp
180 185 190
Ala Lys Ile Ser Asn Met Thr Leu Ser Asn Gly Lys Leu Arg Val Asn
195 200 205
Gln Asp Gly Phe Tyr Tyr Leu Tyr Ala Asn Ile Cys Phe Arg His His
210 215 220
Glu Thr Ser Gly Ser Val Pro Thr Asp Tyr Leu Gln Leu Met Val Tyr
225 230 235 240
Val Val Lys Thr Ser Ile Lys Ile Pro Ser Ser His Asn Leu Met Lys
245 250 255
Gly Gly Ser Thr Lys Asn Trp Ser Gly Asn Ser Glu Phe His Phe Tyr
260 265 270
Ser Ile Asn Val Gly Gly Phe Phe Lys Leu Arg Ala Gly Glu Glu Ile
275 280 285
Ser Ile Gln Val Ser Asn Pro Ser Leu Leu Asp Pro Asp Gln Asp Ala
290 295 300
Thr Tyr Phe Gly Ala Phe Lys Val Gln Asp Ile Asp
305 310 315
<210>271
<211>316
<212>PRT
<213>小鼠(Mus musculus)
<400>271
Met Arg Arg Ala Ser Arg Asp Tyr Gly Lys Tyr Leu Arg Ser Ser Glu
1 5 10 15
Glu Met Gly Ser Gly Pro Gly Val Pro His Glu Gly Pro Leu His Pro
20 25 30
Ala Pro Ser Ala Pro Ala Pro Ala Pro Pro Pro Ala Ala Ser Arg Ser
35 40 45
Met Phe Leu Ala Leu Leu Gly Leu Gly Leu Gly Gln Val Val Cys Ser
50 55 60
Ile Ala Leu Phe Leu Tyr Phe Arg Ala Gln Met Asp Pro Asn Arg Ile
65 70 75 80
Ser Glu Asp Ser Thr His Cys Phe Tyr Arg Ile Leu Arg Leu His Glu
85 90 95
Asn Ala Gly Leu Gln Asp Ser Thr Leu Glu Ser Glu Asp Thr Leu Pro
100 105 110
Asp Ser Cys Arg Arg Met Lys Gln Ala Phe Gln Gly Ala Val Gln Lys
115 120 125
Glu Leu Gln His Ile Val Gly Pro Gln Arg Phe Ser Gly Ala Pro Ala
130 135 140
Met Met Glu Gly Ser Trp Leu Asp Val Ala Gln Arg Gly Lys Pro Glu
145 150 155 160
Ala Gln Pro Phe Ala His Leu Thr Ile Asn Ala Ala Ser Ile Pro Ser
165 170 175
Gly Ser His Lys Val Thr Leu Ser Ser Trp Tyr His Asp Arg Gly Trp
180 185 190
Ala Lys Ile Ser Asn Met Thr Leu Ser Asn Gly Lys Leu Arg Val Asn
195 200 205
Gln Asp Gly Phe Tyr Tyr Leu Tyr Ala Asn Ile Cys Phe Arg His His
210 215 220
Glu Thr Ser Gly Ser Val Pro Thr Asp Tyr Leu Gln Leu Met Val Tyr
225 230 235 240
Val Val Lys Thr Ser Ile Lys Ile Pro Ser Ser His Asn Leu Met Lys
245 250 255
Gly Gly Ser Thr Lys Asn Trp Ser Gly Asn Ser Glu Phe His Phe Tyr
260 265 270
Ser Ile Asn Val Gly Gly Phe Phe Lys Leu Arg Ala Gly Glu Glu Ile
275 280 285
Ser Ile Gln Val Ser Asn Pro Ser Leu Leu Asp Pro Asp Gln Asp Ala
290 295 300
Thr Tyr Phe Gly Ala Phe Lys Val Gln Asp Ile Asp
305 310 315
<210>272
<211>401
<212>PRT
<213>智人(Homo sapiens)
<400>272
Met Asn Lys Leu Leu Cys Cys Ala Leu Val Phe Leu Asp Ile Ser Ile
1 5 10 15
Lys Trp Thr Thr Gln Glu Thr Phe Pro Pro Lys Tyr Leu His Tyr Asp
20 25 30
Glu Glu Thr Ser His Gln Leu Leu Cys Asp Lys Cys Pro Pro Gly Thr
35 40 45
Tyr Leu Lys Gln His Cys Thr Ala Lys Trp Lys Thr Val Cys Ala Pro
50 55 60
Cys Pro Asp His Tyr Tyr Thr Asp Ser Trp His Thr Ser Asp Glu Cys
65 70 75 80
Leu Tyr Cys Ser Pro Val Cys Lys Glu Leu Gln Tyr Val Lys Gln Glu
85 90 95
Cys Asn Arg Thr His Asn Arg Val Cys Glu Cys Lys Glu Gly Arg Tyr
100 105 110
Leu Glu Ile Glu Phe Cys Leu Lys His Arg Ser Cys Pro Pro Gly Phe
115 120 125
Gly Val Val Gln Ala Gly Thr Pro Glu Arg Asn Thr Val Cys Lys Arg
130 135 140
Cys Pro Asp Gly Phe Phe Ser Asn Glu Thr Ser Ser Lys Ala Pro Cys
145 150 155 160
Arg Lys His Thr Asn Cys Ser Val Phe Gly Leu Leu Leu Thr Gln Lys
165 170 175
Gly Asn Ala Thr His Asp Asn Ile Cys Ser Gly Asn Ser Glu Ser Thr
180 185 190
Gln Lys Cys Gly Ile Asp Val Thr Leu Cys Glu Glu Ala Phe Phe Arg
195 200 205
Phe Ala Val Pro Thr Lys Phe Thr Pro Asn Trp Leu Ser Val Leu Val
210 215 220
Asp Asn Leu Pro Gly Thr Lys Val Asn Ala Glu Ser Val Glu Arg Ile
225 230 235 240
Lys Arg Gln His Ser Ser Gln Glu Gln Thr Phe Gln Leu Leu Lys Leu
245 250 255
Trp Lys His Gln Asn Lys Asp Gln Asp Ile Val Lys Lys Ile Ile Gln
260 265 270
Asp Ile Asp Leu Cys Glu Asn Ser Val Gln Arg His Ile Gly His Ala
275 280 285
Asn Leu Thr Phe Glu Gln Leu Arg Ser Leu Met Glu Ser Leu Pro Gly
290 295 300
Lys Lys Val Gly Ala Glu Asp Ile Glu Lys Thr Ile Lys Ala Cys Lys
305 310 315 320
Pro Ser Asp Gln Ile Leu Lys Leu Leu Ser Leu Trp Arg Ile Lys Asn
325 330 335
Gly Asp Gln Asp Thr Leu Lys Gly Leu Met His Ala Leu Lys His Ser
340 345 350
Lys Thr Tyr His Phe Pro Lys Thr Val Thr Gln Ser Leu Lys Lys Thr
355 360 365
Ile Arg Phe Leu His Ser Phe Thr Met Tyr Lys Leu Tyr Gln Lys Leu
370 375 380
Phe Leu Glu Met Ile Gly Asn Gln Val Gln Ser Val Lys Ile Ser Cys
385 390 395 400
Leu
<210>273
<211>1047
<212>DNA
<213>智人(Homo sapiens)
<400>273
cgaattcccc tatcacctaa gtgtgggcta atgtaacaaa gagggatttc acctacatcc 60
attcagtcag tctttggggg tttaaagaaa ttccaaagag tcatcagaag aggaaaaatg 120
aaggtaatgt tttttcagac aggtaaagtc tttgaaaata tgtgtaatat gtaaaacatt 180
ttgacacccc cataatattt ttccagaatt aacagtataa attgcatctc ttgttcaaga 240
gttccctatc actctcttta atcactactc acagtaacct caactcctgc cacaatgtac 300
aggatgcaac tcctgtcttg cattgcacta agtcttgcac ttgtcacaaa cagtgcacct 360
acttcaagtt ctacaaagaa aacacagcta caactggagc atttactgct ggatttacag 420
atgattttga atggaattaa taattacaag aatcccaaac tcaccaggat gctcacattt 480
aagttttaca tgcccaagaa ggccacagaa ctgaaacatc ttcagtgtct agaagaagaa 540
ctcaaacctc tggaggaagt gctaaattta gctcaaagca aaaactttca cttaagaccc 600
agggacttaa tcagcaatat caacgtaata gttctggaac taaagggatc tgaaacaaca 660
ttcatgtgtg aatatgctga tgagacagca accattgtag aatttctgaa cagatggatt 720
accttttgtc aaagcatcat ctcaacactg acttgataat taagtgcttc ccacttaaaa 780
catatcaggc cttctattta tttaaatatt taaattttat atttattgtt gaatgtatgg 840
tttgctacct attgtaacta ttattcttaa tcttaaaact ataaatatgg atcttttatg 900
attctttttg taagccctag gggctctaaa atggtttcac ttatttatcc caaaatattt 960
attattatgt tgaatgttaa atatagtatc tatgtagatt ggttagtaaa actatttaat 1020
aaatttgata aatataaaaa aaaaaaa 1047
<210>274
<211>939
<212>DNA
<213>小鼠(Mus musculus)
<400>274
atcacccttg ctaatcactc ctcacagtga cctcaagtcc tgcaggcatg tacagcatgc 60
agctcgcatc ctgtgtcaca ttgacacttg tgctccttgt caacagcgca cccacttcaa 120
gctccacttc aagctctaca gcggaagcac agcagcagea gcagcagcag cagcagcagc 180
agcagcacct ggagcagctg ttgatggacc tacaggagct cctgagcagg atggagaatt 240
acaggaacct gaaactcccc aggatgctca ccttcaaatt ttacttgccc aagcaggcca 300
cagaattgaa agatcttcag tgcctagaag atgaacttgg acctctgcgg catgttctgg 360
atttgactca aagcaaaagc tttcaattgg aagatgctga gaatttcatc agcaatatca 420
gagtaactgt tgtaaaacta aagggctctg acaacacatt tgagtgccaa ttcgatgatg 480
agtcagcaac tgtggtggac tttctgagga gatggatagc cttctgtcaa agcatcatct 540
caacaagccc tcaataacta tgtacctcct gcttacaaca cataaggctc tctatttatt 600
taaatattta actttaattt atttttggat gtattgttta ctatcttttg taactactag 660
tcttcagatg ataaatatgg atctttaaag attctttttg taagccccaa gggctcaaaa 720
atgttttaaa ctatttatct gaaattattt attatattga attgttaaat atcatgtgta 780
ggtagactca ttaataaaag tatttagatg attcaaatat aaataagctc agatgtctgt 840
catttttagg acagcacaaa gtaagcgcta aaataacttc tcagttattc ctgtgaactc 900
tatgttaatc agtgttttca agaaataaag ctctcctct 939
<210>275
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>275
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
20 25 30
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu asn Gly Ile
35 40 45
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe
50 55 60
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
65 70 75 80
Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys
85 90 95
Asn Phe His Leu Arg Pro Arg Asp Leu lle Ser Asn Ile Asn Val Ile
100 105 110
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
115 120 125
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe
130 135 140
Cys Gln Ser Ile Ile Ser Thr Leu Thr
145 150
<210>276
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>276
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
20 25 30
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile
35 40 45
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe
50 55 60
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
65 70 75 80
Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys
85 90 95
Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile
100 105 110
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
115 120 125
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe
130 135 140
Cys Gln Ser Ile Ile Ser Thr Leu Thr
145 150
<210>277
<211>156
<212>PRT
<213>智人(Homo sapiens)
<400>277
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ile Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Lys Lys
20 25 30
Thr Gln Leu Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu
35 40 45
Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr
50 55 60
Phe Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys Gln Leu Gln
65 70 75 80
Cys Leu Glu Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala
85 90 95
Gln Ser Lys Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile
100 105 110
Asn Val Ile Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys
115 120 125
Glu Tyr Ala Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp
130 135 140
Ile Thr Phe Cys Gln Ser Ile Ile Ser Thr Leu Thr
145 150 155
<210>278
<211>139
<212>PRT
<213>智人(Homo sapiens)
<220>
<221>MOD_RES
<222>(29)
<223>Variable amino acid
<220>
<221>MOD_RES
<222>(42)
<223>Variable amino acid
<400>278
Gln Leu Leu Phe Cys Ile Ala Leu Ser Leu Ala Leu Val Pro Asn Ser
1 5 10 15
Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Xaa Leu Glu His
20 25 30
Leu Leu Leu Asp Leu Gln Met Ile Leu Xaa Gly Ile Asn Asn Tyr Lys
35 40 45
Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys
50 55 60
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys
65 70 75 80
Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
85 90 95
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
100 105 110
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
115 120 125
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr
130 135
<210>279
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>279
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Leu Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
20 25 30
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile
35 40 45
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe
50 55 60
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
65 70 75 80
Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys
85 90 95
Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile
100 105 110
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
115 120 125
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe
130 135 140
Cys Gln Ser Ile Ile Ser Thr Leu Thr
145 150
<210>280
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>280
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Ala Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
20 25 30
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile
35 40 45
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe
50 55 60
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
65 70 75 80
Glu Glu Leu Lys Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys
85 90 95
Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile
100 105 110
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
115 120 125
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Tle Thr Phe
130 135 140
Cys Gln Ser Ile Ile Ser Thr Leu Thr
145 150
<210>281
<211>133
<212>PRT
<213>智人(Homo sapiens)
<400>281
Met Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 10 15
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
20 25 30
Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys
35 40 45
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys
50 55 60
Pro Leu Glu Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
65 70 75 80
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
85 90 95
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Ser Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
<210>282
<211>38
<212>PRT
<213>智人(Homo sapiens)
<400>282
