基于PDE4D7和DHX9表达的术前风险分层

摘要

本发明涉及前列腺癌对象的术前风险分层的方法，包含确定得自所述对象的生物学样品中磷酸二酯酶4D变体7(PDE4D7)的基因表达谱，确定得自所述对象的相同或另一生物学样品中DExH‑box解旋酶9(DHX9)的基因表达谱，以及基于PDE4D7的基因表达谱和DHX9的基因表达谱确定所述对象的术前预后风险评分。这可以在术前设置中改良对象的分层，可以获得更好的一级治疗决策。例如，对于前列腺癌患者的某些亚群，术前预后风险评分可以对于是否选择主动监测还是主动干预例如根治性前列腺切除术提出更好建议。

说明书

发明领域

本发明涉及前列腺癌对象的术前风险分层的方法。此外，本发明涉及一种诊断试剂盒，涉及所述诊断试剂盒在前列腺癌对象的术前风险分层方法中的应用，及涉及磷酸二酯酶4D变体7(PDE4D7)的基因表达谱和DExH-box解旋酶9(DHX9)的基因表达谱在前列腺癌对象的术前风险分层中的应用，以及涉及相应的计算机程序产品。

发明背景

癌症是其中一组细胞呈现不受控制的生长、侵入和有时转移的一类疾病。癌症的这三种恶性性质使其与良性肿瘤区分开来，良性肿瘤是自限性且不侵入或转移。前列腺癌(PCa)是男性中最常见的非皮肤恶性肿瘤，2012年全世界诊断出约110万新病例(参见Ferlay J.et al.,GLOBOCAN 2012v1.0,Cancer Incidence and Mortality Worldwide:IARC CancerBase No.11[Internet],Lyon,France,International Agency for Researchon Cancer,2013)。

由于人口老龄化，PCa的发病率在未来将进一步增加(见Quon H.et al.,“Dramatic increase in prostate cancer cases by 2021”,BJU International,Vol.108,No.11,pages 1734to1738,2011)。通过确定前列腺特异性抗原(PSA)的血液水平、直肠指检(DRE)和经直肠超声分析(TRUS)的常规诊断导致非癌性、良性前列腺状况的显著一线过度诊断(见Bangma C.H.et al.,“Overdiagnosis and overtreatment of earlydetected prostate cancer”,World Journal of Urology,Vol.25,No.1,pages 3to 9,2007，及

在美国每年大约250,000新检测的PCa病例中，大约200,000最初被定性为局部疾病(见Snyder C.F.et al.,“How does initial treatment choice affect short-termand long-term costs for clinically localized prostate cancer？”,Cancer,Vol.116,No.23,pages 5391to 5399,2010及Cooperberg M.R.et al.,“Contemporarytrends in low risk prostate cancer:risk assessment and treatment”,Journal ofUrology,Vol.173,No.3,Pt.2,pages 14to 19,2007)，即癌症局限于前列腺器官。这种状况在一定程度上可通过一级治疗(primary treatment)方法治愈，例如放射治疗或特别是通过手术(前列腺切除术)部分或完全切除前列腺。然而，这些干预通常伴有严重副作用，特别是尿失禁和/或勃起功能障碍，这是前列腺切除术的非常常见后果。接受根治性前列腺切除术的男性中多达50％会出现尿失禁。研究表明，在手术后一年仍有15％-50％的男性报告这种问题。勃起问题同样是根治性前列腺切除术(RP)的严重副作用。只有大约一半的手术男子能够恢复一些勃起的能力。而且，所有常规应用的局部PCa治疗都很昂贵(通常约为20-30,000美元级别)，每年在美国产生的直接总费用为50亿美元。

在美国经诊断为临床局部疾病的大约200,000名男性中，高达50％的人患有极低风险或低风险的癌症(见Bangma C.H.and Roobol M.J.,“Defining and predictingindolent and low prostate cancer”,Critical Reviews in Oncology/Hematology,Vol.83,No.2,pages235to 241,2012)。因此，NCCN(国家综合癌症网)最近修订了其PCa治疗指南，扩大主动监测(AS)作为用于这种低风险疾病患者的温和及便利治疗选择(见www.nccn.org)。通过将适当的患者转诊至AS，这些患者的生活质量与经历一级治疗的男性相比显著提高，且据报道每位患者AS的5年费用低于10,000美元(见Snyder C.F.et al.)。

此外，在选择手术(相对于AS)作为指定患者的治疗选项的情况中，根据患者肿瘤的潜在进展性对手术范围进行分层具有显著优势。例如，神经保护(nerve-sparing)手术技术可以更普遍地应用于具有预测低风险疾病的男性，以使根治性前列腺切除术的性能力相关副作用最小化。同样，根据欧洲泌尿科学会(EAU)最新的前列腺癌指南，尽管与更有限的方法相比扩大淋巴结清扫术手术过程复杂、耗时且与更高的并发症发生率相关，但仍建议在预测高风险癌症的情况下实施(见Heidenreich A.et al.,“Guidelines on ProstateCancer”,European Association of Urology,2012)。因此，虽然较少限制的淋巴结清扫显示错过大约50％的淋巴结转移(见Heidenreich A.et al.,“Extended pelviclymphadenectomy in patients undergoing radical prostatectomy:high incidenceof lymph node metastasis”,Journal of Urology,Vol.167,No.4,pages 1681to 1686,2002及Bader P.et al,“Is a limited lymph node dissection and adequate stagingprocedure for prostate cancer？”,Journal of Urology,Vo.168,No.2,pages 514to518,2002)，但局部前列腺癌患者的治疗方案需要个体肿瘤的进展性潜力的高度准确的术前预测，以为每名患者提供最佳护理。

WO 2014/028884 A2公开了用于诊断、预后和确定对象中癌症进展的方法、系统和试剂盒。进一步公开了用于确定对象中癌症的治疗方式的方法、系统和试剂盒。所述方法、系统和试剂盒包含基于表达的生物标志物分析。还公开了用于评估对象的癌症状态的探针组。

发明概述

本发明的目的是提供一种前列腺癌对象的术前风险分层的方法，其可以对个体肿瘤的侵袭性潜力进行更好的术前预测。本发明的另一个目的是提供一种诊断试剂盒、所述诊断试剂盒在前列腺癌对象的术前风险分层的方法中的应用、磷酸二酯酶4D变体7(PDE4D7)的基因表达谱和DExH-box解旋酶9(DHX9)的基因表达谱在前列腺癌对象的术前风险分层中的应用，以及相应的计算机程序产品。

在本发明的第一方面，提出了一种前列腺癌对象的术前风险分层的方法，其包含：

-确定得自所述对象的生物学样品中磷酸二酯酶4D变体7(PDE4D7)的基因表达谱，

-确定得自所述对象的相同或另一生物学样品中DExH-box解旋酶9(DHX9)的基因表达谱，和

-基于PDE4D7的基因表达谱和DHX9的基因表达谱确定所述对象的术前预后风险评分。

已知cAMP信号传导通路在前列腺癌的发生和发展中均起重要作用(见MerkleD.and Hoffmann R.,“Roles of cAMP and cAMP-dependent protein kinase in theprogression of prostate cancer:Cross-talk with the androgen receptor”,Cellular Signalling,Vol.23,No.3,pages 507-515,2011)。虽然腺苷酸环化酶家族负责cAMP的合成，但环状核苷酸磷酸二酯酶(PDE)似乎代表了其破坏的唯一细胞机制。PDE既提供信号终止功能，更重要的是提供cAMP信号传导在细胞3D基质内的区室化。这是通过局部性锚定蛋白/信号转导体(signalosomes)隔离的不同PDE同种型的亚群对cAMP的空间离散破坏而实现的(见例如Conti M.and Beavo J.,“Biochemistry and physiology ofcyclic nucleotide phosphodiesterases:essential components in cyclicnucleotide signaling”,Annual Review of Biochemistry,Vol.76,pages 481-511,2007)。因此，不同PDE同种型的表达和/或活性的变化可以改变疾病发生和进展期间下游信号传导通路，为新生物标志物和靶向治疗干预提供潜在靶。事实上，降解cAMP的PDE4家族成员的表达的改变似乎与许多不同疾病有关，包括卒中、肢端骨发育不全、精神分裂症和COPD。近年来，显示特定PDE4同种型(PDE4D7)的下调对前列腺癌可能有影响(见例如

新兴证据表明，人解旋酶如DHX9可以充当细胞网络中的枢纽，以协调细胞应激反应，维持细胞稳态以生存或触发细胞死亡。有趣的是，最近已显示出一系列人癌细胞系在体外和体内都易于抑制DHX9解旋酶的活性。DHX9抑制后肿瘤细胞的基因表达谱分析揭示了参与肿瘤发生或发展的一系列通路的脱调节。此外，DHX9近来已被描述为是解决R环相关DNA损伤的主要参与者，其支持维持基因组稳定性。由于基因组水平上的重排，这个过程的破坏可能导致癌症发生和进展，这一现象已在许多癌症中得到证实。这些新近的发现得到本发明人产生的数据的有力支持，示出DHX9基因表达与在纵向随访中临床前列腺癌患者队列中前列腺癌复发时间显著相关(未公开的数据)。

本发明人鉴别并证实了前列腺癌细胞中PDE4D7和解旋酶DHX9之间的相互作用。另外，可以示出DHX9的N-末端结构域在体外通过cAMP依赖性蛋白激酶A(PKA)磷酸化。这就提出了一个问题，即这种通过PKA的翻译后修饰是否对DHX9的活性或细胞定位有任何调节作用，以及与PDE4D7的相互作用是否通过调节环AMP影响DHX9的微结构域中的磷酸化。有鉴于此，作为新鉴别的DHX9的相互作用因子，PDE4D7可能在直接或间接控制DHX9在前列腺癌发生中的功能中起关键作用。

通过基于PDE4D7和DHX9二者的基因表达谱确定前列腺癌对象的术前预后风险评分，获得了代表疾病生物学的额外分子学信息。通过基于PDE4D7和DHX9二者的基因表达谱确定术前预后风险评分，PDE4D7和DHX9的预后能力可用于术前患者风险评估。这样可以在术前设置中改良对象的分层，可以获得更好的一级治疗决策。例如，对于前列腺癌患者的某些亚群，术前预后风险评分可以就是否选择主动监测还是主动干预例如根治性前列腺切除术提出更好建议。

术语“磷酸二酯酶4D7”或“PDE4D7”是指人磷酸二酯酶PDE4D的剪接变体7，即人磷酸二酯酶PDE4D7基因，例如NCBI参考序列：NM_001165899.1中所定义的序列，特别是SEQ IDNO：19所示的核苷酸序列，其对应于上述PDE4D7转录物的NCBI参考序列的序列，以及还涉及相应的氨基酸序列，例如SEQ ID NO：20所示，其对应于编码PDE4D7多肽的NCBI蛋白质登录参考序列NP_001159371.1中定义的蛋白质序列。术语“磷酸二酯酶4D7”或“PDE4D7”还涉及可由引物对PDE4D7_正向(SEQ ID NO：21)和PDE4D7_反向(SEQ ID NO：22)生成并可由探针SEQ ID NO：23检测的扩增子。

PDE4D7多肽也可以用引物对PDE4D7-2_正向(SEQ ID NO：24)和PDE4D7_反向(SEQID NO：25)检测并可以用探针SEQ ID NO：26检测。

术语“PDE4D7”还包含与PDE4D7具有高度同源性的核苷酸序列，例如与SEQ ID NO：19所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的核酸序列，或者与SEQ ID NO：20所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的氨基酸序列，或者编码与SEQID NO：20所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的氨基酸序列的核酸序列，或者由与SEQ ID NO：19所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的核酸序列编码的氨基酸序列。

术语“DExH-box解旋酶9”或“DHX9”是指人DExH-box解旋酶9基因，例如NCBI参考序列：NM_001357.4(Ensembl：ENSG00000135829)中定义的序列，特别是SEQ ID NO：74所示核苷酸序列，其对应于上述DHX9转录物的NCBI参考序列的序列，还涉及例如SEQ ID NO：75所示相应氨基酸序列，其对应于编码DHX9多肽的NCBI蛋白质登录参考序列NP_001348.2中定义的蛋白质序列。

术语“DHX9”还包含与DHX9具有高度同源性的核苷酸序列，例如与SEQ ID NO：74所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的核酸序列，或者与SEQ ID NO：75所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的氨基酸序列，或者编码与SEQID NO：75所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的氨基酸序列的核酸序列，或者由与SEQ ID NO：74所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的核酸序列编码的氨基酸序列。

术语“生物学样品”或“得自对象的样品”是指通过本领域技术人员已知的合适方法从对象例如前列腺癌患者获得的任何生物学材料。可以以临床上可接受的方式例如以保存核酸(特别是RNA)或蛋白质的方式来收集所使用的生物学样品。

所述生物学样品可以包括机体组织和/或体液，例如但不限于血液、汗液和尿液。此外，生物学样品可以包含来源于上皮细胞的细胞提取物或包括上皮细胞的细胞群，例如癌上皮细胞或来源于怀疑是癌性组织的上皮细胞。所述生物学样品可以包含源自腺组织的细胞群，例如所述样品可以源自男性对象的前列腺。另外，如果需要，可以从获得的机体组织和体液中纯化细胞，然后用作生物学样品。在一些实例中，所述样品可以是组织样品、尿液样品、尿沉渣样品、血液样品、唾液样品、精液样品、包括循环肿瘤细胞的样品、细胞外囊泡、包含前列腺分泌的外泌体的样品，或者细胞系或癌细胞系。

在一特定实例中，可以获取和/或使用活检或切除术样品。这种样品可以包括细胞或细胞裂解物。

还可以想到的是，将生物学样品的内容物进行富集步骤。例如，可以将样品与特异于某些细胞类型例如前列腺细胞的细胞膜或细胞器的配体接触，所述配体例如被磁性颗粒功能化。被磁性颗粒浓缩的材料可随后用于如上文或下文所述的检测和分析步骤。

此外，可以通过流体或液体样品例如血液、尿液等的过滤方法来富集细胞例如肿瘤细胞。这种过滤方法还可以与如上所述基于配体特异性相互作用的富集步骤组合。

术语“前列腺癌”是指男性生殖系统前列腺的癌症，其在前列腺细胞突变并开始失控增殖时发生。通常，前列腺癌与升高水平的前列腺特异性抗原(PSA)相关。在本发明的一个实施方案中，术语“前列腺癌”涉及示出PSA水平高于4.0的癌症。在另一个实施方案中，该术语涉及示出PSA水平高于2.0的癌症。术语“PSA水平”是指血液中PSA浓度，单位为ng/ml。

术语“非进行性前列腺癌状态”是指个体样品未示出指示“生化复发”和/或“临床复发”的参数值。

术语“进行性前列腺癌状态”是指个体样品示出指示“生化复发”和/或“临床复发”的参数值。

术语“生化复发”通常是指增加的PSA复发生物学值，表明样品中存在前列腺癌细胞。然而，也可以使用可用于检测存在或疑似这种存在的其它标记物。

术语“临床复发”是指存在指示肿瘤细胞存在的临床迹象，例如使用体内成像测量。

如本文所用，术语“预后前列腺癌”是指例如在一段时间内、在治疗期间或治疗后，预测经诊断或检测的前列腺癌的进程或结局。该术语还指确定对象从疾病中存活或恢复的机会，以及预测对象的预期存活时间。具体地，预后可包括确定对象在未来一段时间例如6个月、1年、2年、3年、5年、10年或任何其它时间段内存活的可能性。

优选将PDE4D7的基因表达谱和DHX9的基因表达谱与得自一群前列腺癌对象的回归函数组合。

回归分析帮助人们理解，当任意一个自变量发生变化而其它自变量保持固定时，因变量(或“标准变量”)的典型值将如何变化。在回归函数中记录了因变量和自变量之间的这种关系，可用于在给定自变量值的情况下预测因变量。因变量可以是例如二元变量，例如手术后5年内的生化复发。在这种情况下，回归是基于自变量(在此包括PDE4D7的基因表达谱和DHX9的基因表达谱或由PDE4D7的基因表达谱和DHX9的基因表达谱组成)的对数函数的对数回归。借助回归函数，可以改良预测例如手术后5年生化复发风险。

优选所述方法进一步包含：

-基于术前预后风险评分，为对象建议一级治疗，其中所述一级治疗选自：(i)至少部分前列腺切除术；(ii)选自放射治疗、激素治疗、化学疗法及其组合的主动治疗；和(iii)主动监测。

各种国家和国际指南根据未来疾病进展的风险和预期寿命，建议对前列腺癌对象采用不同治疗。例如，通常建议对患有极低和低风险前列腺癌的男性进行主动监测(AS)，而对于高风险癌症则可能指示根治性前列腺切除术。然而，已知的临床风险描述符不能有效地描述疾病的程度或其对所有患者的侵袭性。例如，已经发现，在国家综合癌症网络(NCCN)极低风险和低风险组中，存在一个明显的患者群亚组，其在一级治疗后有10％-25％癌症复发风险。同样，已知在中等风险组中，存在一个亚群，具有低生化进展风险。通过根据术前预后风险评分为对象建议一级治疗，在以下方面提供更好的建议：对于前列腺癌患者的某些亚群，可以决定是否选择主动监测还是主动干预如根治性前列腺切除术。

进一步优选所述方法包含：

-相对于选自以下的一或多个参考基因，将PDE4D7的基因表达谱和/或DHX9的基因表达谱标准化：智人次黄嘌呤磷酸核糖基转移酶1(HPRT1)，微管蛋白-α-1b(TUBA1B)，智人pumilio RNA结合家族成员(PUM1)和智人TATA盒结合蛋白(TBP)，其中基于标准化的基因表达谱确定术前预后风险评分。

通过针对一或多个参考基因对基因表达谱进行标准化及基于标准化的基因表达谱确定术前预后风险评分，可以降低确定术前预后风险评分中的可变性。这使得可以区分基因表达谱的实际变化和由于测量方法所致变化。在这方面，已经发现HPRT1、TUBA1B、PUM1和TBP特别适合用作标准化PDE4D7和/或DHX9基因表达谱的参考基因。

可以通过使用一或多个引物和/或探针和/或一或多组引物和/或探针检测mRNA表达来确定基因表达谱。此外，可以通过基于扩增的方法和/或微阵列分析和/或RNA测序确定基因表达谱。基因表达谱的确定可以包括对从生物学样品中提取的RNA进行实时定量聚合酶链反应(RT-qPCR)。在其它实施方案中，通过RNA测序、常规PCR(使用例如通过凝胶电泳的终点分析)或多重PCR确定基因表达谱。在RT-qPCR的情况中，基因表达谱的确定可以包括确定PDE4D7和/或DHX9以及所述一或多个参考基因中每一个的阈值循环(Ct)值。可以用至少一个引物和/或探针进行PCR以测量选自HPRT1、TUBA1B、PUM1和TBP的参考基因。

优选所述一或多个参考基因包括HPRT1、TUBA1B、PUM1和TBP中的至少两个、或至少三个、或所有。

可以另外地或替代地用于标准化PDE4D7和/或DHX9基因表达谱的其它参考基因包括：智人肌动蛋白βmRNA(ACTB)；智人60S酸性核糖体磷蛋白P0 mRNA(RPLP0)；聚合酶(RNA)II(DNA定向)多肽A，220kDa(POLR2A)；β-2-微球蛋白(B2M)；及氨基乙酰丙酸-δ-合酶(ALAS-1)。

在一些优选的实施方案中，使用合适的转换函数，将标准化的PDE4D7和/或DHX9的基因表达谱转换为预定值范围，例如1-5的范围。转换函数优选得自对应的标准化的基因表达谱，例如对于源自一群前列腺癌对象(其有力地可以与用于获得回归函数的群体相同)的生物学样品，相对于HPRT1、TUBA1B、PUM1和TBP所有对PDE4D7和/DHX9标准化的基因表达谱。在一个优选的实例中，转换函数可以是线性转换，其将标准化的基因表达谱转换为预定的值范围。这种转换可以通过考虑对于前列腺癌对象群体的生物学样品针对例如PDE4D7(或DHX9)的标准化的基因表达谱值的频率分布以及通过确定将频率分布转换为期望范围的转换而确定。通过利用这种转换函数，可以以用户直观的方式表示所述基因表达谱，例如小的正值范围。这类似于临床常规中使用的其它类别，例如组织病理学分级(Gleason)或多参数MRI放射评分(PIRADS)。

在一个特定实例中，转化的标准化的基因表达谱如下确定：

TNGEP＝(((GENE_norm+A)*B)+1)， (1)

其中“TNGEP”是转换的标准化的基因表达谱，“GENE_norm”是标准化的PDE4D7或DHX9基因表达谱值，A和B是变量并适当地选择以将“GENE_norm”映射为期望的值范围。

特别优选地，确定PDE4D7的基因表达谱和/或DHX9的基因表达谱包括对从生物学样品中提取的RNA进行RT-qPCR，其中确定PDE4D7和/或DHX9和/或所述一或多个参考基因中每一个的Cq值，其中确定术前风险评分包括使用所述一或多个参考基因中每一个的Cq值标准化PDE4D7和/或DHX9的Cq值及基于标准化的Cq值计算术前风险评分。

例如，可以通过应用下式产生PDE4D7的标准化的Cq值：

N(Cq

其中N(Cq

同样，可以通过应用下式产生DHX9的标准化的Cq值：

N(Cq

其中N(Cq

在本发明的另一方面，提出了一种诊断试剂盒，其包含：

至少一个引物和/或探针，用于确定得自前列腺癌对象的生物学样品中磷酸二酯酶4D变体7(PDE4D7)的基因表达谱；

至少一个引物和/或探针，用于确定得自所述对象的相同或另一生物学样品中DExH-box解旋酶9(DHX9)的基因表达谱；和

任选地，用于确定一或多个参考基因的基因表达谱的至少一个引物和/或探针，所述参考基因选自：智人次黄嘌呤磷酸核糖基转移酶1(HPRT1)，微管蛋白α-1b(TUBA1B)，智人pumilio RNA结合家族成员(PUM1)和智人TATA盒结合蛋白(TBP)；

其中所述诊断试剂盒进一步包含用于基于PDE4D7的基因表达谱和DHX9的基因表达谱计算术前预后风险评分的指令，所述指令存储在计算机程序产品上，当计算机执行时，其执行一种方法，所述方法包含：

-基于PDE4D7的基因表达谱和DHX9的基因表达谱确定所述对象的术前预后风险评分，任选地，其中所述方法包含：

-相对于所述一或多个参考基因标准化PDE4D7的基因表达谱和/或DHX9的基因表达谱，

其中，基于标准化的基因表达谱确定术前预后风险评分。

优选地，用于计算术前预后风险评分的指令包含将PDE4D7的基因表达谱和DHX9的基因表达谱与得自一群前列腺癌对象的回归函数组合的指令。

在本发明的另一方面，提供了如权利要求7或8所述的诊断试剂盒在前列腺癌对象的术前风险分层的方法中的应用。

在本发明的另一方面，提供了磷酸二酯酶4D变体7(PDE4D7)的基因表达谱和DExH-box解旋酶9(DHX9)的基因表达谱在前列腺癌对象的术前风险分层中的应用，包含：

-确定得自所述对象的生物学样品中PDE4D7的基因表达谱，

-确定得自所述对象的相同或另一生物学样品中DHX9的基因表达谱，和

-基于PDE4D7的基因表达谱和DHX9的基因表达谱确定所述对象的术前预后风险评分。

优选将PDE4D7的基因表达谱和DHX9的基因表达谱与得自一群前列腺癌对象的回归函数组合。

在本发明的另一方面，提供了一种包含指令的计算机程序产品，当计算机执行程序时，所述指令使计算机执行一种方法，所述方法包含：

-基于磷酸二酯酶4D变体7(PDE4D7)的基因表达谱和DExH-box解旋酶9(DHX9)的基因表达谱确定前列腺癌对象的术前预后风险评分，

其中PDE4D7的基因表达谱在得自所述对象的生物学样品中确定，并且DHX9的基因表达谱在得自所述对象的相同或另一生物学样品中确定。

优选将PDE4D7的基因表达谱和DHX9的基因表达谱与得自一群前列腺癌对象的回归函数组合。

在进一步优选的实施方案中，基于术前预后风险评分和术后临床风险评分CAPRA-S确定所述对象的术后预后风险评分。

优选将术前预后风险评分和术后临床风险评分CAPRA-S与得自一群前列腺癌对象的回归函数组合。

这些进一步优选的实施方案可以通过权利要求1的方法、权利要求7的诊断试剂盒、权利要求9的诊断试剂盒的应用、权利要求10的基因表达谱的应用以及权利要求12的计算机程序来实现。

应当理解，权利要求1的方法、权利要求7的诊断试剂盒、权利要求9的诊断试剂盒的应用、权利要求10的基因表达谱的应用和权利要求12的计算机程序具有相似和/或相同的优选实施方案，特别是如所附权利要求书中所定义。

应当理解，本发明的优选实施方案也可以是所附权利要求书或以上实施方案和各个独立权利要求的任意组合。

参考下文描述的实施方案，本发明的这些和其它方面将变得明显并得到阐明。

附图简述

在如下图示中：

图1图示示例说明对前列腺癌对象的术前风险分层方法实施方案的流程图，

图2示出RP患者队列中前列腺癌手术后5年生化复发(BCR)的ROC曲线分析的结果，

图3示出RP患者队列中前列腺癌手术后10年临床复发(CR)的ROC曲线分析的结果，以及

图4示出RP患者队列中前列腺癌手术后10年前列腺癌特异性死亡的ROC曲线分析的结果。

实施方案详述

术前风险分层综述

图1图示示例说明前列腺癌对象的术前风险分层方法实施方案的流程图。

所述方法在步骤S100起始。

在步骤S102，从经诊断患有前列腺癌的第一组患者(对象)中每个患者获得一或多个生物学样品。优选地，在获得生物学样品之后，例如至少一年、或至少两年、或大约五年的一段时间，对这些前列腺癌患者进行前列腺癌监测。

在步骤S104，例如通过对从每个生物学样品中提取的RNA进行RT-qPCR(实时定量PCR)，对从第一组患者中每个患者中获得的相同或不同生物学样品获得PDE4D7和DHX9的基因表达谱。示例的基因表达谱包括PDE4D7和DHX9的表达水平(例如值)，可以使用一组参考基因例如HPRT1、TUBA1B、PUM1和/或TBP中每个基因的值将其标准化。在一个实例中，相对于选自HPRT1、TUBA1B、PUM1和TBP的一或多个参考基因、例如至少一个或至少两个基因或至少三个或优选所有这些参考基因将PDE4D7和DHX9的基因表达谱值标准化。

在步骤S106，基于对得自第一组患者的至少一些生物学样品获得的PDE4D7和DHX9的基因表达谱和得自所述监测的各个结果，确定赋予术前预后风险评分的回归函数。在一个可能的实例中，首先使用合适的转换函数将PDE4D7和/或DHX9的标准化的基因表达谱转换为预定的值范围，例如上述1-5的范围。如上所述，这种转换可以通过考虑例如一群前列腺癌对象(在此为第一组患者)的生物学样品的PDE4D7(或DHX9)的标准化的基因表达谱值的频率分布以及通过确定将频率分布转换为期望范围的转换而确定。在一个特定实例中，如上文等式(1)所示确定标准化的转换的基因表达谱值。

在步骤S108，从患者(对象或个体)获得一或多个生物学样品。所述患者可以是新患者或第一组中的一个。

在步骤S110，例如通过对生物学样品进行PCR而获得PDE4D7和DHX9的基因表达谱。在一个实例中，相对于选自HPRT1、TUBA1B、PUM1和TBP的一或多个参考基因、例如至少一个或至少两个或至少三个或优选所有这些参考基因，将PDE4D7和DHX9的基因表达谱值标准化。这与步骤S104基本相同。此外，PDE4D7和/或DHX9的标准化的基因表达谱可以如关于步骤S106所述进行预转换。

可以在步骤S104和S110中另外或替代地使用的其它参考基因包括：智人肌动蛋白βmRNA(ACTB)；智人60S酸性核糖体磷蛋白P0 mRNA(RPLP0)；聚合酶(RNA)II(DNA定向)多肽A，220kDa(POLR2A)；β-2-微球蛋白(B2M)；以及氨基乙酰丙酸-δ-合酶(ALAS-1)。

在步骤S112，基于PDE4D7和DHX9的基因表达谱，使用回归函数确定患者的术前预后风险评分。稍后将在说明书中对此进行更详细地描述。为了使术前预后评分对于用户直观，还可以确定其值在预定义的数值范围内，例如1-5的范围。这可以通过回归函数本身实现，也可以通过随后将回归函数的输出值转换为期望的值范围的合适转换实现。同样，这类似于临床常规中使用的其它类别，例如组织病理学分级(Gleason)或多参数MRI放射评分(PIRADS)。

在步骤S114，可以基于术前预后风险评分为例如患者或其监护人、医生或其它医护人员提供治疗建议。为此，可以基于术前预后风险评分的值将术前预后风险评分分类为预定风险组之一。提供治疗建议可包括以下一或多项：a)基于指派的风险组为患者提出治疗方案，其中至少两个风险组与不同治疗相关；b)计算在前列腺手术之前或之后患者的疾病进展风险预测；和c)计算在前列腺手术之前或之后患者的治疗反应预测。示例治疗包括至少部分前列腺切除术，选自放射治疗、化学治疗及其组合的主动治疗，以及单独观察，即不进行前列腺切除术或主动治疗(即主动监测)。

所述方法在步骤S116结束。

每个风险组都可能与各自的提议治疗相关，其侵袭性有所不同。每种提议的治疗可以基于指派给该风险组的第一组患者的结果，而且是被预测为提供不超过发生前列腺癌的阈值临床风险的最小侵袭性治疗。在某些情况下，与使用其它风险分析方法例如使用Gleason评分、NCCN风险类别或术前CAPRA评分的情况相比，这可以将新患者指派至与低侵袭性提议治疗相关的风险组中。

在一个实施方案中，通过使用一或多个引物和/或探针和/或一或多组引物和/或探针检测mRNA表达来确定在步骤S104和S110的基因表达谱。

表1示出PDE4D7、DHX9和所述一或多个参考基因的详细说明，包括其转录物ID(NCBI RefSeq)以及引物对和探针的相应氨基酸序列。这个表还示出了每个基因的有义引物和反义引物，以及与扩增子特异性结合的探针序列。

表1：示例引物和探针核酸序列

代替使用RT-qPCR，在其它实施方案中，步骤S104和S110的PDE4D7和/或DHX9的基因表达谱可以通过其它方式例如通过根据标准方法(Illumina，Inc.)进行RNA下一代测序(NGS RNAseq)来确定。在这种情况下，也可以对NGS RNAseq提供的基因表达谱如上述转换为预定的数值范围。

为探讨PDE4D7和DHX9在术前患者风险评估中的预后能力，研究了其与疾病复发的相关性。

在外科手术队列中开发了基于PDE4D7和DHX9基因表达谱的组合模型，并针对不同纵向临床结果对该模型进行验证。结果表明，PDE4D7和DHX9的基因表达谱的组合在改善的术前预后风险评分中可以允许更好的患者分层以优化一级治疗决策。

实施例

患者队列与样品

使用根治性前列腺切除术(RP)患者队列，其人口统计数据示于表2。对于RP患者队列，从575名患者切除的前列腺的代表性肿瘤区域收集小的活检穿孔组织(约1mm×2mm)，所述患者已在2000年至2004年之间相继在德国一个大型临床中心进行手术。

表2：根治性前列腺切除术(RP)患者队列的人口统计学数据

表中示出了队列中患者年龄、术前PSA、活检中肿瘤百分比、前列腺体积和PSA密度的最小值和最大值，而中位数值在括号中示出。对于CAPRA-S风险类别，示出了每个风险组的患者人数和百分比。术后病理学以病理学Gleason评分和Gleason分级组、病理阶段、前列腺切除术后的手术切缘状态、精囊和盆腔淋巴结的肿瘤浸润状态示出(按患者数量和百分比)。在这方面，要注意的是囊外延伸不是作为主要参数提供，而是从病理学阶段pT3a得出的。随访表明所有患者术后数月的平均和中位随访期。结果类别示例了手术一级治疗后的累积5年和10年生化复发(BCR)以及临床复发至转移(CR)。治疗类别列出了手术后累积5年和10年开始至抢救性放射治疗(SRT)或抢救性雄激素剥夺治疗(SADT)。死亡率以前列腺癌特异生存期(PCSS)以及总体生存期(OS)示出。对于所有结果，示出了各自5年或10年随访的经历所述结果的男性人数/总男性人数，其中事件的百分比在括号中给出。

实验室方法

所有使用的实验室方法，包括用于RT-qPCR(定量实时PCR)的寡核苷酸引物和探针、RNA提取以及在统计分析中包括/放弃样品的质量控制和过程，均如之前

结果

PDE4D7和DHX9表达的逻辑回归建模

在逻辑回归建模中使用PDE4D7和DHX9的表达值来创建组合模型。如下表1所示，在完整5年结果历史的RP患者队列的481例RP患者亚队列中(169个事件，35.14％)，以前列腺癌手术后的5年生化复发(BCR)作为因变量。将logit(p)回归函数转换为p＝1/(1+e^(-logit(p))，以计算每个患者在手术后5年内经历生化复发的概率p。表2-6示出组合PDE4D7和DHX9的表达值的逻辑回归建模结果。表1以队列大小(#481)和5年生化复发(BCR)阳性病例数和无5年BCR的阴性病例数描述了逻辑回归建模的输入。表2提供了有关模型拟合的信息，表3概述了回归模型的系数(或权重)以及相应的统计数据。表4概述了PDE4D7和DHX9的比值比，而表5和表6概述了“PDE4D7&DHX9”回归模型的分类表和ROC曲线分析数据。

表1：逻辑回归建模的输入

表2：整体模式拟合

表3：系数和标准误差

表4：比值比和95％置信区间

表5：分类表(截断值p＝0.5).

