CN110753552A - 用于降低嵌合Notch受体的免疫原性的方法和组合物 - Google Patents

用于降低嵌合Notch受体的免疫原性的方法和组合物 Download PDF

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CN110753552A
CN110753552A CN201880039563.8A CN201880039563A CN110753552A CN 110753552 A CN110753552 A CN 110753552A CN 201880039563 A CN201880039563 A CN 201880039563A CN 110753552 A CN110753552 A CN 110753552A
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A.吉尔伯特
V.斯勒普希金
P.埃姆塔格
A.列夫斯卡雅
S.斯科特
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Cell Design Labs Inc
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Abstract

本发明涉及降低嵌合Notch受体的免疫原性的方法和组合物，并具体涉及对于控制通过此类嵌合Notch受体递送至组织的基因表达有用的转录因子。

Description

用于降低嵌合Notch受体的免疫原性的方法和组合物
相关申请的交叉引用
本申请要求2017年6月19日提交的美国临时专利申请序列号62/603,993和2017年9月11日提交的美国临时专利申请序列号62/556,765的优先权，其两者在此通过引用整体并入。
技术领域
本发明涉及分子生物学，并具体涉及用于降低某些受体的免疫原性的方法和组合物以及它们的应用，所述受体对控制单核细胞/巨噬细胞谱系的细胞中的选择性基因表达有用。
背景
限制人类基因疗法的发展的重要问题是治疗性基因表达的调节，使得基因表达或用于实现表达的媒介物不会产生导致宿主排斥的增强的免疫原性。实现基因表达的一种方式描述于美国专利号9,670,281和Roybal et al.,Cell,Feb.11,2016中。描述了使用嵌合North受体的基因表达的激活。
Notch受体是介导细胞-细胞接触信号传导并在发育和两个接触细胞之间的细胞对细胞通信的其他方面发挥核心作用的单次跨膜蛋白，所述两个接触细胞中的一个接触细胞具有Notch受体，并且另一个接触细胞是在其表面展示与相应的Notch受体结合的配体的细胞。天然Notch和它的天然配体Delta的接合导致Notch受体的两步蛋白水解，其最终引起该受体的细胞内部分从膜释放到细胞质中，在细胞质中它移动至细胞核。在那里，释放的结构域通过作为转录调节物发挥作用来改变细胞行为。Notch受体参与并对于发育期间的多种细胞功能是必需的，并且对于物种间众多细胞类型的功能至关重要。
美国专利号9,670,281中描述了嵌合Notch受体，其显示Notch表达细胞可以在细胞表面上具有一个或多个不同的结合部分，仅举几例，例如scFV、纳米抗体、单链T细胞受体，所述结合部分识别与细胞相关联的配体最终引起受体的细胞内转录调节部分从膜释放到细胞质中，导致转录调节。然后将携带遇到其特异性靶抗原的嵌合Notch受体的工程化细胞切割，使得它们的胞质片段自由易位到细胞核中，以调节在合成启动子的控制下的任何开放阅读框(ORF)的转录。表达的ORF可以是局部诱导和募集免疫活性到靶抗原检测位置的细胞因子。进一步地，表达的ORF可以是嵌合抗原T细胞受体(CAR-T)，其仅在检测到由嵌合Notch受体检测到的引发靶抗原(priming target antigen)后靶向单独的、不同的靶抗原用于靶细胞杀伤。这使得高度特异性组合抗原模式识别能够允许在患病或癌细胞与健康细胞之间进行更好的区分。这可以极大地使工程化CAR-T细胞的应用能够安全地靶向更广范围的肿瘤，对健康组织的副作用更小。
迄今为止，在嵌合Notch构建体中使用的转录机器是GAL4-VP16。由于DNA结合片段GAL4是酵母源，并且VP16是单纯疱疹病毒蛋白的高度酸性部分，因此GAL4-VP16具有高度免疫原性，并因此限制了嵌合Notch受体用于治疗人类疾病的用途。
在用于实体瘤的许多基于免疫疗法的方法(包括细胞疗法)的功效的另一个主要障碍是在实体瘤中药物的递送或免疫细胞的激活。单核细胞/巨噬细胞谱系的细胞构成浸润到实体瘤中的免疫细胞的主要成分(Long et al.,Oncoimmunology 2:e26860,2013doi:10.4161/onci26860)。因为这些细胞类型被积极募集并保留在实体瘤中，所以它们可以是用于基因疗法递送的重要细胞类型。
由于巨噬细胞中HIV-1感染的抑制，使用临床批准的载体(例如基于HIV-1的慢病毒)的巨噬细胞的基因工程一直是困难的。Hrecka等人(“Vpx relieves the inhibitionof HIV-1 infection of macrophages mediated by the SAMHD1protein,”Nature 474(7353):658-661,2011)证明在HIV-2和猿猴免疫缺陷病毒中发现的病毒粒子相关Vpx辅助蛋白的添加通过巨噬细胞限制因子SAMHD1的降解来减轻巨噬细胞的HIV-1感染的抑制。随后，已经证明单核细胞衍生的巨噬细胞可以用编码来自巨噬细胞的生产细胞因子的Vpx+慢病毒有效转导，旨在调节肿瘤微环境(Moyes et al.,Human Gene Therapy 28(2):200-215,2017)。
发明内容
本发明涉及用于降低嵌合Notch受体的免疫原性的方法和组合物。本文描述的Notch受体可以在单核细胞/巨噬细胞谱系的细胞中进行基因工程化改造。
本发明的另一个实施方案涉及通过人源化转录因子来降低嵌合Notch受体的免疫原性的方法和组合物，所述转录因子对控制通过嵌合Notch受体递送至组织的基因表达有用。
在本发明的另一个实施方案中的是通过人源化转录因子来降低嵌合Notch受体的免疫原性的方法和组合物，所述人源化转录因子用于在含有所述嵌合Notch受体的细胞中表达基因，其中此类转录因子包含来自肝细胞核因子(Hepatocyte Nuclear Factor)转录因子家族的转录因子。
本发明还涉及HNF1转录因子(例如HNF1 alpha和vHNF1 beta)的DNA结合结构域(DBD)用于生成具有降低的免疫原性的嵌合转录因子的用途，其对于将具有嵌合Notch受体的转基因递送至优选不表达内源性HNF1或vHNF1的组织有用。美国专利申请号200301096678。
本发明的另一个实施方案是人HNF1 DNA结合结构域，其与人转录激活物(TAD)或阻遏物结构域以及任选地人调节结构域结合使用。
本发明的另一个实施方案是人HNF1 DNA结合结构域，其与衍生自WWTR1(TAZ)蛋白的人转录激活物结构域(TAD)结合使用。
本发明的另一个实施方案是人HNF1 DNA结合结构域，其与衍生自CREB3(LZIP)蛋白的人转录激活物结构域(TAD)结合使用。
本发明的另一个实施方案是人HNF1 DNA结合结构域，其与衍生自NF-κB系统因子p65(RelA)的人转录激活物结构域(TAD)结合使用。
本发明还涉及核酸分子和蛋白质，其对在真核细胞和生物体中使用具有低免疫原性的嵌合Notch受体调节基因的表达有用。
本发明进一步提供了低免疫原性嵌合Notch受体多肽、包含编码嵌合Notch受体多肽的核苷酸序列的核酸以及用核酸进行基因修饰的宿主细胞，其中通过包含人HNF1 DNA结合结构域的转录因子与衍生自NF-κB系统因子p65(RelA)人转录激活物结构域(TAD)结合使用来实现低免疫原性。
在本发明的一个具体实施方案中，人源化嵌合notch受体由以下序列，5’至3’组成：
-人CD8a信号肽1-22(NP_001139345氨基酸1-22，(MALPVTALLLPLALLLHAARPS)(SEQID NO:1))-指导蛋白质表达到细胞表面。
-Myc标签(EQKLISEEDL)(SEQ ID NO:2)–用于表面表达的合成受体的抗体标记的肽标签。Myc抗体：Cell Signaling Techology，Myc标签(9B11)小鼠mAb(Alexa
Figure BDA0002316769660000041
647Conjugate；Catalogue No.2233)。
-抗人B细胞(CD19)抗体，克隆FMC63。
-包含三个NLR结构域、跨膜结构域以及包括人Notch3的天然核定位序列(NLS)的短胞质片段的人Notch3核心(gi|134244285|NP_000426.2氨基酸1374-1738)。
-GS柔性接头(GSAAAGGSGGSGGS)(SEQ ID NO:3)。
-包含人肝细胞核因子1-alpha同种型1的二聚化和DNA结合结构域(DBD)的人HNF1alpha(gi|807201167|NP_001293108.1氨基酸1-283)。
-GS柔性接头(GGGSGGGS)(SEQ ID NO:4)。
-包含转录因子p65同种型1[人]的转录激活结构域的人Rel-A(p65)(gi|223468676|NP_068810.3氨基酸1-551)。
本文还提供了治疗受试者(例如人)中的疾病(包括癌症)的方法，其包括向受试者施用包含人源化嵌合Notch受体的哺乳动物细胞。在一些实施方案中，哺乳动物细胞可以是单核细胞/巨噬细胞。
本发明的其他特征和优点将从以下发明详述和权利要求中变得显而易见。然而，应该理解的是，详细描述和具体实施例虽然表明了本发明的优选实施方案，但仅以说明的方式给出，因为本发明的精神和范围内的各种变化和修改对于本领域技术人员来说将从该详细描述中变得显而易见。
附图的简要说明
以下附图构成本说明书的一部分，并且包括在内以进一步说明本发明的某些方面。通过参考这些附图中的一个或多个并结合本文提出的具体实施方案的详细描述，可以更好地理解本发明。
图1.合成的Notch受体和包含它的组成结构域的示意图。
图2.实验数据显示四种人Notch同源物在通过外部myc标签结合抗原对携带myc的珠子结合的刺激后，释放GAL4-vp64的相对表现。hsNotch2和hsNotch3是仅有的显示出强烈活性的同源物。
图3A.实验数据显示与p65转录激活结构域融合的人DNA结合结构域上调GFP表达的功能性行为。
图3B.实验数据显示具有p65转录激活结构域的两个工作的合成Notch人DNA结合结构域上调GFP表达的功能性行为。
图4.实验数据显示人单核细胞衍生的巨噬细胞中嵌合notch受体的表达。实验数据显示相对于未转导的单核细胞衍生的巨噬细胞(右)，小鼠Notch1蛋白/Gal4和VP64转录因子(上)以及人Notch3蛋白/HNF 1a和p65转录因子(下)的转导百分比。
图5A.实验数据显示在人单核细胞衍生的巨噬细胞中与p65转录激活结构域融合的人Notch3和人DNA结合结构域上调GFP表达的功能性行为。
图5B.实验数据显示在人髓样细胞中与VP64转录激活融合的小鼠Notch1和非人Gal4结合结构域上调GFP表达的功能性行为。
通过引用并入：本文提及的所有出版物，包括专利、专利申请出版物和科学论文，均通过引用整体并入。
发明详述
定义
“嵌合Notch多肽”也称为“嵌合Notch受体多肽”或者“嵌合Notch”或“synNotch”描述于美国专利号9,670,281中，并且从N末端到C末端并以共价连接的方式包含：a)包含特异性结合对的第一成员的细胞外结构域；b)其中Notch受体多肽具有50个氨基酸至1000个氨基酸的长度，并包含一个或多个配体可诱导的蛋白水解切割位点；以及c)细胞内结构域，其中特异性结合对的第一成员与Notch受体多肽是异源的，并且其中特异性结合对的第一成员与特异性结合对的第二成员的结合诱导Notch受体多肽在一个或多个配体可诱导的蛋白水解切割位点的切割，由此释放细胞内结构域。在一些情况下，Notch受体多肽具有300个氨基酸至400个氨基酸的长度。
进一步地，“嵌合Notch受体多肽”包含置于细胞外结构域和Notch受体多肽之间的接头。在一些情况下，细胞内结构域为转录激活物。在一些情况下，细胞内结构域为转录阻遏物。在一些情况下，特异性结合对的第一成员包含基于抗体的识别支架。在一些情况下，特异性结合对的第一成员包含抗体。在一些情况下，当特异性结合对的第一成员是抗体时，所述抗体特异性结合肿瘤特异性抗原、疾病相关抗原或细胞外基质成分。在一些情况下，当特异性结合对的第一成员是抗体时，所述抗体特异性结合细胞表面抗原、可溶性抗原或固定在不溶性底物上的抗原。在一些情况下，当特异性结合对的第一成员是抗体时，所述抗体为单链Fv。在一些情况下，特异性结合对的第一成员为纳米抗体、单结构域抗体、双抗体、三抗体或微抗体。在一些情况下，特异性结合对的第一成员为非基于抗体的识别支架。在一些情况下，当特异性结合对的第一成员是非基于抗体的识别支架时，所述非基于抗体的识别支架为avimer、DARPin、adnectin、avimer、亲和体(affibody)、anticalin或affilin。在一些情况下，特异性结合对的第一成员为抗原。在一些情况下，当特异性结合对的第一成员是抗原时，所述抗原为内源性抗原。在一些情况下，当特异性结合对的第一成员是抗原时，所述抗原为外源性抗原。在一些情况下，特异性结合对的第一成员为受体的配体。在一些情况下，特异性结合对的第一成员为受体。在一些情况下，特异性结合对的第一成员为细胞粘附分子(例如，细胞粘附分子的细胞外区域的全部或一部分)。
术语“跨膜结构域”是指多肽的结构域，其包括当在哺乳动物细胞中表达时存在于相应的内源性多肽中时穿过脂质双分子层的至少一个连续的氨基酸序列。例如，跨膜结构域可以包括一个、两个、三个、四个、五个、六个、七个、八个、九个或十个连续的氨基酸序列，其当在哺乳动物细胞中表达时存在于相应的内源性多肽中时各自穿过脂质双分子层。如本领域中所知，跨膜结构域可以例如包括至少一个(例如，两个、三个、四个、五个、六个、七个、八个、九个或十个)在脂质双分子层中具有α-螺旋二级结构的连续的氨基酸序列(其当在哺乳动物细胞中表达时存在于相应的内源性多肽中时穿过脂质双分子层)。在一些实施方案中，跨膜结构域可以包括两个或更多个在脂质双分子层中形成β-桶二级结构的连续的氨基酸序列(其当在哺乳动物细胞中表达时存在于相应的内源性多肽中时各自穿过脂质双分子层)。本文描述了跨膜结构域的非限制性实例。本领域中已知跨膜结构域的另外的实例。
用于描述多肽位置的短语“质膜的细胞外侧”是指所述多肽包括至少一个穿过质膜的跨膜结构域和至少一个位于细胞外空间中的结构域(例如，至少一个抗原结合结构域)。
“GFP”或绿色荧光蛋白(GFP)是基因表达的常用报告蛋白。Arun et al.,J.Pharmacol.Toxicol.Methods 51(1):1–23,2005。
通过“HNF1结合位点”意指任何已知形式的HNF的任何特异性结合位点。HNF1(也称LF-B1或HNF1alpha)是628 aa长的蛋白DNA结合蛋白，其被认为是几个基因的肝细胞特异性转录的主要决定因素(Frain,Cell 59,145-157,1990)。
在一些实施方案中，人源的DNA结合结构域为HNF1转录因子(例如，本文描述的或本领域中已知的任何HNF1转录因子)的DNA结合结构域并且转录激活结构域为人RelA蛋白或它的一部分。
在一些实施方案中，HNF1alpha的氨基酸序列为NCBI号NP_001293108.1、NP_000536.5或XP_005253988.1。在一些实施方案中，人源化嵌合Notch受体的转录调节物的氨基酸序列包含肝细胞核因子1-alpha同种型1(NP_001293108.1)、肝细胞核因子1-alpha同种型1(NP_000536.5)或肝细胞核因子1-alpha同种型X1(XP_005253988.1)或它们的一部分。在一些实施方案中，人源化嵌合Notch受体的转录调节物的氨基酸序列包含SEQ ID NO:5、SEQ ID NO:6或SEQ ID NO:7的全部或一部分。
如本文所用，多肽或蛋白质的“一部分”是指参考序列的至少十个氨基酸，例如参考序列的10至200、25至300、50至400、100至500、200至600、300至700、400至800、500至900或600至1000或更多个氨基酸。在一些实施方案中，多肽或蛋白质的一部分是有功能的。在一些实施方案中，转录调节物是或包含肝细胞核因子1-alpha同种型1(NP_001293108.1)、肝细胞核因子1-alpha同种型1(NP_000536.5)或肝细胞核因子1-alpha同种型X1(XP_005253988.1)的二聚化和DNA结合结构域(DBD)。在一些实施方案中，人源化Notch受体的转录调节物的氨基酸序列是或包含SEQ ID NO:5、SEQ ID NO:6或SEQ ID NO:7的二聚化和DNA结合结构域(DBD)。在一些实施方案中，人源化Notch受体的转录调节物的氨基酸序列是或包含SEQ ID NO:5的氨基酸1-283。
人肝细胞核因子1-alpha同种型1 NP_001293108.1(SEQ ID NO:5)
MVSKLSQLQTELLAALLESGLSKEALIQALGEPGPYLLAGEGPLDKGESCGGGRGELAELPNGLGETRGSEDETDDDGEDFTPPILKELENLSPEEAAHQKAVVETLLQEDPWRVAKMVKSYLQQHNIPQREVVDTTGLNQSHLSQHLNKGTPMKTQKRAALYTWYVRKQREVAQQFTHAGQGGLIEEPTGDELPTKKGRRNRFKWGPASQQILFQAYERQKNPSKEERETLVEECNRAECIQRGVSPSQAQGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDTYSGPPPGPGPGPALPAHSSPGLPPPALSPSKVHGVRYGQPATSETAEVPSSSGGPLVTVSTPLHQVSPTGLEPSHSLLSTEAKLVSAAGGPLPPVSTLTALHSLEQTSPGLNQQPQNLIMASLPGVMTIGPGEPASLGPTFTNTGASTLVIGLASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPVQSHVTQSPFMATMAQLQSPHALYSHKPEVAQYTHTGLLPQTMLITDTTNLSALASLTPTKQEAALLPQVFTSDTEASSESGLHTPASQATTLHVPSQDPAGIQHLQPAHRLSASPTVSSSSLVLYQSSDSSNGQSHLLPSNHSVIETFISTQMASSSQ
人肝细胞核因子1-alpha同种型2 NP_000536.5(SEQ ID NO: 6)
MVSKLSQLQTELLAALLESGLSKEALIQALGEPGPYLLAGEGPLDKGESCGGGRGELAELPNGLGETRGSEDETDDDGEDFTPPILKELENLSPEEAAHQKAVVETLLQEDPWRVAKMVKSYLQQHNIPQREVVDTTGLNQSHLSQHLNKGTPMKTQKRAALYTWYVRKQREVAQQFTHAGQGGLIEEPTGDELPTKKGRRNRFKWGPASQQILFQAYERQKNPSKEERETLVEECNRAECIQRGVSPSQAQGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDTYSGPPPGPGPGPALPAHSSPGLPPPALSPSKVHGVRYGQPATSETAEVPSSSGGPLVTVSTPLHQVSPTGLEPSHSLLSTEAKLVSAAGGPLPPVSTLTALHSLEQTSPGLNQQPQNLIMASLPGVMTIGPGEPASLGPTFTNTGASTLVIGLASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPVQSHVTQSPFMATMAQLQSPHALYSHKPEVAQYTHTGLLPQTMLITDTTNLSALASLTPTKQVFTSDTEASSESGLHTPASQATTLHVPSQDPAGIQHLQPAHRLSASPTVSSSSLVLYQSSDSSNGQSHLLPSNHSVIETFISTQMASSSQ
人肝细胞核因子1-alpha同种型X1(预测)XP_005253988.1(SEQ ID NO:7)
MVSKLSQLQTELLAALLESGLSKEALIQALGEPGPYLLAGEGPLDKGESCGGGRGELAELPNGLGETRGSEDETDDDGEDFTPPILKELENLSPEEAAHQKAVVETLLQEDPWRVAKMVKSYLQQHNIPQREVVDTTGLNQSHLSQHLNKGTPMKTQKRAALYTWYVRKQREVAQQFTHAGQGGLIEEPTGDELPTKKGRRNRFKWGPASQQILFQAYERQKNPSKEERETLVEECNRAECIQRGVSPSQAQGLGSNLVTEVRVYNWFANRRKEEAFRHKLAMDTYSGPPPGPGPGPALPAHSSPGLPPPALSPSKVHGVRYGQPATSETAEVPSSSGGPLVTVSTPLHQVSPTGLEPSHSLLSTEAKLVSAAGGPLPPVSTLTALHSLEQTSPGLNQQPQNLIMASLPGVMTIGPGEPASLGPTFTNTGASTLVIGLASTQAQSVPVINSMGSSLTTLQPVQFSQPLHPSYQQPLMPPVQSHVTQSPFMATMAQLQSPHALYSHKPEVAQYTHTGLLPQTMLITDTTNLSALASLTPTKQVRSRPAGPPLACDRAPHPHIPRAQEAALLPQVFTSDTEASSESGLHTPASQATTLHVPSQDPASIQHLQPAHRLSASPTVSSSSLVLYQSSDSSNGQSHLLPSNHSVIETFISTQMASSSQ
在一些实施方案中，HNF1alpha或它的一部分的氨基酸序列，如本文所述，与SEQID NO: 5、SEQ ID NO:6或SEQ ID NO: 7中相应的氨基酸序列至少80％相同。在一些实施方案中，HNF1alpha或它的一部分的氨基酸序列与SEQ ID NO:5、SEQ ID NO:6或SEQ ID NO:7中相应的氨基酸序列80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同。在一些实施方案中，HNF1alpha或它的一部分的氨基酸序列，如本文所述，可以与SEQ ID NO:5、SEQ ID NO:6或SEQ ID NO:7中相应的氨基酸序列有1个氨基酸、2个氨基酸、3个氨基酸、4个氨基酸、5个氨基酸、6个氨基酸、7个氨基酸、8个氨基酸、9个氨基酸或10个或更多氨基酸的不同。
在一些实施方案中，HFN1alpha的mRNA序列为NCBI号NM_001306179.1、NM_00545.6或XM_005253931.3。在一些实施方案中，HFN1alpha的mRNA序列为SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:10。
人HNF1同源异型框A(HNF1A)，转录变体1，mRNA NM_001306179.1(SEQ ID NO:8)
GGGGCCCTGATTCACGGGCCGCTGGGGCCAGGGTTGGGGGTTGGGGGTGCCCACAGGGCTTGGCTAGTGGGGTTTTGGGGGGGCAGTGGGTGCAAGGAGTTTGGTTTGTGTCTGCCGGCCGGCAGGCAAACGCAACCCACGCGGTGGGGGAGGCGGCTAGCGTGGTGGACCCGGGCCGCGTGGCCCTGTGGCAGCCGAGCCATGGTTTCTAAACTGAGCCAGCTGCAGACGGAGCTCCTGGCGGCCCTGCTCGAGTCAGGGCTGAGCAAAGAGGCACTGATCCAGGCACTGGGTGAGCCGGGGCCCTACCTCCTGGCTGGAGAAGGCCCCCTGGACAAGGGGGAGTCCTGCGGCGGCGGTCGAGGGGAGCTGGCTGAGCTGCCCAATGGGCTGGGGGAGACTCGGGGCTCCGAGGACGAGACGGACGACGATGGGGAAGACTTCACGCCACCCATCCTCAAAGAGCTGGAGAACCTCAGCCCTGAGGAGGCGGCCCACCAGAAAGCCGTGGTGGAGACCCTTCTGCAGGAGGACCCGTGGCGTGTGGCGAAGATGGTCAAGTCCTACCTGCAGCAGCACAACATCCCACAGCGGGAGGTGGTCGATACCACTGGCCTCAACCAGTCCCACCTGTCCCAACACCTCAACAAGGGCACTCCCATGAAGACGCAGAAGCGGGCCGCCCTGTACACCTGGTACGTCCGCAAGCAGCGAGAGGTGGCGCAGCAGTTCACCCATGCAGGGCAGGGAGGGCTGATTGAAGAGCCCACAGGTGATGAGCTACCAACCAAGAAGGGGCGGAGGAACCGTTTCAAGTGGGGCCCAGCATCCCAGCAGATCCTGTTCCAGGCCTATGAGAGGCAGAAGAACCCTAGCAAGGAGGAGCGAGAGACGCTAGTGGAGGAGTGCAATAGGGCGGAATGCATCCAGAGAGGGGTGTCCCCATCACAGGCACAGGGGCTGGGCTCCAACCTCGTCACGGAGGTGCGTGTCTACAACTGGTTTGCCAACCGGCGCAAAGAAGAAGCCTTCCGGCACAAGCTGGCCATGGACACGTACAGCGGGCCCCCCCCAGGGCCAGGCCCGGGACCTGCGCTGCCCGCTCACAGCTCCCCTGGCCTGCCTCCACCTGCCCTCTCCCCCAGTAAGGTCCACGGTGTGCGCTATGGACAGCCTGCGACCAGTGAGACTGCAGAAGTACCCTCAAGCAGCGGCGGTCCCTTAGTGACAGTGTCTACACCCCTCCACCAAGTGTCCCCCACGGGCCTGGAGCCCAGCCACAGCCTGCTGAGTACAGAAGCCAAGCTGGTCTCAGCAGCTGGGGGCCCCCTCCCCCCTGTCAGCACCCTGACAGCACTGCACAGCTTGGAGCAGACATCCCCAGGCCTCAACCAGCAGCCCCAGAACCTCATCATGGCCTCACTTCCTGGGGTCATGACCATCGGGCCTGGTGAGCCTGCCTCCCTGGGTCCTACGTTCACCAACACAGGTGCCTCCACCCTGGTCATCGGCCTGGCCTCCACGCAGGCACAGAGTGTGCCGGTCATCAACAGCATGGGCAGCAGCCTGACCACCCTGCAGCCCGTCCAGTTCTCCCAGCCGCTGCACCCCTCCTACCAGCAGCCGCTCATGCCACCTGTGCAGAGCCATGTGACCCAGAGCCCCTTCATGGCCACCATGGCTCAGCTGCAGAGCCCCCACGCCCTCTACAGCCACAAGCCCGAGGTGGCCCAGTACACCCACACGGGCCTGCTCCCGCAGACTATGCTCATCACCGACACCACCAACCTGAGCGCCCTGGCCAGCCTCACGCCCACCAAGCAGGAGGCTGCTCTGCTCCCCCAGGTCTTCACCTCAGACACTGAGGCCTCCAGTGAGTCCGGGCTTCACACGCCGGCATCTCAGGCCACCACCCTCCACGTCCCCAGCCAGGACCCTGCCGGCATCCAGCACCTGCAGCCGGCCCACCGGCTCAGCGCCAGCCCCACAGTGTCCTCCAGCAGCCTGGTGCTGTACCAGAGCTCAGACTCCAGCAATGGCCAGAGCCACCTGCTGCCATCCAACCACAGCGTCATCGAGACCTTCATCTCCACCCAGATGGCCTCTTCCTCCCAGTAACCACGGCACCTGGGCCCTGGGGCCTGTACTGCCTGCTTGGGGGGTGATGAGGGCAGCAGCCAGCCCTGCCTGGAGGACCTGAGCCTGCCGAGCAACCGTGGCCCTTCCTGGACAGCTGTGCCTCGCTCCCCACTCTGCTCTGATGCATCAGAAAGGGAGGGCTCTGAGGCGCCCCAACCCGTGGAGGCTGCTCGGGGTGCACAGGAGGGGGTCGTGGAGAGCTAGGAGCAAAGCCTGTTCATGGCAGATGTAGGAGGGACTGTCGCTGCTTCGTGGGATACAGTCTTCTTACTTGGAACTGAAGGGGGCGGCCTATGACTTGGGCACCCCCAGCCTGGGCCTATGGAGAGCCCTGGGACCGCTACACCACTCTGGCAGCCACACTTCTCAGGACACAGGCCTGTGTAGCTGTGACCTGCTGAGCTCTGAGAGGCCCTGGATCAGCGTGGCCTTGTTCTGTCACCAATGTACCCACCGGGCCACTCCTTCCTGCCCCAACTCCTTCCAGCTAGTGACCCACATGCCATTTGTACTGACCCCATCACCTACTCACACAGGCATTTCCTGGGTGGCTACTCTGTGCCAGAGCCTGGGGCTCTAACGCCTGAGCCCAGGGAGGCCGAAGCTAACAGGGAAGGCAGGCAGGGCTCTCCTGGCTTCCCATCCCCAGCGATTCCCTCTCCCAGGCCCCATGACCTCCAGCTTTCCTGTATTTGTTCCCAAGAGCATCATGCCTCTGAGGCCAGCCTGGCCTCCTGCCTCTACTGGGAAGGCTACTTCGGGGCTGGGAAGTCGTCCTTACTCCTGTGGGAGCCTCGCAACCCGTGCCAAGTCCAGGTCCTGGTGGGGCAGCTCCTCTGTCTCGAGCGCCCTGCAGACCCTGCCCTTGTTTGGGGCAGGAGTAGCTGAGCTCACAAGGCAGCAAGGCCCGAGCAGCTGAGCAGGGCCGGGGAACTGGCCAAGCTGAGGTGCCCAGGAGAAGAAAGAGGTGACCCCAGGGCACAGGAGCTACCTGTGTGGACAGGACTAACACTCAGAAGCCTGGGGGCCTGGCTGGCTGAGGGCAGTTCGCAGCCACCCTGAGGAGTCTGAGGTCCTGAGCACTGCCAGGAGGGACAAAGGAGCCTGTGAACCCAGGACAAGCATGGTCCCACATCCCTGGGCCTGCTGCTGAGAACCTGGCCTTCAGTGTACCGCGTCTACCCTGGGATTCAGGAAAAGGCCTGGGGTGACCCGGCACCCCCTGCAGCTTGTAGCCAGCCGGGGCGAGTGGCACGTTTATTTAACTTTTAGTAAAGTCAAGGAGAAATGCGGTGGAAA
人HNF1同源异型框A(HNF1A)，转录变体2，mRNA NM_000545.6(SEQ ID NO:9)
GGGGCCCTGATTCACGGGCCGCTGGGGCCAGGGTTGGGGGTTGGGGGTGCCCACAGGGCTTGGCTAGTGGGGTTTTGGGGGGGCAGTGGGTGCAAGGAGTTTGGTTTGTGTCTGCCGGCCGGCAGGCAAACGCAACCCACGCGGTGGGGGAGGCGGCTAGCGTGGTGGACCCGGGCCGCGTGGCCCTGTGGCAGCCGAGCCATGGTTTCTAAACTGAGCCAGCTGCAGACGGAGCTCCTGGCGGCCCTGCTCGAGTCAGGGCTGAGCAAAGAGGCACTGATCCAGGCACTGGGTGAGCCGGGGCCCTACCTCCTGGCTGGAGAAGGCCCCCTGGACAAGGGGGAGTCCTGCGGCGGCGGTCGAGGGGAGCTGGCTGAGCTGCCCAATGGGCTGGGGGAGACTCGGGGCTCCGAGGACGAGACGGACGACGATGGGGAAGACTTCACGCCACCCATCCTCAAAGAGCTGGAGAACCTCAGCCCTGAGGAGGCGGCCCACCAGAAAGCCGTGGTGGAGACCCTTCTGCAGGAGGACCCGTGGCGTGTGGCGAAGATGGTCAAGTCCTACCTGCAGCAGCACAACATCCCACAGCGGGAGGTGGTCGATACCACTGGCCTCAACCAGTCCCACCTGTCCCAACACCTCAACAAGGGCACTCCCATGAAGACGCAGAAGCGGGCCGCCCTGTACACCTGGTACGTCCGCAAGCAGCGAGAGGTGGCGCAGCAGTTCACCCATGCAGGGCAGGGAGGGCTGATTGAAGAGCCCACAGGTGATGAGCTACCAACCAAGAAGGGGCGGAGGAACCGTTTCAAGTGGGGCCCAGCATCCCAGCAGATCCTGTTCCAGGCCTATGAGAGGCAGAAGAACCCTAGCAAGGAGGAGCGAGAGACGCTAGTGGAGGAGTGCAATAGGGCGGAATGCATCCAGAGAGGGGTGTCCCCATCACAGGCACAGGGGCTGGGCTCCAACCTCGTCACGGAGGTGCGTGTCTACAACTGGTTTGCCAACCGGCGCAAAGAAGAAGCCTTCCGGCACAAGCTGGCCATGGACACGTACAGCGGGCCCCCCCCAGGGCCAGGCCCGGGACCTGCGCTGCCCGCTCACAGCTCCCCTGGCCTGCCTCCACCTGCCCTCTCCCCCAGTAAGGTCCACGGTGTGCGCTATGGACAGCCTGCGACCAGTGAGACTGCAGAAGTACCCTCAAGCAGCGGCGGTCCCTTAGTGACAGTGTCTACACCCCTCCACCAAGTGTCCCCCACGGGCCTGGAGCCCAGCCACAGCCTGCTGAGTACAGAAGCCAAGCTGGTCTCAGCAGCTGGGGGCCCCCTCCCCCCTGTCAGCACCCTGACAGCACTGCACAGCTTGGAGCAGACATCCCCAGGCCTCAACCAGCAGCCCCAGAACCTCATCATGGCCTCACTTCCTGGGGTCATGACCATCGGGCCTGGTGAGCCTGCCTCCCTGGGTCCTACGTTCACCAACACAGGTGCCTCCACCCTGGTCATCGGCCTGGCCTCCACGCAGGCACAGAGTGTGCCGGTCATCAACAGCATGGGCAGCAGCCTGACCACCCTGCAGCCCGTCCAGTTCTCCCAGCCGCTGCACCCCTCCTACCAGCAGCCGCTCATGCCACCTGTGCAGAGCCATGTGACCCAGAGCCCCTTCATGGCCACCATGGCTCAGCTGCAGAGCCCCCACGCCCTCTACAGCCACAAGCCCGAGGTGGCCCAGTACACCCACACGGGCCTGCTCCCGCAGACTATGCTCATCACCGACACCACCAACCTGAGCGCCCTGGCCAGCCTCACGCCCACCAAGCAGGTCTTCACCTCAGACACTGAGGCCTCCAGTGAGTCCGGGCTTCACACGCCGGCATCTCAGGCCACCACCCTCCACGTCCCCAGCCAGGACCCTGCCGGCATCCAGCACCTGCAGCCGGCCCACCGGCTCAGCGCCAGCCCCACAGTGTCCTCCAGCAGCCTGGTGCTGTACCAGAGCTCAGACTCCAGCAATGGCCAGAGCCACCTGCTGCCATCCAACCACAGCGTCATCGAGACCTTCATCTCCACCCAGATGGCCTCTTCCTCCCAGTAACCACGGCACCTGGGCCCTGGGGCCTGTACTGCCTGCTTGGGGGGTGATGAGGGCAGCAGCCAGCCCTGCCTGGAGGACCTGAGCCTGCCGAGCAACCGTGGCCCTTCCTGGACAGCTGTGCCTCGCTCCCCACTCTGCTCTGATGCATCAGAAAGGGAGGGCTCTGAGGCGCCCCAACCCGTGGAGGCTGCTCGGGGTGCACAGGAGGGGGTCGTGGAGAGCTAGGAGCAAAGCCTGTTCATGGCAGATGTAGGAGGGACTGTCGCTGCTTCGTGGGATACAGTCTTCTTACTTGGAACTGAAGGGGGCGGCCTATGACTTGGGCACCCCCAGCCTGGGCCTATGGAGAGCCCTGGGACCGCTACACCACTCTGGCAGCCACACTTCTCAGGACACAGGCCTGTGTAGCTGTGACCTGCTGAGCTCTGAGAGGCCCTGGATCAGCGTGGCCTTGTTCTGTCACCAATGTACCCACCGGGCCACTCCTTCCTGCCCCAACTCCTTCCAGCTAGTGACCCACATGCCATTTGTACTGACCCCATCACCTACTCACACAGGCATTTCCTGGGTGGCTACTCTGTGCCAGAGCCTGGGGCTCTAACGCCTGAGCCCAGGGAGGCCGAAGCTAACAGGGAAGGCAGGCAGGGCTCTCCTGGCTTCCCATCCCCAGCGATTCCCTCTCCCAGGCCCCATGACCTCCAGCTTTCCTGTATTTGTTCCCAAGAGCATCATGCCTCTGAGGCCAGCCTGGCCTCCTGCCTCTACTGGGAAGGCTACTTCGGGGCTGGGAAGTCGTCCTTACTCCTGTGGGAGCCTCGCAACCCGTGCCAAGTCCAGGTCCTGGTGGGGCAGCTCCTCTGTCTCGAGCGCCCTGCAGACCCTGCCCTTGTTTGGGGCAGGAGTAGCTGAGCTCACAAGGCAGCAAGGCCCGAGCAGCTGAGCAGGGCCGGGGAACTGGCCAAGCTGAGGTGCCCAGGAGAAGAAAGAGGTGACCCCAGGGCACAGGAGCTACCTGTGTGGACAGGACTAACACTCAGAAGCCTGGGGGCCTGGCTGGCTGAGGGCAGTTCGCAGCCACCCTGAGGAGTCTGAGGTCCTGAGCACTGCCAGGAGGGACAAAGGAGCCTGTGAACCCAGGACAAGCATGGTCCCACATCCCTGGGCCTGCTGCTGAGAACCTGGCCTTCAGTGTACCGCGTCTACCCTGGGATTCAGGAAAAGGCCTGGGGTGACCCGGCACCCCCTGCAGCTTGTAGCCAGCCGGGGCGAGTGGCACGTTTATTTAACTTTTAGTAAAGTCAAGGAGAAATGCGGTGGAAA
人HNF1同源异型框A(HNF1A)，转录变体X1，mRNA XM_005253931.3(SEQ ID NO:10)