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
20 25 30
Gln Leu Glu His Leu Leu
35
<210>283
<211>133
<212>PRT
<213>智人(Homo sapiens)
<400>283
Met Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu Gln Leu Glu His
1 5 10 15
Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys
20 25 30
Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys
35 40 45
Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu Glu Glu Leu Lys
50 55 60
Pro Leu Lys Glu Val Leu Asn Leu Ala Gln Ser Lys Asn Phe His Leu
65 70 75 80
Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile Val Leu Glu Leu
85 90 95
Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala Asp Glu Thr Ala
100 105 110
Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe Ser Gln Ser Ile
115 120 125
Ile Ser Thr Leu Thr
130
<210>284
<211>37
<212>PRT
<213>智人(Homo sapiens)
<400>284
Gln Met Ile Leu Asn Gly Ile Asn Asn Tyr Lys Asn Pro Lys Leu Thr
1 5 10 15
Arg Met Leu Thr Phe Lys Phe Tyr Met Pro Lys Lys Ala Thr Glu Leu
20 25 30
Lys His Leu Gln Cys
35
<210>285
<211>150
<212>PRT
<213>智人(Homo sapiens)
<400>285
Met Tyr Arg Met Gln Leu Leu Ser Cys Ile Ala Leu Ser Leu Ala Leu
1 5 10 15
Val Thr Asn Ser Ala Pro Thr Ser Ser Ser Thr Lys Lys Thr Gln Leu
20 25 30
Gln Leu Glu His Leu Leu Leu Asp Leu Gln Met Ile Leu Asn Gly Ile
35 40 45
Asn Asn Tyr Lys Asn Pro Lys Leu Thr Arg Met Leu Thr Phe Lys Phe
50 55 60
Tyr Met Pro Lys Lys Ala Thr Glu Leu Lys His Leu Gln Cys Leu Glu
65 70 75 80
Glu Glu Leu Lys Pro Leu Glu alu Val Leu Asn Leu Ala Gln Ser Lys
85 90 95
Asn Phe His Leu Arg Pro Arg Asp Leu Ile Ser Asn Ile Asn Val Ile
100 105 110
Val Leu Glu Leu Lys Gly Ser Glu Thr Thr Phe Met Cys Glu Tyr Ala
115 120 125
Asp Glu Thr Ala Thr Ile Val Glu Phe Leu Asn Arg Trp Ile Thr Phe
130 135 140
Cys Gln Ser Ile Ile Ser
145 150
<210>286
<211>169
<212>PRT
<213>小鼠(Mus musculus)
<400>286
Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu
1 5 10 15
Leu Val Asn Ser Ala Pro Thr Ser Ser Ser Thr Ser Ser Ser Thr Ala
20 25 30
Glu Ala Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln His Leu
35 40 45
Glu Gln Leu Leu Met Asp Leu Gln Glu Leu Leu Ser Arg Met Glu Asn
50 55 60
Tyr Arg Asn Leu Lys Leu Pro Arg Met Leu Thr Phe Lys Phe Tyr Leu
65 70 75 80
Pro Lys Gln Ala Thr Glu Leu Lys Asp Leu Gln Cys Leu Glu Asp Glu
85 90 95
Leu Gly Pro Leu Arg His Val Leu Asp Leu Thr Gln Ser Lys Ser Phe
100 105 110
Gln Leu Glu Asp Ala Glu Asn Phe Ile Ser Asn Ile Arg Val Thr Val
115 120 125
Val Lys Leu Lys Gly Ser Asp Asn Thr Phe Glu Cys Gln Phe Asp Asp
130 135 140
Glu Ser Ala Thr Val Val Asp Phe Leu Arg Arg Trp Ile Ala Phe Cys
145 150 155 160
Gln Ser Ile Ile Ser Thr Ser Pro Gln
165
<210>287
<211>169
<212>PRT
<213>小鼠(Mus musculus)
<400>287
Met Tyr Ser Met Gln Leu Ala Ser Cys Val Thr Leu Thr Leu Val Leu
1 5 10 15
Leu Val Asn Ser Ala Pro Thr Ser Ser Ser Thr Ser Ser Ser Thr Ala
20 25 30
Glu Ala Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln His Leu
35 40 45
Glu Gln Leu Leu Met Asp Leu Gln Glu Leu Leu Ser Arg Met Glu Asn
50 55 60
Tyr Arg Asn Leu Lys Leu Pro Arg Met Leu Thr Phe Lys Phe Tyr Leu
65 70 75 80
Pro Lys Gln Ala Thr Glu Leu Lys Asp Leu Gln Cys Leu Glu Asp Glu
85 90 95
Leu Gly Pro Leu Arg His Val Leu Asp Leu Thr Gln Ser Lys Ser Phe
100 105 110
Gln Leu Glu Asp Ala Glu Asn Phe Ile Ser Asn Ile Arg Val Thr Val
115 120 125
Val Lys Leu Lys Gly Ser Asp Asn Thr Phe Glu Cys Gln Phe Asp Asp
130 135 140
Glu Ser Ala Thr Val Val Asp Phe Leu Arg Arg Trp Ile Ala Phe Cys
145 150 155 160
Gln Ser Ile Ile Ser Thr Ser Pro Gln
165
<210>288
<211>921
<212>DNA
<213>智人(Homo sapiens)
<400>288
ttctatgcaa agcaaaaagc cagcagcagc cccaagctga taagattaat ctaaagagca 60
aattatggtg taatttccta tgctgaaact ttgtagttaa ttttttaaaa aggtttcatt 120
ttcctattgg tctgatttca caggaacatt ttacctgttt gtgaggcatt ttttctcctg 180
gaagagaggt gctgattggc cccaagtgac tgacaatctg gtgtaacgaa aatttccaat 240
gtaaactcat tttccctcgg tttcagcaat tttaaatcta tatatagaga tatctttgtc 300
agcattgcat cgttagcttc tcctgataaa ctaattgcct cacattgtca ctgcaaatcg 360
acacctatta atgggtctca cctcccaact gcttccccct ctgttcttcc tgctagcatg 420
tgccggcaac tttgtccacg gacacaagtg cgatatcacc ttacaggaga tcatcaaaac 480
tttgaacagc ctcacagagc agaagactct gtgcaccgag ttgaccgtaa cagacatctt 540
tgctgcctcc aagaacacaa ctgagaagga aaccttctgc agggctgcga ctgtgctccg 600
gcagttctac agccaccatg agaaggacac tcgctgcctg ggtgcgactg cacagcagtt 660
ccacaggcac aagcagctga tccgattcct gaaacggctc gacaggaacc tctggggcct 720
ggcgggcttg aattcctgtc ctgtgaagga agccaaccag agtacgttgg aaaacttctt 780
ggaaaggcta aagacgatca tgagagagaa atattcaaag tgttcgagct gaatatttta 840
atttatgagt ttttgatagc tttatttttt aagtatttat atatttataa ctcatcataa 900
aataaagtat atatagaatc t 921
<210>289
<211>873
<212>DNA
<213>智人(Homo sapiens)
<400>289
ttctatgcaa agcaaaaagc cagcagcagc cccaagctga taagattaat ctaaagagca 60
aattatggtg taatttccta tgctgaaact ttgtagttaa ttttttaaaa aggtttcatt 120
ttcctattgg tctgatttca caggaacatt ttacctgttt gtgaggcatt ttttctcctg 180
gaagagaggt gctgattggc cccaagtgac tgacaatctg gtgtaacgaa aatttccaat 240
gtaaactcat tttccctcgg tttcagcaat tttaaatcta tatatagaga tatctttgtc 300
agcattgcat cgttagcttc tcctgataaa ctaattgcct cacattgtca ctgcaaatcg 360
acacctatta atgggtctca cctcccaact gcttccccct ctgttcttcc tgctagcatg 420
tgccggcaac tttgtccacg gacacaagtg cgatatcacc ttacaggaga tcatcaaaac 480
tttgaacagc ctcacagagc agaagaacac aactgagaag gaaaccttct gcagggctgc 540
gactgtgctc cggcagttct acagccacca tgagaaggac actcgctgcc tgggtgcgac 600
tgcacagcag ttccacaggc acaagcagct gatccgattc ctgaaacggc tcgacaggaa 660
cctctggggc ctggcgggct tgaattcctg tcctgtgaag gaagccaacc agagtacgtt 720
ggaaaacttc ttggaaaggc taaagacgat catgagagag aaatattcaa agtgttcgag 780
ctgaatattt taatttatga gtttttgata gctttatttt ttaagtattt atatatttat 840
aactcatcat aaaataaagt atatatagaa tct 873
<210>290
<211>605
<212>DNA
<213>小鼠(Mus musculus)
<400>290
ggatccccgg gcagagctgg ggggggattt gttagcatct cttgataaac ttaattgtct 60
ctcgtcactg acggcacaga gctattgatg ggtctcaacc cccagctagt tgtcatcctg 120
ctcttctttc tcgaatgtac caggagccat atccacggat gcgacaaaaa tcacttgaga 180
gagatcatcg gcattttgaa cgaggtcaca ggagaaggga cgccatgcac ggagatggat 240
gtgccaaacg tcctcacagc aacgaagaac accacagaga gtgagctcgt ctgtagggct 300
tccaaggtgc ttcgcatatt ttatttaaaa catgggaaaa ctccatgctt gaagaagaac 360
tctagtgttc tcatggagct gcagagactc tttcgggctt ttcgatgcct ggattcatcg 420
ataagctgca ccatgaatga gtccaagtcc acatcactga aagacttcct ggaaagccta 480
aagagcatca tgcaaatgga ttactcgtag tactgagcca ccatgcttta acttatgaat 540
ttttaatggt tttattttaa tatttatata tttataattc ataaaataaa atatttgtat 600
aatgt 605
<210>291
<211>137
<212>PRT
<213>智人(Homo sapiens)
<400>291
Met Gly Leu Thr Ser Gln Leu Leu Pro Pro Leu Phe Phe Leu Leu Ala
1 5 10 15
Cys Ala Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln
20 25 30
Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Asn Thr Thr
35 40 45
Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr
50 55 60
Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln
65 70 75 80
Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg
85 90 95
Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala
100 105 110
Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met
115 120 125
Arg Glu Lys Tyr Ser Lys Cys Ser Ser
130 135
<210>292
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>292
Met Gly Leu Thr Ser Gln Leu Leu Pro Pro Leu Phe Phe Leu Leu Ala
1 5 10 15
Cys Ala Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln
20 25 30
Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys
35 40 45
Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr
50 55 60
Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr
65 70 75 80
Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln
85 90 95
Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg
100 105 110
Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala
115 120 125
Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met
130 135 140
Arg Glu Lys Tyr Ser Lys Cys Ser Ser
145 150
<210>293
<211>137
<212>PRT
<213>智人(Homo sapiens)
<400>293
Met Gly Leu Thr Ser Gln Leu Leu Pro Pro Leu Phe Phe Leu Leu Ala
1 5 10 15
Cys Ala Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln
20 25 30
Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Asn Thr Thr
35 40 45
Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr
50 55 60
Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln
65 70 75 80
Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg
85 90 95
Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala
100 105 110
Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met
115 120 125
Arg Glu Lys Tyr Ser Lys Cys Ser Ser
130 135
<210>294
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>294
Met Gly Leu Thr Ser Gln Leu Leu Pro Pro Leu Phe Phe Leu Leu Ala
1 5 10 15
Cys Ala Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln
20 25 30
Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys
35 40 45
Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr
50 55 60
Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr
65 70 75 80
Ser His Arg Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln
85 90 95
Phe His Arg His Lys Gln Leu Ile Arg Phe Leu Lys Arg Leu Asp Arg
100 105 110
Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala
115 120 125
Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met
130 135 140
Arg Glu Lys Tyr Ser Lys Cys Ser Ser
145 150
<210>295
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>295
Met Gly Leu Thr Ser Gln Leu Leu Pro Pro Leu Phe Phe Leu Leu Ala
1 5 10 15
Cys Ala Gly Asn Phe Val His Gly His Lys Cys Asp Ile Thr Leu Gln
20 25 30
Glu Ile Ile Lys Thr Leu Asn Ser Leu Thr Glu Gln Lys Thr Leu Cys
35 40 45
Thr Glu Leu Thr Val Thr Asp Ile Phe Ala Ala Ser Lys Asn Thr Thr
50 55 60
Glu Lys Glu Thr Phe Cys Arg Ala Ala Thr Val Leu Arg Gln Phe Tyr
65 70 75 80
Ser His His Glu Lys Asp Thr Arg Cys Leu Gly Ala Thr Ala Gln Gln
85 90 95
Phe His Arg His Lys Gln Pro Ile Arg Phe Leu Lys Arg Leu Asp Arg
100 105 110
Asn Leu Trp Gly Leu Ala Gly Leu Asn Ser Cys Pro Val Lys Glu Ala
115 120 125
Asn Gln Ser Thr Leu Glu Asn Phe Leu Glu Arg Leu Lys Thr Ile Met
130 135 140
Arg Glu Lys Tyr Ser Lys Cys Ser Ser
145 150
<210>296
<211>114
<212>PRT
<213>智人(Homo sapiens)
<400>296
Gly His Lys Cys Asp Ile Thr Leu Gln Glu Ile Ile Lys Thr Leu Asn
1 5 10 15
Ser Leu Thr Glu Gln Lys Asn Thr Thr Glu Lys Glu Thr Phe Cys Arg
20 25 30
Ala Ala Thr Val Leu Arg Gln Phe Tyr Ser His His Glu Lys Asp Thr
35 40 45
Arg Cys Leu Gly Ala Thr Ala Gln Gln Phe His Gly His Lys Gln Leu
50 55 60
Ile Arg Phe Leu Lys Arg Leu Asp Arg Asn Leu Trp Gly Leu Ala Gly
65 70 75 80
Leu Asn Ser Cys Pro Val Lys Glu Ala Asn Gln Ser Thr Leu Glu Asn
85 90 95
Phe Leu Glu Arg Leu Lys Thr Ile Met Arg Glu Lys Tyr Ser Lys Cys
100 105 110
Ser Ser
<210>297
<211>140
<212>PRT
<213>小鼠(Mus musculus)
<400>297
Met Gly Leu Asn Pro Gln Leu Val Val Ile Leu Leu Phe Phe Leu Glu
1 5 10 15
Cys Thr Arg Ser His Ile His Gly Cys Asp Lys Asn His Leu Arg Glu
20 25 30
Ile Ile Gly Ile Leu Asn Glu Val Thr Gly Glu Gly Thr Pro Cys Thr
35 40 45
Glu Met Asp Val Pro Asn Val Leu Thr Ala Thr Lys Asn Thr Thr Glu
50 55 60
Ser Glu Leu Val Cys Arg Ala Ser Lys Val Leu Arg Ile Phe Tyr Leu
65 70 75 80
Lys His Gly Lys Thr Pro Cys Leu Lys Lys Asn Ser Ser Val Leu Met
85 90 95
Glu Leu Gln Arg Leu Phe Arg Ala Phe Arg Cys Leu Asp Ser Ser Ile
100 105 110
Ser Cys Thr Met Asn Glu Ser Lys Ser Thr Ser Leu Lys Asp Phe Leu
115 120 125
Glu Ser Leu Lys Ser Ile Met Gln Met Asp Tyr Ser
130 135 140
<210>298
<211>140
<212>PRT
<213>小鼠(Mus musculus)
<400>298
Met Gly Leu Asn Pro Gln Leu Val Val Ile Leu Leu Phe Phe Leu Glu
1 5 10 15