表6：ROC曲线分析

验证不同纵向临床结果的组合模型

对所述组合模型进行测试，预测手术后的各种临床相关终点，例如生化复发(BCR)、临床复发(进展为局部和/或远端转移)(CR)和前列腺癌特异性死亡。对于相同的各种临床相关终点，比较组合模型的预后能力与仅PDE4D7或DHX9的预后能力。

图2示出具有完整5年随访的RP患者队列的患者亚队列(#481)在前列腺癌手术后5年生化复发(BCR)的ROC曲线分析结果(也见表7)。如表8详细说明，计算的5年AUC(曲线下面积)对于单独的PDE4D7为0.659，对于单独的DHX9为0.624，对于组合模型为0.713(在图2和表8中表示为“PDE4D7&DHX9”)。标准误差分别为0.0254(PDE4D7)、0.0280(DHX9)和0.0242(PDE4D7和DHX9)，95％置信区间分别为0.615-0.702(PDE4D7)，0.579-0.667(DHX9)和0.670-0.753(PDE4D7&DHX9)。表9示出ROC曲线的成对比较。可以看出，单独的PDE4D7以及PDE4D7&DHX9组合模型的AUC经检验是显著差异的(p＝0.0022)。即使对于单独的DHX9以及PDE4D7&DHX9组合模型的AUC，也是如此，甚至略微更为显著(p＝0.0008)。

表7：亚队列

表8：ROC曲线分析

表9：ROC曲线的成对比较

图3示出对具有完整10年随访的RP患者队列的患者亚队列(#335)在前列腺癌手术后10年临床复发(CR)的ROC曲线分析结果(也见表10)。如表11详细说明，计算的10年AUC(曲线下的面积)对于单独的PDE4D7为0.666，对于单独的DHX9为0.691，对于组合模型为0.748(在图3和表11中表示为“PDE4D7&DHX9”)。标准误差分别为0.0364(PDE4D7)、0.0384(DHX9)和0.0314(PDE4D7&DHX9)，95％置信区间分别为0.613-0.717(PDE4D7)、0.639-0.740(DHX9)和0.698-0.794(PDE4D7&DHX9)。表12示出ROC曲线的成对比较。可以看出，单独的PDE4D7以及PDE4D7&DHX9组合模型的AUC经检验是显著差异的(p＝0.0039)。

表10：亚队列

表11：ROC曲线分析

表12：ROC曲线的成对比较

图4示出具有完整10年随访的RP患者队列的患者亚队列(#302)在前列腺癌手术后10年前列腺癌特异性死亡的ROC曲线分析结果(也见表13)。如表14详细说明，计算的10年AUC(曲线下的面积)对于单独的PDE4D7为0.729，对于单独的DHX9为0.622，对于组合模型为0.754(在图4和表14中表示为“PDE4D7&DHX9”)。标准误差分别为0.0588(PDE4D7)、0.0593(DHX9)和0.0481(PDE4D7&DHX9)，95％置信区间分别为0.676-0.779(PDE4D7)、0.564-0.676(DHX9)和0.702-0.802(PDE4D7&DHX9)。表15示出ROC曲线的成对比较。可以看出，单独的DHX9以及PDE4D7&DHX9组合模型的AUC经检验是显著差异的(p＝0.0403)。

表13：亚队列

表14：ROC曲线分析

表15：ROC曲线的成对比较

提供的结果表明，使用PDE4D7和DHX9基因表达值的组合逻辑回归模型预测手术后5年生化复发改良了ROC分析中的曲线下面积(AUC)，与单独使用PDE4D7作为预后指标相比改良2.5％(对于前列腺癌特异性死亡作为终点)至8％(对于临床复发作为终点)。

在自变量数据集中对组合模型预测前列腺癌手术后的转移进行自变量测试

图5示出在自变量数据集中对组合模型(表16中表示为“PDE4D7&DHX9”)预测前列腺癌手术后的转移进行自变量测试(数据来自Taylor B.S.et al.,“Integrative genomicprofiling of human prostate cancer”,Cancer Cell,Vol.18,No.1,pages 11to 22,2010)。如表16中详述，计算的转移类别AUC(曲线下面积)对于PDE4D7&DHX9为0.736。标准误差为0.0777，95％置信区间为0.651-0.809。

表16：自变量数据集

表17：ROC曲线分析

表18：Youden指数

PDE4D7&DHX9组合模型与手术后临床风险评分CAPRA-S的逻辑回归建模以预测手术后转移

将PDE4D7&DHX9组合模型以及手术后临床风险评分CAPRA-S用于其它逻辑回归建模中，产生进一步的组合模型(在下文中表示为“PDE4D7&DHX9&CAPRA-S”)。如下表19所示，在来自Tayler B.S.等的自变量数据中，将因变量作为前列腺癌手术后的转移类别(见上)。将logit(p)回归函数转换为p＝1/(1+e^(-logit(p))以计算每个患者术后出现转移的概率p。表20-26示出组合PDE4D7&DHX9与CAPRA-S评分的逻辑回归建模的结果。表19描述了根据样本大小(#129)以及有转移的阳性病例和无转移的阴性病例数目的逻辑回归建模的输入。表20提供了有关模型拟合的信息，表21概述了具有相应统计信息的回归模型的系数(或权重)。表22概述了PDE4D7&DHX9与CAPRA-S评分的比值比，而表23和24示出回归模型的校准测试结果(根据Hosmer&Lemeshow测试)。最后，表25和26概述了“PDE4D7&DHX9&CAPRA-S”回归模型的分类表的数据以及ROC曲线分析。

表19：逻辑回归建模的输入

表20：整体模型拟合

表21：系数和标准误差

表22：比值比和95％置信区间

表23：Hosmer&Lemeshow检验

表24：Hosmer&Lemeshow检验的列联表

表25：分类表(截断值p＝0.5)

表26：ROC曲线分析

图6示出了PDE4D7&DHX9以及PDE4D7&DHX9&CAPRA-S组合模型预测前列腺癌手术后转移的ROC分析(数据得自Taylor B.S.et al.,“Integrative genomic profiling ofhuman prostate cancer”,Cancer Cell,Vol.18,No.1,pages 11to 22,2010)。如表28详细说明，经计算的转移类别AUC(曲线下的面积)对于单独的PDE4D7&DHX9为0.736，对于PDE4D7&DHX9&CAPRA-S为0.840。标准误差分别为0.0777(PDE4D7&DHX9)和0.0636(PDE4D7&DHX9&CAPRA-S)，95％置信区间分别为0.651-0.809(PDE4D7&DHX9)和0.765-0.899(PDE4D7&DHX9&CAPRA-S)。表29示出ROC曲线的成对比较。可以看出，单独的PDE4D7&DHX9与PDE4D7&DHX9&CAPRA-S组合模型的AUC经检验是显著差异的(p＝0.0323)，AUC差异为0.104(或10.4％)。

表27：自变量数据集

表28：ROC曲线分析

表29：ROC曲线的成对比较

讨论

原发性局限性前列腺癌的治疗决策在很大程度上取决于未来疾病进展的风险和预期寿命的组合。提供的数据表明，与单独使用PDE4D7作为预后标志物相比，在术前风险评分中使用PDE4D7和DHX9组合可增加价值。因此，DHX9在临床预测模型中可以为PDE4D7增加对疾病特定结果的预后价值，例如手术后进展为生化复发或临床复发至转移以及预测癌症特异生存率以支持治疗决策确定。

通过研究附图、公开内容和所附权利要求，本领域技术人员在实践请求保护的发明时可以理解和实现所公开的实施方案的其它变型。

在权利要求术中，单词“包含”不排除其它元素或步骤，不定冠词“a”或“an”不排除多个。

图1所示方法的一或多个步骤可以在可在计算机上执行的计算机程序产品中执行。所述计算机程序产品可以包含其上记录(存储)有控制程序的永久性计算机可读记录介质，例如磁盘、硬盘驱动器等。永久性计算机可读介质的常见形式包括例如软盘(floppydisks)、软盘(flexible disks)、硬盘、磁带或任何其它磁性存储介质、CD-ROM、DVD或任何其它光学介质、RAM、PROM、EPROM、FLASH-EPROM或其它存储芯片或盒式磁带，或者计算机可读和使用的任何其它永久性介质。

或者，所述方法的一或多个吧步骤可以在暂时性介质中实施，例如可传输的载波，其中控制程序使用如声波或光波之类的传输介质作为数据信号呈现，例如在无线电波和红外数据通信期间产生的那些。

示例方法可以在一或多个通用计算机、专用计算机、编程微处理器或微控制器和外围集成电路元件、ASIC或其它集成电路、数字信号处理器、硬连线电子或逻辑电路例如独立元件电路、可编程逻辑装置如PLD、PLA、FPGA，图形卡CPU(GPU)或PAL上执行。通常，能执行有限状态机且能执行图1所示流程图的任何设备都可用于执行风险分层方法的一或多个步骤，用于前列腺患者的治疗选择。如将理解的，虽然所述方法的步骤可全部是计算机执行的，在一些实施方案中一或多个步骤可至少部分手动执行。

计算机程序指令也可以加载到计算机、其它可编程数据处理装置或其它设备上，以使得在所述计算机、其它可编程装置或其它设备上执行一系列操作步骤，产生计算机执行过程，由此使得在计算机或其它可编程装置上执行的指令提供执行在此指定的函数/行为的程序。

尽管到目前为止本发明已经基于PDE4D7的基因表达谱进行了描述，其可以包括PDE4D7的表达水平(例如值)，所述表达水平可以使用一组参考基因的每个基因的值进行标准化，所述基因表达谱可以进一步包括来自其它PDE4D变体的表达信息。例如，其它PDE4D变体可以包括PDE4D1、PDE4D2、PDE4D3、PDE4D4、PDE4D5、PDE4D6、PDE4D8和PDE4D9中的一或多个。然后，诊断试剂盒可以另外包含至少一个引物和/或探针，用于确定得自前列腺癌对象的生物学样品中其它PDE4D变体每一个的基因表达谱。然而，优选仅使用PDE4D7的基因表达谱，特别是可以使用一组参考基因的每个基因的值进行标准化的PDE4D7的表达水平(例如值)。

术语“磷酸二酯酶4D1”或“PDE4D1”涉及人磷酸二酯酶PDE4D的剪接变体1，即人磷酸二酯酶PDE4D1基因，例如NCBI参考序列：NM_001197222.1中所定义的序列，特别是SEQ IDNO:1所示核苷酸序列，其对应于上述PDE4D1转录物的NCBI参考序列的序列，还涉及例如SEQID NO:2所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001184151.1中定义的编码PDE4D1多肽的蛋白质序列。术语“磷酸二酯酶4D1”或“PDE4D1”还涉及可以由引物对PDE1D1D2_正向(SEQ ID NO:3)和PDE1D1D2_反向(SEQ ID NO:4)产生且可以通过探针SEQID NO:5检测的扩增子。

术语“磷酸二酯酶4D2”或“PDE4D2”是指人磷酸二酯酶PDE4D的剪接变体2，即人磷酸二酯酶PDE4D2基因，例如NCBI参考序列：NM_001197221.1中所定义的序列，特别是SEQ IDNO:6所示核苷酸序列，其对应于上述PDE4D2转录物的NCBI参考序列的序列，还涉及例如SEQID NO:7所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001184150.1中定义的编码PDE4D2多肽的蛋白质序列。

术语“磷酸二酯酶4D3”或“PDE4D3”是指人磷酸二酯酶PDE4D的剪接变体3，即人磷酸二酯酶PDE4D3基因，例如NCBI参考序列：NM_006203.4中所定义的序列，特别是SEQ IDNO:8所示核苷酸0序列，其对应于上述PDE4D3转录物的NCBI参考序列的序列，还涉及例如SEQ ID NO:9所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_006194.2中定义的编码PDE4D3多肽的蛋白质序列。

术语“磷酸二酯酶4D4”或“PDE4D4”是指人磷酸二酯酶PDE4D的剪接变体4，即人磷酸二酯酶PDE4D4基因，例如NCBI参考序列：NM_001104631.1中所定义的序列，特别是SEQ IDNO:10所示核苷酸序列，其对应于上述PDE4D4转录物的NCBI参考序列的序列，还涉及例如SEQ ID NO:11所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001098101.1中定义的编码PDE4D4多肽的蛋白质序列。

术语“磷酸二酯酶4D5”或“PDE4D5”是指人磷酸二酯酶PDE4D的剪接变体5，即人磷酸二酯酶PDE4D5基因，例如NCBI参考序列：NM_001197218.1中所定义的序列，特别是SEQ IDNO:12所示核苷酸序列，其对应于上述PDE4D5转录物的NCBI参考序列的序列，还涉及例如SEQ ID NO:13所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001184147.1中定义的编码PDE4D5多肽的蛋白质序列。术语“磷酸二酯酶4D5”或“PDE4D5”还涉及可由引物对PDE4D5_正向(SEQ ID NO:14)和PDE4D5_反向(SEQ ID NO:15)产生且可由探针SEQ IDNO:16检测的扩增子。

术语“磷酸二酯酶4D6”或“PDE4D6”是指人磷酸二酯酶PDE4D的剪接变体6，即人磷酸二酯酶PDE4D6基因，例如NCBI参考序列：NM_001197223.1中所定义的序列，特别是SEQ IDNO:17所示核苷酸序列，其对应于上述PDE4D6转录物的NCBI参考序列的序列，还涉及例如SEQ ID NO:18所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001184152.1中定义的编码PDE4D6多肽的蛋白质序列。

术语“磷酸二酯酶4D8”或“PDE4D8”涉及人磷酸二酯酶PDE4D的剪接变体8，即人磷酸二酯酶PDE4D8基因，例如NCBI参考序列：NM_001197219.1中所定义的序列，特别是SEQ IDNO:27所示核苷酸序列，其对应于上述PDE4D8转录物的NCBI参考序列的序列，还涉及例如SEQ ID NO:28所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001184148.1中定义的编码PDE4D8多肽的蛋白质序列。

术语“磷酸二酯酶4D9”或“PDE4D9”涉及人磷酸二酯酶PDE4D的剪接变体9，即人磷酸二酯酶PDE4D9基因，例如NCBI参考序列：NM_001197220.1中所定义的序列，特别是SEQ IDNO:29所示核苷酸序列，其对应于上述PDE4D9转录物的NCBI参考序列的序列，还涉及例如SEQ ID NO:30所示的相应氨基酸序列，其对应于NCBI蛋白质登录参考序列NP_001184149.1中定义的编码PDE4D9多肽的蛋白质序列。术语“磷酸二酯酶4D9”或“PDE4D9”还涉及可由引物对PDE4D9_正向(SEQ ID NO:31)和PDE4D9_反向(SEQ ID NO:32)产生且可由探针SEQ IDNO:33检测的扩增子。

术语“PDE4D1”、“PDE4D2”、“PDE4D3”、“PDE4D4”、“PDE4D5”、“PDE4D6”、“PDE4D8”和“PDE4D9”也包含分别与PDE4D1、PDE4D2、PDE4D3、PDE4D4、PDE4D5、PDE4D6、PDE4D8和PDE4D9示出高度同源性的核苷酸序列，例如分别与SEQ ID NO:1、6、8、10、12、17、27或29所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的核酸序列，或者分别与SEQ ID NO:2、7、9、11、13、18、28或30所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的氨基酸序列，或者编码与SEQ ID NO:2、7、9、11、13、13、18、28或30所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的氨基酸序列的核酸序列，或者或由与SEQ ID NO:1、6、8、10、12、17、27或29所示序列具有至少75％、80％、85％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同性的核酸序列编码的氨基酸序列。

权利要求书中的任何参考标记都不应被解释为限制范围。

本发明涉及前列腺癌对象的术前风险分层的方法，包含确定得自所述对象的生物学样品中磷酸二酯酶4D变体7(PDE4D7)的基因表达谱，确定得自所述对象的相同或另一生物学样品中DExH-box解旋酶9(DHX9)的基因表达谱，及基于PDE4D7的基因表达谱和DHX9的基因表达谱确定所述对象的术前预后风险评分。这可以在术前设置中改善对象的分层，可以导致更好的一级治疗决策。例如，对于前列腺癌患者的某些亚群，术前预后风险评分可以就是选择主动监测还是主动干预例如根治性前列腺切除术提出更好建议。