ATAAATATGAACCTTGGAGAATTTCCCCAGCTCCAATGTAAACAGAACAGGCAGGGGCCCTGATTCACGGGCCGCTGGGGCCAGGGTTGGGGGTTGGGGGTGCCCACAGGGCTTGGCTAGTGGGGTTTTGGGGGGGCAGTGGGTGCAAGGAGTTTGGTTTGTGTCTGCCGGCCGGCAGGCAAACGCAACCCACGCGGTGGGGGAGGCGGCTAGCGTGGTGGACCCGGGCCGCGTGGCCCTGTGGCAGCCGAGCCATGGTTTCTAAACTGAGCCAGCTGCAGACGGAGCTCCTGGCGGCCCTGCTCGAGTCAGGGCTGAGCAAAGAGGCACTGATCCAGGCACTGGGTGAGCCGGGGCCCTACCTCCTGGCTGGAGAAGGCCCCCTGGACAAGGGGGAGTCCTGCGGCGGCGGTCGAGGGGAGCTGGCTGAGCTGCCCAATGGGCTGGGGGAGACTCGGGGCTCCGAGGACGAGACGGACGACGATGGGGAAGACTTCACGCCACCCATCCTCAAAGAGCTGGAGAACCTCAGCCCTGAGGAGGCGGCCCACCAGAAAGCCGTGGTGGAGACCCTTCTGCAGGAGGACCCGTGGCGTGTGGCGAAGATGGTCAAGTCCTACCTGCAGCAGCACAACATCCCACAGCGGGAGGTGGTCGATACCACTGGCCTCAACCAGTCCCACCTGTCCCAACACCTCAACAAGGGCACTCCCATGAAGACGCAGAAGCGGGCCGCCCTGTACACCTGGTACGTCCGCAAGCAGCGAGAGGTGGCGCAGCAGTTCACCCATGCAGGGCAGGGAGGGCTGATTGAAGAGCCCACAGGTGATGAGCTACCAACCAAGAAGGGGCGGAGGAACCGTTTCAAGTGGGGCCCAGCATCCCAGCAGATCCTGTTCCAGGCCTATGAGAGGCAGAAGAACCCTAGCAAGGAGGAGCGAGAGACGCTAGTGGAGGAGTGCAATAGGGCGGAATGCATCCAGAGAGGGGTGTCCCCATCACAGGCACAGGGGCTGGGCTCCAACCTCGTCACGGAGGTGCGTGTCTACAACTGGTTTGCCAACCGGCGCAAAGAAGAAGCCTTCCGGCACAAGCTGGCCATGGACACGTACAGCGGGCCCCCCCCAGGGCCAGGCCCGGGACCTGCGCTGCCCGCTCACAGCTCCCCTGGCCTGCCTCCACCTGCCCTCTCCCCCAGTAAGGTCCACGGTGTGCGCTATGGACAGCCTGCGACCAGTGAGACTGCAGAAGTACCCTCAAGCAGCGGCGGTCCCTTAGTGACAGTGTCTACACCCCTCCACCAAGTGTCCCCCACGGGCCTGGAGCCCAGCCACAGCCTGCTGAGTACAGAAGCCAAGCTGGTCTCAGCAGCTGGGGGCCCCCTCCCCCCTGTCAGCACCCTGACAGCACTGCACAGCTTGGAGCAGACATCCCCAGGCCTCAACCAGCAGCCCCAGAACCTCATCATGGCCTCACTTCCTGGGGTCATGACCATCGGGCCTGGTGAGCCTGCCTCCCTGGGTCCTACGTTCACCAACACAGGTGCCTCCACCCTGGTCATCGGCCTGGCCTCCACGCAGGCACAGAGTGTGCCGGTCATCAACAGCATGGGCAGCAGCCTGACCACCCTGCAGCCCGTCCAGTTCTCCCAGCCGCTGCACCCCTCCTACCAGCAGCCGCTCATGCCACCTGTGCAGAGCCATGTGACCCAGAGCCCCTTCATGGCCACCATGGCTCAGCTGCAGAGCCCCCACGCCCTCTACAGCCACAAGCCCGAGGTGGCCCAGTACACCCACACGGGCCTGCTCCCGCAGACTATGCTCATCACCGACACCACCAACCTGAGCGCCCTGGCCAGCCTCACGCCCACCAAGCAGGTAAGGTCCAGGCCTGCTGGCCCTCCCTTGGCCTGTGACAGAGCCCCTCACCCCCACATCCCCCGGGCTCAGGAGGCTGCTCTGCTCCCCCAGGTCTTCACCTCAGACACTGAGGCCTCCAGTGAGTCCGGGCTTCACACGCCGGCATCTCAGGCCACCACCCTCCACGTCCCCAGCCAGGACCCTGCCAGCATCCAGCACCTGCAGCCGGCCCACCGGCTCAGCGCCAGCCCCACAGTGTCCTCCAGCAGCCTGGTGCTGTACCAGAGCTCAGACTCCAGCAATGGCCAGAGCCACCTGCTGCCATCCAACCACAGCGTCATCGAGACCTTCATCTCCACCCAGATGGCCTCTTCCTCCCAGTAACCACGGCACCTGGGCCCTGGGGCCTGTACTGCCTGCTTGGGGGGTGATGAGGGCAGCAGCCAGCCCTGCCTGGAGGACCTGAGCCTGCCGAGCAACCGTGGCCCTTCCTGGACAGCTGTGCCTCGCTCCCCACTCTGCTCTGATGCATCAGAAAGGGAGGGCTCTGAGGCGCCCCAACCCGTGGAGGCTGCTCGGGGTGCACAGGAGGGGGTCGTGGAGAGCTAGGAGCAAAGCCTGTTCATGGCAGATGTAGGAGGGACTGTCGCTGCTTCGTGGGATACAGTCTTCTTACTTGGAACTGAAGGGGGCGGCCTATGACTTGGGCACCCCCAGCCTGGGCCTATGGAGAGCCCTGGGACCGCTACACCACTCTGGCAGCCACACTTCTCAGGACACAGGCCTGTGTAGCTGTGACCTGCTGAGCTCTGAGAGGCCCTGGATCAGCGTGGCCTTGTTCTGTCACCAATGTACCCACCGGGCCACTCCTTCCTGCCCCAACTCCTTCCAGCTAGTGACCCACATGCCATTTGTACTGACCCCATCACCTACTCACACAGGCATTTCCTGGGTGGCTACTCTGTGCCAGAGCCTGGGGCTCTAACGCCTGAGCCCAGGGAGGCCGAAGCTAACAGGGAAGGCAGGCAGGGCTCTCCTGGCTTCCCATCCCCAGCGATTCCCTCTCCCAGGCCCCATGACCTCCAGCTTTCCTGTATTTGTTCCCAAGAGCATCATGCCTCTGAGGCCAGCCTGGCCTCCTGCCTCTACTGGGAAGGCTACTTCGGGGCTGGGAAGTCGTCCTTACTCCTGTGGGAGCCTCGCAACCCGTGCCAAGTCCAGGTCCTGGTGGGGCAGCTCCTCTGTCTCGAGCGCCCTGCAGACCCTGCCCTTGTTTGGGGCAGGAGTAGCTGAGCTCACAAGGCAGCAAGGCCCGAGCAGCTGAGCAGGGCCGGGGAACTGGCCAAGCTGAGGTGCCCAGGAGAAGAAAGAGGTGACCCCAGGGCACAGGAGCTACCTGTGTGGACAGGACTAACACTCAGAAGCCTGGGGGCCTGGCTGGCTGAGGGCAGTTCGCAGCCACCCTGAGGAGTCTGAGGTCCTGAGCACTGCCAGGAGGGACAAAGGAGCCTGTGAACCCAGGACAAGCATGGTCCCACATCCCTGGGCCTGCTGCTGAGAACCTGGCCTTCAGTGTACCGCGTCTACCCTGGGATTCAGGAAAAGGCCTGGGGTGACCCGGCACCCCCTGCAGCTTGTAGCCAGCCGGGGCGAGTGGCACGTTTATTTAACTTTTAGTAAAGTCAAGGAGAAATGCGGTGGAAA
在一些实施方案中，HNF1alpha与反向回文序列5-GTTAATNATTAAC-3(SEQ ID NO:11)结合。
在一些实施方案中，编码HNF1alpha的核酸序列，如本文所述，与SEQ ID NO:8、SEQID NO:9或SEQ ID NO:10的序列至少80％相同。在一些实施方案中，编码HNF1alpha的核酸序列与SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:10的序列80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同。在一些实施方案中，编码HNF1alpha的核酸核苷酸序列，如本文所述，可以与SEQ ID NO:8、SEQ ID NO:9或SEQ ID NO:10的序列有1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30或更多个核苷酸的不同。
在一些实施方案中，Rel-A(p65)的氨基酸序列为NCBI号NP_068810.3、NP_001138610.1、NP_001230913.1、NP_001230914.1、XP_011543508.1或XP_011543509.1。在一些实施方案中，Rel-A(p65)的氨基酸序列是或包含SEQ ID NO:12、SEQ ID NO:13、SEQ IDNO:14、SEQ ID NO:15、SEQ ID NO:16或SEQ ID NO:17的全部或一部分。在一些实施方案中，人源化嵌合Notch受体的转录激活结构域的氨基酸序列包含转录因子p65同种型1(NP_068810.3)、转录因子p65同种型2(NP_001138610.1)、转录因子p65同种型3(NP_001230913.1)、转录因子p65同种型4(NP_001230914.1)、转录因子p65同种型X1(XP_011543508.1)或转录因子p65同种型X2(XP_011543509.1)的全部或一部分。在一些实施方案中，人源化Notch受体的转录激活结构域的氨基酸序列包含SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16或SEQ ID NO:17的全部或一部分。在一些实施方案中，人源化Notch受体的转录激活结构域的氨基酸序列是或包含SEQ ID NO:12的氨基酸1-551。
人转录因子p65同种型1 NP_068810.3(SEQ ID NO:12)
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS
人转录因子p65同种型2 NP_001138610.1(SEQ ID NO:13)
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS
人转录因子p65同种型3 NP_001230913.1(SEQ ID NO:14)
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS
人转录因子p65同种型4 NP_001230914.1(SEQ ID NO:15)
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS
人转录因子p65同种型X1 XP_011543508.1(SEQ ID NO:16)
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS
人转录因子p65同种型X2 XP_011543509.1(SEQ ID NO:17)
MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNHDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS
在一些实施方案中，Rel-A(p65)的氨基酸序列，如本文所述，与SEQ ID NO:12、SEQID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16或SEQ ID NO:17的氨基酸序列至少80％相同。在一些实施方案中，Rel-A(p65)的氨基酸序列与SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16或SEQ ID NO:17的氨基酸序列80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同。在一些实施方案中，Rel-A(p65)的氨基酸序列，如本文所述，可以与SEQ ID NO:12、SEQ ID NO:13、SEQ ID NO:14、SEQ ID NO:15、SEQ ID NO:16或SEQ ID NO:17的氨基酸序列有1个氨基酸、2个氨基酸、3个氨基酸、4个氨基酸、5个氨基酸、6个氨基酸、7个氨基酸、8个氨基酸、9个氨基酸或10个或更多氨基酸的不同。
在一些实施方案中，编码Rel-A(p65)的核酸序列由NCBI号NM_021975.3、NM_001145138.1、NM_001243984.1、NM_001243985.1、XM_011545206.1或XM_011545207.1提供。在一些实施方案中，编码Rel-A(p65)的核酸序列是或包含SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22或SEQ ID NO:23。
人RELA原癌基因，NF-kB亚基(RELA)，转录变体1，mRNA NM_021975.3(SEQ ID NO:18)
AGCGCGCAGGCGCGGCCGGATTCCGGGCAGTGACGCGACGGCGGGCCGCGCGGCGCATTTCCGCCTCTGGCGAATGGCTCGTCTGTAGTGCACGCCGCGGGCCCAGCTGCGACCCCGGCCCCGCCCCCGGGACCCCGGCCATGGACGAACTGTTCCCCCTCATCTTCCCGGCAGAGCCAGCCCAGGCCTCTGGCCCCTATGTGGAGATCATTGAGCAGCCCAAGCAGCGGGGCATGCGCTTCCGCTACAAGTGCGAGGGGCGCTCCGCGGGCAGCATCCCAGGCGAGAGGAGCACAGATACCACCAAGACCCACCCCACCATCAAGATCAATGGCTACACAGGACCAGGGACAGTGCGCATCTCCCTGGTCACCAAGGACCCTCCTCACCGGCCTCACCCCCACGAGCTTGTAGGAAAGGACTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCGCTGCATCCACAGTTTCCAGAACCTGGGAATCCAGTGTGTGAAGAAGCGGGACCTGGAGCAGGCTATCAGTCAGCGCATCCAGACCAACAACAACCCCTTCCAAGTTCCTATAGAAGAGCAGCGTGGGGACTACGACCTGAATGCTGTGCGGCTCTGCTTCCAGGTGACAGTGCGGGACCCATCAGGCAGGCCCCTCCGCCTGCCGCCTGTCCTTTCTCATCCCATCTTTGACAATCGTGCCCCCAACACTGCCGAGCTCAAGATCTGCCGAGTGAACCGAAACTCTGGCAGCTGCCTCGGTGGGGATGAGATCTTCCTACTGTGTGACAAGGTGCAGAAAGAGGACATTGAGGTGTATTTCACGGGACCAGGCTGGGAGGCCCGAGGCTCCTTTTCGCAAGCTGATGTGCACCGACAAGTGGCCATTGTGTTCCGGACCCCTCCCTACGCAGACCCCAGCCTGCAGGCTCCTGTGCGTGTCTCCATGCAGCTGCGGCGGCCTTCCGACCGGGAGCTCAGTGAGCCCATGGAATTCCAGTACCTGCCAGATACAGACGATCGTCACCGGATTGAGGAGAAACGTAAAAGGACATATGAGACCTTCAAGAGCATCATGAAGAAGAGTCCTTTCAGCGGACCCACCGACCCCCGGCCTCCACCTCGACGCATTGCTGTGCCTTCCCGCAGCTCAGCTTCTGTCCCCAAGCCAGCACCCCAGCCCTATCCCTTTACGTCATCCCTGAGCACCATCAACTATGATGAGTTTCCCACCATGGTGTTTCCTTCTGGGCAGATCAGCCAGGCCTCGGCCTTGGCCCCGGCCCCTCCCCAAGTCCTGCCCCAGGCTCCAGCCCCTGCCCCTGCTCCAGCCATGGTATCAGCTCTGGCCCAGGCCCCAGCCCCTGTCCCAGTCCTAGCCCCAGGCCCTCCTCAGGCTGTGGCCCCACCTGCCCCCAAGCCCACCCAGGCTGGGGAAGGAACGCTGTCAGAGGCCCTGCTGCAGCTGCAGTTTGATGATGAAGACCTGGGGGCCTTGCTTGGCAACAGCACAGACCCAGCTGTGTTCACAGACCTGGCATCCGTCGACAACTCCGAGTTTCAGCAGCTGCTGAACCAGGGCATACCTGTGGCCCCCCACACAACTGAGCCCATGCTGATGGAGTACCCTGAGGCTATAACTCGCCTAGTGACAGGGGCCCAGAGGCCCCCCGACCCAGCTCCTGCTCCACTGGGGGCCCCGGGGCTCCCCAATGGCCTCCTTTCAGGAGATGAAGACTTCTCCTCCATTGCGGACATGGACTTCTCAGCCCTGCTGAGTCAGATCAGCTCCTAAGGGGGTGACGCCTGCCCTCCCCAGAGCACTGGGTTGCAGGGGATTGAAGCCCTCCAAAAGCACTTACGGATTCTGGTGGGGTGTGTTCCAACTGCCCCCAACTTTGTGGATGTCTTCCTTGGAGGGGGGAGCCATATTTTATTCTTTTATTGTCAGTATCTGTATCTCTCTCTCTTTTTGGAGGTGCTTAAGCAGAAGCATTAACTTCTCTGGAAAGGGGGGAGCTGGGGAAACTCAAACTTTTCCCCTGTCCTGATGGTCAGCTCCCTTCTCTGTAGGGAACTCTGGGGTCCCCCATCCCCATCCTCCAGCTTCTGGTACTCTCCTAGAGACAGAAGCAGGCTGGAGGTAAGGCCTTTGAGCCCACAAAGCCTTATCAAGTGTCTTCCATCATGGATTCATTACAGCTTAATCAAAATAACGCCCCAGATACCAGCCCCTGTATGGCACTGGCATTGTCCCTGTGCCTAACACCAGCGTTTGAGGGGCTGGCCTTCCTGCCCTACAGAGGTCTCTGCCGGCTCTTTCCTTGCTCAACCATGGCTGAAGGAAACCAGTGCAACAGCACTGGCTCTCTCCAGGATCCAGAAGGGGTTTGGTCTGGGACTTCCTTGCTCTCCCTCTTCTCAAGTGCCTTAATAGTAGGGTAAGTTGTTAAGAGTGGGGGAGAGCAGGCTGGCAGCTCTCCAGTCAGGAGGCATAGTTTTTACTGAACAATCAAAGCACTTGGACTCTTGCTCTTTCTACTCTGAACTAATAAATCTGTTGCCAAGCTGGCTAGAAAAAAAAAAAAAAAAAA
人RELA原癌基因，NF-kB亚基(RELA)，转录变体2，mRNA NM_001145138.1(SEQ IDNO:19)
AGCGCGCAGGCGCGGCCGGATTCCGGGCAGTGACGCGACGGCGGGCCGCGCGGCGCATTTCCGCCTCTGGCGAATGGCTCGTCTGTAGTGCACGCCGCGGGCCCAGCTGCGACCCCGGCCCCGCCCCCGGGACCCCGGCCATGGACGAACTGTTCCCCCTCATCTTCCCGGCAGAGCCAGCCCAGGCCTCTGGCCCCTATGTGGAGATCATTGAGCAGCCCAAGCAGCGGGGCATGCGCTTCCGCTACAAGTGCGAGGGGCGCTCCGCGGGCAGCATCCCAGGCGAGAGGAGCACAGATACCACCAAGACCCACCCCACCATCAAGATCAATGGCTACACAGGACCAGGGACAGTGCGCATCTCCCTGGTCACCAAGGACCCTCCTCACCGGCCTCACCCCCACGAGCTTGTAGGAAAGGACTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCGCTGCATCCACAGTTTCCAGAACCTGGGAATCCAGTGTGTGAAGAAGCGGGACCTGGAGCAGGCTATCAGTCAGCGCATCCAGACCAACAACAACCCCTTCCAAGAAGAGCAGCGTGGGGACTACGACCTGAATGCTGTGCGGCTCTGCTTCCAGGTGACAGTGCGGGACCCATCAGGCAGGCCCCTCCGCCTGCCGCCTGTCCTTTCTCATCCCATCTTTGACAATCGTGCCCCCAACACTGCCGAGCTCAAGATCTGCCGAGTGAACCGAAACTCTGGCAGCTGCCTCGGTGGGGATGAGATCTTCCTACTGTGTGACAAGGTGCAGAAAGAGGACATTGAGGTGTATTTCACGGGACCAGGCTGGGAGGCCCGAGGCTCCTTTTCGCAAGCTGATGTGCACCGACAAGTGGCCATTGTGTTCCGGACCCCTCCCTACGCAGACCCCAGCCTGCAGGCTCCTGTGCGTGTCTCCATGCAGCTGCGGCGGCCTTCCGACCGGGAGCTCAGTGAGCCCATGGAATTCCAGTACCTGCCAGATACAGACGATCGTCACCGGATTGAGGAGAAACGTAAAAGGACATATGAGACCTTCAAGAGCATCATGAAGAAGAGTCCTTTCAGCGGACCCACCGACCCCCGGCCTCCACCTCGACGCATTGCTGTGCCTTCCCGCAGCTCAGCTTCTGTCCCCAAGCCAGCACCCCAGCCCTATCCCTTTACGTCATCCCTGAGCACCATCAACTATGATGAGTTTCCCACCATGGTGTTTCCTTCTGGGCAGATCAGCCAGGCCTCGGCCTTGGCCCCGGCCCCTCCCCAAGTCCTGCCCCAGGCTCCAGCCCCTGCCCCTGCTCCAGCCATGGTATCAGCTCTGGCCCAGGCCCCAGCCCCTGTCCCAGTCCTAGCCCCAGGCCCTCCTCAGGCTGTGGCCCCACCTGCCCCCAAGCCCACCCAGGCTGGGGAAGGAACGCTGTCAGAGGCCCTGCTGCAGCTGCAGTTTGATGATGAAGACCTGGGGGCCTTGCTTGGCAACAGCACAGACCCAGCTGTGTTCACAGACCTGGCATCCGTCGACAACTCCGAGTTTCAGCAGCTGCTGAACCAGGGCATACCTGTGGCCCCCCACACAACTGAGCCCATGCTGATGGAGTACCCTGAGGCTATAACTCGCCTAGTGACAGGGGCCCAGAGGCCCCCCGACCCAGCTCCTGCTCCACTGGGGGCCCCGGGGCTCCCCAATGGCCTCCTTTCAGGAGATGAAGACTTCTCCTCCATTGCGGACATGGACTTCTCAGCCCTGCTGAGTCAGATCAGCTCCTAAGGGGGTGACGCCTGCCCTCCCCAGAGCACTGGGTTGCAGGGGATTGAAGCCCTCCAAAAGCACTTACGGATTCTGGTGGGGTGTGTTCCAACTGCCCCCAACTTTGTGGATGTCTTCCTTGGAGGGGGGAGCCATATTTTATTCTTTTATTGTCAGTATCTGTATCTCTCTCTCTTTTTGGAGGTGCTTAAGCAGAAGCATTAACTTCTCTGGAAAGGGGGGAGCTGGGGAAACTCAAACTTTTCCCCTGTCCTGATGGTCAGCTCCCTTCTCTGTAGGGAACTCTGGGGTCCCCCATCCCCATCCTCCAGCTTCTGGTACTCTCCTAGAGACAGAAGCAGGCTGGAGGTAAGGCCTTTGAGCCCACAAAGCCTTATCAAGTGTCTTCCATCATGGATTCATTACAGCTTAATCAAAATAACGCCCCAGATACCAGCCCCTGTATGGCACTGGCATTGTCCCTGTGCCTAACACCAGCGTTTGAGGGGCTGGCCTTCCTGCCCTACAGAGGTCTCTGCCGGCTCTTTCCTTGCTCAACCATGGCTGAAGGAAACCAGTGCAACAGCACTGGCTCTCTCCAGGATCCAGAAGGGGTTTGGTCTGGGACTTCCTTGCTCTCCCTCTTCTCAAGTGCCTTAATAGTAGGGTAAGTTGTTAAGAGTGGGGGAGAGCAGGCTGGCAGCTCTCCAGTCAGGAGGCATAGTTTTTACTGAACAATCAAAGCACTTGGACTCTTGCTCTTTCTACTCTGAACTAATAAATCTGTTGCCAAGCTGGCTAGAAAAAAAAAAAAAAAAAA
人RELA原癌基因，NF-kB亚基(RELA)，转录变体3，mRNA NM_001243984.1(SEQ IDNO:20)
AGCGCGCAGGCGCGGCCGGATTCCGGGCAGTGACGCGACGGCGGGCCGCGCGGCGCATTTCCGCCTCTGGCGAATGGCTCGTCTGTAGTGCACGCCGCGGGCCCAGCTGCGACCCCGGCCCCGCCCCCGGGACCCCGGCCATGGACGAACTGTTCCCCCTCATCTTCCCGGCAGAGCCAGCCCAGGCCTCTGGCCCCTATGTGGAGATCATTGAGCAGCCCAAGCAGCGGGGCATGCGCTTCCGCTACAAGTGCGAGGGGCGCTCCGCGGGCAGCATCCCAGGCGAGAGGAGCACAGATACCACCAAGACCCACCCCACCATCAAGATCAATGGCTACACAGGACCAGGGACAGTGCGCATCTCCCTGGTCACCAAGGACCCTCCTCACCGGCCTCACCCCCACGAGCTTGTAGGAAAGGACTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCGCTGCATCCACAGTTTCCAGAACCTGGGAATCCAGTGTGTGAAGAAGCGGGACCTGGAGCAGGCTATCAGTCAGCGCATCCAGACCAACAACAACCCCTTCCAAGTTCCTATAGAAGAGCAGCGTGGGGACTACGACCTGAATGCTGTGCGGCTCTGCTTCCAGGTGACAGTGCGGGACCCATCAGGCAGGCCCCTCCGCCTGCCGCCTGTCCTTTCTCATCCCATCTTTGACAATCGTGCCCCCAACACTGCCGAGCTCAAGATCTGCCGAGTGAACCGAAACTCTGGCAGCTGCCTCGGTGGGGATGAGATCTTCCTACTGTGTGACAAGGTGCAGAAAGAGGACATTGAGGTGTATTTCACGGGACCAGGCTGGGAGGCCCGAGGCTCCTTTTCGCAAGCTGATGTGCACCGACAAGTGGCCATTGTGTTCCGGACCCCTCCCTACGCAGACCCCAGCCTGCAGGCTCCTGTGCGTGTCTCCATGCAGCTGCGGCGGCCTTCCGACCGGGAGCTCAGTGAGCCCATGGAATTCCAGTACCTGCCAGATACAGACGATCGTCACCGGATTGAGGAGAAACGTAAAAGGACATATGAGACCTTCAAGAGCATCATGAAGAAGAGTCCTTTCAGCGGACCCACCGACCCCCGGCCTCCACCTCGACGCATTGCTGTGCCTTCCCGCAGCTCAGCTTCTGTCCCCAAGCCAGCCCCAGGCCCTCCTCAGGCTGTGGCCCCACCTGCCCCCAAGCCCACCCAGGCTGGGGAAGGAACGCTGTCAGAGGCCCTGCTGCAGCTGCAGTTTGATGATGAAGACCTGGGGGCCTTGCTTGGCAACAGCACAGACCCAGCTGTGTTCACAGACCTGGCATCCGTCGACAACTCCGAGTTTCAGCAGCTGCTGAACCAGGGCATACCTGTGGCCCCCCACACAACTGAGCCCATGCTGATGGAGTACCCTGAGGCTATAACTCGCCTAGTGACAGGGGCCCAGAGGCCCCCCGACCCAGCTCCTGCTCCACTGGGGGCCCCGGGGCTCCCCAATGGCCTCCTTTCAGGAGATGAAGACTTCTCCTCCATTGCGGACATGGACTTCTCAGCCCTGCTGAGTCAGATCAGCTCCTAAGGGGGTGACGCCTGCCCTCCCCAGAGCACTGGGTTGCAGGGGATTGAAGCCCTCCAAAAGCACTTACGGATTCTGGTGGGGTGTGTTCCAACTGCCCCCAACTTTGTGGATGTCTTCCTTGGAGGGGGGAGCCATATTTTATTCTTTTATTGTCAGTATCTGTATCTCTCTCTCTTTTTGGAGGTGCTTAAGCAGAAGCATTAACTTCTCTGGAAAGGGGGGAGCTGGGGAAACTCAAACTTTTCCCCTGTCCTGATGGTCAGCTCCCTTCTCTGTAGGGAACTCTGGGGTCCCCCATCCCCATCCTCCAGCTTCTGGTACTCTCCTAGAGACAGAAGCAGGCTGGAGGTAAGGCCTTTGAGCCCACAAAGCCTTATCAAGTGTCTTCCATCATGGATTCATTACAGCTTAATCAAAATAACGCCCCAGATACCAGCCCCTGTATGGCACTGGCATTGTCCCTGTGCCTAACACCAGCGTTTGAGGGGCTGGCCTTCCTGCCCTACAGAGGTCTCTGCCGGCTCTTTCCTTGCTCAACCATGGCTGAAGGAAACCAGTGCAACAGCACTGGCTCTCTCCAGGATCCAGAAGGGGTTTGGTCTGGGACTTCCTTGCTCTCCCTCTTCTCAAGTGCCTTAATAGTAGGGTAAGTTGTTAAGAGTGGGGGAGAGCAGGCTGGCAGCTCTCCAGTCAGGAGGCATAGTTTTTACTGAACAATCAAAGCACTTGGACTCTTGCTCTTTCTACTCTGAACTAATAAATCTGTTGCCAAGCTGGCTAGAAAAAAAAAAAAAAAAAA
人RELA原癌基因，NF-kB亚基(RELA)，转录变体4，mRNA NM_001243985.1(SEQ IDNO:21)
AGCGCGCAGGCGCGGCCGGATTCCGGGCAGTGACGCGACGGCGGGCCGCGCGGCGCATTTCCGCCTCTGGCGAATGGCTCGTCTGTAGTGCACGCCGCGGGCCCAGCTGCGACCCCGGCCCCGCCCCCGGGACCCCGGCCATGGACGAACTGTTCCCCCTCATCTTCCCGGCAGAGCCAGCCCAGGCCTCTGGCCCCTATGTGGAGATCATTGAGCAGCCCAAGCAGCGGGGCATGCGCTTCCGCTACAAGTGCGAGGGGCGCTCCGCGGGCAGCATCCCAGGCGAGAGGAGCACAGATACCACCAAGACCCACCCCACCATCAAGATCAATGGCTACACAGGACCAGGGACAGTGCGCATCTCCCTGGTCACCAAGGACCCTCCTCACCGGCCTCACCCCCACGAGCTTGTAGGAAAGGACTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCGCTGCATCCACAGTTTCCAGAACCTGGGAATCCAGTGTGTGAAGAAGCGGGACCTGGAGCAGGCTATCAGTCAGCGCATCCAGACCAACAACAACCCCTTCCAAGTTCCTATAGAAGAGCAGCGTGGGGACTACGACCTGAATGCTGTGCGGCTCTGCTTCCAGGTGACAGTGCGGGACCCATCAGGCAGGCCCCTCCGCCTGCCGCCTGTCCTTTCTCATCCCATCTTTGACAATCGTGCCCCCAACACTGCCGAGCTCAAGATCTGCCGAGTGAACCGAAACTCTGGCAGCTGCCTCGGTGGGGATGAGATCTTCCTACTGTGTGACAAGGTGCAGAAAGAGGACATTGAGGTGTATTTCACGGGACCAGGCTGGGAGGCCCGAGGCTCCTTTTCGCAAGCTGATGTGCACCGACAAGTGGCCATTGTGTTCCGGACCCCTCCCTACGCAGACCCCAGCCTGCAGGCTCCTGTGCGTGTCTCCATGCAGCTGCGGCGGCCTTCCGACCGGGAGCTCAGTGAGCCCATGGAATTCCAGTACCTGCCAGATACAGACGATCGTCACCGGATTGAGGAGAAACGTAAAAGGACATATGAGACCTTCAAGAGCATCATGAAGAAGAGTCCTTTCAGCGGACCCACCGACCCCCGGCCTCCACCTCGACGCATTGCTGTGCCTTCCCGCAGCTCAGCTTCTGTCCCCAAGCCAGCACCCCAGCCCTATCCCTTTACGTCATCCCTGAGCACCATCAACTATGATGAGTTTCCCACCATGGTGTTTCCTTCTGGGCAGATCAGCCAGGCCTCGGCCTTGGCCCCGGCCCCTCCCCAAGTCCTGCCCCAGGCTCCAGCCCCTGCCCCTGCTCCAGCCATGGTATCAGCTCTGGCCCAGAGGCCCCCCGACCCAGCTCCTGCTCCACTGGGGGCCCCGGGGCTCCCCAATGGCCTCCTTTCAGGAGATGAAGACTTCTCCTCCATTGCGGACATGGACTTCTCAGCCCTGCTGAGTCAGATCAGCTCCTAAGGGGGTGACGCCTGCCCTCCCCAGAGCACTGGGTTGCAGGGGATTGAAGCCCTCCAAAAGCACTTACGGATTCTGGTGGGGTGTGTTCCAACTGCCCCCAACTTTGTGGATGTCTTCCTTGGAGGGGGGAGCCATATTTTATTCTTTTATTGTCAGTATCTGTATCTCTCTCTCTTTTTGGAGGTGCTTAAGCAGAAGCATTAACTTCTCTGGAAAGGGGGGAGCTGGGGAAACTCAAACTTTTCCCCTGTCCTGATGGTCAGCTCCCTTCTCTGTAGGGAACTCTGGGGTCCCCCATCCCCATCCTCCAGCTTCTGGTACTCTCCTAGAGACAGAAGCAGGCTGGAGGTAAGGCCTTTGAGCCCACAAAGCCTTATCAAGTGTCTTCCATCATGGATTCATTACAGCTTAATCAAAATAACGCCCCAGATACCAGCCCCTGTATGGCACTGGCATTGTCCCTGTGCCTAACACCAGCGTTTGAGGGGCTGGCCTTCCTGCCCTACAGAGGTCTCTGCCGGCTCTTTCCTTGCTCAACCATGGCTGAAGGAAACCAGTGCAACAGCACTGGCTCTCTCCAGGATCCAGAAGGGGTTTGGTCTGGGACTTCCTTGCTCTCCCTCTTCTCAAGTGCCTTAATAGTAGGGTAAGTTGTTAAGAGTGGGGGAGAGCAGGCTGGCAGCTCTCCAGTCAGGAGGCATAGTTTTTACTGAACAATCAAAGCACTTGGACTCTTGCTCTTTCTACTCTGAACTAATAAATCTGTTGCCAAGCTGGCTAGAAAAAAAAAAAAAAAAAA
人RELA原癌基因，NF-kB亚基(RELA)，转录变体X1，mRNA XM_011545206.1(SEQ IDNO:22)
ATTCCGGGCAGTGACGCGACGGCGGGCCGCGCGGCGCATTTCCGCCTCTGGCGAATGGCTCGTCTGTAGTGCACGCCGCGGGCCCAGCTGCGACCCCGGCCCCGCCCCCGGGACCCCGGCCATGGACGAACTGTTCCCCCTCATCTTCCCGGCAGAGCCAGCCCAGGCCTCTGGCCCCTATGTGGAGATCATTGAGCAGCCCAAGCAGCGGGGCATGCGCTTCCGCTACAAGTGCGAGGGGCGCTCCGCGGGCAGCATCCCAGGCGAGAGGAGCACAGATACCACCAAGACCCACCCCACCATCAAGATCAATGGCTACACAGGACCAGGGACAGTGCGCATCTCCCTGGTCACCAAGGACCCTCCTCACCGGCCTCACCCCCACGAGCTTGTAGGAAAGGACTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCGCTGCATCCACAGTTTCCAGAACCTGGGAATCCAGTGTGTGAAGAAGCGGGACCTGGAGCAGGCTATCAGTCAGCGCATCCAGACCAACAACAACCCCTTCCAAGTTCCTATAGAAGAGCAGCGTGGGGACTACGACCTGAATGCTGTGCGGCTCTGCTTCCAGGTGACAGTGCGGGACCCATCAGGCAGGCCCCTCCGCCTGCCGCCTGTCCTTTCTCATCCCATCTTTGACAATCGTGCCCCCAACACTGCCGAGCTCAAGATCTGCCGAGTGAACCGAAACTCTGGCAGCTGCCTCGGTGGGGATGAGATCTTCCTACTGTGTGACAAGGTGCAGAAAGACGATCGTCACCGGATTGAGGAGAAACGTAAAAGGACATATGAGACCTTCAAGAGCATCATGAAGAAGAGTCCTTTCAGCGGACCCACCGACCCCCGGCCTCCACCTCGACGCATTGCTGTGCCTTCCCGCAGCTCAGCTTCTGTCCCCAAGCCAGCACCCCAGCCCTATCCCTTTACGTCATCCCTGAGCACCATCAACTATGATGAGTTTCCCACCATGGTGTTTCCTTCTGGGCAGATCAGCCAGGCCTCGGCCTTGGCCCCGGCCCCTCCCCAAGTCCTGCCCCAGGCTCCAGCCCCTGCCCCTGCTCCAGCCATGGTATCAGCTCTGGCCCAGGCCCCAGCCCCTGTCCCAGTCCTAGCCCCAGGCCCTCCTCAGGCTGTGGCCCCACCTGCCCCCAAGCCCACCCAGGCTGGGGAAGGAACGCTGTCAGAGGCCCTGCTGCAGCTGCAGTTTGATGATGAAGACCTGGGGGCCTTGCTTGGCAACAGCACAGACCCAGCTGTGTTCACAGACCTGGCATCCGTCGACAACTCCGAGTTTCAGCAGCTGCTGAACCAGGGCATACCTGTGGCCCCCCACACAACTGAGCCCATGCTGATGGAGTACCCTGAGGCTATAACTCGCCTAGTGACAGGGGCCCAGAGGCCCCCCGACCCAGCTCCTGCTCCACTGGGGGCCCCGGGGCTCCCCAATGGCCTCCTTTCAGGAGATGAAGACTTCTCCTCCATTGCGGACATGGACTTCTCAGCCCTGCTGAGTCAGATCAGCTCCTAAGGGGGTGACGCCTGCCCTCCCCAGAGCACTGGGTTGCAGGGGATTGAAGCCCTCCAAAAGCACTTACGGATTCTGGTGGGGTGTGTTCCAACTGCCCCCAACTTTGTGGATGTCTTCCTTGGAGGGGGGAGCCATATTTTATTCTTTTATTGTCAGTATCTGTATCTCTCTCTCTTTTTGGAGGTGCTTAAGCAGAAGCATTAACTTCTCTGGAAAGGGGGGAGCTGGGGAAACTCAAACTTTTCCCCTGTCCTGATGGTCAGCTCCCTTCTCTGTAGGGAACTCTGGGGTCCCCCATCCCCATCCTCCAGCTTCTGGTACTCTCCTAGAGACAGAAGCAGGCTGGAGGTAAGGCCTTTGAGCCCACAAAGCCTTATCAAGTGTCTTCCATCATGGATTCATTACAGCTTAATCAAAATAACGCCCCAGATACCAGCCCCTGTATGGCACTGGCATTGTCCCTGTGCCTAACACCAGCGTTTGAGGGGCTGGCCTTCCTGCCCTACAGAGGTCTCTGCCGGCTCTTTCCTTGCTCAACCATGGCTGAAGGAAACCAGTGCAACAGCACTGGCTCTCTCCAGGATCCAGAAGGGGTTTGGTCTGGGACTTCCTTGCTCTCCCTCTTCTCAAGTGCCTTAATAGTAGGGTAAGTTGTTAAGAGTGGGGGAGAGCAGGCTGGCAGCTCTCCAGTCAGGAGGCATAGTTTTTACTGAACAATCAAAGCACTTGGACTCTTGCTCTTTCTACTCTGAACTAATAAATCTGTTGCCAAGCTGG
人RELA原癌基因，NF-kB亚基(RELA)，转录变体X2，mRNA XM_011545207.1(SEQ IDNO:23)
ATTCCGGGCAGTGACGCGACGGCGGGCCGCGCGGCGCATTTCCGCCTCTGGCGAATGGCTCGTCTGTAGTGCACGCCGCGGGCCCAGCTGCGACCCCGGCCCCGCCCCCGGGACCCCGGCCATGGACGAACTGTTCCCCCTCATCTTCCCGGCAGAGCCAGCCCAGGCCTCTGGCCCCTATGTGGAGATCATTGAGCAGCCCAAGCAGCGGGGCATGCGCTTCCGCTACAAGTGCGAGGGGCGCTCCGCGGGCAGCATCCCAGGCGAGAGGAGCACAGATACCACCAAGACCCACCCCACCATCAAGATCAATGGCTACACAGGACCAGGGACAGTGCGCATCTCCCTGGTCACCAAGGACCCTCCTCACCGGCCTCACCCCCACGAGCTTGTAGGAAAGGACTGCCGGGATGGCTTCTATGAGGCTGAGCTCTGCCCGGACCGCTGCATCCACAGTTTCCAGAACCTGGGAATCCAGTGTGTGAAGAAGCGGGACCTGGAGCAGGCTATCAGTCAGCGCATCCAGACCAACAACAACCCCTTCCAAGTTCCTATAGAAGAGCAGCGTGGGGACTACGACCTGAATGCTGTGCGGCTCTGCTTCCAGGTGACAGTGCGGGACCCATCAGGCAGGCCCCTCCGCCTGCCGCCTGTCCTTTCTCATCCCATCTTTGACAATCACGATCGTCACCGGATTGAGGAGAAACGTAAAAGGACATATGAGACCTTCAAGAGCATCATGAAGAAGAGTCCTTTCAGCGGACCCACCGACCCCCGGCCTCCACCTCGACGCATTGCTGTGCCTTCCCGCAGCTCAGCTTCTGTCCCCAAGCCAGCACCCCAGCCCTATCCCTTTACGTCATCCCTGAGCACCATCAACTATGATGAGTTTCCCACCATGGTGTTTCCTTCTGGGCAGATCAGCCAGGCCTCGGCCTTGGCCCCGGCCCCTCCCCAAGTCCTGCCCCAGGCTCCAGCCCCTGCCCCTGCTCCAGCCATGGTATCAGCTCTGGCCCAGGCCCCAGCCCCTGTCCCAGTCCTAGCCCCAGGCCCTCCTCAGGCTGTGGCCCCACCTGCCCCCAAGCCCACCCAGGCTGGGGAAGGAACGCTGTCAGAGGCCCTGCTGCAGCTGCAGTTTGATGATGAAGACCTGGGGGCCTTGCTTGGCAACAGCACAGACCCAGCTGTGTTCACAGACCTGGCATCCGTCGACAACTCCGAGTTTCAGCAGCTGCTGAACCAGGGCATACCTGTGGCCCCCCACACAACTGAGCCCATGCTGATGGAGTACCCTGAGGCTATAACTCGCCTAGTGACAGGGGCCCAGAGGCCCCCCGACCCAGCTCCTGCTCCACTGGGGGCCCCGGGGCTCCCCAATGGCCTCCTTTCAGGAGATGAAGACTTCTCCTCCATTGCGGACATGGACTTCTCAGCCCTGCTGAGTCAGATCAGCTCCTAAGGGGGTGACGCCTGCCCTCCCCAGAGCACTGGGTTGCAGGGGATTGAAGCCCTCCAAAAGCACTTACGGATTCTGGTGGGGTGTGTTCCAACTGCCCCCAACTTTGTGGATGTCTTCCTTGGAGGGGGGAGCCATATTTTATTCTTTTATTGTCAGTATCTGTATCTCTCTCTCTTTTTGGAGGTGCTTAAGCAGAAGCATTAACTTCTCTGGAAAGGGGGGAGCTGGGGAAACTCAAACTTTTCCCCTGTCCTGATGGTCAGCTCCCTTCTCTGTAGGGAACTCTGGGGTCCCCCATCCCCATCCTCCAGCTTCTGGTACTCTCCTAGAGACAGAAGCAGGCTGGAGGTAAGGCCTTTGAGCCCACAAAGCCTTATCAAGTGTCTTCCATCATGGATTCATTACAGCTTAATCAAAATAACGCCCCAGATACCAGCCCCTGTATGGCACTGGCATTGTCCCTGTGCCTAACACCAGCGTTTGAGGGGCTGGCCTTCCTGCCCTACAGAGGTCTCTGCCGGCTCTTTCCTTGCTCAACCATGGCTGAAGGAAACCAGTGCAACAGCACTGGCTCTCTCCAGGATCCAGAAGGGGTTTGGTCTGGGACTTCCTTGCTCTCCCTCTTCTCAAGTGCCTTAATAGTAGGGTAAGTTGTTAAGAGTGGGGGAGAGCAGGCTGGCAGCTCTCCAGTCAGGAGGCATAGTTTTTACTGAACAATCAAAGCACTTGGACTCTTGCTCTTTCTACTCTGAACTAATAAATCTGTTGCCAAGCTGG