Cys Thr Arg Ser His Ile His Gly Cys Asp Lys Asn His Leu Arg Glu
20 25 30
Ile Ile Gly Ile Leu Asn Glu Val Thr Gly Glu Gly Thr Pro Cys Thr
35 40 45
Glu Met Asp Val Pro Asn Val Leu Thr Ala Thr Lys Asn Thr Thr Glu
50 55 60
Ser Glu Leu Val Cys Arg Ala Ser Lys Val Leu Arg Ile Phe Tyr Leu
65 70 75 80
Lys His Gly Lys Thr Pro Cys Leu Lys Lys Asn Ser Ser Val Leu Met
85 90 95
Glu Leu Gln Arg Leu Phe Arg Ala Phe Arg Cys Leu Asp Ser Ser Ile
100 105 110
Ser Cys Thr Met Asn Glu Ser Lys Ser Thr Ser Leu Lys Asp Phe Leu
115 120 125
Glu Ser Leu Lys Ser lle Met Gln Met Asp Tyr Ser
130 135 140
<210>299
<211>140
<212>PRT
<213>小鼠(Mus musculus)
<400>299
Met Gly Leu Asn Pro Gln Leu Val Val Ile Leu Leu Phe Phe Leu Glu
1 5 10 15
Cys Thr Arg Ser His Ile His Gly Cys Asp Lys Asn His Leu Arg Glu
20 25 30
Ile Ile Gly Ile Leu Asn Glu Val Thr Gly Glu Gly Thr Pro Cys Thr
35 40 45
Glu Met Asp Val Pro Asn Val Leu Thr Ala Thr Lys Asn Thr Thr Glu
50 55 60
Ser Glu Leu Val Cys Arg Ala Ser Lys Val Leu Arg Ile Phe Tyr Leu
65 70 75 80
Lys His Gly Lys Thr Pro Cys Leu Lys Lys Asn Ser Ser Val Leu Met
85 90 95
Glu Leu Gln Arg Leu Phe Arg Ala Phe Arg Cys Leu Asp Ser Ser Ile
100 105 110
Ser Cys Thr Met Asn Glu Ser Lys Ser Thr Ser Leu Lys Asp Phe Leu
115 120 125
Glu Ser Leu Lys Ser IIe Met Gln Met Asp Tyr Ser
130 135 140
<210>300
<211>1282
<212>DNA
<213>智人(Homo sapiens)
<400>300
aagccaccca gcctatgcat ccgctcctca atcctctcct gttggcactg ggcctcatgg 60
cgcttttgtt gaccacggtc attgctctca cttgccttgg cggctttgcc tccccaggcc 120
ctgtgcctcc ctctacagcc ctcagggagc tcattgagga gctggtcaac atcacccaga 180
accagaaggc tccgctctgc aatggcagca tggtatggag catcaacctg acagctggca 240
tgtactgtgc agccctggaa tccctgatca acgtgtcagg ctgcagtgcc atcgagaaga 300
cccagaggat gctgagcgga ttctgcccgc acaaggtctc agctgggcag ttttccagct 360
tgcatgtccg agacaccaaa atcgaggtgg cccagtttgt aaaggacctg ctcttacatt 420
taaagaaact ttttcgcgag ggacagttca actgaaactt cgaaagcatc attatttgca 480
gagacaggac ctgactattg aagttgcaga ttcatttttc tttctgatgt caaaaatgtc 540
ttgggtaggc gggaaggagg gttagggagg ggtaaaattc cttagcttag acctcagcct 600
gtgctgcccg tcttcagcct agccgacctc agccttcccc ttgcccaggg ctcagcctgg 660
tgggcctcct ctgtccaggg ccctgagctc ggtggaccca gggatgacat gtccctacac 720
ccctcccctg ccctagagca cactgtagca ttacagtggg tgcccccctt gccagacatg 780
tggtgggaca gggacccact tcacacacag gcaactgagg cagacagcag ctcaggcaca 840
cttcttcttg gtcttattta ttattgtgtg ttatttaaat gagtgtgttt gtcaccgttg 900
gggattgggg aagactgtgg ctgctagcac ttggagccaa gggttcagag actcagggcc 960
ccagcactaa agcagtggac accaggagtc cctggtaata agtactgtgt acagaattct 1020
gctacctcac tggggtcctg gggcctcgga gcctcatccg aggcagggtc aggagagggg 1080
cagaacagcc gctcctgtct gccagccagc agccagctct cagccaacga gtaatttatt 1140
gtttttcctt gtatttaaat attaaatatg ttagcaaaga gttaatatat agaagggtac 1200
cttgaacact gggggagggg acattgaaca agttgtttca ttgactatca aactgaagcc 1260
agaaataaag ttggtgacag at 1282
<210>301
<211>1207
<212>DNA
<213>小鼠(Mus musculus)
<400>301
gacaagccag cagcctaggc cagcccacag ttctacagct ccctggttct ctcactggct 60
ctgggcttca tggcgctctg ggtgactgca gtcctggctc ttgcttgcct tggtggtctc 120
gccgccccag ggccggtgcc aagatctgtg tctctccctc tgacccttaa ggagcttatt 180
gaggagctga gcaacatcac acaagaccag actcccctgt gcaacggcag catggtatgg 240
agtgtggacc tggccgctgg cgggttctgt gtagccctgg attccctgac caacatctcc 300
aattgcaatg ccatctacag gacccagagg atattgcatg gcctctgtaa ccgcaaggcc 360
cccactacgg tctccagcct ccccgatacc aaaatcgaag tagcccactt tataacaaaa 420
ctgctcagct acacaaagca actgtttcgc cacggcccct tctaatgagg agagaccatc 480
cctgggcatc tcagctgtgg actcattttc ctttctcaca tcagactttg ctggggagag 540
gcagggagga gggttgagga ggaagggaga tgcctcagct ttggcctcag cctgcactgc 600
ctgcctagtg ctcagggtct cagcctggca acacccccac cccaccccca cccccgccgc 660
cccatcccat ccctacagaa aactgcagca agaccgtgag tccagcctgt ggcctggtcc 720
acacagggca actgaggcag gcagcagctt gagcacattt cttcttgatc ttatttatta 780
tggttgtgtg ttatttaaat gagtctgtca gtatcccggt ggggacatgg tttgctgcct 840
atgccctggg ggctccagca ttgaagcagt gggctctggg gtccctggca atattactgt 900
atacataact ctgctacctc actgtagcct ccaggtctca ccccaggcag ggagatggga 960
ggggaggcca gagcaacact cctgtctgcc acggcagcaa ccagccctca gccatgaaat 1020
aacttattgt tttgttctta tatttaaagt attaaatagc ttagcaaaga gttaataata 1080
tatggaagaa tggcctgtta cactcaaggt gatgtgtagt gaatgggggg agggtggtgg 1140
gtttgtcact gaacaaactt ttcattgact gtcaaactag aaaccggaaa taaagatggt 1200
gacagat 1207
<210>302
<211>146
<212>PRT
<213>智人(Homo sapiens)
<400>302
Met His Pro Leu Leu Asn Pro Leu Leu Leu Ala Leu Gly Leu Met Ala
1 5 10 15
Leu Leu Leu Thr Thr Val Ile Ala Leu Thr Cys Leu Gly Gly Phe Ala
20 25 30
Ser Pro Gly Pro Val Pro Pro Ser Thr Ala Leu Arg Glu Leu Ile Glu
35 40 45
Glu Leu Val Asn Ile Thr Gln Asn Gln Lys Ala Pro Leu Cys Asn Gly
50 55 60
Ser Met Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala
65 70 75 80
Leu Glu Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu Lys Thr
85 90 95
Gln Arg Met Leu Ser Gly Phe Cys Pro His Lys Val Ser Ala Gly Gln
100 105 110
Phe Ser Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala Gln Phe
115 120 125
Val Lys Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Gln
130 135 140
Phe Asn
145
<210>303
<211>132
<212>PRT
<213>智人(Homo sapiens)
<400>303
Met Ala Leu Leu Leu Thr Thr Val Ile Ala Leu Thr Cys Leu Gly Gly
1 5 10 15
Phe Ala Ser Pro Gly Pro Val Pro Pro Ser Thr Ala Leu Arg Glu Leu
20 25 30
Ile Glu Glu Leu Val Asn Ile Thr Gln Asn Gln Lys Ala Pro Leu Cys
35 40 45
Asn Gly Ser Met Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys
50 55 60
Ala Ala Leu Glu Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu
65 70 75 80
Lys Thr Gln Arg Met Leu Ser Gly Phe Cys Pro His Lys Val Ser Ala
85 90 95
Gly Gln Phe Ser Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala
100 105 110
Gln Phe Val Lys Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu
115 120 125
Gly Arg Phe Asn
130
<210>304
<211>159
<212>PRT
<213>智人(Homo sapiens)
<400>304
Met His Pro Leu Leu Asn Pro Leu Leu Leu Ala Leu Gly Leu Met Ala
1 5 10 15
Leu Leu Leu Thr Thr Val Ile Ala Leu Thr Cys Leu Gly Gly Phe Ala
20 25 30
Ser Pro Gly Pro Val Pro Pro Ser Thr Ala Leu Arg Glu Leu Ile Glu
35 40 45
Glu Leu Val Asn Ile Thr Gln Asn Gln Lys Ala Pro Leu Cys Asn Gly
50 55 60
Ser Met Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala
65 70 75 80
Leu Glu Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu Lys Thr
85 90 95
Gln Arg Met Leu Ser Gly Phe Cys Pro His Lys Val Ser Ala Gly Gln
100 105 110
Phe Ser Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala Gln Phe
115 120 125
Val Lys Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Gln
130 135 140
Phe Asn Arg Asn Phe Glu Ser Ile Ile Ile Cys Arg Asp Arg Thr
145 150 155
<210>305
<211>81
<212>PRT
<213>智人(Homo sapiens)
<400>305
Met Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala Leu
1 5 10 15
Glu Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu Lys Thr Gln
20 25 30
Arg Met Leu Ser Gly Phe Cys Pro His Lys Val Ser Ala Gly Gln Phe
35 40 45
Ser Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala Gln Phe Val
50 55 60
Lys Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Arg Phe
65 70 75 80
Asn
<210>306
<211>146
<212>PRT
<213>智人(Homo sapiens)
<400>306
Met His Pro Leu Leu Asn Pro Leu Leu Leu Ala Leu Gly Leu Met Ala
1 5 10 15
Leu Leu Leu Thr Thr Val Ile Ala Leu Thr Cys Leu Gly Gly Phe Ala
20 25 30
Ser Pro Gly Pro Val Pro Pro Ser Thr Ala Leu Arg Glu Leu Ile Glu
35 40 45
Glu Leu Val Asn Ile Thr Gln Asn Gln Lys Ala Pro Leu Cys Asn Gly
50 55 60
Ser Met Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala
65 70 75 80
Leu Glu Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu Lys Thr
85 90 95
Gln Arg Met Leu Ser Gly Phe Cys Pro His Lys Val Ser Ala Gly Gln
100 105 110
Phe Ser Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala Gln Phe
115 120 125
Val Lys Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Gln
130 135 140
Phe Asn
145
<210>307
<211>81
<212>PRT
<213>智人(Homo sapiens)
<400>307
Met Val Trp Ser Ile Asn Leu Thr Ala Gly Met Tyr Cys Ala Ala Leu
1 5 10 15
Glu Ser Leu Ile Asn Val Ser Gly Cys Ser Ala Ile Glu Lys Thr Gln
20 25 30
Arg Met Leu Ser Gly Phe Cys Pro His Lys Val Ser Ala Gly Gln Phe
35 40 45
Ser Ser Leu His Val Arg Asp Thr Lys Ile Glu Val Ala Gln Phe Val
50 55 60
Lys Asp Leu Leu Leu His Leu Lys Lys Leu Phe Arg Glu Gly Gln Phe
65 70 75 80
Asn
<210>308
<211>131
<212>PRT
<213>小鼠(Mus musculus)
<400>308
Met Ala Leu Trp Val Thr Ala Val Leu Ala Leu Ala Cys Leu Gly Gly
1 5 10 15
Leu Ala Ala Pro Gly Pro Val Pro Arg Ser Val Ser Leu Pro Leu Thr
20 25 30
Leu Lys Glu Leu Ile Glu Glu Leu Ser Asn Ile Thr Gln Asp Gln Thr
35 40 45
Pro Leu Cys Asn Gly Ser Met Val Trp Ser Val Asp Leu Ala Ala Gly
50 55 60
Gly Phe Cys Val Ala Leu Asp Ser Leu Thr Asn Ile Ser Asn Cys Asn
65 70 75 80
Ala Ile Tyr Arg Thr Gln Arg Ile Leu His Gly Leu Cys Asn Arg Lys
85 90 95
Ala Pro Thr Thr Val Ser Ser Leu Pro Asp Thr Lys Ile Glu Val Ala
100 105 110
His Phe Ile Thr Lys Leu Leu Ser Tyr Thr Lys Gln Leu Phe Arg His
115 120 125
Gly Pro Phe
130
<210>309
<211>131
<212>PRT
<213>小鼠(Mus musculus)
<400>309
Met Ala Leu Trp Val Thr Ala Val Leu Ala Leu Ala Cys Leu Gly Gly
1 5 10 15
Leu Ala Ala Pro Gly Pro Val Pro Arg Ser Val Ser Leu Pro Leu Thr
20 25 30
Leu Lys Glu Leu Ile Glu Glu Leu Ser Asn Ile Thr Gln Asp Gln Thr
35 40 45
Pro Leu Cys Asn Gly Ser Met Val Trp Ser Val Asp Leu Ala Ala Gly
50 55 60
Gly Phe Cys Val Ala Leu Asp Ser Leu Thr Asn Ile Ser Asn Cys Asn
65 70 75 80
Ala Ile Tyr Arg Thr Gln Arg Ile Leu His Gly Leu Cys Asn Arg Lys
85 90 95
Ala Pro Thr Thr Val Ser Ser Leu Pro Asp Thr Lys Ile Glu Val Ala
100 105 110
His Phe Ile Thr Lys Leu Leu Ser Tyr Thr Lys Gln Leu Phe Arg His
115 120 125
Gly Pro Phe
130
<210>310
<211>131
<212>PRT
<213>小鼠(Mus musculus)
<400>310
Met Ala Leu Trp Val Thr Ala Val Leu Ala Leu Ala Cys Leu Gly Gly
1 5 10 15
Leu Ala Ala Pro Gly Pro Val Pro Arg Ser Val Ser Leu Pro Leu Thr
20 25 30
Leu Lys Glu Leu Ile Glu Glu Leu Ser Asn Ile Thr Gln Asp Gln Thr
35 40 45
Pro Leu Cys Asn Gly Ser Met Val Trp Ser Val Asp Leu Ala Ala Gly
50 55 60
Gly Phe Cys Val Ala Leu Asp Ser Leu Thr Asn Ile Ser Asn Cys Asn
65 70 75 80
Ala Ile Tyr Arg Thr Gln Arg Ile Leu His Gly Leu Cys Asn Arg Lys
85 90 95
Ala Pro Thr Thr Val Ser Ser Leu Pro Asp Thr Lys Ile Glu Val Ala
100 105 110
His Phe Ile Thr Lys Leu Leu Ser Tyr Thr Lys Gln Leu Phe Arg His
115 120 125
Gly Pro Phe
130
<210>311
<211>1498
<212>DNA
<213>智人(Homo sapiens)
<400>311
accaaacctc ttcgaggcac aaggcacaac aggctgctct gggattctct tcagccaatc 60
ttcattgctc aagtgtctga agcagccatg gcagaagtac ctgagctcgc cagtgaaatg 120
atggcttatt acagtggcaa tgaggatgac ttgttctttg aagctgatgg ccctaaacag 180
atgaagtgct ccttccagga cctggacctc tgccctctgg atggcggcat ccagctacga 240
atctccgacc accactacag caagggcttc aggcaggccg cgtcagttgt tgtggccatg 300
gacaagctga ggaagatgct ggttccctgc ccacagacct tccaggagaa tgacctgagc 360
accttctttc ccttcatctt tgaagaagaa cctatcttct tcgacacatg ggataacgag 420
gcttatgtgc acgatgcacc tgtacgatca ctgaactgca cgctccggga ctcacagcaa 480
aaaagcttgg tgatgtctgg tccatatgaa ctgaaagctc tccacctcca gggacaggat 540
atggagcaac aagtggtgtt ctccatgtcc tttgtacaag gagaagaaag taatgacaaa 600
atacctgtgg ccttgggcct caaggaaaag aatctgtacc tgtcctgcgt gttgaaagat 660
gataagccca ctctacagct ggagagtgta gatcccaaaa attacccaaa gaagaagatg 720
gaaaagcgat ttgtcttcaa caagatagaa atcaataaca agctggaatt tgagtctgcc 780
cagttcccca actggtacat cagcacctct caagcagaaa acatgcccgt cttcctggga 840
gggaccaaag gcggccagga tataactgac ttcaccatgc aatttgtgtc ttcctaaaga 900
gagctgtacc cagagagtcc tgtgctgaat gtggactcaa tccctagggc tggcagaaag 960
ggaacagaaa ggtttttgag tacggctata gcctggactt tcctgttgtc tacaccaatg 1020