所附标题为2018PF00399_序列表_ST25的序列表以其全文并入本文参考。

序列表

<110> 皇家飞利浦有限公司

格拉斯哥大学委员会

<120> 基于PDE4D7和DHX9表达的术前风险分层

<130> 2018PF00399

<160> 75

<170> PatentIn version 3.5

<210> 1

<211> 7801

<212> DNA

<213> 智人

<400> 1

gtggtggccg cgcacccggc cgcggctgat tcattcactt caagtgccgt gcagaaggct 60

cggcaggcgg ggcgggcgtg gggccgcggc tccgggttgg ggaccgagga gatccggctg 120

tggaccagac gctcctctgc ggggcgggca cccaagcgcg ctcgccaccc cctcgccatc 180

cgctagagcc gggctcctgg actgggactc gggcccgccg cacagttgaa aagtcgcata 240

gtggtttttc cgctcgcgtc gctgtgtgaa agttggctcg ccgctctttg cacgccctcc 300

ctggaggccg acccgagacg ccaagctgga gagaccgtgc ctccccgagg ccggccgccc 360

cgcgagcaca gcctccgccc ccgttgcact gccgggctgg gcaatatgaa ggagcagccc 420

tcatgtgccg gcaccgggca tccgagcatg gcggggtatg gcaggatggc cccctttgaa 480

ctcgctagcg gacccgtgaa gcgcttgaga actgagtccc cctttccctg tctcttcgca 540

gaggaggcct accagaaact ggccagcgag accctggagg agctggactg gtgtctggac 600

cagctagaga ccctacagac caggcactcc gtcagtgaga tggcctccaa caagtttaaa 660

aggatgctta atcgggagct cacccatctc tctgaaatga gtcggtctgg aaatcaagtg 720

tcagagttta tatcaaacac attcttagat aagcaacatg aagtggaaat tccttctcca 780

actcagaagg aaaaggagaa aaagaaaaga ccaatgtctc agatcagtgg agtcaagaaa 840

ttgatgcaca gctctagtct gactaattca agtatcccaa ggtttggagt taaaactgaa 900

caagaagatg tccttgccaa ggaactagaa gatgtgaaca aatggggtct tcatgttttc 960

agaatagcag agttgtctgg taaccggccc ttgactgtta tcatgcacac catttttcag 1020

gaacgggatt tattaaaaac atttaaaatt ccagtagata ctttaattac atatcttatg 1080

actctcgaag accattacca tgctgatgtg gcctatcaca acaatatcca tgctgcagat 1140

gttgtccagt ctactcatgt gctattatct acacctgctt tggaggctgt gtttacagat 1200

ttggagattc ttgcagcaat ttttgccagt gcaatacatg atgtagatca tcctggtgtg 1260

tccaatcaat ttctgatcaa tacaaactct gaacttgcct tgatgtacaa tgattcctca 1320

gtcttagaga accatcattt ggctgtgggc tttaaattgc ttcaggaaga aaactgtgac 1380

attttccaga atttgaccaa aaaacaaaga caatctttaa ggaaaatggt cattgacatc 1440

gtacttgcaa cagatatgtc aaaacacatg aatctactgg ctgatttgaa gactatggtt 1500

gaaactaaga aagtgacaag ctctggagtt cttcttcttg ataattattc cgataggatt 1560

caggttcttc agaatatggt gcactgtgca gatctgagca acccaacaaa gcctctccag 1620

ctgtaccgcc agtggacgga ccggataatg gaggagttct tccgccaagg agaccgagag 1680

agggaacgtg gcatggagat aagccccatg tgtgacaagc acaatgcttc cgtggaaaaa 1740

tcacaggtgg gcttcataga ctatattgtt catcccctct gggagacatg ggcagacctc 1800

gtccaccctg acgcccagga tattttggac actttggagg acaatcgtga atggtaccag 1860

agcacaatcc ctcagagccc ctctcctgca cctgatgacc cagaggaggg ccggcagggt 1920

caaactgaga aattccagtt tgaactaact ttagaggaag atggtgagtc agacacggaa 1980

aaggacagtg gcagtcaagt ggaagaagac actagctgca gtgactccaa gactctttgt 2040

actcaagact cagagtctac tgaaattccc cttgatgaac aggttgaaga ggaggcagta 2100

ggggaagaag aggaaagcca gcctgaagcc tgtgtcatag atgatcgttc tcctgacacg 2160

taacagtgca aaaactttca tgcctttttt ttttttaagt agaaaaattg tttccaaagt 2220

gcatgtcaca tgccacaacc acggtcacac ctcactgtca tctgccagga cgtttgttga 2280

acaaaactga ccttgactac tcagtccagc gctcaggaat atcgtaacca gttttttcac 2340

ctccatgtca tccgagcaag gtggacatct tcacgaacag cgtttttaac aagatttcag 2400

cttggtagag ctgacaaagc agataaaatc tactccaaat tattttcaag agagtgtgac 2460

tcatcaggca gcccaaaagt ttattggact tggggtttct attccttttt atttgtttgc 2520

aatattttca gaagaaaggc attgcacaga gtgaacttaa tggacgaagc aacaaatatg 2580

tcaagaacag gacatagcac gaatctgtta ccagtaggag gaggatgagc cacagaaatt 2640

gcataatttt ctaatttcaa gtcttcctga tacatgactg aatagtgtgg ttcagtgagc 2700

tgcactgacc tctacatttt gtatgatatg taaaacagat tttttgtaga gcttactttt 2760

attattaaat gtattgaggt attatattta aaaaaaacta tgttcagaac ttcatctgcc 2820

actggttatt tttttctaag gagtaacttg caagttttca gtacaaatct gtgctacact 2880

ggataaaaat ctaatttatg aattttactt gcaccttata gttcatagca attaactgat 2940

ttgtagtgat tcattgtttg ttttatatac caatgacttc catattttaa aagagaaaaa 3000

caactttatg ttgcaggaaa ccctttttgt aagtctttat tatttacttt gcattttgtt 3060

tcactctttc cagataagca gagttgctct tcaccagtgt ttttcttcat gtgcaaagtg 3120

actatttgtt ctataatact tttatgtgtg ttatatcaaa tgtgtcttaa gcttcatgca 3180

aactcagtca tcagttcgtg ttgtctgaag caagtgggag atatataaat acccagtagc 3240

taaaatggtc agtctttttt agatgttttc ctacttagta tctcctaata acgttttgct 3300

gtgtcactag atgttcattt cacaagtgca tgtctttcta ataatccaca catttcatgc 3360

tctaataatc cacacatttc atgctcattt ttattgtttt tacagccagt tatagtaaga 3420

aaaaggtttt tccccttgtg ctgctttata atttagcgtg tgtctgaacc ttatccatgt 3480

ttgctagatg aggtcttgtc aaatatatca ctaccattgt caccggtgaa aagaaacagg 3540

tagttaagtt agggttaaca ttcatttcaa ccacgaggtt gtatatcatg actagctttt 3600

actcttggtt tacagagaaa agttaaacag ccaactaggc agtttttaag aatattaaca 3660

atatattaac aaacaccaat acaactaatc ctatttggtt ttaatgattt caccatggga 3720

ttaagaacta tatcaggaac atccctgaga aacggtttta agtgtagcaa ctactcttcc 3780

ttaatggaca gccacataac gtgtaggaag tcctttatca cttatcctcg atccataagc 3840

atatcttgca gaggggaact acttctttaa acacatggag ggaaagaaga tgatgccact 3900

ggcaccagag ggttagtact gtgatgcatc ctaaaatatt tattatattg gtaaaaattc 3960

tggttaaata aaaaattaga gatcactctt ggctgatttc agcaccagga actgtattac 4020

agttttagag attaattcct agtgtttacc tgattatagc agttggcatc atggggcatt 4080

taattctgac tttatcccca cgtcagcctt aataaagtct tctttacctt ctctatgaag 4140

actttaaagc ccaaataatc atttttcaca ttgatattca agaattgaga tagatagaag 4200

ccaaagtggg tatctgacaa gtggaaaatc aaacgtttaa gaagaattac aactctgaaa 4260

agcatttata tgtggaactt ctcaaggagc ctcctgggga ctggaaagta agtcatcagc 4320

caggcaaatg actcatgctg aagagagtcc ccatttcagt cccctgagat ctagctgatg 4380

cttagatcct ttgaaataaa aattatgtct ttataactct gatcttttac ataaagcaga 4440

agaggaatca actagttaat tgcaaggttt ctactctgtt tcctctgtaa agatcagatg 4500

gtaatctttc aaataagaaa aaaataaaga cgtatgtttg accaagtagt ttcacaagaa 4560

tatttgggaa cttgtttctt ttaattttat ttgtccctga gtgaagtcta gaaagaaagg 4620

taaagagtct agagtttatt cctctttcca aaacattctc attcctctcc tccctacact 4680

tagtatttcc cccacagagt gcctagaatc ttaataatga ataaaataaa aagcagcaat 4740

atgtcattaa caaatccaga cctgaaaggg taaagggttt ataactgcac taataaagag 4800

aggctctttt tttttcttcc agtttgttgg tttttaatgg taccgtgttg taaagatacc 4860

cactaatgga caatcaaatt gcagaaaagg ctcaatatcc aagagacagg gactaatgca 4920

ctgtacaatc tgcttatcct tgcccttctc tcttgccaaa gtgtgcttca gaaatatata 4980

ctgctttaaa aaagaataaa agaatatcct tttacaagtg gctttacatt tcctaaaatg 5040

ccataagaaa atgcaatatc tgggtactgt atggggaaaa aaatgtccaa gtttgtgtaa 5100

aaccagtgca tttcagcttg caagttactg aacacaataa tgctgtttta attttgtttt 5160

atatcagtta aaattcacaa taatgtagat agaacaaatt acagacaagg aaagaaaaaa 5220

cttgaatgaa atggatttta cagaaagctt tatgataatt tttgaatgca ttatttattt 5280

tttgtgccat gcattttttt tctcaccaaa tgaccttacc tgtaatacag tcttgtttgt 5340

ctgtttacaa ccatgtattt attgcaatgt acatactgta atgttaattg taaattatct 5400

gttcttatta aaacatcatc ccatgatggg atggtgttga tatatttgga aactcttggt 5460

gagagaatga atggtgtgta tacatactct gtacattttt cttttctcct gtaatatagt 5520

cttgtcacct tagagcttgt ttatggaaga ttcaagaaaa ctataaaata cttaaagata 5580

tataaattta aaaaaacata gctgcaggtc tttggtccca gggctgtgcc ttaactttaa 5640

ccaatatttt cttctgtttt gctgcatttg aaaggtaaca gtggagctag ggctgggcat 5700

tttacatcca ggcttttaat tgattagaat tctgccaata ggtggatttt acaaaaccac 5760

agacaacctc tgaaagattc tgagaccctt ttgagacaga agctcttaag tacttcttgc 5820

cagggagcag cactgcatgt gtgatggttg tttgccatct gttgatcagg aactacttca 5880

gctacttgca tttgattatt tccttttttt ttttttttaa ctcggaaaca caactgggga 5940

aatatattct ttcccagtga ttataaacaa tctttttctt ttttttaagt ccttttggct 6000

tctagagctc ataggaaaat ggacttgatt tgaaattgga gccagagttt actcgtgttg 6060

gttatctatt catcagcttc ctgacatgtt aagagaatac attaaagaga aaatactgtt 6120

ttttaatcct aaaatttttc ttccactaag ataaaccaaa tgtccttaca tatatgtaaa 6180

cccatctatt taaacgcaaa ggtgggttga tgtcagttta catagcagaa agcattcact 6240

atcctctaag atttgtttct gcaaaacttt cattgcttta gaattttaaa atttcacctt 6300

gtacaatggc cagcccctaa agcaggaaac atttataatg gattatatgg aaacatcctc 6360

ccagtacttg cccagccctt gaatcatgtg gcttttcagt gaaaggaaag attctttttc 6420

taggaaaaat gagcctattt tattttattt tattttattt tttgacacaa actgtagatt 6480

ttagcagccc tggcccaaag gaatttgatt acttttgttt taaacagtac aaaggggaca 6540

ctataattac aaaaacatcc ttaactgatt tgagttgttt ttatttcttt ggatatattt 6600

tcagagtggt aaattgtgtg tgagaattac aaatgattat tcttttagtg gtttcttagc 6660

ctctcttaca gcccacgggg atagtactgt acatcaatac cttcatatga aatttttata 6720

tgcaatgaaa ataaaagcat gggttgattc tgcctattta tgactcaatc ttttacaaat 6780

aaaagattat tcattttaaa ttatagttca atcagcatgt ctcttaggat actgaacgtg 6840

gttgaaatga aaggatagtg acatcataag ttagtactga tattcataac caaataaagc 6900

caacttgagt aattttgcta cattaaaaat taccaaaatt acttagatgg cctataagat 6960

taagcatggt gttttctaag caagctttga aaggggcctt ccatacttac ttaattgaat 7020

attctgggat attgaaaatt attcagatac ttgacaatta tttttggtta cctactccgc 7080

aaactacaaa gttttaagga ctcaacaata agttaatgag acacagtgtt tgctttcatg 7140

gagcttacag tctggagggg acaaaggctt aaacaatact catataatta tatatgtgat 7200

cagtacaatg aaggagctca gtggggtaaa taagcaggaa cctgaacttg atctgttccg 7260

gagggccaca gaaggcttcc ttgaggcctt gagaaagtga tttgcatctg agttctgaag 7320

gattgtaaga ggtaactagg gaaaaagttg acaggaagag gaaggggatc cagacaagaa 7380

acatttgcaa agatcttgag gcataaatga gcttgagaca tctggagaaa ctgaggaaaa 7440

gtgagagagt aggcagggcc tggagccgca gagccattgc taaccatcct gtgtgagata 7500

tcccccattc tgtagcttta ttctcataac cctgctcaat tttctttata acacttctca 7560

cagatttata tacgtgtttg tttttgttat ctgtctctcc caccagacca cagctccatg 7620

agagcaaggt ctttgcttac caatatatca ctagcactta aaactatgcc tggtacacag 7680

taggttctta atatgtgttg aatatagcca tcaaattgat attggatata attcaatctg 7740

ataagatatt ttgagatatt aaagagtttt taacttgata ccataaaaaa aaaaaaaaaa 7800

a 7801

<210> 2

<211> 585

<212> PRT

<213> 智人

<400> 2

Met Lys Glu Gln Pro Ser Cys Ala Gly Thr Gly His Pro Ser Met Ala

1 5 10 15

Gly Tyr Gly Arg Met Ala Pro Phe Glu Leu Ala Ser Gly Pro Val Lys

20 25 30

Arg Leu Arg Thr Glu Ser Pro Phe Pro Cys Leu Phe Ala Glu Glu Ala

35 40 45

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

50 55 60

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

65 70 75 80

Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser

85 90 95

Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser Asn Thr

100 105 110

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

115 120 125

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

130 135 140

Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe

145 150 155 160

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

165 170 175

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

180 185 190

Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp

195 200 205

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

210 215 220

Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn

225 230 235 240

Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr

245 250 255

Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile

260 265 270

Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln

275 280 285

Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser

290 295 300

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

305 310 315 320

Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln

325 330 335

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

340 345 350

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

355 360 365

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

370 375 380

Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro

385 390 395 400

Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu

405 410 415

Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile

420 425 430

Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val

435 440 445

Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp

450 455 460

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

465 470 475 480

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

485 490 495

Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe Gln Phe

500 505 510

Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser

515 520 525

Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys Thr Leu

530 535 540

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

545 550 555 560

Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys

565 570 575

Val Ile Asp Asp Arg Ser Pro Asp Thr

580 585

<210> 3

<211> 21

<212> DNA

<213> 人工序列

<220>

<223> PDE4D1D2_正向引物

<400> 3

aatatgaagg agcagccctc a 21

<210> 4

<211> 18

<212> DNA

<213> 人工序列

<220>

<223> PDE4D1D2_反向引物

<400> 4

gtctcgctgg ccagtttc 18

<210> 5

<211> 18

<212> DNA

<213> 人工序列

<220>

<223> PDE4D1D2探针

<400> 5

catccgagca tggcggga 18

<210> 6

<211> 7715

<212> DNA

<213> 智人

<400> 6

gtggtggccg cgcacccggc cgcggctgat tcattcactt caagtgccgt gcagaaggct 60

cggcaggcgg ggcgggcgtg gggccgcggc tccgggttgg ggaccgagga gatccggctg 120

tggaccagac gctcctctgc ggggcgggca cccaagcgcg ctcgccaccc cctcgccatc 180

cgctagagcc gggctcctgg actgggactc gggcccgccg cacagttgaa aagtcgcata 240

gtggtttttc cgctcgcgtc gctgtgtgaa agttggctcg ccgctctttg cacgccctcc 300

ctggaggccg acccgagacg ccaagctgga gagaccgtgc ctccccgagg ccggccgccc 360

cgcgagcaca gcctccgccc ccgttgcact gccgggctgg gcaatatgaa ggagcagccc 420

tcatgtgccg gcaccgggca tccgagcatg gcgggaggag gcctaccaga aactggccag 480

cgagaccctg gaggagctgg actggtgtct ggaccagcta gagaccctac agaccaggca 540

ctccgtcagt gagatggcct ccaacaagtt taaaaggatg cttaatcggg agctcaccca 600

tctctctgaa atgagtcggt ctggaaatca agtgtcagag tttatatcaa acacattctt 660

agataagcaa catgaagtgg aaattccttc tccaactcag aaggaaaagg agaaaaagaa 720

aagaccaatg tctcagatca gtggagtcaa gaaattgatg cacagctcta gtctgactaa 780

ttcaagtatc ccaaggtttg gagttaaaac tgaacaagaa gatgtccttg ccaaggaact 840

agaagatgtg aacaaatggg gtcttcatgt tttcagaata gcagagttgt ctggtaaccg 900

gcccttgact gttatcatgc acaccatttt tcaggaacgg gatttattaa aaacatttaa 960

aattccagta gatactttaa ttacatatct tatgactctc gaagaccatt accatgctga 1020

tgtggcctat cacaacaata tccatgctgc agatgttgtc cagtctactc atgtgctatt 1080

atctacacct gctttggagg ctgtgtttac agatttggag attcttgcag caatttttgc 1140

cagtgcaata catgatgtag atcatcctgg tgtgtccaat caatttctga tcaatacaaa 1200

ctctgaactt gccttgatgt acaatgattc ctcagtctta gagaaccatc atttggctgt 1260

gggctttaaa ttgcttcagg aagaaaactg tgacattttc cagaatttga ccaaaaaaca 1320

aagacaatct ttaaggaaaa tggtcattga catcgtactt gcaacagata tgtcaaaaca 1380

catgaatcta ctggctgatt tgaagactat ggttgaaact aagaaagtga caagctctgg 1440

agttcttctt cttgataatt attccgatag gattcaggtt cttcagaata tggtgcactg 1500

tgcagatctg agcaacccaa caaagcctct ccagctgtac cgccagtgga cggaccggat 1560

aatggaggag ttcttccgcc aaggagaccg agagagggaa cgtggcatgg agataagccc 1620

catgtgtgac aagcacaatg cttccgtgga aaaatcacag gtgggcttca tagactatat 1680

tgttcatccc ctctgggaga catgggcaga cctcgtccac cctgacgccc aggatatttt 1740

ggacactttg gaggacaatc gtgaatggta ccagagcaca atccctcaga gcccctctcc 1800

tgcacctgat gacccagagg agggccggca gggtcaaact gagaaattcc agtttgaact 1860

aactttagag gaagatggtg agtcagacac ggaaaaggac agtggcagtc aagtggaaga 1920

agacactagc tgcagtgact ccaagactct ttgtactcaa gactcagagt ctactgaaat 1980

tccccttgat gaacaggttg aagaggaggc agtaggggaa gaagaggaaa gccagcctga 2040

agcctgtgtc atagatgatc gttctcctga cacgtaacag tgcaaaaact ttcatgcctt 2100

tttttttttt aagtagaaaa attgtttcca aagtgcatgt cacatgccac aaccacggtc 2160

acacctcact gtcatctgcc aggacgtttg ttgaacaaaa ctgaccttga ctactcagtc 2220

cagcgctcag gaatatcgta accagttttt tcacctccat gtcatccgag caaggtggac 2280

atcttcacga acagcgtttt taacaagatt tcagcttggt agagctgaca aagcagataa 2340

aatctactcc aaattatttt caagagagtg tgactcatca ggcagcccaa aagtttattg 2400

gacttggggt ttctattcct ttttatttgt ttgcaatatt ttcagaagaa aggcattgca 2460

cagagtgaac ttaatggacg aagcaacaaa tatgtcaaga acaggacata gcacgaatct 2520

gttaccagta ggaggaggat gagccacaga aattgcataa ttttctaatt tcaagtcttc 2580

ctgatacatg actgaatagt gtggttcagt gagctgcact gacctctaca ttttgtatga 2640

tatgtaaaac agattttttg tagagcttac ttttattatt aaatgtattg aggtattata 2700

tttaaaaaaa actatgttca gaacttcatc tgccactggt tatttttttc taaggagtaa 2760

cttgcaagtt ttcagtacaa atctgtgcta cactggataa aaatctaatt tatgaatttt 2820

acttgcacct tatagttcat agcaattaac tgatttgtag tgattcattg tttgttttat 2880

ataccaatga cttccatatt ttaaaagaga aaaacaactt tatgttgcag gaaacccttt 2940

ttgtaagtct ttattattta ctttgcattt tgtttcactc tttccagata agcagagttg 3000

ctcttcacca gtgtttttct tcatgtgcaa agtgactatt tgttctataa tacttttatg 3060

tgtgttatat caaatgtgtc ttaagcttca tgcaaactca gtcatcagtt cgtgttgtct 3120

gaagcaagtg ggagatatat aaatacccag tagctaaaat ggtcagtctt ttttagatgt 3180

tttcctactt agtatctcct aataacgttt tgctgtgtca ctagatgttc atttcacaag 3240

tgcatgtctt tctaataatc cacacatttc atgctctaat aatccacaca tttcatgctc 3300

atttttattg tttttacagc cagttatagt aagaaaaagg tttttcccct tgtgctgctt 3360

tataatttag cgtgtgtctg aaccttatcc atgtttgcta gatgaggtct tgtcaaatat 3420

atcactacca ttgtcaccgg tgaaaagaaa caggtagtta agttagggtt aacattcatt 3480

tcaaccacga ggttgtatat catgactagc ttttactctt ggtttacaga gaaaagttaa 3540

acagccaact aggcagtttt taagaatatt aacaatatat taacaaacac caatacaact 3600

aatcctattt ggttttaatg atttcaccat gggattaaga actatatcag gaacatccct 3660

gagaaacggt tttaagtgta gcaactactc ttccttaatg gacagccaca taacgtgtag 3720

gaagtccttt atcacttatc ctcgatccat aagcatatct tgcagagggg aactacttct 3780

ttaaacacat ggagggaaag aagatgatgc cactggcacc agagggttag tactgtgatg 3840

catcctaaaa tatttattat attggtaaaa attctggtta aataaaaaat tagagatcac 3900

tcttggctga tttcagcacc aggaactgta ttacagtttt agagattaat tcctagtgtt 3960

tacctgatta tagcagttgg catcatgggg catttaattc tgactttatc cccacgtcag 4020

ccttaataaa gtcttcttta ccttctctat gaagacttta aagcccaaat aatcattttt 4080

cacattgata ttcaagaatt gagatagata gaagccaaag tgggtatctg acaagtggaa 4140

aatcaaacgt ttaagaagaa ttacaactct gaaaagcatt tatatgtgga acttctcaag 4200

gagcctcctg gggactggaa agtaagtcat cagccaggca aatgactcat gctgaagaga 4260

gtccccattt cagtcccctg agatctagct gatgcttaga tcctttgaaa taaaaattat 4320

gtctttataa ctctgatctt ttacataaag cagaagagga atcaactagt taattgcaag 4380

gtttctactc tgtttcctct gtaaagatca gatggtaatc tttcaaataa gaaaaaaata 4440

aagacgtatg tttgaccaag tagtttcaca agaatatttg ggaacttgtt tcttttaatt 4500

ttatttgtcc ctgagtgaag tctagaaaga aaggtaaaga gtctagagtt tattcctctt 4560

tccaaaacat tctcattcct ctcctcccta cacttagtat ttcccccaca gagtgcctag 4620

aatcttaata atgaataaaa taaaaagcag caatatgtca ttaacaaatc cagacctgaa 4680

agggtaaagg gtttataact gcactaataa agagaggctc tttttttttc ttccagtttg 4740

ttggttttta atggtaccgt gttgtaaaga tacccactaa tggacaatca aattgcagaa 4800

aaggctcaat atccaagaga cagggactaa tgcactgtac aatctgctta tccttgccct 4860

tctctcttgc caaagtgtgc ttcagaaata tatactgctt taaaaaagaa taaaagaata 4920

tccttttaca agtggcttta catttcctaa aatgccataa gaaaatgcaa tatctgggta 4980

ctgtatgggg aaaaaaatgt ccaagtttgt gtaaaaccag tgcatttcag cttgcaagtt 5040

actgaacaca ataatgctgt tttaattttg ttttatatca gttaaaattc acaataatgt 5100

agatagaaca aattacagac aaggaaagaa aaaacttgaa tgaaatggat tttacagaaa 5160

gctttatgat aatttttgaa tgcattattt attttttgtg ccatgcattt tttttctcac 5220

caaatgacct tacctgtaat acagtcttgt ttgtctgttt acaaccatgt atttattgca 5280

atgtacatac tgtaatgtta attgtaaatt atctgttctt attaaaacat catcccatga 5340

tgggatggtg ttgatatatt tggaaactct tggtgagaga atgaatggtg tgtatacata 5400

ctctgtacat ttttcttttc tcctgtaata tagtcttgtc accttagagc ttgtttatgg 5460

aagattcaag aaaactataa aatacttaaa gatatataaa tttaaaaaaa catagctgca 5520

ggtctttggt cccagggctg tgccttaact ttaaccaata ttttcttctg ttttgctgca 5580

tttgaaaggt aacagtggag ctagggctgg gcattttaca tccaggcttt taattgatta 5640

gaattctgcc aataggtgga ttttacaaaa ccacagacaa cctctgaaag attctgagac 5700

ccttttgaga cagaagctct taagtacttc ttgccaggga gcagcactgc atgtgtgatg 5760

gttgtttgcc atctgttgat caggaactac ttcagctact tgcatttgat tatttccttt 5820

tttttttttt ttaactcgga aacacaactg gggaaatata ttctttccca gtgattataa 5880

acaatctttt tctttttttt aagtcctttt ggcttctaga gctcatagga aaatggactt 5940

gatttgaaat tggagccaga gtttactcgt gttggttatc tattcatcag cttcctgaca 6000

tgttaagaga atacattaaa gagaaaatac tgttttttaa tcctaaaatt tttcttccac 6060

taagataaac caaatgtcct tacatatatg taaacccatc tatttaaacg caaaggtggg 6120

ttgatgtcag tttacatagc agaaagcatt cactatcctc taagatttgt ttctgcaaaa 6180

ctttcattgc tttagaattt taaaatttca ccttgtacaa tggccagccc ctaaagcagg 6240

aaacatttat aatggattat atggaaacat cctcccagta cttgcccagc ccttgaatca 6300

tgtggctttt cagtgaaagg aaagattctt tttctaggaa aaatgagcct attttatttt 6360

attttatttt attttttgac acaaactgta gattttagca gccctggccc aaaggaattt 6420

gattactttt gttttaaaca gtacaaaggg gacactataa ttacaaaaac atccttaact 6480

gatttgagtt gtttttattt ctttggatat attttcagag tggtaaattg tgtgtgagaa 6540

ttacaaatga ttattctttt agtggtttct tagcctctct tacagcccac ggggatagta 6600

ctgtacatca ataccttcat atgaaatttt tatatgcaat gaaaataaaa gcatgggttg 6660

attctgccta tttatgactc aatcttttac aaataaaaga ttattcattt taaattatag 6720

ttcaatcagc atgtctctta ggatactgaa cgtggttgaa atgaaaggat agtgacatca 6780

taagttagta ctgatattca taaccaaata aagccaactt gagtaatttt gctacattaa 6840

aaattaccaa aattacttag atggcctata agattaagca tggtgttttc taagcaagct 6900

ttgaaagggg ccttccatac ttacttaatt gaatattctg ggatattgaa aattattcag 6960

atacttgaca attatttttg gttacctact ccgcaaacta caaagtttta aggactcaac 7020

aataagttaa tgagacacag tgtttgcttt catggagctt acagtctgga ggggacaaag 7080

gcttaaacaa tactcatata attatatatg tgatcagtac aatgaaggag ctcagtgggg 7140

taaataagca ggaacctgaa cttgatctgt tccggagggc cacagaaggc ttccttgagg 7200

ccttgagaaa gtgatttgca tctgagttct gaaggattgt aagaggtaac tagggaaaaa 7260

gttgacagga agaggaaggg gatccagaca agaaacattt gcaaagatct tgaggcataa 7320

atgagcttga gacatctgga gaaactgagg aaaagtgaga gagtaggcag ggcctggagc 7380

cgcagagcca ttgctaacca tcctgtgtga gatatccccc attctgtagc tttattctca 7440

taaccctgct caattttctt tataacactt ctcacagatt tatatacgtg tttgtttttg 7500

ttatctgtct ctcccaccag accacagctc catgagagca aggtctttgc ttaccaatat 7560

atcactagca cttaaaacta tgcctggtac acagtaggtt cttaatatgt gttgaatata 7620

gccatcaaat tgatattgga tataattcaa tctgataaga tattttgaga tattaaagag 7680

tttttaactt gataccataa aaaaaaaaaa aaaaa 7715

<210> 7

<211> 507

<212> PRT

<213> 智人

<400> 7

Met Ala Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His

1 5 10 15

Leu Ser Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser

20 25 30

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

35 40 45

Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly

50 55 60

Val Lys Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro

65 70 75 80

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

85 90 95

Glu Asp Val Asn Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu Leu

100 105 110

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

115 120 125

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

130 135 140

Tyr Leu Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His

145 150 155 160

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

165 170 175

Ser Thr Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala

180 185 190

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

195 200 205

Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn

210 215 220

Asp Ser Ser Val Leu Glu Asn His His Leu Ala Val Gly Phe Lys Leu

225 230 235 240

Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln

245 250 255

Arg Gln Ser Leu Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp

260 265 270

Met Ser Lys His Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val Glu

275 280 285

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

290 295 300

Asp Arg Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser

305 310 315 320

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

325 330 335

Met Glu Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met

340 345 350

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

355 360 365

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

370 375 380

Ala Asp Leu Val His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu Glu

385 390 395 400

Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro

405 410 415

Ala Pro Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe

420 425 430

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

435 440 445

Asp Ser Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys

450 455 460

Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu

465 470 475 480

Gln Val Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu

485 490 495

Ala Cys Val Ile Asp Asp Arg Ser Pro Asp Thr

500 505

<210> 8

<211> 7783

<212> DNA

<213> 智人

<400> 8

aatacttgtt gcaataattg cccacgatag ctgctcaaac aagagagttg gaattcatct 60

gtaaaaatca ctacatgtaa cgtaggagac aagaaaaata ttaatgacag aagatctgcg 120

aacatgatgc acgtgaataa ttttcccttt agaaggcatt cctggatatg ttttgatgtg 180

gacaatggca catctgcggg acggagtccc ttggatccca tgaccagccc aggatccggg 240

ctaattctcc aagcaaattt tgtccacagt caacgacggg agtccttcct gtatcgatcc 300

gacagcgatt atgacctctc tccaaagtct atgtcccgga actcctccat tgccagtgat 360

atacacggag atgacttgat tgtgactcca tttgctcagg tcttggccag tctgcgaact 420

gtacgaaaca actttgctgc attaactaat ttgcaagatc gagcacctag caaaagatca 480

cccatgtgca accaaccatc catcaacaaa gccaccataa cagaggaggc ctaccagaaa 540

ctggccagcg agaccctgga ggagctggac tggtgtctgg accagctaga gaccctacag 600

accaggcact ccgtcagtga gatggcctcc aacaagttta aaaggatgct taatcgggag 660

ctcacccatc tctctgaaat gagtcggtct ggaaatcaag tgtcagagtt tatatcaaac 720

acattcttag ataagcaaca tgaagtggaa attccttctc caactcagaa ggaaaaggag 780

aaaaagaaaa gaccaatgtc tcagatcagt ggagtcaaga aattgatgca cagctctagt 840

ctgactaatt caagtatccc aaggtttgga gttaaaactg aacaagaaga tgtccttgcc 900

aaggaactag aagatgtgaa caaatggggt cttcatgttt tcagaatagc agagttgtct 960

ggtaaccggc ccttgactgt tatcatgcac accatttttc aggaacggga tttattaaaa 1020

acatttaaaa ttccagtaga tactttaatt acatatctta tgactctcga agaccattac 1080

catgctgatg tggcctatca caacaatatc catgctgcag atgttgtcca gtctactcat 1140

gtgctattat ctacacctgc tttggaggct gtgtttacag atttggagat tcttgcagca 1200

atttttgcca gtgcaataca tgatgtagat catcctggtg tgtccaatca atttctgatc 1260

aatacaaact ctgaacttgc cttgatgtac aatgattcct cagtcttaga gaaccatcat 1320

ttggctgtgg gctttaaatt gcttcaggaa gaaaactgtg acattttcca gaatttgacc 1380

aaaaaacaaa gacaatcttt aaggaaaatg gtcattgaca tcgtacttgc aacagatatg 1440

tcaaaacaca tgaatctact ggctgatttg aagactatgg ttgaaactaa gaaagtgaca 1500

agctctggag ttcttcttct tgataattat tccgatagga ttcaggttct tcagaatatg 1560

gtgcactgtg cagatctgag caacccaaca aagcctctcc agctgtaccg ccagtggacg 1620

gaccggataa tggaggagtt cttccgccaa ggagaccgag agagggaacg tggcatggag 1680

ataagcccca tgtgtgacaa gcacaatgct tccgtggaaa aatcacaggt gggcttcata 1740

gactatattg ttcatcccct ctgggagaca tgggcagacc tcgtccaccc tgacgcccag 1800

gatattttgg acactttgga ggacaatcgt gaatggtacc agagcacaat ccctcagagc 1860

ccctctcctg cacctgatga cccagaggag ggccggcagg gtcaaactga gaaattccag 1920

tttgaactaa ctttagagga agatggtgag tcagacacgg aaaaggacag tggcagtcaa 1980

gtggaagaag acactagctg cagtgactcc aagactcttt gtactcaaga ctcagagtct 2040

actgaaattc cccttgatga acaggttgaa gaggaggcag taggggaaga agaggaaagc 2100

cagcctgaag cctgtgtcat agatgatcgt tctcctgaca cgtaacagtg caaaaacttt 2160

catgcctttt ttttttttaa gtagaaaaat tgtttccaaa gtgcatgtca catgccacaa 2220

ccacggtcac acctcactgt catctgccag gacgtttgtt gaacaaaact gaccttgact 2280

actcagtcca gcgctcagga atatcgtaac cagttttttc acctccatgt catccgagca 2340

aggtggacat cttcacgaac agcgttttta acaagatttc agcttggtag agctgacaaa 2400

gcagataaaa tctactccaa attattttca agagagtgtg actcatcagg cagcccaaaa 2460

gtttattgga cttggggttt ctattccttt ttatttgttt gcaatatttt cagaagaaag 2520

gcattgcaca gagtgaactt aatggacgaa gcaacaaata tgtcaagaac aggacatagc 2580

acgaatctgt taccagtagg aggaggatga gccacagaaa ttgcataatt ttctaatttc 2640

aagtcttcct gatacatgac tgaatagtgt ggttcagtga gctgcactga cctctacatt 2700

ttgtatgata tgtaaaacag attttttgta gagcttactt ttattattaa atgtattgag 2760

gtattatatt taaaaaaaac tatgttcaga acttcatctg ccactggtta tttttttcta 2820

aggagtaact tgcaagtttt cagtacaaat ctgtgctaca ctggataaaa atctaattta 2880

tgaattttac ttgcacctta tagttcatag caattaactg atttgtagtg attcattgtt 2940

tgttttatat accaatgact tccatatttt aaaagagaaa aacaacttta tgttgcagga 3000

aacccttttt gtaagtcttt attatttact ttgcattttg tttcactctt tccagataag 3060

cagagttgct cttcaccagt gtttttcttc atgtgcaaag tgactatttg ttctataata 3120

cttttatgtg tgttatatca aatgtgtctt aagcttcatg caaactcagt catcagttcg 3180

tgttgtctga agcaagtggg agatatataa atacccagta gctaaaatgg tcagtctttt 3240

ttagatgttt tcctacttag tatctcctaa taacgttttg ctgtgtcact agatgttcat 3300

ttcacaagtg catgtctttc taataatcca cacatttcat gctctaataa tccacacatt 3360

tcatgctcat ttttattgtt tttacagcca gttatagtaa gaaaaaggtt tttccccttg 3420

tgctgcttta taatttagcg tgtgtctgaa ccttatccat gtttgctaga tgaggtcttg 3480

tcaaatatat cactaccatt gtcaccggtg aaaagaaaca ggtagttaag ttagggttaa 3540

cattcatttc aaccacgagg ttgtatatca tgactagctt ttactcttgg tttacagaga 3600

aaagttaaac agccaactag gcagttttta agaatattaa caatatatta acaaacacca 3660

atacaactaa tcctatttgg ttttaatgat ttcaccatgg gattaagaac tatatcagga 3720

acatccctga gaaacggttt taagtgtagc aactactctt ccttaatgga cagccacata 3780

acgtgtagga agtcctttat cacttatcct cgatccataa gcatatcttg cagaggggaa 3840

ctacttcttt aaacacatgg agggaaagaa gatgatgcca ctggcaccag agggttagta 3900

ctgtgatgca tcctaaaata tttattatat tggtaaaaat tctggttaaa taaaaaatta 3960

gagatcactc ttggctgatt tcagcaccag gaactgtatt acagttttag agattaattc 4020

ctagtgttta cctgattata gcagttggca tcatggggca tttaattctg actttatccc 4080

cacgtcagcc ttaataaagt cttctttacc ttctctatga agactttaaa gcccaaataa 4140

tcatttttca cattgatatt caagaattga gatagataga agccaaagtg ggtatctgac 4200

aagtggaaaa tcaaacgttt aagaagaatt acaactctga aaagcattta tatgtggaac 4260

ttctcaagga gcctcctggg gactggaaag taagtcatca gccaggcaaa tgactcatgc 4320

tgaagagagt ccccatttca gtcccctgag atctagctga tgcttagatc ctttgaaata 4380

aaaattatgt ctttataact ctgatctttt acataaagca gaagaggaat caactagtta 4440

attgcaaggt ttctactctg tttcctctgt aaagatcaga tggtaatctt tcaaataaga 4500

aaaaaataaa gacgtatgtt tgaccaagta gtttcacaag aatatttggg aacttgtttc 4560

ttttaatttt atttgtccct gagtgaagtc tagaaagaaa ggtaaagagt ctagagttta 4620

ttcctctttc caaaacattc tcattcctct cctccctaca cttagtattt cccccacaga 4680

gtgcctagaa tcttaataat gaataaaata aaaagcagca atatgtcatt aacaaatcca 4740

gacctgaaag ggtaaagggt ttataactgc actaataaag agaggctctt tttttttctt 4800

ccagtttgtt ggtttttaat ggtaccgtgt tgtaaagata cccactaatg gacaatcaaa 4860

ttgcagaaaa ggctcaatat ccaagagaca gggactaatg cactgtacaa tctgcttatc 4920

cttgcccttc tctcttgcca aagtgtgctt cagaaatata tactgcttta aaaaagaata 4980

aaagaatatc cttttacaag tggctttaca tttcctaaaa tgccataaga aaatgcaata 5040

tctgggtact gtatggggaa aaaaatgtcc aagtttgtgt aaaaccagtg catttcagct 5100

tgcaagttac tgaacacaat aatgctgttt taattttgtt ttatatcagt taaaattcac 5160

aataatgtag atagaacaaa ttacagacaa ggaaagaaaa aacttgaatg aaatggattt 5220

tacagaaagc tttatgataa tttttgaatg cattatttat tttttgtgcc atgcattttt 5280

tttctcacca aatgacctta cctgtaatac agtcttgttt gtctgtttac aaccatgtat 5340

ttattgcaat gtacatactg taatgttaat tgtaaattat ctgttcttat taaaacatca 5400

tcccatgatg ggatggtgtt gatatatttg gaaactcttg gtgagagaat gaatggtgtg 5460

tatacatact ctgtacattt ttcttttctc ctgtaatata gtcttgtcac cttagagctt 5520

gtttatggaa gattcaagaa aactataaaa tacttaaaga tatataaatt taaaaaaaca 5580

tagctgcagg tctttggtcc cagggctgtg ccttaacttt aaccaatatt ttcttctgtt 5640

ttgctgcatt tgaaaggtaa cagtggagct agggctgggc attttacatc caggctttta 5700

attgattaga attctgccaa taggtggatt ttacaaaacc acagacaacc tctgaaagat 5760

tctgagaccc ttttgagaca gaagctctta agtacttctt gccagggagc agcactgcat 5820

gtgtgatggt tgtttgccat ctgttgatca ggaactactt cagctacttg catttgatta 5880

tttccttttt tttttttttt aactcggaaa cacaactggg gaaatatatt ctttcccagt 5940

gattataaac aatctttttc ttttttttaa gtccttttgg cttctagagc tcataggaaa 6000

atggacttga tttgaaattg gagccagagt ttactcgtgt tggttatcta ttcatcagct 6060

tcctgacatg ttaagagaat acattaaaga gaaaatactg ttttttaatc ctaaaatttt 6120

tcttccacta agataaacca aatgtcctta catatatgta aacccatcta tttaaacgca 6180

aaggtgggtt gatgtcagtt tacatagcag aaagcattca ctatcctcta agatttgttt 6240

ctgcaaaact ttcattgctt tagaatttta aaatttcacc ttgtacaatg gccagcccct 6300