在一些实施方案中，编码Rel-A(p65)的核酸序列，如本文所述，与SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22或SEQ ID NO:23的序列至少80％相同。在一些实施方案中，编码Rel-A(p65)的核酸序列与SEQ ID NO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22或SEQ ID NO:23的序列80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同。在一些实施方案中，编码Rel-A(p65)的核酸，如本文所述，可以与SEQ IDNO:18、SEQ ID NO:19、SEQ ID NO:20、SEQ ID NO:21、SEQ ID NO:22或SEQ ID NO:23的序列有1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30或更多个核苷酸的不同。
“接头”是自然中产生的以分离单个蛋白质中的多个结构域的短氨基酸序列，并且通常可以分为三类：柔性、刚性和可切割。Chen,X.et al.,2013,Adv.Drug Deliv.Rev.,65,1357–1369。接头可以是天然的或合成的。采用许多接头以实现本发明，包括“柔性接头”。后者富含甘氨酸。Klein et al.,Protein Engineering,Design&Selection Vol.27,No.10,pp.325–330,2014；Priyanka et al.,Protein Sci.,2013 Feb；22(2):153–167。
在一些实施方案中，所述接头为合成接头。合成接头可以具有从约10氨基酸至约200氨基酸的长度，例如，从10至25个氨基酸、从25至50个氨基酸、从50至75个氨基酸、从75至100个氨基酸、从100至125个氨基酸、从125至150个氨基酸、从150至175个氨基酸或从175至200个氨基酸。合成接头可以具有从10至30个氨基酸的长度，例如，10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30个氨基酸。合成接头可以具有从30至50个氨基酸的长度，例如，从30至35个氨基酸、从35至40个氨基酸、从40至45个氨基酸或从45至50个氨基酸。
在一些实施方案中，所述接头为柔性接头。在一些实施方案中，所述接头富含甘氨酸(Gly或G)残基。在一些实施方案中，所述接头富含丝氨酸(Ser或S)残基。在一些实施方案中，所述接头富含甘氨酸和丝氨酸残基。在一些实施方案中，所述接头具有一个或多个甘氨酸-丝氨酸残基对(GS)，例如，1、2、3、4、5、6、7、8、9或10或更多个GS对。在一些实施方案中，所述接头具有一个或多个Gly-Gly-Gly-Ser(GGGS)序列，例如，1、2、3、4、5、6、7、8、9或10或更多个GGGS序列。在一些实施方案中，所述接头具有一个或多个Gly-Gly-Gly-Gly-Ser(GGGGS)序列，例如，1、2、3、4、5、6、7、8、9或10或更多个GGGGS序列。在一些实施方案中，所述接头具有一个或多个Gly-Gly-Ser-Gly(GGSG)序列，例如，1、2、3、4、5、6、7、8、9或10或更多个GGSG序列。在一些实施方案中，所述接头为GSAAAGGSGGSGGS(SEQ ID NO:3)。在一些实施方案中，所述接头为GGGSGGGS(SEQ ID NO:4)。
“天然的或自然的Notch”意指涵盖所有已知形式的Notch受体。在人中，已知四种形式的Notch。Joanna Pancewicz:BMC Cancer 11(1):502·November2011。人Notch家族包括四种受体和五种配体。
在一些实施方案中，嵌合Notch受体多肽含有人Notch1、Notch2、Notch3或Notch4的全部或一部分。在一些实施方案中，嵌合Notch受体多肽含有SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27或SEQ ID NO:28的全部或一部分。在一些实施方案中，Notch的“一部分”包含三个NLR结构域、跨膜结构域以及包括Notch的天然核定位序列(NLS)的短胞质片段。
人神经原基因座notch同源蛋白质1前蛋白NP_060087.3(SEQ ID NO:24)
MPPLLAPLLCLALLPALAARGPRCSQPGETCLNGGKCEAANGTEACVCGGAFVGPRCQDPNPCLSTPCKNAGTCHVVDRRGVADYACSCALGFSGPLCLTPLDNACLTNPCRNGGTCDLLTLTEYKCRCPPGWSGKSCQQADPCASNPCANGGQCLPFEASYICHCPPSFHGPTCRQDVNECGQKPGLCRHGGTCHNEVGSYRCVCRATHTGPNCERPYVPCSPSPCQNGGTCRPTGDVTHECACLPGFTGQNCEENIDDCPGNNCKNGGACVDGVNTYNCRCPPEWTGQYCTEDVDECQLMPNACQNGGTCHNTHGGYNCVCVNGWTGEDCSENIDDCASAACFHGATCHDRVASFYCECPHGRTGLLCHLNDACISNPCNEGSNCDTNPVNGKAICTCPSGYTGPACSQDVDECSLGANPCEHAGKCINTLGSFECQCLQGYTGPRCEIDVNECVSNPCQNDATCLDQIGEFQCICMPGYEGVHCEVNTDECASSPCLHNGRCLDKINEFQCECPTGFTGHLCQYDVDECASTPCKNGAKCLDGPNTYTCVCTEGYTGTHCEVDIDECDPDPCHYGSCKDGVATFTCLCRPGYTGHHCETNINECSSQPCRHGGTCQDRDNAYLCFCLKGTTGPNCEINLDDCASSPCDSGTCLDKIDGYECACEPGYTGSMCNINIDECAGNPCHNGGTCEDGINGFTCRCPEGYHDPTCLSEVNECNSNPCVHGACRDSLNGYKCDCDPGWSGTNCDINNNECESNPCVNGGTCKDMTSGYVCTCREGFSGPNCQTNINECASNPCLNQGTCIDDVAGYKCNCLLPYTGATCEVVLAPCAPSPCRNGGECRQSEDYESFSCVCPTGWQGQTCEVDINECVLSPCRHGASCQNTHGGYRCHCQAGYSGRNCETDIDDCRPNPCHNGGSCTDGINTAFCDCLPGFRGTFCEEDINECASDPCRNGANCTDCVDSYTCTCPAGFSGIHCENNTPDCTESSCFNGGTCVDGINSFTCLCPPGFTGSYCQHDVNECDSQPCLHGGTCQDGCGSYRCTCPQGYTGPNCQNLVHWCDSSPCKNGGKCWQTHTQYRCECPSGWTGLYCDVPSVSCEVAAQRQGVDVARLCQHGGLCVDAGNTHHCRCQAGYTGSYCEDLVDECSPSPCQNGATCTDYLGGYSCKCVAGYHGVNCSEEIDECLSHPCQNGGTCLDLPNTYKCSCPRGTQGVHCEINVDDCNPPVDPVSRSPKCFNNGTCVDQVGGYSCTCPPGFVGERCEGDVNECLSNPCDARGTQNCVQRVNDFHCECRAGHTGRRCESVINGCKGKPCKNGGTCAVASNTARGFICKCPAGFEGATCENDARTCGSLRCLNGGTCISGPRSPTCLCLGPFTGPECQFPASSPCLGGNPCYNQGTCEPTSESPFYRCLCPAKFNGLLCHILDYSFGGGAGRDIPPPLIEEACELPECQEDAGNKVCSLQCNNHACGWDGGDCSLNFNDPWKNCTQSLQCWKYFSDGHCDSQCNSAGCLFDGFDCQRAEGQCNPLYDQYCKDHFSDGHCDQGCNSAECEWDGLDCAEHVPERLAAGTLVVVVLMPPEQLRNSSFHFLRELSRVLHTNVVFKRDAHGQQMIFPYYGREEELRKHPIKRAAEGWAAPDALLGQVKASLLPGGSEGGRRRRELDPMDVRGSIVYLEIDNRQCVQASSQCFQSATDVAAFLGALASLGSLNIPYKIEAVQSETVEPPPPAQLHFMYVAAAAFVLLFFVGCGVLLSRKRRRQHGQLWFPEGFKVSEASKKKRREPLGEDSVGLKPLKNASDGALMDDNQNEWGDEDLETKKFRFEEPVVLPDLDDQTDHRQWTQQHLDAADLRMSAMAPTPPQGEVDADCMDVNVRGPDGFTPLMIASCSGGGLETGNSEEEEDAPAVISDFIYQGASLHNQTDRTGETALHLAARYSRSDAAKRLLEASADANIQDNMGRTPLHAAVSADAQGVFQILIRNRATDLDARMHDGTTPLILAARLAVEGMLEDLINSHADVNAVDDLGKSALHWAAAVNNVDAAVVLLKNGANKDMQNNREETPLFLAAREGSYETAKVLLDHFANRDITDHMDRLPRDIAQERMHHDIVRLLDEYNLVRSPQLHGAPLGGTPTLSPPLCSPNGYLGSLKPGVQGKKVRKPSSKGLACGSKEAKDLKARRKKSQDGKGCLLDSSGMLSPVDSLESPHGYLSDVASPPLLPSPFQQSPSVPLNHLPGMPDTHLGIGHLNVAAKPEMAALGGGGRLAFETGPPRLSHLPVASGTSTVLGSSSGGALNFTVGGSTSLNGQCEWLSRLQSGMVPNQYNPLRGSVAPGPLSTQAPSLQHGMVGPLHSSLAASALSQMMSYQGLPSTRLATQPHLVQTQQVQPQNLQMQQQNLQPANIQQQQSLQPPPPPPQPHLGVSSAASGHLGRSFLSGEPSQADVQPLGPSSLAVHTILPQESPALPTSLPSSLVPPVTAAQFLTPPSQHSYSSPVDNTPSHQLQVPEHPFLTPSPESPDQWSSSSPHSNVSDWSEGVSSPPTSMQSQIARIPEAFK
人神经原基因座notch同源蛋白质2同种型1前蛋白NP_077719.2(SEQ ID NO:25)
MPALRPALLWALLALWLCCAAPAHALQCRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGEYCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYSTSHPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWTDACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCETDVNECDIPGHCQHGGTCLNLPGSYQCQCPQGFTGQYCDSLYVPCAPSPCVNGGTCRQTGDFTFECNCLPGFEGSTCERNIDDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVDECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPGSTCIDRVASFSCMCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYICTCPQGYKGADCTEDVDECAMANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMDINECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELEINECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTPCLNGAKCIDHPNGYECQCATGFTGVLCEENIDNCDPDPCHHGQCQDGIDSYTCICNPGYMGAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEINFDDCASNPCIHGICMDGINRYSCVCSPGFTGQRCNIDIDECASNPCRKGATCINGVNGFRCICPEGPHHPSCYSQVNECLSNPCIHGNCTGGLSGYKCLCDAGWVGINCEVDKNECLSNPCQNGGTCDNLVNGYRCTCKKGFKGYNCQVNIDECASNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTVLAPCSPNPCENAAVCKESPNFESYTCLCAPGWQGQRCTIDIDECISKPCMNHGLCHNTQGSYMCECPPGFSGMDCEEDIDDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTDMNECLSEPCKNGGTCSDYVNSYTCKCQAGFDGVHCENNINECTESSCFNGGTCVDGINSFSCLCPVGFTGSFCLHEINECSSHPCLNEGTCVDGLGTYRCSCPLGYTGKNCQTLVNLCSRSPCKNKGTCVQKKAESQCLCPSGWAGAYCDVPNVSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLGYTGSYCEEQLDECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGGTCIDLVNHFKCSCPPGTRGLLCEENIDDCARGPHCLNGGQCMDRIGGYSCRCLPGFAGERCEGDINECLSNPCSSEGSLDCIQLTNDYLCVCRSAFTGRHCETFVDVCPQMPCLNGGTCAVASNMPDGFICRCPPGFSGARCQSSCGQVKCRKGEQCVHTASGPRCFCPSPRDCESGCASSPCQHGGSCHPQRQPPYYSCQCAPPFSGSRCELYTAPPSTPPATCLSQYCADKARDGVCDEACNSHACQWDGGDCSLTMENPWANCSSPLPCWDYINNQCDELCNTVECLFDNFECQGNSKTCKYDKYCADHFKDNHCDQGCNSEECGWDGLDCAADQPENLAEGTLVIVVLMPPEQLLQDARSFLRALGTLLHTNLRIKRDSQGELMVYPYYGEKSAAMKKQRMTRRSLPGEQEQEVAGSKVFLEIDNRQCVQDSDHCFKNTDAAAALLASHAIQGTLSYPLVSVVSESLTPERTQLLYLLAVAVVIILFIILLGVIMAKRKRKHGSLWLPEGFTLRRDASNHKRREPVGQDAVGLKNLSVQVSEANLIGTGTSEHWVDDEGPQPKKVKAEDEALLSEEDDPIDRRPWTQQHLEAADIRRTPSLALTPPQAEQEVDVLDVNVRGPDGCTPLMLASLRGGSSDLSDEDEDAEDSSANIITDLVYQGASLQAQTDRTGEMALHLAARYSRADAAKRLLDAGADANAQDNMGRCPLHAAVAADAQGVFQILIRNRVTDLDARMNDGTTPLILAARLAVEGMVAELINCQADVNAVDDHGKSALHWAAAVNNVEATLLLLKNGANRDMQDNKEETPLFLAAREGSYEAAKILLDHFANRDITDHMDRLPRDVARDRMHHDIVRLLDEYNVTPSPPGTVLTSALSPVICGPNRSFLSLKHTPMGKKSRRPSAKSTMPTSLPNLAKEAKDAKGSRRKKSLSEKVQLSESSVTLSPVDSLESPHTYVSDTTSSPMITSPGILQASPNPMLATAAPPAPVHAQHALSFSNLHEMQPLAHGASTVLPSVSQLLSHHHIVSPGSGSAGSLSRLHPVPVPADWMNRMEVNETQYNEMFGMVLAPAEGTHPGIAPQSRPPEGKHITTPREPLPPIVTFQLIPKGSIAQPAGAPQPQSTCPPAVAGPLPTMYQIPEMARLPSVAFPTAMMPQQDGQVAQTILPAYHPFPASVGKYPTPPSQHSYASSNAAERTPSHSGHLQGEHPYLTPSPESPDQWSSSSPHSASDWSDVTTSPTPGGAGGGQRGPGTHMSEPPHNNMQVYA
人神经原基因座notch同源蛋白质2同种型2前体NP_001186930.1(SEQ ID NO:26)
MPALRPALLWALLALWLCCAAPAHALQCRDGYEPCVNEGMCVTYHNGTGYCKCPEGFLGEYCQHRDPCEKNRCQNGGTCVAQAMLGKATCRCASGFTGEDCQYSTSHPCFVSRPCLNGGTCHMLSRDTYECTCQVGFTGKECQWTDACLSHPCANGSTCTTVANQFSCKCLTGFTGQKCETDVNECDIPGHCQHGGTCLNLPGSYQCQCPQGFTGQYCDSLYVPCAPSPCVNGGTCRQTGDFTFECNCLPGFEGSTCERNIDDCPNHRCQNGGVCVDGVNTYNCRCPPQWTGQFCTEDVDECLLQPNACQNGGTCANRNGGYGCVCVNGWSGDDCSENIDDCAFASCTPGSTCIDRVASFSCMCPEGKAGLLCHLDDACISNPCHKGALCDTNPLNGQYICTCPQGYKGADCTEDVDECAMANSNPCEHAGKCVNTDGAFHCECLKGYAGPRCEMDINECHSDPCQNDATCLDKIGGFTCLCMPGFKGVHCELEINECQSNPCVNNGQCVDKVNRFQCLCPPGFTGPVCQIDIDDCSSTPCLNGAKCIDHPNGYECQCATGFTGVLCEENIDNCDPDPCHHGQCQDGIDSYTCICNPGYMGAICSDQIDECYSSPCLNDGRCIDLVNGYQCNCQPGTSGVNCEINFDDCASNPCIHGICMDGINRYSCVCSPGFTGQRCNIDIDECASNPCRKGATCINGVNGFRCICPEGPHHPSCYSQVNECLSNPCIHGNCTGGLSGYKCLCDAGWVGINCEVDKNECLSNPCQNGGTCDNLVNGYRCTCKKGFKGYNCQVNIDECASNPCLNQGTCFDDISGYTCHCVLPYTGKNCQTVLAPCSPNPCENAAVCKESPNFESYTCLCAPGWQGQRCTIDIDECISKPCMNHGLCHNTQGSYMCECPPGFSGMDCEEDIDDCLANPCQNGGSCMDGVNTFSCLCLPGFTGDKCQTDMNECLSEPCKNGGTCSDYVNSYTCKCQAGFDGVHCENNINECTESSCFNGGTCVDGINSFSCLCPVGFTGSFCLHEINECSSHPCLNEGTCVDGLGTYRCSCPLGYTGKNCQTLVNLCSRSPCKNKGTCVQKKAESQCLCPSGWAGAYCDVPNVSCDIAASRRGVLVEHLCQHSGVCINAGNTHYCQCPLGYTGSYCEEQLDECASNPCQHGATCSDFIGGYRCECVPGYQGVNCEYEVDECQNQPCQNGGTCIDLVNHFKCSCPPGTRGMKSSLSIFHPGHCLKL
人神经原基因座notch同源蛋白质3前体NP_000426.2(SEQ ID NO:27)
MGPGARGRRRRRRPMSPPPPPPPVRALPLLLLLAGPGAAAPPCLDGSPCANGGRCTQLPSREAACLCPPGWVGERCQLEDPCHSGPCAGRGVCQSSVVAGTARFSCRCPRGFRGPDCSLPDPCLSSPCAHGARCSVGPDGRFLCSCPPGYQGRSCRSDVDECRVGEPCRHGGTCLNTPGSFRCQCPAGYTGPLCENPAVPCAPSPCRNGGTCRQSGDLTYDCACLPGFEGQNCEVNVDDCPGHRCLNGGTCVDGVNTYNCQCPPEWTGQFCTEDVDECQLQPNACHNGGTCFNTLGGHSCVCVNGWTGESCSQNIDDCATAVCFHGATCHDRVASFYCACPMGKTGLLCHLDDACVSNPCHEDAICDTNPVNGRAICTCPPGFTGGACDQDVDECSIGANPCEHLGRCVNTQGSFLCQCGRGYTGPRCETDVNECLSGPCRNQATCLDRIGQFTCICMAGFTGTYCEVDIDECQSSPCVNGGVCKDRVNGFSCTCPSGFSGSTCQLDVDECASTPCRNGAKCVDQPDGYECRCAEGFEGTLCDRNVDDCSPDPCHHGRCVDGIASFSCACAPGYTGTRCESQVDECRSQPCRHGGKCLDLVDKYLCRCPSGTTGVNCEVNIDDCASNPCTFGVCRDGINRYDCVCQPGFTGPLCNVEINECASSPCGEGGSCVDGENGFRCLCPPGSLPPLCLPPSHPCAHEPCSHGICYDAPGGFRCVCEPGWSGPRCSQSLARDACESQPCRAGGTCSSDGMGFHCTCPPGVQGRQCELLSPCTPNPCEHGGRCESAPGQLPVCSCPQGWQGPRCQQDVDECAGPAPCGPHGICTNLAGSFSCTCHGGYTGPSCDQDINDCDPNPCLNGGSCQDGVGSFSCSCLPGFAGPRCARDVDECLSNPCGPGTCTDHVASFTCTCPPGYGGFHCEQDLPDCSPSSCFNGGTCVDGVNSFSCLCRPGYTGAHCQHEADPCLSRPCLHGGVCSAAHPGFRCTCLESFTGPQCQTLVDWCSRQPCQNGGRCVQTGAYCLCPPGWSGRLCDIRSLPCREAAAQIGVRLEQLCQAGGQCVDEDSSHYCVCPEGRTGSHCEQEVDPCLAQPCQHGGTCRGYMGGYMCECLPGYNGDNCEDDVDECASQPCQHGGSCIDLVARYLCSCPPGTLGVLCEINEDDCGPGPPLDSGPRCLHNGTCVDLVGGFRCTCPPGYTGLRCEADINECRSGACHAAHTRDCLQDPGGGFRCLCHAGFSGPRCQTVLSPCESQPCQHGGQCRPSPGPGGGLTFTCHCAQPFWGPRCERVARSCRELQCPVGVPCQQTPRGPRCACPPGLSGPSCRSFPGSPPGASNASCAAAPCLHGGSCRPAPLAPFFRCACAQGWTGPRCEAPAAAPEVSEEPRCPRAACQAKRGDQRCDRECNSPGCGWDGGDCSLSVGDPWRQCEALQCWRLFNNSRCDPACSSPACLYDNFDCHAGGRERTCNPVYEKYCADHFADGRCDQGCNTEECGWDGLDCASEVPALLARGVLVLTVLLPPEELLRSSADFLQRLSAILRTSLRFRLDAHGQAMVFPYHRPSPGSEPRARRELAPEVIGSVVMLEIDNRLCLQSPENDHCFPDAQSAADYLGALSAVERLDFPYPLRDVRGEPLEPPEPSVPLLPLLVAGAVLLLVILVLGVMVARRKREHSTLWFPEGFSLHKDVASGHKGRREPVGQDALGMKNMAKGESLMGEVATDWMDTECPEAKRLKVEEPGMGAEEAVDCRQWTQHHLVAADIRVAPAMALTPPQGDADADGMDVNVRGPDGFTPLMLASFCGGALEPMPTEEDEADDTSASIISDLICQGAQLGARTDRTGETALHLAARYARADAAKRLLDAGADTNAQDHSGRTPLHTAVTADAQGVFQILIRNRSTDLDARMADGSTALILAARLAVEGMVEELIASHADVNAVDELGKSALHWAAAVNNVEATLALLKNGANKDMQDSKEETPLFLAAREGSYEAAKLLLDHFANREITDHLDRLPRDVAQERLHQDIVRLLDQPSGPRSPPGPHGLGPLLCPPGAFLPGLKAAQSGSKKSRRPPGKAGLGPQGPRGRGKKLTLACPGPLADSSVTLSPVDSLDSPRPFGGPPASPGGFPLEGPYAAATATAVSLAQLGGPGRAGLGRQPPGGCVLSLGLLNPVAVPLDWARLPPPAPPGPSFLLPLAPGPQLLNPGTPVSPQERPPPYLAVPGHGEEYPAAGAHSSPPKARFLRVPSEHPYLTPSPESPEHWASPSPPSLSDWSESTPSPATATGAMATTTGALPAQPLPLSVPSSLAQAQTQLGPQPEVTPKRQVLA
人神经原基因座notch同源蛋白质4前蛋白NP_004548.3(SEQ ID NO:28)
MQPPSLLLLLLLLLLLCVSVVRPRGLLCGSFPEPCANGGTCLSLSLGQGTCQCAPGFLGETCQFPDPCQNAQLCQNGGSCQALLPAPLGLPSSPSPLTPSFLCTCLPGFTGERCQAKLEDPCPPSFCSKRGRCHIQASGRPQCSCMPGWTGEQCQLRDFCSANPCVNGGVCLATYPQIQCHCPPGFEGHACERDVNECFQDPGPCPKGTSCHNTLGSFQCLCPVGQEGPRCELRAGPCPPRGCSNGGTCQLMPEKDSTFHLCLCPPGFIGPDCEVNPDNCVSHQCQNGGTCQDGLDTYTCLCPETWTGWDCSEDVDECETQGPPHCRNGGTCQNSAGSFHCVCVSGWGGTSCEENLDDCIAATCAPGSTCIDRVGSFSCLCPPGRTGLLCHLEDMCLSQPCHGDAQCSTNPLTGSTLCLCQPGYSGPTCHQDLDECLMAQQGPSPCEHGGSCLNTPGSFNCLCPPGYTGSRCEADHNECLSQPCHPGSTCLDLLATFHCLCPPGLEGQLCEVETNECASAPCLNHADCHDLLNGFQCICLPGFSGTRCEEDIDECRSSPCANGGQCQDQPGAFHCKCLPGFEGPRCQTEVDECLSDPCPVGASCLDLPGAFFCLCPSGFTGQLCEVPLCAPNLCQPKQICKDQKDKANCLCPDGSPGCAPPEDNCTCHHGHCQRSSCVCDVGWTGPECEAELGGCISAPCAHGGTCYPQPSGYNCTCPTGYTGPTCSEEMTACHSGPCLNGGSCNPSPGGYYCTCPPSHTGPQCQTSTDYCVSAPCFNGGTCVNRPGTFSCLCAMGFQGPRCEGKLRPSCADSPCRNRATCQDSPQGPRCLCPTGYTGGSCQTLMDLCAQKPCPRNSHCLQTGPSFHCLCLQGWTGPLCNLPLSSCQKAALSQGIDVSSLCHNGGLCVDSGPSYFCHCPPGFQGSLCQDHVNPCESRPCQNGATCMAQPSGYLCQCAPGYDGQNCSKELDACQSQPCHNHGTCTPKPGGFHCACPPGFVGLRCEGDVDECLDQPCHPTGTAACHSLANAFYCQCLPGHTGQWCEVEIDPCHSQPCFHGGTCEATAGSPLGFICHCPKGFEGPTCSHRAPSCGFHHCHHGGLCLPSPKPGFPPRCACLSGYGGPDCLTPPAPKGCGPPSPCLYNGSCSETTGLGGPGFRCSCPHSSPGPRCQKPGAKGCEGRSGDGACDAGCSGPGGNWDGGDCSLGVPDPWKGCPSHSRCWLLFRDGQCHPQCDSEECLFDGYDCETPPACTPAYDQYCHDHFHNGHCEKGCNTAECGWDGGDCRPEDGDPEWGPSLALLVVLSPPALDQQLFALARVLSLTLRVGLWVRKDRDGRDMVYPYPGARAEEKLGGTRDPTYQERAAPQTQPLGKETDSLSAGFVVVMGVDLSRCGPDHPASRCPWDPGLLLRFLAAMAAVGALEPLLPGPLLAVHPHAGTAPPANQLPWPVLCSPVAGVILLALGALLVLQLIRRRRREHGALWLPPGFTRRPRTQSAPHRRRPPLGEDSIGLKALKPKAEVDEDGVVMCSGPEEGEEVGQAEETGPPSTCQLWSLSGGCGALPQAAMLTPPQESEMEAPDLDTRGPDGVTPLMSAVCCGEVQSGTFQGAWLGCPEPWEPLLDGGACPQAHTVGTGETPLHLAARFSRPTAARRLLEAGANPNQPDRAGRTPLHAAVAADAREVCQLLLRSRQTAVDARTEDGTTPLMLAARLAVEDLVEELIAAQADVGARDKWGKTALHWAAAVNNARAARSLLQAGADKDAQDNREQTPLFLAAREGAVEVAQLLLGLGAARELRDQAGLAPADVAHQRNHWDLLTLLEGAGPPEARHKATPGREAGPFPRARTVSVSVPPHGGGALPRCRTLSAGAGPRGGGACLQARTWSVDLAARGGGAYSHCRSLSGVGAGGGPTPRGRRFSAGMRGPRPNPAIMRGRYGVAAGRGGRVSTDDWPCDWVALGACGSASNIPIPPPCLTPSPERGSPQLDCGPPALQEMPINQGGEGKK
在一些实施方案中，嵌合Notch受体多肽的Notch核心含有SEQ ID NO:24、SEQ IDNO:25、SEQ ID NO:26、SEQ ID NO:27或SEQ ID NO:28的一部分。在一些实施方案中，嵌合Notch受体多肽含有SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27或SEQ IDNO:28的50至1000个氨基酸。在一些实施方案中，嵌合Notch受体多肽含有SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27或SEQ ID NO:28的50至900个氨基酸、100至800个氨基酸、200至700个氨基酸、300至600个氨基酸、400至500个氨基酸。在一些实施方案中，嵌合Notch受体多肽含有SEQ ID NO:27的氨基酸1374至1734。
在一些实施方案中，Notch的氨基酸序列，如本文所述，与SEQ ID NO:24、SEQ IDNO:25、SEQ ID NO:26、SEQ ID NO:27或SEQ ID NO:28中相应的氨基酸序列至少80％相同。在一些实施方案中，Notch的氨基酸序列与SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27或SEQ ID NO:28中相应的氨基酸序列80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同。在一些实施方案中，Notch的氨基酸序列，如本文所述，可以与SEQ ID NO:24、SEQ ID NO:25、SEQ ID NO:26、SEQ ID NO:27或SEQ ID NO:28的氨基酸序列有1至50个氨基酸的不同，例如，1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、25、30、35、40、45、50、55、60、65、70、75、80、85、90、95或100个氨基酸的不同。
在一些实施方案中，Notch的mRNA序列，如本文所述，为SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32或SEQ ID NO:33。
人notch 1(NOTCH1)mRNA NM_017617.4(SEQ ID NO:29)
ATGCCGCCGCTCCTGGCGCCCCTGCTCTGCCTGGCGCTGCTGCCCGCGCTCGCCGCACGAGGCCCGCGATGCTCCCAGCCCGGTGAGACCTGCCTGAATGGCGGGAAGTGTGAAGCGGCCAATGGCACGGAGGCCTGCGTCTGTGGCGGGGCCTTCGTGGGCCCGCGATGCCAGGACCCCAACCCGTGCCTCAGCACCCCCTGCAAGAACGCCGGGACATGCCACGTGGTGGACCGCAGAGGCGTGGCAGACTATGCCTGCAGCTGTGCCCTGGGCTTCTCTGGGCCCCTCTGCCTGACACCCCTGGACAATGCCTGCCTCACCAACCCCTGCCGCAACGGGGGCACCTGCGACCTGCTCACGCTGACGGAGTACAAGTGCCGCTGCCCGCCCGGCTGGTCAGGGAAATCGTGCCAGCAGGCTGACCCGTGCGCCTCCAACCCCTGCGCCAACGGTGGCCAGTGCCTGCCCTTCGAGGCCTCCTACATCTGCCACTGCCCACCCAGCTTCCATGGCCCCACCTGCCGGCAGGATGTCAACGAGTGTGGCCAGAAGCCCGGGCTTTGCCGCCACGGAGGCACCTGCCACAACGAGGTCGGCTCCTACCGCTGCGTCTGCCGCGCCACCCACACTGGCCCCAACTGCGAGCGGCCCTACGTGCCCTGCAGCCCCTCGCCCTGCCAGAACGGGGGCACCTGCCGCCCCACGGGCGACGTCACCCACGAGTGTGCCTGCCTGCCAGGCTTCACCGGCCAGAACTGTGAGGAAAATATCGACGATTGTCCAGGAAACAACTGCAAGAACGGGGGTGCCTGTGTGGACGGCGTGAACACCTACAACTGCCGCTGCCCGCCAGAGTGGACAGGTCAGTACTGTACCGAGGATGTGGACGAGTGCCAGCTGATGCCAAATGCCTGCCAGAACGGCGGGACCTGCCACAACACCCACGGTGGCTACAACTGCGTGTGTGTCAACGGCTGGACTGGTGAGGACTGCAGCGAGAACATTGATGACTGTGCCAGCGCCGCCTGCTTCCACGGCGCCACCTGCCATGACCGTGTGGCCTCCTTCTACTGCGAGTGTCCCCATGGCCGCACAGGTCTGCTGTGCCACCTCAACGACGCATGCATCAGCAACCCCTGTAACGAGGGCTCCAACTGCGACACCAACCCTGTCAATGGCAAGGCCATCTGCACCTGCCCCTCGGGGTACACGGGCCCGGCCTGCAGCCAGGACGTGGATGAGTGCTCGCTGGGTGCCAACCCCTGCGAGCATGCGGGCAAGTGCATCAACACGCTGGGCTCCTTCGAGTGCCAGTGTCTGCAGGGCTACACGGGCCCCCGATGCGAGATCGACGTCAACGAGTGCGTCTCGAACCCGTGCCAGAACGACGCCACCTGCCTGGACCAGATTGGGGAGTTCCAGTGCATCTGCATGCCCGGCTACGAGGGTGTGCACTGCGAGGTCAACACAGACGAGTGTGCCAGCAGCCCCTGCCTGCACAATGGCCGCTGCCTGGACAAGATCAATGAGTTCCAGTGCGAGTGCCCCACGGGCTTCACTGGGCATCTGTGCCAGTACGATGTGGACGAGTGTGCCAGCACCCCCTGCAAGAATGGTGCCAAGTGCCTGGACGGACCCAACACTTACACCTGTGTGTGCACGGAAGGGTACACGGGGACGCACTGCGAGGTGGACATCGATGAGTGCGACCCCGACCCCTGCCACTACGGCTCCTGCAAGGACGGCGTCGCCACCTTCACCTGCCTCTGCCGCCCAGGCTACACGGGCCACCACTGCGAGACCAACATCAACGAGTGCTCCAGCCAGCCCTGCCGCCACGGGGGCACCTGCCAGGACCGCGACAACGCCTACCTCTGCTTCTGCCTGAAGGGGACCACAGGACCCAACTGCGAGATCAACCTGGATGACTGTGCCAGCAGCCCCTGCGACTCGGGCACCTGTCTGGACAAGATCGATGGCTACGAGTGTGCCTGTGAGCCGGGCTACACAGGGAGCATGTGTAACATCAACATCGATGAGTGTGCGGGCAACCCCTGCCACAACGGGGGCACCTGCGAGGACGGCATCAATGGCTTCACCTGCCGCTGCCCCGAGGGCTACCACGACCCCACCTGCCTGTCTGAGGTCAATGAGTGCAACAGCAACCCCTGCGTCCACGGGGCCTGCCGGGACAGCCTCAACGGGTACAAGTGCGACTGTGACCCTGGGTGGAGTGGGACCAACTGTGACATCAACAACAATGAGTGTGAATCCAACCCTTGTGTCAACGGCGGCACCTGCAAAGACATGACCAGTGGCTACGTGTGCACCTGCCGGGAGGGCTTCAGCGGTCCCAACTGCCAGACCAACATCAACGAGTGTGCGTCCAACCCATGTCTGAACCAGGGCACGTGTATTGACGACGTTGCCGGGTACAAGTGCAACTGCCTGCTGCCCTACACAGGTGCCACGTGTGAGGTGGTGCTGGCCCCGTGTGCCCCCAGCCCCTGCAGAAACGGCGGGGAGTGCAGGCAATCCGAGGACTATGAGAGCTTCTCCTGTGTCTGCCCCACGGGCTGGCAAGGGCAGACCTGTGAGGTCGACATCAACGAGTGCGTTCTGAGCCCGTGCCGGCACGGCGCATCCTGCCAGAACACCCACGGCGGCTACCGCTGCCACTGCCAGGCCGGCTACAGTGGGCGCAACTGCGAGACCGACATCGACGACTGCCGGCCCAACCCGTGTCACAACGGGGGCTCCTGCACAGACGGCATCAACACGGCCTTCTGCGACTGCCTGCCCGGCTTCCGGGGCACTTTCTGTGAGGAGGACATCAACGAGTGTGCCAGTGACCCCTGCCGCAACGGGGCCAACTGCACGGACTGCGTGGACAGCTACACGTGCACCTGCCCCGCAGGCTTCAGCGGGATCCACTGTGAGAACAACACGCCTGACTGCACAGAGAGCTCCTGCTTCAACGGTGGCACCTGCGTGGACGGCATCAACTCGTTCACCTGCCTGTGTCCACCCGGCTTCACGGGCAGCTACTGCCAGCACGATGTCAATGAGTGCGACTCACAGCCCTGCCTGCATGGCGGCACCTGTCAGGACGGCTGCGGCTCCTACAGGTGCACCTGCCCCCAGGGCTACACTGGCCCCAACTGCCAGAACCTTGTGCACTGGTGTGACTCCTCGCCCTGCAAGAACGGCGGCAAATGCTGGCAGACCCACACCCAGTACCGCTGCGAGTGCCCCAGCGGCTGGACCGGCCTTTACTGCGACGTGCCCAGCGTGTCCTGTGAGGTGGCTGCGCAGCGACAAGGTGTTGACGTTGCCCGCCTGTGCCAGCATGGAGGGCTCTGTGTGGACGCGGGCAACACGCACCACTGCCGCTGCCAGGCGGGCTACACAGGCAGCTACTGTGAGGACCTGGTGGACGAGTGCTCACCCAGCCCCTGCCAGAACGGGGCCACCTGCACGGACTACCTGGGCGGCTACTCCTGCAAGTGCGTGGCCGGCTACCACGGGGTGAACTGCTCTGAGGAGATCGACGAGTGCCTCTCCCACCCCTGCCAGAACGGGGGCACCTGCCTCGACCTCCCCAACACCTACAAGTGCTCCTGCCCACGGGGCACTCAGGGTGTGCACTGTGAGATCAACGTGGACGACTGCAATCCCCCCGTTGACCCCGTGTCCCGGAGCCCCAAGTGCTTTAACAACGGCACCTGCGTGGACCAGGTGGGCGGCTACAGCTGCACCTGCCCGCCGGGCTTCGTGGGTGAGCGCTGTGAGGGGGATGTCAACGAGTGCCTGTCCAATCCCTGCGACGCCCGTGGCACCCAGAACTGCGTGCAGCGCGTCAATGACTTCCACTGCGAGTGCCGTGCTGGTCACACCGGGCGCCGCTGCGAGTCCGTCATCAATGGCTGCAAAGGCAAGCCCTGCAAGAATGGGGGCACCTGCGCCGTGGCCTCCAACACCGCCCGCGGGTTCATCTGCAAGTGCCCTGCGGGCTTCGAGGGCGCCACGTGTGAGAATGACGCTCGTACCTGCGGCAGCCTGCGCTGCCTCAACGGCGGCACATGCATCTCCGGCCCGCGCAGCCCCACCTGCCTGTGCCTGGGCCCCTTCACGGGCCCCGAATGCCAGTTCCCGGCCAGCAGCCCCTGCCTGGGCGGCAACCCCTGCTACAACCAGGGGACCTGTGAGCCCACATCCGAGAGCCCCTTCTACCGTTGCCTGTGCCCCGCCAAATTCAACGGGCTCTTGTGCCACATCCTGGACTACAGCTTCGGGGGTGGGGCCGGGCGCGACATCCCCCCGCCGCTGATCGAGGAGGCGTGCGAGCTGCCCGAGTGCCAGGAGGACGCGGGCAACAAGGTCTGCAGCCTGCAGTGCAACAACCACGCGTGCGGCTGGGACGGCGGTGACTGCTCCCTCAACTTCAATGACCCCTGGAAGAACTGCACGCAGTCTCTGCAGTGCTGGAAGTACTTCAGTGACGGCCACTGTGACAGCCAGTGCAACTCAGCCGGCTGCCTCTTCGACGGCTTTGACTGCCAGCGTGCGGAAGGCCAGTGCAACCCCCTGTACGACCAGTACTGCAAGGACCACTTCAGCGACGGGCACTGCGACCAGGGCTGCAACAGCGCGGAGTGCGAGTGGGACGGGCTGGACTGTGCGGAGCATGTACCCGAGAGGCTGGCGGCCGGCACGCTGGTGGTGGTGGTGCTGATGCCGCCGGAGCAGCTGCGCAACAGCTCCTTCCACTTCCTGCGGGAGCTCAGCCGCGTGCTGCACACCAACGTGGTCTTCAAGCGTGACGCACACGGCCAGCAGATGATCTTCCCCTACTACGGCCGCGAGGAGGAGCTGCGCAAGCACCCCATCAAGCGTGCCGCCGAGGGCTGGGCCGCACCTGACGCCCTGCTGGGCCAGGTGAAGGCCTCGCTGCTCCCTGGTGGCAGCGAGGGTGGGCGGCGGCGGAGGGAGCTGGACCCCATGGACGTCCGCGGCTCCATCGTCTACCTGGAGATTGACAACCGGCAGTGTGTGCAGGCCTCCTCGCAGTGCTTCCAGAGTGCCACCGACGTGGCCGCATTCCTGGGAGCGCTCGCCTCGCTGGGCAGCCTCAACATCCCCTACAAGATCGAGGCCGTGCAGAGTGAGACCGTGGAGCCGCCCCCGCCGGCGCAGCTGCACTTCATGTACGTGGCGGCGGCCGCCTTTGTGCTTCTGTTCTTCGTGGGCTGCGGGGTGCTGCTGTCCCGCAAGCGCCGGCGGCAGCATGGCCAGCTCTGGTTCCCTGAGGGCTTCAAAGTGTCTGAGGCCAGCAAGAAGAAGCGGCGGGAGCCCCTCGGCGAGGACTCCGTGGGCCTCAAGCCCCTGAAGAACGCTTCAGACGGTGCCCTCATGGACGACAACCAGAATGAGTGGGGGGACGAGGACCTGGAGACCAAGAAGTTCCGGTTCGAGGAGCCCGTGGTTCTGCCTGACCTGGACGACCAGACAGACCACCGGCAGTGGACTCAGCAGCACCTGGATGCCGCTGACCTGCGCATGTCTGCCATGGCCCCCACACCGCCCCAGGGTGAGGTTGACGCCGACTGCATGGACGTCAATGTCCGCGGGCCTGATGGCTTCACCCCGCTCATGATCGCCTCCTGCAGCGGGGGCGGCCTGGAGACGGGCAACAGCGAGGAAGAGGAGGACGCGCCGGCCGTCATCTCCGACTTCATCTACCAGGGCGCCAGCCTGCACAACCAGACAGACCGCACGGGCGAGACCGCCTTGCACCTGGCCGCCCGCTACTCACGCTCTGATGCCGCCAAGCGCCTGCTGGAGGCCAGCGCAGATGCCAACATCCAGGACAACATGGGCCGCACCCCGCTGCATGCGGCTGTGTCTGCCGACGCACAAGGTGTCTTCCAGATCCTGATCCGGAACCGAGCCACAGACCTGGATGCCCGCATGCATGATGGCACGACGCCACTGATCCTGGCTGCCCGCCTGGCCGTGGAGGGCATGCTGGAGGACCTCATCAACTCACACGCCGACGTCAACGCCGTAGATGACCTGGGCAAGTCCGCCCTGCACTGGGCCGCCGCCGTGAACAATGTGGATGCCGCAGTTGTGCTCCTGAAGAACGGGGCTAACAAAGATATGCAGAACAACAGGGAGGAGACACCCCTGTTTCTGGCCGCCCGGGAGGGCAGCTACGAGACCGCCAAGGTGCTGCTGGACCACTTTGCCAACCGGGACATCACGGATCATATGGACCGCCTGCCGCGCGACATCGCACAGGAGCGCATGCATCACGACATCGTGAGGCTGCTGGACGAGTACAACCTGGTGCGCAGCCCGCAGCTGCACGGAGCCCCGCTGGGGGGCACGCCCACCCTGTCGCCCCCGCTCTGCTCGCCCAACGGCTACCTGGGCAGCCTCAAGCCCGGCGTGCAGGGCAAGAAGGTCCGCAAGCCCAGCAGCAAAGGCCTGGCCTGTGGAAGCAAGGAGGCCAAGGACCTCAAGGCACGGAGGAAGAAGTCCCAGGACGGCAAGGGCTGCCTGCTGGACAGCTCCGGCATGCTCTCGCCCGTGGACTCCCTGGAGTCACCCCATGGCTACCTGTCAGACGTGGCCTCGCCGCCACTGCTGCCCTCCCCGTTCCAGCAGTCTCCGTCCGTGCCCCTCAACCACCTGCCTGGGATGCCCGACACCCACCTGGGCATCGGGCACCTGAACGTGGCGGCCAAGCCCGAGATGGCGGCGCTGGGTGGGGGCGGCCGGCTGGCCTTTGAGACTGGCCCACCTCGTCTCTCCCACCTGCCTGTGGCCTCTGGCACCAGCACCGTCCTGGGCTCCAGCAGCGGAGGGGCCCTGAATTTCACTGTGGGCGGGTCCACCAGTTTGAATGGTCAATGCGAGTGGCTGTCCCGGCTGCAGAGCGGCATGGTGCCGAACCAATACAACCCTCTGCGGGGGAGTGTGGCACCAGGCCCCCTGAGCACACAGGCCCCCTCCCTGCAGCATGGCATGGTAGGCCCGCTGCACAGTAGCCTTGCTGCCAGCGCCCTGTCCCAGATGATGAGCTACCAGGGCCTGCCCAGCACCCGGCTGGCCACCCAGCCTCACCTGGTGCAGACCCAGCAGGTGCAGCCACAAAACTTACAGATGCAGCAGCAGAACCTGCAGCCAGCAAACATCCAGCAGCAGCAAAGCCTGCAGCCGCCACCACCACCACCACAGCCGCACCTTGGCGTGAGCTCAGCAGCCAGCGGCCACCTGGGCCGGAGCTTCCTGAGTGGAGAGCCGAGCCAGGCAGACGTGCAGCCACTGGGCCCCAGCAGCCTGGCGGTGCACACTATTCTGCCCCAGGAGAGCCCCGCCCTGCCCACGTCGCTGCCATCCTCGCTGGTCCCACCCGTGACCGCAGCCCAGTTCCTGACGCCCCCCTCGCAGCACAGCTACTCCTCGCCTGTGGACAACACCCCCAGCCACCAGCTACAGGTGCCTGAGCACCCCTTCCTCACCCCGTCCCCTGAGTCCCCTGACCAGTGGTCCAGCTCGTCCCCGCATTCCAACGTCTCCGACTGGTCCGAGGGCGTCTCCAGCCCTCCCACCAGCATGCAGTCCCAGATCGCCCGCATTCCGGAGGCCTTCAAGTAAACGGCGCGCCCCACGAGACCCCGGCTTCCTTTCCCAAGCCTTCGGGCGTCTGTGTGCGCTCTGTGGATGCCAGGGCCGACCAGAGGAGCCTTTTTAAAACACATGTTTTTATACAAAATAAGAACGAGGATTTTAATTTTTTTTAGTATTTATTTATGTACTTTTATTTTACACAGAAACACTGCCTTTTTATTTATATGTACTGTTTTATCTGGCCCCAGGTAGAAACTTTTATCTATTCTGAGAAAACAAGCAAGTTCTGAGAGCCAGGGTTTTCCTACGTAGGATGAAAAGATTCTTCTGTGTTTATAAAATATAAACAAAGATTCATGATTTATAAATGCCATTTATTTATTGATTCCTTTTTTCAAAATCCAAAAAGAAATGATGTTGGAGAAGGGAAGTTGAACGAGCATAGTCCAAAAAGCTCCTGGGGCGTCCAGGCCGCGCCCTTTCCCCGACGCCCACCCAACCCCAAGCCAGCCCGGCCGCTCCACCAGCATCACCTGCCTGTTAGGAGAAGCTGCATCCAGAGGCAAACGGAGGCAAAGCTGGCTCACCTTCCGCACGCGGATTAATTTGCATCTGAAATAGGAAACAAGTGAAAGCATATGGGTTAGATGTTGCCATGTGTTTTAGATGGTTTCTTGCAAGCATGCTTGTGAAAATGTGTTCTCGGAGTGTGTATGCCAAGAGTGCACCCATGGTACCAATCATGAATCTTTGTTTCAGGTTCAGTATTATGTAGTTGTTCGTTGGTTATACAAGTTCTTGGTCCCTCCAGAACCACCCCGGCCCCCTGCCCGTTCTTGAAATGTAGGCATCATGCATGTCAAACATGAGATGTGTGGACTGTGGCACTTGCCTGGGTCACACACGGAGGCATCCTACCCTTTTCTGGGGAAAGACACTGCCTGGGCTGACCCCGGTGGCGGCCCCAGCACCTCAGCCTGCACAGTGTCCCCCAGGTTCCGAAGAAGATGCTCCAGCAACACAGCCTGGGCCCCAGCTCGCGGGACCCGACCCCCCGTGGGCTCCCGTGTTTTGTAGGAGACTTGCCAGAGCCGGGCACATTGAGCTGTGCAACGCCGTGGGCTGCGTCCTTTGGTCCTGTCCCCGCAGCCCTGGCAGGGGGCATGCGGTCGGGCAGGGGCTGGAGGGAGGCGGGGGCTGCCCTTGGGCCACCCCTCCTAGTTTGGGAGGAGCAGATTTTTGCAATACCAAGTATAGCCTATGGCAGAAAAAATGTCTGTAAATATGTTTTTAAAGGTGGATTTTGTTTAAAAAATCTTAATGAATGAGTCTGTTGTGTGTCATGCCAGTGAGGGACGTCAGACTTGGCTCAGCTCGGGGAGCCTTAGCCGCCCATGCACTGGGGACGCTCCGCTGCCGTGCCGCCTGCACTCCTCAGGGCAGCCTCCCCCGGCTCTACGGGGGCCGCGTGGTGCCATCCCCAGGGGGCATGACCAGATGCGTCCCAAGATGTTGATTTTTACTGTGTTTTATAAAATAGAGTGTAGTTTACAGAAAAAGACTTTAAAAGTGATCTACATGAGGAACTGTAGATGATGTATTTTTTTCATCTTTTTTGTTAACTGATTTGCAATAAAAATGATACTGATGGTGATCTGGCTTCCAAAAAAAAAAAAAAAAA
人notch 2(NOTCH2)，转录变体1，mRNA NM_024408.3(SEQ ID NO:30)
GCTTGCGGTGGGAGGAGGCGGCTGAGGCGGAAGGACACACGAGGCTGCTTCGTTGCACACCCGAGAAAGTTTCAGCCAAACTTCGGGCGGCGGCTGAGGCGGCGGCCGAGGAGCGGCGGACTCGGGGCGCGGGGAGTCGAGGCATTTGCGCCTGGGCTTCGGAGCGTAGCGCCAGGGCCTGAGCCTTTGAAGCAGGAGGAGGGGAGGAGAGAGTGGGGCTCCTCTATCGGGACCCCCTCCCCATGTGGATCTGCCCAGGCGGCGGCGGCGGCGGCGGAGGAGGAGGCGACCGAGAAGATGCCCGCCCTGCGCCCCGCTCTGCTGTGGGCGCTGCTGGCGCTCTGGCTGTGCTGCGCGGCCCCCGCGCATGCATTGCAGTGTCGAGATGGCTATGAACCCTGTGTAAATGAAGGAATGTGTGTTACCTACCACAATGGCACAGGATACTGCAAATGTCCAGAAGGCTTCTTGGGGGAATATTGTCAACATCGAGACCCCTGTGAGAAGAACCGCTGCCAGAATGGTGGGACTTGTGTGGCCCAGGCCATGCTGGGGAAAGCCACGTGCCGATGTGCCTCAGGGTTTACAGGAGAGGACTGCCAGTACTCAACATCTCATCCATGCTTTGTGTCTCGACCCTGCCTGAATGGCGGCACATGCCATATGCTCAGCCGGGATACCTATGAGTGCACCTGTCAAGTCGGGTTTACAGGTAAGGAGTGCCAATGGACGGATGCCTGCCTGTCTCATCCCTGTGCAAATGGAAGTACCTGTACCACTGTGGCCAACCAGTTCTCCTGCAAATGCCTCACAGGCTTCACAGGGCAGAAATGTGAGACTGATGTCAATGAGTGTGACATTCCAGGACACTGCCAGCATGGTGGCACCTGCCTCAACCTGCCTGGTTCCTACCAGTGCCAGTGCCCTCAGGGCTTCACAGGCCAGTACTGTGACAGCCTGTATGTGCCCTGTGCACCCTCACCTTGTGTCAATGGAGGCACCTGTCGGCAGACTGGTGACTTCACTTTTGAGTGCAACTGCCTTCCAGGTTTTGAAGGGAGCACCTGTGAGAGGAATATTGATGACTGCCCTAACCACAGGTGTCAGAATGGAGGGGTTTGTGTGGATGGGGTCAACACTTACAACTGCCGCTGTCCCCCACAATGGACAGGACAGTTCTGCACAGAGGATGTGGATGAATGCCTGCTGCAGCCCAATGCCTGTCAAAATGGGGGCACCTGTGCCAACCGCAATGGAGGCTATGGCTGTGTATGTGTCAACGGCTGGAGTGGAGATGACTGCAGTGAGAACATTGATGATTGTGCCTTCGCCTCCTGTACTCCAGGCTCCACCTGCATCGACCGTGTGGCCTCCTTCTCTTGCATGTGCCCAGAGGGGAAGGCAGGTCTCCTGTGTCATCTGGATGATGCATGCATCAGCAATCCTTGCCACAAGGGGGCACTGTGTGACACCAACCCCCTAAATGGGCAATATATTTGCACCTGCCCACAAGGCTACAAAGGGGCTGACTGCACAGAAGATGTGGATGAATGTGCCATGGCCAATAGCAATCCTTGTGAGCATGCAGGAAAATGTGTGAACACGGATGGCGCCTTCCACTGTGAGTGTCTGAAGGGTTATGCAGGACCTCGTTGTGAGATGGACATCAATGAGTGCCATTCAGACCCCTGCCAGAATGATGCTACCTGTCTGGATAAGATTGGAGGCTTCACATGTCTGTGCATGCCAGGTTTCAAAGGTGTGCATTGTGAATTAGAAATAAATGAATGTCAGAGCAACCCTTGTGTGAACAATGGGCAGTGTGTGGATAAAGTCAATCGTTTCCAGTGCCTGTGTCCTCCTGGTTTCACTGGGCCAGTTTGCCAGATTGATATTGATGACTGTTCCAGTACTCCGTGTCTGAATGGGGCAAAGTGTATCGATCACCCGAATGGCTATGAATGCCAGTGTGCCACAGGTTTCACTGGTGTGTTGTGTGAGGAGAACATTGACAACTGTGACCCCGATCCTTGCCACCATGGTCAGTGTCAGGATGGTATTGATTCCTACACCTGCATCTGCAATCCCGGGTACATGGGCGCCATCTGCAGTGACCAGATTGATGAATGTTACAGCAGCCCTTGCCTGAACGATGGTCGCTGCATTGACCTGGTCAATGGCTACCAGTGCAACTGCCAGCCAGGCACGTCAGGGGTTAATTGTGAAATTAATTTTGATGACTGTGCAAGTAACCCTTGTATCCATGGAATCTGTATGGATGGCATTAATCGCTACAGTTGTGTCTGCTCACCAGGATTCACAGGGCAGAGATGTAACATTGACATTGATGAGTGTGCCTCCAATCCCTGTCGCAAGGGTGCAACATGTATCAACGGTGTGAATGGTTTCCGCTGTATATGCCCCGAGGGACCCCATCACCCCAGCTGCTACTCACAGGTGAACGAATGCCTGAGCAATCCCTGCATCCATGGAAACTGTACTGGAGGTCTCAGTGGATATAAGTGTCTCTGTGATGCAGGCTGGGTTGGCATCAACTGTGAAGTGGACAAAAATGAATGCCTTTCGAATCCATGCCAGAATGGAGGAACTTGTGACAATCTGGTGAATGGATACAGGTGTACTTGCAAGAAGGGCTTTAAAGGCTATAACTGCCAGGTGAATATTGATGAATGTGCCTCAAATCCATGCCTGAACCAAGGAACCTGCTTTGATGACATAAGTGGCTACACTTGCCACTGTGTGCTGCCATACACAGGCAAGAATTGTCAGACAGTATTGGCTCCCTGTTCCCCAAACCCTTGTGAGAATGCTGCTGTTTGCAAAGAGTCACCAAATTTTGAGAGTTATACTTGCTTGTGTGCTCCTGGCTGGCAAGGTCAGCGGTGTACCATTGACATTGACGAGTGTATCTCCAAGCCCTGCATGAACCATGGTCTCTGCCATAACACCCAGGGCAGCTACATGTGTGAATGTCCACCAGGCTTCAGTGGTATGGACTGTGAGGAGGACATTGATGACTGCCTTGCCAATCCTTGCCAGAATGGAGGTTCCTGTATGGATGGAGTGAATACTTTCTCCTGCCTCTGCCTTCCGGGTTTCACTGGGGATAAGTGCCAGACAGACATGAATGAGTGTCTGAGTGAACCCTGTAAGAATGGAGGGACCTGCTCTGACTACGTCAACAGTTACACTTGCAAGTGCCAGGCAGGATTTGATGGAGTCCATTGTGAGAACAACATCAATGAGTGCACTGAGAGCTCCTGTTTCAATGGTGGCACATGTGTTGATGGGATTAACTCCTTCTCTTGCTTGTGCCCTGTGGGTTTCACTGGATCCTTCTGCCTCCATGAGATCAATGAATGCAGCTCTCATCCATGCCTGAATGAGGGAACGTGTGTTGATGGCCTGGGTACCTACCGCTGCAGCTGCCCCCTGGGCTACACTGGGAAAAACTGTCAGACCCTGGTGAATCTCTGCAGTCGGTCTCCATGTAAAAACAAAGGTACTTGCGTTCAGAAAAAAGCAGAGTCCCAGTGCCTATGTCCATCTGGATGGGCTGGTGCCTATTGTGACGTGCCCAATGTCTCTTGTGACATAGCAGCCTCCAGGAGAGGTGTGCTTGTTGAACACTTGTGCCAGCACTCAGGTGTCTGCATCAATGCTGGCAACACGCATTACTGTCAGTGCCCCCTGGGCTATACTGGGAGCTACTGTGAGGAGCAACTCGATGAGTGTGCGTCCAACCCCTGCCAGCACGGGGCAACATGCAGTGACTTCATTGGTGGATACAGATGCGAGTGTGTCCCAGGCTATCAGGGTGTCAACTGTGAGTATGAAGTGGATGAGTGCCAGAATCAGCCCTGCCAGAATGGAGGCACCTGTATTGACCTTGTGAACCATTTCAAGTGCTCTTGCCCACCAGGCACTCGGGGCCTACTCTGTGAAGAGAACATTGATGACTGTGCCCGGGGTCCCCATTGCCTTAATGGTGGTCAGTGCATGGATAGGATTGGAGGCTACAGTTGTCGCTGCTTGCCTGGCTTTGCTGGGGAGCGTTGTGAGGGAGACATCAACGAGTGCCTCTCCAACCCCTGCAGCTCTGAGGGCAGCCTGGACTGTATACAGCTCACCAATGACTACCTGTGTGTTTGCCGTAGTGCCTTTACTGGCCGGCACTGTGAAACCTTCGTCGATGTGTGTCCCCAGATGCCCTGCCTGAATGGAGGGACTTGTGCTGTGGCCAGTAACATGCCTGATGGTTTCATTTGCCGTTGTCCCCCGGGATTTTCCGGGGCAAGGTGCCAGAGCAGCTGTGGACAAGTGAAATGTAGGAAGGGGGAGCAGTGTGTGCACACCGCCTCTGGACCCCGCTGCTTCTGCCCCAGTCCCCGGGACTGCGAGTCAGGCTGTGCCAGTAGCCCCTGCCAGCACGGGGGCAGCTGCCACCCTCAGCGCCAGCCTCCTTATTACTCCTGCCAGTGTGCCCCACCATTCTCGGGTAGCCGCTGTGAACTCTACACGGCACCCCCCAGCACCCCTCCTGCCACCTGTCTGAGCCAGTATTGTGCCGACAAAGCTCGGGATGGCGTCTGTGATGAGGCCTGCAACAGCCATGCCTGCCAGTGGGATGGGGGTGACTGTTCTCTCACCATGGAGAACCCCTGGGCCAACTGCTCCTCCCCACTTCCCTGCTGGGATTATATCAACAACCAGTGTGATGAGCTGTGCAACACGGTCGAGTGCCTGTTTGACAACTTTGAATGCCAGGGGAACAGCAAGACATGCAAGTATGACAAATACTGTGCAGACCACTTCAAAGACAACCACTGTGACCAGGGGTGCAACAGTGAGGAGTGTGGTTGGGATGGGCTGGACTGTGCTGCTGACCAACCTGAGAACCTGGCAGAAGGTACCCTGGTTATTGTGGTATTGATGCCACCTGAACAACTGCTCCAGGATGCTCGCAGCTTCTTGCGGGCACTGGGTACCCTGCTCCACACCAACCTGCGCATTAAGCGGGACTCCCAGGGGGAACTCATGGTGTACCCCTATTATGGTGAGAAGTCAGCTGCTATGAAGAAACAGAGGATGACACGCAGATCCCTTCCTGGTGAACAAGAACAGGAGGTGGCTGGCTCTAAAGTCTTTCTGGAAATTGACAACCGCCAGTGTGTTCAAGACTCAGACCACTGCTTCAAGAACACGGATGCAGCAGCAGCTCTCCTGGCCTCTCACGCCATACAGGGGACCCTGTCATACCCTCTTGTGTCTGTCGTCAGTGAATCCCTGACTCCAGAACGCACTCAGCTCCTCTATCTCCTTGCTGTTGCTGTTGTCATCATTCTGTTTATTATTCTGCTGGGGGTAATCATGGCAAAACGAAAGCGTAAGCATGGCTCTCTCTGGCTGCCTGAAGGTTTCACTCTTCGCCGAGATGCAAGCAATCACAAGCGTCGTGAGCCAGTGGGACAGGATGCTGTGGGGCTGAAAAATCTCTCAGTGCAAGTCTCAGAAGCTAACCTAATTGGTACTGGAACAAGTGAACACTGGGTCGATGATGAAGGGCCCCAGCCAAAGAAAGTAAAGGCTGAAGATGAGGCCTTACTCTCAGAAGAAGATGACCCCATTGATCGACGGCCATGGACACAGCAGCACCTTGAAGCTGCAGACATCCGTAGGACACCATCGCTGGCTCTCACCCCTCCTCAGGCAGAGCAGGAGGTGGATGTGTTAGATGTGAATGTCCGTGGCCCAGATGGCTGCACCCCATTGATGTTGGCTTCTCTCCGAGGAGGCAGCTCAGATTTGAGTGATGAAGATGAAGATGCAGAGGACTCTTCTGCTAACATCATCACAGACTTGGTCTACCAGGGTGCCAGCCTCCAGGCCCAGACAGACCGGACTGGTGAGATGGCCCTGCACCTTGCAGCCCGCTACTCACGGGCTGATGCTGCCAAGCGTCTCCTGGATGCAGGTGCAGATGCCAATGCCCAGGACAACATGGGCCGCTGTCCACTCCATGCTGCAGTGGCAGCTGATGCCCAAGGTGTCTTCCAGATTCTGATTCGCAACCGAGTAACTGATCTAGATGCCAGGATGAATGATGGTACTACACCCCTGATCCTGGCTGCCCGCCTGGCTGTGGAGGGAATGGTGGCAGAACTGATCAACTGCCAAGCGGATGTGAATGCAGTGGATGACCATGGAAAATCTGCTCTTCACTGGGCAGCTGCTGTCAATAATGTGGAGGCAACTCTTTTGTTGTTGAAAAATGGGGCCAACCGAGACATGCAGGACAACAAGGAAGAGACACCTCTGTTTCTTGCTGCCCGGGAGGGGAGCTATGAAGCAGCCAAGATCCTGTTAGACCATTTTGCCAATCGAGACATCACAGACCATATGGATCGTCTTCCCCGGGATGTGGCTCGGGATCGCATGCACCATGACATTGTGCGCCTTCTGGATGAATACAATGTGACCCCAAGCCCTCCAGGCACCGTGTTGACTTCTGCTCTCTCACCTGTCATCTGTGGGCCCAACAGATCTTTCCTCAGCCTGAAGCACACCCCAATGGGCAAGAAGTCTAGACGGCCCAGTGCCAAGAGTACCATGCCTACTAGCCTCCCTAACCTTGCCAAGGAGGCAAAGGATGCCAAGGGTAGTAGGAGGAAGAAGTCTCTGAGTGAGAAGGTCCAACTGTCTGAGAGTTCAGTAACTTTATCCCCTGTTGATTCCCTAGAATCTCCTCACACGTATGTTTCCGACACCACATCCTCTCCAATGATTACATCCCCTGGGATCTTACAGGCCTCACCCAACCCTATGTTGGCCACTGCCGCCCCTCCTGCCCCAGTCCATGCCCAGCATGCACTATCTTTTTCTAACCTTCATGAAATGCAGCCTTTGGCACATGGGGCCAGCACTGTGCTTCCCTCAGTGAGCCAGTTGCTATCCCACCACCACATTGTGTCTCCAGGCAGTGGCAGTGCTGGAAGCTTGAGTAGGCTCCATCCAGTCCCAGTCCCAGCAGATTGGATGAACCGCATGGAGGTGAATGAGACCCAGTACAATGAGATGTTTGGTATGGTCCTGGCTCCAGCTGAGGGCACCCATCCTGGCATAGCTCCCCAGAGCAGGCCACCTGAAGGGAAGCACATAACCACCCCTCGGGAGCCCTTGCCCCCCATTGTGACTTTCCAGCTCATCCCTAAAGGCAGTATTGCCCAACCAGCGGGGGCTCCCCAGCCTCAGTCCACCTGCCCTCCAGCTGTTGCGGGCCCCCTGCCCACCATGTACCAGATTCCAGAAATGGCCCGTTTGCCCAGTGTGGCTTTCCCCACTGCCATGATGCCCCAGCAGGACGGGCAGGTAGCTCAGACCATTCTCCCAGCCTATCATCCTTTCCCAGCCTCTGTGGGCAAGTACCCCACACCCCCTTCACAGCACAGTTATGCTTCCTCAAATGCTGCTGAGCGAACACCCAGTCACAGTGGTCACCTCCAGGGTGAGCATCCCTACCTGACACCATCCCCAGAGTCTCCTGACCAGTGGTCAAGTTCATCACCCCACTCTGCTTCTGACTGGTCAGATGTGACCACCAGCCCTACCCCTGGGGGTGCTGGAGGAGGTCAGCGGGGACCTGGGACACACATGTCTGAGCCACCACACAACAACATGCAGGTTTATGCGTGAGAGAGTCCACCTCCAGTGTAGAGACATAACTGACTTTTGTAAATGCTGCTGAGGAACAAATGAAGGTCATCCGGGAGAGAAATGAAGAAATCTCTGGAGCCAGCTTCTAGAGGTAGGAAAGAGAAGATGTTCTTATTCAGATAATGCAAGAGAAGCAATTCGTCAGTTTCACTGGGTATCTGCAAGGCTTATTGATTATTCTAATCTAATAAGACAAGTTTGTGGAAATGCAAGATGAATACAAGCCTTGGGTCCATGTTTACTCTCTTCTATTTGGAGAATAAGATGGATGCTTATTGAAGCCCAGACATTCTTGCAGCTTGGACTGCATTTTAAGCCCTGCAGGCTTCTGCCATATCCATGAGAAGATTCTACACTAGCGTCCTGTTGGGAATTATGCCCTGGAATTCTGCCTGAATTGACCTACGCATCTCCTCCTCCTTGGACATTCTTTTGTCTTCATTTGGTGCTTTTGGTTTTGCACCTCTCCGTGATTGTAGCCCTACCAGCATGTTATAGGGCAAGACCTTTGTGCTTTTGATCATTCTGGCCCATGAAAGCAACTTTGGTCTCCTTTCCCCTCCTGTCTTCCCGGTATCCCTTGGAGTCTCACAAGGTTTACTTTGGTATGGTTCTCAGCACAAACCTTTCAAGTATGTTGTTTCTTTGGAAAATGGACATACTGTATTGTGTTCTCCTGCATATATCATTCCTGGAGAGAGAAGGGGAGAAGAATACTTTTCTTCAACAAATTTTGGGGGCAGGAGATCCCTTCAAGAGGCTGCACCTTAATTTTTCTTGTCTGTGTGCAGGTCTTCATATAAACTTTACCAGGAAGAAGGGTGTGAGTTTGTTGTTTTTCTGTGTATGGGCCTGGTCAGTGTAAAGTTTTATCCTTGATAGTCTAGTTACTATGACCCTCCCCACTTTTTTAAAACCAGAAAAAGGTTTGGAATGTTGGAATGACCAAGAGACAAGTTAACTCGTGCAAGAGCCAGTTACCCACCCACAGGTCCCCCTACTTCCTGCCAAGCATTCCATTGACTGCCTGTATGGAACACATTTGTCCCAGATCTGAGCATTCTAGGCCTGTTTCACTCACTCACCCAGCATATGAAACTAGTCTTAACTGTTGAGCCTTTCCTTTCATATCCACAGAAGACACTGTCTCAAATGTTGTACCCTTGCCATTTAGGACTGAACTTTCCTTAGCCCAAGGGACCCAGTGACAGTTGTCTTCCGTTTGTCAGATGATCAGTCTCTACTGATTATCTTGCTGCTTAAAGGCCTGCTCACCAATCTTTCTTTCACACCGTGTGGTCCGTGTTACTGGTATACCCAGTATGTTCTCACTGAAGACATGGACTTTATATGTTCAAGTGCAGGAATTGGAAAGTTGGACTTGTTTTCTATGATCCAAAACAGCCCTATAAGAAGGTTGGAAAAGGAGGAACTATATAGCAGCCTTTGCTATTTTCTGCTACCATTTCTTTTCCTCTGAAGCGGCCATGACATTCCCTTTGGCAACTAACGTAGAAACTCAACAGAACATTTTCCTTTCCTAGAGTCACCTTTTAGATGATAATGGACAACTATAGACTTGCTCATTGTTCAGACTGATTGCCCCTCACCTGAATCCACTCTCTGTATTCATGCTCTTGGCAATTTCTTTGACTTTCTTTTAAGGGCAGAAGCATTTTAGTTAATTGTAGATAAAGAATAGTTTTCTTCCTCTTCTCCTTGGGCCAGTTAATAATTGGTCCATGGCTACACTGCAACTTCCGTCCAGTGCTGTGATGCCCATGACACCTGCAAAATAAGTTCTGCCTGGGCATTTTGTAGATATTAACAGGTGAATTCCCGACTCTTTTGGTTTGAATGACAGTTCTCATTCCTTCTATGGCTGCAAGTATGCATCAGTGCTTCCCACTTACCTGATTTGTCTGTCGGTGGCCCCATATGGAAACCCTGCGTGTCTGTTGGCATAATAGTTTACAAATGGTTTTTTCAGTCCTATCCAAATTTATTGAACCAACAAAAATAATTACTTCTGCCCTGAGATAAGCAGATTAAGTTTGTTCATTCTCTGCTTTATTCTCTCCATGTGGCAACATTCTGTCAGCCTCTTTCATAGTGTGCAAACATTTTATCATTCTAAATGGTGACTCTCTGCCCTTGGACCCATTTATTATTCACAGATGGGGAGAACCTATCTGCATGGACCTCTGTGGACCACAGCGTACCTGCCCCTTTCTGCCCTCCTGCTCCAGCCCCACTTCTGAAAGTATCAGCTACTGATCCAGCCACTGGATATTTTATATCCTCCCTTTTCCTTAAGCACAATGTCAGACCAAATTGCTTGTTTCTTTTTCTTGGACTACTTTAATTTGGATCCTTTGGGTTTGGAGAAAGGGAATGTGAAAGCTGTCATTACAGACAACAGGTTTCAGTGATGAGGAGGACAACACTGCCTTTCAAACTTTTTACTGATCTCTTAGATTTTAAGAACTCTTGAATTGTGTGGTATCTAATAAAAGGGAAGGTAAGATGGATAATCACTTTCTCATTTGGGTTCTGAATTGGAGACTCAGTTTTTATGAGACACATCTTTTATGCCATGTATAGATCCTCCCCTGCTATTTTTGGTTTATTTTTATTGTTATAAATGCTTTCTTTCTTTGACTCCTCTTCTGCCTGCCTTTGGGGATAGGTTTTTTTGTTTGTTTATTTGCTTCCTCTGTTTTGTTTTAAGCATCATTTTCTTATGTGAGGTGGGGAAGGGAAAGGTATGAGGGAAAGAGAGTCTGAGAATTAAAATATTTTAGTATAAGCAATTGGCTGTGATGCTCAAATCCATTGCATCCTCTTATTGAATTTGCCAATTTGTAATTTTTGCATAATAAAGAACCAAAGGTGTAATGTTTTGTTGAGAGGTGGTTTAGGGATTTTGGCCCTAACCAATACATTGAATGTATGATGACTATTTGGGAGGACACATTTATGTACCCAGAGGCCCCCACTAATAAGTGGTACTATGGTTACTTCCTTGTGTACATTTCTCTTAAAAGTGATATTATATCTGTTTGTATGAGAAACCCAGTAACCAATAAAATGACCGCATATTCCTGACTAAACGTAGTAAGGAAAATGCACACTTTGTTTTTACTTTTCCGTTTCATTCTAAAGGTAGTTAAGATGAAATTTATATGAAAGCATTTTTATCACAAAATAAAAAAGGTTTGCCAAGCTCAGTGGTGTTGTATTTTTTATTTTCCAATACTGCATCCATGGCCTGGCAGTGTTACCTCATGATGTCATAATTTGCTGAGAGAGCAAATTTTCTTTTCTTTCTGAATCCCACAAAGCCTAGCACCAAACTTCTTTTTTTCTTCCTTTAATTAGATCATAAATAAATGATCCTGGGGAAAAAGCATCTGTCAAATAGGAAACATCACAAAACTGAGCACTCTTCTGTGCACTAGCCATAGCTGGTGACAAACAGATGGTTGCTCAGGGACAAGGTGCCTTCCAATGGAAATGCGAAGTAGTTGCTATAGCAAGAATTGGGAACTGGGATATAAGTCATAATATTAATTATGCTGTTATGTAAATGATTGGTTTGTAACATTCCTTAAGTGAAATTTGTGTAGAACTTAATATACAGGATTATAAAATAATATTTTGTGTATAAATTTGTTATAAGTTCACATTCATACATTTATTTATAAAGTCAGTGAGATATTTGAACATGAAAAAAAAAA
人notch 2(NOTCH2)，转录变体2，mRNA NM_001200001.1(SEQ ID NO:31)
GCTTGCGGTGGGAGGAGGCGGCTGAGGCGGAAGGACACACGAGGCTGCTTCGTTGCACACCCGAGAAAGTTTCAGCCAAACTTCGGGCGGCGGCTGAGGCGGCGGCCGAGGAGCGGCGGACTCGGGGCGCGGGGAGTCGAGGCATTTGCGCCTGGGCTTCGGAGCGTAGCGCCAGGGCCTGAGCCTTTGAAGCAGGAGGAGGGGAGGAGAGAGTGGGGCTCCTCTATCGGGACCCCCTCCCCATGTGGATCTGCCCAGGCGGCGGCGGCGGCGGCGGAGGAGGAGGCGACCGAGAAGATGCCCGCCCTGCGCCCCGCTCTGCTGTGGGCGCTGCTGGCGCTCTGGCTGTGCTGCGCGGCCCCCGCGCATGCATTGCAGTGTCGAGATGGCTATGAACCCTGTGTAAATGAAGGAATGTGTGTTACCTACCACAATGGCACAGGATACTGCAAATGTCCAGAAGGCTTCTTGGGGGAATATTGTCAACATCGAGACCCCTGTGAGAAGAACCGCTGCCAGAATGGTGGGACTTGTGTGGCCCAGGCCATGCTGGGGAAAGCCACGTGCCGATGTGCCTCAGGGTTTACAGGAGAGGACTGCCAGTACTCAACATCTCATCCATGCTTTGTGTCTCGACCCTGCCTGAATGGCGGCACATGCCATATGCTCAGCCGGGATACCTATGAGTGCACCTGTCAAGTCGGGTTTACAGGTAAGGAGTGCCAATGGACGGATGCCTGCCTGTCTCATCCCTGTGCAAATGGAAGTACCTGTACCACTGTGGCCAACCAGTTCTCCTGCAAATGCCTCACAGGCTTCACAGGGCAGAAATGTGAGACTGATGTCAATGAGTGTGACATTCCAGGACACTGCCAGCATGGTGGCACCTGCCTCAACCTGCCTGGTTCCTACCAGTGCCAGTGCCCTCAGGGCTTCACAGGCCAGTACTGTGACAGCCTGTATGTGCCCTGTGCACCCTCACCTTGTGTCAATGGAGGCACCTGTCGGCAGACTGGTGACTTCACTTTTGAGTGCAACTGCCTTCCAGGTTTTGAAGGGAGCACCTGTGAGAGGAATATTGATGACTGCCCTAACCACAGGTGTCAGAATGGAGGGGTTTGTGTGGATGGGGTCAACACTTACAACTGCCGCTGTCCCCCACAATGGACAGGACAGTTCTGCACAGAGGATGTGGATGAATGCCTGCTGCAGCCCAATGCCTGTCAAAATGGGGGCACCTGTGCCAACCGCAATGGAGGCTATGGCTGTGTATGTGTCAACGGCTGGAGTGGAGATGACTGCAGTGAGAACATTGATGATTGTGCCTTCGCCTCCTGTACTCCAGGCTCCACCTGCATCGACCGTGTGGCCTCCTTCTCTTGCATGTGCCCAGAGGGGAAGGCAGGTCTCCTGTGTCATCTGGATGATGCATGCATCAGCAATCCTTGCCACAAGGGGGCACTGTGTGACACCAACCCCCTAAATGGGCAATATATTTGCACCTGCCCACAAGGCTACAAAGGGGCTGACTGCACAGAAGATGTGGATGAATGTGCCATGGCCAATAGCAATCCTTGTGAGCATGCAGGAAAATGTGTGAACACGGATGGCGCCTTCCACTGTGAGTGTCTGAAGGGTTATGCAGGACCTCGTTGTGAGATGGACATCAATGAGTGCCATTCAGACCCCTGCCAGAATGATGCTACCTGTCTGGATAAGATTGGAGGCTTCACATGTCTGTGCATGCCAGGTTTCAAAGGTGTGCATTGTGAATTAGAAATAAATGAATGTCAGAGCAACCCTTGTGTGAACAATGGGCAGTGTGTGGATAAAGTCAATCGTTTCCAGTGCCTGTGTCCTCCTGGTTTCACTGGGCCAGTTTGCCAGATTGATATTGATGACTGTTCCAGTACTCCGTGTCTGAATGGGGCAAAGTGTATCGATCACCCGAATGGCTATGAATGCCAGTGTGCCACAGGTTTCACTGGTGTGTTGTGTGAGGAGAACATTGACAACTGTGACCCCGATCCTTGCCACCATGGTCAGTGTCAGGATGGTATTGATTCCTACACCTGCATCTGCAATCCCGGGTACATGGGCGCCATCTGCAGTGACCAGATTGATGAATGTTACAGCAGCCCTTGCCTGAACGATGGTCGCTGCATTGACCTGGTCAATGGCTACCAGTGCAACTGCCAGCCAGGCACGTCAGGGGTTAATTGTGAAATTAATTTTGATGACTGTGCAAGTAACCCTTGTATCCATGGAATCTGTATGGATGGCATTAATCGCTACAGTTGTGTCTGCTCACCAGGATTCACAGGGCAGAGATGTAACATTGACATTGATGAGTGTGCCTCCAATCCCTGTCGCAAGGGTGCAACATGTATCAACGGTGTGAATGGTTTCCGCTGTATATGCCCCGAGGGACCCCATCACCCCAGCTGCTACTCACAGGTGAACGAATGCCTGAGCAATCCCTGCATCCATGGAAACTGTACTGGAGGTCTCAGTGGATATAAGTGTCTCTGTGATGCAGGCTGGGTTGGCATCAACTGTGAAGTGGACAAAAATGAATGCCTTTCGAATCCATGCCAGAATGGAGGAACTTGTGACAATCTGGTGAATGGATACAGGTGTACTTGCAAGAAGGGCTTTAAAGGCTATAACTGCCAGGTGAATATTGATGAATGTGCCTCAAATCCATGCCTGAACCAAGGAACCTGCTTTGATGACATAAGTGGCTACACTTGCCACTGTGTGCTGCCATACACAGGCAAGAATTGTCAGACAGTATTGGCTCCCTGTTCCCCAAACCCTTGTGAGAATGCTGCTGTTTGCAAAGAGTCACCAAATTTTGAGAGTTATACTTGCTTGTGTGCTCCTGGCTGGCAAGGTCAGCGGTGTACCATTGACATTGACGAGTGTATCTCCAAGCCCTGCATGAACCATGGTCTCTGCCATAACACCCAGGGCAGCTACATGTGTGAATGTCCACCAGGCTTCAGTGGTATGGACTGTGAGGAGGACATTGATGACTGCCTTGCCAATCCTTGCCAGAATGGAGGTTCCTGTATGGATGGAGTGAATACTTTCTCCTGCCTCTGCCTTCCGGGTTTCACTGGGGATAAGTGCCAGACAGACATGAATGAGTGTCTGAGTGAACCCTGTAAGAATGGAGGGACCTGCTCTGACTACGTCAACAGTTACACTTGCAAGTGCCAGGCAGGATTTGATGGAGTCCATTGTGAGAACAACATCAATGAGTGCACTGAGAGCTCCTGTTTCAATGGTGGCACATGTGTTGATGGGATTAACTCCTTCTCTTGCTTGTGCCCTGTGGGTTTCACTGGATCCTTCTGCCTCCATGAGATCAATGAATGCAGCTCTCATCCATGCCTGAATGAGGGAACGTGTGTTGATGGCCTGGGTACCTACCGCTGCAGCTGCCCCCTGGGCTACACTGGGAAAAACTGTCAGACCCTGGTGAATCTCTGCAGTCGGTCTCCATGTAAAAACAAAGGTACTTGCGTTCAGAAAAAAGCAGAGTCCCAGTGCCTATGTCCATCTGGATGGGCTGGTGCCTATTGTGACGTGCCCAATGTCTCTTGTGACATAGCAGCCTCCAGGAGAGGTGTGCTTGTTGAACACTTGTGCCAGCACTCAGGTGTCTGCATCAATGCTGGCAACACGCATTACTGTCAGTGCCCCCTGGGCTATACTGGGAGCTACTGTGAGGAGCAACTCGATGAGTGTGCGTCCAACCCCTGCCAGCACGGGGCAACATGCAGTGACTTCATTGGTGGATACAGATGCGAGTGTGTCCCAGGCTATCAGGGTGTCAACTGTGAGTATGAAGTGGATGAGTGCCAGAATCAGCCCTGCCAGAATGGAGGCACCTGTATTGACCTTGTGAACCATTTCAAGTGCTCTTGCCCACCAGGCACTCGGGGTATGAAATCATCCTTATCCATTTTCCATCCAGGGCATTGTCTTAAGTTATAAATCCATTCTTAGTGTTCAGGGGATTTTATAAAATTAAAGATAGGAAGACTAGCTTCATTCCAAGCATTTAGTTCTACATCCTAGTAATTCAAGCCATTTTATTCTCCCATCTCTTGCTAGCTCTGATGTTGTGGTTTATGTTGTCAGTTTTATCTGGTTGTTTGGCATCTTGATATTCCATGAAACACAGAATATGGAAGGGATACAACATTAGCATAACATTAAAAAATTAGCCTGGTCAGTAAGATTTCTTGTTGCTTCACAGAAAAGCAACTAATGGCCTCTAAAATAAACAATTTACATTTAAAAAAAAAAAAAAAA