cccaactgcc tgccttaggg tagtgctaag aggatctcct gtccatcagc caggacagtc 1080
agctctctcc tttcagggcc aatccccagc ccttttgttg agccaggcct ctctcacctc 1140
tcctactcac ttaaagcccg cctgacagaa accacggcca catttggttc taagaaaccc 1200
tctgtcattc gctcccacat tctgatgagc aaccgcttcc ctatttattt atttatttgt 1260
ttgtttgttt tattcattgg tctaatttat tcaaaggggg caagaagtag cagtgtctgt 1320
aaaagagcct agtttttaat agctatggaa tcaattcaat ttggactggt gtgctctctt 1380
taaatcaagt cctttaatta agactgaaaa tatataagct cagattattt aaatgggaat 1440
atttataaat gagcaaatat catactgttc aatggttctg aaataaactt cactgaag 1498
<210>312
<211>1345
<212>DNA
<213>小鼠(Mus musculus)
<400>312
cgaggcctaa taggctcatc tgggatcctc tccagccaag cttccttgtg caagtgtctg 60
aagcagctat ggcaactgtt cctgaactca actgtgaaat gccacctttt gacagtgatg 120
agaatgacct gttctttgaa gttgacggac cccaaaagat gaagggctgc ttccaaacct 180
ttgacctggg ctgtccagat gagagcatcc agcttcaaat ctcacagcag cacatcaaca 240
agagcttcag gcaggcagta tcactcattg tggctgtgga gaagctgtgg cagctacctg 300
tgtctttccc gtggaccttc caggatgagg acatgagcac cttcttttcc ttcatctttg 360
aagaagagcc catcctctgt gactcatggg atgatgatga taacctgctg gtgtgtgacg 420
ttcccattag acagctgcac tacaggctcc gagatgaaca acaaaaaagc ctcgtgctgt 480
cggacccata tgagctgaaa gctctccacc tcaatggaca gaatatcaac caacaagtga 540
tattctccat gagctttgta caaggagaac caagcaacga caaaatacct gtggccttgg 600
gcctcaaagg aaagaatcta tacctgtcct gtgtaatgaa agacggcaca cccaccctgc 660
agctggagag tgtggatccc aagcaatacc caaagaagaa gatggaaaag cggtttgtct 720
tcaacaagat agaagtcaag agcaaagtgg agtttgagtc tgcagagttc cccaactggt 780
acatcagcac ctcacaagca gagcacaagc ctgtcttcct gggaaacaac agtggtcagg 840
acataattga cttcaccatg gaatctgtgt cttcctaaag tatgggctgg actgtttcta 900
atgccttccc cagggcatgt gaaggagctc ccttgtcatg aatgagcaga cagctcaatc 960
tctaggagac tccttagtcc tcggccaaga caggtcgctc agggtcacaa gaaaccatgg 1020
cacattctgt tcaaagagag cctgtgtttt cctccttgcc tctgatgggc aaccacttac 1080
ctatttattt atgtatttat tgattggttg atctatttaa gttgattcaa ggggacatta 1140
ggcagcactc tctagaacag aacctagctg tcaacgtgtg ggggatgaat tggtcatagc 1200
ctgcactgag gtctttcatt gaagctgaga ataaataggt tcctataata tggatgagaa 1260
tttttatgaa tgaagcacca gcacattgct ttgatgagta tgaaataaat ttcattaaaa 1320
caaacaaaaa aaaaaaaaaa aaaaa 1345
<210>313
<211>269
<212>PRT
<213>智人(Homo sapiens)
<400>313
Met Ala Glu Val Pro Glu Leu Ala Ser Glu Met Met Ala Tyr Tyr Ser
1 5 10 15
Gly Asn Glu Asp Asp Leu Phe Phe Glu Ala Asp Gly Pro Lys Gln Met
20 25 30
Lys Cys Ser Phe Gln Asp Leu Asp Leu Cys Pro Leu Asp Gly Gly Ile
35 40 45
Gln Leu Arg Ile Ser Asp His His Tyr Ser Lys Gly Phe Arg Gln Ala
50 55 60
Ala Ser Val Val Val Ala Met Asp Lys Leu Arg Lys Met Leu Val Pro
65 70 75 80
Cys Pro Gln Thr Phe Gln Glu Asn Asp Leu Ser Thr Phe Phe Pro Phe
85 90 95
Ile Phe Glu Glu Glu Pro Ile Phe Phe Asp Thr Trp Asp Asn Glu Ala
100 105 110
Tyr Val His Asp Ala Pro Val Arg Ser Leu Asn Cys Thr Leu Arg Asp
115 120 125
Ser Gln Gln Lys Ser Leu Val Met Ser Gly Pro Tyr Glu Leu Lys Ala
130 135 140
Leu His Leu Gln Gly Gln Asp Met Glu Gln Gln Val Val Phe Ser Met
145 150 155 160
Ser Phe Val Gln Gly Glu Glu Ser Asn Asp Lys Ile Pro Val Ala Leu
165 170 175
Gly Leu Lys Glu Lys Asn Leu Tyr Leu Ser Cys Val Leu Lys Asp Asp
180 185 190
Lys Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Asn Tyr Pro Lys
195 200 205
Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Ile Asn Asn
210 215 220
Lys Leu Glu Phe Glu Ser Ala Gln Phe Pro Asn Trp Tyr Ile Ser Thr
225 230 235 240
Ser Gln Ala Glu Asn Met Pro Val Phe Leu Gly Gly Thr Lys Gly Gly
245 250 255
Gln Asp Ile Thr Asp Phe Thr Met Gln Phe Val Ser Ser
260 265
<210>314
<211>153
<212>PRT
<213>智人(Homo sapiens)
<400>314
Ala Pro Val Arg Ser Leu Tyr Cys Thr Leu Arg Asp Ser Gln Gln Lys
1 5 10 15
Ser Leu Val Met Ser Gly Pro Tyr Glu Leu Lys Ala Leu His Leu Gln
20 25 30
Gly Gln Asp Met Glu Gln Gln Val Val Phe Ser Met Ser Phe Val Gln
35 40 45
Gly Glu Glu Ser Asn Asp Lys Ile Pro Val Ala Leu Gly Leu Lys Glu
50 55 60
Lys Asn Leu Tyr Leu Ser Cys Val Leu Lys Asp Asp Lys Pro Thr Leu
65 70 75 80
Gln Leu Glu Ser Val Asp Pro Lys Asn Tyr Pro Lys Lys Lys Met Glu
85 90 95
Lys Arg Phe Val Phe Asn Lys Ile Glu Ile Asn Asn Lys Leu Glu Phe
100 105 110
Glu Ser Ala Gln Phe Pro Asn Trp Tyr Ile Ser Thr Ser Gln Ala Glu
115 120 125
Asn Met Pro Val Phe Leu Gly Gly Thr Lys Gly Gly Gln Asp Ile Thr
130 135 140
Asp Phe Thr Met Gln Phe Val Ser Ser
145 150
<210>315
<211>269
<212>PRT
<213>智人(Homo sapiens)
<400>315
Met Ala Glu Val Pro Glu Leu Ala Ser Glu Met Met Ala Tyr Tyr Ser
1 5 10 15
Gly Asn Glu Asp Asp Leu Phe Phe Glu Ala Asp Gly Pro Lys Gln Met
20 25 30
Lys Cys Ser Phe Gln Asp Leu Asp Leu Cys Pro Leu Asp Gly Gly Ile
35 40 45
Gln Leu Arg Ile Ser Asp His His Tyr Ser Lys Gly Phe Arg Gln Ala
50 55 60
Ala Ser Val Val Val Ala Met Asp Lys Leu Arg Lys Met Leu Val Pro
65 70 75 80
Cys Pro Gln Thr Phe Gln Glu Asn Asp Leu Ser Thr Phe Phe Pro Phe
85 90 95
Ile Phe Glu Glu Glu Pro Ile Phe Phe Asp Thr Trp Asp Asn Glu Ala
100 105 110
Tyr Val His Asp Ala Pro Val Arg Ser Leu Asn Cys Thr Leu Arg Asp
115 120 125
Ser Gln Gln Lys Ser Leu Val Met Ser Gly Pro Tyr Glu Leu Lys Ala
130 135 140
Leu His Leu Gln Gly Gln Asp Met Glu Gln Gln Val Val Phe Ser Met
145 150 155 160
Ser Phe Val Gln Gly Glu Glu Ser Asn Asp Lys Ile Pro Val Ala Leu
165 170 175
Gly Leu Lys Glu Lys Asn Leu Tyr Leu Ser Cys Val Leu Lys Asp Asp
180 185 190
Lys Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Asn Tyr Pro Lys
195 200 205
Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Ile Asn Asn
210 215 220
Lys Leu Glu Phe Glu Ser Ala Gln Phe Pro Asn Trp Tyr Ile Ser Thr
225 230 235 240
Ser Gln Ala Glu Asn Met Pro Val Phe Leu Gly Gly Thr Lys Gly Gly
245 250 255
Gln Asp Ile Thr Asp Phe Thr Met Gln Phe Val Ser Ser
260 265
<210>316
<211>269
<212>PRT
<213>智人(Homo sapiens)
<400>316
Met Ala Glu Val Pro Lys Leu Ala Ser Glu Met Met Ala Tyr Tyr Ser
1 5 10 15
Gly Asn Glu Asp Asp Leu Phe Phe Glu Ala Asp Gly Pro Lys Gln Met
20 25 30
Lys Cys Ser Phe Gln Asp Leu Asp Leu Cys Pro Leu Asp Gly Gly Ile
35 40 45
Gln Leu Arg Ile Ser Asp His His Tyr Ser Lys Gly Phe Arg Gln Ala
50 55 60
Ala Ser Val Val Val Ala Met Asp Lys Leu Arg Lys Met Leu Val Pro
65 70 75 80
Cys Pro Gln Thr Phe Gln Glu Asn Asp Leu Ser Thr Phe Phe Pro Phe
85 90 95
Ile Phe Glu Glu Glu Pro Ile Phe Phe Asp Thr Trp Asp Asn Glu Ala
100 105 110
Tyr Val His Asp Ala Pro Val Arg Ser Leu Asn Cys Thr Leu Arg Asp
115 120 125
Ser Gln Gln Lys Ser Leu Val Met Ser Gly Pro Tyr Glu Leu Lys Ala
130 135 140
Leu His Leu Gln Gly Gln Asp Met Glu Gln Gln Val Val Phe Ser Met
145 150 155 160
Ser Phe Val Gln Gly Glu Glu Ser Asn Asp Lys Ile Pro Val Ala Leu
165 170 175
Gly Leu Lys Glu Lys Asn Leu Tyr Leu Ser Cys Val Leu Lys Asp Asp
180 185 190
Lys Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Asn Tyr Pro Lys
195 200 205
Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Ile Asn Asn
210 215 220
Lys Leu Glu Phe Glu Ser Ala Gln Phe Pro Asn Trp Tyr Ile Ser Thr
225 230 235 240
Ser Gln Ala Glu Asn Met Pro Val Phe Leu Gly Gly Thr Lys Gly Gly
245 250 255
Gln Asp Ile Thr Asp Phe Thr Met Gln Phe Val Ser Ser
260 265
<210>317
<211>269
<212>PRT
<213>智人(Homo sapiens)
<400>317
Met Ala Glu Val Pro Glu Leu Ala Ser Glu Met Met Ala Tyr Tyr Ser
1 5 10 15
Gly Asn Glu Asp Asp Leu Phe Phe Glu Ala Asp Gly Pro Lys Gln Met
20 25 30
Lys Cys Ser Phe Gln Asp Leu Asp Leu Cys Pro Leu Asp Gly Gly Ile
35 40 45
Gln Leu Arg Ile Ser Asp His His Tyr Ser Lys Gly Phe Arg Gln Ala
50 55 60
Ala Ser Val Val Val Ala Met Asp Lys Leu Arg Lys Met Leu Val Pro
65 70 75 80
Cys Pro Gln Thr Phe Gln Glu Asn Asp Leu Ser Thr Phe Phe Pro Phe
85 90 95
Ile Phe Glu Glu Glu Pro Ile Phe Phe Asp Thr Trp Asp Asn Glu Ala
100 105 110
Tyr Val His Asp Ala Pro Val Arg Ser Leu Asn Cys Thr Leu Arg Asp
115 120 125
Ser Gln Gln Lys Ser Leu Val Met Ser Gly Pro Tyr Glu Leu Lys Ala
130 135 140
Leu His Leu Gln Gly Gln Asp Met Glu Gln Gln Val Val Phe Ser Met
145 150 155 160
Ser Phe Val Gln Gly Glu Glu Ser Asn Asp Lys Ile Pro Val Ala Leu
165 170 175
Gly Leu Lys Glu Lys Asn Leu Tyr Leu Ser Cys Val Leu Lys Asp Asp
180 185 190
Lys Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Asn Tyr Pro Lys
195 200 205
Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Ile Asn Asn
210 215 220
Lys Leu Glu Phe Glu Ser Ala Gln Phe Pro Asn Trp Tyr Ile Ser Thr
225 230 235 240
Ser Gln Ala Glu Asn Met Pro Val Phe Leu Gly Gly Thr Lys Gly Gly
245 250 255
Gln Asp Ile Thr Asp Phe Thr Met Gln Phe Val Ser Ser
260 265
<210>318
<211>269
<212>PRT
<213>小鼠(Mus musculus)
<400>318
Met Ala Thr Val Pro Glu Leu Asn Cys Glu Met Pro Pro Phe Asp Ser
1 5 10 15
Asp Glu Asn Asp Leu Phe Phe Glu Val Asp Gly Pro Gln Lys Met Lys
20 25 30
Gly Cys Phe Gln Thr Phe Asp Leu Gly Cys Pro Asp Glu Ser Ile Gln
35 40 45
Leu Gln Ile Ser Gln Gln His Ile Asn Lys Ser Phe Arg Gln Ala Val
50 55 60
Ser Leu Ile Val Ala Val Glu Lys Leu Trp Gln Leu Pro Val Ser Phe
65 70 75 80
Pro Trp Thr Phe Gln Asp Glu Asp Met Ser Thr Phe Phe Ser Phe Ile
85 90 95
Phe Glu Glu Glu Pro Ile Leu Cys Asp Ser Trp Asp Asp Asp Asp Asn
100 105 110
Leu Leu Val Cys Asp Val Pro Ile Arg Gln Leu His Tyr Arg Leu Arg
115 120 125
Asp Glu Gln Gln Lys Ser Leu Val Leu Ser Asp Pro Tyr Glu Leu Lys
130 135 140
Ala Leu His Leu Asn Gly Gln Asn Ile Asn Gln Gln Val Ile Phe Ser
145 150 155 160
Met Ser Phe Val Gln Gly Glu Pro Ser Asn Asp Lys Ile Pro Val Ala
165 170 175
Leu Gly Leu Lys Gly Lys Asn Leu Tyr Leu Ser Cys Val Met Lys Asp
180 185 190
Gly Thr Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Gln Tyr Pro
195 200 205
Lys Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Val Lys
210 215 220
Ser Lys Val Glu Phe Glu Ser Ala Glu Phe Pro Asn Trp Tyr Ile Ser
225 230 235 240
Thr Ser Gln Ala Glu His Lys Pro Val Phe Leu Gly Asn Asn Ser Gly
245 250 255
Gln Asp Ile Ile Asp Phe Thr Met Glu Ser Val Ser Ser
260 265
<210>319
<211>269
<212>PRT
<213>小鼠(Mus musculus)
<400>319
Met Ala Thr Val Pro Glu Leu Asn Cys Glu Met Pro Pro Phe Asp Ser
1 5 10 15
Asp Glu Asn Asp Leu Phe Phe Glu Val Asp Gly Pro Gln Lys Met Lys
20 25 30
Gly Cys Phe Gln Thr Phe Asp Leu Gly Cys Pro Asp Glu Ser Ile Gln
35 40 45
Leu Gln Ile Ser Gln Gln His Ile Asn Lys Ser Phe Arg Gln Ala Val
50 55 60
Ser Leu Ile Val Ala Val Glu Lys Leu Trp Gln Leu Pro Val Ser Phe
65 70 75 80
Pro Trp Thr Phe Gln Asp Glu Asp Met Ser Thr Phe Phe Ser Phe Ile
85 90 95
Phe Glu Glu Glu Pro Ile Leu Cys Asp Ser Trp Asp Asp Asp Asp Asn
100 105 110
Leu Leu Val Cys Asp Val Pro Ile Arg Gln Leu His Tyr Arg Leu Arg
115 120 125
Asp Glu Gln Gln Lys Ser Leu Val Leu Ser Asp Pro Tyr Glu Leu Lys
130 135 140
Ala Leu His Leu Asn Gly Gln Asn Ile Asn Gln Gln Val Ile Phe Ser
145 150 155 160
Met Ser Phe Val Gln Gly Glu Pro Ser Asn Asp Lys Ile Pro Val Ala
165 170 175
Leu Gly Leu Lys Gly Lys Asn Leu Tyr Leu Ser Cys Val Met Lys Asp
180 185 190
Gly Thr Pro Thr Leu Gln Leu Glu Ser Val Asp Pro Lys Gln Tyr Pro
195 200 205
Lys Lys Lys Met Glu Lys Arg Phe Val Phe Asn Lys Ile Glu Val Lys
210 215 220
Ser Lys Val Glu Phe Glu Ser Ala Glu Phe Pro Asn Trp Tyr Ile Ser
225 230 235 240
Thr Ser Gln Ala Glu Hi s Lys Pro Val Phe Leu Gly Asn Asn Ser Gly
245 250 255
Gln Asp Ile Ile Asp Phe Thr Met Glu Ser Val Ser Ser
260 265
<210>320
<211>396
<212>DNA
<213>小鼠(Mus musculus)
<400>320
tttcgaagtc tttgacctca acatgaagat ttccacactt ctatgcctcc tgctcatagc 60
taccaccatc agtcctcagg tattggctgg accagatgcg gtgagcaccc cagtcacgtg 120
ctgttataat gttgttaagc agaagattca cgtccggaag ctgaagagct acaggagaat 180
cacaagcagc cagtgtcccc gggaagctgt gatcttcagg accatactgg ataaggagat 240
ctgtgctgac cccaaggaga agtgggttaa gaattccata aaccacttgg ataagacgtc 300
tcgaacgtag catccttgaa ccttcatgtc taggctgaga gttccaaaaa ctcttacgta 360