aaagcaggaa acatttataa tggattatat ggaaacatcc tcccagtact tgcccagccc 6360

ttgaatcatg tggcttttca gtgaaaggaa agattctttt tctaggaaaa atgagcctat 6420

tttattttat tttattttat tttttgacac aaactgtaga ttttagcagc cctggcccaa 6480

aggaatttga ttacttttgt tttaaacagt acaaagggga cactataatt acaaaaacat 6540

ccttaactga tttgagttgt ttttatttct ttggatatat tttcagagtg gtaaattgtg 6600

tgtgagaatt acaaatgatt attcttttag tggtttctta gcctctctta cagcccacgg 6660

ggatagtact gtacatcaat accttcatat gaaattttta tatgcaatga aaataaaagc 6720

atgggttgat tctgcctatt tatgactcaa tcttttacaa ataaaagatt attcatttta 6780

aattatagtt caatcagcat gtctcttagg atactgaacg tggttgaaat gaaaggatag 6840

tgacatcata agttagtact gatattcata accaaataaa gccaacttga gtaattttgc 6900

tacattaaaa attaccaaaa ttacttagat ggcctataag attaagcatg gtgttttcta 6960

agcaagcttt gaaaggggcc ttccatactt acttaattga atattctggg atattgaaaa 7020

ttattcagat acttgacaat tatttttggt tacctactcc gcaaactaca aagttttaag 7080

gactcaacaa taagttaatg agacacagtg tttgctttca tggagcttac agtctggagg 7140

ggacaaaggc ttaaacaata ctcatataat tatatatgtg atcagtacaa tgaaggagct 7200

cagtggggta aataagcagg aacctgaact tgatctgttc cggagggcca cagaaggctt 7260

ccttgaggcc ttgagaaagt gatttgcatc tgagttctga aggattgtaa gaggtaacta 7320

gggaaaaagt tgacaggaag aggaagggga tccagacaag aaacatttgc aaagatcttg 7380

aggcataaat gagcttgaga catctggaga aactgaggaa aagtgagaga gtaggcaggg 7440

cctggagccg cagagccatt gctaaccatc ctgtgtgaga tatcccccat tctgtagctt 7500

tattctcata accctgctca attttcttta taacacttct cacagattta tatacgtgtt 7560

tgtttttgtt atctgtctct cccaccagac cacagctcca tgagagcaag gtctttgctt 7620

accaatatat cactagcact taaaactatg cctggtacac agtaggttct taatatgtgt 7680

tgaatatagc catcaaattg atattggata taattcaatc tgataagata ttttgagata 7740

ttaaagagtt tttaacttga taccataaaa aaaaaaaaaa aaa 7783

<210> 9

<211> 673

<212> PRT

<213> 智人

<400> 9

Met Met His Val Asn Asn Phe Pro Phe Arg Arg His Ser Trp Ile Cys

1 5 10 15

Phe Asp Val Asp Asn Gly Thr Ser Ala Gly Arg Ser Pro Leu Asp Pro

20 25 30

Met Thr Ser Pro Gly Ser Gly Leu Ile Leu Gln Ala Asn Phe Val His

35 40 45

Ser Gln Arg Arg Glu Ser Phe Leu Tyr Arg Ser Asp Ser Asp Tyr Asp

50 55 60

Leu Ser Pro Lys Ser Met Ser Arg Asn Ser Ser Ile Ala Ser Asp Ile

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

Leu Glu Glu Leu Asp Trp Cys Leu Asp Gln Leu Glu Thr Leu Gln Thr

145 150 155 160

Arg His Ser Val Ser Glu Met Ala Ser Asn Lys Phe Lys Arg Met Leu

165 170 175

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

180 185 190

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

195 200 205

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

210 215 220

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

225 230 235 240

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

245 250 255

Val Leu Ala Lys Glu Leu Glu Asp Val Asn Lys Trp Gly Leu His Val

260 265 270

Phe Arg Ile Ala Glu Leu Ser Gly Asn Arg Pro Leu Thr Val Ile Met

275 280 285

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

290 295 300

Val Asp Thr Leu Ile Thr Tyr Leu Met Thr Leu Glu Asp His Tyr His

305 310 315 320

Ala Asp Val Ala Tyr His Asn Asn Ile His Ala Ala Asp Val Val Gln

325 330 335

Ser Thr His Val Leu Leu Ser Thr Pro Ala Leu Glu Ala Val Phe Thr

340 345 350

Asp Leu Glu Ile Leu Ala Ala Ile Phe Ala Ser Ala Ile His Asp Val

355 360 365

Asp His Pro Gly Val Ser Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu

370 375 380

Leu Ala Leu Met Tyr Asn Asp Ser Ser Val Leu Glu Asn His His Leu

385 390 395 400

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

405 410 415

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

420 425 430

Ile Val Leu Ala Thr Asp Met Ser Lys His Met Asn Leu Leu Ala Asp

435 440 445

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

450 455 460

Leu Leu Asp Asn Tyr Ser Asp Arg Ile Gln Val Leu Gln Asn Met Val

465 470 475 480

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

485 490 495

Gln Trp Thr Asp Arg Ile Met Glu Glu Phe Phe Arg Gln Gly Asp Arg

500 505 510

Glu Arg Glu Arg Gly Met Glu Ile Ser Pro Met Cys Asp Lys His Asn

515 520 525

Ala Ser Val Glu Lys Ser Gln Val Gly Phe Ile Asp Tyr Ile Val His

530 535 540

Pro Leu Trp Glu Thr Trp Ala Asp Leu Val His Pro Asp Ala Gln Asp

545 550 555 560

Ile Leu Asp Thr Leu Glu Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile

565 570 575

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

580 585 590

Gly Gln Thr Glu Lys Phe Gln Phe Glu Leu Thr Leu Glu Glu Asp Gly

595 600 605

Glu Ser Asp Thr Glu Lys Asp Ser Gly Ser Gln Val Glu Glu Asp Thr

610 615 620

Ser Cys Ser Asp Ser Lys Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr

625 630 635 640

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

645 650 655

Glu Glu Ser Gln Pro Glu Ala Cys Val Ile Asp Asp Arg Ser Pro Asp

660 665 670

Thr

<210> 10

<211> 8240

<212> DNA

<213> 智人

<400> 10

cccctctcgg tagccctgag gctctggcgc cttcaagtga gaagctaagc accagcctct 60

gctgggctgc agaagcggcg gcggcggcag cagcagcagc agcatcagga aggcgctcgg 120

gccagcgcgg tgaacccggg ctgggcagca ggtcgcggag ccgcgagcca ggatggaggc 180

agagggcagc agcgcgccgg cccgggcggg cagcggagag ggcagcgaca gcgccggcgg 240

ggccacgctc aaagccccca agcatctctg gaggcacgag cagcaccacc agtacccgct 300

ccggcagccc cagttccgcc tcctgcatcc ccatcaccac ctgcccccgc cgccgccacc 360

ctcgccccag ccccagcccc agtgtccgct acagccgccg ccgccgcccc ccctgccgcc 420

gcccccgccg ccgcccgggg ctgcccgcgg ccgctacgcc tcgagcgggg ccaccggccg 480

cgtccggcat cgcggctact cggacaccga gcgctacctg tactgtcgcg ccatggaccg 540

cacctcctac gcggtggaga ccggccaccg gcccggcctg aagaaatcca ggatgtcctg 600

gccctcctcg ttccagggac tcaggcgttt tgatgtggac aatggcacat ctgcgggacg 660

gagtcccttg gatcccatga ccagcccagg atccgggcta attctccaag caaattttgt 720

ccacagtcaa cgacgggagt ccttcctgta tcgatccgac agcgattatg acctctctcc 780

aaagtctatg tcccggaact cctccattgc cagtgatata cacggagatg acttgattgt 840

gactccattt gctcaggtct tggccagtct gcgaactgta cgaaacaact ttgctgcatt 900

aactaatttg caagatcgag cacctagcaa aagatcaccc atgtgcaacc aaccatccat 960

caacaaagcc accataacag aggaggccta ccagaaactg gccagcgaga ccctggagga 1020

gctggactgg tgtctggacc agctagagac cctacagacc aggcactccg tcagtgagat 1080

ggcctccaac aagtttaaaa ggatgcttaa tcgggagctc acccatctct ctgaaatgag 1140

tcggtctgga aatcaagtgt cagagtttat atcaaacaca ttcttagata agcaacatga 1200

agtggaaatt ccttctccaa ctcagaagga aaaggagaaa aagaaaagac caatgtctca 1260

gatcagtgga gtcaagaaat tgatgcacag ctctagtctg actaattcaa gtatcccaag 1320

gtttggagtt aaaactgaac aagaagatgt ccttgccaag gaactagaag atgtgaacaa 1380

atggggtctt catgttttca gaatagcaga gttgtctggt aaccggccct tgactgttat 1440

catgcacacc atttttcagg aacgggattt attaaaaaca tttaaaattc cagtagatac 1500

tttaattaca tatcttatga ctctcgaaga ccattaccat gctgatgtgg cctatcacaa 1560

caatatccat gctgcagatg ttgtccagtc tactcatgtg ctattatcta cacctgcttt 1620

ggaggctgtg tttacagatt tggagattct tgcagcaatt tttgccagtg caatacatga 1680

tgtagatcat cctggtgtgt ccaatcaatt tctgatcaat acaaactctg aacttgcctt 1740

gatgtacaat gattcctcag tcttagagaa ccatcatttg gctgtgggct ttaaattgct 1800

tcaggaagaa aactgtgaca ttttccagaa tttgaccaaa aaacaaagac aatctttaag 1860

gaaaatggtc attgacatcg tacttgcaac agatatgtca aaacacatga atctactggc 1920

tgatttgaag actatggttg aaactaagaa agtgacaagc tctggagttc ttcttcttga 1980

taattattcc gataggattc aggttcttca gaatatggtg cactgtgcag atctgagcaa 2040

cccaacaaag cctctccagc tgtaccgcca gtggacggac cggataatgg aggagttctt 2100

ccgccaagga gaccgagaga gggaacgtgg catggagata agccccatgt gtgacaagca 2160

caatgcttcc gtggaaaaat cacaggtggg cttcatagac tatattgttc atcccctctg 2220

ggagacatgg gcagacctcg tccaccctga cgcccaggat attttggaca ctttggagga 2280

caatcgtgaa tggtaccaga gcacaatccc tcagagcccc tctcctgcac ctgatgaccc 2340

agaggagggc cggcagggtc aaactgagaa attccagttt gaactaactt tagaggaaga 2400

tggtgagtca gacacggaaa aggacagtgg cagtcaagtg gaagaagaca ctagctgcag 2460

tgactccaag actctttgta ctcaagactc agagtctact gaaattcccc ttgatgaaca 2520

ggttgaagag gaggcagtag gggaagaaga ggaaagccag cctgaagcct gtgtcataga 2580

tgatcgttct cctgacacgt aacagtgcaa aaactttcat gccttttttt tttttaagta 2640

gaaaaattgt ttccaaagtg catgtcacat gccacaacca cggtcacacc tcactgtcat 2700

ctgccaggac gtttgttgaa caaaactgac cttgactact cagtccagcg ctcaggaata 2760

tcgtaaccag ttttttcacc tccatgtcat ccgagcaagg tggacatctt cacgaacagc 2820

gtttttaaca agatttcagc ttggtagagc tgacaaagca gataaaatct actccaaatt 2880

attttcaaga gagtgtgact catcaggcag cccaaaagtt tattggactt ggggtttcta 2940

ttccttttta tttgtttgca atattttcag aagaaaggca ttgcacagag tgaacttaat 3000

ggacgaagca acaaatatgt caagaacagg acatagcacg aatctgttac cagtaggagg 3060

aggatgagcc acagaaattg cataattttc taatttcaag tcttcctgat acatgactga 3120

atagtgtggt tcagtgagct gcactgacct ctacattttg tatgatatgt aaaacagatt 3180

ttttgtagag cttactttta ttattaaatg tattgaggta ttatatttaa aaaaaactat 3240

gttcagaact tcatctgcca ctggttattt ttttctaagg agtaacttgc aagttttcag 3300

tacaaatctg tgctacactg gataaaaatc taatttatga attttacttg caccttatag 3360

ttcatagcaa ttaactgatt tgtagtgatt cattgtttgt tttatatacc aatgacttcc 3420

atattttaaa agagaaaaac aactttatgt tgcaggaaac cctttttgta agtctttatt 3480

atttactttg cattttgttt cactctttcc agataagcag agttgctctt caccagtgtt 3540

tttcttcatg tgcaaagtga ctatttgttc tataatactt ttatgtgtgt tatatcaaat 3600

gtgtcttaag cttcatgcaa actcagtcat cagttcgtgt tgtctgaagc aagtgggaga 3660

tatataaata cccagtagct aaaatggtca gtctttttta gatgttttcc tacttagtat 3720

ctcctaataa cgttttgctg tgtcactaga tgttcatttc acaagtgcat gtctttctaa 3780

taatccacac atttcatgct ctaataatcc acacatttca tgctcatttt tattgttttt 3840

acagccagtt atagtaagaa aaaggttttt ccccttgtgc tgctttataa tttagcgtgt 3900

gtctgaacct tatccatgtt tgctagatga ggtcttgtca aatatatcac taccattgtc 3960

accggtgaaa agaaacaggt agttaagtta gggttaacat tcatttcaac cacgaggttg 4020

tatatcatga ctagctttta ctcttggttt acagagaaaa gttaaacagc caactaggca 4080

gtttttaaga atattaacaa tatattaaca aacaccaata caactaatcc tatttggttt 4140

taatgatttc accatgggat taagaactat atcaggaaca tccctgagaa acggttttaa 4200

gtgtagcaac tactcttcct taatggacag ccacataacg tgtaggaagt cctttatcac 4260

ttatcctcga tccataagca tatcttgcag aggggaacta cttctttaaa cacatggagg 4320

gaaagaagat gatgccactg gcaccagagg gttagtactg tgatgcatcc taaaatattt 4380

attatattgg taaaaattct ggttaaataa aaaattagag atcactcttg gctgatttca 4440

gcaccaggaa ctgtattaca gttttagaga ttaattccta gtgtttacct gattatagca 4500

gttggcatca tggggcattt aattctgact ttatccccac gtcagcctta ataaagtctt 4560

ctttaccttc tctatgaaga ctttaaagcc caaataatca tttttcacat tgatattcaa 4620

gaattgagat agatagaagc caaagtgggt atctgacaag tggaaaatca aacgtttaag 4680

aagaattaca actctgaaaa gcatttatat gtggaacttc tcaaggagcc tcctggggac 4740

tggaaagtaa gtcatcagcc aggcaaatga ctcatgctga agagagtccc catttcagtc 4800

ccctgagatc tagctgatgc ttagatcctt tgaaataaaa attatgtctt tataactctg 4860

atcttttaca taaagcagaa gaggaatcaa ctagttaatt gcaaggtttc tactctgttt 4920

cctctgtaaa gatcagatgg taatctttca aataagaaaa aaataaagac gtatgtttga 4980

ccaagtagtt tcacaagaat atttgggaac ttgtttcttt taattttatt tgtccctgag 5040

tgaagtctag aaagaaaggt aaagagtcta gagtttattc ctctttccaa aacattctca 5100

ttcctctcct ccctacactt agtatttccc ccacagagtg cctagaatct taataatgaa 5160

taaaataaaa agcagcaata tgtcattaac aaatccagac ctgaaagggt aaagggttta 5220

taactgcact aataaagaga ggctcttttt ttttcttcca gtttgttggt ttttaatggt 5280

accgtgttgt aaagataccc actaatggac aatcaaattg cagaaaaggc tcaatatcca 5340

agagacaggg actaatgcac tgtacaatct gcttatcctt gcccttctct cttgccaaag 5400

tgtgcttcag aaatatatac tgctttaaaa aagaataaaa gaatatcctt ttacaagtgg 5460

ctttacattt cctaaaatgc cataagaaaa tgcaatatct gggtactgta tggggaaaaa 5520

aatgtccaag tttgtgtaaa accagtgcat ttcagcttgc aagttactga acacaataat 5580

gctgttttaa ttttgtttta tatcagttaa aattcacaat aatgtagata gaacaaatta 5640

cagacaagga aagaaaaaac ttgaatgaaa tggattttac agaaagcttt atgataattt 5700

ttgaatgcat tatttatttt ttgtgccatg catttttttt ctcaccaaat gaccttacct 5760

gtaatacagt cttgtttgtc tgtttacaac catgtattta ttgcaatgta catactgtaa 5820

tgttaattgt aaattatctg ttcttattaa aacatcatcc catgatggga tggtgttgat 5880

atatttggaa actcttggtg agagaatgaa tggtgtgtat acatactctg tacatttttc 5940

ttttctcctg taatatagtc ttgtcacctt agagcttgtt tatggaagat tcaagaaaac 6000

tataaaatac ttaaagatat ataaatttaa aaaaacatag ctgcaggtct ttggtcccag 6060

ggctgtgcct taactttaac caatattttc ttctgttttg ctgcatttga aaggtaacag 6120

tggagctagg gctgggcatt ttacatccag gcttttaatt gattagaatt ctgccaatag 6180

gtggatttta caaaaccaca gacaacctct gaaagattct gagacccttt tgagacagaa 6240

gctcttaagt acttcttgcc agggagcagc actgcatgtg tgatggttgt ttgccatctg 6300

ttgatcagga actacttcag ctacttgcat ttgattattt cctttttttt tttttttaac 6360

tcggaaacac aactggggaa atatattctt tcccagtgat tataaacaat ctttttcttt 6420

tttttaagtc cttttggctt ctagagctca taggaaaatg gacttgattt gaaattggag 6480

ccagagttta ctcgtgttgg ttatctattc atcagcttcc tgacatgtta agagaataca 6540

ttaaagagaa aatactgttt tttaatccta aaatttttct tccactaaga taaaccaaat 6600

gtccttacat atatgtaaac ccatctattt aaacgcaaag gtgggttgat gtcagtttac 6660

atagcagaaa gcattcacta tcctctaaga tttgtttctg caaaactttc attgctttag 6720

aattttaaaa tttcaccttg tacaatggcc agcccctaaa gcaggaaaca tttataatgg 6780

attatatgga aacatcctcc cagtacttgc ccagcccttg aatcatgtgg cttttcagtg 6840

aaaggaaaga ttctttttct aggaaaaatg agcctatttt attttatttt attttatttt 6900

ttgacacaaa ctgtagattt tagcagccct ggcccaaagg aatttgatta cttttgtttt 6960

aaacagtaca aaggggacac tataattaca aaaacatcct taactgattt gagttgtttt 7020

tatttctttg gatatatttt cagagtggta aattgtgtgt gagaattaca aatgattatt 7080

cttttagtgg tttcttagcc tctcttacag cccacgggga tagtactgta catcaatacc 7140

ttcatatgaa atttttatat gcaatgaaaa taaaagcatg ggttgattct gcctatttat 7200

gactcaatct tttacaaata aaagattatt cattttaaat tatagttcaa tcagcatgtc 7260

tcttaggata ctgaacgtgg ttgaaatgaa aggatagtga catcataagt tagtactgat 7320

attcataacc aaataaagcc aacttgagta attttgctac attaaaaatt accaaaatta 7380

cttagatggc ctataagatt aagcatggtg ttttctaagc aagctttgaa aggggccttc 7440

catacttact taattgaata ttctgggata ttgaaaatta ttcagatact tgacaattat 7500

ttttggttac ctactccgca aactacaaag ttttaaggac tcaacaataa gttaatgaga 7560

cacagtgttt gctttcatgg agcttacagt ctggagggga caaaggctta aacaatactc 7620

atataattat atatgtgatc agtacaatga aggagctcag tggggtaaat aagcaggaac 7680

ctgaacttga tctgttccgg agggccacag aaggcttcct tgaggccttg agaaagtgat 7740

ttgcatctga gttctgaagg attgtaagag gtaactaggg aaaaagttga caggaagagg 7800

aaggggatcc agacaagaaa catttgcaaa gatcttgagg cataaatgag cttgagacat 7860

ctggagaaac tgaggaaaag tgagagagta ggcagggcct ggagccgcag agccattgct 7920

aaccatcctg tgtgagatat cccccattct gtagctttat tctcataacc ctgctcaatt 7980

ttctttataa cacttctcac agatttatat acgtgtttgt ttttgttatc tgtctctccc 8040

accagaccac agctccatga gagcaaggtc tttgcttacc aatatatcac tagcacttaa 8100

aactatgcct ggtacacagt aggttcttaa tatgtgttga atatagccat caaattgata 8160

ttggatataa ttcaatctga taagatattt tgagatatta aagagttttt aacttgatac 8220

cataaaaaaa aaaaaaaaaa 8240

<210> 11

<211> 809

<212> PRT

<213> 智人

<400> 11

Met Glu Ala Glu Gly Ser Ser Ala Pro Ala Arg Ala Gly Ser Gly Glu

1 5 10 15

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

20 25 30

Trp Arg His Glu Gln His His Gln Tyr Pro Leu Arg Gln Pro Gln Phe

35 40 45

Arg Leu Leu His Pro His His His Leu Pro Pro Pro Pro Pro Pro Ser

50 55 60

Pro Gln Pro Gln Pro Gln Cys Pro Leu Gln Pro Pro Pro Pro Pro Pro

65 70 75 80

Leu Pro Pro Pro Pro Pro Pro Pro Gly Ala Ala Arg Gly Arg Tyr Ala

85 90 95

Ser Ser Gly Ala Thr Gly Arg Val Arg His Arg Gly Tyr Ser Asp Thr

100 105 110

Glu Arg Tyr Leu Tyr Cys Arg Ala Met Asp Arg Thr Ser Tyr Ala Val

115 120 125

Glu Thr Gly His Arg Pro Gly Leu Lys Lys Ser Arg Met Ser Trp Pro

130 135 140

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

145 150 155 160

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

165 170 175

Ile Leu Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu Ser Phe Leu

180 185 190

Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser Met Ser Arg

195 200 205

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

210 215 220

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

225 230 235 240

Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys Arg Ser Pro

245 250 255

Met Cys Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr Glu Glu Ala

260 265 270

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

275 280 285

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

290 295 300

Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser

305 310 315 320

Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser Asn Thr

325 330 335

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

340 345 350

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

355 360 365

Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe

370 375 380

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

385 390 395 400

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

405 410 415

Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp

420 425 430

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

435 440 445

Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn

450 455 460

Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr

465 470 475 480

Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile

485 490 495

Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln

500 505 510

Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser

515 520 525

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

530 535 540

Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln

545 550 555 560

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

565 570 575

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

580 585 590

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

595 600 605

Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro

610 615 620

Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu

625 630 635 640

Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile

645 650 655

Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val

660 665 670

Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp

675 680 685

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

690 695 700

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

705 710 715 720

Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe Gln Phe

725 730 735

Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser

740 745 750

Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys Thr Leu

755 760 765

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

770 775 780

Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys

785 790 795 800

Val Ile Asp Asp Arg Ser Pro Asp Thr

805

<210> 12

<211> 7979

<212> DNA

<213> 智人

<400> 12

cagcagcagg ctcagacctg cttccctgga catttccggg accgtgagcg agggaaccac 60

gttgccctgg attcttgcca gctgtacaaa gttgaccagg aaaatggctc agcagacaag 120

cccggacact ttaacagtac ctgaagtgga taatccgcat tgtccaaacc cgtggctgaa 180

cgaagacctt gtgaaatcct tgcgagaaaa cctgttgcag catgagaagt ccaagacagc 240

gaggaaatcg gtttctccca agctctctcc agtgatctct ccgagaaatt cccccaggct 300

tctgcgcaga atgcttctca gcagcaacat ccccaaacag cggcgtttca cggtggcaca 360

tacatgtttt gatgtggaca atggcacatc tgcgggacgg agtcccttgg atcccatgac 420

cagcccagga tccgggctaa ttctccaagc aaattttgtc cacagtcaac gacgggagtc 480

cttcctgtat cgatccgaca gcgattatga cctctctcca aagtctatgt cccggaactc 540

ctccattgcc agtgatatac acggagatga cttgattgtg actccatttg ctcaggtctt 600

ggccagtctg cgaactgtac gaaacaactt tgctgcatta actaatttgc aagatcgagc 660

acctagcaaa agatcaccca tgtgcaacca accatccatc aacaaagcca ccataacaga 720

ggaggcctac cagaaactgg ccagcgagac cctggaggag ctggactggt gtctggacca 780

gctagagacc ctacagacca ggcactccgt cagtgagatg gcctccaaca agtttaaaag 840

gatgcttaat cgggagctca cccatctctc tgaaatgagt cggtctggaa atcaagtgtc 900

agagtttata tcaaacacat tcttagataa gcaacatgaa gtggaaattc cttctccaac 960

tcagaaggaa aaggagaaaa agaaaagacc aatgtctcag atcagtggag tcaagaaatt 1020

gatgcacagc tctagtctga ctaattcaag tatcccaagg tttggagtta aaactgaaca 1080

agaagatgtc cttgccaagg aactagaaga tgtgaacaaa tggggtcttc atgttttcag 1140

aatagcagag ttgtctggta accggccctt gactgttatc atgcacacca tttttcagga 1200

acgggattta ttaaaaacat ttaaaattcc agtagatact ttaattacat atcttatgac 1260

tctcgaagac cattaccatg ctgatgtggc ctatcacaac aatatccatg ctgcagatgt 1320

tgtccagtct actcatgtgc tattatctac acctgctttg gaggctgtgt ttacagattt 1380

ggagattctt gcagcaattt ttgccagtgc aatacatgat gtagatcatc ctggtgtgtc 1440

caatcaattt ctgatcaata caaactctga acttgccttg atgtacaatg attcctcagt 1500

cttagagaac catcatttgg ctgtgggctt taaattgctt caggaagaaa actgtgacat 1560

tttccagaat ttgaccaaaa aacaaagaca atctttaagg aaaatggtca ttgacatcgt 1620

acttgcaaca gatatgtcaa aacacatgaa tctactggct gatttgaaga ctatggttga 1680

aactaagaaa gtgacaagct ctggagttct tcttcttgat aattattccg ataggattca 1740

ggttcttcag aatatggtgc actgtgcaga tctgagcaac ccaacaaagc ctctccagct 1800

gtaccgccag tggacggacc ggataatgga ggagttcttc cgccaaggag accgagagag 1860

ggaacgtggc atggagataa gccccatgtg tgacaagcac aatgcttccg tggaaaaatc 1920

acaggtgggc ttcatagact atattgttca tcccctctgg gagacatggg cagacctcgt 1980

ccaccctgac gcccaggata ttttggacac tttggaggac aatcgtgaat ggtaccagag 2040

cacaatccct cagagcccct ctcctgcacc tgatgaccca gaggagggcc ggcagggtca 2100

aactgagaaa ttccagtttg aactaacttt agaggaagat ggtgagtcag acacggaaaa 2160

ggacagtggc agtcaagtgg aagaagacac tagctgcagt gactccaaga ctctttgtac 2220

tcaagactca gagtctactg aaattcccct tgatgaacag gttgaagagg aggcagtagg 2280

ggaagaagag gaaagccagc ctgaagcctg tgtcatagat gatcgttctc ctgacacgta 2340

acagtgcaaa aactttcatg cctttttttt ttttaagtag aaaaattgtt tccaaagtgc 2400

atgtcacatg ccacaaccac ggtcacacct cactgtcatc tgccaggacg tttgttgaac 2460

aaaactgacc ttgactactc agtccagcgc tcaggaatat cgtaaccagt tttttcacct 2520

ccatgtcatc cgagcaaggt ggacatcttc acgaacagcg tttttaacaa gatttcagct 2580

tggtagagct gacaaagcag ataaaatcta ctccaaatta ttttcaagag agtgtgactc 2640

atcaggcagc ccaaaagttt attggacttg gggtttctat tcctttttat ttgtttgcaa 2700

tattttcaga agaaaggcat tgcacagagt gaacttaatg gacgaagcaa caaatatgtc 2760

aagaacagga catagcacga atctgttacc agtaggagga ggatgagcca cagaaattgc 2820

ataattttct aatttcaagt cttcctgata catgactgaa tagtgtggtt cagtgagctg 2880

cactgacctc tacattttgt atgatatgta aaacagattt tttgtagagc ttacttttat 2940

tattaaatgt attgaggtat tatatttaaa aaaaactatg ttcagaactt catctgccac 3000

tggttatttt tttctaagga gtaacttgca agttttcagt acaaatctgt gctacactgg 3060

ataaaaatct aatttatgaa ttttacttgc accttatagt tcatagcaat taactgattt 3120

gtagtgattc attgtttgtt ttatatacca atgacttcca tattttaaaa gagaaaaaca 3180

actttatgtt gcaggaaacc ctttttgtaa gtctttatta tttactttgc attttgtttc 3240

actctttcca gataagcaga gttgctcttc accagtgttt ttcttcatgt gcaaagtgac 3300

tatttgttct ataatacttt tatgtgtgtt atatcaaatg tgtcttaagc ttcatgcaaa 3360

ctcagtcatc agttcgtgtt gtctgaagca agtgggagat atataaatac ccagtagcta 3420

aaatggtcag tcttttttag atgttttcct acttagtatc tcctaataac gttttgctgt 3480

gtcactagat gttcatttca caagtgcatg tctttctaat aatccacaca tttcatgctc 3540

taataatcca cacatttcat gctcattttt attgttttta cagccagtta tagtaagaaa 3600

aaggtttttc cccttgtgct gctttataat ttagcgtgtg tctgaacctt atccatgttt 3660

gctagatgag gtcttgtcaa atatatcact accattgtca ccggtgaaaa gaaacaggta 3720

gttaagttag ggttaacatt catttcaacc acgaggttgt atatcatgac tagcttttac 3780

tcttggttta cagagaaaag ttaaacagcc aactaggcag tttttaagaa tattaacaat 3840

atattaacaa acaccaatac aactaatcct atttggtttt aatgatttca ccatgggatt 3900

aagaactata tcaggaacat ccctgagaaa cggttttaag tgtagcaact actcttcctt 3960

aatggacagc cacataacgt gtaggaagtc ctttatcact tatcctcgat ccataagcat 4020

atcttgcaga ggggaactac ttctttaaac acatggaggg aaagaagatg atgccactgg 4080

caccagaggg ttagtactgt gatgcatcct aaaatattta ttatattggt aaaaattctg 4140

gttaaataaa aaattagaga tcactcttgg ctgatttcag caccaggaac tgtattacag 4200

ttttagagat taattcctag tgtttacctg attatagcag ttggcatcat ggggcattta 4260

attctgactt tatccccacg tcagccttaa taaagtcttc tttaccttct ctatgaagac 4320

tttaaagccc aaataatcat ttttcacatt gatattcaag aattgagata gatagaagcc 4380

aaagtgggta tctgacaagt ggaaaatcaa acgtttaaga agaattacaa ctctgaaaag 4440

catttatatg tggaacttct caaggagcct cctggggact ggaaagtaag tcatcagcca 4500

ggcaaatgac tcatgctgaa gagagtcccc atttcagtcc cctgagatct agctgatgct 4560

tagatccttt gaaataaaaa ttatgtcttt ataactctga tcttttacat aaagcagaag 4620

aggaatcaac tagttaattg caaggtttct actctgtttc ctctgtaaag atcagatggt 4680

aatctttcaa ataagaaaaa aataaagacg tatgtttgac caagtagttt cacaagaata 4740

tttgggaact tgtttctttt aattttattt gtccctgagt gaagtctaga aagaaaggta 4800

aagagtctag agtttattcc tctttccaaa acattctcat tcctctcctc cctacactta 4860

gtatttcccc cacagagtgc ctagaatctt aataatgaat aaaataaaaa gcagcaatat 4920

gtcattaaca aatccagacc tgaaagggta aagggtttat aactgcacta ataaagagag 4980

gctctttttt tttcttccag tttgttggtt tttaatggta ccgtgttgta aagataccca 5040

ctaatggaca atcaaattgc agaaaaggct caatatccaa gagacaggga ctaatgcact 5100

gtacaatctg cttatccttg cccttctctc ttgccaaagt gtgcttcaga aatatatact 5160

gctttaaaaa agaataaaag aatatccttt tacaagtggc tttacatttc ctaaaatgcc 5220

ataagaaaat gcaatatctg ggtactgtat ggggaaaaaa atgtccaagt ttgtgtaaaa 5280

ccagtgcatt tcagcttgca agttactgaa cacaataatg ctgttttaat tttgttttat 5340

atcagttaaa attcacaata atgtagatag aacaaattac agacaaggaa agaaaaaact 5400

tgaatgaaat ggattttaca gaaagcttta tgataatttt tgaatgcatt atttattttt 5460

tgtgccatgc attttttttc tcaccaaatg accttacctg taatacagtc ttgtttgtct 5520

gtttacaacc atgtatttat tgcaatgtac atactgtaat gttaattgta aattatctgt 5580

tcttattaaa acatcatccc atgatgggat ggtgttgata tatttggaaa ctcttggtga 5640

gagaatgaat ggtgtgtata catactctgt acatttttct tttctcctgt aatatagtct 5700

tgtcacctta gagcttgttt atggaagatt caagaaaact ataaaatact taaagatata 5760

taaatttaaa aaaacatagc tgcaggtctt tggtcccagg gctgtgcctt aactttaacc 5820

aatattttct tctgttttgc tgcatttgaa aggtaacagt ggagctaggg ctgggcattt 5880

tacatccagg cttttaattg attagaattc tgccaatagg tggattttac aaaaccacag 5940

acaacctctg aaagattctg agaccctttt gagacagaag ctcttaagta cttcttgcca 6000

gggagcagca ctgcatgtgt gatggttgtt tgccatctgt tgatcaggaa ctacttcagc 6060

tacttgcatt tgattatttc cttttttttt ttttttaact cggaaacaca actggggaaa 6120

tatattcttt cccagtgatt ataaacaatc tttttctttt ttttaagtcc ttttggcttc 6180

tagagctcat aggaaaatgg acttgatttg aaattggagc cagagtttac tcgtgttggt 6240

tatctattca tcagcttcct gacatgttaa gagaatacat taaagagaaa atactgtttt 6300

ttaatcctaa aatttttctt ccactaagat aaaccaaatg tccttacata tatgtaaacc 6360

catctattta aacgcaaagg tgggttgatg tcagtttaca tagcagaaag cattcactat 6420

cctctaagat ttgtttctgc aaaactttca ttgctttaga attttaaaat ttcaccttgt 6480

acaatggcca gcccctaaag caggaaacat ttataatgga ttatatggaa acatcctccc 6540

agtacttgcc cagcccttga atcatgtggc ttttcagtga aaggaaagat tctttttcta 6600

ggaaaaatga gcctatttta ttttatttta ttttattttt tgacacaaac tgtagatttt 6660

agcagccctg gcccaaagga atttgattac ttttgtttta aacagtacaa aggggacact 6720

ataattacaa aaacatcctt aactgatttg agttgttttt atttctttgg atatattttc 6780

agagtggtaa attgtgtgtg agaattacaa atgattattc ttttagtggt ttcttagcct 6840

ctcttacagc ccacggggat agtactgtac atcaatacct tcatatgaaa tttttatatg 6900

caatgaaaat aaaagcatgg gttgattctg cctatttatg actcaatctt ttacaaataa 6960

aagattattc attttaaatt atagttcaat cagcatgtct cttaggatac tgaacgtggt 7020

tgaaatgaaa ggatagtgac atcataagtt agtactgata ttcataacca aataaagcca 7080

acttgagtaa ttttgctaca ttaaaaatta ccaaaattac ttagatggcc tataagatta 7140

agcatggtgt tttctaagca agctttgaaa ggggccttcc atacttactt aattgaatat 7200

tctgggatat tgaaaattat tcagatactt gacaattatt tttggttacc tactccgcaa 7260

actacaaagt tttaaggact caacaataag ttaatgagac acagtgtttg ctttcatgga 7320

gcttacagtc tggaggggac aaaggcttaa acaatactca tataattata tatgtgatca 7380

gtacaatgaa ggagctcagt ggggtaaata agcaggaacc tgaacttgat ctgttccgga 7440

gggccacaga aggcttcctt gaggccttga gaaagtgatt tgcatctgag ttctgaagga 7500

ttgtaagagg taactaggga aaaagttgac aggaagagga aggggatcca gacaagaaac 7560

atttgcaaag atcttgaggc ataaatgagc ttgagacatc tggagaaact gaggaaaagt 7620

gagagagtag gcagggcctg gagccgcaga gccattgcta accatcctgt gtgagatatc 7680

ccccattctg tagctttatt ctcataaccc tgctcaattt tctttataac acttctcaca 7740

gatttatata cgtgtttgtt tttgttatct gtctctccca ccagaccaca gctccatgag 7800

agcaaggtct ttgcttacca atatatcact agcacttaaa actatgcctg gtacacagta 7860

ggttcttaat atgtgttgaa tatagccatc aaattgatat tggatataat tcaatctgat 7920

aagatatttt gagatattaa agagttttta acttgatacc ataaaaaaaa aaaaaaaaa 7979

<210> 13

<211> 745

<212> PRT

<213> 智人

<400> 13

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

1 5 10 15

Asn Pro His Cys Pro Asn Pro Trp Leu Asn Glu Asp Leu Val Lys Ser

20 25 30

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

35 40 45

Ser Val Ser Pro Lys Leu Ser Pro Val Ile Ser Pro Arg Asn Ser Pro

50 55 60

Arg Leu Leu Arg Arg Met Leu Leu Ser Ser Asn Ile Pro Lys Gln Arg

65 70 75 80

Arg Phe Thr Val Ala His Thr Cys Phe Asp Val Asp Asn Gly Thr Ser

85 90 95

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

100 105 110

Ile Leu Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu Ser Phe Leu

115 120 125

Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser Met Ser Arg

130 135 140

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

145 150 155 160

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

165 170 175

Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys Arg Ser Pro

180 185 190

Met Cys Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr Glu Glu Ala

195 200 205

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

210 215 220

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

225 230 235 240

Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser

245 250 255

Glu Met Ser Arg Ser Gly Asn Gln Val Ser Glu Phe Ile Ser Asn Thr

260 265 270

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

275 280 285

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

290 295 300

Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe

305 310 315 320

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

325 330 335

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

340 345 350

Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp

355 360 365

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

370 375 380

Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn

385 390 395 400

Ile His Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr

405 410 415

Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile

420 425 430

Phe Ala Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln

435 440 445

Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser

450 455 460

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

465 470 475 480

Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln

485 490 495

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

500 505 510

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

515 520 525

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

530 535 540

Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro

545 550 555 560

Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu

565 570 575

Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile

580 585 590

Ser Pro Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val

595 600 605

Gly Phe Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp

610 615 620

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

625 630 635 640

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

645 650 655

Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys Phe Gln Phe

660 665 670

Glu Leu Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser

675 680 685

Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser Lys Thr Leu

690 695 700

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

705 710 715 720

Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys

725 730 735

Val Ile Asp Asp Arg Ser Pro Asp Thr

740 745

<210> 14

<211> 19

<212> DNA

<213> 人工序列

<220>

<223> PDE4D5_正向引物

<400> 14

gcttctcagc agcaacatc 19

<210> 15

<211> 20

<212> DNA

<213> 人工序列

<220>

<223> PDE4D5_反向引物

<400> 15

tgccattgtc cacatcaaaa 20

<210> 16

<211> 24

<212> DNA

<213> 人工序列

<220>

<223> PDE4D5探针

<400> 16