人notch 3(NOTCH3)，mRNA NM_000435.2(SEQ ID NO:32)
GCGGCGCGGAGGCTGGCCCGGGACGCGCCCGGAGCCCAGGGAAGGAGGGAGGAGGGGAGGGTCGCGGCCGGCCGCCATGGGGCCGGGGGCCCGTGGCCGCCGCCGCCGCCGTCGCCCGATGTCGCCGCCACCGCCACCGCCACCCGTGCGGGCGCTGCCCCTGCTGCTGCTGCTAGCGGGGCCGGGGGCTGCAGCCCCCCCTTGCCTGGACGGAAGCCCGTGTGCAAATGGAGGTCGTTGCACCCAGCTGCCCTCCCGGGAGGCTGCCTGCCTGTGCCCGCCTGGCTGGGTGGGTGAGCGGTGTCAGCTGGAGGACCCCTGTCACTCAGGCCCCTGTGCTGGCCGTGGTGTCTGCCAGAGTTCAGTGGTGGCTGGCACCGCCCGATTCTCATGCCGGTGCCCCCGTGGCTTCCGAGGCCCTGACTGCTCCCTGCCAGATCCCTGCCTCAGCAGCCCTTGTGCCCACGGTGCCCGCTGCTCAGTGGGGCCCGATGGACGCTTCCTCTGCTCCTGCCCACCTGGCTACCAGGGCCGCAGCTGCCGAAGCGACGTGGATGAGTGCCGGGTGGGTGAGCCCTGCCGCCATGGTGGCACCTGCCTCAACACACCTGGCTCCTTCCGCTGCCAGTGTCCAGCTGGCTACACAGGGCCACTATGTGAGAACCCCGCGGTGCCCTGTGCACCCTCACCATGCCGTAACGGGGGCACCTGCAGGCAGAGTGGCGACCTCACTTACGACTGTGCCTGTCTTCCTGGGTTTGAGGGTCAGAATTGTGAAGTGAACGTGGACGACTGTCCAGGACACCGATGTCTCAATGGGGGGACATGCGTGGATGGCGTCAACACCTATAACTGCCAGTGCCCTCCTGAGTGGACAGGCCAGTTCTGCACGGAGGACGTGGATGAGTGTCAGCTGCAGCCCAACGCCTGCCACAATGGGGGTACCTGCTTCAACACGCTGGGTGGCCACAGCTGCGTGTGTGTCAATGGCTGGACAGGCGAGAGCTGCAGTCAGAATATCGATGACTGTGCCACAGCCGTGTGCTTCCATGGGGCCACCTGCCATGACCGCGTGGCTTCTTTCTACTGTGCCTGCCCCATGGGCAAGACTGGCCTCCTGTGTCACCTGGATGACGCCTGTGTCAGCAACCCCTGCCACGAGGATGCTATCTGTGACACAAATCCGGTGAACGGCCGGGCCATTTGCACCTGTCCTCCCGGCTTCACGGGTGGGGCATGTGACCAGGATGTGGACGAGTGCTCTATCGGCGCCAACCCCTGCGAGCACTTGGGCAGGTGCGTGAACACGCAGGGCTCCTTCCTGTGCCAGTGCGGTCGTGGCTACACTGGACCTCGCTGTGAGACCGATGTCAACGAGTGTCTGTCGGGGCCCTGCCGAAACCAGGCCACGTGCCTCGACCGCATAGGCCAGTTCACCTGTATCTGTATGGCAGGCTTCACAGGAACCTATTGCGAGGTGGACATTGACGAGTGTCAGAGTAGCCCCTGTGTCAACGGTGGGGTCTGCAAGGACCGAGTCAATGGCTTCAGCTGCACCTGCCCCTCGGGCTTCAGCGGCTCCACGTGTCAGCTGGACGTGGACGAATGCGCCAGCACGCCCTGCAGGAATGGCGCCAAATGCGTGGACCAGCCCGATGGCTACGAGTGCCGCTGTGCCGAGGGCTTTGAGGGCACGCTGTGTGATCGCAACGTGGACGACTGCTCCCCTGACCCATGCCACCATGGTCGCTGCGTGGATGGCATCGCCAGCTTCTCATGTGCCTGTGCTCCTGGCTACACGGGCACACGCTGCGAGAGCCAGGTGGACGAATGCCGCAGCCAGCCCTGCCGCCATGGCGGCAAATGCCTAGACCTGGTGGACAAGTACCTCTGCCGCTGCCCTTCTGGGACCACAGGTGTGAACTGCGAAGTGAACATTGACGACTGTGCCAGCAACCCCTGCACCTTTGGAGTCTGCCGTGATGGCATCAACCGCTACGACTGTGTCTGCCAACCTGGCTTCACAGGGCCCCTTTGTAACGTGGAGATCAATGAGTGTGCTTCCAGCCCATGCGGCGAGGGAGGTTCCTGTGTGGATGGGGAAAATGGCTTCCGCTGCCTCTGCCCGCCTGGCTCCTTGCCCCCACTCTGCCTCCCCCCGAGCCATCCCTGTGCCCATGAGCCCTGCAGTCACGGCATCTGCTATGATGCACCTGGCGGGTTCCGCTGTGTGTGTGAGCCTGGCTGGAGTGGCCCCCGCTGCAGCCAGAGCCTGGCCCGAGACGCCTGTGAGTCCCAGCCGTGCAGGGCCGGTGGGACATGCAGCAGCGATGGAATGGGTTTCCACTGCACCTGCCCGCCTGGTGTCCAGGGACGTCAGTGTGAACTCCTCTCCCCCTGCACCCCGAACCCCTGTGAGCATGGGGGCCGCTGCGAGTCTGCCCCTGGCCAGCTGCCTGTCTGCTCCTGCCCCCAGGGCTGGCAAGGCCCACGATGCCAGCAGGATGTGGACGAGTGTGCTGGCCCCGCACCCTGTGGCCCTCATGGTATCTGCACCAACCTGGCAGGGAGTTTCAGCTGCACCTGCCATGGAGGGTACACTGGCCCTTCCTGCGATCAGGACATCAATGACTGTGACCCCAACCCATGCCTGAACGGTGGCTCGTGCCAAGACGGCGTGGGCTCCTTTTCCTGCTCCTGCCTCCCTGGTTTCGCCGGCCCACGATGCGCCCGCGATGTGGATGAGTGCCTGAGCAACCCCTGCGGCCCGGGCACCTGTACCGACCACGTGGCCTCCTTCACCTGCACCTGCCCGCCAGGCTACGGAGGCTTCCACTGCGAACAGGACCTGCCCGACTGCAGCCCCAGCTCCTGCTTCAATGGCGGGACCTGTGTGGACGGCGTGAACTCGTTCAGCTGCCTGTGCCGTCCCGGCTACACAGGAGCCCACTGCCAACATGAGGCAGACCCCTGCCTCTCGCGGCCCTGCCTACACGGGGGCGTCTGCAGCGCCGCCCACCCTGGCTTCCGCTGCACCTGCCTCGAGAGCTTCACGGGCCCGCAGTGCCAGACGCTGGTGGATTGGTGCAGCCGCCAGCCTTGTCAAAACGGGGGTCGCTGCGTCCAGACTGGGGCCTATTGCCTTTGTCCCCCTGGATGGAGCGGACGCCTCTGTGACATCCGAAGCTTGCCCTGCAGGGAGGCCGCAGCCCAGATCGGGGTGCGGCTGGAGCAGCTGTGTCAGGCGGGTGGGCAGTGTGTGGATGAAGACAGCTCCCACTACTGCGTGTGCCCAGAGGGCCGTACTGGTAGCCACTGTGAGCAGGAGGTGGACCCCTGCTTGGCCCAGCCCTGCCAGCATGGGGGGACCTGCCGTGGCTATATGGGGGGCTACATGTGTGAGTGTCTTCCTGGCTACAATGGTGATAACTGTGAGGACGACGTGGACGAGTGTGCCTCCCAGCCCTGCCAGCACGGGGGTTCATGCATTGACCTCGTGGCCCGCTATCTCTGCTCCTGTCCCCCAGGAACGCTGGGGGTGCTCTGCGAGATTAATGAGGATGACTGCGGCCCAGGCCCACCGCTGGACTCAGGGCCCCGGTGCCTACACAATGGCACCTGCGTGGACCTGGTGGGTGGTTTCCGCTGCACCTGTCCCCCAGGATACACTGGTTTGCGCTGCGAGGCAGACATCAATGAGTGTCGCTCAGGTGCCTGCCACGCGGCACACACCCGGGACTGCCTGCAGGACCCAGGCGGAGGTTTCCGTTGCCTTTGTCATGCTGGCTTCTCAGGTCCTCGCTGTCAGACTGTCCTGTCTCCCTGCGAGTCCCAGCCATGCCAGCATGGAGGCCAGTGCCGTCCTAGCCCGGGTCCTGGGGGTGGGCTGACCTTCACCTGTCACTGTGCCCAGCCGTTCTGGGGTCCGCGTTGCGAGCGGGTGGCGCGCTCCTGCCGGGAGCTGCAGTGCCCGGTGGGCGTCCCATGCCAGCAGACGCCCCGCGGGCCGCGCTGCGCCTGCCCCCCAGGGTTGTCGGGACCCTCCTGCCGCAGCTTCCCGGGGTCGCCGCCGGGGGCCAGCAACGCCAGCTGCGCGGCCGCCCCCTGTCTCCACGGGGGCTCCTGCCGCCCCGCGCCGCTCGCGCCCTTCTTCCGCTGCGCTTGCGCGCAGGGCTGGACCGGGCCGCGCTGCGAGGCGCCCGCCGCGGCACCCGAGGTCTCGGAGGAGCCGCGGTGCCCGCGCGCCGCCTGCCAGGCCAAGCGCGGGGACCAGCGCTGCGACCGCGAGTGCAACAGCCCAGGCTGCGGCTGGGACGGCGGCGACTGCTCGCTGAGCGTGGGCGACCCCTGGCGGCAATGCGAGGCGCTGCAGTGCTGGCGCCTCTTCAACAACAGCCGCTGCGACCCCGCCTGCAGCTCGCCCGCCTGCCTCTACGACAACTTCGACTGCCACGCCGGTGGCCGCGAGCGCACTTGCAACCCGGTGTACGAGAAGTACTGCGCCGACCACTTTGCCGACGGCCGCTGCGACCAGGGCTGCAACACGGAGGAGTGCGGCTGGGATGGGCTGGATTGTGCCAGCGAGGTGCCGGCCCTGCTGGCCCGCGGCGTGCTGGTGCTCACAGTGCTGCTGCCGCCAGAGGAGCTACTGCGTTCCAGCGCCGACTTTCTGCAGCGGCTCAGCGCCATCCTGCGCACCTCGCTGCGCTTCCGCCTGGACGCGCACGGCCAGGCCATGGTCTTCCCTTACCACCGGCCTAGTCCTGGCTCCGAACCCCGGGCCCGTCGGGAGCTGGCCCCCGAGGTGATCGGCTCGGTAGTAATGCTGGAGATTGACAACCGGCTCTGCCTGCAGTCGCCTGAGAATGATCACTGCTTCCCCGATGCCCAGAGCGCCGCTGACTACCTGGGAGCGTTGTCAGCGGTGGAGCGCCTGGACTTCCCGTACCCACTGCGGGACGTGCGGGGGGAGCCGCTGGAGCCTCCAGAACCCAGCGTCCCGCTGCTGCCACTGCTAGTGGCGGGCGCTGTCTTGCTGCTGGTCATTCTCGTCCTGGGTGTCATGGTGGCCCGGCGCAAGCGCGAGCACAGCACCCTCTGGTTCCCTGAGGGCTTCTCACTGCACAAGGACGTGGCCTCTGGTCACAAGGGCCGGCGGGAACCCGTGGGCCAGGACGCGCTGGGCATGAAGAACATGGCCAAGGGTGAGAGCCTGATGGGGGAGGTGGCCACAGACTGGATGGACACAGAGTGCCCAGAGGCCAAGCGGCTAAAGGTAGAGGAGCCAGGCATGGGGGCTGAGGAGGCTGTGGATTGCCGTCAGTGGACTCAACACCATCTGGTTGCTGCTGACATCCGCGTGGCACCAGCCATGGCACTGACACCACCACAGGGCGACGCAGATGCTGATGGCATGGATGTCAATGTGCGTGGCCCAGATGGCTTCACCCCGCTAATGCTGGCTTCCTTCTGTGGGGGGGCTCTGGAGCCAATGCCAACTGAAGAGGATGAGGCAGATGACACATCAGCTAGCATCATCTCCGACCTGATCTGCCAGGGGGCTCAGCTTGGGGCACGGACTGACCGTACTGGCGAGACTGCTTTGCACCTGGCTGCCCGTTATGCCCGTGCTGATGCAGCCAAGCGGCTGCTGGATGCTGGGGCAGACACCAATGCCCAGGACCACTCAGGCCGCACTCCCCTGCACACAGCTGTCACAGCCGATGCCCAGGGTGTCTTCCAGATTCTCATCCGAAACCGCTCTACAGACTTGGATGCCCGCATGGCAGATGGCTCAACGGCACTGATCCTGGCGGCCCGCCTGGCAGTAGAGGGCATGGTGGAAGAGCTCATCGCCAGCCATGCTGATGTCAATGCTGTGGATGAGCTTGGGAAATCAGCCTTACACTGGGCTGCGGCTGTGAACAACGTGGAAGCCACTTTGGCCCTGCTCAAAAATGGAGCCAATAAGGACATGCAGGATAGCAAGGAGGAGACCCCCCTATTCCTGGCCGCCCGCGAGGGCAGCTATGAGGCTGCCAAGCTGCTGTTGGACCACTTTGCCAACCGTGAGATCACCGACCACCTGGACAGGCTGCCGCGGGACGTAGCCCAGGAGAGACTGCACCAGGACATCGTGCGCTTGCTGGATCAACCCAGTGGGCCCCGCAGCCCCCCCGGTCCCCACGGCCTGGGGCCTCTGCTCTGTCCTCCAGGGGCCTTCCTCCCTGGCCTCAAAGCGGCACAGTCGGGGTCCAAGAAGAGCAGGAGGCCCCCCGGGAAGGCGGGGCTGGGGCCGCAGGGGCCCCGGGGGCGGGGCAAGAAGCTGACGCTGGCCTGCCCGGGCCCCCTGGCTGACAGCTCGGTCACGCTGTCGCCCGTGGACTCGCTGGACTCCCCGCGGCCTTTCGGTGGGCCCCCTGCTTCCCCTGGTGGCTTCCCCCTTGAGGGGCCCTATGCAGCTGCCACTGCCACTGCAGTGTCTCTGGCACAGCTTGGTGGCCCAGGCCGGGCGGGTCTAGGGCGCCAGCCCCCTGGAGGATGTGTACTCAGCCTGGGCCTGCTGAACCCTGTGGCTGTGCCCCTCGATTGGGCCCGGCTGCCCCCACCTGCCCCTCCAGGCCCCTCGTTCCTGCTGCCACTGGCGCCGGGACCCCAGCTGCTCAACCCAGGGACCCCCGTCTCCCCGCAGGAGCGGCCCCCGCCTTACCTGGCAGTCCCAGGACATGGCGAGGAGTACCCGGCGGCTGGGGCACACAGCAGCCCCCCAAAGGCCCGCTTCCTGCGGGTTCCCAGTGAGCACCCTTACCTGACCCCATCCCCCGAATCCCCTGAGCACTGGGCCAGCCCCTCACCTCCCTCCCTCTCAGACTGGTCCGAATCCACGCCTAGCCCAGCCACTGCCACTGGGGCCATGGCCACCACCACTGGGGCACTGCCTGCCCAGCCACTTCCCTTGTCTGTTCCCAGCTCCCTTGCTCAGGCCCAGACCCAGCTGGGGCCCCAGCCGGAAGTTACCCCCAAGAGGCAAGTGTTGGCCTGAGACGCTCGTCAGTTCTTAGATCTTGGGGGCCTAAAGAGACCCCCGTCCTGCCTCCTTTCTTTCTCTGTCTCTTCCTTCCTTTTAGTCTTTTTCATCCTCTTCTCTTTCCACCAACCCTCCTGCATCCTTGCCTTGCAGCGTGACCGAGATAGGTCATCAGCCCAGGGCTTCAGTCTTCCTTTATTTATAATGGGTGGGGGCTACCACCCACCCTCTCAGTCTTGTGAAGAGTCTGGGACCTCCTTCTTCCCCACTTCTCTCTTCCCTCATTCCTTTCTCTCTCCTTCTGGCCTCTCATTTCCTTACACTCTGACATGAATGAATTATTATTATTTTTATTTTTCTTTTTTTTTTTACATTTTGTATAGAAACAAATTCATTTAAACAAACTTATTATTATTATTTTTTACAAAATATATATATGGAGATGCTCCCTCCCCCTGTGAACCCCCCAGTGCCCCCGTGGGGCTGAGTCTGTGGGCCCATTCGGCCAAGCTGGATTCTGTGTACCTAGTACACAGGCATGACTGGGATCCCGTGTACCGAGTACACGACCCAGGTATGTACCAAGTAGGCACCCTTGGGCGCACCCACTGGGGCCAGGGGTCGGGGGAGTGTTGGGAGCCTCCTCCCCACCCCACCTCCCTCACTTCACTGCATTCCAGATGGGACATGTTCCATAGCCTTGCTGGGGAAGGGCCCACTGCCAACTCCCTCTGCCCCAGCCCCACCCTTGGCCATCTCCCTTTGGGAACTAGGGGGCTGCTGGTGGGAAATGGGAGCCAGGGCAGATGTATGCATTCCTTTGTGTCCCTGTAAATGTGGGACTACAAGAAGAGGAGCTGCCTGAGTGGTACTTTCTCTTCCTGGTAATCCTCTGGCCCAGCCTCATGGCAGAATAGAGGTATTTTTAGGCTATTTTTGTAATATGGCTTCTGGTCAAAATCCCTGTGTAGCTGAATTCCCAAGCCCTGCATTGTACAGCCCCCCACTCCCCTCACCACCTAATAAAGGAATAGTTAACACTCAAAAAAAAAAAAAAAAAAA
人notch 4(NOTCH4)mRNA NM_004557.3(SEQ ID NO:33)
AGACGTGAGGCTTGCAGCAGGCCGAGGAGGAAGAAGAGGGGCAGTGGGAGCAGAGGAGGTGGCTCCTGCCCCAGTGAGAGCTCTGAGGGTCCCTGCCTGAAGAGGGACAGGGACCGGGGCTTGGAGAAGGGGCTGTGGAATGCAGCCCCCTTCACTGCTGCTGCTGCTGCTGCTGCTGCTGCTGCTATGTGTCTCAGTGGTCAGACCCAGAGGGCTGCTGTGTGGGAGTTTCCCAGAACCCTGTGCCAATGGAGGCACCTGCCTGAGCCTGTCTCTGGGACAAGGGACCTGCCAGTGTGCCCCTGGCTTCCTGGGTGAGACGTGCCAGTTTCCTGACCCCTGCCAGAACGCCCAGCTCTGCCAAAATGGAGGCAGCTGCCAAGCCCTGCTTCCCGCTCCCCTAGGGCTCCCCAGCTCTCCCTCTCCATTGACACCCAGCTTCTTGTGCACTTGCCTCCCTGGCTTCACTGGTGAGAGATGCCAGGCCAAGCTTGAAGACCCTTGTCCTCCCTCCTTCTGTTCCAAAAGGGGCCGCTGCCACATCCAGGCCTCGGGCCGCCCACAGTGCTCCTGCATGCCTGGATGGACAGGTGAGCAGTGCCAGCTTCGGGACTTCTGTTCAGCCAACCCATGTGTTAATGGAGGGGTGTGTCTGGCCACATACCCCCAGATCCAGTGCCACTGCCCACCGGGCTTCGAGGGCCATGCCTGTGAACGTGATGTCAACGAGTGCTTCCAGGACCCAGGACCCTGCCCCAAAGGCACCTCCTGCCATAACACCCTGGGCTCCTTCCAGTGCCTCTGCCCTGTGGGGCAGGAGGGTCCACGTTGTGAGCTGCGGGCAGGACCCTGCCCTCCTAGGGGCTGTTCGAATGGGGGCACCTGCCAGCTGATGCCAGAGAAAGACTCCACCTTTCACCTCTGCCTCTGTCCCCCAGGTTTCATAGGCCCAGACTGTGAGGTGAATCCAGACAACTGTGTCAGCCACCAGTGTCAGAATGGGGGCACTTGCCAGGATGGGCTGGACACCTACACCTGCCTCTGCCCAGAAACCTGGACAGGCTGGGACTGCTCCGAAGATGTGGATGAGTGTGAGACCCAGGGTCCCCCTCACTGCAGAAACGGGGGCACCTGCCAGAACTCTGCTGGTAGCTTTCACTGCGTGTGTGTGAGTGGCTGGGGCGGCACAAGCTGTGAGGAGAACCTGGATGACTGTATTGCTGCCACCTGTGCCCCGGGATCCACCTGCATTGACCGGGTGGGCTCTTTCTCCTGCCTCTGCCCACCTGGACGCACAGGACTCCTGTGCCACTTGGAAGACATGTGTCTGAGCCAGCCGTGCCATGGGGATGCCCAATGCAGCACCAACCCCCTCACAGGCTCCACACTCTGCCTGTGTCAGCCTGGCTATTCGGGGCCCACCTGCCACCAGGACCTGGACGAGTGTCTGATGGCCCAGCAAGGCCCAAGTCCCTGTGAACATGGCGGTTCCTGCCTCAACACTCCTGGCTCCTTCAACTGCCTCTGTCCACCTGGCTACACAGGCTCCCGTTGTGAGGCTGATCACAATGAGTGCCTCTCCCAGCCCTGCCACCCAGGAAGCACCTGTCTGGACCTACTTGCCACCTTCCACTGCCTCTGCCCGCCAGGCTTAGAAGGGCAGCTCTGTGAGGTGGAGACCAACGAGTGTGCCTCAGCTCCCTGCCTGAACCACGCGGATTGCCATGACCTGCTCAACGGCTTCCAGTGCATCTGCCTGCCTGGATTCTCCGGCACCCGATGTGAGGAGGATATCGATGAGTGCAGAAGCTCTCCCTGTGCCAATGGTGGGCAGTGCCAGGACCAGCCTGGAGCCTTCCACTGCAAGTGTCTCCCAGGCTTTGAAGGGCCACGCTGTCAAACAGAGGTGGATGAGTGCCTGAGTGACCCATGTCCCGTTGGAGCCAGCTGCCTTGATCTTCCAGGAGCCTTCTTTTGCCTCTGCCCCTCTGGTTTCACAGGCCAGCTCTGTGAGGTTCCCCTGTGTGCTCCCAACCTGTGCCAGCCCAAGCAGATATGTAAGGACCAGAAAGACAAGGCCAACTGCCTCTGTCCTGATGGAAGCCCTGGCTGTGCCCCACCTGAGGACAACTGCACCTGCCACCACGGGCACTGCCAGAGATCCTCATGTGTGTGTGACGTGGGTTGGACGGGGCCAGAGTGTGAGGCAGAGCTAGGGGGCTGCATCTCTGCACCCTGTGCCCATGGGGGGACCTGCTACCCCCAGCCCTCTGGCTACAACTGCACCTGCCCTACAGGCTACACAGGACCCACCTGTAGTGAGGAGATGACAGCTTGTCACTCAGGGCCATGTCTCAATGGCGGCTCCTGCAACCCTAGCCCTGGAGGCTACTACTGCACCTGCCCTCCAAGCCACACAGGGCCCCAGTGCCAAACCAGCACTGACTACTGTGTGTCTGCCCCGTGCTTCAATGGGGGTACCTGTGTGAACAGGCCTGGCACCTTCTCCTGCCTCTGTGCCATGGGCTTCCAGGGCCCGCGCTGTGAGGGAAAGCTCCGCCCCAGCTGTGCAGACAGCCCCTGTAGGAATAGGGCAACCTGCCAGGACAGCCCTCAGGGTCCCCGCTGCCTCTGCCCCACTGGCTACACCGGAGGCAGCTGCCAGACTCTGATGGACTTATGTGCCCAGAAGCCCTGCCCACGCAATTCCCACTGCCTCCAGACTGGGCCCTCCTTCCACTGCTTGTGCCTCCAGGGATGGACCGGGCCTCTCTGCAACCTTCCACTGTCCTCCTGCCAGAAGGCTGCACTGAGCCAAGGCATAGACGTCTCTTCCCTTTGCCACAATGGAGGCCTCTGTGTCGACAGCGGCCCCTCCTATTTCTGCCACTGCCCCCCTGGATTCCAAGGCAGCCTGTGCCAGGATCACGTGAACCCATGTGAGTCCAGGCCTTGCCAGAACGGGGCCACCTGCATGGCCCAGCCCAGTGGGTATCTCTGCCAGTGTGCCCCAGGCTACGATGGACAGAACTGCTCAAAGGAACTCGATGCTTGTCAGTCCCAACCCTGTCACAACCATGGAACCTGTACTCCCAAACCTGGAGGATTCCACTGTGCCTGCCCTCCAGGCTTTGTGGGGCTACGCTGTGAGGGAGACGTGGACGAGTGTCTGGACCAGCCCTGCCACCCCACAGGCACTGCAGCCTGCCACTCTCTGGCCAATGCCTTCTACTGCCAGTGTCTGCCTGGACACACAGGCCAGTGGTGTGAGGTGGAGATAGACCCCTGCCACAGCCAACCCTGCTTTCATGGAGGGACCTGTGAGGCCACAGCAGGATCACCCCTGGGTTTCATCTGCCACTGCCCCAAGGGTTTTGAAGGCCCCACCTGCAGCCACAGGGCCCCTTCCTGCGGCTTCCATCACTGCCACCACGGAGGCCTGTGTCTGCCCTCCCCTAAGCCAGGCTTCCCACCACGCTGTGCCTGCCTCAGTGGCTATGGGGGTCCTGACTGCCTGACCCCACCAGCTCCTAAAGGCTGTGGCCCTCCCTCCCCATGCCTATACAATGGCAGCTGCTCAGAGACCACGGGCTTGGGGGGCCCAGGCTTTCGATGCTCCTGCCCTCACAGCTCTCCAGGGCCCCGGTGTCAGAAACCCGGAGCCAAGGGGTGTGAGGGCAGAAGTGGAGATGGGGCCTGCGATGCTGGCTGCAGTGGCCCGGGAGGAAACTGGGATGGAGGGGACTGCTCTCTGGGAGTCCCAGACCCCTGGAAGGGCTGCCCCTCCCACTCTCGGTGCTGGCTTCTCTTCCGGGACGGGCAGTGCCACCCACAGTGTGACTCTGAAGAGTGTCTGTTTGATGGCTACGACTGTGAGACCCCTCCAGCCTGCACTCCAGCCTATGACCAGTACTGCCATGATCACTTCCACAACGGGCACTGTGAGAAAGGCTGCAACACTGCAGAGTGTGGCTGGGATGGAGGTGACTGCAGGCCTGAAGATGGGGACCCAGAGTGGGGGCCCTCCCTGGCCCTGCTGGTGGTACTGAGCCCCCCAGCCCTAGACCAGCAGCTGTTTGCCCTGGCCCGGGTGCTGTCCCTGACTCTGAGGGTAGGACTCTGGGTAAGGAAGGATCGTGATGGCAGGGACATGGTGTACCCCTATCCTGGGGCCCGGGCTGAAGAAAAGCTAGGAGGAACTCGGGACCCCACCTATCAGGAGAGAGCAGCCCCTCAAACGCAGCCCCTGGGCAAGGAGACCGACTCCCTCAGTGCTGGGTTTGTGGTGGTCATGGGTGTGGATTTGTCCCGCTGTGGCCCTGACCACCCGGCATCCCGCTGTCCCTGGGACCCTGGGCTTCTACTCCGCTTCCTTGCTGCGATGGCTGCAGTGGGAGCCCTGGAGCCCCTGCTGCCTGGACCACTGCTGGCTGTCCACCCTCATGCAGGGACCGCACCCCCTGCCAACCAGCTTCCCTGGCCTGTGCTGTGCTCCCCAGTGGCCGGGGTGATTCTCCTGGCCCTAGGGGCTCTTCTCGTCCTCCAGCTCATCCGGCGTCGACGCCGAGAGCATGGAGCTCTCTGGCTGCCCCCTGGTTTCACTCGACGGCCTCGGACTCAGTCAGCTCCCCACCGACGCCGGCCCCCACTAGGCGAGGACAGCATTGGTCTCAAGGCACTGAAGCCAAAGGCAGAAGTTGATGAGGATGGAGTTGTGATGTGCTCAGGCCCTGAGGAGGGAGAGGAGGTGGGCCAGGCTGAAGAAACAGGCCCACCCTCCACGTGCCAGCTCTGGTCTCTGAGTGGTGGCTGTGGGGCGCTCCCTCAGGCAGCCATGCTAACTCCTCCCCAGGAATCTGAGATGGAAGCCCCTGACCTGGACACCCGTGGACCTGATGGGGTGACACCCCTGATGTCAGCAGTTTGCTGTGGGGAAGTACAGTCCGGGACCTTCCAAGGGGCATGGTTGGGATGTCCTGAGCCCTGGGAACCTCTGCTGGATGGAGGGGCCTGTCCCCAGGCTCACACCGTGGGCACTGGGGAGACCCCCCTGCACCTGGCTGCCCGATTCTCCCGGCCAACCGCTGCCCGCCGCCTCCTTGAGGCTGGAGCCAACCCCAACCAGCCAGACCGGGCAGGGCGCACACCCCTTCATGCTGCTGTGGCTGCTGATGCTCGGGAGGTCTGCCAGCTTCTGCTCCGTAGCAGACAAACTGCAGTGGACGCTCGCACAGAGGACGGGACCACACCCTTGATGCTGGCTGCCAGGCTGGCGGTGGAAGACCTGGTTGAAGAACTGATTGCAGCCCAAGCAGACGTGGGGGCCAGAGATAAATGGGGGAAAACTGCGCTGCACTGGGCTGCTGCCGTGAACAACGCCCGAGCCGCCCGCTCGCTTCTCCAGGCCGGAGCCGATAAAGATGCCCAGGACAACAGGGAGCAGACGCCGCTATTCCTGGCGGCGCGGGAAGGAGCGGTGGAAGTAGCCCAGCTACTGCTGGGGCTGGGGGCAGCCCGAGAGCTGCGGGACCAGGCTGGGCTAGCGCCGGCGGACGTCGCTCACCAACGTAACCACTGGGATCTGCTGACGCTGCTGGAAGGGGCTGGGCCACCAGAGGCCCGTCACAAAGCCACGCCGGGCCGCGAGGCTGGGCCCTTCCCGCGCGCACGGACGGTGTCAGTAAGCGTGCCCCCGCATGGGGGCGGGGCTCTGCCGCGCTGCCGGACGCTGTCAGCCGGAGCAGGCCCTCGTGGGGGCGGAGCTTGTCTGCAGGCTCGGACTTGGTCCGTAGACTTGGCTGCGCGGGGGGGCGGGGCCTATTCTCATTGCCGGAGCCTCTCGGGAGTAGGAGCAGGAGGAGGCCCGACCCCTCGCGGCCGTAGGTTTTCTGCAGGCATGCGCGGGCCTCGGCCCAACCCTGCGATAATGCGAGGAAGATACGGAGTGGCTGCCGGGCGCGGAGGCAGGGTCTCAACGGATGACTGGCCCTGTGATTGGGTGGCCCTGGGAGCTTGCGGTTCTGCCTCCAACATTCCGATCCCGCCTCCTTGCCTTACTCCGTCCCCGGAGCGGGGATCACCTCAACTTGACTGTGGTCCCCCAGCCCTCCAAGAAATGCCCATAAACCAAGGAGGAGAGGGTAAAAAATAGAAGAATACATGGTAGGGAGGAATTCCAAAAATGATTACCCATTAAAAGGCAGGCTGGAAGGCCTTCCTGGTTTTAAGATGGATCCCCCAAAATGAAGGGTTGTGAGTTTAGTTTCTCTCCTAAAATGAATGTATGCCCACCAGAGCAGACATCTTCCACGTGGAGAAGCTGCAGCTCTGGAAAGAGGGTTTAAGATGCTAGGATGAGGCAGGCCCAGTCCTCCTCCAGAAAATAAGACAGGCCACAGGAGGGCAGAGTGGAGTGGAAATACCCCTAAGTTGGAACCAAGAATTGCAGGCATATGGGATGTAAGATGTTCTTTCCTATATATGGTTTCCAAAGGGTGCCCCTATGATCCATTGTCCCCACTGCCCACAAATGGCTGACAAATATTTATTGGGCACCTACTATGTGCCAGGCACTGTGTAGGTGCTGAAAAGTGGCCAAGGGCCACCCCCGCTGATGACTCCTTGCATTCCCTCCCCTCACAACAAAGAACTCCACTGTGGGGATGAAGCGCTTCTTCTAGCCACTGCTATCGCTATTTAAGAACCCTAAATCTGTCACCCATAATAAAGCTGATTTGAAGTGTTAAAAAAAAAAAAAAAAAA
在一些实施方案中，编码Notch的核酸序列，如本文所述，与SEQ ID NO:29、SEQ IDNO:30、SEQ ID NO:31、SEQ ID NO:32或SEQ ID NO:33的序列至少80％相同。在一些实施方案中，编码Notch的核酸序列与SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32或SEQ ID NO:33的序列80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％相同。在一些实施方案中，Notch的核酸序列，如本文所述，可以与SEQ ID NO:29、SEQ ID NO:30、SEQ ID NO:31、SEQ ID NO:32或SEQ ID NO:33的序列有1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29或30或更多个核苷酸的不同。
本公开的“嵌合Notch受体多肽”包含：a)包含特异性结合对的第一成员的细胞外结构域；b)Notch受体多肽，其中Notch受体多肽具有从50个氨基酸至1000个氨基酸的长度，并且包含一个或多个配体可诱导的蛋白水解切割位点；以及c)细胞内结构域。特异性结合对的第一成员与特异性结合对的第二成员的结合诱导Notch受体多肽在一个或多个配体可诱导的蛋白水解切割位点的切割，由此释放细胞内结构域。细胞内结构域的释放调控生成嵌合Notch受体多肽的细胞的活性。细胞外结构域包含特异性结合对的第一成员；特异性结合对的第一成员包含与Notch受体多肽异源的氨基酸序列。细胞内结构域包含与Notch受体多肽异源的氨基酸序列。
术语“抗原结合结构域”是指与靶抗原特异性结合的结构域。在一些实施例中，抗原结合结构域可以由单链多肽中存在的氨基酸形成。在其他实例中，抗原结合结构域可以由第一单链多肽中存在的氨基酸以及一个或多个另外的单链多肽(例如，第二单链多肽)中存在的氨基酸形成。本文描述了抗原结合结构域的非限制性实例，包括，没有限制，scFvs或生长因子的LBD(配体结合结构域)。本领域已知抗原结合结构域的另外的实例。
如本文所用，术语“抗原”通常是指由本文所述的抗原结合结构域特异性识别的结合配偶体。例示性的抗原包括不同种类的分子，例如但不限于，多肽和它的肽片段、小分子、脂质、碳水化合物和核酸。抗原或多个抗原的非限制性实例可以由本文描述的任何抗原结合结构域特异性结合。本领域已知可以由任何抗原结合结构域特异性结合的抗原或多个抗原的另外的实例。
术语“抗体”和“免疫球蛋白”包括任何同种型的抗体或免疫球蛋白，保留与抗原特异性结合的抗体的片段，包括但不限于，Fab、Fv、scFv和Fd片段、嵌合抗体、人源化抗体、单链抗体(scAb)、单结构域抗体(dAb)、单结构域重链抗体、单结构域轻链抗体、纳米抗体、双特异性抗体、多特异性抗体以及包含抗体或非抗体蛋白质的抗原-结合(本文也称为抗原结合)部分的融合蛋白。所述术语也涵盖Fab′、Fv、F(ab′).sub.2和/或保留与抗原特异性结合的其他抗体片段，以及单克隆抗体。可以使用杂交瘤生产技术生产单克隆抗体，也可以使用本领域技术人员已知的其他生产方法(例如，衍生自抗体噬菌体展示文库的抗体)。抗体可以是单价的或二价的。
本文所用的术语“人源化免疫球蛋白”是指包含不同来源的免疫球蛋白的部分的免疫球蛋白，其中至少一部分包含人源的氨基酸序列。例如，人源化抗体可以包含衍生自具有必需特异性的非人源的免疫球蛋白，例如小鼠，以及衍生自人源的免疫球蛋白序列(例如嵌合免疫球蛋白)的部分，通过常规技术以化学方式连接在一起(例如合成)或者使用基因工程技术制备为连续多肽(例如，可以表达编码嵌合抗体的蛋白质部分的DNA以生产连续多肽链)。人源化免疫球蛋白的另一个实例是含有一个或多个包含衍生自非人源的抗体的互补决定区(CDR)和衍生自人源的轻和/或重链的框架区的免疫球蛋白链的免疫球蛋白(例如，有或没有框架改变的CDR移植抗体)。术语人源化免疫球蛋白也涵盖嵌合或CDR移植单链抗体。关于单链抗体，参见例如Cabilly et al.，美国专利号4,816,567；Boss et al.，美国专利号4,816,397；Neuberger,M.S.et al.，WO 86/01533；Winter,美国专利号5,225,539；也参见，Ladner et al.，美国专利号4,946,778；Huston,美国专利号5,476,786；以及Bird,R.E.et al.，Science,242:423-426(1988))。