tttccccctg aagttcccca cgggcagtgt gatatt 396
<210>321
<211>95
<212>PRT
<213>小鼠(Mus musculus)
<400>321
Met Lys Ile Ser Thr Leu Leu Cys Leu Leu Leu Ile Ala Thr Thr Ile
1 5 10 15
Ser Pro Gln Val Leu Ala Gly Pro Asp Ala Val Ser Thr Pro Val Thr
20 25 30
Cys Cys Tyr Asn Val Val Lys Gln Lys Ile His Val Arg Lys Leu Lys
35 40 45
Ser Tyr Arg Arg Ile Thr Ser Ser Gln Cys Pro Arg Glu Ala Val Ile
50 55 60
Phe Arg Thr Ile Leu Asp Lys Glu Ile Cys Ala Asp Pro Lys Glu Lys
65 70 75 80
Trp Val Lys Asn Ser Ile Asn His Leu Asp Lys Thr Ser Arg Thr
85 90 95
<210>322
<211>104
<212>PRT
<213>小鼠(Mus musculus)
<400>322
Met Lys Ile Ser Thr Leu Leu Cys Leu Leu Leu Ile Ala Thr Thr Ile
1 5 10 15
Ser Pro Gln Val Leu Ala Gly Pro Asp Ala Val Ser Thr Pro Val Thr
20 25 30
Cys Cys Tyr Asn Val Val Lys Gln Lys Ile His Val Arg Lys Leu Lys
35 40 45
Ser Tyr Arg Arg Ile Thr Ser Ser Gln Cys Pro Arg Glu Ala Val Ile
50 55 60
Phe Arg Thr Ile Leu Asp Lys Glu Ile Cys Ala Asp Pro Lys Glu Lys
65 70 75 80
Trp Val Lys Asn Ser Ile Asn His Leu Asp Lys Thr Ser Gln Thr Phe
85 90 95
Ile Leu Glu Pro Ser Cys Leu Gly
100
<210>323
<211>104
<212>PRT
<213>小鼠(Mus musculus)
<400>323
Met Lys Ile Ser Thr Leu Leu Cys Leu Leu Leu Ile Ala Thr Thr Ile
1 5 10 15
Ser Pro Gln Val Leu Ala Gly Pro Asp Ala Val Ser Thr Pro Val Thr
20 25 30
Cys Cys Tyr Asn Val Val Lys Gln Lys Ile His Val Arg Lys Leu Lys
35 40 45
Ser Tyr Arg Arg Ile Thr Ser Ser Gln Cys Pro Arg Glu Ala Val Ile
50 55 60
Phe Arg Thr Ile Leu Asp Lys Glu Ile Cys Ala Asp Pro Lys Glu Lys
65 70 75 80
Trp Val Lys Asn Ser Ile Asn His Leu Asp Lys Thr Ser Gln Thr Phe
85 90 95
Ile Leu Glu Pro Ser Cys Leu Gly
100
<210>324
<211>104
<212>PRT
<213>小鼠(Mus musculus)
<400>324
Met Lys Ile Ser Thr Leu Leu Cys Leu Leu Leu Ile Ala Thr Thr Ile
1 5 10 15
Ser Pro Gln Val Leu Ala Gly Pro Asp Ala Val Ser Thr Pro Val Thr
20 25 30
Cys Cys Tyr Asn Val Val Lys Gln Lys Ile His Val Arg Lys Leu Lys
35 40 45
Ser Tyr Arg Arg Ile Thr Ser Ser Gln Cys Pro Arg Glu Ala Val Ile
50 55 60
Phe Arg Thr Ile Leu Asp Lys Glu Ile Cys Ala Asp Pro Lys Glu Lys
65 70 75 80
Trp Val Lys Asn Ser Ile Asn His Leu Asp Lys Thr Ser Gln Thr Phe
85 90 95
Ile Leu Glu Pro Ser Cys Leu Gly
100
<210>325
<211>3008
<212>DNA
<213>小鼠(Mus musculus)
<400>325
actgcacact gttccctctc ttagaactag catgttgggt gttatgtagt caaaggaggg 60
cattatgagc tgtaccccag ggacttcctg atcctcttac atgtataaat agcaagaccg 120
ggccaggaac agcaagcagt ctgaaggcca gctgggtctg cccactaaga agatgaagcc 180
ttttcatact gccctctcct tcctcattct tacaactgct cttggaatct gggcccagat 240
cacacatgca acagagacaa aagaagtcca gagcagtctg aaggcacagc aagggcttga 300
aattgaaatg tttcacatgg gctttcaaga ctcttcagat tgctgcctgt cctataactc 360
acggattcag tgttcaagat ttataggtta ttttcccacc agtggtgggt gtaccaggcc 420
gggcatcatc tttatcagca agagggggtt ccaggtctgt gccaacccca gtgatcggag 480
agttcagaga tgcattgaaa gattggagca aaactcacaa ccacggacct acaaacaata 540
acatttgctt gaagagaagg gtgtgaactg ccagctactt tctttggtct tccccagtga 600
ccacctaagt ggctctaagt gtttattttt ataggtatat aaacattttt tttttctgtt 660
ccactttaaa gtggcatatc tggctttgtc acagagggga aacttgtctg tgccaacccc 720
agtcatctga aaactcagat gcctggaagg tctgaagctg acctcaatga ctacacataa 780
tatttgattg agataaatgg gcaaggtctg gagagatggc ttggtggtta agagcacctg 840
ctgctcttcc agaggacctg ggttcaattc ccacttagat ggcagctcaa actatctata 900
attccaattc caaagaaaac tgatgcccta ttttgccctt tagttagtag tatttacagt 960
attctttata aattcacctt gacatgacca tcttgagcta cagccatcct aactgcctca 1020
gaatcactca agttcttcca ctcggtttcc cagcggattt taagtggata aactgtgaga 1080
gtggtctgtg ggactttgga atgtgtctgg ttctgatagt cacttatggc aacccaggta 1140
cattcaacta ggatgaaata aattctgcct tagcccagta gtatgtctgt gtttgtaagg 1200
acccagctga ttttcccacc acccctccat cagtaagcca ctaataaagt gcatctatgc 1260
agccacaggt ctgtctgcct cttttgcttc agtttcctag gactatgggc tgaaattggg 1320
ctgttaggga gaaagcatct cactcgcttt tattgaatct gcagtggaaa agaaacagag 1380
ggagtcaggt aactttgaat attttcttca aaacaaaaga tatcatggta caattttttt 1440
ttaatttttt gtttgtttgt ttttgttttt cgagacaggg tttctctgtg tagccctggc 1500
tgtcctggaa ctcactctgt agaccaggtt ggcctccaac tcagaaatcc gcctgcctct 1560
gcctcccgag tgctgggatt aaaggcgtgc gccaccacca cccggcccat ggtacaattt 1620
ttaaatttcc agaaatatag tttattccaa tgtagacttc atatcaagga tgtattttac 1680
ccactataga gagaatcatt aaagtgatct acaaatcttt ggaagttctc cctgttcgat 1740
aagatcctca attctattcg aggatctcaa cttggtcagc ttgtttttat accagtctca 1800
tgctgttttt ttactgtggc tctgtatgat aatcccttca gcagtgtctc tattgttcag 1860
gggtgtttgg gttacctaag atcttttgtg tttccatatg aattttaaga ttgttatttt 1920
caaaatctgt gaagaattgc attggaattt tgatgggaat tgcaatgaat ctataaattt 1980
tttttgataa gctgaccatt gtcaaaatat taaactagac catgagcata ggtggtcttt 2040
ccatcttctg ggtcttcttt gattgtttta gagttttcat tgtataggcc ttttgcttta 2100
ttcattaggt ttattccaag atattatttt gcaggtattg agagtgggat tttcctccca 2160
atttcttcct cagtatgttt gtcatttgct tataggaaga ctattggttt ttttgtatgt 2220
gcagatcgtg tcctgacact tggctgaaag tgtttatcag ctctacgagt tttctagtgt 2280
agcatttagg gccttttata gagagagaaa gaatgatatc atctgccaat gaatattgct 2340
tgacttcttc ctttcctgtt tgaatccatc ttgtctcctt ctcttgcctt actgctgtag 2400
caaaaacttc aagtactcag ctgaaaagaa gtactgagag aaagtatcca tgtccctttc 2460
ctgattttta gcagaaatgc ttccagtttt tctccggtta gcattccgtt ggctacaggc 2520
ttgttgtata tttcctttat tgtattgaaa tacgttcctt gtatttctgt tgtcttcagg 2580
gctttaataa tgaagagctg ttggttttca ccacaggcat tttctgaatc tactttctgc 2640
tttcttgaat tgagtccatt tatacagtgg atctcattta ctgatttatg tatgttgaac 2700
atccctgcaa gtctggaatg aagctcttta tgatttcaga aaacagattt ttcttagtcc 2760
tcatttgtaa cctctccccc tagcctgaaa cctggctgct caggtttcac tgttagcagg 2820
aagagagcgt ggggtggacc taccgcccta tcgttctgcc actcccactg cggctgcctg 2880
ccacctagct gttcctgagc caacacgtgg tcacctgcaa ctggactcct aggatgattt 2940
ggcgggaatg ggcccctccc cctttttata acccagtgtc tggaatagta aaattgaacc 3000
ttggtcag 3008
<210>326
<211>122
<212>PRT
<213>小鼠(Mus musculus)
<400>326
Met Lys Pro Phe His Thr Ala Leu Ser Phe Leu Ile Leu Thr Thr Ala
1 5 10 15
Leu Gly Ile Trp Ala Gln Ile Thr His Ala Thr Glu Thr Lys Glu Val
20 25 30
Gln Ser Ser Leu Lys Ala Gln Gln Gly Leu Glu Ile Glu Met Phe His
35 40 45
Met Gly Phe Gln Asp Ser Ser Asp Cys Cys Leu Ser Tyr Asn Ser Arg
50 55 60
Ile Gln Cys Ser Arg Phe Ile Gly Tyr Phe Pro Thr Ser Gly Gly Cys
65 70 75 80
Thr Arg Pro Gly Ile Ile Phe Ile Ser Lys Arg Gly Phe Gln Val Cys
85 90 95
Ala Asn Pro Ser Asp Arg Arg Val Gln Arg Cys Ile Glu Arg Leu Glu
100 105 110
Gln Asn Ser Gln Pro Arg Thr Tyr Lys Gln
115 120
<210>327
<211>122
<212>PRT
<213>小鼠(Mus musculus)
<400>327
Met Lys Pro Phe His Thr Ala Leu Ser Phe Leu Ile Leu Thr Thr Ala
1 5 10 15
Leu Gly Ile Trp Ala Gln Ile Thr His Ala Thr Glu Thr Lys Glu Val
20 25 30
Gln Ser Ser Leu Lys Ala Gln Gln Gly Leu Glu Ile Glu Met Phe His
35 40 45
Met Gly Phe Gln Asp Ser Ser Asp Cys Cys Leu Ser Tyr Asn Ser Arg
50 55 60
Ile Gln Cys Ser Arg Phe Ile Gly Tyr Phe Pro Thr Ser Gly Gly Cys
65 70 75 80
Thr Arg Pro Gly Ile Ile Phe Ile Ser Lys Arg Gly Phe Gln Val Cys
85 90 95
Ala Asn Pro Ser Asp Arg Arg Val Gln Arg Cys Ile Glu Arg Leu Glu
100 105 110
Gln Asn Ser Gln Pro Arg Thr Tyr Lys Gln
115 120
<210>328
<211>122
<212>PRT
<213>小鼠(Mus musculus)
<400>328
Met Lys Pro Phe His Thr Ala Leu Ser Phe Leu Ile Leu Thr Thr Ala
1 5 10 15
Leu Gly Ile Trp Ala Gln Ile Thr His Ala Thr Glu Thr Lys Glu Val
20 25 30
Gln Ser Ser Leu Lys Ala Gln Gln Gly Leu Glu Ile Glu Met Phe His
35 40 45
Met Gly Phe Gln Asp Ser Ser Asp Cys Cys Leu Ser Tyr Asn Ser Arg
50 55 60
Ile Gln Cys Ser Arg Phe Ile Gly Tyr Phe Pro Thr Ser Gly Gly Cys
65 70 75 80
Thr Arg Pro Gly Ile Ile Phe Ile Ser Lys Arg Gly Phe Gln Val Cys
85 90 95
Ala Asn Pro Ser Asp Arg Arg Val Gln Arg Cys Ile Glu Arg Leu Glu
100 105 110
Gln Asn Ser Gln Pro Arg Thr Tyr Lys Gln
115 120
<210>329
<211>1103
<212>DNA
<213>智人(Homo sapiens)
<400>329
cacagagccc gggccgcagg cacctcctcg ccagctcttc cgctcctctc acagccgcca 60
gacccgcctg ctgagcccca tggcccgcgc tgctctctcc gccgccccca gcaatccccg 120
gctcctgcga gtggcactgc tgctcctgct cctggtagcc gctggccggc gcgcagcagg 180
agcgtccgtg gccactgaac tgcgctgcca gtgcttgcag accctgcagg gaattcaccc 240
caagaacatc caaagtgtga acgtgaagtc ccccggaccc cactgcgccc aaaccgaagt 300
catagccaca ctcaagaatg ggcggaaagc ttgcctcaat cctgcatccc ccatagttaa 360
gaaaatcatc gaaaagatgc tgaacagtga caaatccaac tgaccagaag ggaggaggaa 420
gctcactggt ggctgttcct gaaggaggcc ctgcccttat aggaacagaa gaggaaagag 480
agacacagct gcagaggcca cctggattgt gcctaatgtg tttgagcatc gcttaggaga 540
agtcttctat ttatttattt attcattagt tttgaagatt ctatgttaat attttaggtg 600
taaaataatt aagggtatga ttaactctac ctgcacactg tcctattata ttcattcttt 660
ttgaaatgtc aaccccaagt tagttcaatc tggattcata tttaatttga aggtagaatg 720
ttttcaaatg ttctccagtc attatgttaa tatttctgag gagcctgcaa catgccagcc 780
actgtgatag aggctggcgg atccaagcaa atggccaatg agatcattgt gaaggcaggg 840
gaatgtatgt gcacatctgt tttgtaactg tttagatgaa tgtcagttgt tatttattga 900
aatgatttca cagtgtgtgg tcaacatttc tcatgttgaa actttaagaa ctaaaatgtt 960
ctaaatatcc cttggacatt ttatgtcttt cttgtaaggc atactgcctt gtttaatggt 1020
agttttacag tgtttctggc ttagaacaaa ggggcttaat tattgatgtt ttcatagaga 1080
atataaaaat aaagcactta tag 1103
<210>330
<211>884
<212>DNA
<213>小鼠(Mus musculus)
<400>330
catgatccca gccacccgct cgcttctctg tgcagcgctg ctgctgctgg ccaccagccg 60
cctggccaca ggggcgccta tcgccaatga gctgcgctgt cagtgcctgc agaccatggc 120
tgggattcac ctcaagaaca tccagagctt gaaggtgttg ccctcagggc cccactgcac 180
ccaaaccgaa gtcatagcca cactcaagaa tggtcgcgag gcttgccttg accctgaagc 240
tcccttggtt cagaaaattg tccaaaagat gctaaaaggt gtccccaagt aacggagaaa 300
gaagacagac tgctctgatg gcaccgtctg gtgaacgctg gcttctgaca acactataca 360
atttcttttg agggtcctat ttatttatgt atttatttat tccacaaagt gtgtggtttt 420
tattttacat taatatttaa cagtgtggat acatttcatc gatggtagtt cagttctgct 480
tgttcagttt aaagatggta ggcttaaaat atttcattaa aactaatatt tattgggaga 540
ccactaagtg tcaaccactg tgctagtaga agggtgttgt gcgaaaagaa gtgcagagag 600
atagagttta gtattatgtt ttgtatgtat tagggtgagg acatgtgtgg gaggctgtgt 660
ttgtatgtct tgaaaagaat gtcagttatt tattgaaagt cgtctttcat attgtatggt 720
caacacgcac gtgttgacgc ttcccttgga cattttgtgt ctagttggta gcccataatg 780
ggcttttaca ttctttaacc ctgtttctcc tggtctcgtc tcgctcggga cagagacgtt 840
caaaggactg ttacaaatga agtaaaaata aaagttttat taag 884
<210>331
<211>107
<212>PRT
<213>智人(Homo sapiens)
<400>331
Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala
20 25 30
Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr
35 40 45
Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser
50 55 60
Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn
65 70 75 80
Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys Ile
85 90 95
Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn
100 105
<210>332
<211>107
<212>PRT
<213>智人(Homo sapiens)
<400>332
Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala
20 25 30
Ala Gly Ala Ser Val Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr
35 40 45
Leu Gln Gly Ile His Pro Lys Asn Ile Gln Ser Val Asn Val Lys Ser
50 55 60
Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn
65 70 75 80
Gly Arg Lys Ala Cys Leu Asn Pro Ala Ser Pro Ile Val Lys Lys lle
85 90 95
Ile Glu Lys Met Leu Asn Ser Asp Lys Ser Asn
100 105
<210>333
<211>33
<212>PRT
<213>智人(Homo sapiens)
<400>333
Met Ala Arg Ala Ala Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Gly Arg Arg Ala
20 25 30
Ala
<210>334
<211>96
<212>PRT
<213>小鼠(Mus musculus)
<400>334
Met Ile Pro Ala Thr Arg Ser Leu Leu Cys Ala Ala Leu Leu Leu Leu
1 5 10 15
Ala Thr Ser Arg Leu Ala Thr Gly Ala Pro Ile Ala Asn Glu Leu Arg
20 25 30
Cys Gln Cys Leu Gln Thr Met Ala Gly Ile His Leu Lys Asn Ile Gln
35 40 45