acagcggcgt ttcacggtgg caca 24

<210> 17

<211> 7591

<212> DNA

<213> 智人

<400> 17

agttccttat ttggtagctt ttgacaggac tagcctttct tgcaactaag catcttgaca 60

tacattattc attaagccct ggagctcggg agagaaagat gcagaccctt agatctttag 120

atattccttt atcacgtgga ttttctttat tcagaatagt tgctgaattt tgtgccattc 180

tggagtctta caaatggcat gtattcgatg ggaagacggc tggatgggat ttaatgcgag 240

gctttcttat gtatacttaa ttaccaaaaa tctttaaaaa ctcatactct gcgtggcttg 300

tggaggttgt taaagtgtcg agattttgaa gctaaataca ttttagagct tactatatat 360

atacatatat atatatatac atataatcaa tcaaaaatgc ctgaagcaaa ctatttactg 420

tcagtgtctt ggggctacat aaagtttaaa aggatgctta atcgggagct cacccatctc 480

tctgaaatga gtcggtctgg aaatcaagtg tcagagttta tatcaaacac attcttagat 540

aagcaacatg aagtggaaat tccttctcca actcagaagg aaaaggagaa aaagaaaaga 600

ccaatgtctc agatcagtgg agtcaagaaa ttgatgcaca gctctagtct gactaattca 660

agtatcccaa ggtttggagt taaaactgaa caagaagatg tccttgccaa ggaactagaa 720

gatgtgaaca aatggggtct tcatgttttc agaatagcag agttgtctgg taaccggccc 780

ttgactgtta tcatgcacac catttttcag gaacgggatt tattaaaaac atttaaaatt 840

ccagtagata ctttaattac atatcttatg actctcgaag accattacca tgctgatgtg 900

gcctatcaca acaatatcca tgctgcagat gttgtccagt ctactcatgt gctattatct 960

acacctgctt tggaggctgt gtttacagat ttggagattc ttgcagcaat ttttgccagt 1020

gcaatacatg atgtagatca tcctggtgtg tccaatcaat ttctgatcaa tacaaactct 1080

gaacttgcct tgatgtacaa tgattcctca gtcttagaga accatcattt ggctgtgggc 1140

tttaaattgc ttcaggaaga aaactgtgac attttccaga atttgaccaa aaaacaaaga 1200

caatctttaa ggaaaatggt cattgacatc gtacttgcaa cagatatgtc aaaacacatg 1260

aatctactgg ctgatttgaa gactatggtt gaaactaaga aagtgacaag ctctggagtt 1320

cttcttcttg ataattattc cgataggatt caggttcttc agaatatggt gcactgtgca 1380

gatctgagca acccaacaaa gcctctccag ctgtaccgcc agtggacgga ccggataatg 1440

gaggagttct tccgccaagg agaccgagag agggaacgtg gcatggagat aagccccatg 1500

tgtgacaagc acaatgcttc cgtggaaaaa tcacaggtgg gcttcataga ctatattgtt 1560

catcccctct gggagacatg ggcagacctc gtccaccctg acgcccagga tattttggac 1620

actttggagg acaatcgtga atggtaccag agcacaatcc ctcagagccc ctctcctgca 1680

cctgatgacc cagaggaggg ccggcagggt caaactgaga aattccagtt tgaactaact 1740

ttagaggaag atggtgagtc agacacggaa aaggacagtg gcagtcaagt ggaagaagac 1800

actagctgca gtgactccaa gactctttgt actcaagact cagagtctac tgaaattccc 1860

cttgatgaac aggttgaaga ggaggcagta ggggaagaag aggaaagcca gcctgaagcc 1920

tgtgtcatag atgatcgttc tcctgacacg taacagtgca aaaactttca tgcctttttt 1980

ttttttaagt agaaaaattg tttccaaagt gcatgtcaca tgccacaacc acggtcacac 2040

ctcactgtca tctgccagga cgtttgttga acaaaactga ccttgactac tcagtccagc 2100

gctcaggaat atcgtaacca gttttttcac ctccatgtca tccgagcaag gtggacatct 2160

tcacgaacag cgtttttaac aagatttcag cttggtagag ctgacaaagc agataaaatc 2220

tactccaaat tattttcaag agagtgtgac tcatcaggca gcccaaaagt ttattggact 2280

tggggtttct attccttttt atttgtttgc aatattttca gaagaaaggc attgcacaga 2340

gtgaacttaa tggacgaagc aacaaatatg tcaagaacag gacatagcac gaatctgtta 2400

ccagtaggag gaggatgagc cacagaaatt gcataatttt ctaatttcaa gtcttcctga 2460

tacatgactg aatagtgtgg ttcagtgagc tgcactgacc tctacatttt gtatgatatg 2520

taaaacagat tttttgtaga gcttactttt attattaaat gtattgaggt attatattta 2580

aaaaaaacta tgttcagaac ttcatctgcc actggttatt tttttctaag gagtaacttg 2640

caagttttca gtacaaatct gtgctacact ggataaaaat ctaatttatg aattttactt 2700

gcaccttata gttcatagca attaactgat ttgtagtgat tcattgtttg ttttatatac 2760

caatgacttc catattttaa aagagaaaaa caactttatg ttgcaggaaa ccctttttgt 2820

aagtctttat tatttacttt gcattttgtt tcactctttc cagataagca gagttgctct 2880

tcaccagtgt ttttcttcat gtgcaaagtg actatttgtt ctataatact tttatgtgtg 2940

ttatatcaaa tgtgtcttaa gcttcatgca aactcagtca tcagttcgtg ttgtctgaag 3000

caagtgggag atatataaat acccagtagc taaaatggtc agtctttttt agatgttttc 3060

ctacttagta tctcctaata acgttttgct gtgtcactag atgttcattt cacaagtgca 3120

tgtctttcta ataatccaca catttcatgc tctaataatc cacacatttc atgctcattt 3180

ttattgtttt tacagccagt tatagtaaga aaaaggtttt tccccttgtg ctgctttata 3240

atttagcgtg tgtctgaacc ttatccatgt ttgctagatg aggtcttgtc aaatatatca 3300

ctaccattgt caccggtgaa aagaaacagg tagttaagtt agggttaaca ttcatttcaa 3360

ccacgaggtt gtatatcatg actagctttt actcttggtt tacagagaaa agttaaacag 3420

ccaactaggc agtttttaag aatattaaca atatattaac aaacaccaat acaactaatc 3480

ctatttggtt ttaatgattt caccatggga ttaagaacta tatcaggaac atccctgaga 3540

aacggtttta agtgtagcaa ctactcttcc ttaatggaca gccacataac gtgtaggaag 3600

tcctttatca cttatcctcg atccataagc atatcttgca gaggggaact acttctttaa 3660

acacatggag ggaaagaaga tgatgccact ggcaccagag ggttagtact gtgatgcatc 3720

ctaaaatatt tattatattg gtaaaaattc tggttaaata aaaaattaga gatcactctt 3780

ggctgatttc agcaccagga actgtattac agttttagag attaattcct agtgtttacc 3840

tgattatagc agttggcatc atggggcatt taattctgac tttatcccca cgtcagcctt 3900

aataaagtct tctttacctt ctctatgaag actttaaagc ccaaataatc atttttcaca 3960

ttgatattca agaattgaga tagatagaag ccaaagtggg tatctgacaa gtggaaaatc 4020

aaacgtttaa gaagaattac aactctgaaa agcatttata tgtggaactt ctcaaggagc 4080

ctcctgggga ctggaaagta agtcatcagc caggcaaatg actcatgctg aagagagtcc 4140

ccatttcagt cccctgagat ctagctgatg cttagatcct ttgaaataaa aattatgtct 4200

ttataactct gatcttttac ataaagcaga agaggaatca actagttaat tgcaaggttt 4260

ctactctgtt tcctctgtaa agatcagatg gtaatctttc aaataagaaa aaaataaaga 4320

cgtatgtttg accaagtagt ttcacaagaa tatttgggaa cttgtttctt ttaattttat 4380

ttgtccctga gtgaagtcta gaaagaaagg taaagagtct agagtttatt cctctttcca 4440

aaacattctc attcctctcc tccctacact tagtatttcc cccacagagt gcctagaatc 4500

ttaataatga ataaaataaa aagcagcaat atgtcattaa caaatccaga cctgaaaggg 4560

taaagggttt ataactgcac taataaagag aggctctttt tttttcttcc agtttgttgg 4620

tttttaatgg taccgtgttg taaagatacc cactaatgga caatcaaatt gcagaaaagg 4680

ctcaatatcc aagagacagg gactaatgca ctgtacaatc tgcttatcct tgcccttctc 4740

tcttgccaaa gtgtgcttca gaaatatata ctgctttaaa aaagaataaa agaatatcct 4800

tttacaagtg gctttacatt tcctaaaatg ccataagaaa atgcaatatc tgggtactgt 4860

atggggaaaa aaatgtccaa gtttgtgtaa aaccagtgca tttcagcttg caagttactg 4920

aacacaataa tgctgtttta attttgtttt atatcagtta aaattcacaa taatgtagat 4980

agaacaaatt acagacaagg aaagaaaaaa cttgaatgaa atggatttta cagaaagctt 5040

tatgataatt tttgaatgca ttatttattt tttgtgccat gcattttttt tctcaccaaa 5100

tgaccttacc tgtaatacag tcttgtttgt ctgtttacaa ccatgtattt attgcaatgt 5160

acatactgta atgttaattg taaattatct gttcttatta aaacatcatc ccatgatggg 5220

atggtgttga tatatttgga aactcttggt gagagaatga atggtgtgta tacatactct 5280

gtacattttt cttttctcct gtaatatagt cttgtcacct tagagcttgt ttatggaaga 5340

ttcaagaaaa ctataaaata cttaaagata tataaattta aaaaaacata gctgcaggtc 5400

tttggtccca gggctgtgcc ttaactttaa ccaatatttt cttctgtttt gctgcatttg 5460

aaaggtaaca gtggagctag ggctgggcat tttacatcca ggcttttaat tgattagaat 5520

tctgccaata ggtggatttt acaaaaccac agacaacctc tgaaagattc tgagaccctt 5580

ttgagacaga agctcttaag tacttcttgc cagggagcag cactgcatgt gtgatggttg 5640

tttgccatct gttgatcagg aactacttca gctacttgca tttgattatt tccttttttt 5700

ttttttttaa ctcggaaaca caactgggga aatatattct ttcccagtga ttataaacaa 5760

tctttttctt ttttttaagt ccttttggct tctagagctc ataggaaaat ggacttgatt 5820

tgaaattgga gccagagttt actcgtgttg gttatctatt catcagcttc ctgacatgtt 5880

aagagaatac attaaagaga aaatactgtt ttttaatcct aaaatttttc ttccactaag 5940

ataaaccaaa tgtccttaca tatatgtaaa cccatctatt taaacgcaaa ggtgggttga 6000

tgtcagttta catagcagaa agcattcact atcctctaag atttgtttct gcaaaacttt 6060

cattgcttta gaattttaaa atttcacctt gtacaatggc cagcccctaa agcaggaaac 6120

atttataatg gattatatgg aaacatcctc ccagtacttg cccagccctt gaatcatgtg 6180

gcttttcagt gaaaggaaag attctttttc taggaaaaat gagcctattt tattttattt 6240

tattttattt tttgacacaa actgtagatt ttagcagccc tggcccaaag gaatttgatt 6300

acttttgttt taaacagtac aaaggggaca ctataattac aaaaacatcc ttaactgatt 6360

tgagttgttt ttatttcttt ggatatattt tcagagtggt aaattgtgtg tgagaattac 6420

aaatgattat tcttttagtg gtttcttagc ctctcttaca gcccacgggg atagtactgt 6480

acatcaatac cttcatatga aatttttata tgcaatgaaa ataaaagcat gggttgattc 6540

tgcctattta tgactcaatc ttttacaaat aaaagattat tcattttaaa ttatagttca 6600

atcagcatgt ctcttaggat actgaacgtg gttgaaatga aaggatagtg acatcataag 6660

ttagtactga tattcataac caaataaagc caacttgagt aattttgcta cattaaaaat 6720

taccaaaatt acttagatgg cctataagat taagcatggt gttttctaag caagctttga 6780

aaggggcctt ccatacttac ttaattgaat attctgggat attgaaaatt attcagatac 6840

ttgacaatta tttttggtta cctactccgc aaactacaaa gttttaagga ctcaacaata 6900

agttaatgag acacagtgtt tgctttcatg gagcttacag tctggagggg acaaaggctt 6960

aaacaatact catataatta tatatgtgat cagtacaatg aaggagctca gtggggtaaa 7020

taagcaggaa cctgaacttg atctgttccg gagggccaca gaaggcttcc ttgaggcctt 7080

gagaaagtga tttgcatctg agttctgaag gattgtaaga ggtaactagg gaaaaagttg 7140

acaggaagag gaaggggatc cagacaagaa acatttgcaa agatcttgag gcataaatga 7200

gcttgagaca tctggagaaa ctgaggaaaa gtgagagagt aggcagggcc tggagccgca 7260

gagccattgc taaccatcct gtgtgagata tcccccattc tgtagcttta ttctcataac 7320

cctgctcaat tttctttata acacttctca cagatttata tacgtgtttg tttttgttat 7380

ctgtctctcc caccagacca cagctccatg agagcaaggt ctttgcttac caatatatca 7440

ctagcactta aaactatgcc tggtacacag taggttctta atatgtgttg aatatagcca 7500

tcaaattgat attggatata attcaatctg ataagatatt ttgagatatt aaagagtttt 7560

taacttgata ccataaaaaa aaaaaaaaaa a 7591

<210> 18

<211> 518

<212> PRT

<213> 智人

<400> 18

Met Pro Glu Ala Asn Tyr Leu Leu Ser Val Ser Trp Gly Tyr Ile Lys

1 5 10 15

Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser Glu Met Ser

20 25 30

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

35 40 45

Lys Gln His Glu Val Glu Ile Pro Ser Pro Thr Gln Lys Glu Lys Glu

50 55 60

Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly Val Lys Lys Leu Met

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn Ile His Ala

165 170 175

Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr Pro Ala Leu

180 185 190

Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile Phe Ala Ser

195 200 205

Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln Phe Leu Ile

210 215 220

Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser Ser Val Leu

225 230 235 240

Glu Asn His His Leu Ala Val Gly Phe Lys Leu Leu Gln Glu Glu Asn

245 250 255

Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln Ser Leu Arg

260 265 270

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

275 280 285

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

290 295 300

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

305 310 315 320

Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro Thr Lys Pro

325 330 335

Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu Glu Phe Phe

340 345 350

Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile Ser Pro Met

355 360 365

Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val Gly Phe Ile

370 375 380

Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp Leu Val His

385 390 395 400

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

405 410 415

Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro Ala Pro Asp Asp Pro

420 425 430

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

435 440 445

Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser Gly Ser Gln

450 455 460

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

465 470 475 480

Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu Gln Val Glu Glu Glu

485 490 495

Ala Val Gly Glu Glu Glu Glu Ser Gln Pro Glu Ala Cys Val Ile Asp

500 505 510

Asp Arg Ser Pro Asp Thr

515

<210> 19

<211> 8130

<212> DNA

<213> 智人

<400> 19

agattatagc ccagcgtacg agaagcacga gtcctatagt tggcgtaccc tgaggcctgc 60

cagttcctgc cttaatgcat atgtagtcgt aattgagttc tgacacggcc ttggatgttt 120

ctgtcctaaa tagctgacat tgcatcttca agactgtcat tccagttggc ttttgagtgg 180

atacgtgcag tgagatcatt gacactggaa acactagttc ccattttaat tacttaaaac 240

accacgatga aaagaaatac ctgtgatttg ctttctcgga gcaaaagtgc ctctgaggaa 300

acactacatt ccagtaatga agaggaagac cctttccgcg gaatggaacc ctatcttgtc 360

cggagacttt catgtcgcaa tattcagctt ccccctctcg ccttcagaca gttggaacaa 420

gctgacttga aaagtgaatc agagaacatt caacgaccaa ccagcctccc cctgaagatt 480

ctgccgctga ttgctatcac ttctgcagaa tccagtggtt ttgatgtgga caatggcaca 540

tctgcgggac ggagtccctt ggatcccatg accagcccag gatccgggct aattctccaa 600

gcaaattttg tccacagtca acgacgggag tccttcctgt atcgatccga cagcgattat 660

gacctctctc caaagtctat gtcccggaac tcctccattg ccagtgatat acacggagat 720

gacttgattg tgactccatt tgctcaggtc ttggccagtc tgcgaactgt acgaaacaac 780

tttgctgcat taactaattt gcaagatcga gcacctagca aaagatcacc catgtgcaac 840

caaccatcca tcaacaaagc caccataaca gaggaggcct accagaaact ggccagcgag 900

accctggagg agctggactg gtgtctggac cagctagaga ccctacagac caggcactcc 960

gtcagtgaga tggcctccaa caagtttaaa aggatgctta atcgggagct cacccatctc 1020

tctgaaatga gtcggtctgg aaatcaagtg tcagagttta tatcaaacac attcttagat 1080

aagcaacatg aagtggaaat tccttctcca actcagaagg aaaaggagaa aaagaaaaga 1140

ccaatgtctc agatcagtgg agtcaagaaa ttgatgcaca gctctagtct gactaattca 1200

agtatcccaa ggtttggagt taaaactgaa caagaagatg tccttgccaa ggaactagaa 1260

gatgtgaaca aatggggtct tcatgttttc agaatagcag agttgtctgg taaccggccc 1320

ttgactgtta tcatgcacac catttttcag gaacgggatt tattaaaaac atttaaaatt 1380

ccagtagata ctttaattac atatcttatg actctcgaag accattacca tgctgatgtg 1440

gcctatcaca acaatatcca tgctgcagat gttgtccagt ctactcatgt gctattatct 1500

acacctgctt tggaggctgt gtttacagat ttggagattc ttgcagcaat ttttgccagt 1560

gcaatacatg atgtagatca tcctggtgtg tccaatcaat ttctgatcaa tacaaactct 1620

gaacttgcct tgatgtacaa tgattcctca gtcttagaga accatcattt ggctgtgggc 1680

tttaaattgc ttcaggaaga aaactgtgac attttccaga atttgaccaa aaaacaaaga 1740

caatctttaa ggaaaatggt cattgacatc gtacttgcaa cagatatgtc aaaacacatg 1800

aatctactgg ctgatttgaa gactatggtt gaaactaaga aagtgacaag ctctggagtt 1860

cttcttcttg ataattattc cgataggatt caggttcttc agaatatggt gcactgtgca 1920

gatctgagca acccaacaaa gcctctccag ctgtaccgcc agtggacgga ccggataatg 1980

gaggagttct tccgccaagg agaccgagag agggaacgtg gcatggagat aagccccatg 2040

tgtgacaagc acaatgcttc cgtggaaaaa tcacaggtgg gcttcataga ctatattgtt 2100

catcccctct gggagacatg ggcagacctc gtccaccctg acgcccagga tattttggac 2160

actttggagg acaatcgtga atggtaccag agcacaatcc ctcagagccc ctctcctgca 2220

cctgatgacc cagaggaggg ccggcagggt caaactgaga aattccagtt tgaactaact 2280

ttagaggaag atggtgagtc agacacggaa aaggacagtg gcagtcaagt ggaagaagac 2340

actagctgca gtgactccaa gactctttgt actcaagact cagagtctac tgaaattccc 2400

cttgatgaac aggttgaaga ggaggcagta ggggaagaag aggaaagcca gcctgaagcc 2460

tgtgtcatag atgatcgttc tcctgacacg taacagtgca aaaactttca tgcctttttt 2520

ttttttaagt agaaaaattg tttccaaagt gcatgtcaca tgccacaacc acggtcacac 2580

ctcactgtca tctgccagga cgtttgttga acaaaactga ccttgactac tcagtccagc 2640

gctcaggaat atcgtaacca gttttttcac ctccatgtca tccgagcaag gtggacatct 2700

tcacgaacag cgtttttaac aagatttcag cttggtagag ctgacaaagc agataaaatc 2760

tactccaaat tattttcaag agagtgtgac tcatcaggca gcccaaaagt ttattggact 2820

tggggtttct attccttttt atttgtttgc aatattttca gaagaaaggc attgcacaga 2880

gtgaacttaa tggacgaagc aacaaatatg tcaagaacag gacatagcac gaatctgtta 2940

ccagtaggag gaggatgagc cacagaaatt gcataatttt ctaatttcaa gtcttcctga 3000

tacatgactg aatagtgtgg ttcagtgagc tgcactgacc tctacatttt gtatgatatg 3060

taaaacagat tttttgtaga gcttactttt attattaaat gtattgaggt attatattta 3120

aaaaaaacta tgttcagaac ttcatctgcc actggttatt tttttctaag gagtaacttg 3180

caagttttca gtacaaatct gtgctacact ggataaaaat ctaatttatg aattttactt 3240

gcaccttata gttcatagca attaactgat ttgtagtgat tcattgtttg ttttatatac 3300

caatgacttc catattttaa aagagaaaaa caactttatg ttgcaggaaa ccctttttgt 3360

aagtctttat tatttacttt gcattttgtt tcactctttc cagataagca gagttgctct 3420

tcaccagtgt ttttcttcat gtgcaaagtg actatttgtt ctataatact tttatgtgtg 3480

ttatatcaaa tgtgtcttaa gcttcatgca aactcagtca tcagttcgtg ttgtctgaag 3540

caagtgggag atatataaat acccagtagc taaaatggtc agtctttttt agatgttttc 3600

ctacttagta tctcctaata acgttttgct gtgtcactag atgttcattt cacaagtgca 3660

tgtctttcta ataatccaca catttcatgc tctaataatc cacacatttc atgctcattt 3720

ttattgtttt tacagccagt tatagtaaga aaaaggtttt tccccttgtg ctgctttata 3780

atttagcgtg tgtctgaacc ttatccatgt ttgctagatg aggtcttgtc aaatatatca 3840

ctaccattgt caccggtgaa aagaaacagg tagttaagtt agggttaaca ttcatttcaa 3900

ccacgaggtt gtatatcatg actagctttt actcttggtt tacagagaaa agttaaacag 3960

ccaactaggc agtttttaag aatattaaca atatattaac aaacaccaat acaactaatc 4020

ctatttggtt ttaatgattt caccatggga ttaagaacta tatcaggaac atccctgaga 4080

aacggtttta agtgtagcaa ctactcttcc ttaatggaca gccacataac gtgtaggaag 4140

tcctttatca cttatcctcg atccataagc atatcttgca gaggggaact acttctttaa 4200

acacatggag ggaaagaaga tgatgccact ggcaccagag ggttagtact gtgatgcatc 4260

ctaaaatatt tattatattg gtaaaaattc tggttaaata aaaaattaga gatcactctt 4320

ggctgatttc agcaccagga actgtattac agttttagag attaattcct agtgtttacc 4380

tgattatagc agttggcatc atggggcatt taattctgac tttatcccca cgtcagcctt 4440

aataaagtct tctttacctt ctctatgaag actttaaagc ccaaataatc atttttcaca 4500

ttgatattca agaattgaga tagatagaag ccaaagtggg tatctgacaa gtggaaaatc 4560

aaacgtttaa gaagaattac aactctgaaa agcatttata tgtggaactt ctcaaggagc 4620

ctcctgggga ctggaaagta agtcatcagc caggcaaatg actcatgctg aagagagtcc 4680

ccatttcagt cccctgagat ctagctgatg cttagatcct ttgaaataaa aattatgtct 4740

ttataactct gatcttttac ataaagcaga agaggaatca actagttaat tgcaaggttt 4800

ctactctgtt tcctctgtaa agatcagatg gtaatctttc aaataagaaa aaaataaaga 4860

cgtatgtttg accaagtagt ttcacaagaa tatttgggaa cttgtttctt ttaattttat 4920

ttgtccctga gtgaagtcta gaaagaaagg taaagagtct agagtttatt cctctttcca 4980

aaacattctc attcctctcc tccctacact tagtatttcc cccacagagt gcctagaatc 5040

ttaataatga ataaaataaa aagcagcaat atgtcattaa caaatccaga cctgaaaggg 5100

taaagggttt ataactgcac taataaagag aggctctttt tttttcttcc agtttgttgg 5160

tttttaatgg taccgtgttg taaagatacc cactaatgga caatcaaatt gcagaaaagg 5220

ctcaatatcc aagagacagg gactaatgca ctgtacaatc tgcttatcct tgcccttctc 5280

tcttgccaaa gtgtgcttca gaaatatata ctgctttaaa aaagaataaa agaatatcct 5340

tttacaagtg gctttacatt tcctaaaatg ccataagaaa atgcaatatc tgggtactgt 5400

atggggaaaa aaatgtccaa gtttgtgtaa aaccagtgca tttcagcttg caagttactg 5460

aacacaataa tgctgtttta attttgtttt atatcagtta aaattcacaa taatgtagat 5520

agaacaaatt acagacaagg aaagaaaaaa cttgaatgaa atggatttta cagaaagctt 5580

tatgataatt tttgaatgca ttatttattt tttgtgccat gcattttttt tctcaccaaa 5640

tgaccttacc tgtaatacag tcttgtttgt ctgtttacaa ccatgtattt attgcaatgt 5700

acatactgta atgttaattg taaattatct gttcttatta aaacatcatc ccatgatggg 5760

atggtgttga tatatttgga aactcttggt gagagaatga atggtgtgta tacatactct 5820

gtacattttt cttttctcct gtaatatagt cttgtcacct tagagcttgt ttatggaaga 5880

ttcaagaaaa ctataaaata cttaaagata tataaattta aaaaaacata gctgcaggtc 5940

tttggtccca gggctgtgcc ttaactttaa ccaatatttt cttctgtttt gctgcatttg 6000

aaaggtaaca gtggagctag ggctgggcat tttacatcca ggcttttaat tgattagaat 6060

tctgccaata ggtggatttt acaaaaccac agacaacctc tgaaagattc tgagaccctt 6120

ttgagacaga agctcttaag tacttcttgc cagggagcag cactgcatgt gtgatggttg 6180

tttgccatct gttgatcagg aactacttca gctacttgca tttgattatt tccttttttt 6240

ttttttttaa ctcggaaaca caactgggga aatatattct ttcccagtga ttataaacaa 6300

tctttttctt ttttttaagt ccttttggct tctagagctc ataggaaaat ggacttgatt 6360

tgaaattgga gccagagttt actcgtgttg gttatctatt catcagcttc ctgacatgtt 6420

aagagaatac attaaagaga aaatactgtt ttttaatcct aaaatttttc ttccactaag 6480

ataaaccaaa tgtccttaca tatatgtaaa cccatctatt taaacgcaaa ggtgggttga 6540

tgtcagttta catagcagaa agcattcact atcctctaag atttgtttct gcaaaacttt 6600

cattgcttta gaattttaaa atttcacctt gtacaatggc cagcccctaa agcaggaaac 6660

atttataatg gattatatgg aaacatcctc ccagtacttg cccagccctt gaatcatgtg 6720

gcttttcagt gaaaggaaag attctttttc taggaaaaat gagcctattt tattttattt 6780

tattttattt tttgacacaa actgtagatt ttagcagccc tggcccaaag gaatttgatt 6840

acttttgttt taaacagtac aaaggggaca ctataattac aaaaacatcc ttaactgatt 6900

tgagttgttt ttatttcttt ggatatattt tcagagtggt aaattgtgtg tgagaattac 6960

aaatgattat tcttttagtg gtttcttagc ctctcttaca gcccacgggg atagtactgt 7020

acatcaatac cttcatatga aatttttata tgcaatgaaa ataaaagcat gggttgattc 7080

tgcctattta tgactcaatc ttttacaaat aaaagattat tcattttaaa ttatagttca 7140

atcagcatgt ctcttaggat actgaacgtg gttgaaatga aaggatagtg acatcataag 7200

ttagtactga tattcataac caaataaagc caacttgagt aattttgcta cattaaaaat 7260

taccaaaatt acttagatgg cctataagat taagcatggt gttttctaag caagctttga 7320

aaggggcctt ccatacttac ttaattgaat attctgggat attgaaaatt attcagatac 7380

ttgacaatta tttttggtta cctactccgc aaactacaaa gttttaagga ctcaacaata 7440

agttaatgag acacagtgtt tgctttcatg gagcttacag tctggagggg acaaaggctt 7500

aaacaatact catataatta tatatgtgat cagtacaatg aaggagctca gtggggtaaa 7560

taagcaggaa cctgaacttg atctgttccg gagggccaca gaaggcttcc ttgaggcctt 7620

gagaaagtga tttgcatctg agttctgaag gattgtaaga ggtaactagg gaaaaagttg 7680

acaggaagag gaaggggatc cagacaagaa acatttgcaa agatcttgag gcataaatga 7740

gcttgagaca tctggagaaa ctgaggaaaa gtgagagagt aggcagggcc tggagccgca 7800

gagccattgc taaccatcct gtgtgagata tcccccattc tgtagcttta ttctcataac 7860

cctgctcaat tttctttata acacttctca cagatttata tacgtgtttg tttttgttat 7920

ctgtctctcc caccagacca cagctccatg agagcaaggt ctttgcttac caatatatca 7980

ctagcactta aaactatgcc tggtacacag taggttctta atatgtgttg aatatagcca 8040

tcaaattgat attggatata attcaatctg ataagatatt ttgagatatt aaagagtttt 8100

taacttgata ccataaaaaa aaaaaaaaaa 8130

<210> 20

<211> 748

<212> PRT

<213> 智人

<400> 20

Met Lys Arg Asn Thr Cys Asp Leu Leu Ser Arg Ser Lys Ser Ala Ser

1 5 10 15

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

20 25 30

Met Glu Pro Tyr Leu Val Arg Arg Leu Ser Cys Arg Asn Ile Gln Leu

35 40 45

Pro Pro Leu Ala Phe Arg Gln Leu Glu Gln Ala Asp Leu Lys Ser Glu

50 55 60

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

65 70 75 80

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

85 90 95

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

100 105 110

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

115 120 125

Ser Phe Leu Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser

130 135 140

Met Ser Arg Asn Ser Ser Ile Ala Ser Asp Ile His Gly Asp Asp Leu

145 150 155 160

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

165 170 175

Asn Asn Phe Ala Ala Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys

180 185 190

Arg Ser Pro Met Cys Asn Gln Pro Ser Ile Asn Lys Ala Thr Ile Thr

195 200 205

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

210 215 220

Trp Cys Leu Asp Gln Leu Glu Thr Leu Gln Thr Arg His Ser Val Ser

225 230 235 240

Glu Met Ala Ser Asn Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr

245 250 255

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

260 265 270

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

275 280 285

Thr Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser

290 295 300

Gly Val Lys Lys Leu Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile

305 310 315 320

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

325 330 335

Leu Glu Asp Val Asn Lys Trp Gly Leu His Val Phe Arg Ile Ala Glu

340 345 350

Leu Ser Gly Asn Arg Pro Leu Thr Val Ile Met His Thr Ile Phe Gln

355 360 365

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

370 375 380

Thr Tyr Leu Met Thr Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr

385 390 395 400

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

405 410 415

Leu Ser Thr Pro Ala Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu

420 425 430

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

435 440 445

Ser Asn Gln Phe Leu Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr

450 455 460

Asn Asp Ser Ser Val Leu Glu Asn His His Leu Ala Val Gly Phe Lys

465 470 475 480

Leu Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys

485 490 495

Gln Arg Gln Ser Leu Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr

500 505 510

Asp Met Ser Lys His Met Asn Leu Leu Ala Asp Leu Lys Thr Met Val

515 520 525

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

530 535 540

Ser Asp Arg Ile Gln Val Leu Gln Asn Met Val His Cys Ala Asp Leu

545 550 555 560

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

565 570 575

Ile Met Glu Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly

580 585 590

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

595 600 605

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

610 615 620

Trp Ala Asp Leu Val His Pro Asp Ala Gln Asp Ile Leu Asp Thr Leu

625 630 635 640

Glu Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser

645 650 655

Pro Ala Pro Asp Asp Pro Glu Glu Gly Arg Gln Gly Gln Thr Glu Lys

660 665 670

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

675 680 685

Lys Asp Ser Gly Ser Gln Val Glu Glu Asp Thr Ser Cys Ser Asp Ser

690 695 700

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

705 710 715 720

Glu Gln Val Glu Glu Glu Ala Val Gly Glu Glu Glu Glu Ser Gln Pro

725 730 735

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

740 745

<210> 21

<211> 20

<212> DNA

<213> 人工序列

<220>

<223> PDE4D7_正向引物

<400> 21

gaacattcaa cgaccaacca 20

<210> 22

<211> 20

<212> DNA

<213> 人工序列

<220>

<223> PDE4D7_反向引物

<400> 22

tgccattgtc cacatcaaaa 20

<210> 23

<211> 27

<212> DNA

<213> 人工序列

<220>

<223> PDE4D7探针

<400> 23

ctgccgctga ttgctatcac ttctgca 27

<210> 24

<211> 22

<212> DNA

<213> 人工序列

<220>

<223> PDE4D7正向引物2

<400> 24

cgctgattgc tatcacttct gc 22

<210> 25

<211> 24

<212> DNA

<213> 人工序列

<220>

<223> PDE4D7反向引物

<400> 25

gtcgttgact gtggacaaaa tttg 24

<210> 26

<211> 34

<212> DNA

<213> 人工序列

<220>

<223> PDE4D7探针2

<400> 26

ttcccttgga tcccatgacc agcccataag ggaa 34

<210> 27

<211> 8130

<212> DNA

<213> 智人

<400> 27

agattatagc ccagcgtacg agaagcacga gtcctatagt tggcgtaccc tgaggcctgc 60

cagttcctgc cttaatgcat atgtagtcgt aattgagttc tgacacggcc ttggatgttt 120

ctgtcctaaa tagctgacat tgcatcttca agactgtcat tccagttggc ttttgagtgg 180

atacgtgcag tgagatcatt gacactggaa acactagttc ccattttaat tacttaaaac 240

accacgatga aaagaaatac ctgtgatttg ctttctcgga gcaaaagtgc ctctgaggaa 300

acactacatt ccagtaatga agaggaagac cctttccgcg gaatggaacc ctatcttgtc 360

cggagacttt catgtcgcaa tattcagctt ccccctctcg ccttcagaca gttggaacaa 420

gctgacttga aaagtgaatc agagaacatt caacgaccaa ccagcctccc cctgaagatt 480

ctgccgctga ttgctatcac ttctgcagaa tccagtggtt ttgatgtgga caatggcaca 540

tctgcgggac ggagtccctt ggatcccatg accagcccag gatccgggct aattctccaa 600

gcaaattttg tccacagtca acgacgggag tccttcctgt atcgatccga cagcgattat 660

gacctctctc caaagtctat gtcccggaac tcctccattg ccagtgatat acacggagat 720

gacttgattg tgactccatt tgctcaggtc ttggccagtc tgcgaactgt acgaaacaac 780

tttgctgcat taactaattt gcaagatcga gcacctagca aaagatcacc catgtgcaac 840

caaccatcca tcaacaaagc caccataaca gaggaggcct accagaaact ggccagcgag 900

accctggagg agctggactg gtgtctggac cagctagaga ccctacagac caggcactcc 960

gtcagtgaga tggcctccaa caagtttaaa aggatgctta atcgggagct cacccatctc 1020

tctgaaatga gtcggtctgg aaatcaagtg tcagagttta tatcaaacac attcttagat 1080

aagcaacatg aagtggaaat tccttctcca actcagaagg aaaaggagaa aaagaaaaga 1140

ccaatgtctc agatcagtgg agtcaagaaa ttgatgcaca gctctagtct gactaattca 1200

agtatcccaa ggtttggagt taaaactgaa caagaagatg tccttgccaa ggaactagaa 1260

gatgtgaaca aatggggtct tcatgttttc agaatagcag agttgtctgg taaccggccc 1320

ttgactgtta tcatgcacac catttttcag gaacgggatt tattaaaaac atttaaaatt 1380

ccagtagata ctttaattac atatcttatg actctcgaag accattacca tgctgatgtg 1440

gcctatcaca acaatatcca tgctgcagat gttgtccagt ctactcatgt gctattatct 1500

acacctgctt tggaggctgt gtttacagat ttggagattc ttgcagcaat ttttgccagt 1560

gcaatacatg atgtagatca tcctggtgtg tccaatcaat ttctgatcaa tacaaactct 1620

gaacttgcct tgatgtacaa tgattcctca gtcttagaga accatcattt ggctgtgggc 1680

tttaaattgc ttcaggaaga aaactgtgac attttccaga atttgaccaa aaaacaaaga 1740

caatctttaa ggaaaatggt cattgacatc gtacttgcaa cagatatgtc aaaacacatg 1800

aatctactgg ctgatttgaa gactatggtt gaaactaaga aagtgacaag ctctggagtt 1860

cttcttcttg ataattattc cgataggatt caggttcttc agaatatggt gcactgtgca 1920

gatctgagca acccaacaaa gcctctccag ctgtaccgcc agtggacgga ccggataatg 1980

gaggagttct tccgccaagg agaccgagag agggaacgtg gcatggagat aagccccatg 2040

tgtgacaagc acaatgcttc cgtggaaaaa tcacaggtgg gcttcataga ctatattgtt 2100

catcccctct gggagacatg ggcagacctc gtccaccctg acgcccagga tattttggac 2160

actttggagg acaatcgtga atggtaccag agcacaatcc ctcagagccc ctctcctgca 2220

cctgatgacc cagaggaggg ccggcagggt caaactgaga aattccagtt tgaactaact 2280

ttagaggaag atggtgagtc agacacggaa aaggacagtg gcagtcaagt ggaagaagac 2340

actagctgca gtgactccaa gactctttgt actcaagact cagagtctac tgaaattccc 2400

cttgatgaac aggttgaaga ggaggcagta ggggaagaag aggaaagcca gcctgaagcc 2460

tgtgtcatag atgatcgttc tcctgacacg taacagtgca aaaactttca tgcctttttt 2520

ttttttaagt agaaaaattg tttccaaagt gcatgtcaca tgccacaacc acggtcacac 2580

ctcactgtca tctgccagga cgtttgttga acaaaactga ccttgactac tcagtccagc 2640

gctcaggaat atcgtaacca gttttttcac ctccatgtca tccgagcaag gtggacatct 2700

tcacgaacag cgtttttaac aagatttcag cttggtagag ctgacaaagc agataaaatc 2760

tactccaaat tattttcaag agagtgtgac tcatcaggca gcccaaaagt ttattggact 2820

tggggtttct attccttttt atttgtttgc aatattttca gaagaaaggc attgcacaga 2880

gtgaacttaa tggacgaagc aacaaatatg tcaagaacag gacatagcac gaatctgtta 2940

ccagtaggag gaggatgagc cacagaaatt gcataatttt ctaatttcaa gtcttcctga 3000

tacatgactg aatagtgtgg ttcagtgagc tgcactgacc tctacatttt gtatgatatg 3060

taaaacagat tttttgtaga gcttactttt attattaaat gtattgaggt attatattta 3120

aaaaaaacta tgttcagaac ttcatctgcc actggttatt tttttctaag gagtaacttg 3180

caagttttca gtacaaatct gtgctacact ggataaaaat ctaatttatg aattttactt 3240

gcaccttata gttcatagca attaactgat ttgtagtgat tcattgtttg ttttatatac 3300

caatgacttc catattttaa aagagaaaaa caactttatg ttgcaggaaa ccctttttgt 3360

aagtctttat tatttacttt gcattttgtt tcactctttc cagataagca gagttgctct 3420

tcaccagtgt ttttcttcat gtgcaaagtg actatttgtt ctataatact tttatgtgtg 3480

ttatatcaaa tgtgtcttaa gcttcatgca aactcagtca tcagttcgtg ttgtctgaag 3540

caagtgggag atatataaat acccagtagc taaaatggtc agtctttttt agatgttttc 3600

ctacttagta tctcctaata acgttttgct gtgtcactag atgttcattt cacaagtgca 3660

tgtctttcta ataatccaca catttcatgc tctaataatc cacacatttc atgctcattt 3720

ttattgtttt tacagccagt tatagtaaga aaaaggtttt tccccttgtg ctgctttata 3780

atttagcgtg tgtctgaacc ttatccatgt ttgctagatg aggtcttgtc aaatatatca 3840

ctaccattgt caccggtgaa aagaaacagg tagttaagtt agggttaaca ttcatttcaa 3900

ccacgaggtt gtatatcatg actagctttt actcttggtt tacagagaaa agttaaacag 3960

ccaactaggc agtttttaag aatattaaca atatattaac aaacaccaat acaactaatc 4020

ctatttggtt ttaatgattt caccatggga ttaagaacta tatcaggaac atccctgaga 4080

aacggtttta agtgtagcaa ctactcttcc ttaatggaca gccacataac gtgtaggaag 4140

tcctttatca cttatcctcg atccataagc atatcttgca gaggggaact acttctttaa 4200

acacatggag ggaaagaaga tgatgccact ggcaccagag ggttagtact gtgatgcatc 4260

ctaaaatatt tattatattg gtaaaaattc tggttaaata aaaaattaga gatcactctt 4320

ggctgatttc agcaccagga actgtattac agttttagag attaattcct agtgtttacc 4380

tgattatagc agttggcatc atggggcatt taattctgac tttatcccca cgtcagcctt 4440

aataaagtct tctttacctt ctctatgaag actttaaagc ccaaataatc atttttcaca 4500

ttgatattca agaattgaga tagatagaag ccaaagtggg tatctgacaa gtggaaaatc 4560

aaacgtttaa gaagaattac aactctgaaa agcatttata tgtggaactt ctcaaggagc 4620

ctcctgggga ctggaaagta agtcatcagc caggcaaatg actcatgctg aagagagtcc 4680

ccatttcagt cccctgagat ctagctgatg cttagatcct ttgaaataaa aattatgtct 4740

ttataactct gatcttttac ataaagcaga agaggaatca actagttaat tgcaaggttt 4800

ctactctgtt tcctctgtaa agatcagatg gtaatctttc aaataagaaa aaaataaaga 4860

cgtatgtttg accaagtagt ttcacaagaa tatttgggaa cttgtttctt ttaattttat 4920

ttgtccctga gtgaagtcta gaaagaaagg taaagagtct agagtttatt cctctttcca 4980

aaacattctc attcctctcc tccctacact tagtatttcc cccacagagt gcctagaatc 5040

ttaataatga ataaaataaa aagcagcaat atgtcattaa caaatccaga cctgaaaggg 5100

taaagggttt ataactgcac taataaagag aggctctttt tttttcttcc agtttgttgg 5160

tttttaatgg taccgtgttg taaagatacc cactaatgga caatcaaatt gcagaaaagg 5220

ctcaatatcc aagagacagg gactaatgca ctgtacaatc tgcttatcct tgcccttctc 5280