术语“纳米抗体”(Nb)是指衍生自天然存在的重链抗体的最小抗原结合片段或单可变结构域(V.sub.HH)。它们衍生自骆驼科动物中所见仅有重链的抗体。在“骆驼科动物”的科中发现了缺乏轻多肽链的免疫球蛋白。“骆驼科动物”包含旧大陆骆驼科动物(双峰驼(Camelus bactrianus)和单峰驼(Camelus dromedarius))以及新大陆骆驼科动物(例如，羊驼(Llama paccos)、美洲驼(Llama glama)、原驼(Llama guanicoe)和骆马(Llamavicugna))。单可变结构域重链抗体在本文中是指纳米抗体或VHH抗体。
“抗体片段”包含完整抗体的一部分，例如，完整抗体的抗原结合或可变区。抗体片段的实例包括Fab、Fab′、F(ab′)2和Fv片段；双抗体；线性抗体(Zapata et al.,ProteinEng.8(10):1057-1062(1995))；结构域抗体(dAb；Holt et al.,Trends Biotechnol.21:484,2003)；单链抗体分子；以及由抗体片段形成的多特异性抗体。木瓜蛋白酶消化抗体生成两个相同的抗原结合片段，称为“Fab”片段，每个具有单个抗原结合位点，以及残留的“Fc”片段，名称反映了容易结晶的能力。胃蛋白酶处理产生F(ab′)2片段，其具有两个抗原结合位点并仍然能够交联抗原。
“Fv”是含有完整抗原识别和结合位点的最小抗体片段。该区域由以紧密的非共价结合的一个重链和一个轻链可变结构域的二聚体组成。在该构型中，每个可变结构域的三个CDRS相互作用以在VH-VL二聚体的表面上限定抗原结合位点。六个CDR共同赋予抗体以抗原结合特异性。然而，即使单个可变结构域(或仅包含三个对抗原特异的CDR的Fv的一半)也具有识别和结合抗原的能力，尽管是以比完整结合位点更低的亲和力。
“Fab”片段也含有轻链的恒定结构域和重链的第一恒定结构域(CH1)。Fab片段与Fab′片段的不同之处在于在重链CH1结构域的羧基末端添加少数残基，包括来自抗体铰链区的一个或多个半胱氨酸。Fab′-SH是本文中关于Fab′的名称，其中恒定结构域的半胱氨酸残基带有游离巯基。F(ab′)2抗体片段最初是作为Fab′片段对生成的，它们之间具有铰链半胱氨酸。还已知抗体片段的其他化学偶联。
可以基于其恒定结构域的氨基酸序列将来自任何脊椎动物物种的抗体(免疫球蛋白)的“轻链”分配为称为kappa和lambda的两种明显不同的类型之一。根据其重链的恒定结构域的氨基酸序列，可以将免疫球蛋白分配为不同的种类。有五个免疫球蛋白的主要种类：IgA、IgD、IgE、IgG和IgM，并且这些种类的一些可以进一步划分为子类(同种型)，例如，IgG1、IgG2、IgG3、IgG4、IgA和IgA2。子类可以进一步划分为类型，例如，IgG2a和IgG2b。
“单链Fv”或“sFv”或“scFv”抗体片段包含抗体的VH和VL结构域，其中这些结构域存在于单个多肽链中。在一些实施方案中，Fv多肽在VH和VL结构域之间进一步包含多肽接头，使sFV能够形成抗原结合所需的结构。关于sFv的综述，参见Pluckthun in ThePharmacology of Monoclonal Antibodies,Vol.113,Rosenburg and Moore eds.,Springer-Verlag,New York,pp.269-315(1994)。
术语“双抗体”是指具有两个抗原结合位点的小抗体片段，其片段包含在同一多肽链(VH-VL)中与轻链可变结构域(VL)连接的重链可变结构域(VH)。双抗体描述于EP 404,097；WO 93/11161；和Hollinger et al.,Proc.Natl.Acad.Sci.U.S.A.90:6444-6448,1993。
术语“多肽”、“肽”和“蛋白质”(本文中可互换使用)是指任何长度的聚合形式的氨基酸，其可以包括基因编码氨基酸和非基因编码氨基酸、以化学或生物化学方式修饰的或衍生化的氨基酸以及具有经修饰的肽骨架的多肽。所述术语包括融合蛋白，包括但不限于，具有异源氨基酸序列的融合蛋白，与异源和同源前导序列的融合，有或没有N末端甲硫氨酸残基；免疫标记的蛋白质等。
“分离的”多肽是已经从其天然环境的成分中鉴定和分离和/或回收的多肽。其天然环境的污染成分是会干扰多肽的诊断或治疗用途的物质，并且可以包括酶、激素和其他蛋白质的或非蛋白质的溶质。在一些实施方案中，可以将多肽纯化至大于90％、大于95％或大于98％。
术语“嵌合抗原受体”和“CAR”(本文中可互换使用)是指能够触发或抑制免疫细胞激活的人工多模块分子，其通常但不排他地包含细胞外结构域(例如，配体/抗原结合结构域)、跨膜结构域和一个或多个细胞内信号传导结构域。术语CAR不特别限于CAR分子，还包括CAR变体，即描述于例如PCT申请号US2014/016527；Fedorov et al.,Sci Transl.Med.5(215):215ra172,2013；Glienke et al.,Front.Pharmacol.6:21,2015；Kakarla&Gottschalk,Cancer J.20(2):151-155,2014；Riddell et al.,Cancer J.20(2):141-144,2014；Pegram et al.,Cancer J.20(2):127-33,2014；Cheadle et al.,Immunol Rev.257(1):91-106,2014；Barrett et al.,Ann.Rev.Med.65:333-347,2014；Sadelain et al.,Cancer Discov.3(4):388-98,2013；以及Cartellieri et al.,J.Biomed.Biotechnol.956304,2010中的CAR变体；其公开内容通过引用整体并入本文。
在本发明中，核苷酸序列的转录通过由与不同的多肽融合的以高选择性与所选择的DNA序列结合的HNF1 DNA结合结构域(例如，人HNF1 DNA结合结构域)组成的转录激活物融合蛋白激活，所述不同的多肽负责转录激活物的配体依赖性活性以及它的转录活性(例如，人RelA蛋白)。本发明的融合蛋白对调控与所选择的HNF1 DNA结合位点连接的任何靶基因的转录水平有用。融合蛋白可以用于在缺乏内源性HNF1和vHNF1蛋白的组织中特异性激活由HNF1应答启动子控制的基因的转录。本发明的融合蛋白主要由人元件组成。完全人类蛋白质减轻了转录激活物免疫识别的风险。阻遏物也以类似的方式提供。
美国专利号9,670,281描述各种嵌合Notch受体、如何构建它们以及使用它们的方法。下文描述的详述如何人源化嵌合Notch受体以具有低免疫原性的实例可以采用美国专利号9,670,281中所示的嵌合Notch受体，例如，在单核细胞/巨噬细胞谱系的细胞中。
始终使用某些缩写词以描述四种人Notch蛋白的结构域。这些是：NEC：细胞外亚基；NTM：跨膜亚基；EGF：表皮生长因子；HD：异源二聚化结构域；ICN：细胞内结构域；LNR：富含半胱氨酸的LNR重复；TM：跨膜结构域；RAM：RAM结构域；NLS：核定位信号；ANK：锚蛋白重复域；NCR：半胱氨酸反应区；TAD：转录激活结构域；PEST：富含脯氨酸(P)、谷氨酰胺(E)、丝氨酸(S)和苏氨酸(T)残基的区域。
方法
除了用于基因疗法的用途之外，掺入本发明的人源化DBD的配体依赖性转录因子可以用于调控基因的表达，所述基因包含在重组病毒载体中并且可以在生产过程中干扰包装细胞系中病毒的生长。这些重组病毒可以是腺病毒、逆转录病毒、慢病毒、疱疹病毒、腺相关病毒和本领域技术人员熟悉的其他病毒的衍生物。另一个用途是使用体外培养的细胞提供感兴趣的毒性蛋白质的大规模生产，所述培养细胞不含有内源性HNF1/vHNF1，并且经修饰以含有编码转录激活物的核酸以及编码感兴趣的蛋白质的基因，所述转录激活物以适于在细胞中表达转录激活物的形式含有编码携带本发明的DBD，并且所述基因可操作地连接例如HNF1依赖性启动子。
为了在体内诱导或抑制转录，可以将配体施用于机体或感兴趣的组织(例如，通过注射)。待治疗的机体可以是动物，特别是哺乳动物，其可以是人或非人，例如兔、豚鼠、大鼠、小鼠或其他啮齿动物、猫、狗、猪、绵羊、山羊、牛或马，或者是鸟，例如鸡。适合的施用途径包括口服，腹膜内、肌肉内或静脉注射。
生产根据本发明的多肽或融合蛋白的一个便利方式是通过在表达系统中使用核酸来表达编码它的核酸。因此，本发明还在各个方面提供了编码本发明的转录激活物或阻遏物的核酸，其可以用于所编码的蛋白质的生产。
通常，无论是否编码依照本发明的蛋白质或成分，作为分离物、以分离的和/或纯化的形式、或者没有或基本上没有与其天然相关的物质(例如，除了可能用于表达的一个或多个调节序列，没有或基本上没有在人基因组中基因侧翼的核酸)来提供核酸。核酸可以是完全或部分合成的，并且可以包括基因组DNA、cDNA或RNA。当根据本发明的核酸包括RNA时，应将对所示序列的引用解释为涵盖对RNA等同物(用U取代T)的引用。
本领域技术人员使用本文包含的信息和参考文献以及本领域已知的技术可以容易地制备编码依照本发明的多肽或融合蛋白的核酸序列。Sambrook et al.,A MolecularCloning,A Laboratory Manual,Cold Spring Harbor LaboratoryPress(1989-2016)和Ausubel et al.,Current Protocols in Molecular Biology,John Wiley and Sons,(1994-2016)。这些技术包括(i)使用聚合酶链式反应(PCR)以扩增此类核酸的样品，例如从基因组来源，(ii)化学合成，或者(iii)制备cDNA序列。可以以本领域技术人员已知的任何适合的方式生成并使用编码全长编码序列的一部分的DNA(例如，DNA结合结构域，或视情况而定的调节结构域)，包括通过采用编码DNA，在待表达部分的任一侧鉴定适合的限制酶识别位点，并从DNA中切除所述部分。然后可以将该部分与标准市售表达系统中的适合的启动子可操作地连接。另一种重组方法是用适合的PCR引物扩增DNA的相关部分。可以例如使用定点突变对相关序列进行修饰，以导致经修饰肽的表达或以考虑用于表达核酸的宿主细胞中的密码子偏好。
为了获得核酸序列的表达，可以将序列掺入具有一个或多个与核酸可操作连接的控制序列以控制其表达的载体中。载体可以包括其他序列例如启动子或增强子以驱动插入的核酸、核酸序列的表达，使得多肽或肽作为融合物生成和/或编码分泌信号的核酸的表达，使得从细胞中分泌宿主细胞中生成的多肽。然后可以通过将载体转化到载体有功能的宿主细胞中，培养宿主细胞使得生成多肽以及从宿主细胞或周围培养基中回收多肽来获得多肽。在本领域中使用原核和真核细胞用于此目的，包括大肠杆菌的菌株、酵母以及真核细胞例如COS或CHO细胞。
因此，本发明还涵盖制备所公开的多肽或融合蛋白的方法，所述方法包括从编码产物的核酸的表达(通常为依照本发明的核酸)。这可以通过在导致或允许多肽表达的适当的条件下在培养物中培养含有此类载体的宿主细胞来方便地实现。也可以在体外系统中表达多肽。
公知在多种不同的宿主细胞中克隆和表达多肽的系统。适合的宿主细胞包括细菌、真核细胞例如哺乳动物的和酵母以及杆状病毒系统。本领域中可获得的用于表达异源多肽的哺乳动物细胞系包括中国仓鼠卵巢细胞、HeLa细胞、幼仓鼠肾细胞、COS细胞和许多其他细胞。常见的优选细菌宿主是大肠杆菌。
可以选择或构建含有适当的调节序列的适合的载体，其包括启动子序列、终止子片段、多腺苷酸化序列、增强子序列、标志物基因和其他适当的序列。载体可以适当地是质粒、病毒，例如噬菌体或噬菌粒。更多详情参见例如，Molecular cloning:a LaboratoryManual:4th edition,Green and Sambrook etal.,2012,Cold Spring HarborLaboratory Press。许多已知的用于操纵核酸的技术和规程，例如制备核酸构建体、诱变、测序、将DNA导入细胞和基因表达、以及蛋白质分析，详细描述于Current Protocols inMolecular Biology,Ausubel et al.,Eds.,John Wiley&Sons,2016。
为了在哺乳动物细胞中使用，可以通过病毒遗传物质提供重组表达载体的控制功能。例示性的启动子包括衍生自多瘤病毒、腺病毒2、巨细胞病毒和SV40的那些。
在本发明中使用的重组表达载体的调节序列可以指导在特定细胞类型中优选表达多肽或融合蛋白，即可以使用组织特异性调节元件。在一个实施方案中，本发明的重组表达载体为质粒。或者，本发明的重组表达载体可以是病毒或它的一部分，其允许导入到病毒核酸中的核酸的表达。例如，可以使用复制缺陷型逆转录病毒、腺病毒和腺相关病毒。用于生成重组逆转录病毒和用此类病毒体外或体内感染细胞的规程可以在Ausubel等人(同上)中找到。可以操纵病毒例如腺病毒的基因组使得其编码并表达转录激活物蛋白或阻遏物蛋白，但就其在正常裂解病毒生命周期中复制的能力而言是失活的。
因此，本发明的另一方面提供了含有本文公开的异源核酸的宿主细胞。
更进一步地，可以设计重组表达载体以允许编码转录激活物或阻遏物的核酸与宿主细胞中的靶基因之间的同源重组。可以使用此类同源重组载体以产生表达本发明的融合蛋白的同源重组动物。
可以使用的哺乳动物细胞系的实例包括CHO dhfr-细胞(Urlaub and Chasin,Proc.Natl.Acad.Sci.U.S.A.77:4216-4220,1980)、293细胞(Graham et al.,J.Gen.Virol.36:59,1977)和骨髓瘤细胞如SP2或NS0(Meth.Enzymol.73(B):3-46,2016)。除细胞系外，本发明适用于正常细胞，例如用于基因疗法目的修饰的细胞或为了产生转基因或同源重组动物修饰的胚胎细胞。用于基因疗法目的的特别感兴趣的细胞类型的实例包括造血干细胞、成肌细胞、肝细胞、淋巴细胞、肌细胞、神经细胞和皮肤上皮以及气道上皮。此外，对于转基因或同源重组动物，可以修饰胚胎干细胞和受精卵以含有编码转录激活物融合蛋白或阻遏物融合蛋白的核酸。
实施例
包括以下实施例以说明本发明的优选实施方案。本领域技术人员应该理解，以下实施例中公开的技术代表发明人发现的在本发明的实践中很好地发挥作用的技术，并因此可以认为是构成其实践的优选模式。然而，根据本公开内容，本领域技术人员应该理解，在不脱离本发明的精神和范围的情况下，可以对所公开的具体实施方案进行许多改变并仍然获得相同或相似的结果。
测试了所有四种人Notch蛋白(Notch 1-4)的核心LNR、HD和跨膜结构域响应N末端细胞外CD19 scFv融合物与其同源抗原结合，选择性释放与其细胞内部分C末端融合的GAL4-VP16转录因子的能力。人Notch2和Notch3在抗原结合后释放出功能性量的转录因子。人Notch1响应抗原结合释放出少量转录因子，而人Notch4没有释放出可检测量的转录因子。人Notch3显示出响应抗原结合的转录因子的最佳功能性释放，并用于许多设计。
我们进一步改进了最小LIN12-HD跨膜“核心”Notch2和Notch3结构域以包括额外的、短(～60aa)细胞内结构域，所述细胞内结构域包括天然Notch核定位序列(NLS)以改进自切割和释放转录因子结构域后的核输入。
为了使嵌合Notch受体的免疫原性最小化，设计并由以下构建一系列合成的人源化转录因子：(1)最小化的人DNA结合结构域(DBD)和(2)最小化的强转录激活结构域(TAD)。产生非天然但人源化的嵌合体的原因是消除不想要的内源性辅因子相互作用，所述相互作用在嵌合Notch受体释放的人源化转录因子和与全长人转录因子相互作用的天然结合配偶体之间。这是为了在利用人源化抗原受体的细胞应用中改进嵌合抗原受体诱导的转录反应的稳健性和可预测性。
为了找到天然DNA结合结构域以满足以下几个标准，进行人转录因子的全面筛选：(1)DNA结合结构域属于通常不在靶宿主细胞类型中天然表达的转录因子。在本实施方案中，我们寻找任何造血谱系中不存在的DNA结合结构域，包括特别是淋巴样和T细胞谱系；以及(2)DNA结合结构域以高亲和力与其靶DNA序列结合，其中解离常数等于或低于10 nM。
首先通过表达与天然转录激活结构域融合的DNA结合结构域来测试DNA结合结构域与多位点合成启动子结合的能力，以证实它可以上调由合成多位点启动子驱动的GFP。这证实了设计的同源启动子-DNA结合结构域对是正确的。
然后测试作为与synNotch以及强转录激活结构域的融合物的经证实的DNA结合结构域，并测定它们在外源抗原刺激下并释放至细胞核时上调驱动GFP的同源多位点启动子的能力。
用该策略测试的人DNA结合结构域的实例为取自以下的那些：人CRX(Furukawa,Takahisa,Eric M.Morrow,and Constance L.Cepko."Crx,a novel otx-like homeoboxgene,shows photoreceptor-specific expression and regulates photoreceptordifferentiation."Cell 91.4(1997):531-541,//doi.org/10.1016/S0092-8674(00)80439-0)、POU1F1(Jacobson,Eric M.,et al."Structure of Pit-1 POU domain boundto DNA as a dimer:unexpected arrangement and flexibility."Genes&Development11.2(1997):198-212,doi:10.1101/gad.11.2.198)、HNF1A、EGR1(Thiel,Gerald,andGiuseppe Cibelli."Regulation of life and death by the zinc fingertranscription factor Egr-1."Journal of cellular physiology 193.3(2002):287-292,DOI:10.1002/jcp.10178)、ZBTB18(Najafabadi,Hamed S.,et al."C2H2 zinc fingerproteins greatly expand the human regulatory lexicon."Nature biotechnology33.5(2015):555-562.doi:10.1038/nbt.3128)以及ZNF528(Najafabadi,Hamed S.,etal."C2H2 zinc finger proteins greatly expand the human regulatory lexicon."Nature biotechnology 33.5(2015):555-562,doi:10.1038/nbt.3128)。当表达为可溶性转录因子时，所有DNA结合结构域能够诱导在其同源启动子的控制下的强GFP表达。然而，当从嵌合Notch融合构建体表达和释放时，仅HNF1A和EGR1的DNA结合结构域能够诱导在其同源启动子下的可检测的GFP表达。只有一小部分表达的嵌合Notch蛋白在响应抗原结合刺激后会自切割，因此与直接表达的转录因子相比，释放的核输入转录因子的有效浓度将低得多。因此，为了有功能性，嵌合Notch释放的转录因子必须展现出与其同源启动子极强的结合。
通过在同源Gal4多位点启动子的控制下将它们作为与Gal4 DNA结合结构域的融合物表达并测量GFP表达的相对水平来在嵌合Notch设计的背景下筛选人转录激活结构域的活性。还将这些与由非人VP64转录激活结构域诱导的GFP表达水平进行比较。
以这种方式筛选的人转录激活结构域的实例包括RelA(p65)(Wang,Weixin,etal."The nuclear factor-κB RelA transcription factor is constitutivelyactivated in human pancreatic adenocarcinoma cells."Clinical Cancer Research5.1(1999):119-127)、YAP(Lian,Ian,et al."The role of YAPtranscriptioncoactivator in regulating stem cell self-renewal and differentiation."Genes&development 24.11(2010):1106-1118,doi:10.1101/gad.1903310)、WWTR1(TAZ)(Hong,Jeong-Ho,et al."TAZ,a transcriptional modulator of mesenchymal stem celldifferentiation."Science 309.5737(2005):1074-1078,doi:10.1126/science.1110955)、CREB3(LZIP)(Omori,Yoshihiro,et al."CREB-H:a novel mammaliantranscription factor belonging to the CREB/ATF family and functioning via thebox-B element with a liver-specific expression."Nucleic acids research 29.10(2001):2154-2162,doi://doi.org/10.1093/nar/29.10.2154)以及MyoD(Weintraub,Harold,and Robert Davis."The myoD gene family:nodal point duringspecification of the muscle cell lineage."Science 251.4995(1991):761,doi:10.1126/science.1846704)。其中，RelA(p65)、WWTR1(TAZ)和CREB3(LZIP)的转录激活结构域在嵌合Notch中显示出活性。RelA(p65)的转录激活结构域在诱导GFP表达中测量为最强。
结合表现最佳的人Notch结构域、表现最佳的DNA结合结构域和表现最佳的转录激活结构域产生了Notch3-HNF1a-p65设计用于嵌合的人源化Notch受体。
人源化嵌合Notch受体的应用很多。这可以例如，递送CAR或t细胞受体来治疗疾病。美国专利号9,670,281。
下面提及的核苷酸或蛋白质序列通常是指国家生物技术信息中心(NCBI)(ncbi.nlm.niv.gov)中的序列。核苷酸序列均为5′至3′。
实施例1：用Notch3、HNF1alpha的DNA结合结构域和p65转录激活结构域构建嵌合Notch。
定购以下序列作为双链合成DNA片段(IDT gBlocks)或单链长寡核苷酸(IDTultramers)，所述单链长寡核苷酸通过用短3′反向互补寡核苷酸退火和通过Phusion聚合酶(Thermo ScientificTM PhusionTM High-Fidelity DNA Polymerase；CatalogueNo.F534S)进行第二链合成来制成双链。
从Integrated DNA Technologies(IDT)定购的四种合成dsDNA片段包含：
1.人CD8a信号肽1-22(NP_001139345氨基酸1-22，(MALPVTALLLPLALLLHAARPS)(SEQ ID NO:1))、Myc标签(EQKLISEEDL)(SEQ ID NO:2)、抗人B细胞(CD19)抗体，克隆FMC63。
2.人Notch3核心(gi|134244285|NP_000426.2氨基酸1374-1734)。
3.GS柔性接头(GSAAAGGSGGSGGS)(SEQ ID NO:3)、人HNF1alpha(gi|807201167|NP_001293108.1氨基酸1-283)、GS柔性接头(GGGSGGGS)(SEQ ID NO:4)。
4.人Rel-A(p65)(gi|223468676|NP_068810.3氨基酸1-551)加上终止密码子。
设计这些以掺入与5′和3′相邻片段同源性的20nt，用于通过In-fusion克隆系统(Clontech)进行体外重组。通过In-fusion将所有片段组装到自失活慢病毒载体pHR-SIN:SFFV(Addgene；Catalogue No.79121)的MluI/NotI切割载体骨架中。
通过组装以下三个合成dsDNA片段构建第二报告基因构建体：
1.对于HNF1a DNA结合结构域二聚体的4x重复回文DNA结合序列，紧跟着最小CMV启动子
atcgatGTTAATaATTAACatatatGTTAATcATTAACtatataGTTAATtATTAACcgctatGTTAATgATTAACactagttaggcgtgtacggtgggaggcctatataagcagagctcgtttagtgaaccgtcagatcgcctggagacgccatccacgctgttttgacctccatagaagacaccgggaccgatccagc(SEQ ID NO:34)
2.Kozak序列(GCCGCCACC)(SEQ ID NO:35)和EGFP的编码序列。
3.EF1ɑ启动子序列
4.Kozak序列(GCCGCCACC)(SEQ ID NO:35)和mCherry的编码序列。
设计这些片段以掺入与5′和3′相邻片段同源性的另外20-25nt，用于通过In-fusion克隆系统(Clontech)进行体外重组。通过In-fusion反应将所有片段组装到自失活慢病毒载体pHR-SIN:SFFV的MluI/NotI切割载体骨架中。
然后使用转染试剂FuGENE HD(Roche)将慢病毒构建体与病毒包装质粒pCMVdR8.91和pMD2.G一起共转染到293T细胞中。48小时后收集上清液中的双嗜性VSV-G假型慢病毒颗粒。
来自synnotch和报告基因构建体两者的病毒颗粒用于同时转导Jurkat细胞或来自人供体的原代CD4+/CD8+pan-T细胞。可以在Morsut et al.Cell.2016Feb 11；164(4):780-91中找到慢病毒方案的扩展描述。
转导后2天测试转导的Jurkat细胞的表达，转导后7天测试转导的人原代pan-T细胞的表达。通过用alexa-647-缀合的抗myc抗体(Cell Signaling Techology,Myc标签(9B11)小鼠mAb(Alexa
Figure BDA0002316769660000571
647 Conjugate；Catalogue No.2233))标记表达的细胞表面Myc标签标志物来测试synnotch构建体的表达。
通过观察由报告载体生成的组成型mCherry表达来测试同源报告构建体对于synnotch的表达。分选双阳性细胞用于进一步测定。
通过用包覆有抗Myc标签抗体的磁珠(从Thermofisher Scientific获得，Catalognumber:88842)，或包覆有抗HA标签抗体的磁珠(从PierceTM Anti-HA Magnetic Beads获得，catalog number 88836)作为阴性对照刺激细胞24小时，来测定表达synnotch构建体和其报告基因两者的细胞的synnotch活性。对于经刺激的细胞相对阴性对照经刺激的细胞，测量了响应抗体结合刺激的报告基因EGFP表达的平均荧光强度。
通过与表达高水平CD19抗原的Raji细胞系(美国典型培养物保藏中心(ATCC)CCL-86TM(Raji))共温育以及与细胞表面CD19阴性的细胞系共温育刺激细胞24小时来另外测定表达synnotch构建体和其报告基因两者的细胞的synnotch活性。对于经刺激的细胞相对阴性对照经刺激的细胞，测量了响应细胞结合抗原刺激的共转导的报告基因EGFP表达的平均荧光强度。
实施例2：用Notch3、EGR1的DNA结合结构域和p65转录激活结构域构建嵌合Notch。
载体构建与实施例1的相似，不同之处在于用含有人EGR1 DNA结合结构域的以下片段替代含有人HNF1a的DNA结合结构域的合成DNA片段：
GS柔性接头(GSAAAGGSGGSGGS)(SEQ ID NO:3)、人EGR1(genbank NP_001955氨基酸333-423)、GS柔性接头(GGGSGGGS)(SEQ ID NO:4)
报告基因构建体含有同源4x结合位点和对于EGR1 DNA结合结构域二聚体的5x重复DNA结合序列，紧跟着最小CMV启动子：
acccggggggacagcagagatccagtttatcgatGCGTGGGCGataGCGGGGGCGtatGCGTGGGCGattGCGGGGGCGttaGCGTGGGCGactagttaggcgtgtacggtgggaggcctatataagcagagctcgtttagtgaaccgtcagatcgcctggagacgccatccacgctgttttgacctccatagaagacaccgggaccgatccagc(SEQID NO:34)
实施例3：用WWTR1(TAZ)转录激活结构域构建上述实施例。
载体构建与实施例1和2的相同，不同之处在于用含有人WWTR1的转录激活结构域的以下片段替代含有人RelA(p65)的转录激活结构域的合成DNA片段：
人WWTR1(TAZ)(Genpept NP_056287.1氨基酸165-395)加上终止密码子。
实施例4：用CREB3(LZIP)转录激活结构域构建上述实施例。
载体构建与实施例1和2的相同，不同之处在于用含有人CREB3(LZIP)的转录激活结构域的以下片段替代含有人RelA(p65)的转录激活结构域的合成DNA片段：
人CREB3(LZIP)(Genpept NP_006359.3氨基酸1-95)加上终止密码子。
实施例5：使用人Notch2结构域构建上述实施例。
载体构建与上述实施例的相同，不同之处在于用含有人notch2的最小化LIN12-HD-NLS结构域的以下片段替代含有最小化人notch3 lin12-HD-NLS结构域的合成DNA片段：人Notch2核心(gi|24041035|NP_077719.2)氨基酸1413-1780。
实施例6：用Notch3、HNF1alpha的DNA结合结构域和p65转录激活结构域制备的嵌合Notch转导单核细胞衍生的巨噬细胞。
测试了在人单核细胞衍生的巨噬细胞中，小鼠Notch 1和人Notch 3蛋白的核心LNR、HD和跨膜结构域响应每种蛋白的N末端细胞外CD19 scFv融合部分与其同源抗原的结合选择性释放转录因子的能力，所述转录因子对于小鼠Notch蛋白是Gal4-VP64或者对于人Notch蛋白是HNF1a-p65，其与蛋白质的细胞内部分C末端融合。如本文所述构建人Notch嵌合蛋白质。如美国专利号9,670,281中所述构建小鼠Notch嵌合蛋白质。
使用转染试剂FuGENE HD(Roche)将慢病毒构建体与病毒包装质粒pCMV-dR8.91和pMD2.G以及pVpx质粒一起共转染到293T细胞中。48小时后收集上清液中的双嗜性VSV-G假型慢病毒颗粒。用不同稀释度的病毒上清液感染Jurkat细胞并且感染后7天通过使用ddPCR确定VCN。
人巨噬细胞衍生自从新鲜分离的(8小时内)健康成人人血(AllCells Inc.)中分离的单核细胞。利用RosetteSep阴性选择(STEMCELL Technologies,RosetteSepTM HumanMonocyte Enrichment Cocktail,Catalogue No.15028)从血液中富集CD14+单核细胞。如前所述(Hrecka et al.,Nature 2011)，将CD14+细胞分化为巨噬细胞。简而言之，将CD14+细胞以3 x 105个细胞/mL的密度以1mL培养基置于24孔板中。培养基由Dulbecco’sModified Eagle Media组成，补充有10％热灭活的胎牛血清、2mM L-谷氨酰胺、100u/ml青霉素-G、100ug/mL链霉素、巨噬细胞集落刺激因子(M-CSF,Miltenyi Biotec)，所述巨噬细胞集落刺激因子从第0天至第2天为10ng/mL，然后从第2天开始为20ng/mL。
来自synNotch和报告基因构建体两者的病毒颗粒用于在分离4天后同时转导来自人供体的单核细胞衍生的巨噬细胞。用人Notch3、HNF1a的DNA结合结构域和p65转录激活结构域(hNotch3/HNF1a/p65)或小鼠Notch 1、Gal4的DNA结合结构域和VP64转录激活结构域(mNotch1/Gal4/VP64)以一系列感染复数(0.1至1)转导细胞。可以在Morsut L,etal.Cell.2016 Feb11；164(4):780-91中找到慢病毒方案的扩展描述。
通过流式细胞术在转导后7天测试转导的人原代髓样细胞的表达。通过用PE-Cy7抗CD14+抗体(BD Biosciences,PE-CyTM7小鼠抗人CD14抗体(Clone M5E2(RUO)),CatalogueNo.557907)和具有alexa-647-缀合的抗myc抗体(Cell Signaling Techology,Myc标签(9B11)小鼠mAb(Alexa
Figure BDA0002316769660000591
647 Conjugate；Catalogue No.2233))的细胞表面表达的Myc标签标志物标记髓样细胞来测试髓样细胞中synNotch构建体的表达。
通过流式细胞术测量由报告基因载体生成的组成型mCherry表达来测试synNotch的同源报告基因构建体的表达。
通过与表达高水平CD19抗原的Daudi细胞系(美国典型培养物保藏中心(ATCC)CCL-213TM细胞(Daudi细胞))以及细胞表面CD19阴性的细胞系共培养刺激细胞24小时来测定细胞的synNotch活性。
对于这些当用抗原阳性CD19+细胞刺激时的CD14+单核细胞衍生的巨噬细胞相对阴性对照经刺激的细胞，测量了响应细胞结合抗原刺激的共转导报告基因的EGFP表达的荧光强度。
总而言之，在单核细胞衍生的巨噬细胞中，嵌合人源化Notch受体人Notch3-HNF1a-p65诱导报告基因构建体未经调节的表达。蛋白质的Notch、DNA结合结构域和转录激活结构域成分在巨噬细胞中有功能。嵌合小鼠Notch受体Notch1-Gal4-VP64与没有任何CD19表达的阴性对照相比，不诱导响应与其同源抗体结合的N末端细胞外CD19 scFv融合的GFP的选择性表达。参见，图2、3A、3B、4、5A和5B。
序列表
<110> 细胞设计实验室股份有限公司
<120> 用于降低嵌合Notch受体的免疫原性的方法和组合物
<130> 43159-0066WO1
<150> US 62/603,993
<151> 2017-06-19
<150> US 62/556,765
<151> 2017-09-11
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<212> PRT
<213> 人
<400> 7
Met Val Ser Lys Leu Ser Gln Leu Gln Thr Glu Leu Leu Ala Ala Leu
1 5 10 15
Leu Glu Ser Gly Leu Ser Lys Glu Ala Leu Ile Gln Ala Leu Gly Glu
20 25 30
Pro Gly Pro Tyr Leu Leu Ala Gly Glu Gly Pro Leu Asp Lys Gly Glu
35 40 45
Ser Cys Gly Gly Gly Arg Gly Glu Leu Ala Glu Leu Pro Asn Gly Leu
50 55 60
Gly Glu Thr Arg Gly Ser Glu Asp Glu Thr Asp Asp Asp Gly Glu Asp
65 70 75 80
Phe Thr Pro Pro Ile Leu Lys Glu Leu Glu Asn Leu Ser Pro Glu Glu
85 90 95
Ala Ala His Gln Lys Ala Val Val Glu Thr Leu Leu Gln Glu Asp Pro
100 105 110
Trp Arg Val Ala Lys Met Val Lys Ser Tyr Leu Gln Gln His Asn Ile
115 120 125
Pro Gln Arg Glu Val Val Asp Thr Thr Gly Leu Asn Gln Ser His Leu
130 135 140
Ser Gln His Leu Asn Lys Gly Thr Pro Met Lys Thr Gln Lys Arg Ala
145 150 155 160
Ala Leu Tyr Thr Trp Tyr Val Arg Lys Gln Arg Glu Val Ala Gln Gln
165 170 175
Phe Thr His Ala Gly Gln Gly Gly Leu Ile Glu Glu Pro Thr Gly Asp
180 185 190
Glu Leu Pro Thr Lys Lys Gly Arg Arg Asn Arg Phe Lys Trp Gly Pro
195 200 205
Ala Ser Gln Gln Ile Leu Phe Gln Ala Tyr Glu Arg Gln Lys Asn Pro
210 215 220
Ser Lys Glu Glu Arg Glu Thr Leu Val Glu Glu Cys Asn Arg Ala Glu
225 230 235 240
Cys Ile Gln Arg Gly Val Ser Pro Ser Gln Ala Gln Gly Leu Gly Ser
245 250 255
Asn Leu Val Thr Glu Val Arg Val Tyr Asn Trp Phe Ala Asn Arg Arg
260 265 270
Lys Glu Glu Ala Phe Arg His Lys Leu Ala Met Asp Thr Tyr Ser Gly
275 280 285
Pro Pro Pro Gly Pro Gly Pro Gly Pro Ala Leu Pro Ala His Ser Ser
290 295 300
Pro Gly Leu Pro Pro Pro Ala Leu Ser Pro Ser Lys Val His Gly Val
305 310 315 320
Arg Tyr Gly Gln Pro Ala Thr Ser Glu Thr Ala Glu Val Pro Ser Ser
325 330 335
Ser Gly Gly Pro Leu Val Thr Val Ser Thr Pro Leu His Gln Val Ser
340 345 350
Pro Thr Gly Leu Glu Pro Ser His Ser Leu Leu Ser Thr Glu Ala Lys
355 360 365
Leu Val Ser Ala Ala Gly Gly Pro Leu Pro Pro Val Ser Thr Leu Thr
370 375 380
Ala Leu His Ser Leu Glu Gln Thr Ser Pro Gly Leu Asn Gln Gln Pro
385 390 395 400
Gln Asn Leu Ile Met Ala Ser Leu Pro Gly Val Met Thr Ile Gly Pro
405 410 415
Gly Glu Pro Ala Ser Leu Gly Pro Thr Phe Thr Asn Thr Gly Ala Ser
420 425 430
Thr Leu Val Ile Gly Leu Ala Ser Thr Gln Ala Gln Ser Val Pro Val
435 440 445
Ile Asn Ser Met Gly Ser Ser Leu Thr Thr Leu Gln Pro Val Gln Phe
450 455 460
Ser Gln Pro Leu His Pro Ser Tyr Gln Gln Pro Leu Met Pro Pro Val
465 470 475 480
Gln Ser His Val Thr Gln Ser Pro Phe Met Ala Thr Met Ala Gln Leu
485 490 495
Gln Ser Pro His Ala Leu Tyr Ser His Lys Pro Glu Val Ala Gln Tyr
500 505 510
Thr His Thr Gly Leu Leu Pro Gln Thr Met Leu Ile Thr Asp Thr Thr
515 520 525
Asn Leu Ser Ala Leu Ala Ser Leu Thr Pro Thr Lys Gln Val Arg Ser
530 535 540
Arg Pro Ala Gly Pro Pro Leu Ala Cys Asp Arg Ala Pro His Pro His
545 550 555 560
Ile Pro Arg Ala Gln Glu Ala Ala Leu Leu Pro Gln Val Phe Thr Ser
565 570 575
Asp Thr Glu Ala Ser Ser Glu Ser Gly Leu His Thr Pro Ala Ser Gln
580 585 590
Ala Thr Thr Leu His Val Pro Ser Gln Asp Pro Ala Ser Ile Gln His
595 600 605
Leu Gln Pro Ala His Arg Leu Ser Ala Ser Pro Thr Val Ser Ser Ser
610 615 620
Ser Leu Val Leu Tyr Gln Ser Ser Asp Ser Ser Asn Gly Gln Ser His
625 630 635 640
Leu Leu Pro Ser Asn His Ser Val Ile Glu Thr Phe Ile Ser Thr Gln
645 650 655
Met Ala Ser Ser Ser Gln
660
<210> 8
<211> 3438
<212> DNA
<213> 人
<400> 8
ggggccctga ttcacgggcc gctggggcca gggttggggg ttgggggtgc ccacagggct 60
tggctagtgg ggttttgggg gggcagtggg tgcaaggagt ttggtttgtg tctgccggcc 120
ggcaggcaaa cgcaacccac gcggtggggg aggcggctag cgtggtggac ccgggccgcg 180