Ser Leu Lys Val Leu Pro Ser Gly Pro His Cys Thr Gln Thr Glu Val
50 55 60
Ile Ala Thr Leu Lys Asn Gly Arg Glu Ala Cys Leu Asp Pro Glu Ala
65 70 75 80
Pro Leu Val Gln Lys Ile Val Gln Lys Met Leu Lys Gly Val Pro Lys
85 90 95
<210>335
<211>96
<212>PRT
<213>小鼠(Mus musculus)
<400>335
Met Ile Pro Ala Thr Arg Ser Leu Leu Cys Ala Ala Leu Leu Leu Leu
1 5 10 15
Ala Thr Ser Arg Leu Ala Thr Gly Ala Pro Ile Ala Asn Glu Leu Arg
20 25 30
Cys Gln Cys Leu Gln Thr Met Ala Gly Ile His Leu Lys Asn Ile Gln
35 40 45
Ser Leu Lys Val Leu Pro Ser Gly Pro His Cys Thr Gln Thr Glu Val
50 55 60
Ile Ala Thr Leu Lys Asn Gly Arg Glu Ala Cys Leu Asp Pro Glu Ala
65 70 75 80
Pro Leu Val Gln Lys Ile Val Gln Lys Met Leu Lys Gly Val Pro Lys
85 90 95
<210>336
<211>107
<212>PRT
<213>小鼠(Mus musculus)
<400>336
Pro Arg Val Arg Ala Thr Leu Gln His Ser Thr Met Ile Pro Ala Thr
1 5 10 15
Arg Ser Leu Leu Cys Ala Ala Leu Leu Leu Leu Ala Thr Ser Arg Leu
20 25 30
Ala Thr Gly Ala Pro Ile Ala Asn Glu Leu Arg Cys Gln Cys Leu Gln
35 40 45
Thr Met Ala Gly Ile His Leu Lys Asn Ile Gln Ser Leu Lys Val Leu
50 55 60
Pro Ser Gly Pro His Cys Thr Gln Thr Glu Val Ile Ala Thr Leu Lys
65 70 75 80
Asn Gly Arg Glu Ala Cys Leu Asp Pro Glu Ala Pro Leu Val Gln Lys
85 90 95
Ile Val Gln Lys Met Leu Lys Gly Val Pro Lys
100 105
<210>337
<211>1110
<212>DNA
<213>智人(Homo sapiens)
<400>337
gacagagccc gggccacgga gctccttgcc agctctcctc ctcgcacagc cgctcgaacc 60
gcctgctgag ccccatggcc cgcgccacgc tctccgccgc ccccagcaat ccccggctcc 120
tgcgggtggc gctgctgctc ctgctcctgg tggccgccag ccggcgcgca gcaggagcgc 180
ccctggccac tgaactgcgc tgccagtgct tgcagaccct gcagggaatt cacetcaaga 240
acatccaaag tgtgaaggtg aagtcccccg gaccccactg cgcccaaacc gaagtcatag 300
ccacactcaa gaatgggcag aaagcttgtc tcaaccccgc atcgcceatg gttaagaaaa 360
tcatcgaaaa gatgctgaaa aatggcaaat ccaactgacc agaaggaagg aggaagctta 420
ttggtggctg ttcctgaagg aggccctgcc ttacaggaac agaagaggaa agagagacac 480
agctgcagag gccacctggc ttgcgcctaa tgtgtttgag catacttagg agaagtcttc 540
tatttattta tttatttatt tatttgtttg ttttagaaga ttctatgtta atattttatg 600
tgtaaaataa ggttatgatt gaatctactt gcacactctc ccattatatt tattgtttat 660
tttaggtcaa acccaagtta gttcaatcct gattcatatt taatttgaag atagaaggtt 720
tgcagatatt ctctagtcat ttgttaatat ttcttcgtga tgacatatca catgtcagcc 780
actgtgatag aggctgagga atccaagaaa atggccagta agatcaatgt gacggcaggg 840
aaatgtatgt gtgtctattt tgtaactgta aagatgaatg tcagttgtta tttattgaaa 900
tgatttcaca gtgtgtggtc aacatttctc atgttgaagc tttaagaact aaaatgttct 960
aaatatccct tggcatttta tgtctttctt gtaagatact gccttgttta atgttaatta 1020
tgcagtgttt ccctctgtgt tagagcagag aggtttcgat atttattgat gttttcacaa 1080
agaacaggaa aataaaatat ttaaaaatat 1110
<210>338
<211>1083
<212>DNA
<213>小鼠(Mus musculus)
<400>338
gcttcctcgg gcactccaga ctccagccac acttcagcct agcgccatgg cccctcccac 60
ctgccggctc ctcagtgctg cactggtcct gctgctgctg ctggccacca accaccaggc 120
tacaggggct gttgtggcca gtgaactgcg ctgtcaatgc ctgaagaccc tgccaagggt 180
tgacttcaag aacatccaga gcttgagtgt gacgccccca ggaccccact gcgcccagac 240
agaagtcata gccactctca agggcggtca aaaagtttgc cttgaccctg aagcccccct 300
ggttcagaaa atcatccaaa agatactgaa caaaggcaag gctaactgac ctggaaagga 360
ggagcctggg ctgctgtccc tcaacggaag aaccaaagag aaagaaaaaa acaaacagca 420
cccgggaagc ctggatcgta cctgatgtgc ctcgctgtct gagagttcac ttatttattt 480
atctatgtat ttatttattt attaattcca ttgcccagat gttgttatgt ttattatgat 540
atttaaagat atcgattcgc taattcactg taatatctta aaaggtcatt ttaatatgtt 600
aaagtttatt ttaataatgt ttaatgtgtt caattaaagt tatttaactt atatagttgg 660
aaggtgatac atttttaaac ctatttattc attagtttct ggggagaggg tgagttggga 720
actagctaca tcccacccac acagtgaaag agactgggga taaggggtgg gggtggggac 780
aaatagatgc agtcggatgg ctttcatgga agtagtgtgc atgttcacat catttttttg 840
taagcaccga ggagagtaga acagctgtta tttaggtttc agtgtttgta aactgtatgt 900
acaacatttt tgatgctgga tttcaatgta atgttgtgag taacccttgg acattttatg 960
tcttcctcgt aaggcacagt gccttgctta gcaattgttt tgtcatgcct tttcgtgtct 1020
tgaagtggac acatttattt attcatgtat ttttacaaat aacaaaaaat aaaaacgtct 1080
gtt 1083
<210>339
<211>107
<212>PRT
<213>智人(Homo sapiens)
<400>339
Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala
20 25 30
Ala Gly Ala Pro Leu Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr
35 40 45
Leu Gln Gly Ile His Leu Lys Asn Ile Gln Ser Val Lys Val Lys Ser
50 55 60
Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn
65 70 75 80
Gly Gln Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys Ile
85 90 95
Ile Glu Lys Met Leu Lys Asn Gly Lys Ser Asn
100 105
<210>340
<211>107
<212>PRT
<213>智人(Homo sapiens)
<400>340
Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala
20 25 30
Ala Gly Ala Pro Leu Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr
35 40 45
Leu Gln Gly Ile His Leu Lys Asn Ile Gln Ser Val Lys Val Lys Ser
50 55 60
Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn
65 70 75 80
Gly Gln Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys Ile
85 90 95
Ile Glu Lys Met Leu Lys Asn Gly Lys Ser Asn
100 105
<210>341
<211>107
<212>PRT
<213>智人(Homo sapiens)
<400>341
Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala
20 25 30
Ala Gly Ala Pro Leu Ala Thr Glu Leu Arg Cys Gln Cys Leu Gln Thr
35 40 45
Leu Gln Gly Ile His Leu Lys Asn Ile Gln Ser Val Lys Val Lys Ser
50 55 60
Pro Gly Pro His Cys Ala Gln Thr Glu Val Ile Ala Thr Leu Lys Asn
65 70 75 80
Gly Gln Lys Ala Cys Leu Asn Pro Ala Ser Pro Met Val Lys Lys Ile
85 90 95
Ile Glu Lys Met Leu Lys Asn Gly Lys Ser Asn
100 105
<210>342
<211>33
<212>PRT
<213>智人(Homo sapiens)
<400>342
Met Ala Arg Ala Thr Leu Ser Ala Ala Pro Ser Asn Pro Arg Leu Leu
1 5 10 15
Arg Val Ala Leu Leu Leu Leu Leu Leu Val Ala Ala Ser Arg Arg Ala
20 25 30
Ala
<210>343
<211>100
<212>PRT
<213>小鼠(Mus musculus)
<400>343
Met Ala Pro Pro Thr Cys Arg Leu Leu Ser Ala Ala Leu Val Leu Leu
1 5 10 15
Leu Leu Leu Ala Thr Asn His Gln Ala Thr Gly Ala Val Val Ala Ser
20 25 30
Glu Leu Arg Cys Gln Cys Leu Lys Thr Leu Pro Arg Val Asp Phe Lys
35 40 45
Asn Ile Gln Ser Leu Ser Val Thr Pro Pro Gly Pro His Cys Ala Gln
50 55 60
Thr Glu Val Ile Ala Thr Leu Lys Gly Gly Gln Lys Val Cys Leu Asp
65 70 75 80
Pro Glu Ala Pro Leu Val Gln Lys Ile Ile Gln Lys Ile Leu Asn Lys
85 90 95
Gly Lys Ala Asn
100
<210>344
<211>100
<212>PRT
<213>小鼠(Mus musculus)
<400>344
Met Ala Pro Pro Thr Cys Arg Leu Leu Ser Ala Ala Leu Val Leu Leu
1 5 10 15
Leu Leu Leu Ala Thr Asn His Gln Ala Thr Gly Ala Val Val Ala Ser
20 25 30
Glu Leu Arg Cys Gln Cys Leu Lys Thr Leu Pro Arg Val Asp Phe Lys
35 40 45
Asn Ile Gln Ser Leu Ser Val Thr Pro Pro Gly Pro His Cys Ala Gln
50 55 60
Thr Glu Val Ile Ala Thr Leu Lys Gly Gly Gln Lys Val Cys Leu Asp
65 70 75 80
Pro Glu Ala Pro Leu Val Gln Lys Ile Ile Gln Lys Ile Leu Asn Lys
85 90 95
Gly Lys Ala Asn
100
<210>345
<211>2347
<212>DNA
<213>智人(Homo sapiens)
<400>345
ctgtttcagg gccattggac tctccgtcct gcccagagca agatgtgtca ccagcagttg 60
gtcatctctt ggttttccct ggtttttctg gcatctcccc tcgtggccat atgggaactg 120
aagaaagatg tttatgtcgt agaattggat tggtatccgg atgcccctgg agaaatggtg 180
gtcctcacct gtgacaccce tgaagaagat ggtatcacct ggaccttgga ccagagcagt 240
gaggtcttag gctctggcaa aaccctgacc atccaagtca aagagtttgg agatgctggc 300
cagtacacct gtcacaaagg aggcgaggtt ctaagccatt cgctcctgct gcttcacaaa 360
aaggaagatg gaatttggtc cactgatatt ttaaaggacc agaaagaacc caaaaataag 420
acctttctaa gatgcgaggc caagaattat tctggacgtt tcacctgctg gtggctgacg 480
acaatcagta ctgatttgac attcagtgtc aaaagcagca gaggctcttc tgacccccaa 540
ggggtgacgt gcggagctgc tacactctct gcagagagag tcagagggga caacaaggag 600
tatgagtact cagtggagtg ccaggaggac agtgcctgcc cagctgctga ggagagtctg 660
cccattgagg tcatggtgga tgccgttcac aagctcaagt atgaaaacta caccagcagc 720
ttcttcatca gggacatcat caaacctgac ccacccaaga acttgcagct gaagccatta 780
aagaattctc ggcaggtgga ggtcagctgg gagtaccctg acacctggag tactccacat 840
tcctacttct ccctgacatt ctgcgttcag gtccagggca agagcaagag agaaaagaaa 900
gatagagtct tcacggacaa gacctcagcc acggtcatct gccgcaaaaa tgccagcatt 960
agcgtgcggg cccaggaccg ctactatagc tcatcttgga gcgaatgggc atctgtgccc 1020
tgcagttagg ttctgatcca ggatgaaaat ttggaggaaa agtggaagat attaagcaaa 1080
atgtttaaag acacaacgga atagacccaa aaagataatt tctatctgat ttgctttaaa 1140
acgttttttt aggatcacaa tgatatcttt gctgtatttg tatagttaga tgctaaatgc 1200
tcattgaaac aatcagctaa tttatgtata gattttccag ctctcaagtt gccatgggcc 1260
ttcatgctat ttaaatattt aagtaattta tgtatttatt agtatattac tgttatttaa 1320
cgtttgtctg ccaggatgta tggaatgttt catactctta tgacctgatc catcaggatc 1380
agtccctatt atgcaaaatg tgaatttaat tttatttgta ctgacaactt ttcaagcaag 1440
gctgcaagta catcagtttt atgacaatca ggaagaatgc agtgttctga taccagtgcc 1500
atcatacact tgtgatggat gggaacgcaa gagatactta catggaaacc tgacaatgca 1560
aacctgttga gaagatccag gagaacaaga tgctagttcc catgtctgtg aagacttcct 1620
ggagatggtg ttgataaagc aatttagggc cacttacact tctaagcaag tttaatcttt 1680
ggatgcctga attttaaaag ggctagaaaa aaatgattga ccagcctggg aaacataaca 1740
agaccccgtc tctacaaaaa aaatttaaaa ttagccaggc gtggtggctc atgcttgtgg 1800
tcccagctgt tcaggaggat gaggcaggag gatctcttga gcccaggagg tcaaggctat 1860
ggtgagccgt gattgtgcca ctgcatacca gcctaggtga cagaatgaga ccctgtctca 1920
aaaaaaaaaa tgattgaaat taaaattcag ctttagcttc catggcagtc ctcaccccca 1980
cctctctaaa agacacagga ggatgacaca gaaacaccgt aagtgtctgg aaggcaaaaa 2040
gatcttaaga ttcaagagag aggacaagta gttatggcta aggacatgaa attgtcagaa 2100
tggcaggtgg cttcttaaca gccctgtgag aagcagacag atgcaaagaa aatctggaat 2160
ccctttctca ttagcatgaa tgaacctgat acacaattat gaccagaaaa tatggctcca 2220
tgaaggtgct acttttaagt aatgtatgtg cgctctgtaa agtgattaca tttgtttcct 2280
gtttgtttat ttatttattt atttttgcat tctgaggctg aactaataaa aactcttctt 2340
tgtaatc 2347
<210>346
<211>1951
<212>DNA
<213>小鼠(Mus musculus)
<400>346
agaaggaaca gtgggtgtcc aggcacatca gaccaggcag ctcgcagcaa agcaaggtaa 60
gttctctcct cttccctgtc gctaactccc tgcatctaga ggctgtccag attcagactc 120
caggggacag gctacccctg aaccaggcag cgtgggagtg ggatgtgtcc tcagaagcta 180
accatctcct ggtttgccat cgttttgctg gtgtctccac tcatggccat gtgggagctg 240
gagaaagacg tttatgttgt agaggtggac tggactcccg atgcccctgg agaaacagtg 300
aacctcacct gtgacacgcc tgaagaagat gacatcacct ggacctcaga ccagagacat 360
ggagtcatag gctctggaaa gaccctgacc atcactgtca aagagtttct agatgctggc 420
cagtacacct gccacaaagg aggcgagact ctgagccact cacatctgct gctccacaag 480
aaggaaaatg gaatttggtc cactgaaatt ttaaaaaatt tcaaaaacaa gactttcctg 540
aagtgtgaag caccaaatta ctccggacgg ttcacgtgct catggctggt gcaaagaaac 600
atggacttga agttcaacat caagagcagt agcagttccc ctgactctcg ggcagtgaca 660
tgtggaatgg cgtctctgtc tgcagagaag gtcacactgg accaaaggga ctatgagaag 720
tattcagtgt cctgccagga ggatgtcacc tgcccaactg ccgaggagac cctgcccatt 780
gaactggcgt tggaagcacg gcagcagaat aaatatgaga actacagcac cagcttcttc 840
atcagggaca tcatcaaacc agacccgccc aagaacttgc agatgaagcc tttgaagaac 900
tcacaggtgg aggtcagctg ggagtaccct gactcctgga gcactcccca ttcctacttc 960
tccctcaagt tctttgttcg aatccagcgc aagaaagaaa agatgaagga gacagaggag 1020
gggtgtaacc agaaaggtgc gttcctcgta gagaagacat ctaccgaagt ccaatgcaaa 1080
ggcgggaatg tctgcgtgca agctcaggat cgctattaca attcctcgtg cagcaagtgg 1140
gcatgtgttc cctgcagggt ccgatcctag gatgcaacgt tggaaaggaa agaaaagtgg 1200
aagacattaa ggaagaaaaa tttaaactca ggatggaaga gtcccccaaa agctgtcttc 1260
tgcttggttg gctttttcca gttttcctaa gttcatcatg acacctttgc tgatttctac 1320
atgtaaatgt taaatgcccg cagagccagg gagctaatgt atgcatagat attctagcat 1380
tccacttggc cttatgctgt tgaaatattt aagtaattta tgtatttatt aatttatttc 1440
tgcatttcac atttgtatac caagatgtat tgaatatttc atgtgcttgt ggcctgatcc 1500
actgggacca ggccctatta tgcaaattgt gagcttgtta tcttcttcaa cagctcttca 1560
atcagggctt cgtaggtaca ttagcttttg tgacaaccaa taagaacata atattctgac 1620
acaagcagtg ttacatattt gtgaccagta aagacatagg tggtatttgg agacatgaag 1680