tcttgccaaa gtgtgcttca gaaatatata ctgctttaaa aaagaataaa agaatatcct 5340

tttacaagtg gctttacatt tcctaaaatg ccataagaaa atgcaatatc tgggtactgt 5400

atggggaaaa aaatgtccaa gtttgtgtaa aaccagtgca tttcagcttg caagttactg 5460

aacacaataa tgctgtttta attttgtttt atatcagtta aaattcacaa taatgtagat 5520

agaacaaatt acagacaagg aaagaaaaaa cttgaatgaa atggatttta cagaaagctt 5580

tatgataatt tttgaatgca ttatttattt tttgtgccat gcattttttt tctcaccaaa 5640

tgaccttacc tgtaatacag tcttgtttgt ctgtttacaa ccatgtattt attgcaatgt 5700

acatactgta atgttaattg taaattatct gttcttatta aaacatcatc ccatgatggg 5760

atggtgttga tatatttgga aactcttggt gagagaatga atggtgtgta tacatactct 5820

gtacattttt cttttctcct gtaatatagt cttgtcacct tagagcttgt ttatggaaga 5880

ttcaagaaaa ctataaaata cttaaagata tataaattta aaaaaacata gctgcaggtc 5940

tttggtccca gggctgtgcc ttaactttaa ccaatatttt cttctgtttt gctgcatttg 6000

aaaggtaaca gtggagctag ggctgggcat tttacatcca ggcttttaat tgattagaat 6060

tctgccaata ggtggatttt acaaaaccac agacaacctc tgaaagattc tgagaccctt 6120

ttgagacaga agctcttaag tacttcttgc cagggagcag cactgcatgt gtgatggttg 6180

tttgccatct gttgatcagg aactacttca gctacttgca tttgattatt tccttttttt 6240

ttttttttaa ctcggaaaca caactgggga aatatattct ttcccagtga ttataaacaa 6300

tctttttctt ttttttaagt ccttttggct tctagagctc ataggaaaat ggacttgatt 6360

tgaaattgga gccagagttt actcgtgttg gttatctatt catcagcttc ctgacatgtt 6420

aagagaatac attaaagaga aaatactgtt ttttaatcct aaaatttttc ttccactaag 6480

ataaaccaaa tgtccttaca tatatgtaaa cccatctatt taaacgcaaa ggtgggttga 6540

tgtcagttta catagcagaa agcattcact atcctctaag atttgtttct gcaaaacttt 6600

cattgcttta gaattttaaa atttcacctt gtacaatggc cagcccctaa agcaggaaac 6660

atttataatg gattatatgg aaacatcctc ccagtacttg cccagccctt gaatcatgtg 6720

gcttttcagt gaaaggaaag attctttttc taggaaaaat gagcctattt tattttattt 6780

tattttattt tttgacacaa actgtagatt ttagcagccc tggcccaaag gaatttgatt 6840

acttttgttt taaacagtac aaaggggaca ctataattac aaaaacatcc ttaactgatt 6900

tgagttgttt ttatttcttt ggatatattt tcagagtggt aaattgtgtg tgagaattac 6960

aaatgattat tcttttagtg gtttcttagc ctctcttaca gcccacgggg atagtactgt 7020

acatcaatac cttcatatga aatttttata tgcaatgaaa ataaaagcat gggttgattc 7080

tgcctattta tgactcaatc ttttacaaat aaaagattat tcattttaaa ttatagttca 7140

atcagcatgt ctcttaggat actgaacgtg gttgaaatga aaggatagtg acatcataag 7200

ttagtactga tattcataac caaataaagc caacttgagt aattttgcta cattaaaaat 7260

taccaaaatt acttagatgg cctataagat taagcatggt gttttctaag caagctttga 7320

aaggggcctt ccatacttac ttaattgaat attctgggat attgaaaatt attcagatac 7380

ttgacaatta tttttggtta cctactccgc aaactacaaa gttttaagga ctcaacaata 7440

agttaatgag acacagtgtt tgctttcatg gagcttacag tctggagggg acaaaggctt 7500

aaacaatact catataatta tatatgtgat cagtacaatg aaggagctca gtggggtaaa 7560

taagcaggaa cctgaacttg atctgttccg gagggccaca gaaggcttcc ttgaggcctt 7620

gagaaagtga tttgcatctg agttctgaag gattgtaaga ggtaactagg gaaaaagttg 7680

acaggaagag gaaggggatc cagacaagaa acatttgcaa agatcttgag gcataaatga 7740

gcttgagaca tctggagaaa ctgaggaaaa gtgagagagt aggcagggcc tggagccgca 7800

gagccattgc taaccatcct gtgtgagata tcccccattc tgtagcttta ttctcataac 7860

cctgctcaat tttctttata acacttctca cagatttata tacgtgtttg tttttgttat 7920

ctgtctctcc caccagacca cagctccatg agagcaaggt ctttgcttac caatatatca 7980

ctagcactta aaactatgcc tggtacacag taggttctta atatgtgttg aatatagcca 8040

tcaaattgat attggatata attcaatctg ataagatatt ttgagatatt aaagagtttt 8100

taacttgata ccataaaaaa aaaaaaaaaa 8130

<210> 28

<211> 687

<212> PRT

<213> 智人

<400> 28

Met Ala Phe Val Trp Asp Pro Leu Gly Ala Thr Val Pro Gly Pro Ser

1 5 10 15

Thr Arg Ala Lys Ser Arg Leu Arg Phe Ser Lys Ser Tyr Ser Phe Asp

20 25 30

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

35 40 45

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

50 55 60

Arg Arg Glu Ser Phe Leu Tyr Arg Ser Asp Ser Asp Tyr Asp Leu Ser

65 70 75 80

Pro Lys Ser Met Ser Arg Asn Ser Ser Ile Ala Ser Asp Ile His Gly

85 90 95

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

100 105 110

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

115 120 125

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

130 135 140

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

145 150 155 160

Glu Leu Asp Trp Cys Leu Asp Gln Leu Glu Thr Leu Gln Thr Arg His

165 170 175

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

180 185 190

Glu Leu Thr His Leu Ser Glu Met Ser Arg Ser Gly Asn Gln Val Ser

195 200 205

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

210 215 220

Pro Ser Pro Thr Gln Lys Glu Lys Glu Lys Lys Lys Arg Pro Met Ser

225 230 235 240

Gln Ile Ser Gly Val Lys Lys Leu Met His Ser Ser Ser Leu Thr Asn

245 250 255

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

260 265 270

Ala Lys Glu Leu Glu Asp Val Asn Lys Trp Gly Leu His Val Phe Arg

275 280 285

Ile Ala Glu Leu Ser Gly Asn Arg Pro Leu Thr Val Ile Met His Thr

290 295 300

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

305 310 315 320

Thr Leu Ile Thr Tyr Leu Met Thr Leu Glu Asp His Tyr His Ala Asp

325 330 335

Val Ala Tyr His Asn Asn Ile His Ala Ala Asp Val Val Gln Ser Thr

340 345 350

His Val Leu Leu Ser Thr Pro Ala Leu Glu Ala Val Phe Thr Asp Leu

355 360 365

Glu Ile Leu Ala Ala Ile Phe Ala Ser Ala Ile His Asp Val Asp His

370 375 380

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

385 390 395 400

Leu Met Tyr Asn Asp Ser Ser Val Leu Glu Asn His His Leu Ala Val

405 410 415

Gly Phe Lys Leu Leu Gln Glu Glu Asn Cys Asp Ile Phe Gln Asn Leu

420 425 430

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

435 440 445

Leu Ala Thr Asp Met Ser Lys His Met Asn Leu Leu Ala Asp Leu Lys

450 455 460

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

465 470 475 480

Asp Asn Tyr Ser Asp Arg Ile Gln Val Leu Gln Asn Met Val His Cys

485 490 495

Ala Asp Leu Ser Asn Pro Thr Lys Pro Leu Gln Leu Tyr Arg Gln Trp

500 505 510

Thr Asp Arg Ile Met Glu Glu Phe Phe Arg Gln Gly Asp Arg Glu Arg

515 520 525

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

530 535 540

Val Glu Lys Ser Gln Val Gly Phe Ile Asp Tyr Ile Val His Pro Leu

545 550 555 560

Trp Glu Thr Trp Ala Asp Leu Val His Pro Asp Ala Gln Asp Ile Leu

565 570 575

Asp Thr Leu Glu Asp Asn Arg Glu Trp Tyr Gln Ser Thr Ile Pro Gln

580 585 590

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

595 600 605

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

610 615 620

Asp Thr Glu Lys Asp Ser Gly Ser Gln Val Glu Glu Asp Thr Ser Cys

625 630 635 640

Ser Asp Ser Lys Thr Leu Cys Thr Gln Asp Ser Glu Ser Thr Glu Ile

645 650 655

Pro Leu Asp Glu Gln Val Glu Glu Glu Ala Val Gly Glu Glu Glu Glu

660 665 670

Ser Gln Pro Glu Ala Cys Val Ile Asp Asp Arg Ser Pro Asp Thr

675 680 685

<210> 29

<211> 8395

<212> DNA

<213> 智人

<400> 29

ttctcactgc cctgcggtgt tttgaactgc cttcttacag acgtcataca gcccttgagg 60

aatagtttct gcctggtgag attgaatgat agttctcatt cacaaaaccc tggattctaa 120

gcagggacac acagaaatta ctttcgcagg taaatcagcc cacccagcca aagtgtggag 180

agatttgttc cttggctgac ttctttgctc cacggagagg agtgttttcc tgtgcttgcc 240

ctgaaatgga acttccttga cagctctccc gtgttacagt acctcccggt cattttcttt 300

ttctctctct ctacctgcgc tcttcgagtg tcagaaacct ttaaagctgt tactatggaa 360

ttgcaaaaaa gagatcaagt gactctttca ctatgctggt ttcccttgtg acccagatga 420

agaatcaatt cagaattcag ttcctccctt ggcattgcaa gacacagaag aaactgtcac 480

ttcctaacag cctagtactg gagtaaattc agtatgaagg aagaaagcgc tcctgcgtgt 540

tagaaccttg cccatgagct ggaccgagga caggagatgg actccaggaa aattggattt 600

cttcaagcag cctcccttgg aaatggaata tctttaaaat cttctttgca gaaagacagt 660

tagaatgtat taatcagaat agttgaagac ttattttcct ttttattttt tttcaaaatg 720

agcattatta tgaagccaag atcccgatct acaagttccc taaggactgc agaggcagtt 780

tgttttgatg tggacaatgg cacatctgcg ggacggagtc ccttggatcc catgaccagc 840

ccaggatccg ggctaattct ccaagcaaat tttgtccaca gtcaacgacg ggagtccttc 900

ctgtatcgat ccgacagcga ttatgacctc tctccaaagt ctatgtcccg gaactcctcc 960

attgccagtg atatacacgg agatgacttg attgtgactc catttgctca ggtcttggcc 1020

agtctgcgaa ctgtacgaaa caactttgct gcattaacta atttgcaaga tcgagcacct 1080

agcaaaagat cacccatgtg caaccaacca tccatcaaca aagccaccat aacagaggag 1140

gcctaccaga aactggccag cgagaccctg gaggagctgg actggtgtct ggaccagcta 1200

gagaccctac agaccaggca ctccgtcagt gagatggcct ccaacaagtt taaaaggatg 1260

cttaatcggg agctcaccca tctctctgaa atgagtcggt ctggaaatca agtgtcagag 1320

tttatatcaa acacattctt agataagcaa catgaagtgg aaattccttc tccaactcag 1380

aaggaaaagg agaaaaagaa aagaccaatg tctcagatca gtggagtcaa gaaattgatg 1440

cacagctcta gtctgactaa ttcaagtatc ccaaggtttg gagttaaaac tgaacaagaa 1500

gatgtccttg ccaaggaact agaagatgtg aacaaatggg gtcttcatgt tttcagaata 1560

gcagagttgt ctggtaaccg gcccttgact gttatcatgc acaccatttt tcaggaacgg 1620

gatttattaa aaacatttaa aattccagta gatactttaa ttacatatct tatgactctc 1680

gaagaccatt accatgctga tgtggcctat cacaacaata tccatgctgc agatgttgtc 1740

cagtctactc atgtgctatt atctacacct gctttggagg ctgtgtttac agatttggag 1800

attcttgcag caatttttgc cagtgcaata catgatgtag atcatcctgg tgtgtccaat 1860

caatttctga tcaatacaaa ctctgaactt gccttgatgt acaatgattc ctcagtctta 1920

gagaaccatc atttggctgt gggctttaaa ttgcttcagg aagaaaactg tgacattttc 1980

cagaatttga ccaaaaaaca aagacaatct ttaaggaaaa tggtcattga catcgtactt 2040

gcaacagata tgtcaaaaca catgaatcta ctggctgatt tgaagactat ggttgaaact 2100

aagaaagtga caagctctgg agttcttctt cttgataatt attccgatag gattcaggtt 2160

cttcagaata tggtgcactg tgcagatctg agcaacccaa caaagcctct ccagctgtac 2220

cgccagtgga cggaccggat aatggaggag ttcttccgcc aaggagaccg agagagggaa 2280

cgtggcatgg agataagccc catgtgtgac aagcacaatg cttccgtgga aaaatcacag 2340

gtgggcttca tagactatat tgttcatccc ctctgggaga catgggcaga cctcgtccac 2400

cctgacgccc aggatatttt ggacactttg gaggacaatc gtgaatggta ccagagcaca 2460

atccctcaga gcccctctcc tgcacctgat gacccagagg agggccggca gggtcaaact 2520

gagaaattcc agtttgaact aactttagag gaagatggtg agtcagacac ggaaaaggac 2580

agtggcagtc aagtggaaga agacactagc tgcagtgact ccaagactct ttgtactcaa 2640

gactcagagt ctactgaaat tccccttgat gaacaggttg aagaggaggc agtaggggaa 2700

gaagaggaaa gccagcctga agcctgtgtc atagatgatc gttctcctga cacgtaacag 2760

tgcaaaaact ttcatgcctt tttttttttt aagtagaaaa attgtttcca aagtgcatgt 2820

cacatgccac aaccacggtc acacctcact gtcatctgcc aggacgtttg ttgaacaaaa 2880

ctgaccttga ctactcagtc cagcgctcag gaatatcgta accagttttt tcacctccat 2940

gtcatccgag caaggtggac atcttcacga acagcgtttt taacaagatt tcagcttggt 3000

agagctgaca aagcagataa aatctactcc aaattatttt caagagagtg tgactcatca 3060

ggcagcccaa aagtttattg gacttggggt ttctattcct ttttatttgt ttgcaatatt 3120

ttcagaagaa aggcattgca cagagtgaac ttaatggacg aagcaacaaa tatgtcaaga 3180

acaggacata gcacgaatct gttaccagta ggaggaggat gagccacaga aattgcataa 3240

ttttctaatt tcaagtcttc ctgatacatg actgaatagt gtggttcagt gagctgcact 3300

gacctctaca ttttgtatga tatgtaaaac agattttttg tagagcttac ttttattatt 3360

aaatgtattg aggtattata tttaaaaaaa actatgttca gaacttcatc tgccactggt 3420

tatttttttc taaggagtaa cttgcaagtt ttcagtacaa atctgtgcta cactggataa 3480

aaatctaatt tatgaatttt acttgcacct tatagttcat agcaattaac tgatttgtag 3540

tgattcattg tttgttttat ataccaatga cttccatatt ttaaaagaga aaaacaactt 3600

tatgttgcag gaaacccttt ttgtaagtct ttattattta ctttgcattt tgtttcactc 3660

tttccagata agcagagttg ctcttcacca gtgtttttct tcatgtgcaa agtgactatt 3720

tgttctataa tacttttatg tgtgttatat caaatgtgtc ttaagcttca tgcaaactca 3780

gtcatcagtt cgtgttgtct gaagcaagtg ggagatatat aaatacccag tagctaaaat 3840

ggtcagtctt ttttagatgt tttcctactt agtatctcct aataacgttt tgctgtgtca 3900

ctagatgttc atttcacaag tgcatgtctt tctaataatc cacacatttc atgctctaat 3960

aatccacaca tttcatgctc atttttattg tttttacagc cagttatagt aagaaaaagg 4020

tttttcccct tgtgctgctt tataatttag cgtgtgtctg aaccttatcc atgtttgcta 4080

gatgaggtct tgtcaaatat atcactacca ttgtcaccgg tgaaaagaaa caggtagtta 4140

agttagggtt aacattcatt tcaaccacga ggttgtatat catgactagc ttttactctt 4200

ggtttacaga gaaaagttaa acagccaact aggcagtttt taagaatatt aacaatatat 4260

taacaaacac caatacaact aatcctattt ggttttaatg atttcaccat gggattaaga 4320

actatatcag gaacatccct gagaaacggt tttaagtgta gcaactactc ttccttaatg 4380

gacagccaca taacgtgtag gaagtccttt atcacttatc ctcgatccat aagcatatct 4440

tgcagagggg aactacttct ttaaacacat ggagggaaag aagatgatgc cactggcacc 4500

agagggttag tactgtgatg catcctaaaa tatttattat attggtaaaa attctggtta 4560

aataaaaaat tagagatcac tcttggctga tttcagcacc aggaactgta ttacagtttt 4620

agagattaat tcctagtgtt tacctgatta tagcagttgg catcatgggg catttaattc 4680

tgactttatc cccacgtcag ccttaataaa gtcttcttta ccttctctat gaagacttta 4740

aagcccaaat aatcattttt cacattgata ttcaagaatt gagatagata gaagccaaag 4800

tgggtatctg acaagtggaa aatcaaacgt ttaagaagaa ttacaactct gaaaagcatt 4860

tatatgtgga acttctcaag gagcctcctg gggactggaa agtaagtcat cagccaggca 4920

aatgactcat gctgaagaga gtccccattt cagtcccctg agatctagct gatgcttaga 4980

tcctttgaaa taaaaattat gtctttataa ctctgatctt ttacataaag cagaagagga 5040

atcaactagt taattgcaag gtttctactc tgtttcctct gtaaagatca gatggtaatc 5100

tttcaaataa gaaaaaaata aagacgtatg tttgaccaag tagtttcaca agaatatttg 5160

ggaacttgtt tcttttaatt ttatttgtcc ctgagtgaag tctagaaaga aaggtaaaga 5220

gtctagagtt tattcctctt tccaaaacat tctcattcct ctcctcccta cacttagtat 5280

ttcccccaca gagtgcctag aatcttaata atgaataaaa taaaaagcag caatatgtca 5340

ttaacaaatc cagacctgaa agggtaaagg gtttataact gcactaataa agagaggctc 5400

tttttttttc ttccagtttg ttggttttta atggtaccgt gttgtaaaga tacccactaa 5460

tggacaatca aattgcagaa aaggctcaat atccaagaga cagggactaa tgcactgtac 5520

aatctgctta tccttgccct tctctcttgc caaagtgtgc ttcagaaata tatactgctt 5580

taaaaaagaa taaaagaata tccttttaca agtggcttta catttcctaa aatgccataa 5640

gaaaatgcaa tatctgggta ctgtatgggg aaaaaaatgt ccaagtttgt gtaaaaccag 5700

tgcatttcag cttgcaagtt actgaacaca ataatgctgt tttaattttg ttttatatca 5760

gttaaaattc acaataatgt agatagaaca aattacagac aaggaaagaa aaaacttgaa 5820

tgaaatggat tttacagaaa gctttatgat aatttttgaa tgcattattt attttttgtg 5880

ccatgcattt tttttctcac caaatgacct tacctgtaat acagtcttgt ttgtctgttt 5940

acaaccatgt atttattgca atgtacatac tgtaatgtta attgtaaatt atctgttctt 6000

attaaaacat catcccatga tgggatggtg ttgatatatt tggaaactct tggtgagaga 6060

atgaatggtg tgtatacata ctctgtacat ttttcttttc tcctgtaata tagtcttgtc 6120

accttagagc ttgtttatgg aagattcaag aaaactataa aatacttaaa gatatataaa 6180

tttaaaaaaa catagctgca ggtctttggt cccagggctg tgccttaact ttaaccaata 6240

ttttcttctg ttttgctgca tttgaaaggt aacagtggag ctagggctgg gcattttaca 6300

tccaggcttt taattgatta gaattctgcc aataggtgga ttttacaaaa ccacagacaa 6360

cctctgaaag attctgagac ccttttgaga cagaagctct taagtacttc ttgccaggga 6420

gcagcactgc atgtgtgatg gttgtttgcc atctgttgat caggaactac ttcagctact 6480

tgcatttgat tatttccttt tttttttttt ttaactcgga aacacaactg gggaaatata 6540

ttctttccca gtgattataa acaatctttt tctttttttt aagtcctttt ggcttctaga 6600

gctcatagga aaatggactt gatttgaaat tggagccaga gtttactcgt gttggttatc 6660

tattcatcag cttcctgaca tgttaagaga atacattaaa gagaaaatac tgttttttaa 6720

tcctaaaatt tttcttccac taagataaac caaatgtcct tacatatatg taaacccatc 6780

tatttaaacg caaaggtggg ttgatgtcag tttacatagc agaaagcatt cactatcctc 6840

taagatttgt ttctgcaaaa ctttcattgc tttagaattt taaaatttca ccttgtacaa 6900

tggccagccc ctaaagcagg aaacatttat aatggattat atggaaacat cctcccagta 6960

cttgcccagc ccttgaatca tgtggctttt cagtgaaagg aaagattctt tttctaggaa 7020

aaatgagcct attttatttt attttatttt attttttgac acaaactgta gattttagca 7080

gccctggccc aaaggaattt gattactttt gttttaaaca gtacaaaggg gacactataa 7140

ttacaaaaac atccttaact gatttgagtt gtttttattt ctttggatat attttcagag 7200

tggtaaattg tgtgtgagaa ttacaaatga ttattctttt agtggtttct tagcctctct 7260

tacagcccac ggggatagta ctgtacatca ataccttcat atgaaatttt tatatgcaat 7320

gaaaataaaa gcatgggttg attctgccta tttatgactc aatcttttac aaataaaaga 7380

ttattcattt taaattatag ttcaatcagc atgtctctta ggatactgaa cgtggttgaa 7440

atgaaaggat agtgacatca taagttagta ctgatattca taaccaaata aagccaactt 7500

gagtaatttt gctacattaa aaattaccaa aattacttag atggcctata agattaagca 7560

tggtgttttc taagcaagct ttgaaagggg ccttccatac ttacttaatt gaatattctg 7620

ggatattgaa aattattcag atacttgaca attatttttg gttacctact ccgcaaacta 7680

caaagtttta aggactcaac aataagttaa tgagacacag tgtttgcttt catggagctt 7740

acagtctgga ggggacaaag gcttaaacaa tactcatata attatatatg tgatcagtac 7800

aatgaaggag ctcagtgggg taaataagca ggaacctgaa cttgatctgt tccggagggc 7860

cacagaaggc ttccttgagg ccttgagaaa gtgatttgca tctgagttct gaaggattgt 7920

aagaggtaac tagggaaaaa gttgacagga agaggaaggg gatccagaca agaaacattt 7980

gcaaagatct tgaggcataa atgagcttga gacatctgga gaaactgagg aaaagtgaga 8040

gagtaggcag ggcctggagc cgcagagcca ttgctaacca tcctgtgtga gatatccccc 8100

attctgtagc tttattctca taaccctgct caattttctt tataacactt ctcacagatt 8160

tatatacgtg tttgtttttg ttatctgtct ctcccaccag accacagctc catgagagca 8220

aggtctttgc ttaccaatat atcactagca cttaaaacta tgcctggtac acagtaggtt 8280

cttaatatgt gttgaatata gccatcaaat tgatattgga tataattcaa tctgataaga 8340

tattttgaga tattaaagag tttttaactt gataccataa aaaaaaaaaa aaaaa 8395

<210> 30

<211> 679

<212> PRT

<213> 智人

<400> 30

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

1 5 10 15

Thr Ala Glu Ala Val Cys Phe Asp Val Asp Asn Gly Thr Ser Ala Gly

20 25 30

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

35 40 45

Gln Ala Asn Phe Val His Ser Gln Arg Arg Glu Ser Phe Leu Tyr Arg

50 55 60

Ser Asp Ser Asp Tyr Asp Leu Ser Pro Lys Ser Met Ser Arg Asn Ser

65 70 75 80

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

85 90 95

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

100 105 110

Leu Thr Asn Leu Gln Asp Arg Ala Pro Ser Lys Arg Ser Pro Met Cys

115 120 125

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

130 135 140

Lys Leu Ala Ser Glu Thr Leu Glu Glu Leu Asp Trp Cys Leu Asp Gln

145 150 155 160

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

165 170 175

Lys Phe Lys Arg Met Leu Asn Arg Glu Leu Thr His Leu Ser Glu Met

180 185 190

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

195 200 205

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

210 215 220

Glu Lys Lys Lys Arg Pro Met Ser Gln Ile Ser Gly Val Lys Lys Leu

225 230 235 240

Met His Ser Ser Ser Leu Thr Asn Ser Ser Ile Pro Arg Phe Gly Val

245 250 255

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

260 265 270

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

275 280 285

Pro Leu Thr Val Ile Met His Thr Ile Phe Gln Glu Arg Asp Leu Leu

290 295 300

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

305 310 315 320

Leu Glu Asp His Tyr His Ala Asp Val Ala Tyr His Asn Asn Ile His

325 330 335

Ala Ala Asp Val Val Gln Ser Thr His Val Leu Leu Ser Thr Pro Ala

340 345 350

Leu Glu Ala Val Phe Thr Asp Leu Glu Ile Leu Ala Ala Ile Phe Ala

355 360 365

Ser Ala Ile His Asp Val Asp His Pro Gly Val Ser Asn Gln Phe Leu

370 375 380

Ile Asn Thr Asn Ser Glu Leu Ala Leu Met Tyr Asn Asp Ser Ser Val

385 390 395 400

Leu Glu Asn His His Leu Ala Val Gly Phe Lys Leu Leu Gln Glu Glu

405 410 415

Asn Cys Asp Ile Phe Gln Asn Leu Thr Lys Lys Gln Arg Gln Ser Leu

420 425 430

Arg Lys Met Val Ile Asp Ile Val Leu Ala Thr Asp Met Ser Lys His

435 440 445

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

450 455 460

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

465 470 475 480

Val Leu Gln Asn Met Val His Cys Ala Asp Leu Ser Asn Pro Thr Lys

485 490 495

Pro Leu Gln Leu Tyr Arg Gln Trp Thr Asp Arg Ile Met Glu Glu Phe

500 505 510

Phe Arg Gln Gly Asp Arg Glu Arg Glu Arg Gly Met Glu Ile Ser Pro

515 520 525

Met Cys Asp Lys His Asn Ala Ser Val Glu Lys Ser Gln Val Gly Phe

530 535 540

Ile Asp Tyr Ile Val His Pro Leu Trp Glu Thr Trp Ala Asp Leu Val

545 550 555 560

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

565 570 575

Trp Tyr Gln Ser Thr Ile Pro Gln Ser Pro Ser Pro Ala Pro Asp Asp

580 585 590

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

595 600 605

Thr Leu Glu Glu Asp Gly Glu Ser Asp Thr Glu Lys Asp Ser Gly Ser

610 615 620

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

625 630 635 640

Gln Asp Ser Glu Ser Thr Glu Ile Pro Leu Asp Glu Gln Val Glu Glu

645 650 655

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

660 665 670

Asp Asp Arg Ser Pro Asp Thr

675

<210> 31

<211> 26

<212> DNA

<213> 人工序列

<220>

<223> PDE4D9_正向引物

<400> 31

atgagcatta ttatgaagcc aagatc 26

<210> 32

<211> 22

<212> DNA

<213> 人工序列

<220>

<223> PDE4D9_反向引物

<400> 32

gtgccattgt ccacatcaaa ac 22

<210> 33

<211> 27

<212> DNA

<213> 人工序列

<220>

<223> PDE4D9探针

<400> 33

ctacaagttc cctaaggact gcagagg 27

<210> 34

<211> 1435

<212> DNA

<213> 智人

<400> 34

ggcggggcct gcttctcctc agcttcaggc ggctgcgacg agccctcagg cgaacctctc 60

ggctttcccg cgcggcgccg cctcttgctg cgcctccgcc tcctcctctg ctccgccacc 120

ggcttcctcc tcctgagcag tcagcccgcg cgccggccgg ctccgttatg gcgacccgca 180

gccctggcgt cgtgattagt gatgatgaac caggttatga ccttgattta ttttgcatac 240

ctaatcatta tgctgaggat ttggaaaggg tgtttattcc tcatggacta attatggaca 300

ggactgaacg tcttgctcga gatgtgatga aggagatggg aggccatcac attgtagccc 360

tctgtgtgct caaggggggc tataaattct ttgctgacct gctggattac atcaaagcac 420

tgaatagaaa tagtgataga tccattccta tgactgtaga ttttatcaga ctgaagagct 480

attgtaatga ccagtcaaca ggggacataa aagtaattgg tggagatgat ctctcaactt 540

taactggaaa gaatgtcttg attgtggaag atataattga cactggcaaa acaatgcaga 600

ctttgctttc cttggtcagg cagtataatc caaagatggt caaggtcgca agcttgctgg 660

tgaaaaggac cccacgaagt gttggatata agccagactt tgttggattt gaaattccag 720

acaagtttgt tgtaggatat gcccttgact ataatgaata cttcagggat ttgaatcatg 780

tttgtgtcat tagtgaaact ggaaaagcaa aatacaaagc ctaagatgag agttcaagtt 840

gagtttggaa acatctggag tcctattgac atcgccagta aaattatcaa tgttctagtt 900

ctgtggccat ctgcttagta gagctttttg catgtatctt ctaagaattt tatctgtttt 960

gtactttaga aatgtcagtt gctgcattcc taaactgttt atttgcacta tgagcctata 1020

gactatcagt tccctttggg cggattgttg tttaacttgt aaatgaaaaa attctcttaa 1080

accacagcac tattgagtga aacattgaac tcatatctgt aagaaataaa gagaagatat 1140

attagttttt taattggtat tttaattttt atatatgcag gaaagaatag aagtgattga 1200

atattgttaa ttataccacc gtgtgttaga aaagtaagaa gcagtcaatt ttcacatcaa 1260

agacagcatc taagaagttt tgttctgtcc tggaattatt ttagtagtgt ttcagtaatg 1320

ttgactgtat tttccaactt gttcaaatta ttaccagtga atctttgtca gcagttccct 1380

tttaaatgca aatcaataaa ttcccaaaaa tttaaaaaaa aaaaaaaaaa aaaaa 1435

<210> 35

<211> 218

<212> PRT

<213> 智人

<400> 35

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

1 5 10 15

Tyr Asp Leu Asp Leu Phe Cys Ile Pro Asn His Tyr Ala Glu Asp Leu

20 25 30

Glu Arg Val Phe Ile Pro His Gly Leu Ile Met Asp Arg Thr Glu Arg

35 40 45

Leu Ala Arg Asp Val Met Lys Glu Met Gly Gly His His Ile Val Ala

50 55 60

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

65 70 75 80

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

85 90 95

Val Asp Phe Ile Arg Leu Lys Ser Tyr Cys Asn Asp Gln Ser Thr Gly

100 105 110

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

115 120 125

Asn Val Leu Ile Val Glu Asp Ile Ile Asp Thr Gly Lys Thr Met Gln

130 135 140

Thr Leu Leu Ser Leu Val Arg Gln Tyr Asn Pro Lys Met Val Lys Val

145 150 155 160

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

165 170 175

Asp Phe Val Gly Phe Glu Ile Pro Asp Lys Phe Val Val Gly Tyr Ala

180 185 190

Leu Asp Tyr Asn Glu Tyr Phe Arg Asp Leu Asn His Val Cys Val Ile

195 200 205

Ser Glu Thr Gly Lys Ala Lys Tyr Lys Ala

210 215

<210> 36

<211> 24

<212> DNA

<213> 人工序列

<220>

<223> HPRT1_正向引物

<400> 36

gaggatttgg aaagggtgtt tatt 24

<210> 37

<211> 21

<212> DNA

<213> 人工序列

<220>

<223> HPRT1_反向引物

<400> 37

acagagggct acaatgtgat g 21

<210> 38

<211> 26

<212> DNA

<213> 人工序列

<220>

<223> HPRT1探针

<400> 38

acgtcttgct cgagatgtga tgaagg 26

<210> 39

<211> 1771

<212> DNA

<213> 智人

<400> 39

ggcggccagg ccgggcgcgg agtgggcgcg cggggccgga ggaggggcca gcgaccgcgg 60

caccgcctgt gcccgcccgc ccctccgcag ccgctactta agaggctcca gcgccggccc 120

cgccctagtg cgttacttac ctcgactctt agcttgtcgg ggacggtaac cgggacccgg 180

tgtctgctcc tgtcgccttc gcctcctaat ccctagccac tatgcgtgag tgcatctcca 240

tccacgttgg ccaggctggt gtccagattg gcaatgcctg ctgggagctc tactgcctgg 300

aacacggcat ccagcccgat ggccagatgc caagtgacaa gaccattggg ggaggagatg 360

actccttcaa caccttcttc agtgagacgg gcgctggcaa gcacgtgccc cgggctgtgt 420

ttgtagactt ggaacccaca gtcattgatg aagttcgcac tggcacctac cgccagctct 480

tccaccctga gcagctcatc acaggcaagg aagatgctgc caataactat gcccgagggc 540

actacaccat tggcaaggag atcattgacc ttgtgttgga ccgaattcgc aagctggctg 600

accagtgcac cggtcttcag ggcttcttgg ttttccacag ctttggtggg ggaactggtt 660

ctgggttcac ctccctgctc atggaacgtc tctcagttga ttatggcaag aagtccaagc 720

tggagttctc catttaccca gcaccccagg tttccacagc tgtagttgag ccctacaact 780

ccatcctcac cacccacacc accctggagc actctgattg tgccttcatg gtagacaatg 840

aggccatcta tgacatctgt cgtagaaacc tcgatatcga gcgcccaacc tacactaacc 900

ttaaccgcct tattagccag attgtgtcct ccatcactgc ttccctgaga tttgatggag 960

ccctgaatgt tgacctgaca gaattccaga ccaacctggt gccctacccc cgcatccact 1020

tccctctggc cacatatgcc cctgtcatct ctgctgagaa agcctaccat gaacagcttt 1080

ctgtagcaga gatcaccaat gcttgctttg agccagccaa ccagatggtg aaatgtgacc 1140

ctcgccatgg taaatacatg gcttgctgcc tgttgtaccg tggtgacgtg gttcccaaag 1200

atgtcaatgc tgccattgcc accatcaaaa ccaagcgcag catccagttt gtggattggt 1260

gccccactgg cttcaaggtt ggcatcaact accagcctcc cactgtggtg cctggtggag 1320

acctggccaa ggtacagaga gctgtgtgca tgctgagcaa caccacagcc attgctgagg 1380

cctgggctcg cctggaccac aagtttgacc tgatgtatgc caagcgtgcc tttgttcact 1440

ggtacgtggg tgaggggatg gaggaaggcg agttttcaga ggcccgtgaa gatatggctg 1500

cccttgagaa ggattatgag gaggttggtg tggattctgt tgaaggagag ggtgaggaag 1560

aaggagagga atactaatta tccattcctt ttggccctgc agcatgtcat gctcccagaa 1620

tttcagcttc agcttaactg acagacgtta aagctttctg gttagattgt tttcacttgg 1680

tgatcatgtc ttttccatgt gtacctgtaa tatttttcca tcatatctca aagtaaagtc 1740

attaacatca aaaaaaaaaa aaaaaaaaaa a 1771

<210> 40

<211> 451

<212> PRT

<213> 智人

<400> 40

Met Arg Glu Cys Ile Ser Ile His Val Gly Gln Ala Gly Val Gln Ile

1 5 10 15

Gly Asn Ala Cys Trp Glu Leu Tyr Cys Leu Glu His Gly Ile Gln Pro

20 25 30

Asp Gly Gln Met Pro Ser Asp Lys Thr Ile Gly Gly Gly Asp Asp Ser

35 40 45

Phe Asn Thr Phe Phe Ser Glu Thr Gly Ala Gly Lys His Val Pro Arg

50 55 60

Ala Val Phe Val Asp Leu Glu Pro Thr Val Ile Asp Glu Val Arg Thr

65 70 75 80

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

85 90 95

Glu Asp Ala Ala Asn Asn Tyr Ala Arg Gly His Tyr Thr Ile Gly Lys

100 105 110

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

115 120 125

Cys Thr Gly Leu Gln Gly Phe Leu Val Phe His Ser Phe Gly Gly Gly

130 135 140

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

145 150 155 160

Tyr Gly Lys Lys Ser Lys Leu Glu Phe Ser Ile Tyr Pro Ala Pro Gln

165 170 175

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

180 185 190

Thr Thr Leu Glu His Ser Asp Cys Ala Phe Met Val Asp Asn Glu Ala

195 200 205

Ile Tyr Asp Ile Cys Arg Arg Asn Leu Asp Ile Glu Arg Pro Thr Tyr

210 215 220

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

225 230 235 240

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

245 250 255

Thr Asn Leu Val Pro Tyr Pro Arg Ile His Phe Pro Leu Ala Thr Tyr

260 265 270

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

275 280 285

Ala Glu Ile Thr Asn Ala Cys Phe Glu Pro Ala Asn Gln Met Val Lys

290 295 300

Cys Asp Pro Arg His Gly Lys Tyr Met Ala Cys Cys Leu Leu Tyr Arg

305 310 315 320

Gly Asp Val Val Pro Lys Asp Val Asn Ala Ala Ile Ala Thr Ile Lys

325 330 335

Thr Lys Arg Ser Ile Gln Phe Val Asp Trp Cys Pro Thr Gly Phe Lys

340 345 350

Val Gly Ile Asn Tyr Gln Pro Pro Thr Val Val Pro Gly Gly Asp Leu

355 360 365

Ala Lys Val Gln Arg Ala Val Cys Met Leu Ser Asn Thr Thr Ala Ile

370 375 380

Ala Glu Ala Trp Ala Arg Leu Asp His Lys Phe Asp Leu Met Tyr Ala

385 390 395 400

Lys Arg Ala Phe Val His Trp Tyr Val Gly Glu Gly Met Glu Glu Gly

405 410 415

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

420 425 430

Glu Glu Val Gly Val Asp Ser Val Glu Gly Glu Gly Glu Glu Glu Gly

435 440 445

Glu Glu Tyr

450

<210> 41

<211> 22

<212> DNA

<213> 人工序列

<220>

<223> TUBA1B_正向引物

<400> 41

tgactccttc aacaccttct tc 22

<210> 42

<211> 18

<212> DNA

<213> 人工序列

<220>

<223> TUBA1B_反向引物

<400> 42

tgccagtgcg aacttcat 18

<210> 43

<211> 24

<212> DNA

<213> 人工序列

<220>

<223> TUBA1B探针

<400> 43

ccgggctgtg tttgtagact tgga 24

<210> 44

<211> 5416

<212> DNA

<213> 智人

<400> 44

agtgggccgc catgttgtcg gagtgaaagg taagggggag cgagagcgcc agagagagaa 60

gatcgggggg ctgaaatcca tcttcatcct accgctccgc ccgtgttggt ggaatgagcg 120

ttgcatgtgt cttgaagaga aaagcagtgc tttggcagga ctctttcagc ccccacctga 180

aacatcaccc tcaagaacca gctaatccca acatgcctgt tgttttgaca tctggaacag 240

ggtcgcaagc gcagccacaa ccagctgcaa atcaggctct tgcagctggg actcactcca 300

gccctgtccc aggatctata ggagttgcag gccgttccca ggacgacgct atggtggact 360

acttctttca gaggcagcat ggtgagcagc ttgggggagg aggaagtgga ggaggcggct 420

ataataatag caaacatcga tggcctactg gggataacat tcatgcagaa catcaggtgc 480

gttccatgga tgaactgaat catgattttc aagcacttgc tctggaggga agagcgatgg 540

gagagcagct cttgccaggt aaaaagtttt gggaaacaga tgaatccagc aaagatggac 600

caaaaggaat attcctgggt gatcaatggc gagacagtgc ctggggaaca tcagatcatt 660

cagtttccca gccaatcatg gtgcagagaa gacctggtca gagtttccat gtgaacagtg 720

aggtcaattc tgtactgtcc ccacgatcgg agagtggggg actaggcgtt agcatggtgg 780

agtatgtgtt gagctcatcc ccgggcgatt cctgtctaag aaaaggagga tttggcccaa 840

gggatgcaga cagtgatgaa aacgacaaag gtgaaaagaa gaacaagggt acgtttgatg 900

gagataagct aggagatttg aaggaggagg gtgatgtgat ggacaagacc aatggtttac 960

cagtgcagaa tgggattgat gcagacgtca aagattttag ccgtacccct ggtaattgcc 1020

agaactctgc taatgaagtg gatcttctgg gtccaaacca gaatggttct gagggcttag 1080

cccagctgac cagcaccaat ggtgccaagc ctgtggagga tttctccaac atggagtccc 1140

agagtgtccc cttggacccc atggaacatg tgggcatgga gcctcttcag tttgattatt 1200

caggcacgca ggtacctgtg gactcagcag cagcaactgt gggacttttt gactacaatt 1260

ctcaacaaca gctgttccaa agacctaatg cgcttgctgt ccagcagttg acagctgctc 1320

agcagcagca gtatgcactg gcagctgctc atcagccgca catcggttta gctcccgctg 1380

cgtttgtccc caatccatac atcatcagcg ctgctccccc agggacggac ccctacacag 1440

ctggattggc tgcagcagcg acactaggcc cagctgtggt ccctcaccag tattatggag 1500

ttactccctg gggagtctac cctgccagtc ttttccagca gcaagctgcc gctgccgctg 1560

cagcaactaa ttcagctaat caacagacca ccccacaggc tcagcaagga cagcagcagg 1620

ttctccgtgg aggagccagc caacgtcctt tgaccccaaa ccagaaccag cagggacagc 1680

aaacggatcc ccttgtggca gctgcagcag tgaattctgc ccttgcattt ggacaaggtc 1740

tggcagcagg catgccaggt tatccggtgt tggctcctgc tgcttactat gaccaaactg 1800

gtgcccttgt agtgaatgca ggcgcgagaa atggtcttgg agctcctgtt cgacttgtag 1860

ctcctgcccc agtcatcatt agttcctcag ctgcacaagc agctgttgca gcagccgcag 1920

cttcagcaaa tggagcagct ggtggtcttg ctggaacaac aaatggacca tttcgccctt 1980

taggaacaca gcagcctcag ccccagcccc agcagcagcc caataacaac ctggcatcca 2040

gttctttcta cggcaacaac tctctgaaca gcaattcaca gagcagctcc ctcttctccc 2100

agggctctgc ccagcctgcc aacacatcct tgggattcgg aagtagcagt tctctcggcg 2160

ccaccctggg atccgccctt ggagggtttg gaacagcagt tgcaaactcc aacactggca 2220

gtggctcccg ccgtgactcc ctgactggca gcagtgacct ttataagagg acatcgagca 2280

gcttgacccc cattggacac agtttttata acggccttag cttttcctcc tctcctggac 2340

ccgtgggcat gcctctccct agtcagggac caggacattc acagacacca cctccttccc 2400

tctcttcaca tggatcctct tcaagcttaa acctgggagg actcacgaat ggcagtggaa 2460

gatacatctc tgctgctcca ggcgctgaag ccaagtaccg cagtgcaagc agcgcctcca 2520

gcctcttcag cccgagcagc actcttttct cttcctctcg tttgcgatat ggaatgtctg 2580

atgtcatgcc ttctggcagg agcaggcttt tggaagattt tcgaaacaac cggtacccca 2640

atttacaact gcgggagatt gctggacata taatggaatt ttcccaagac cagcatgggt 2700

ccagattcat tcagctgaaa ctggagcgtg ccacaccagc tgagcgccag cttgtcttca 2760

atgaaatcct ccaggctgcc taccaactca tggtggatgt gtttggtaat tacgtcattc 2820

agaagttctt tgaatttggc agtcttgaac agaagctggc tttggcagaa cggattcgag 2880

gccacgtcct gtcattggca ctacagatgt atggctgccg tgttatccag aaagctcttg 2940

agtttattcc ttcagaccag caggtaatta atgagatggt tcgggaacta gatggccatg 3000

tcttgaagtg tgtgaaagat cagaatggca atcacgtggt tcagaaatgc attgaatgtg 3060