tggccctgtg gcagccgagc catggtttct aaactgagcc agctgcagac ggagctcctg 240
gcggccctgc tcgagtcagg gctgagcaaa gaggcactga tccaggcact gggtgagccg 300
gggccctacc tcctggctgg agaaggcccc ctggacaagg gggagtcctg cggcggcggt 360
cgaggggagc tggctgagct gcccaatggg ctgggggaga ctcggggctc cgaggacgag 420
acggacgacg atggggaaga cttcacgcca cccatcctca aagagctgga gaacctcagc 480
cctgaggagg cggcccacca gaaagccgtg gtggagaccc ttctgcagga ggacccgtgg 540
cgtgtggcga agatggtcaa gtcctacctg cagcagcaca acatcccaca gcgggaggtg 600
gtcgatacca ctggcctcaa ccagtcccac ctgtcccaac acctcaacaa gggcactccc 660
atgaagacgc agaagcgggc cgccctgtac acctggtacg tccgcaagca gcgagaggtg 720
gcgcagcagt tcacccatgc agggcaggga gggctgattg aagagcccac aggtgatgag 780
ctaccaacca agaaggggcg gaggaaccgt ttcaagtggg gcccagcatc ccagcagatc 840
ctgttccagg cctatgagag gcagaagaac cctagcaagg aggagcgaga gacgctagtg 900
gaggagtgca atagggcgga atgcatccag agaggggtgt ccccatcaca ggcacagggg 960
ctgggctcca acctcgtcac ggaggtgcgt gtctacaact ggtttgccaa ccggcgcaaa 1020
gaagaagcct tccggcacaa gctggccatg gacacgtaca gcgggccccc cccagggcca 1080
ggcccgggac ctgcgctgcc cgctcacagc tcccctggcc tgcctccacc tgccctctcc 1140
cccagtaagg tccacggtgt gcgctatgga cagcctgcga ccagtgagac tgcagaagta 1200
ccctcaagca gcggcggtcc cttagtgaca gtgtctacac ccctccacca agtgtccccc 1260
acgggcctgg agcccagcca cagcctgctg agtacagaag ccaagctggt ctcagcagct 1320
gggggccccc tcccccctgt cagcaccctg acagcactgc acagcttgga gcagacatcc 1380
ccaggcctca accagcagcc ccagaacctc atcatggcct cacttcctgg ggtcatgacc 1440
atcgggcctg gtgagcctgc ctccctgggt cctacgttca ccaacacagg tgcctccacc 1500
ctggtcatcg gcctggcctc cacgcaggca cagagtgtgc cggtcatcaa cagcatgggc 1560
agcagcctga ccaccctgca gcccgtccag ttctcccagc cgctgcaccc ctcctaccag 1620
cagccgctca tgccacctgt gcagagccat gtgacccaga gccccttcat ggccaccatg 1680
gctcagctgc agagccccca cgccctctac agccacaagc ccgaggtggc ccagtacacc 1740
cacacgggcc tgctcccgca gactatgctc atcaccgaca ccaccaacct gagcgccctg 1800
gccagcctca cgcccaccaa gcaggaggct gctctgctcc cccaggtctt cacctcagac 1860
actgaggcct ccagtgagtc cgggcttcac acgccggcat ctcaggccac caccctccac 1920
gtccccagcc aggaccctgc cggcatccag cacctgcagc cggcccaccg gctcagcgcc 1980
agccccacag tgtcctccag cagcctggtg ctgtaccaga gctcagactc cagcaatggc 2040
cagagccacc tgctgccatc caaccacagc gtcatcgaga ccttcatctc cacccagatg 2100
gcctcttcct cccagtaacc acggcacctg ggccctgggg cctgtactgc ctgcttgggg 2160
ggtgatgagg gcagcagcca gccctgcctg gaggacctga gcctgccgag caaccgtggc 2220
ccttcctgga cagctgtgcc tcgctcccca ctctgctctg atgcatcaga aagggagggc 2280
tctgaggcgc cccaacccgt ggaggctgct cggggtgcac aggagggggt cgtggagagc 2340
taggagcaaa gcctgttcat ggcagatgta ggagggactg tcgctgcttc gtgggataca 2400
gtcttcttac ttggaactga agggggcggc ctatgacttg ggcaccccca gcctgggcct 2460
atggagagcc ctgggaccgc tacaccactc tggcagccac acttctcagg acacaggcct 2520
gtgtagctgt gacctgctga gctctgagag gccctggatc agcgtggcct tgttctgtca 2580
ccaatgtacc caccgggcca ctccttcctg ccccaactcc ttccagctag tgacccacat 2640
gccatttgta ctgaccccat cacctactca cacaggcatt tcctgggtgg ctactctgtg 2700
ccagagcctg gggctctaac gcctgagccc agggaggccg aagctaacag ggaaggcagg 2760
cagggctctc ctggcttccc atccccagcg attccctctc ccaggcccca tgacctccag 2820
ctttcctgta tttgttccca agagcatcat gcctctgagg ccagcctggc ctcctgcctc 2880
tactgggaag gctacttcgg ggctgggaag tcgtccttac tcctgtggga gcctcgcaac 2940
ccgtgccaag tccaggtcct ggtggggcag ctcctctgtc tcgagcgccc tgcagaccct 3000
gcccttgttt ggggcaggag tagctgagct cacaaggcag caaggcccga gcagctgagc 3060
agggccgggg aactggccaa gctgaggtgc ccaggagaag aaagaggtga ccccagggca 3120
caggagctac ctgtgtggac aggactaaca ctcagaagcc tgggggcctg gctggctgag 3180
ggcagttcgc agccaccctg aggagtctga ggtcctgagc actgccagga gggacaaagg 3240
agcctgtgaa cccaggacaa gcatggtccc acatccctgg gcctgctgct gagaacctgg 3300
ccttcagtgt accgcgtcta ccctgggatt caggaaaagg cctggggtga cccggcaccc 3360
cctgcagctt gtagccagcc ggggcgagtg gcacgtttat ttaactttta gtaaagtcaa 3420
ggagaaatgc ggtggaaa 3438
<210> 9
<211> 3417
<212> DNA
<213> 人
<400> 9
ggggccctga ttcacgggcc gctggggcca gggttggggg ttgggggtgc ccacagggct 60
tggctagtgg ggttttgggg gggcagtggg tgcaaggagt ttggtttgtg tctgccggcc 120
ggcaggcaaa cgcaacccac gcggtggggg aggcggctag cgtggtggac ccgggccgcg 180
tggccctgtg gcagccgagc catggtttct aaactgagcc agctgcagac ggagctcctg 240
gcggccctgc tcgagtcagg gctgagcaaa gaggcactga tccaggcact gggtgagccg 300
gggccctacc tcctggctgg agaaggcccc ctggacaagg gggagtcctg cggcggcggt 360
cgaggggagc tggctgagct gcccaatggg ctgggggaga ctcggggctc cgaggacgag 420
acggacgacg atggggaaga cttcacgcca cccatcctca aagagctgga gaacctcagc 480
cctgaggagg cggcccacca gaaagccgtg gtggagaccc ttctgcagga ggacccgtgg 540
cgtgtggcga agatggtcaa gtcctacctg cagcagcaca acatcccaca gcgggaggtg 600
gtcgatacca ctggcctcaa ccagtcccac ctgtcccaac acctcaacaa gggcactccc 660
atgaagacgc agaagcgggc cgccctgtac acctggtacg tccgcaagca gcgagaggtg 720
gcgcagcagt tcacccatgc agggcaggga gggctgattg aagagcccac aggtgatgag 780
ctaccaacca agaaggggcg gaggaaccgt ttcaagtggg gcccagcatc ccagcagatc 840
ctgttccagg cctatgagag gcagaagaac cctagcaagg aggagcgaga gacgctagtg 900
gaggagtgca atagggcgga atgcatccag agaggggtgt ccccatcaca ggcacagggg 960
ctgggctcca acctcgtcac ggaggtgcgt gtctacaact ggtttgccaa ccggcgcaaa 1020
gaagaagcct tccggcacaa gctggccatg gacacgtaca gcgggccccc cccagggcca 1080
ggcccgggac ctgcgctgcc cgctcacagc tcccctggcc tgcctccacc tgccctctcc 1140
cccagtaagg tccacggtgt gcgctatgga cagcctgcga ccagtgagac tgcagaagta 1200
ccctcaagca gcggcggtcc cttagtgaca gtgtctacac ccctccacca agtgtccccc 1260
acgggcctgg agcccagcca cagcctgctg agtacagaag ccaagctggt ctcagcagct 1320
gggggccccc tcccccctgt cagcaccctg acagcactgc acagcttgga gcagacatcc 1380
ccaggcctca accagcagcc ccagaacctc atcatggcct cacttcctgg ggtcatgacc 1440
atcgggcctg gtgagcctgc ctccctgggt cctacgttca ccaacacagg tgcctccacc 1500
ctggtcatcg gcctggcctc cacgcaggca cagagtgtgc cggtcatcaa cagcatgggc 1560
agcagcctga ccaccctgca gcccgtccag ttctcccagc cgctgcaccc ctcctaccag 1620
cagccgctca tgccacctgt gcagagccat gtgacccaga gccccttcat ggccaccatg 1680
gctcagctgc agagccccca cgccctctac agccacaagc ccgaggtggc ccagtacacc 1740
cacacgggcc tgctcccgca gactatgctc atcaccgaca ccaccaacct gagcgccctg 1800
gccagcctca cgcccaccaa gcaggtcttc acctcagaca ctgaggcctc cagtgagtcc 1860
gggcttcaca cgccggcatc tcaggccacc accctccacg tccccagcca ggaccctgcc 1920
ggcatccagc acctgcagcc ggcccaccgg ctcagcgcca gccccacagt gtcctccagc 1980
agcctggtgc tgtaccagag ctcagactcc agcaatggcc agagccacct gctgccatcc 2040
aaccacagcg tcatcgagac cttcatctcc acccagatgg cctcttcctc ccagtaacca 2100
cggcacctgg gccctggggc ctgtactgcc tgcttggggg gtgatgaggg cagcagccag 2160
ccctgcctgg aggacctgag cctgccgagc aaccgtggcc cttcctggac agctgtgcct 2220
cgctccccac tctgctctga tgcatcagaa agggagggct ctgaggcgcc ccaacccgtg 2280
gaggctgctc ggggtgcaca ggagggggtc gtggagagct aggagcaaag cctgttcatg 2340
gcagatgtag gagggactgt cgctgcttcg tgggatacag tcttcttact tggaactgaa 2400
gggggcggcc tatgacttgg gcacccccag cctgggccta tggagagccc tgggaccgct 2460
acaccactct ggcagccaca cttctcagga cacaggcctg tgtagctgtg acctgctgag 2520
ctctgagagg ccctggatca gcgtggcctt gttctgtcac caatgtaccc accgggccac 2580
tccttcctgc cccaactcct tccagctagt gacccacatg ccatttgtac tgaccccatc 2640
acctactcac acaggcattt cctgggtggc tactctgtgc cagagcctgg ggctctaacg 2700
cctgagccca gggaggccga agctaacagg gaaggcaggc agggctctcc tggcttccca 2760
tccccagcga ttccctctcc caggccccat gacctccagc tttcctgtat ttgttcccaa 2820
gagcatcatg cctctgaggc cagcctggcc tcctgcctct actgggaagg ctacttcggg 2880
gctgggaagt cgtccttact cctgtgggag cctcgcaacc cgtgccaagt ccaggtcctg 2940
gtggggcagc tcctctgtct cgagcgccct gcagaccctg cccttgtttg gggcaggagt 3000
agctgagctc acaaggcagc aaggcccgag cagctgagca gggccgggga actggccaag 3060
ctgaggtgcc caggagaaga aagaggtgac cccagggcac aggagctacc tgtgtggaca 3120
ggactaacac tcagaagcct gggggcctgg ctggctgagg gcagttcgca gccaccctga 3180
ggagtctgag gtcctgagca ctgccaggag ggacaaagga gcctgtgaac ccaggacaag 3240
catggtccca catccctggg cctgctgctg agaacctggc cttcagtgta ccgcgtctac 3300
cctgggattc aggaaaaggc ctggggtgac ccggcacccc ctgcagcttg tagccagccg 3360
gggcgagtgg cacgtttatt taacttttag taaagtcaag gagaaatgcg gtggaaa 3417
<210> 10
<211> 3563
<212> DNA
<213> 人
<400> 10
ataaatatga accttggaga atttccccag ctccaatgta aacagaacag gcaggggccc 60
tgattcacgg gccgctgggg ccagggttgg gggttggggg tgcccacagg gcttggctag 120
tggggttttg ggggggcagt gggtgcaagg agtttggttt gtgtctgccg gccggcaggc 180
aaacgcaacc cacgcggtgg gggaggcggc tagcgtggtg gacccgggcc gcgtggccct 240
gtggcagccg agccatggtt tctaaactga gccagctgca gacggagctc ctggcggccc 300
tgctcgagtc agggctgagc aaagaggcac tgatccaggc actgggtgag ccggggccct 360
acctcctggc tggagaaggc cccctggaca agggggagtc ctgcggcggc ggtcgagggg 420
agctggctga gctgcccaat gggctggggg agactcgggg ctccgaggac gagacggacg 480
acgatgggga agacttcacg ccacccatcc tcaaagagct ggagaacctc agccctgagg 540
aggcggccca ccagaaagcc gtggtggaga cccttctgca ggaggacccg tggcgtgtgg 600
cgaagatggt caagtcctac ctgcagcagc acaacatccc acagcgggag gtggtcgata 660
ccactggcct caaccagtcc cacctgtccc aacacctcaa caagggcact cccatgaaga 720
cgcagaagcg ggccgccctg tacacctggt acgtccgcaa gcagcgagag gtggcgcagc 780
agttcaccca tgcagggcag ggagggctga ttgaagagcc cacaggtgat gagctaccaa 840
ccaagaaggg gcggaggaac cgtttcaagt ggggcccagc atcccagcag atcctgttcc 900
aggcctatga gaggcagaag aaccctagca aggaggagcg agagacgcta gtggaggagt 960
gcaatagggc ggaatgcatc cagagagggg tgtccccatc acaggcacag gggctgggct 1020
ccaacctcgt cacggaggtg cgtgtctaca actggtttgc caaccggcgc aaagaagaag 1080
ccttccggca caagctggcc atggacacgt acagcgggcc ccccccaggg ccaggcccgg 1140
gacctgcgct gcccgctcac agctcccctg gcctgcctcc acctgccctc tcccccagta 1200
aggtccacgg tgtgcgctat ggacagcctg cgaccagtga gactgcagaa gtaccctcaa 1260
gcagcggcgg tcccttagtg acagtgtcta cacccctcca ccaagtgtcc cccacgggcc 1320
tggagcccag ccacagcctg ctgagtacag aagccaagct ggtctcagca gctgggggcc 1380
ccctcccccc tgtcagcacc ctgacagcac tgcacagctt ggagcagaca tccccaggcc 1440
tcaaccagca gccccagaac ctcatcatgg cctcacttcc tggggtcatg accatcgggc 1500
ctggtgagcc tgcctccctg ggtcctacgt tcaccaacac aggtgcctcc accctggtca 1560
tcggcctggc ctccacgcag gcacagagtg tgccggtcat caacagcatg ggcagcagcc 1620
tgaccaccct gcagcccgtc cagttctccc agccgctgca cccctcctac cagcagccgc 1680
tcatgccacc tgtgcagagc catgtgaccc agagcccctt catggccacc atggctcagc 1740
tgcagagccc ccacgccctc tacagccaca agcccgaggt ggcccagtac acccacacgg 1800
gcctgctccc gcagactatg ctcatcaccg acaccaccaa cctgagcgcc ctggccagcc 1860
tcacgcccac caagcaggta aggtccaggc ctgctggccc tcccttggcc tgtgacagag 1920
cccctcaccc ccacatcccc cgggctcagg aggctgctct gctcccccag gtcttcacct 1980
cagacactga ggcctccagt gagtccgggc ttcacacgcc ggcatctcag gccaccaccc 2040
tccacgtccc cagccaggac cctgccagca tccagcacct gcagccggcc caccggctca 2100
gcgccagccc cacagtgtcc tccagcagcc tggtgctgta ccagagctca gactccagca 2160
atggccagag ccacctgctg ccatccaacc acagcgtcat cgagaccttc atctccaccc 2220
agatggcctc ttcctcccag taaccacggc acctgggccc tggggcctgt actgcctgct 2280
tggggggtga tgagggcagc agccagccct gcctggagga cctgagcctg ccgagcaacc 2340
gtggcccttc ctggacagct gtgcctcgct ccccactctg ctctgatgca tcagaaaggg 2400
agggctctga ggcgccccaa cccgtggagg ctgctcgggg tgcacaggag ggggtcgtgg 2460
agagctagga gcaaagcctg ttcatggcag atgtaggagg gactgtcgct gcttcgtggg 2520
atacagtctt cttacttgga actgaagggg gcggcctatg acttgggcac ccccagcctg 2580
ggcctatgga gagccctggg accgctacac cactctggca gccacacttc tcaggacaca 2640
ggcctgtgta gctgtgacct gctgagctct gagaggccct ggatcagcgt ggccttgttc 2700
tgtcaccaat gtacccaccg ggccactcct tcctgcccca actccttcca gctagtgacc 2760
cacatgccat ttgtactgac cccatcacct actcacacag gcatttcctg ggtggctact 2820
ctgtgccaga gcctggggct ctaacgcctg agcccaggga ggccgaagct aacagggaag 2880
gcaggcaggg ctctcctggc ttcccatccc cagcgattcc ctctcccagg ccccatgacc 2940
tccagctttc ctgtatttgt tcccaagagc atcatgcctc tgaggccagc ctggcctcct 3000
gcctctactg ggaaggctac ttcggggctg ggaagtcgtc cttactcctg tgggagcctc 3060
gcaacccgtg ccaagtccag gtcctggtgg ggcagctcct ctgtctcgag cgccctgcag 3120
accctgccct tgtttggggc aggagtagct gagctcacaa ggcagcaagg cccgagcagc 3180
tgagcagggc cggggaactg gccaagctga ggtgcccagg agaagaaaga ggtgacccca 3240
gggcacagga gctacctgtg tggacaggac taacactcag aagcctgggg gcctggctgg 3300
ctgagggcag ttcgcagcca ccctgaggag tctgaggtcc tgagcactgc caggagggac 3360
aaaggagcct gtgaacccag gacaagcatg gtcccacatc cctgggcctg ctgctgagaa 3420
cctggccttc agtgtaccgc gtctaccctg ggattcagga aaaggcctgg ggtgacccgg 3480
caccccctgc agcttgtagc cagccggggc gagtggcacg tttatttaac ttttagtaaa 3540
gtcaaggaga aatgcggtgg aaa 3563
<210> 11
<211> 13
<212> DNA
<213> 人工序列
<220>
<223> 合成序列
<220>
<221> misc_feature
<222> (7)..(7)
<223> HNF1-alpha结合序列
<400> 11
gttaatnatt aac 13
<210> 12
<211> 551
<212> PRT
<213> 人
<400> 12
Met Asp Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala
1 5 10 15
Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met
20 25 30
Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly
35 40 45
Glu Arg Ser Thr Asp Thr Thr Lys Thr His Pro Thr Ile Lys Ile Asn
50 55 60
Gly Tyr Thr Gly Pro Gly Thr Val Arg Ile Ser Leu Val Thr Lys Asp
65 70 75 80
Pro Pro His Arg Pro His Pro His Glu Leu Val Gly Lys Asp Cys Arg
85 90 95
Asp Gly Phe Tyr Glu Ala Glu Leu Cys Pro Asp Arg Cys Ile His Ser
100 105 110
Phe Gln Asn Leu Gly Ile Gln Cys Val Lys Lys Arg Asp Leu Glu Gln
115 120 125
Ala Ile Ser Gln Arg Ile Gln Thr Asn Asn Asn Pro Phe Gln Val Pro
130 135 140
Ile Glu Glu Gln Arg Gly Asp Tyr Asp Leu Asn Ala Val Arg Leu Cys
145 150 155 160
Phe Gln Val Thr Val Arg Asp Pro Ser Gly Arg Pro Leu Arg Leu Pro
165 170 175
Pro Val Leu Ser His Pro Ile Phe Asp Asn Arg Ala Pro Asn Thr Ala
180 185 190
Glu Leu Lys Ile Cys Arg Val Asn Arg Asn Ser Gly Ser Cys Leu Gly
195 200 205
Gly Asp Glu Ile Phe Leu Leu Cys Asp Lys Val Gln Lys Glu Asp Ile
210 215 220
Glu Val Tyr Phe Thr Gly Pro Gly Trp Glu Ala Arg Gly Ser Phe Ser
225 230 235 240
Gln Ala Asp Val His Arg Gln Val Ala Ile Val Phe Arg Thr Pro Pro
245 250 255
Tyr Ala Asp Pro Ser Leu Gln Ala Pro Val Arg Val Ser Met Gln Leu
260 265 270
Arg Arg Pro Ser Asp Arg Glu Leu Ser Glu Pro Met Glu Phe Gln Tyr
275 280 285
Leu Pro Asp Thr Asp Asp Arg His Arg Ile Glu Glu Lys Arg Lys Arg
290 295 300
Thr Tyr Glu Thr Phe Lys Ser Ile Met Lys Lys Ser Pro Phe Ser Gly
305 310 315 320
Pro Thr Asp Pro Arg Pro Pro Pro Arg Arg Ile Ala Val Pro Ser Arg
325 330 335
Ser Ser Ala Ser Val Pro Lys Pro Ala Pro Gln Pro Tyr Pro Phe Thr
340 345 350
Ser Ser Leu Ser Thr Ile Asn Tyr Asp Glu Phe Pro Thr Met Val Phe
355 360 365
Pro Ser Gly Gln Ile Ser Gln Ala Ser Ala Leu Ala Pro Ala Pro Pro
370 375 380
Gln Val Leu Pro Gln Ala Pro Ala Pro Ala Pro Ala Pro Ala Met Val
385 390 395 400
Ser Ala Leu Ala Gln Ala Pro Ala Pro Val Pro Val Leu Ala Pro Gly
405 410 415
Pro Pro Gln Ala Val Ala Pro Pro Ala Pro Lys Pro Thr Gln Ala Gly
420 425 430
Glu Gly Thr Leu Ser Glu Ala Leu Leu Gln Leu Gln Phe Asp Asp Glu
435 440 445
Asp Leu Gly Ala Leu Leu Gly Asn Ser Thr Asp Pro Ala Val Phe Thr
450 455 460
Asp Leu Ala Ser Val Asp Asn Ser Glu Phe Gln Gln Leu Leu Asn Gln
465 470 475 480
Gly Ile Pro Val Ala Pro His Thr Thr Glu Pro Met Leu Met Glu Tyr
485 490 495
Pro Glu Ala Ile Thr Arg Leu Val Thr Gly Ala Gln Arg Pro Pro Asp
500 505 510
Pro Ala Pro Ala Pro Leu Gly Ala Pro Gly Leu Pro Asn Gly Leu Leu
515 520 525
Ser Gly Asp Glu Asp Phe Ser Ser Ile Ala Asp Met Asp Phe Ser Ala
530 535 540
Leu Leu Ser Gln Ile Ser Ser
545 550
<210> 13
<211> 548
<212> PRT
<213> 人
<400> 13
Met Asp Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala
1 5 10 15
Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met
20 25 30
Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly
35 40 45
Glu Arg Ser Thr Asp Thr Thr Lys Thr His Pro Thr Ile Lys Ile Asn
50 55 60
Gly Tyr Thr Gly Pro Gly Thr Val Arg Ile Ser Leu Val Thr Lys Asp
65 70 75 80
Pro Pro His Arg Pro His Pro His Glu Leu Val Gly Lys Asp Cys Arg
85 90 95
Asp Gly Phe Tyr Glu Ala Glu Leu Cys Pro Asp Arg Cys Ile His Ser
100 105 110
Phe Gln Asn Leu Gly Ile Gln Cys Val Lys Lys Arg Asp Leu Glu Gln
115 120 125
Ala Ile Ser Gln Arg Ile Gln Thr Asn Asn Asn Pro Phe Gln Glu Glu
130 135 140
Gln Arg Gly Asp Tyr Asp Leu Asn Ala Val Arg Leu Cys Phe Gln Val
145 150 155 160
Thr Val Arg Asp Pro Ser Gly Arg Pro Leu Arg Leu Pro Pro Val Leu
165 170 175
Ser His Pro Ile Phe Asp Asn Arg Ala Pro Asn Thr Ala Glu Leu Lys
180 185 190
Ile Cys Arg Val Asn Arg Asn Ser Gly Ser Cys Leu Gly Gly Asp Glu
195 200 205
Ile Phe Leu Leu Cys Asp Lys Val Gln Lys Glu Asp Ile Glu Val Tyr
210 215 220
Phe Thr Gly Pro Gly Trp Glu Ala Arg Gly Ser Phe Ser Gln Ala Asp
225 230 235 240
Val His Arg Gln Val Ala Ile Val Phe Arg Thr Pro Pro Tyr Ala Asp
245 250 255
Pro Ser Leu Gln Ala Pro Val Arg Val Ser Met Gln Leu Arg Arg Pro
260 265 270
Ser Asp Arg Glu Leu Ser Glu Pro Met Glu Phe Gln Tyr Leu Pro Asp
275 280 285
Thr Asp Asp Arg His Arg Ile Glu Glu Lys Arg Lys Arg Thr Tyr Glu
290 295 300
Thr Phe Lys Ser Ile Met Lys Lys Ser Pro Phe Ser Gly Pro Thr Asp
305 310 315 320
Pro Arg Pro Pro Pro Arg Arg Ile Ala Val Pro Ser Arg Ser Ser Ala
325 330 335
Ser Val Pro Lys Pro Ala Pro Gln Pro Tyr Pro Phe Thr Ser Ser Leu
340 345 350
Ser Thr Ile Asn Tyr Asp Glu Phe Pro Thr Met Val Phe Pro Ser Gly
355 360 365
Gln Ile Ser Gln Ala Ser Ala Leu Ala Pro Ala Pro Pro Gln Val Leu
370 375 380
Pro Gln Ala Pro Ala Pro Ala Pro Ala Pro Ala Met Val Ser Ala Leu
385 390 395 400
Ala Gln Ala Pro Ala Pro Val Pro Val Leu Ala Pro Gly Pro Pro Gln
405 410 415
Ala Val Ala Pro Pro Ala Pro Lys Pro Thr Gln Ala Gly Glu Gly Thr
420 425 430
Leu Ser Glu Ala Leu Leu Gln Leu Gln Phe Asp Asp Glu Asp Leu Gly
435 440 445
Ala Leu Leu Gly Asn Ser Thr Asp Pro Ala Val Phe Thr Asp Leu Ala
450 455 460
Ser Val Asp Asn Ser Glu Phe Gln Gln Leu Leu Asn Gln Gly Ile Pro
465 470 475 480
Val Ala Pro His Thr Thr Glu Pro Met Leu Met Glu Tyr Pro Glu Ala
485 490 495
Ile Thr Arg Leu Val Thr Gly Ala Gln Arg Pro Pro Asp Pro Ala Pro
500 505 510
Ala Pro Leu Gly Ala Pro Gly Leu Pro Asn Gly Leu Leu Ser Gly Asp
515 520 525
Glu Asp Phe Ser Ser Ile Ala Asp Met Asp Phe Ser Ala Leu Leu Ser
530 535 540
Gln Ile Ser Ser
545
<210> 14
<211> 482
<212> PRT
<213> 人
<400> 14
Met Asp Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala
1 5 10 15
Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met
20 25 30
Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly
35 40 45
Glu Arg Ser Thr Asp Thr Thr Lys Thr His Pro Thr Ile Lys Ile Asn
50 55 60
Gly Tyr Thr Gly Pro Gly Thr Val Arg Ile Ser Leu Val Thr Lys Asp
65 70 75 80
Pro Pro His Arg Pro His Pro His Glu Leu Val Gly Lys Asp Cys Arg
85 90 95
Asp Gly Phe Tyr Glu Ala Glu Leu Cys Pro Asp Arg Cys Ile His Ser
100 105 110
Phe Gln Asn Leu Gly Ile Gln Cys Val Lys Lys Arg Asp Leu Glu Gln
115 120 125
Ala Ile Ser Gln Arg Ile Gln Thr Asn Asn Asn Pro Phe Gln Val Pro
130 135 140
Ile Glu Glu Gln Arg Gly Asp Tyr Asp Leu Asn Ala Val Arg Leu Cys
145 150 155 160
Phe Gln Val Thr Val Arg Asp Pro Ser Gly Arg Pro Leu Arg Leu Pro
165 170 175
Pro Val Leu Ser His Pro Ile Phe Asp Asn Arg Ala Pro Asn Thr Ala
180 185 190
Glu Leu Lys Ile Cys Arg Val Asn Arg Asn Ser Gly Ser Cys Leu Gly
195 200 205
Gly Asp Glu Ile Phe Leu Leu Cys Asp Lys Val Gln Lys Glu Asp Ile
210 215 220
Glu Val Tyr Phe Thr Gly Pro Gly Trp Glu Ala Arg Gly Ser Phe Ser
225 230 235 240