aagctgtaaa gttgactctg aagagtttag cactagtttc aacaccaaga aagacttttt 1740
agaagtgata ttgataagaa accagggcct tctttagaag ggtacctaaa tttaaaagaa 1800
ttttgaaagg ctgggtatcg gtggtatatg cttttaattc cagcactcag gagaccaagg 1860
caggcagatc tctgtgagtt tgaggacagc ctggtgtaca gagggagttc cagcacagcc 1920
agtgccacac agaaattctg tctcaaaaac a 1951
<210>347
<211>328
<212>PRT
<213>智人(Homo sapiens)
<400>347
Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu
1 5 10 15
Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val
20 25 30
Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln
50 55 60
Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys
65 70 75 80
Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val
85 90 95
Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp
100 105 110
Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe
115 120 125
Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp
130 135 140
Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg
145 150 155 160
Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser
165 170 175
Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu
180 185 190
Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile
195 200 205
Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr
210 215 220
Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn
225 230 235 240
Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp
245 250 255
Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr
260 265 270
Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg
275 280 285
Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala
290 295 300
Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser
305 310 315 320
Glu Trp Ala Ser Val Pro Cys Ser
325
<210>348
<211>328
<212>PRT
<213>智人(Homo sapiens)
<400>348
Met Cys His Gln Gln Leu Val Ile Ser Trp Phe Ser Leu Val Phe Leu
1 5 10 15
Ala Ser Pro Leu Val Ala Ile Trp Glu Leu Lys Lys Asp Val Tyr Val
20 25 30
Val Glu Leu Asp Trp Tyr Pro Asp Ala Pro Gly Glu Met Val Val Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Gly Ile Thr Trp Thr Leu Asp Gln
50 55 60
Ser Ser Glu Val Leu Gly Ser Gly Lys Thr Leu Thr Ile Gln Val Lys
65 70 75 80
Glu Phe Gly Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Val
85 90 95
Leu Ser His Ser Leu Leu Leu Leu His Lys Lys Glu Asp Gly Ile Trp
100 105 110
Ser Thr Asp Ile Leu Lys Asp Gln Lys Glu Pro Lys Asn Lys Thr Phe
115 120 125
Leu Arg Cys Glu Ala Lys Asn Tyr Ser Gly Arg Phe Thr Cys Trp Trp
130 135 140
Leu Thr Thr Ile Ser Thr Asp Leu Thr Phe Ser Val Lys Ser Ser Arg
145 150 155 160
Gly Ser Ser Asp Pro Gln Gly Val Thr Cys Gly Ala Ala Thr Leu Ser
165 170 175
Ala Glu Arg Val Arg Gly Asp Asn Lys Glu Tyr Glu Tyr Ser Val Glu
180 185 190
Cys Gln Glu Asp Ser Ala Cys Pro Ala Ala Glu Glu Ser Leu Pro Ile
195 200 205
Glu Val Met Val Asp Ala Val His Lys Leu Lys Tyr Glu Asn Tyr Thr
210 215 220
Ser Ser Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn
225 230 235 240
Leu Gln Leu Lys Pro Leu Lys Asn Ser Arg Gln Val Glu Val Ser Trp
245 250 255
Glu Tyr Pro Asp Thr Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Thr
260 265 270
Phe Cys Val Gln Val Gln Gly Lys Ser Lys Arg Glu Lys Lys Asp Arg
275 280 285
Val Phe Thr Asp Lys Thr Ser Ala Thr Val Ile Cys Arg Lys Asn Ala
290 295 300
Ser Ile Ser Val Arg Ala Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser
305 310 315 320
Glu Trp Ala Ser Val Pro Cys Ser
325
<210>349
<211>18
<212>PRT
<213>智人(Homo sapiens)
<400>349
Gln Asp Arg Tyr Tyr Ser Ser Ser Trp Ser Glu Trp Ala Ser Val Pro
1 5 10 15
Cys Ser
<210>350
<211>335
<212>PRT
<213>小鼠(Mus musculus)
<400>350
Met Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val Leu Leu
1 5 10 15
Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val Tyr Val
20 25 30
Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln
50 55 60
Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys
65 70 75 80
Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr
85 90 95
Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp
100 105 110
Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys
115 120 125
Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln
130 135 140
Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro
145 150 155 160
Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys
165 170 175
Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln
180 185 190
Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu
195 200 205
Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser
210 215 220
Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln
225 230 235 240
Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro
245 250 255
Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val
260 265 270
Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys
275 280 285
Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln
290 295 300
Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn
305 310 315 320
Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser
325 330 335
<210>351
<211>335
<212>PRT
<213>小鼠(Mus musculus)
<400>351
Met Cys Pro Gln Lys Leu Thr Ile Ser Trp Phe Ala Ile Val Leu Leu
1 5 10 15
Val Ser Pro Leu Met Ala Met Trp Glu Leu Glu Lys Asp Val Tyr Val
20 25 30
Val Glu Val Asp Trp Thr Pro Asp Ala Pro Gly Glu Thr Val Asn Leu
35 40 45
Thr Cys Asp Thr Pro Glu Glu Asp Asp Ile Thr Trp Thr Ser Asp Gln
50 55 60
Arg His Gly Val Ile Gly Ser Gly Lys Thr Leu Thr Ile Thr Val Lys
65 70 75 80
Glu Phe Leu Asp Ala Gly Gln Tyr Thr Cys His Lys Gly Gly Glu Thr
85 90 95
Leu Ser His Ser His Leu Leu Leu His Lys Lys Glu Asn Gly Ile Trp
100 105 110
Ser Thr Glu Ile Leu Lys Asn Phe Lys Asn Lys Thr Phe Leu Lys Cys
115 120 125
Glu Ala Pro Asn Tyr Ser Gly Arg Phe Thr Cys Ser Trp Leu Val Gln
130 135 140
Arg Asn Met Asp Leu Lys Phe Asn Ile Lys Ser Ser Ser Ser Ser Pro
145 150 155 160
Asp Ser Arg Ala Val Thr Cys Gly Met Ala Ser Leu Ser Ala Glu Lys
165 170 175
Val Thr Leu Asp Gln Arg Asp Tyr Glu Lys Tyr Ser Val Ser Cys Gln
180 185 190
Glu Asp Val Thr Cys Pro Thr Ala Glu Glu Thr Leu Pro Ile Glu Leu
195 200 205
Ala Leu Glu Ala Arg Gln Gln Asn Lys Tyr Glu Asn Tyr Ser Thr Ser
210 215 220
Phe Phe Ile Arg Asp Ile Ile Lys Pro Asp Pro Pro Lys Asn Leu Gln
225 230 235 240
Met Lys Pro Leu Lys Asn Ser Gln Val Glu Val Ser Trp Glu Tyr Pro
245 250 255
Asp Ser Trp Ser Thr Pro His Ser Tyr Phe Ser Leu Lys Phe Phe Val
260 265 270
Arg Ile Gln Arg Lys Lys Glu Lys Met Lys Glu Thr Glu Glu Gly Cys
275 280 285
Asn Gln Lys Gly Ala Phe Leu Val Glu Lys Thr Ser Thr Glu Val Gln
290 295 300
Cys Lys Gly Gly Asn Val Cys Val Gln Ala Gln Asp Arg Tyr Tyr Asn
305 310 315 320
Ser Ser Cys Ser Lys Trp Ala Cys Val Pro Cys Arg Val Arg Ser
325 330 335
<210>352
<211>3426
<212>DNA
<213>智人(Homo sapiens)
<400>352
gtaggaatcg cagcgccaac ggttgcaagg cccaagaagc catcctggga aggaaaatgc 60
attggggaac cctgtgcgga ttcttgtggc tttggcccta tcttttctat gtccaagctg 120
tgcccatcca aaaagtccaa gatgacacca aaaccctcat caagacaatt gtcaccagga 180
tcaatgacat ttcacacacg cagtcagtct cctccaaaca gaaagtcacc ggtttggact 240
tcattcctgg gctccacccc atcctgacct tatccaagat ggaccagaca ctggcagtct 300
accaacagat cctcaccagt atgccttcca gaaacgtgat ccaaatatcc aacgacctgg 360
agaacctccg ggatcttctt cacgtgctgg ccttctctaa gagctgccac ttgccctggg 420
ccagtggcct ggagaccttg gacagcctgg ggggtgtcct ggaagcttca ggctactcca 480
cagaggtggt ggccctgagc aggctgcagg ggtctctgca ggacatgctg tggcagctgg 540
acctcagccc tgggtgctga ggccttgaag gtcactcttc ctgcaaggac tacgttaagg 600
gaaggaactc tggcttccag gtatctccag gattgaagag cattgcatgg acacccctta 660
tccaggactc tgtcaatttc cctgactcct ctaagccact cttccaaagg cataagaccc 720
taagcctcct tttgcttgaa accaaagata tatacacagg atcctattct caccaggaag 780
ggggtccacc cagcaaagag tgggctgcat ctgggattcc caccaaggtc ttcagccatc 840
aacaagagtt gtcttgtccc ctcttgaccc atctccccct cactgaatgc ctcaatgtga 900
ccaggggtga tttcagagag ggcagagggg taggcagagc ctttggatga ccagaacaag 960
gttccctctg agaattccaa ggagttccat gaagaccaca tccacacacg caggaactcc 1020
cagcaacaca agctggaagc acatgtttat ttattctgca ttttattctg gatggatttg 1080
aagcaaagca ccagcttctc caggctcttt ggggtcagcc agggccaggg gtctccctgg 1140
agtgcagttt ccaatcccat agatgggtct ggctgagctg aacccatttt gagtgactcg 1200
agggttgggt tcatctgagc aagagctggc aaaggtggct ctccagttag ttctctcgta 1260
actggtttca tttctactgt gactgatgtt acatcacagt gtttgcaatg gtgttgccct 1320
gagtggatct ccaaggacca ggttatttta aaaagatttg ttttgtcaag tgtcatatgt 1380
aggtgtctgc acccaggggt ggggaatgtt tgggcagaag ggagaaggat ctagaatgtg 1440
ttttctgaat aacatttgtg tggtgggttc tttggaagga gtgagatcat tttcttatct 1500
tctgcaattg cttaggatgt ttttcatgaa aatagctctt tcaggggggt tgtgaggcct 1560
ggccaggcac cccctggaga gaagtttctg gccctggctg accccaaaga gcctggagaa 1620
gctgatgctt tgcttcaaat ccatccagaa taaaacgcaa agggctgaaa gccatttgtt 1680
ggggcagtgg taagctctgg ctttctccga ctgctaggga gtggtctttc ctatcatgga 1740
gtgacggtcc cacactggtg actgcgatct tcagagcagg ggtccttggt gtgaccctct 1800
gaatgggtcc agggttgatc acactctggg tttattacat ggcagtgttc ctatttgggg 1860
cttgcatgcc aaattgtagt tcttgtctga ttggctcacc caagcaaggc caaaattacc 1920
aaaaatcttg gggggttttt actccagtgg tgaagaaaac tcctttagca ggtggtcctg 1980
agacctgaca agcactgcta ggcgagtgcc aggactcccc aggccaggcc accaggatgc 2040
ccttcccact ggaggtcaca ttcaggaaga tgaaagagga ggtttggggt ctgccaccat 2100
cctgctgctg tgtttttgct atcacacagt gggtggtgga tctgtccaag gaaacttgaa 2160
tcaaagcagt taactttaag actgagcacc tgcttcatgc tcagccctga ctggtgctat 2220
aggctggaga agctcaccca ataaacatta agattgaggc ctgccctcag ggatcttgcg 2280
ttcccagtgg tcaaaccgca ctcacccatg tgccaaggtg gggtatttac cacagcagct 2340
gaacagccaa atgcatggtg cagttgacag caggtgggaa atggtatgag ctgagggggg 2400
ccgtgcccag gggcccacag ggaaccctgc ttgcactttg taacatgttt acttttcagg 2460
gcatcttagc ttctattata gccacatccc tttgaaacaa gataactgag aatttaaaaa 2520
taagaaaata cataagacca taacagccaa caggtggcag gaccaggact atagcccagg 2580
tcctctgata cccagagcat tacgtgagcc aggtaatgag ggactggaac cagggagacc 2640
gagcgctttc tggaaaagag gagtttcgag gtagagtttg aaggaggtga gggatgtgaa 2700
ttgcctgcag agagaagcct gttttgttgg aaggtttggt gtgtggagat gcagaggtaa 2760
aagtgtgagc agtgagttac agcgagaggc agagaaagaa gagacaggag ggcaagggcc 2820
atgctgaagg gaccttgaag ggtaaagaag tttgatatta aaggagttaa gagtagcaag 2880
ttctagagaa gaggctggtg ctgtggccag ggtgagagct gctctggaaa atgtgaccca 2940
gatcctcaca accacctaat caggctgagg tgtcttaagc cttttgctca caaaacctgg 3000
cacaatggct aattcccaga gtgtgaaact tcctaagtat aaatggttgt ctgtttttgt 3060
aacttaaaaa aaaaaaaaaa agtttggccg ggtgcggtgg ctcacgcctg taatcccagc 3120
actttgggag gccaaggtgg ggggatcaca aggtcactag atggcgagca tcctggccaa 3180
catggtgaaa ccccgtctct actaaaaaca caaaagttag ctgagcgtgg tggcgggcgc 3240
ctgtagtccc agccactcgg gaggctgaga caggagaatc gcttaaacct gggaggcgga 3300
gagtacagtg agccaagatc gcgccactgc actccggcct gatgacagag cgagattccg 3360
tcttaaaaaa aaaaaaaaaa aaagtttgtt tttaaaaaaa tctaaataaa ataactttgc 3420
cccctg 3426
<210>353
<211>3257
<212>DNA
<213>小鼠(Mus musculus)
<400>353
gagggatccc tgctccagca gctgcaaggt gcaagaagaa gaagatccca gggaggaaaa 60
tgtgctggag acccctgtgt cggttcctgt ggctttggtc ctatctgtct tatgttcaag 120
cagtgcctat ccagaaagtc caggatgaca ccaaaaccct catcaagacc attgtcacca 180
ggatcaatga catttcacac acgcagtcgg tatccgccaa gcagagggtc actggcttgg 240
acttcattcc tgggcttcac cccattctga gtttgtccaa gatggaccag actctggcag 300
tctatcaaca ggtcctcacc agcctgcctt cccaaaatgt gctgcagata gccaatgacc 360
tggagaatct ccgagacctc ctccatctgc tggccttctc caagagctgc tccctgcctc 420
agaccagtgg cctgcagaag ccagagagcc tggatggcgt cctggaagcc tcactctact 480
ccacagaggt ggtggctttg agcaggctgc agggctctct gcaggacatt cttcaacagt 540
tggatgttag ccctgaatgc tgaagtttca aaggccacca ggctcccaag aatcatgtag 600