tacagcccca gtctttgcaa tttatcatcg atgcgtttaa gggacaggta tttgccttat 3120

ccacacatcc ttatggctgc cgagtgattc agagaatcct ggagcactgt ctccctgacc 3180

agacactccc tattttagag gagcttcacc agcacacaga gcagcttgta caggatcaat 3240

atggaaatta tgtaatccaa catgtactgg agcacggtcg tcctgaggat aaaagcaaaa 3300

ttgtagcaga aatccgaggc aatgtacttg tattgagtca gcacaaattt gcaagcaatg 3360

ttgtggagaa gtgtgttact cacgcctcac gtacggagcg cgctgtgctc atcgatgagg 3420

tgtgcaccat gaacgacggt ccccacagtg ccttatacac catgatgaag gaccagtatg 3480

ccaactacgt ggtccagaag atgattgacg tggcggagcc aggccagcgg aagatcgtca 3540

tgcataagat ccggccccac atcgcaactc ttcgtaagta cacctatggc aagcacattc 3600

tggccaagct ggagaagtac tacatgaaga acggtgttga cttagggccc atctgtggcc 3660

cccctaatgg tatcatctga ggcagtgtca cccgctgttc cctcattccc gctgacctca 3720

ctggcccact ggcaaatcca accagcaacc agaaatgttc tagtgtagag tctgagacgg 3780

gcaagtggtt gctccaggat tactccctcc tccaaaaaag gaatcaaatc cacgagtgga 3840

aaagcctttg taaatttaat tttattacac ataacatgta ctattttttt taattgacta 3900

attgccctgc tgttttactg gtgtatagga tacttgtaca taggtaacca atgtacatgg 3960

gaggccacat attttgttca ctgttgtatc tatatttcac atgtggaaac tttcagggtg 4020

gttggtttaa caaaaaaaaa aagctttaaa aaaaaaagaa aaaaaggaaa aggtttttag 4080

ctcatttgcc tggccggcaa gttttgcaaa tagctcttcc ccacctcctc attttagtaa 4140

aaaacaaaca aaaacaaaaa aacctgagaa gtttgaattg tagttaaatg accccaaact 4200

ggcatttaac actgtttata aaaaatatat atatatatat atatatatat aatgaaaaag 4260

gtttcagagt tgctaaagct tcagtttgtg acattaagtt tatgaaattc taaaaaatgc 4320

cttttttgga gactatatta tgctgaagaa ggctgttcgt gaggaggaga tgcgagcacc 4380

cagaacgtct tttgaggctg ggcgggtgtg attgtttact gcctactgga tttttttcta 4440

ttaacattga aaggtaaaat ctgattattt agcatgagaa aaaaaaatcc aactctgctt 4500

ttggtcttgc ttctataaat atatagtgta tacttggtgt agactttgca tatatacaaa 4560

tttgtagtat tttcttgttt tgatgtctaa tctgtatcta taatgtaccc tagtagtcga 4620

acatactttt gattgtacaa ttgtacattt gtatacctgt aatgtaaatg tggagaagtt 4680

tgaatcaaca taaacacgtt ttttggtaag aaaagagaat tagccagccc tgtgcattca 4740

gtgtatattc tcacctttta tggtcgtagc atatagtgtt gtatattgta aattgtaatt 4800

tcaaccagaa gtaaattttt ttcttttgaa ggaataaatg ttctttatac agcctagtta 4860

atgtttaaaa agaaaaaaat agcttggttt tatttgtcat ctagtctcaa gtatagcgag 4920

attctttcta aatgttattc aagattgagt tctcactagt gtttttttaa tcctaaaaaa 4980

gtaatgtttt gattttgtga cagtcaaaag gacgtgcaaa agtctagcct tgcccgagct 5040

ttccttacaa tcagagcccc tctcaccttg taaagtgtga atcgcccttc ccttttgtac 5100

agaagatgaa ctgtattttg cattttgtct acttgtaagt gaatgtaaca tactgtcaat 5160

tttccttgtt tgaatataga attgtaacac tacacggtgt acatttccag agccttgtgt 5220

atatttccaa tgaacttttt tgcaagcaca cttgtaacca tatgtgtata attaacaaac 5280

ctgtgtatgc ttatgcctgg gcaactattt tttgtaactc ttgtgtagat tgtctctaaa 5340

caatgtgtga tctttatttt gaaaaataca gaactttgga atctgaaaaa aaaaaaaaaa 5400

aaaaaaaaaa aaaaaa 5416

<210> 45

<211> 5410

<212> DNA

<213> 智人

<400> 45

agtgggccgc catgttgtcg gagtgaaagg taagggggag cgagagcgcc agagagagaa 60

gatcgggggg ctgaaatcca tcttcatcct accgctccgc ccgtgttggt ggaatgagcg 120

ttgcatgtgt cttgaagaga aaagcagtgc tttggcagga ctctttcagc ccccacctga 180

aacatcaccc tcaagaacca gctaatccca acatgcctgt tgttttgaca tctggaacag 240

ggtcgcaagc gcagccacaa ccagctgcaa atcaggctct tgcagctggg actcactcca 300

gccctgtccc aggatctata ggagttgcag gccgttccca ggacgacgct atggtggact 360

acttctttca gaggcagcat ggtgagcagc ttgggggagg aggaagtgga ggaggcggct 420

ataataatag caaacatcga tggcctactg gggataacat tcatgcagaa catcaggtgc 480

gttccatgga tgaactgaat catgattttc aagcacttgc tctggaggga agagcgatgg 540

gagagcagct cttgccaggt aaaaagtttt gggaaacaga tgaatccagc aaagatggac 600

caaaaggaat attcctgggt gatcaatggc gagacagtgc ctggggaaca tcagatcatt 660

cagtttccca gccaatcatg gtgcagagaa gacctggtca gagtttccat gtgaacagtg 720

aggtcaattc tgtactgtcc ccacgatcgg agagtggggg actaggcgtt agcatggtgg 780

agtatgtgtt gagctcatcc ccgggcgatt cctgtctaag aaaaggagga tttggcccaa 840

gggatgcaga cagtgatgaa aacgacaaag gtgaaaagaa gaacaagggt acgtttgatg 900

gagataagct aggagatttg aaggaggagg gtgatgtgat ggacaagacc aatggtttac 960

cagtgcagaa tgggattgat gcagacgtca aagattttag ccgtacccct ggtaattgcc 1020

agaactctgc taatgaagtg gatcttctgg gtccaaacca gaatggttct gagggcttag 1080

cccagctgac cagcaccaat ggtgccaagc ctgtggagga tttctccaac atggagtccc 1140

agagtgtccc cttggacccc atggaacatg tgggcatgga gcctcttcag tttgattatt 1200

caggcacgca ggtacctgtg gactcagcag cagcaactgt gggacttttt gactacaatt 1260

ctcaacaaca gctgttccaa agacctaatg cgcttgctgt ccagcagttg acagctgctc 1320

agcagcagca gtatgcactg gcagctgctc atcagccgca catcggttta gctcccgctg 1380

cgtttgtccc caatccatac atcatcagcg ctgctccccc agggacggac ccctacacag 1440

ctggattggc tgcagcagcg acactaggcc cagctgtggt ccctcaccag tattatggag 1500

ttactccctg gggagtctac cctgccagtc ttttccagca gcaagctgcc gctgccgctg 1560

cagcaactaa ttcagctaat caacagacca ccccacaggc tcagcaagga cagcagcagg 1620

ttctccgtgg aggagccagc caacgtcctt tgaccccaaa ccagaaccag cagggacagc 1680

aaacggatcc ccttgtggca gctgcagcag tgaattctgc ccttgcattt ggacaaggtc 1740

tggcagcagg catgccaggt tatccggtgt tggctcctgc tgcttactat gaccaaactg 1800

gtgcccttgt agtgaatgca ggcgcgagaa atggtcttgg agctcctgtt cgacttgtag 1860

ctcctgcccc agtcatcatt agttcctcag ctgcacaagc agctgttgca gcagccgcag 1920

cttcagcaaa tggagcagct ggtggtcttg ctggaacaac aaatggacca tttcgccctt 1980

taggaacaca gcagcctcag ccccagcccc agcagcagcc caataacaac ctggcatcca 2040

gttctttcta cggcaacaac tctctgaaca gcaattcaca gagcagctcc ctcttctccc 2100

agggctctgc ccagcctgcc aacacatcct tgggattcgg aagtagcagt tctctcggcg 2160

ccaccctggg atccgccctt ggagggtttg gaacagcagt tgcaaactcc aacactggca 2220

gtggctcccg ccgtgactcc ctgactggca gcagtgacct ttataagagg acatcgagca 2280

gcttgacccc cattggacac agtttttata acggccttag cttttcctcc tctcctggac 2340

ccgtgggcat gcctctccct agtcagggac caggacattc acagacacca cctccttccc 2400

tctcttcaca tggatcctct tcaagcttaa acctgggagg actcacgaat ggcagtggaa 2460

gatacatctc tgctgctcca ggcgctgaag ccaagtaccg cagtgcaagc agcgcctcca 2520

gcctcttcag cccgagcagc actcttttct cttcctctcg tttgcgatat ggaatgtctg 2580

atgtcatgcc ttctggcagg agcaggcttt tggaagattt tcgaaacaac cggtacccca 2640

atttacaact gcgggagatt gctggacata taatggaatt ttcccaagac cagcatgggt 2700

ccagattcat tcagctgaaa ctggagcgtg ccacaccagc tgagcgccag cttgtcttca 2760

atgaaatcct ccaggctgcc taccaactca tggtggatgt gtttggtaat tacgtcattc 2820

agaagttctt tgaatttggc agtcttgaac agaagctggc tttggcagaa cggattcgag 2880

gccacgtcct gtcattggca ctacagatgt atggctgccg tgttatccag aaagctcttg 2940

agtttattcc ttcagaccag cagaatgaga tggttcggga actagatggc catgtcttga 3000

agtgtgtgaa agatcagaat ggcaatcacg tggttcagaa atgcattgaa tgtgtacagc 3060

cccagtcttt gcaatttatc atcgatgcgt ttaagggaca ggtatttgcc ttatccacac 3120

atccttatgg ctgccgagtg attcagagaa tcctggagca ctgtctccct gaccagacac 3180

tccctatttt agaggagctt caccagcaca cagagcagct tgtacaggat caatatggaa 3240

attatgtaat ccaacatgta ctggagcacg gtcgtcctga ggataaaagc aaaattgtag 3300

cagaaatccg aggcaatgta cttgtattga gtcagcacaa atttgcaagc aatgttgtgg 3360

agaagtgtgt tactcacgcc tcacgtacgg agcgcgctgt gctcatcgat gaggtgtgca 3420

ccatgaacga cggtccccac agtgccttat acaccatgat gaaggaccag tatgccaact 3480

acgtggtcca gaagatgatt gacgtggcgg agccaggcca gcggaagatc gtcatgcata 3540

agatccggcc ccacatcgca actcttcgta agtacaccta tggcaagcac attctggcca 3600

agctggagaa gtactacatg aagaacggtg ttgacttagg gcccatctgt ggccccccta 3660

atggtatcat ctgaggcagt gtcacccgct gttccctcat tcccgctgac ctcactggcc 3720

cactggcaaa tccaaccagc aaccagaaat gttctagtgt agagtctgag acgggcaagt 3780

ggttgctcca ggattactcc ctcctccaaa aaaggaatca aatccacgag tggaaaagcc 3840

tttgtaaatt taattttatt acacataaca tgtactattt tttttaattg actaattgcc 3900

ctgctgtttt actggtgtat aggatacttg tacataggta accaatgtac atgggaggcc 3960

acatattttg ttcactgttg tatctatatt tcacatgtgg aaactttcag ggtggttggt 4020

ttaacaaaaa aaaaaagctt taaaaaaaaa agaaaaaaag gaaaaggttt ttagctcatt 4080

tgcctggccg gcaagttttg caaatagctc ttccccacct cctcatttta gtaaaaaaca 4140

aacaaaaaca aaaaaacctg agaagtttga attgtagtta aatgacccca aactggcatt 4200

taacactgtt tataaaaaat atatatatat atatatatat atataatgaa aaaggtttca 4260

gagttgctaa agcttcagtt tgtgacatta agtttatgaa attctaaaaa atgccttttt 4320

tggagactat attatgctga agaaggctgt tcgtgaggag gagatgcgag cacccagaac 4380

gtcttttgag gctgggcggg tgtgattgtt tactgcctac tggatttttt tctattaaca 4440

ttgaaaggta aaatctgatt atttagcatg agaaaaaaaa atccaactct gcttttggtc 4500

ttgcttctat aaatatatag tgtatacttg gtgtagactt tgcatatata caaatttgta 4560

gtattttctt gttttgatgt ctaatctgta tctataatgt accctagtag tcgaacatac 4620

ttttgattgt acaattgtac atttgtatac ctgtaatgta aatgtggaga agtttgaatc 4680

aacataaaca cgttttttgg taagaaaaga gaattagcca gccctgtgca ttcagtgtat 4740

attctcacct tttatggtcg tagcatatag tgttgtatat tgtaaattgt aatttcaacc 4800

agaagtaaat ttttttcttt tgaaggaata aatgttcttt atacagccta gttaatgttt 4860

aaaaagaaaa aaatagcttg gttttatttg tcatctagtc tcaagtatag cgagattctt 4920

tctaaatgtt attcaagatt gagttctcac tagtgttttt ttaatcctaa aaaagtaatg 4980

ttttgatttt gtgacagtca aaaggacgtg caaaagtcta gccttgcccg agctttcctt 5040

acaatcagag cccctctcac cttgtaaagt gtgaatcgcc cttccctttt gtacagaaga 5100

tgaactgtat tttgcatttt gtctacttgt aagtgaatgt aacatactgt caattttcct 5160

tgtttgaata tagaattgta acactacacg gtgtacattt ccagagcctt gtgtatattt 5220

ccaatgaact tttttgcaag cacacttgta accatatgtg tataattaac aaacctgtgt 5280

atgcttatgc ctgggcaact attttttgta actcttgtgt agattgtctc taaacaatgt 5340

gtgatcttta ttttgaaaaa tacagaactt tggaatctga aaaaaaaaaa aaaaaaaaaa 5400

aaaaaaaaaa 5410

<210> 46

<211> 1188

<212> PRT

<213> 智人

<400> 46

Met Ser Val Ala Cys Val Leu Lys Arg Lys Ala Val Leu Trp Gln Asp

1 5 10 15

Ser Phe Ser Pro His Leu Lys His His Pro Gln Glu Pro Ala Asn Pro

20 25 30

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

35 40 45

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

50 55 60

Val Pro Gly Ser Ile Gly Val Ala Gly Arg Ser Gln Asp Asp Ala Met

65 70 75 80

Val Asp Tyr Phe Phe Gln Arg Gln His Gly Glu Gln Leu Gly Gly Gly

85 90 95

Gly Ser Gly Gly Gly Gly Tyr Asn Asn Ser Lys His Arg Trp Pro Thr

100 105 110

Gly Asp Asn Ile His Ala Glu His Gln Val Arg Ser Met Asp Glu Leu

115 120 125

Asn His Asp Phe Gln Ala Leu Ala Leu Glu Gly Arg Ala Met Gly Glu

130 135 140

Gln Leu Leu Pro Gly Lys Lys Phe Trp Glu Thr Asp Glu Ser Ser Lys

145 150 155 160

Asp Gly Pro Lys Gly Ile Phe Leu Gly Asp Gln Trp Arg Asp Ser Ala

165 170 175

Trp Gly Thr Ser Asp His Ser Val Ser Gln Pro Ile Met Val Gln Arg

180 185 190

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

195 200 205

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

210 215 220

Val Leu Ser Ser Ser Pro Gly Asp Ser Cys Leu Arg Lys Gly Gly Phe

225 230 235 240

Gly Pro Arg Asp Ala Asp Ser Asp Glu Asn Asp Lys Gly Glu Lys Lys

245 250 255

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

260 265 270

Gly Asp Val Met Asp Lys Thr Asn Gly Leu Pro Val Gln Asn Gly Ile

275 280 285

Asp Ala Asp Val Lys Asp Phe Ser Arg Thr Pro Gly Asn Cys Gln Asn

290 295 300

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

305 310 315 320

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

325 330 335

Phe Ser Asn Met Glu Ser Gln Ser Val Pro Leu Asp Pro Met Glu His

340 345 350

Val Gly Met Glu Pro Leu Gln Phe Asp Tyr Ser Gly Thr Gln Val Pro

355 360 365

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

370 375 380

Gln Gln Leu Phe Gln Arg Pro Asn Ala Leu Ala Val Gln Gln Leu Thr

385 390 395 400

Ala Ala Gln Gln Gln Gln Tyr Ala Leu Ala Ala Ala His Gln Pro His

405 410 415

Ile Gly Leu Ala Pro Ala Ala Phe Val Pro Asn Pro Tyr Ile Ile Ser

420 425 430

Ala Ala Pro Pro Gly Thr Asp Pro Tyr Thr Ala Gly Leu Ala Ala Ala

435 440 445

Ala Thr Leu Gly Pro Ala Val Val Pro His Gln Tyr Tyr Gly Val Thr

450 455 460

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

465 470 475 480

Ala Ala Ala Ala Thr Asn Ser Ala Asn Gln Gln Thr Thr Pro Gln Ala

485 490 495

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

500 505 510

Leu Thr Pro Asn Gln Asn Gln Gln Gly Gln Gln Thr Asp Pro Leu Val

515 520 525

Ala Ala Ala Ala Val Asn Ser Ala Leu Ala Phe Gly Gln Gly Leu Ala

530 535 540

Ala Gly Met Pro Gly Tyr Pro Val Leu Ala Pro Ala Ala Tyr Tyr Asp

545 550 555 560

Gln Thr Gly Ala Leu Val Val Asn Ala Gly Ala Arg Asn Gly Leu Gly

565 570 575

Ala Pro Val Arg Leu Val Ala Pro Ala Pro Val Ile Ile Ser Ser Ser

580 585 590

Ala Ala Gln Ala Ala Val Ala Ala Ala Ala Ala Ser Ala Asn Gly Ala

595 600 605

Ala Gly Gly Leu Ala Gly Thr Thr Asn Gly Pro Phe Arg Pro Leu Gly

610 615 620

Thr Gln Gln Pro Gln Pro Gln Pro Gln Gln Gln Pro Asn Asn Asn Leu

625 630 635 640

Ala Ser Ser Ser Phe Tyr Gly Asn Asn Ser Leu Asn Ser Asn Ser Gln

645 650 655

Ser Ser Ser Leu Phe Ser Gln Gly Ser Ala Gln Pro Ala Asn Thr Ser

660 665 670

Leu Gly Phe Gly Ser Ser Ser Ser Leu Gly Ala Thr Leu Gly Ser Ala

675 680 685

Leu Gly Gly Phe Gly Thr Ala Val Ala Asn Ser Asn Thr Gly Ser Gly

690 695 700

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

705 710 715 720

Ser Ser Ser Leu Thr Pro Ile Gly His Ser Phe Tyr Asn Gly Leu Ser

725 730 735

Phe Ser Ser Ser Pro Gly Pro Val Gly Met Pro Leu Pro Ser Gln Gly

740 745 750

Pro Gly His Ser Gln Thr Pro Pro Pro Ser Leu Ser Ser His Gly Ser

755 760 765

Ser Ser Ser Leu Asn Leu Gly Gly Leu Thr Asn Gly Ser Gly Arg Tyr

770 775 780

Ile Ser Ala Ala Pro Gly Ala Glu Ala Lys Tyr Arg Ser Ala Ser Ser

785 790 795 800

Ala Ser Ser Leu Phe Ser Pro Ser Ser Thr Leu Phe Ser Ser Ser Arg

805 810 815

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

820 825 830

Leu Glu Asp Phe Arg Asn Asn Arg Tyr Pro Asn Leu Gln Leu Arg Glu

835 840 845

Ile Ala Gly His Ile Met Glu Phe Ser Gln Asp Gln His Gly Ser Arg

850 855 860

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

865 870 875 880

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

885 890 895

Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe Glu Phe Gly Ser Leu Glu

900 905 910

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

915 920 925

Ala Leu Gln Met Tyr Gly Cys Arg Val Ile Gln Lys Ala Leu Glu Phe

930 935 940

Ile Pro Ser Asp Gln Gln Val Ile Asn Glu Met Val Arg Glu Leu Asp

945 950 955 960

Gly His Val Leu Lys Cys Val Lys Asp Gln Asn Gly Asn His Val Val

965 970 975

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

980 985 990

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

995 1000 1005

Cys Arg Val Ile Gln Arg Ile Leu Glu His Cys Leu Pro Asp Gln

1010 1015 1020

Thr Leu Pro Ile Leu Glu Glu Leu His Gln His Thr Glu Gln Leu

1025 1030 1035

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

1040 1045 1050

His Gly Arg Pro Glu Asp Lys Ser Lys Ile Val Ala Glu Ile Arg

1055 1060 1065

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

1070 1075 1080

Val Glu Lys Cys Val Thr His Ala Ser Arg Thr Glu Arg Ala Val

1085 1090 1095

Leu Ile Asp Glu Val Cys Thr Met Asn Asp Gly Pro His Ser Ala

1100 1105 1110

Leu Tyr Thr Met Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln

1115 1120 1125

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

1130 1135 1140

His Lys Ile Arg Pro His Ile Ala Thr Leu Arg Lys Tyr Thr Tyr

1145 1150 1155

Gly Lys His Ile Leu Ala Lys Leu Glu Lys Tyr Tyr Met Lys Asn

1160 1165 1170

Gly Val Asp Leu Gly Pro Ile Cys Gly Pro Pro Asn Gly Ile Ile

1175 1180 1185

<210> 47

<211> 1186

<212> PRT

<213> 智人

<400> 47

Met Ser Val Ala Cys Val Leu Lys Arg Lys Ala Val Leu Trp Gln Asp

1 5 10 15

Ser Phe Ser Pro His Leu Lys His His Pro Gln Glu Pro Ala Asn Pro

20 25 30

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

35 40 45

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

50 55 60

Val Pro Gly Ser Ile Gly Val Ala Gly Arg Ser Gln Asp Asp Ala Met

65 70 75 80

Val Asp Tyr Phe Phe Gln Arg Gln His Gly Glu Gln Leu Gly Gly Gly

85 90 95

Gly Ser Gly Gly Gly Gly Tyr Asn Asn Ser Lys His Arg Trp Pro Thr

100 105 110

Gly Asp Asn Ile His Ala Glu His Gln Val Arg Ser Met Asp Glu Leu

115 120 125

Asn His Asp Phe Gln Ala Leu Ala Leu Glu Gly Arg Ala Met Gly Glu

130 135 140

Gln Leu Leu Pro Gly Lys Lys Phe Trp Glu Thr Asp Glu Ser Ser Lys

145 150 155 160

Asp Gly Pro Lys Gly Ile Phe Leu Gly Asp Gln Trp Arg Asp Ser Ala

165 170 175

Trp Gly Thr Ser Asp His Ser Val Ser Gln Pro Ile Met Val Gln Arg

180 185 190

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

195 200 205

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

210 215 220

Val Leu Ser Ser Ser Pro Gly Asp Ser Cys Leu Arg Lys Gly Gly Phe

225 230 235 240

Gly Pro Arg Asp Ala Asp Ser Asp Glu Asn Asp Lys Gly Glu Lys Lys

245 250 255

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

260 265 270

Gly Asp Val Met Asp Lys Thr Asn Gly Leu Pro Val Gln Asn Gly Ile

275 280 285

Asp Ala Asp Val Lys Asp Phe Ser Arg Thr Pro Gly Asn Cys Gln Asn

290 295 300

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

305 310 315 320

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

325 330 335

Phe Ser Asn Met Glu Ser Gln Ser Val Pro Leu Asp Pro Met Glu His

340 345 350

Val Gly Met Glu Pro Leu Gln Phe Asp Tyr Ser Gly Thr Gln Val Pro

355 360 365

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

370 375 380

Gln Gln Leu Phe Gln Arg Pro Asn Ala Leu Ala Val Gln Gln Leu Thr

385 390 395 400

Ala Ala Gln Gln Gln Gln Tyr Ala Leu Ala Ala Ala His Gln Pro His

405 410 415

Ile Gly Leu Ala Pro Ala Ala Phe Val Pro Asn Pro Tyr Ile Ile Ser

420 425 430

Ala Ala Pro Pro Gly Thr Asp Pro Tyr Thr Ala Gly Leu Ala Ala Ala

435 440 445

Ala Thr Leu Gly Pro Ala Val Val Pro His Gln Tyr Tyr Gly Val Thr

450 455 460

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

465 470 475 480

Ala Ala Ala Ala Thr Asn Ser Ala Asn Gln Gln Thr Thr Pro Gln Ala

485 490 495

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

500 505 510

Leu Thr Pro Asn Gln Asn Gln Gln Gly Gln Gln Thr Asp Pro Leu Val

515 520 525

Ala Ala Ala Ala Val Asn Ser Ala Leu Ala Phe Gly Gln Gly Leu Ala

530 535 540

Ala Gly Met Pro Gly Tyr Pro Val Leu Ala Pro Ala Ala Tyr Tyr Asp

545 550 555 560

Gln Thr Gly Ala Leu Val Val Asn Ala Gly Ala Arg Asn Gly Leu Gly

565 570 575

Ala Pro Val Arg Leu Val Ala Pro Ala Pro Val Ile Ile Ser Ser Ser

580 585 590

Ala Ala Gln Ala Ala Val Ala Ala Ala Ala Ala Ser Ala Asn Gly Ala

595 600 605

Ala Gly Gly Leu Ala Gly Thr Thr Asn Gly Pro Phe Arg Pro Leu Gly

610 615 620

Thr Gln Gln Pro Gln Pro Gln Pro Gln Gln Gln Pro Asn Asn Asn Leu

625 630 635 640

Ala Ser Ser Ser Phe Tyr Gly Asn Asn Ser Leu Asn Ser Asn Ser Gln

645 650 655

Ser Ser Ser Leu Phe Ser Gln Gly Ser Ala Gln Pro Ala Asn Thr Ser

660 665 670

Leu Gly Phe Gly Ser Ser Ser Ser Leu Gly Ala Thr Leu Gly Ser Ala

675 680 685

Leu Gly Gly Phe Gly Thr Ala Val Ala Asn Ser Asn Thr Gly Ser Gly

690 695 700

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

705 710 715 720

Ser Ser Ser Leu Thr Pro Ile Gly His Ser Phe Tyr Asn Gly Leu Ser

725 730 735

Phe Ser Ser Ser Pro Gly Pro Val Gly Met Pro Leu Pro Ser Gln Gly

740 745 750

Pro Gly His Ser Gln Thr Pro Pro Pro Ser Leu Ser Ser His Gly Ser

755 760 765

Ser Ser Ser Leu Asn Leu Gly Gly Leu Thr Asn Gly Ser Gly Arg Tyr

770 775 780

Ile Ser Ala Ala Pro Gly Ala Glu Ala Lys Tyr Arg Ser Ala Ser Ser

785 790 795 800

Ala Ser Ser Leu Phe Ser Pro Ser Ser Thr Leu Phe Ser Ser Ser Arg

805 810 815

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

820 825 830

Leu Glu Asp Phe Arg Asn Asn Arg Tyr Pro Asn Leu Gln Leu Arg Glu

835 840 845

Ile Ala Gly His Ile Met Glu Phe Ser Gln Asp Gln His Gly Ser Arg

850 855 860

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

865 870 875 880

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

885 890 895

Phe Gly Asn Tyr Val Ile Gln Lys Phe Phe Glu Phe Gly Ser Leu Glu

900 905 910

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

915 920 925

Ala Leu Gln Met Tyr Gly Cys Arg Val Ile Gln Lys Ala Leu Glu Phe

930 935 940

Ile Pro Ser Asp Gln Gln Asn Glu Met Val Arg Glu Leu Asp Gly His

945 950 955 960

Val Leu Lys Cys Val Lys Asp Gln Asn Gly Asn His Val Val Gln Lys

965 970 975

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

980 985 990

Phe Lys Gly Gln Val Phe Ala Leu Ser Thr His Pro Tyr Gly Cys Arg

995 1000 1005

Val Ile Gln Arg Ile Leu Glu His Cys Leu Pro Asp Gln Thr Leu

1010 1015 1020

Pro Ile Leu Glu Glu Leu His Gln His Thr Glu Gln Leu Val Gln

1025 1030 1035

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

1040 1045 1050

Arg Pro Glu Asp Lys Ser Lys Ile Val Ala Glu Ile Arg Gly Asn

1055 1060 1065

Val Leu Val Leu Ser Gln His Lys Phe Ala Ser Asn Val Val Glu

1070 1075 1080

Lys Cys Val Thr His Ala Ser Arg Thr Glu Arg Ala Val Leu Ile

1085 1090 1095

Asp Glu Val Cys Thr Met Asn Asp Gly Pro His Ser Ala Leu Tyr

1100 1105 1110

Thr Met Met Lys Asp Gln Tyr Ala Asn Tyr Val Val Gln Lys Met

1115 1120 1125

Ile Asp Val Ala Glu Pro Gly Gln Arg Lys Ile Val Met His Lys

1130 1135 1140

Ile Arg Pro His Ile Ala Thr Leu Arg Lys Tyr Thr Tyr Gly Lys

1145 1150 1155

His Ile Leu Ala Lys Leu Glu Lys Tyr Tyr Met Lys Asn Gly Val

1160 1165 1170

Asp Leu Gly Pro Ile Cys Gly Pro Pro Asn Gly Ile Ile

1175 1180 1185

<210> 48

<211> 22

<212> DNA

<213> 人工序列

<220>

<223> PUM1_正向引物

<400> 48

gccagcttgt cttcaatgaa at 22

<210> 49

<211> 21

<212> DNA

<213> 人工序列

<220>

<223> PUM1_反向引物

<400> 49

caaagccagc ttctgttcaa g 21

<210> 50

<211> 24

<212> DNA

<213> 人工序列

<220>

<223> PUM1探针

<400> 50

atccaccatg agttggtagg cagc 24

<210> 51

<211> 1921

<212> DNA

<213> 智人

<400> 51

ggcggaagtg acattatcaa cgcgcgccag gggttcagtg aggtcgggca ggttcgctgt 60

ggcgggcgcc tgggccgccg gctgtttaac ttcgcttccg ctggcccata gtgatctttg 120

cagtgaccca gcatcactgt ttcttggcgt gtgaagataa cccaaggaat tgaggaagtt 180

gctgagaaga gtgtgctgga gatgctctag gaaaaaattg aatagtgaga cgagttccag 240

cgcaagggtt tctggtttgc caagaagaaa gtgaacatca tggatcagaa caacagcctg 300

ccaccttacg ctcagggctt ggcctcccct cagggtgcca tgactcccgg aatccctatc 360

tttagtccaa tgatgcctta tggcactgga ctgaccccac agcctattca gaacaccaat 420

agtctgtcta ttttggaaga gcaacaaagg cagcagcagc aacaacaaca gcagcagcag 480

cagcagcagc agcaacagca acagcagcag cagcagcagc agcagcagca gcagcagcag 540

cagcagcagc agcagcagca acaggcagtg gcagctgcag ccgttcagca gtcaacgtcc 600

cagcaggcaa cacagggaac ctcaggccag gcaccacagc tcttccactc acagactctc 660

acaactgcac ccttgccggg caccactcca ctgtatccct cccccatgac tcccatgacc 720

cccatcactc ctgccacgcc agcttcggag agttctggga ttgtaccgca gctgcaaaat 780

attgtatcca cagtgaatct tggttgtaaa cttgacctaa agaccattgc acttcgtgcc 840

cgaaacgccg aatataatcc caagcggttt gctgcggtaa tcatgaggat aagagagcca 900

cgaaccacgg cactgatttt cagttctggg aaaatggtgt gcacaggagc caagagtgaa 960

gaacagtcca gactggcagc aagaaaatat gctagagttg tacagaagtt gggttttcca 1020

gctaagttct tggacttcaa gattcagaat atggtgggga gctgtgatgt gaagtttcct 1080

ataaggttag aaggccttgt gctcacccac caacaattta gtagttatga gccagagtta 1140

tttcctggtt taatctacag aatgatcaaa cccagaattg ttctccttat ttttgtttct 1200

ggaaaagttg tattaacagg tgctaaagtc agagcagaaa tttatgaagc atttgaaaac 1260

atctacccta ttctaaaggg attcaggaag acgacgtaat ggctctcatg tacccttgcc 1320

tcccccaccc ccttcttttt ttttttttaa acaaatcagt ttgttttggt acctttaaat 1380

ggtggtgttg tgagaagatg gatgttgagt tgcagggtgt ggcaccaggt gatgcccttc 1440

tgtaagtgcc caccgcggga tgccgggaag gggcattatt tgtgcactga gaacaccgcg 1500

cagcgtgact gtgagttgct cataccgtgc tgctatctgg gcagcgctgc ccatttattt 1560

atatgtagat tttaaacact gctgttgaca agttggtttg agggagaaaa ctttaagtgt 1620

taaagccacc tctataattg attggacttt ttaattttaa tgtttttccc catgaaccac 1680

agtttttata tttctaccag aaaagtaaaa atctttttta aaagtgttgt ttttctaatt 1740

tataactcct aggggttatt tctgtgccag acacattcca cctctccagt attgcaggac 1800

agaatatatg tgttaatgaa aatgaatggc tgtacatatt tttttctttc ttcagagtac 1860

tctgtacaat aaatgcagtt tataaaagtg ttagattgtt gttaaaaaaa aaaaaaaaaa 1920

a 1921

<210> 52

<211> 339

<212> PRT

<213> 智人

<400> 52

Met Asp Gln Asn Asn Ser Leu Pro Pro Tyr Ala Gln Gly Leu Ala Ser

1 5 10 15

Pro Gln Gly Ala Met Thr Pro Gly Ile Pro Ile Phe Ser Pro Met Met

20 25 30

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

35 40 45

Leu Ser Ile Leu Glu Glu Gln Gln Arg Gln Gln Gln Gln Gln Gln Gln

50 55 60

Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln

65 70 75 80

Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Ala

85 90 95

Val Ala Ala Ala Ala Val Gln Gln Ser Thr Ser Gln Gln Ala Thr Gln

100 105 110

Gly Thr Ser Gly Gln Ala Pro Gln Leu Phe His Ser Gln Thr Leu Thr

115 120 125

Thr Ala Pro Leu Pro Gly Thr Thr Pro Leu Tyr Pro Ser Pro Met Thr

130 135 140

Pro Met Thr Pro Ile Thr Pro Ala Thr Pro Ala Ser Glu Ser Ser Gly

145 150 155 160

Ile Val Pro Gln Leu Gln Asn Ile Val Ser Thr Val Asn Leu Gly Cys

165 170 175

Lys Leu Asp Leu Lys Thr Ile Ala Leu Arg Ala Arg Asn Ala Glu Tyr

180 185 190

Asn Pro Lys Arg Phe Ala Ala Val Ile Met Arg Ile Arg Glu Pro Arg

195 200 205

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

210 215 220

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

225 230 235 240

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

245 250 255

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

260 265 270

Leu Val Leu Thr His Gln Gln Phe Ser Ser Tyr Glu Pro Glu Leu Phe

275 280 285

Pro Gly Leu Ile Tyr Arg Met Ile Lys Pro Arg Ile Val Leu Leu Ile

290 295 300

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

305 310 315 320

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

325 330 335

Lys Thr Thr

<210> 53

<211> 23

<212> DNA

<213> 人工序列

<220>

<223> TBP_正向引物

<400> 53

gccaagaaga aagtgaacat cat 23

<210> 54

<211> 20

<212> DNA

<213> 人工序列

<220>

<223> TBP_反向引物

<400> 54

atagggattc cgggagtcat 20

<210> 55

<211> 24

<212> DNA

<213> 人工序列

<220>

<223> TBP探针

<400> 55

tcagaacaac agcctgccac ctta 24

<210> 56

<211> 1852

<212> DNA

<213> 智人

<400> 56

accgccgaga ccgcgtccgc cccgcgagca cagagcctcg cctttgccga tccgccgccc 60

gtccacaccc gccgccagct caccatggat gatgatatcg ccgcgctcgt cgtcgacaac 120

ggctccggca tgtgcaaggc cggcttcgcg ggcgacgatg ccccccgggc cgtcttcccc 180

tccatcgtgg ggcgccccag gcaccagggc gtgatggtgg gcatgggtca gaaggattcc 240

tatgtgggcg acgaggccca gagcaagaga ggcatcctca ccctgaagta ccccatcgag 300

cacggcatcg tcaccaactg ggacgacatg gagaaaatct ggcaccacac cttctacaat 360

gagctgcgtg tggctcccga ggagcacccc gtgctgctga ccgaggcccc cctgaacccc 420

aaggccaacc gcgagaagat gacccagatc atgtttgaga ccttcaacac cccagccatg 480

tacgttgcta tccaggctgt gctatccctg tacgcctctg gccgtaccac tggcatcgtg 540

atggactccg gtgacggggt cacccacact gtgcccatct acgaggggta tgccctcccc 600

catgccatcc tgcgtctgga cctggctggc cgggacctga ctgactacct catgaagatc 660

ctcaccgagc gcggctacag cttcaccacc acggccgagc gggaaatcgt gcgtgacatt 720

aaggagaagc tgtgctacgt cgccctggac ttcgagcaag agatggccac ggctgcttcc 780

agctcctccc tggagaagag ctacgagctg cctgacggcc aggtcatcac cattggcaat 840

gagcggttcc gctgccctga ggcactcttc cagccttcct tcctgggcat ggagtcctgt 900

ggcatccacg aaactacctt caactccatc atgaagtgtg acgtggacat ccgcaaagac 960

ctgtacgcca acacagtgct gtctggcggc accaccatgt accctggcat tgccgacagg 1020

atgcagaagg agatcactgc cctggcaccc agcacaatga agatcaagat cattgctcct 1080

cctgagcgca agtactccgt gtggatcggc ggctccatcc tggcctcgct gtccaccttc 1140

cagcagatgt ggatcagcaa gcaggagtat gacgagtccg gcccctccat cgtccaccgc 1200

aaatgcttct aggcggacta tgacttagtt gcgttacacc ctttcttgac aaaacctaac 1260

ttgcgcagaa aacaagatga gattggcatg gctttatttg ttttttttgt tttgttttgg 1320

tttttttttt ttttttggct tgactcagga tttaaaaact ggaacggtga aggtgacagc 1380

agtcggttgg agcgagcatc ccccaaagtt cacaatgtgg ccgaggactt tgattgcaca 1440

ttgttgtttt tttaatagtc attccaaata tgagatgcgt tgttacagga agtcccttgc 1500

catcctaaaa gccaccccac ttctctctaa ggagaatggc ccagtcctct cccaagtcca 1560

cacaggggag gtgatagcat tgctttcgtg taaattatgt aatgcaaaat ttttttaatc 1620

ttcgccttaa tactttttta ttttgtttta ttttgaatga tgagccttcg tgccccccct 1680

tccccctttt ttgtccccca acttgagatg tatgaaggct tttggtctcc ctgggagtgg 1740

gtggaggcag ccagggctta cctgtacact gacttgagac cagttgaata aaagtgcaca 1800

ccttaaaaat gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aa 1852

<210> 57

<211> 375

<212> PRT

<213> 智人

<400> 57

Met Asp Asp Asp Ile Ala Ala Leu Val Val Asp Asn Gly Ser Gly Met

1 5 10 15

Cys Lys Ala Gly Phe Ala Gly Asp Asp Ala Pro Arg Ala Val Phe Pro

20 25 30

Ser Ile Val Gly Arg Pro Arg His Gln Gly Val Met Val Gly Met Gly

35 40 45

Gln Lys Asp Ser Tyr Val Gly Asp Glu Ala Gln Ser Lys Arg Gly Ile

50 55 60

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

65 70 75 80

Asp Met Glu Lys Ile Trp His His Thr Phe Tyr Asn Glu Leu Arg Val

85 90 95

Ala Pro Glu Glu His Pro Val Leu Leu Thr Glu Ala Pro Leu Asn Pro

100 105 110

Lys Ala Asn Arg Glu Lys Met Thr Gln Ile Met Phe Glu Thr Phe Asn

115 120 125

Thr Pro Ala Met Tyr Val Ala Ile Gln Ala Val Leu Ser Leu Tyr Ala

130 135 140

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

145 150 155 160

His Thr Val Pro Ile Tyr Glu Gly Tyr Ala Leu Pro His Ala Ile Leu

165 170 175

Arg Leu Asp Leu Ala Gly Arg Asp Leu Thr Asp Tyr Leu Met Lys Ile

180 185 190

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

195 200 205

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

210 215 220

Gln Glu Met Ala Thr Ala Ala Ser Ser Ser Ser Leu Glu Lys Ser Tyr

225 230 235 240

Glu Leu Pro Asp Gly Gln Val Ile Thr Ile Gly Asn Glu Arg Phe Arg

245 250 255

Cys Pro Glu Ala Leu Phe Gln Pro Ser Phe Leu Gly Met Glu Ser Cys

260 265 270

Gly Ile His Glu Thr Thr Phe Asn Ser Ile Met Lys Cys Asp Val Asp

275 280 285

Ile Arg Lys Asp Leu Tyr Ala Asn Thr Val Leu Ser Gly Gly Thr Thr

290 295 300

Met Tyr Pro Gly Ile Ala Asp Arg Met Gln Lys Glu Ile Thr Ala Leu

305 310 315 320

Ala Pro Ser Thr Met Lys Ile Lys Ile Ile Ala Pro Pro Glu Arg Lys

325 330 335

Tyr Ser Val Trp Ile Gly Gly Ser Ile Leu Ala Ser Leu Ser Thr Phe

340 345 350

Gln Gln Met Trp Ile Ser Lys Gln Glu Tyr Asp Glu Ser Gly Pro Ser

355 360 365

Ile Val His Arg Lys Cys Phe

370 375

<210> 58

<211> 18

<212> DNA

<213> 人工序列

<220>

<223> ACTB_正向引物

<400> 58

ccaaccgcga gaagatga 18

<210> 59

<211> 20

<212> DNA

<213> 人工序列

<220>

<223> ACTB_反向引物

<400> 59

ccagaggcgt acagggatag 20

<210> 60

<211> 23

<212> DNA

<213> 人工序列

<220>

<223> ACTB探针

<400> 60

ccatgtacgt tgctatccag gct 23

<210> 61

<211> 1229

<212> DNA

<213> 智人

<400> 61

gtctgacggg cgatggcgca gccaatagac aggagcgcta tccgcggttt ctgattggct 60

actttgttcg cattataaaa ggcacgcgcg ggcgcgaggc ccttctctcg ccaggcgtcc 120

tcgtggaagt gacatcgtct ttaaaccctg cgtggcaatc cctgacgcac cgccgtgatg 180

cccagggaag acagggcgac ctggaagtcc aactacttcc ttaagatcat ccaactattg 240

gatgattatc cgaaatgttt cattgtggga gcagacaatg tgggctccaa gcagatgcag 300

cagatccgca tgtcccttcg cgggaaggct gtggtgctga tgggcaagaa caccatgatg 360

cgcaaggcca tccgagggca cctggaaaac aacccagctc tggagaaact gctgcctcat 420

atccggggga atgtgggctt tgtgttcacc aaggaggacc tcactgagat cagggacatg 480

ttgctggcca ataaggtgcc agctgctgcc cgtgctggtg ccattgcccc atgtgaagtc 540

actgtgccag cccagaacac tggtctcggg cccgagaaga cctccttttt ccaggcttta 600

ggtatcacca ctaaaatctc caggggcacc attgaaatcc tgagtgatgt gcagctgatc 660

aagactggag acaaagtggg agccagcgaa gccacgctgc tgaacatgct caacatctcc 720

cccttctcct ttgggctggt catccagcag gtgttcgaca atggcagcat ctacaaccct 780

gaagtgcttg atatcacaga ggaaactctg cattctcgct tcctggaggg tgtccgcaat 840

gttgccagtg tctgtctgca gattggctac ccaactgttg catcagtacc ccattctatc 900

atcaacgggt acaaacgagt cctggccttg tctgtggaga cggattacac cttcccactt 960

gctgaaaagg tcaaggcctt cttggctgat ccatctgcct ttgtggctgc tgcccctgtg 1020

gctgctgcca ccacagctgc tcctgctgct gctgcagccc cagctaaggt tgaagccaag 1080

gaagagtcgg aggagtcgga cgaggatatg ggatttggtc tctttgacta atcaccaaaa 1140

agcaaccaac ttagccagtt ttatttgcaa aacaaggaaa taaaggctta cttctttaaa 1200

aagtaaaaaa aaaaaaaaaa aaaaaaaaa 1229

<210> 62

<211> 317

<212> PRT

<213> 智人

<400> 62

Met Pro Arg Glu Asp Arg Ala Thr Trp Lys Ser Asn Tyr Phe Leu Lys

1 5 10 15

Ile Ile Gln Leu Leu Asp Asp Tyr Pro Lys Cys Phe Ile Val Gly Ala

20 25 30

Asp Asn Val Gly Ser Lys Gln Met Gln Gln Ile Arg Met Ser Leu Arg

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Glu Ile Arg Asp Met Leu Leu Ala Asn Lys Val Pro Ala Ala Ala Arg