agggaagaaa ccttggcttc caggggtctt caggagaaga gagccatgtg cacacatcca 660
tcattcattt ctctccctcc tgtagaccac ccatccaaag gcatgactcc acaatgcttg 720
actcaagtta tccacacaac ttcatgagca caaggagggg ccagcctgca gaggggactc 780
tcacctagtt cttcagcaag tagagataag agccatccca tcccctccat gtcccacctg 840
ctccgggtac atgttcctcc gtgggtacac gcttcgctgc ggcccaggag aggtgaggta 900
gggatgggta gagcctttgg gctgtctcag agtctttggg agcaccgtga aggctgcatc 960
cacacacagc tggaaactcc caagcagcac acgatggaag cacttattta tttattctgc 1020
attctatttt ggatggatct gaagcaagcc atcagctttt tcaggctttg ggggtcagcc 1080
aggatgagga aggctcctgg ggtgctgctt tcaatcctat tgatgggtct gcccaaggca 1140
aacctaattt ttgagtgact ggaaggaagg ttgggatctt ccaaacaaga gtctatgcag 1200
gtagcgctca agcttgacct ctggtgactg gttttgtttc tattgtgact gactctatgc 1260
aaacacgttt gcagcggcat tgccgggagc ataggctagg ttattatcaa aagcagatga 1320
attttgtcaa gtgtaatatg tatctatgtg cacctgaggg tagaggatgt gttagaggga 1380
gggtgaagga tccggaagtg ttctctgaat tacatatgtg tggtaggctt ttctgaaagg 1440
gtgaggcatt ttcttacctc tgtggccaca tagtgtggct ttgtgaaaag gacaaaggag 1500
ttgactcttt ccggaacatt tggagtgtac caggcaccct tggaggggct aaagctacag 1560
gccttttgtt ggcatattgc tgagctcagg gagtgagggc cccacatttg agacagtgag 1620
ccccaagaaa agggtccctg gtgtagatct ccaaggttgt ccagggttga tctcacaatg 1680
cgtttcttaa gcaggtagac gtttgcatgc caatatgtgg ttctcatctg attggttcat 1740
ccaaagtaga accctgtctc ccacccattc tgtggggagt tttgttccag tgggaatgag 1800
aaatcactta gcagatggtc ctgagccctg ggccagcact gctgaggaag tgccagggcc 1860
ccaggccagg ctgccagaat tgcccttcgg gctggaggat gaacaaaggg gcttgggttt 1920
ttccatcacc cctgcaccct atgtcaccat caaactgggg ggcagatcag tgagaggaca 1980
cttgatggaa agcaatacac tttaagactg agcacagttt cgtgctcagc tctgtctggt 2040
gctgtgagct agagaagctc accaaataca tataaaaatc agaggctcat gtccctgtgg 2100
ttagacccta ctcacggcgg tgtactccac cacagcagcc ccgcaccgct ggaagtacag 2160
tgctgtcttc aacaggtgtg aaagaacctg agctgagggt gacagtgccc aggggaaccc 2220
tgcttgcagt ctattgcatt tacataccgc atttcagggc acattagcat ccactgctat 2280
ggtagcacac tgttgacacg ggatacctgg ggtcgtaaaa ataagaaaat acaggttgac 2340
tatcccttat ccaaaatgct tgggactaga agagttttgg attttagagt cttttcaggc 2400
ataggtatat ttgagtatat ataaaatgag atatcttggg gatggggccc aagtataaac 2460
atgaagttca tttatatttc ataataccgt atagacactg cttgaagtgt agttttatac 2520
agtgttttaa ataacgttgt atgcatgaaa gacgttttta cagcatgaac ctgtctactc 2580
atgccagcac tcaaaaacct tggggttttg gagcagtttg gatcttgggt tttctgttaa 2640
gagatggtta gcttatacct aaaaccataa tggcaaacag gctgcaggac cagactggat 2700
cctcagccct gaagtgtgcc cttccagcca ggtcataccc tgtggaggtg agcgggatca 2760
ggttttgtgg tgctaagaga ggagttggag gtagattttg gaggatctga ggggtgatgt 2820
gatgttttat tggacacttg gtatgttgaa gggatgaaag tccaaacagg aagtgacagg 2880
gaagactgaa gagaccggga aagagtgaca ggaagtgctg agaggacttt atgggccaca 2940
aaagtggctt ctgaaagatc ccacgtgcca cagtctggag cgaaggctcg tggtggctgg 3000
tgtcagattg ctctggggct gtgctatgcc accttggtca cctcatcaag ctggaatgtc 3060
ctgagccttt cgctcagaga accttgcact atggcttgtt cccagattgt gaaacttccc 3120
atatgcaaaa atgcttggtt tggttttttt ggtttttgtt tttgttttct tttttaaata 3180
catatatata tgtaacaaca gcaacaacaa aattttgttt tattttgtgt caattcaaat 3240
aaattaatga tgcctcc 3257
<210>354
<211>167
<212>PRT
<213>智人(Homo sapiens)
<400>354
Met His Trp Gly Thr Leu Cys Gly Phe Leu Trp Leu Trp Pro Tyr Leu
1 5 10 15
Phe Tyr Val Gln Ala Val Pro Ile Gln Lys Val Gln Asp Asp Thr Lys
20 25 30
Thr Leu Ile Lys Thr Ile Val Thr Arg Ile Asn Asp Ile Ser His Thr
35 40 45
Gln Ser Val Ser Ser Lys Gln Lys Val Thr Gly Leu Asp Phe Ile Pro
50 55 60
Gly Leu His Pro Ile Leu Thr Leu Ser Lys Met Asp Gln Thr Leu Ala
65 70 75 80
Val Tyr Gln Gln Ile Leu Thr Ser Met Pro Ser Arg Asn Val Ile Gln
85 90 95
Ile Ser Asn Asp Leu Glu Asn Leu Arg Asp Leu Leu His Val Leu Ala
100 105 110
Phe Ser Lys Ser Cys His Leu Pro Trp Ala Ser Gly Leu Glu Thr Leu
115 120 125
Asp Ser Leu Gly Gly Val Leu Glu Ala Ser Gly Tyr Ser Thr Glu Val
130 135 140
Val Ala Leu Ser Arg Leu Gln Gly Ser Leu Gln Asp Met Leu Trp Gln
145 150 155 160
Leu Asp Leu Ser Pro Gly Cys
165
<210>355
<211>167
<212>PRT
<213>智人(Homo sapiens)
<400>355
Met His Trp Gly Thr Leu Cys Gly Phe Leu Trp Leu Trp Pro Tyr Leu
1 5 10 15
Phe Tyr Val Gln Ala Val Pro Ile Gln Lys Val Gln Asp Asp Thr Lys
20 25 30
Thr Leu Ile Lys Thr Ile Val Thr Arg Ile Asn Asp Ile Ser His Thr
35 40 45
Gln Ser Val Ser Ser Lys Gln Lys Val Thr Gly Leu Asp Phe Ile Pro
50 55 60
Gly Leu His Pro Ile Leu Thr Leu Ser Lys Met Asp Gln Thr Leu Ala
65 70 75 80
Val Tyr Gln Gln Ile Leu Thr Ser Met Pro Ser Arg Asn Val Ile Gln
85 90 95
Ile Ser Asn Asp Leu Glu Asn Leu Arg Asp Leu Leu His Val Leu Ala
100 105 110
Phe Ser Lys Ser Cys His Leu Pro Trp Ala Ser Gly Leu Glu Thr Leu
115 120 125
Asp Ser Leu Gly Gly Val Leu Glu Ala Ser Gly Tyr Ser Thr Glu Val
130 135 140
Val Ala Leu Ser Arg Leu Gln Gly Ser Leu Gln Asp Met Leu Trp Gln
145 150 155 160
Leu Asp Leu Ser Pro Gly Cys
165
<210>356
<211>38
<212>PRT
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<400>356
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1 5 10 15
Val Gln Asp Asp Thr Lys Thr Leu Ile Lys Thr Ile Val Thr Arg Ile
20 25 30
Asn Asp Ile Ser His Thr
35
<210>357
<211>167
<212>PRT
<213>智人(Homo sapiens)
<400>357
Met His Trp Gly Thr Leu Cys Gly Phe Leu Trp Leu Trp Pro Tyr Leu
1 5 10 15
Phe Tyr Ala Gln Ala Val Pro Ile Gln Lys Val Gln Asp Asp Thr Lys
20 25 30
Thr Leu Ile Lys Thr Ile Val Thr Arg Ile Asn Asp Ile Ser His Thr
35 40 45
Gln Ser Val Ser Ser Lys Gln Lys Val Thr Gly Leu Asp Phe Ile Pro
50 55 60
Gly Leu His Pro Ile Leu Thr Leu Ser Lys Met Asp Gln Thr Leu Ala
65 70 75 80
Val Tyr Gln Gln Ile Leu Thr Ser Met Pro Ser Arg Asn Val Ile Gln
85 90 95
Ile Ser Asn Asp Leu Glu Asn Leu Arg Asp Leu Leu His Val Leu Ala
100 105 110
Phe Ser Lys Ser Cys His Leu Pro Trp Ala Ser Gly Leu Glu Thr Leu
115 120 125
Asp Ser Leu Gly Gly Val Leu Glu Ala Ser Gly Tyr Ser Thr Glu Val
130 135 140
Val Ala Leu Ser Arg Leu Gln Gly Ser Leu Gln Asp Met Leu Trp Gln
145 150 155 160
Leu Asp Leu Ser Pro Gly Cys
165
<210>358
<211>167
<212>PRT
<213>小鼠(Mus musculus)
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Met Cys Trp Arg Pro Leu Cys Arg Phe Leu Trp Leu Trp Ser Tyr Leu
1 5 10 15
Ser Tyr Val Gln Ala Val Pro Ile Gln Lys Val Gln Asp Asp Thr Lys
20 25 30
Thr Leu Ile Lys Thr Ile Val Thr Arg Ile Asn Asp Ile Ser His Thr
35 40 45
Gln Ser Val Ser Ala Lys Gln Arg Val Thr Gly Leu Asp Phe Ile Pro
50 55 60
Gly Leu His Pro Ile Leu Ser Leu Ser Lys Met Asp Gln Thr Leu Ala
65 70 75 80
Val Tyr Gln Gln Val Leu Thr Ser Leu Pro Ser Gln Asn Val Leu Gln
85 90 95
Ile Ala Asn Asp Leu Glu Asn Leu Arg Asp Leu Leu His Leu Leu Ala
100 105 110
Phe Ser Lys Ser Cys Ser Leu Pro Gln Thr Ser Gly Leu Gln Lys Pro
115 120 125
Glu Ser Leu Asp Gly Val Leu Glu Ala Ser Leu Tyr Ser Thr Glu Val
130 135 140
Val Ala Leu Ser Arg Leu Gln Gly Ser Leu Gln Asp Ile Leu Gln Gln
145 150 155 160
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165
<210>359
<211>167
<212>PRT
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Thr Leu IIe Lys Thr Ile Val Thr Arg Ile Asn Asp Ile Ser His Thr
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50 55 60
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65 70 75 80
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85 90 95
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100 105 110
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115 120 125
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Val Ala Leu Ser Arg Leu Gln Gly Ser Leu Gln Asp Ile Leu Gln Gln
145 150 155 160
Leu Asp Val Ser Pro Glu Cys
165
<210>360
<211>167
<212>PRT
<213>小鼠(Mus musculus)
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20 25 30
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35 40 45
Gln Ser Val Ser Ala Lys Gln Arg Val Thr Gly Leu Asp Phe Ile Pro
50 55 60
Gly Leu His Pro Ile Leu Ser Leu Ser Lys Met Asp Gln Thr Leu Ala
65 70 75 80
Val Tyr Gln Gln Val Leu Thr Ser Leu Pro Ser Gln Asn Val Leu Gln
85 90 95
Ile Ala Asn Asp Leu Glu Asn Leu Arg Asp Leu Leu His Leu Leu Ala
100 105 110
Phe Ser Lys Ser Cys Ser Leu Pro Gln Thr Ser Gly Leu Gln Lys Pro
115 120 125
Glu Ser Leu Asp Gly Val Leu Glu Ala Ser Leu Tyr Ser Thr Glu Val
130 135 140
Val Ala Leu Ser Arg Leu Gln Gly Ser Leu Gln Asp Ile Leu Gln Gln
145 150 155 160
Leu Asp Val Ser Pro Glu Cys
165
Claims (33)
1.一种将获自哺乳动物的样品分类的方法,包括:
获得与所述样品相关的数据集,所述数据集包括至少三种选自下组蛋白质标记的定量数据:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1;
将所述数据输入用所述数据分类所述样品的分析方法,其中所述分类选自:动脉粥样硬化性心血管疾病分类、健康分类、用药物接触分类、不用药分类;和
根据所述方法的输出值分类所述样品。
2.如权利要求1所述的方法,其特征在于,所述分析方法使用预测模型。
3.如权利要求1所述的方法,其特征在于,所述分析方法包括比较所述获得的数据集与参比数据集。
4.如权利要求3所述的方法,其特征在于,所述参比数据集包括获自一位或多位健康对照的数据,或包括获自一位或多位诊断患有动脉粥样硬化性疾病的对象的数据。
5.如权利要求3所述的方法,其特征在于,还包括获得所述获得的数据集与所述参比数据集的相似度的统计学指标。
6.如权利要求5所述的方法,其特征在于,所述统计学指标通过将所述获得的数据集的至少三个参数与所述参比数据集的相应参数比较得出。
7.如权利要求1所述的方法,其特征在于,所述至少三种蛋白质标记包括选自下组的标记组:MCP-1,IGF-1,TNFa;MCP-1,IGF-1,M-CSF;ANG-2,IGF-1,M-CSF;和MCP-4,IGF-1,M-CSF。
8.如权利要求1所述的方法,其特征在于,所述数据集包括至少四种选自下组的蛋白质标记的定量数据:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。
9.如权利要求8所述的方法,其特征在于,所述至少四种蛋白质标记包括选自下组的标记组:MCP-1,IGF-1,TNFa,IL-5;MCP-1,IGF-1,M-CSF,MCP-2;ANG-2,IGF-1,M-CSF,IL-5;MCP-1,IGF-1,TNFa,MCP-2;和MCP-4,IGF-1,M-CSF,IL-5。
10.如权利要求1所述的方法,其特征在于,所述数据集包括至少五种选自下组的标记的定量数据:MCP-1、MCP-2、MCP-3、MCP-4、嗜酸细胞活化趋化因子、IP-10、M-CSF、IL-3、TNFa、Ang-2、IL-5、IL-7和IGF-1。
11.如权利要求10所述的方法,其特征在于,所述至少五种蛋白质标记选自下组:MCP-1、IGF-1、TNFa、IL-5、M-CSF;MCP-1、IGF-1、M-CSF、MCP-2、IP-10;ANG-2、IGF-1、M-CSF、IL-5、TNFa;MCP-1、IGF-1、TNFa、MCP-2、IP-10;MCP-4、IGF-1、M-CSF、IL-5、TNFa;和MCP-4、IGF-1、M-CSF、IL-5、MCP-2。
12.一种分类获自哺乳动物的样品的方法,包括
获得与所述样品相关的数据集,其中所述数据集包括至少3种选自下组的蛋白质标记的定量数据:MCP1;MCP2;MCP3;MCP4;嗜酸细胞活化趋化因子;IP10;MCSF;IL3;TNFα;Ang2;IL5;IL7;IGF1;IL10;INFγ;VEGF;MIP1a;RANTES;IL6;IL8;ICAM;TIMP1;CCL19;TCA4/6kine/CCL21;CSF3;TRANCE;IL2;IL4;IL13;Il1b;MCP5;CCL9;CXCL1/GRO1;GROα;IL12;和瘦蛋白;
将所述数据输入用所述数据分类所述样品的预测模型,其中所述分类选自:动脉粥样硬化性心血管疾病分类、健康分类、用药分类、不用药分类,其中所述预测模型的至少一项分类质量指标值为至少0.7;和
根据所述预测模型的输出值分类所述样品。
13.如权利要求12所述的方法,其特征在于,所述预测模型的分类质量指标值为至少0.8。
14.如权利要求13所述的方法,其特征在于,所述预测模型的分类质量指标值为至少0.9。
15.如权利要求12所述的方法,其特征在于,所述质量指标选自:AUC和准确率。
16.如权利要求12所述的方法,其特征在于,调整所述预测模型的限度使得灵敏度或特异性至少其一是至少0.7。
17.如权利要求14所述的方法,其特征在于,调整所述预测模型的限度使得灵敏度或特异性至少其一是至少0.7。
18.如权利要求1所述的方法,其特征在于,所述动脉粥样硬化性疾病分类选自下组:冠状动脉疾病、心肌梗塞和心绞痛。
19.如权利要求1所述的方法,其特征在于,还包括使用所述分类进行动脉粥样硬化诊断、确定动脉粥样硬化阶段、动脉粥样硬化预后、血管炎症水平、评估动脉粥样硬化发展程度、监测治疗反应、预测冠状动脉钙化度、或区分动脉粥样硬化性疾病的稳定和不稳定表现。
20.如权利要求1所述的方法,其特征在于,所述数据集还包括一种或多种临床指标的数据。
21.如权利要求20所述的方法,其特征在于,所述一种或多种临床指征选自下组:年龄、性别、LDL浓度、HDL浓度、甘油三酯浓度、血压、体重指数、CRP浓度、冠状动脉钙化度、腰围、吸烟情况、心血管疾病病史、心血管疾病家族史、心率、空腹胰岛素浓度、空腹葡萄糖浓度、糖尿病状态和使用高血压药物的情况。
22.如权利要求1所述的方法,其特征在于,所述样品包括血液或血液衍生物。
23.如权利要求1所述的方法,其特征在于,所述分析方法包括采用线性辨别分析模型、支持向量机分类算法、递归特征排除模型、微阵列模型预测分析、对数回归模型、CART算法、FlexTree算法、LART算法、随机森林算法、MART算法或机械学习算法。
24.如权利要求23所述的方法,其特征在于,所述方法包括利用线性辨别分析模型或对数回归模型,所述模型包括提供高于0.75的质量指标的参数项。
25.如权利要求1所述的方法,其特征在于,还包括实现对在多个不同时刻获得的对象的多份样品的多种分类。
26.一种将获自哺乳动物的样品分类的方法,包括
获得与所述样品相关的数据集,其中所述数据集包括至少3种选自下组的蛋白质标记的定量数据,各标记显示循环蛋白质浓度与动脉粥样硬化性血管组织RNA浓度之间的关联;
将所述数据输入用所述数据分类所述样品的分析方法,其中所述分类选自:动脉粥样硬化性心血管疾病分类、健康分类、用药分类、不用药分类;和
根据所述方法的输出值分类所述样品。
27.如权利要求26所述的方法,其特征在于,所述关联的特征在于皮尔逊相关系数至少是0.6。
28.如权利要求27所述的方法,其特征在于,所述至少三种蛋白质标记包括一种或多种选自下组的蛋白质标记:MCP-1、CCL21、CCL19、CCLl12、TNFSF11和CCL11。
29.如权利要求26所述的方法,其特征在于,所述哺乳动物是人。
30.一种将获自哺乳动物的样品分类的方法,包括
获得与所述样品相关的数据集,其中所述数据集包括至少3种选自下组的蛋白质标记的定量数据,各标记显示循环蛋白质浓度与动脉粥样硬化性血管组织RNA浓度之间的关联;
将所述数据输入用所述数据分类所述样品的预测模型,其中所述分类选自:动脉粥样硬化性心血管疾病分类、健康分类、用药分类、不用药分类,其中所述预测模型的至少一项分类质量指标值为至少0.7;和
根据所述预测模型的输出值分类所述样品。
31.如权利要求30所述的方法,其特征在于,所述关联的特征在于皮尔逊相关系数至少是0.6。
32.如权利要求31所述的方法,其特征在于,所述至少三种蛋白质标记包括一种或多种选自下组的蛋白质标记:MCP-1、CCL21、CCL19、CCLl12、TNFSF11和CCL11。
33.如权利要求30所述的方法,其特征在于,所述哺乳动物是人。
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