100 105 110

Ala Gly Ala Ile Ala Pro Cys Glu Val Thr Val Pro Ala Gln Asn Thr

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Met Leu Asn Ile Ser Pro Phe Ser Phe Gly Leu Val Ile Gln Gln Val

180 185 190

Phe Asp Asn Gly Ser Ile Tyr Asn Pro Glu Val Leu Asp Ile Thr Glu

195 200 205

Glu Thr Leu His Ser Arg Phe Leu Glu Gly Val Arg Asn Val Ala Ser

210 215 220

Val Cys Leu Gln Ile Gly Tyr Pro Thr Val Ala Ser Val Pro His Ser

225 230 235 240

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

245 250 255

Tyr Thr Phe Pro Leu Ala Glu Lys Val Lys Ala Phe Leu Ala Asp Pro

260 265 270

Ser Ala Phe Val Ala Ala Ala Pro Val Ala Ala Ala Thr Thr Ala Ala

275 280 285

Pro Ala Ala Ala Ala Ala Pro Ala Lys Val Glu Ala Lys Glu Glu Ser

290 295 300

Glu Glu Ser Asp Glu Asp Met Gly Phe Gly Leu Phe Asp

305 310 315

<210> 63

<211> 317

<212> PRT

<213> 智人

<400> 63

Met Pro Arg Glu Asp Arg Ala Thr Trp Lys Ser Asn Tyr Phe Leu Lys

1 5 10 15

Ile Ile Gln Leu Leu Asp Asp Tyr Pro Lys Cys Phe Ile Val Gly Ala

20 25 30

Asp Asn Val Gly Ser Lys Gln Met Gln Gln Ile Arg Met Ser Leu Arg

35 40 45

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

50 55 60

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

65 70 75 80

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

85 90 95

Glu Ile Arg Asp Met Leu Leu Ala Asn Lys Val Pro Ala Ala Ala Arg

100 105 110

Ala Gly Ala Ile Ala Pro Cys Glu Val Thr Val Pro Ala Gln Asn Thr

115 120 125

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

130 135 140

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

145 150 155 160

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

165 170 175

Met Leu Asn Ile Ser Pro Phe Ser Phe Gly Leu Val Ile Gln Gln Val

180 185 190

Phe Asp Asn Gly Ser Ile Tyr Asn Pro Glu Val Leu Asp Ile Thr Glu

195 200 205

Glu Thr Leu His Ser Arg Phe Leu Glu Gly Val Arg Asn Val Ala Ser

210 215 220

Val Cys Leu Gln Ile Gly Tyr Pro Thr Val Ala Ser Val Pro His Ser

225 230 235 240

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

245 250 255

Tyr Thr Phe Pro Leu Ala Glu Lys Val Lys Ala Phe Leu Ala Asp Pro

260 265 270

Ser Ala Phe Val Ala Ala Ala Pro Val Ala Ala Ala Thr Thr Ala Ala

275 280 285

Pro Ala Ala Ala Ala Ala Pro Ala Lys Val Glu Ala Lys Glu Glu Ser

290 295 300

Glu Glu Ser Asp Glu Asp Met Gly Phe Gly Leu Phe Asp

305 310 315

<210> 64

<211> 18

<212> DNA

<213> 人工序列

<220>

<223> RPLP0_正向引物

<400> 64

taaaccctgc gtggcaat 18

<210> 65

<211> 27

<212> DNA

<213> 人工序列

<220>

<223> RPLP0_反向引物

<400> 65

acatttcgga taatcatcca atagttg 27

<210> 66

<211> 24

<212> DNA

<213> 人工序列

<220>

<223> RPLP0探针

<400> 66

aagtagttgg acttccaggt cgcc 24

<210> 67

<211> 2458

<212> DNA

<213> 智人

<400> 67

cagaagaagg cagcgcccaa ggcgcatgcg cagcggtcac tcccgctgta tattaaggcg 60

ccggcgatcg cggcctgagg ctgctcccgg acaagggcaa cgagcgtttc gtttggactt 120

ctcgacttga gtgcccgcct ccttcgccgc cgcctctgca gtcctcagcg cagttatgcc 180

cagttcttcc cgctgtgggg acacgaccac ggaggaatcc ttgcttcagg gactcgggac 240

cctgctggac cccttcctcg ggtttagggg atgtggggac caggagaaag tcaggatccc 300

taagagtctt ccctgcctgg atggatgagt ggcttcttct ccacctagat tctttccaca 360

ggagccagca tacttcctga acatggagag tgttgttcgc cgctgcccat tcttatcccg 420

agtcccccag gcctttctgc agaaagcagg caaatctctg ttgttctatg cccaaaactg 480

ccccaagatg atggaagttg gggccaagcc agcccctcgg gcattgtcca ctgcagcagt 540

acactaccaa cagatcaaag aaacccctcc ggccagtgag aaagacaaaa ctgctaaggc 600

caaggtccaa cagactcctg atggatccca gcagagtcca gatggcacac agcttccgtc 660

tggacacccc ttgcctgcca caagccaggg cactgcaagc aaatgccctt tcctggcagc 720

acagatgaat cagagaggca gcagtgtctt ctgcaaagcc agtcttgagc ttcaggagga 780

tgtgcaggaa atgaatgccg tgaggaaaga ggttgctgaa acctcagcag gccccagtgt 840

ggttagtgtg aaaaccgatg gaggggatcc cagtggactg ctgaagaact tccaggacat 900

catgcaaaag caaagaccag aaagagtgtc tcatcttctt caagataact tgccaaaatc 960

tgtttccact tttcagtatg atcgtttctt tgagaaaaaa attgatgaga aaaagaatga 1020

ccacacctat cgagttttta aaactgtgaa ccggcgagca cacatcttcc ccatggcaga 1080

tgactattca gactccctca tcaccaaaaa gcaagtgtca gtctggtgca gtaatgacta 1140

cctaggaatg agtcgccacc cacgggtgtg tggggcagtt atggacactt tgaaacaaca 1200

tggtgctggg gcaggtggta ctagaaatat ttctggaact agtaaattcc atgtggactt 1260

agagcgggag ctggcagacc tccatgggaa agatgccgca ctcttgtttt cctcgtgctt 1320

tgtggccaat gactcaaccc tcttcaccct ggctaagatg atgccaggct gtgagattta 1380

ctctgattct gggaaccatg cctccatgat ccaagggatt cgaaacagcc gagtgccaaa 1440

gtacatcttc cgccacaatg atgtcagcca cctcagagaa ctgctgcaaa gatctgaccc 1500

ctcagtcccc aagattgtgg catttgaaac tgtccattca atggatgggg cggtgtgccc 1560

actggaagag ctgtgtgatg tggcccatga gtttggagca atcaccttcg tggatgaggt 1620

ccacgcagtg gggctttatg gggctcgagg cggagggatt ggggatcggg atggagtcat 1680

gccaaaaatg gacatcattt ctggaacact tggcaaagcc tttggttgtg ttggagggta 1740

catcgccagc acgagttctc tgattgacac cgtacggtcc tatgctgctg gcttcatctt 1800

caccacctct ctgccaccca tgctgctggc tggagccctg gagtctgtgc ggatcctgaa 1860

gagcgctgag ggacgggtgc ttcgccgcca gcaccagcgc aacgtcaaac tcatgagaca 1920

gatgctaatg gatgccggcc tccctgttgt ccactgcccc agccacatca tccctgtgcg 1980

ggttgcagat gctgctaaaa acacagaagt ctgtgatgaa ctaatgagca gacataacat 2040

ctacgtgcaa gcaatcaatt accctacggt gccccgggga gaagagctcc tacggattgc 2100

ccccacccct caccacacac cccagatgat gaactacttc cttgagaatc tgctagtcac 2160

atggaagcaa gtggggctgg aactgaagcc tcattcctca gctgagtgca acttctgcag 2220

gaggccactg cattttgaag tgatgagtga aagagagaag tcctatttct caggcttgag 2280

caagttggta tctgctcagg cctgagcatg acctcaatta tttcacttaa ccccaggcca 2340

ttatcatatc cagatggtct tcagagttgt ctttatatgt gaattaagtt atattaaatt 2400

ttaatctata gtaaaaacat agtcctggaa ataaattctt gcttaaatgg tgaaaaaa 2458

<210> 68

<211> 2281

<212> DNA

<213> 智人

<400> 68

cagaagaagg cagcgcccaa ggcgcatgcg cagcggtcac tcccgctgta tattaaggcg 60

ccggcgatcg cggcctgagg ctgctcccgg acaagggcaa cgagcgtttc gtttggactt 120

ctcgacttga gtgcccgcct ccttcgccgc cgcctctgca gtcctcagcg cagtctttcc 180

acaggagcca gcatacttcc tgaacatgga gagtgttgtt cgccgctgcc cattcttatc 240

ccgagtcccc caggcctttc tgcagaaagc aggcaaatct ctgttgttct atgcccaaaa 300

ctgccccaag atgatggaag ttggggccaa gccagcccct cgggcattgt ccactgcagc 360

agtacactac caacagatca aagaaacccc tccggccagt gagaaagaca aaactgctaa 420

ggccaaggtc caacagactc ctgatggatc ccagcagagt ccagatggca cacagcttcc 480

gtctggacac cccttgcctg ccacaagcca gggcactgca agcaaatgcc ctttcctggc 540

agcacagatg aatcagagag gcagcagtgt cttctgcaaa gccagtcttg agcttcagga 600

ggatgtgcag gaaatgaatg ccgtgaggaa agaggttgct gaaacctcag caggccccag 660

tgtggttagt gtgaaaaccg atggagggga tcccagtgga ctgctgaaga acttccagga 720

catcatgcaa aagcaaagac cagaaagagt gtctcatctt cttcaagata acttgccaaa 780

atctgtttcc acttttcagt atgatcgttt ctttgagaaa aaaattgatg agaaaaagaa 840

tgaccacacc tatcgagttt ttaaaactgt gaaccggcga gcacacatct tccccatggc 900

agatgactat tcagactccc tcatcaccaa aaagcaagtg tcagtctggt gcagtaatga 960

ctacctagga atgagtcgcc acccacgggt gtgtggggca gttatggaca ctttgaaaca 1020

acatggtgct ggggcaggtg gtactagaaa tatttctgga actagtaaat tccatgtgga 1080

cttagagcgg gagctggcag acctccatgg gaaagatgcc gcactcttgt tttcctcgtg 1140

ctttgtggcc aatgactcaa ccctcttcac cctggctaag atgatgccag gctgtgagat 1200

ttactctgat tctgggaacc atgcctccat gatccaaggg attcgaaaca gccgagtgcc 1260

aaagtacatc ttccgccaca atgatgtcag ccacctcaga gaactgctgc aaagatctga 1320

cccctcagtc cccaagattg tggcatttga aactgtccat tcaatggatg gggcggtgtg 1380

cccactggaa gagctgtgtg atgtggccca tgagtttgga gcaatcacct tcgtggatga 1440

ggtccacgca gtggggcttt atggggctcg aggcggaggg attggggatc gggatggagt 1500

catgccaaaa atggacatca tttctggaac acttggcaaa gcctttggtt gtgttggagg 1560

gtacatcgcc agcacgagtt ctctgattga caccgtacgg tcctatgctg ctggcttcat 1620

cttcaccacc tctctgccac ccatgctgct ggctggagcc ctggagtctg tgcggatcct 1680

gaagagcgct gagggacggg tgcttcgccg ccagcaccag cgcaacgtca aactcatgag 1740

acagatgcta atggatgccg gcctccctgt tgtccactgc cccagccaca tcatccctgt 1800

gcgggttgca gatgctgcta aaaacacaga agtctgtgat gaactaatga gcagacataa 1860

catctacgtg caagcaatca attaccctac ggtgccccgg ggagaagagc tcctacggat 1920

tgcccccacc cctcaccaca caccccagat gatgaactac ttccttgaga atctgctagt 1980

cacatggaag caagtggggc tggaactgaa gcctcattcc tcagctgagt gcaacttctg 2040

caggaggcca ctgcattttg aagtgatgag tgaaagagag aagtcctatt tctcaggctt 2100

gagcaagttg gtatctgctc aggcctgagc atgacctcaa ttatttcact taaccccagg 2160

ccattatcat atccagatgg tcttcagagt tgtctttata tgtgaattaa gttatattaa 2220

attttaatct atagtaaaaa catagtcctg gaaataaatt cttgcttaaa tggtgaaaaa 2280

a 2281

<210> 69

<211> 640

<212> PRT

<213> 智人

<400> 69

Met Glu Ser Val Val Arg Arg Cys Pro Phe Leu Ser Arg Val Pro Gln

1 5 10 15

Ala Phe Leu Gln Lys Ala Gly Lys Ser Leu Leu Phe Tyr Ala Gln Asn

20 25 30

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

35 40 45

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

50 55 60

Ser Glu Lys Asp Lys Thr Ala Lys Ala Lys Val Gln Gln Thr Pro Asp

65 70 75 80

Gly Ser Gln Gln Ser Pro Asp Gly Thr Gln Leu Pro Ser Gly His Pro

85 90 95

Leu Pro Ala Thr Ser Gln Gly Thr Ala Ser Lys Cys Pro Phe Leu Ala

100 105 110

Ala Gln Met Asn Gln Arg Gly Ser Ser Val Phe Cys Lys Ala Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

Gly Asp Pro Ser Gly Leu Leu Lys Asn Phe Gln Asp Ile Met Gln Lys

165 170 175

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

180 185 190

Ser Val Ser Thr Phe Gln Tyr Asp Arg Phe Phe Glu Lys Lys Ile Asp

195 200 205

Glu Lys Lys Asn Asp His Thr Tyr Arg Val Phe Lys Thr Val Asn Arg

210 215 220

Arg Ala His Ile Phe Pro Met Ala Asp Asp Tyr Ser Asp Ser Leu Ile

225 230 235 240

Thr Lys Lys Gln Val Ser Val Trp Cys Ser Asn Asp Tyr Leu Gly Met

245 250 255

Ser Arg His Pro Arg Val Cys Gly Ala Val Met Asp Thr Leu Lys Gln

260 265 270

His Gly Ala Gly Ala Gly Gly Thr Arg Asn Ile Ser Gly Thr Ser Lys

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

Gly Asn His Ala Ser Met Ile Gln Gly Ile Arg Asn Ser Arg Val Pro

340 345 350

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

355 360 365

Gln Arg Ser Asp Pro Ser Val Pro Lys Ile Val Ala Phe Glu Thr Val

370 375 380

His Ser Met Asp Gly Ala Val Cys Pro Leu Glu Glu Leu Cys Asp Val

385 390 395 400

Ala His Glu Phe Gly Ala Ile Thr Phe Val Asp Glu Val His Ala Val

405 410 415

Gly Leu Tyr Gly Ala Arg Gly Gly Gly Ile Gly Asp Arg Asp Gly Val

420 425 430

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

435 440 445

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

450 455 460

Arg Ser Tyr Ala Ala Gly Phe Ile Phe Thr Thr Ser Leu Pro Pro Met

465 470 475 480

Leu Leu Ala Gly Ala Leu Glu Ser Val Arg Ile Leu Lys Ser Ala Glu

485 490 495

Gly Arg Val Leu Arg Arg Gln His Gln Arg Asn Val Lys Leu Met Arg

500 505 510

Gln Met Leu Met Asp Ala Gly Leu Pro Val Val His Cys Pro Ser His

515 520 525

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

530 535 540

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

545 550 555 560

Pro Thr Val Pro Arg Gly Glu Glu Leu Leu Arg Ile Ala Pro Thr Pro

565 570 575

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

580 585 590

Thr Trp Lys Gln Val Gly Leu Glu Leu Lys Pro His Ser Ser Ala Glu

595 600 605

Cys Asn Phe Cys Arg Arg Pro Leu His Phe Glu Val Met Ser Glu Arg

610 615 620

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

625 630 635 640

<210> 70

<211> 640

<212> PRT

<213> 智人

<400> 70

Met Glu Ser Val Val Arg Arg Cys Pro Phe Leu Ser Arg Val Pro Gln

1 5 10 15

Ala Phe Leu Gln Lys Ala Gly Lys Ser Leu Leu Phe Tyr Ala Gln Asn

20 25 30

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

35 40 45

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

50 55 60

Ser Glu Lys Asp Lys Thr Ala Lys Ala Lys Val Gln Gln Thr Pro Asp

65 70 75 80

Gly Ser Gln Gln Ser Pro Asp Gly Thr Gln Leu Pro Ser Gly His Pro

85 90 95

Leu Pro Ala Thr Ser Gln Gly Thr Ala Ser Lys Cys Pro Phe Leu Ala

100 105 110

Ala Gln Met Asn Gln Arg Gly Ser Ser Val Phe Cys Lys Ala Ser Leu

115 120 125

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

130 135 140

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

145 150 155 160

Gly Asp Pro Ser Gly Leu Leu Lys Asn Phe Gln Asp Ile Met Gln Lys

165 170 175

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

180 185 190

Ser Val Ser Thr Phe Gln Tyr Asp Arg Phe Phe Glu Lys Lys Ile Asp

195 200 205

Glu Lys Lys Asn Asp His Thr Tyr Arg Val Phe Lys Thr Val Asn Arg

210 215 220

Arg Ala His Ile Phe Pro Met Ala Asp Asp Tyr Ser Asp Ser Leu Ile

225 230 235 240

Thr Lys Lys Gln Val Ser Val Trp Cys Ser Asn Asp Tyr Leu Gly Met

245 250 255

Ser Arg His Pro Arg Val Cys Gly Ala Val Met Asp Thr Leu Lys Gln

260 265 270

His Gly Ala Gly Ala Gly Gly Thr Arg Asn Ile Ser Gly Thr Ser Lys

275 280 285

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

290 295 300

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

305 310 315 320

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

325 330 335

Gly Asn His Ala Ser Met Ile Gln Gly Ile Arg Asn Ser Arg Val Pro

340 345 350

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

355 360 365

Gln Arg Ser Asp Pro Ser Val Pro Lys Ile Val Ala Phe Glu Thr Val

370 375 380

His Ser Met Asp Gly Ala Val Cys Pro Leu Glu Glu Leu Cys Asp Val

385 390 395 400

Ala His Glu Phe Gly Ala Ile Thr Phe Val Asp Glu Val His Ala Val

405 410 415

Gly Leu Tyr Gly Ala Arg Gly Gly Gly Ile Gly Asp Arg Asp Gly Val

420 425 430

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

435 440 445

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

450 455 460

Arg Ser Tyr Ala Ala Gly Phe Ile Phe Thr Thr Ser Leu Pro Pro Met

465 470 475 480

Leu Leu Ala Gly Ala Leu Glu Ser Val Arg Ile Leu Lys Ser Ala Glu

485 490 495

Gly Arg Val Leu Arg Arg Gln His Gln Arg Asn Val Lys Leu Met Arg

500 505 510

Gln Met Leu Met Asp Ala Gly Leu Pro Val Val His Cys Pro Ser His

515 520 525

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

530 535 540

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

545 550 555 560

Pro Thr Val Pro Arg Gly Glu Glu Leu Leu Arg Ile Ala Pro Thr Pro

565 570 575

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

580 585 590

Thr Trp Lys Gln Val Gly Leu Glu Leu Lys Pro His Ser Ser Ala Glu

595 600 605

Cys Asn Phe Cys Arg Arg Pro Leu His Phe Glu Val Met Ser Glu Arg

610 615 620

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

625 630 635 640

<210> 71

<211> 17

<212> DNA

<213> 人工序列

<220>

<223> ALAS-1_正向引物

<400> 71

agccacatca tccctgt 17

<210> 72

<211> 22

<212> DNA

<213> 人工序列

<220>

<223> ALAS-1_反向引物

<400> 72

cgtagatgtt atgtctgctc at 22

<210> 73

<211> 22

<212> DNA

<213> 人工序列

<220>

<223> ALAS-1探针

<400> 73

tttagcagca tctgcaaccc gc 22

<210> 74

<211> 4543

<212> DNA

<213> 智人

<400> 74

atgcgtacgc tcgctggccc cgccccctag cgccgcggtc ggagccattt cgccgattcc 60

tccatgcgag ttgctgtgcg tttctctgtt gtctcggtag aaggccagag tcacacacgg 120

tcctaagagc tgggcaccag gaagcgaagg ctgatctgaa gaagacactt gaatcatggg 180

tgacgttaaa aattttctgt atgcctggtg tggcaaaagg aagatgaccc catcctatga 240

aattagagca gtggggaaca aaaacaggca gaaattcatg tgtgaggttc aggtggaagg 300

ttataattac actggcatgg gaaattccac caataaaaaa gatgcacaaa gcaatgctgc 360

cagagacttt gttaactatt tggttcgaat aaatgaaata aagagtgaag aagttccagc 420

ttttggggta gcatctccgc ccccacttac tgatactcct gacactacag caaatgctga 480

aggagattta ccaacaacca tgggaggacc tcttcctcca catctggctc tcaaagcaga 540

aaataattct gaggtagggg cctctggcta tggtgttcct gggcccacct gggaccgagg 600

agccaacttg aaggattact actcaagaaa ggaagaacaa gaagtgcaag cgactctaga 660

atcagaagaa gtggatttaa atgctgggct tcatggaaac tggaccttgg aaaatgctaa 720

agctcgtcta aaccaatatt ttcagaaaga aaagatccaa ggagaatata agtacaccca 780

agtgggtcct gatcacaaca ggagctttat tgcagaaatg accatttata tcaagcagct 840

gggcagaagg atttttgcac gagaacatgg atcaaataag aaattggcag cacagtcctg 900

tgccctgtca cttgtcagac aactgtacca tcttggagtg gttgaagctt actccggact 960

tacaaagaag aaggaaggag agacagtgga gccttacaaa gtaaacctct ctcaagattt 1020

agagcatcag ctgcaaaaca tcattcaaga gctaaatctt gagattttgc ccccgcctga 1080

agatccttct gtgccagttg cactcaacat tggcaaattg gctcagttcg aaccatctca 1140

gcgacaaaac caagtgggtg tggttccttg gtcacctcca caatccaact ggaatccttg 1200

gactagtagc aacattgatg aggggcctct ggcttttgct actccagagc aaataagcat 1260

ggacctcaag aatgaattga tgtaccagtt ggaacaggat catgatttgc aagcaatctt 1320

gcaggagaga gagttactgc ctgtgaagaa atttgaaagt gagattctgg aagcaatcag 1380

ccaaaattca gttgtcatta ttagaggggc tactggatgt gggaaaacca cacaggttcc 1440

ccagttcatt ctagatgact ttatccagaa tgaccgagca gcagagtgta acatcgtagt 1500

aactcagccc agaagaatca gtgcggtttc tgtggcagag cgagttgcat ttgaaagagg 1560

agaagagcct ggaaaaagct gtggctacag cgttcgattt gagtctatac ttcctcgtcc 1620

tcatgccagt ataatgtttt gtactgtagg tgtgctcctg agaaaattag aagcaggcat 1680

tcgaggaatc agtcatgtaa ttgtagatga aatacatgaa agagatatta atactgactt 1740

ccttttggta gtactgcgtg atgttgttca ggcttatcct gaagttcgca ttgttcttat 1800

gtctgctact attgatacca gcatgttttg tgaatatttc ttcaattgcc ccatcattga 1860

agtttatggg aggacttacc cagttcaaga atattttctg gaagactgca ttcagatgac 1920

ccactttgtt cctccaccaa aagacaaaaa gaagaaggat aaggatgatg atggtggtga 1980

ggatgatgat gcaaattgca acttgatctg tggtgatgaa tatggtccag aaacaaggtt 2040

gagcatgtct caattgaacg aaaaggaaac tccttttgaa ctcatcgagg ctctacttaa 2100

gtacattgaa acccttaatg ttcctggagc tgtgttggtt tttttgcctg gctggaatct 2160

gatttatact atgcagaagc atttggaaat gaatccacat tttggaagcc atcggtatca 2220

gattctaccc ctgcattctc agattcctcg agaggaacag cgcaaagtgt ttgatccagt 2280

accagttgga gtaaccaagg ttattttgtc cacaaatatt gctgaaacaa gcattaccat 2340

aaacgatgtt gtttatgtca ttgactcctg caagcagaaa gtgaaactct tcactgctca 2400

caacaatatg accaactatg ctaccgtatg ggcatcaaaa acaaaccttg agcaacggaa 2460

agggcgagct ggccgagtac ggcctggatt ctgctttcac ctgtgcagcc gagctcgttt 2520

tgagagactt gaaacccaca tgacaccaga gatgttccga acaccattgc atgaaattgc 2580

tcttagcata aaacttctgc gtctaggagg aattggccaa tttctggcca aagcaattga 2640

acctccccct ttggatgctg tgattgaagc agaacacact cttagagagc ttgatgcatt 2700

agatgccaat gatgagttga ctcctttggg acgaatcctg gctaaactcc ccattgagcc 2760

tcgttttggc aaaatgatga taatggggtg tattttctac gtgggagatg ctatctgtac 2820

cattgctgct gctacctgct ttccagagcc tttcatcaat gaaggaaagc ggctgggcta 2880

tatccatcga aattttgctg gaaacagatt ttctgatcac gtagcccttt tatcagtatt 2940

ccaagcctgg gatgatgcta gaatgggtgg agaagaagca gagatacgtt tttgtgagca 3000

caaaagactt aatatggcta cactaagaat gacctgggaa gccaaagttc agctcaaaga 3060

gattttgatt aattctgggt ttccagaaga ttgtttgttg acacaagtgt ttactaacac 3120

tggaccagat aataatttgg atgttgttat ctccctcctg gcctttggtg tgtaccccaa 3180

tgtatgctat cataaggaaa agaggaagat tctcaccact gaagggcgta atgcacttat 3240

ccacaaatca tctgttaatt gtccttttag tagccaagac atgaagtacc catctccctt 3300

ctttgtattt ggtgaaaaga ttcgaactcg agccatctct gctaaaggca tgactttagt 3360

cacccccctg cagttgcttc tctttgcctc caagaaagtc caatctgatg ggcagattgt 3420

gcttgtagat gactggatta aactgcaaat atctcatgaa gctgctgcct gtatcactgg 3480

tctccgggca gccatggagg ctttggttgt tgaagtaacc aaacaacctg ctatcatcag 3540

ccagttggac cccgtaaatg aacgtatgct gaacatgatc cgtcagatct ctagaccctc 3600

agctgctggt atcaacctta tgattggcag tacacggtat ggagatggtc cacgtcctcc 3660

caagatggcc cgatacgaca atggaagcgg atatagaagg ggaggttcta gttacagtgg 3720

tggaggctat ggcggtggct atagcagtgg aggctatggt agcggaggct atggtggcag 3780

cgccaactcc tttcgggcag gatatggtgc aggtgttggt ggaggctata gaggagtttc 3840

ccgaggtggc tttagaggca actctggagg agactacaga gggcctagtg gaggctacag 3900

aggatctggg ggattccagc gaggaggtgg taggggggcc tatggaactg gctactttgg 3960

acagggaaga ggaggtggcg gctattaaaa cttggttatg tcagttcctg tgtgtagaca 4020

gtaaggaaaa aaaggcatgc tatgtgttac gtgttttttc cagtatgttt atttgccacc 4080

aaaaagtaaa tgcattttca cccattctgt ggttcattgt agtttaagga aaccaagcat 4140

atagatgcat tagtgatttt gtttatatta tgtaaaatat aacgatctct taaaaatacc 4200

acagtttgta ttttttcttt aaggagtaaa gatttgcctt taaataactt ggtattttcc 4260

tggctttcgt ttaatacaat agaaaataaa gtattacacc gaatacttgc cgtgtagttt 4320

gtttgttgac ctcgtatgtt agaaaatttt acaatgccag ctacatctgt tgattttaaa 4380

tgtcagagaa gttgtaccct gtttcaaaag tatactaagt gatactactt gtaatagaat 4440

aaatcatctt ggaattgaat tgttaccttt tgaagtaaat actggcaagt gcacaagcca 4500

cataaacctg aataaaactt ttgacctagg gttgaaaaaa aaa 4543

<210> 75

<211> 1270

<212> PRT

<213> 智人

<400> 75

Met Gly Asp Val Lys Asn Phe Leu Tyr Ala Trp Cys Gly Lys Arg Lys

1 5 10 15

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

20 25 30

Lys Phe Met Cys Glu Val Gln Val Glu Gly Tyr Asn Tyr Thr Gly Met

35 40 45

Gly Asn Ser Thr Asn Lys Lys Asp Ala Gln Ser Asn Ala Ala Arg Asp

50 55 60

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

65 70 75 80

Pro Ala Phe Gly Val Ala Ser Pro Pro Pro Leu Thr Asp Thr Pro Asp

85 90 95

Thr Thr Ala Asn Ala Glu Gly Asp Leu Pro Thr Thr Met Gly Gly Pro

100 105 110

Leu Pro Pro His Leu Ala Leu Lys Ala Glu Asn Asn Ser Glu Val Gly

115 120 125

Ala Ser Gly Tyr Gly Val Pro Gly Pro Thr Trp Asp Arg Gly Ala Asn

130 135 140

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

145 150 155 160

Leu Glu Ser Glu Glu Val Asp Leu Asn Ala Gly Leu His Gly Asn Trp

165 170 175

Thr Leu Glu Asn Ala Lys Ala Arg Leu Asn Gln Tyr Phe Gln Lys Glu

180 185 190

Lys Ile Gln Gly Glu Tyr Lys Tyr Thr Gln Val Gly Pro Asp His Asn

195 200 205

Arg Ser Phe Ile Ala Glu Met Thr Ile Tyr Ile Lys Gln Leu Gly Arg

210 215 220

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

225 230 235 240

Ser Cys Ala Leu Ser Leu Val Arg Gln Leu Tyr His Leu Gly Val Val

245 250 255

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

260 265 270

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

275 280 285

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

290 295 300

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

305 310 315 320

Ser Gln Arg Gln Asn Gln Val Gly Val Val Pro Trp Ser Pro Pro Gln

325 330 335

Ser Asn Trp Asn Pro Trp Thr Ser Ser Asn Ile Asp Glu Gly Pro Leu

340 345 350

Ala Phe Ala Thr Pro Glu Gln Ile Ser Met Asp Leu Lys Asn Glu Leu

355 360 365

Met Tyr Gln Leu Glu Gln Asp His Asp Leu Gln Ala Ile Leu Gln Glu

370 375 380

Arg Glu Leu Leu Pro Val Lys Lys Phe Glu Ser Glu Ile Leu Glu Ala

385 390 395 400

Ile Ser Gln Asn Ser Val Val Ile Ile Arg Gly Ala Thr Gly Cys Gly

405 410 415

Lys Thr Thr Gln Val Pro Gln Phe Ile Leu Asp Asp Phe Ile Gln Asn

420 425 430

Asp Arg Ala Ala Glu Cys Asn Ile Val Val Thr Gln Pro Arg Arg Ile

435 440 445

Ser Ala Val Ser Val Ala Glu Arg Val Ala Phe Glu Arg Gly Glu Glu

450 455 460

Pro Gly Lys Ser Cys Gly Tyr Ser Val Arg Phe Glu Ser Ile Leu Pro

465 470 475 480

Arg Pro His Ala Ser Ile Met Phe Cys Thr Val Gly Val Leu Leu Arg

485 490 495

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

500 505 510

Ile His Glu Arg Asp Ile Asn Thr Asp Phe Leu Leu Val Val Leu Arg

515 520 525

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

530 535 540

Thr Ile Asp Thr Ser Met Phe Cys Glu Tyr Phe Phe Asn Cys Pro Ile

545 550 555 560

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

565 570 575

Asp Cys Ile Gln Met Thr His Phe Val Pro Pro Pro Lys Asp Lys Lys

580 585 590

Lys Lys Asp Lys Asp Asp Asp Gly Gly Glu Asp Asp Asp Ala Asn Cys

595 600 605

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

610 615 620

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

625 630 635 640

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

645 650 655

Leu Pro Gly Trp Asn Leu Ile Tyr Thr Met Gln Lys His Leu Glu Met

660 665 670

Asn Pro His Phe Gly Ser His Arg Tyr Gln Ile Leu Pro Leu His Ser

675 680 685

Gln Ile Pro Arg Glu Glu Gln Arg Lys Val Phe Asp Pro Val Pro Val

690 695 700

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

705 710 715 720

Thr Ile Asn Asp Val Val Tyr Val Ile Asp Ser Cys Lys Gln Lys Val

725 730 735

Lys Leu Phe Thr Ala His Asn Asn Met Thr Asn Tyr Ala Thr Val Trp

740 745 750

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

755 760 765

Arg Pro Gly Phe Cys Phe His Leu Cys Ser Arg Ala Arg Phe Glu Arg

770 775 780

Leu Glu Thr His Met Thr Pro Glu Met Phe Arg Thr Pro Leu His Glu

785 790 795 800

Ile Ala Leu Ser Ile Lys Leu Leu Arg Leu Gly Gly Ile Gly Gln Phe

805 810 815

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

820 825 830

Glu His Thr Leu Arg Glu Leu Asp Ala Leu Asp Ala Asn Asp Glu Leu

835 840 845

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

850 855 860

Gly Lys Met Met Ile Met Gly Cys Ile Phe Tyr Val Gly Asp Ala Ile

865 870 875 880

Cys Thr Ile Ala Ala Ala Thr Cys Phe Pro Glu Pro Phe Ile Asn Glu

885 890 895

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

900 905 910

Ser Asp His Val Ala Leu Leu Ser Val Phe Gln Ala Trp Asp Asp Ala

915 920 925

Arg Met Gly Gly Glu Glu Ala Glu Ile Arg Phe Cys Glu His Lys Arg

930 935 940

Leu Asn Met Ala Thr Leu Arg Met Thr Trp Glu Ala Lys Val Gln Leu

945 950 955 960

Lys Glu Ile Leu Ile Asn Ser Gly Phe Pro Glu Asp Cys Leu Leu Thr

965 970 975

Gln Val Phe Thr Asn Thr Gly Pro Asp Asn Asn Leu Asp Val Val Ile

980 985 990

Ser Leu Leu Ala Phe Gly Val Tyr Pro Asn Val Cys Tyr His Lys Glu

995 1000 1005

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

1010 1015 1020

Lys Ser Ser Val Asn Cys Pro Phe Ser Ser Gln Asp Met Lys Tyr

1025 1030 1035

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

1040 1045 1050

Ile Ser Ala Lys Gly Met Thr Leu Val Thr Pro Leu Gln Leu Leu

1055 1060 1065

Leu Phe Ala Ser Lys Lys Val Gln Ser Asp Gly Gln Ile Val Leu

1070 1075 1080

Val Asp Asp Trp Ile Lys Leu Gln Ile Ser His Glu Ala Ala Ala

1085 1090 1095

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

1100 1105 1110

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

1115 1120 1125

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

1130 1135 1140

Ala Gly Ile Asn Leu Met Ile Gly Ser Thr Arg Tyr Gly Asp Gly

1145 1150 1155

Pro Arg Pro Pro Lys Met Ala Arg Tyr Asp Asn Gly Ser Gly Tyr

1160 1165 1170

Arg Arg Gly Gly Ser Ser Tyr Ser Gly Gly Gly Tyr Gly Gly Gly

1175 1180 1185

Tyr Ser Ser Gly Gly Tyr Gly Ser Gly Gly Tyr Gly Gly Ser Ala

1190 1195 1200

Asn Ser Phe Arg Ala Gly Tyr Gly Ala Gly Val Gly Gly Gly Tyr

1205 1210 1215

Arg Gly Val Ser Arg Gly Gly Phe Arg Gly Asn Ser Gly Gly Asp

1220 1225 1230

Tyr Arg Gly Pro Ser Gly Gly Tyr Arg Gly Ser Gly Gly Phe Gln

1235 1240 1245

Arg Gly Gly Gly Arg Gly Ala Tyr Gly Thr Gly Tyr Phe Gly Gln

1250 1255 1260

Gly Arg Gly Gly Gly Gly Tyr

1265 1270