Gln Ala Asp Val His Arg Gln Val Ala Ile Val Phe Arg Thr Pro Pro
245 250 255
Tyr Ala Asp Pro Ser Leu Gln Ala Pro Val Arg Val Ser Met Gln Leu
260 265 270
Arg Arg Pro Ser Asp Arg Glu Leu Ser Glu Pro Met Glu Phe Gln Tyr
275 280 285
Leu Pro Asp Thr Asp Asp Arg His Arg Ile Glu Glu Lys Arg Lys Arg
290 295 300
Thr Tyr Glu Thr Phe Lys Ser Ile Met Lys Lys Ser Pro Phe Ser Gly
305 310 315 320
Pro Thr Asp Pro Arg Pro Pro Pro Arg Arg Ile Ala Val Pro Ser Arg
325 330 335
Ser Ser Ala Ser Val Pro Lys Pro Ala Pro Gly Pro Pro Gln Ala Val
340 345 350
Ala Pro Pro Ala Pro Lys Pro Thr Gln Ala Gly Glu Gly Thr Leu Ser
355 360 365
Glu Ala Leu Leu Gln Leu Gln Phe Asp Asp Glu Asp Leu Gly Ala Leu
370 375 380
Leu Gly Asn Ser Thr Asp Pro Ala Val Phe Thr Asp Leu Ala Ser Val
385 390 395 400
Asp Asn Ser Glu Phe Gln Gln Leu Leu Asn Gln Gly Ile Pro Val Ala
405 410 415
Pro His Thr Thr Glu Pro Met Leu Met Glu Tyr Pro Glu Ala Ile Thr
420 425 430
Arg Leu Val Thr Gly Ala Gln Arg Pro Pro Asp Pro Ala Pro Ala Pro
435 440 445
Leu Gly Ala Pro Gly Leu Pro Asn Gly Leu Leu Ser Gly Asp Glu Asp
450 455 460
Phe Ser Ser Ile Ala Asp Met Asp Phe Ser Ala Leu Leu Ser Gln Ile
465 470 475 480
Ser Ser
<210> 15
<211> 448
<212> PRT
<213> 人
<400> 15
Met Asp Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala
1 5 10 15
Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met
20 25 30
Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly
35 40 45
Glu Arg Ser Thr Asp Thr Thr Lys Thr His Pro Thr Ile Lys Ile Asn
50 55 60
Gly Tyr Thr Gly Pro Gly Thr Val Arg Ile Ser Leu Val Thr Lys Asp
65 70 75 80
Pro Pro His Arg Pro His Pro His Glu Leu Val Gly Lys Asp Cys Arg
85 90 95
Asp Gly Phe Tyr Glu Ala Glu Leu Cys Pro Asp Arg Cys Ile His Ser
100 105 110
Phe Gln Asn Leu Gly Ile Gln Cys Val Lys Lys Arg Asp Leu Glu Gln
115 120 125
Ala Ile Ser Gln Arg Ile Gln Thr Asn Asn Asn Pro Phe Gln Val Pro
130 135 140
Ile Glu Glu Gln Arg Gly Asp Tyr Asp Leu Asn Ala Val Arg Leu Cys
145 150 155 160
Phe Gln Val Thr Val Arg Asp Pro Ser Gly Arg Pro Leu Arg Leu Pro
165 170 175
Pro Val Leu Ser His Pro Ile Phe Asp Asn Arg Ala Pro Asn Thr Ala
180 185 190
Glu Leu Lys Ile Cys Arg Val Asn Arg Asn Ser Gly Ser Cys Leu Gly
195 200 205
Gly Asp Glu Ile Phe Leu Leu Cys Asp Lys Val Gln Lys Glu Asp Ile
210 215 220
Glu Val Tyr Phe Thr Gly Pro Gly Trp Glu Ala Arg Gly Ser Phe Ser
225 230 235 240
Gln Ala Asp Val His Arg Gln Val Ala Ile Val Phe Arg Thr Pro Pro
245 250 255
Tyr Ala Asp Pro Ser Leu Gln Ala Pro Val Arg Val Ser Met Gln Leu
260 265 270
Arg Arg Pro Ser Asp Arg Glu Leu Ser Glu Pro Met Glu Phe Gln Tyr
275 280 285
Leu Pro Asp Thr Asp Asp Arg His Arg Ile Glu Glu Lys Arg Lys Arg
290 295 300
Thr Tyr Glu Thr Phe Lys Ser Ile Met Lys Lys Ser Pro Phe Ser Gly
305 310 315 320
Pro Thr Asp Pro Arg Pro Pro Pro Arg Arg Ile Ala Val Pro Ser Arg
325 330 335
Ser Ser Ala Ser Val Pro Lys Pro Ala Pro Gln Pro Tyr Pro Phe Thr
340 345 350
Ser Ser Leu Ser Thr Ile Asn Tyr Asp Glu Phe Pro Thr Met Val Phe
355 360 365
Pro Ser Gly Gln Ile Ser Gln Ala Ser Ala Leu Ala Pro Ala Pro Pro
370 375 380
Gln Val Leu Pro Gln Ala Pro Ala Pro Ala Pro Ala Pro Ala Met Val
385 390 395 400
Ser Ala Leu Ala Gln Arg Pro Pro Asp Pro Ala Pro Ala Pro Leu Gly
405 410 415
Ala Pro Gly Leu Pro Asn Gly Leu Leu Ser Gly Asp Glu Asp Phe Ser
420 425 430
Ser Ile Ala Asp Met Asp Phe Ser Ala Leu Leu Ser Gln Ile Ser Ser
435 440 445
<210> 16
<211> 480
<212> PRT
<213> 人
<400> 16
Met Asp Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala
1 5 10 15
Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met
20 25 30
Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly
35 40 45
Glu Arg Ser Thr Asp Thr Thr Lys Thr His Pro Thr Ile Lys Ile Asn
50 55 60
Gly Tyr Thr Gly Pro Gly Thr Val Arg Ile Ser Leu Val Thr Lys Asp
65 70 75 80
Pro Pro His Arg Pro His Pro His Glu Leu Val Gly Lys Asp Cys Arg
85 90 95
Asp Gly Phe Tyr Glu Ala Glu Leu Cys Pro Asp Arg Cys Ile His Ser
100 105 110
Phe Gln Asn Leu Gly Ile Gln Cys Val Lys Lys Arg Asp Leu Glu Gln
115 120 125
Ala Ile Ser Gln Arg Ile Gln Thr Asn Asn Asn Pro Phe Gln Val Pro
130 135 140
Ile Glu Glu Gln Arg Gly Asp Tyr Asp Leu Asn Ala Val Arg Leu Cys
145 150 155 160
Phe Gln Val Thr Val Arg Asp Pro Ser Gly Arg Pro Leu Arg Leu Pro
165 170 175
Pro Val Leu Ser His Pro Ile Phe Asp Asn Arg Ala Pro Asn Thr Ala
180 185 190
Glu Leu Lys Ile Cys Arg Val Asn Arg Asn Ser Gly Ser Cys Leu Gly
195 200 205
Gly Asp Glu Ile Phe Leu Leu Cys Asp Lys Val Gln Lys Asp Asp Arg
210 215 220
His Arg Ile Glu Glu Lys Arg Lys Arg Thr Tyr Glu Thr Phe Lys Ser
225 230 235 240
Ile Met Lys Lys Ser Pro Phe Ser Gly Pro Thr Asp Pro Arg Pro Pro
245 250 255
Pro Arg Arg Ile Ala Val Pro Ser Arg Ser Ser Ala Ser Val Pro Lys
260 265 270
Pro Ala Pro Gln Pro Tyr Pro Phe Thr Ser Ser Leu Ser Thr Ile Asn
275 280 285
Tyr Asp Glu Phe Pro Thr Met Val Phe Pro Ser Gly Gln Ile Ser Gln
290 295 300
Ala Ser Ala Leu Ala Pro Ala Pro Pro Gln Val Leu Pro Gln Ala Pro
305 310 315 320
Ala Pro Ala Pro Ala Pro Ala Met Val Ser Ala Leu Ala Gln Ala Pro
325 330 335
Ala Pro Val Pro Val Leu Ala Pro Gly Pro Pro Gln Ala Val Ala Pro
340 345 350
Pro Ala Pro Lys Pro Thr Gln Ala Gly Glu Gly Thr Leu Ser Glu Ala
355 360 365
Leu Leu Gln Leu Gln Phe Asp Asp Glu Asp Leu Gly Ala Leu Leu Gly
370 375 380
Asn Ser Thr Asp Pro Ala Val Phe Thr Asp Leu Ala Ser Val Asp Asn
385 390 395 400
Ser Glu Phe Gln Gln Leu Leu Asn Gln Gly Ile Pro Val Ala Pro His
405 410 415
Thr Thr Glu Pro Met Leu Met Glu Tyr Pro Glu Ala Ile Thr Arg Leu
420 425 430
Val Thr Gly Ala Gln Arg Pro Pro Asp Pro Ala Pro Ala Pro Leu Gly
435 440 445
Ala Pro Gly Leu Pro Asn Gly Leu Leu Ser Gly Asp Glu Asp Phe Ser
450 455 460
Ser Ile Ala Asp Met Asp Phe Ser Ala Leu Leu Ser Gln Ile Ser Ser
465 470 475 480
<210> 17
<211> 445
<212> PRT
<213> 人
<400> 17
Met Asp Glu Leu Phe Pro Leu Ile Phe Pro Ala Glu Pro Ala Gln Ala
1 5 10 15
Ser Gly Pro Tyr Val Glu Ile Ile Glu Gln Pro Lys Gln Arg Gly Met
20 25 30
Arg Phe Arg Tyr Lys Cys Glu Gly Arg Ser Ala Gly Ser Ile Pro Gly
35 40 45
Glu Arg Ser Thr Asp Thr Thr Lys Thr His Pro Thr Ile Lys Ile Asn
50 55 60
Gly Tyr Thr Gly Pro Gly Thr Val Arg Ile Ser Leu Val Thr Lys Asp
65 70 75 80
Pro Pro His Arg Pro His Pro His Glu Leu Val Gly Lys Asp Cys Arg
85 90 95
Asp Gly Phe Tyr Glu Ala Glu Leu Cys Pro Asp Arg Cys Ile His Ser
100 105 110
Phe Gln Asn Leu Gly Ile Gln Cys Val Lys Lys Arg Asp Leu Glu Gln
115 120 125
Ala Ile Ser Gln Arg Ile Gln Thr Asn Asn Asn Pro Phe Gln Val Pro
130 135 140
Ile Glu Glu Gln Arg Gly Asp Tyr Asp Leu Asn Ala Val Arg Leu Cys
145 150 155 160
Phe Gln Val Thr Val Arg Asp Pro Ser Gly Arg Pro Leu Arg Leu Pro
165 170 175
Pro Val Leu Ser His Pro Ile Phe Asp Asn His Asp Arg His Arg Ile
180 185 190
Glu Glu Lys Arg Lys Arg Thr Tyr Glu Thr Phe Lys Ser Ile Met Lys
195 200 205
Lys Ser Pro Phe Ser Gly Pro Thr Asp Pro Arg Pro Pro Pro Arg Arg
210 215 220
Ile Ala Val Pro Ser Arg Ser Ser Ala Ser Val Pro Lys Pro Ala Pro
225 230 235 240
Gln Pro Tyr Pro Phe Thr Ser Ser Leu Ser Thr Ile Asn Tyr Asp Glu
245 250 255
Phe Pro Thr Met Val Phe Pro Ser Gly Gln Ile Ser Gln Ala Ser Ala
260 265 270
Leu Ala Pro Ala Pro Pro Gln Val Leu Pro Gln Ala Pro Ala Pro Ala
275 280 285
Pro Ala Pro Ala Met Val Ser Ala Leu Ala Gln Ala Pro Ala Pro Val
290 295 300
Pro Val Leu Ala Pro Gly Pro Pro Gln Ala Val Ala Pro Pro Ala Pro
305 310 315 320
Lys Pro Thr Gln Ala Gly Glu Gly Thr Leu Ser Glu Ala Leu Leu Gln
325 330 335
Leu Gln Phe Asp Asp Glu Asp Leu Gly Ala Leu Leu Gly Asn Ser Thr
340 345 350
Asp Pro Ala Val Phe Thr Asp Leu Ala Ser Val Asp Asn Ser Glu Phe
355 360 365
Gln Gln Leu Leu Asn Gln Gly Ile Pro Val Ala Pro His Thr Thr Glu
370 375 380
Pro Met Leu Met Glu Tyr Pro Glu Ala Ile Thr Arg Leu Val Thr Gly
385 390 395 400
Ala Gln Arg Pro Pro Asp Pro Ala Pro Ala Pro Leu Gly Ala Pro Gly
405 410 415
Leu Pro Asn Gly Leu Leu Ser Gly Asp Glu Asp Phe Ser Ser Ile Ala
420 425 430
Asp Met Asp Phe Ser Ala Leu Leu Ser Gln Ile Ser Ser
435 440 445
<210> 18
<211> 2595
<212> DNA
<213> 人
<400> 18
agcgcgcagg cgcggccgga ttccgggcag tgacgcgacg gcgggccgcg cggcgcattt 60
ccgcctctgg cgaatggctc gtctgtagtg cacgccgcgg gcccagctgc gaccccggcc 120
ccgcccccgg gaccccggcc atggacgaac tgttccccct catcttcccg gcagagccag 180
cccaggcctc tggcccctat gtggagatca ttgagcagcc caagcagcgg ggcatgcgct 240
tccgctacaa gtgcgagggg cgctccgcgg gcagcatccc aggcgagagg agcacagata 300
ccaccaagac ccaccccacc atcaagatca atggctacac aggaccaggg acagtgcgca 360
tctccctggt caccaaggac cctcctcacc ggcctcaccc ccacgagctt gtaggaaagg 420
actgccggga tggcttctat gaggctgagc tctgcccgga ccgctgcatc cacagtttcc 480
agaacctggg aatccagtgt gtgaagaagc gggacctgga gcaggctatc agtcagcgca 540
tccagaccaa caacaacccc ttccaagttc ctatagaaga gcagcgtggg gactacgacc 600
tgaatgctgt gcggctctgc ttccaggtga cagtgcggga cccatcaggc aggcccctcc 660
gcctgccgcc tgtcctttct catcccatct ttgacaatcg tgcccccaac actgccgagc 720
tcaagatctg ccgagtgaac cgaaactctg gcagctgcct cggtggggat gagatcttcc 780
tactgtgtga caaggtgcag aaagaggaca ttgaggtgta tttcacggga ccaggctggg 840
aggcccgagg ctccttttcg caagctgatg tgcaccgaca agtggccatt gtgttccgga 900
cccctcccta cgcagacccc agcctgcagg ctcctgtgcg tgtctccatg cagctgcggc 960
ggccttccga ccgggagctc agtgagccca tggaattcca gtacctgcca gatacagacg 1020
atcgtcaccg gattgaggag aaacgtaaaa ggacatatga gaccttcaag agcatcatga 1080
agaagagtcc tttcagcgga cccaccgacc cccggcctcc acctcgacgc attgctgtgc 1140
cttcccgcag ctcagcttct gtccccaagc cagcacccca gccctatccc tttacgtcat 1200
ccctgagcac catcaactat gatgagtttc ccaccatggt gtttccttct gggcagatca 1260
gccaggcctc ggccttggcc ccggcccctc cccaagtcct gccccaggct ccagcccctg 1320
cccctgctcc agccatggta tcagctctgg cccaggcccc agcccctgtc ccagtcctag 1380
ccccaggccc tcctcaggct gtggccccac ctgcccccaa gcccacccag gctggggaag 1440
gaacgctgtc agaggccctg ctgcagctgc agtttgatga tgaagacctg ggggccttgc 1500
ttggcaacag cacagaccca gctgtgttca cagacctggc atccgtcgac aactccgagt 1560
ttcagcagct gctgaaccag ggcatacctg tggcccccca cacaactgag cccatgctga 1620
tggagtaccc tgaggctata actcgcctag tgacaggggc ccagaggccc cccgacccag 1680
ctcctgctcc actgggggcc ccggggctcc ccaatggcct cctttcagga gatgaagact 1740
tctcctccat tgcggacatg gacttctcag ccctgctgag tcagatcagc tcctaagggg 1800
gtgacgcctg ccctccccag agcactgggt tgcaggggat tgaagccctc caaaagcact 1860
tacggattct ggtggggtgt gttccaactg cccccaactt tgtggatgtc ttccttggag 1920
gggggagcca tattttattc ttttattgtc agtatctgta tctctctctc tttttggagg 1980
tgcttaagca gaagcattaa cttctctgga aaggggggag ctggggaaac tcaaactttt 2040
cccctgtcct gatggtcagc tcccttctct gtagggaact ctggggtccc ccatccccat 2100
cctccagctt ctggtactct cctagagaca gaagcaggct ggaggtaagg cctttgagcc 2160
cacaaagcct tatcaagtgt cttccatcat ggattcatta cagcttaatc aaaataacgc 2220
cccagatacc agcccctgta tggcactggc attgtccctg tgcctaacac cagcgtttga 2280
ggggctggcc ttcctgccct acagaggtct ctgccggctc tttccttgct caaccatggc 2340
tgaaggaaac cagtgcaaca gcactggctc tctccaggat ccagaagggg tttggtctgg 2400
gacttccttg ctctccctct tctcaagtgc cttaatagta gggtaagttg ttaagagtgg 2460
gggagagcag gctggcagct ctccagtcag gaggcatagt ttttactgaa caatcaaagc 2520
acttggactc ttgctctttc tactctgaac taataaatct gttgccaagc tggctagaaa 2580
aaaaaaaaaa aaaaa 2595
<210> 19
<211> 2586
<212> DNA
<213> 人
<400> 19
agcgcgcagg cgcggccgga ttccgggcag tgacgcgacg gcgggccgcg cggcgcattt 60
ccgcctctgg cgaatggctc gtctgtagtg cacgccgcgg gcccagctgc gaccccggcc 120
ccgcccccgg gaccccggcc atggacgaac tgttccccct catcttcccg gcagagccag 180
cccaggcctc tggcccctat gtggagatca ttgagcagcc caagcagcgg ggcatgcgct 240
tccgctacaa gtgcgagggg cgctccgcgg gcagcatccc aggcgagagg agcacagata 300
ccaccaagac ccaccccacc atcaagatca atggctacac aggaccaggg acagtgcgca 360
tctccctggt caccaaggac cctcctcacc ggcctcaccc ccacgagctt gtaggaaagg 420
actgccggga tggcttctat gaggctgagc tctgcccgga ccgctgcatc cacagtttcc 480
agaacctggg aatccagtgt gtgaagaagc gggacctgga gcaggctatc agtcagcgca 540
tccagaccaa caacaacccc ttccaagaag agcagcgtgg ggactacgac ctgaatgctg 600
tgcggctctg cttccaggtg acagtgcggg acccatcagg caggcccctc cgcctgccgc 660
ctgtcctttc tcatcccatc tttgacaatc gtgcccccaa cactgccgag ctcaagatct 720
gccgagtgaa ccgaaactct ggcagctgcc tcggtgggga tgagatcttc ctactgtgtg 780
acaaggtgca gaaagaggac attgaggtgt atttcacggg accaggctgg gaggcccgag 840
gctccttttc gcaagctgat gtgcaccgac aagtggccat tgtgttccgg acccctccct 900
acgcagaccc cagcctgcag gctcctgtgc gtgtctccat gcagctgcgg cggccttccg 960
accgggagct cagtgagccc atggaattcc agtacctgcc agatacagac gatcgtcacc 1020
ggattgagga gaaacgtaaa aggacatatg agaccttcaa gagcatcatg aagaagagtc 1080
ctttcagcgg acccaccgac ccccggcctc cacctcgacg cattgctgtg ccttcccgca 1140
gctcagcttc tgtccccaag ccagcacccc agccctatcc ctttacgtca tccctgagca 1200
ccatcaacta tgatgagttt cccaccatgg tgtttccttc tgggcagatc agccaggcct 1260
cggccttggc cccggcccct ccccaagtcc tgccccaggc tccagcccct gcccctgctc 1320
cagccatggt atcagctctg gcccaggccc cagcccctgt cccagtccta gccccaggcc 1380
ctcctcaggc tgtggcccca cctgccccca agcccaccca ggctggggaa ggaacgctgt 1440
cagaggccct gctgcagctg cagtttgatg atgaagacct gggggccttg cttggcaaca 1500
gcacagaccc agctgtgttc acagacctgg catccgtcga caactccgag tttcagcagc 1560
tgctgaacca gggcatacct gtggcccccc acacaactga gcccatgctg atggagtacc 1620
ctgaggctat aactcgccta gtgacagggg cccagaggcc ccccgaccca gctcctgctc 1680
cactgggggc cccggggctc cccaatggcc tcctttcagg agatgaagac ttctcctcca 1740
ttgcggacat ggacttctca gccctgctga gtcagatcag ctcctaaggg ggtgacgcct 1800
gccctcccca gagcactggg ttgcagggga ttgaagccct ccaaaagcac ttacggattc 1860
tggtggggtg tgttccaact gcccccaact ttgtggatgt cttccttgga ggggggagcc 1920
atattttatt cttttattgt cagtatctgt atctctctct ctttttggag gtgcttaagc 1980
agaagcatta acttctctgg aaagggggga gctggggaaa ctcaaacttt tcccctgtcc 2040
tgatggtcag ctcccttctc tgtagggaac tctggggtcc cccatcccca tcctccagct 2100
tctggtactc tcctagagac agaagcaggc tggaggtaag gcctttgagc ccacaaagcc 2160
ttatcaagtg tcttccatca tggattcatt acagcttaat caaaataacg ccccagatac 2220
cagcccctgt atggcactgg cattgtccct gtgcctaaca ccagcgtttg aggggctggc 2280
cttcctgccc tacagaggtc tctgccggct ctttccttgc tcaaccatgg ctgaaggaaa 2340
ccagtgcaac agcactggct ctctccagga tccagaaggg gtttggtctg ggacttcctt 2400
gctctccctc ttctcaagtg ccttaatagt agggtaagtt gttaagagtg ggggagagca 2460
ggctggcagc tctccagtca ggaggcatag tttttactga acaatcaaag cacttggact 2520
cttgctcttt ctactctgaa ctaataaatc tgttgccaag ctggctagaa aaaaaaaaaa 2580
aaaaaa 2586
<210> 20
<211> 2388
<212> DNA
<213> 人
<400> 20
agcgcgcagg cgcggccgga ttccgggcag tgacgcgacg gcgggccgcg cggcgcattt 60
ccgcctctgg cgaatggctc gtctgtagtg cacgccgcgg gcccagctgc gaccccggcc 120
ccgcccccgg gaccccggcc atggacgaac tgttccccct catcttcccg gcagagccag 180
cccaggcctc tggcccctat gtggagatca ttgagcagcc caagcagcgg ggcatgcgct 240
tccgctacaa gtgcgagggg cgctccgcgg gcagcatccc aggcgagagg agcacagata 300
ccaccaagac ccaccccacc atcaagatca atggctacac aggaccaggg acagtgcgca 360
tctccctggt caccaaggac cctcctcacc ggcctcaccc ccacgagctt gtaggaaagg 420
actgccggga tggcttctat gaggctgagc tctgcccgga ccgctgcatc cacagtttcc 480
agaacctggg aatccagtgt gtgaagaagc gggacctgga gcaggctatc agtcagcgca 540
tccagaccaa caacaacccc ttccaagttc ctatagaaga gcagcgtggg gactacgacc 600
tgaatgctgt gcggctctgc ttccaggtga cagtgcggga cccatcaggc aggcccctcc 660
gcctgccgcc tgtcctttct catcccatct ttgacaatcg tgcccccaac actgccgagc 720
tcaagatctg ccgagtgaac cgaaactctg gcagctgcct cggtggggat gagatcttcc 780
tactgtgtga caaggtgcag aaagaggaca ttgaggtgta tttcacggga ccaggctggg 840
aggcccgagg ctccttttcg caagctgatg tgcaccgaca agtggccatt gtgttccgga 900
cccctcccta cgcagacccc agcctgcagg ctcctgtgcg tgtctccatg cagctgcggc 960
ggccttccga ccgggagctc agtgagccca tggaattcca gtacctgcca gatacagacg 1020
atcgtcaccg gattgaggag aaacgtaaaa ggacatatga gaccttcaag agcatcatga 1080
agaagagtcc tttcagcgga cccaccgacc cccggcctcc acctcgacgc attgctgtgc 1140
cttcccgcag ctcagcttct gtccccaagc cagccccagg ccctcctcag gctgtggccc 1200
cacctgcccc caagcccacc caggctgggg aaggaacgct gtcagaggcc ctgctgcagc 1260
tgcagtttga tgatgaagac ctgggggcct tgcttggcaa cagcacagac ccagctgtgt 1320
tcacagacct ggcatccgtc gacaactccg agtttcagca gctgctgaac cagggcatac 1380
ctgtggcccc ccacacaact gagcccatgc tgatggagta ccctgaggct ataactcgcc 1440
tagtgacagg ggcccagagg ccccccgacc cagctcctgc tccactgggg gccccggggc 1500
tccccaatgg cctcctttca ggagatgaag acttctcctc cattgcggac atggacttct 1560
cagccctgct gagtcagatc agctcctaag ggggtgacgc ctgccctccc cagagcactg 1620
ggttgcaggg gattgaagcc ctccaaaagc acttacggat tctggtgggg tgtgttccaa 1680
ctgcccccaa ctttgtggat gtcttccttg gaggggggag ccatatttta ttcttttatt 1740
gtcagtatct gtatctctct ctctttttgg aggtgcttaa gcagaagcat taacttctct 1800
ggaaaggggg gagctgggga aactcaaact tttcccctgt cctgatggtc agctcccttc 1860
tctgtaggga actctggggt cccccatccc catcctccag cttctggtac tctcctagag 1920
acagaagcag gctggaggta aggcctttga gcccacaaag ccttatcaag tgtcttccat 1980
catggattca ttacagctta atcaaaataa cgccccagat accagcccct gtatggcact 2040
ggcattgtcc ctgtgcctaa caccagcgtt tgaggggctg gccttcctgc cctacagagg 2100
tctctgccgg ctctttcctt gctcaaccat ggctgaagga aaccagtgca acagcactgg 2160
ctctctccag gatccagaag gggtttggtc tgggacttcc ttgctctccc tcttctcaag 2220
tgccttaata gtagggtaag ttgttaagag tgggggagag caggctggca gctctccagt 2280
caggaggcat agtttttact gaacaatcaa agcacttgga ctcttgctct ttctactctg 2340
aactaataaa tctgttgcca agctggctag aaaaaaaaaa aaaaaaaa 2388
<210> 21
<211> 2286
<212> DNA
<213> 人
<400> 21
agcgcgcagg cgcggccgga ttccgggcag tgacgcgacg gcgggccgcg cggcgcattt 60
ccgcctctgg cgaatggctc gtctgtagtg cacgccgcgg gcccagctgc gaccccggcc 120
ccgcccccgg gaccccggcc atggacgaac tgttccccct catcttcccg gcagagccag 180
cccaggcctc tggcccctat gtggagatca ttgagcagcc caagcagcgg ggcatgcgct 240
tccgctacaa gtgcgagggg cgctccgcgg gcagcatccc aggcgagagg agcacagata 300
ccaccaagac ccaccccacc atcaagatca atggctacac aggaccaggg acagtgcgca 360
tctccctggt caccaaggac cctcctcacc ggcctcaccc ccacgagctt gtaggaaagg 420
actgccggga tggcttctat gaggctgagc tctgcccgga ccgctgcatc cacagtttcc 480
agaacctggg aatccagtgt gtgaagaagc gggacctgga gcaggctatc agtcagcgca 540
tccagaccaa caacaacccc ttccaagttc ctatagaaga gcagcgtggg gactacgacc 600
tgaatgctgt gcggctctgc ttccaggtga cagtgcggga cccatcaggc aggcccctcc 660
gcctgccgcc tgtcctttct catcccatct ttgacaatcg tgcccccaac actgccgagc 720
tcaagatctg ccgagtgaac cgaaactctg gcagctgcct cggtggggat gagatcttcc 780
tactgtgtga caaggtgcag aaagaggaca ttgaggtgta tttcacggga ccaggctggg 840
aggcccgagg ctccttttcg caagctgatg tgcaccgaca agtggccatt gtgttccgga 900
cccctcccta cgcagacccc agcctgcagg ctcctgtgcg tgtctccatg cagctgcggc 960
ggccttccga ccgggagctc agtgagccca tggaattcca gtacctgcca gatacagacg 1020
atcgtcaccg gattgaggag aaacgtaaaa ggacatatga gaccttcaag agcatcatga 1080
agaagagtcc tttcagcgga cccaccgacc cccggcctcc acctcgacgc attgctgtgc 1140
cttcccgcag ctcagcttct gtccccaagc cagcacccca gccctatccc tttacgtcat 1200
ccctgagcac catcaactat gatgagtttc ccaccatggt gtttccttct gggcagatca 1260
gccaggcctc ggccttggcc ccggcccctc cccaagtcct gccccaggct ccagcccctg 1320
cccctgctcc agccatggta tcagctctgg cccagaggcc ccccgaccca gctcctgctc 1380
cactgggggc cccggggctc cccaatggcc tcctttcagg agatgaagac ttctcctcca 1440
ttgcggacat ggacttctca gccctgctga gtcagatcag ctcctaaggg ggtgacgcct 1500
gccctcccca gagcactggg ttgcagggga ttgaagccct ccaaaagcac ttacggattc 1560
tggtggggtg tgttccaact gcccccaact ttgtggatgt cttccttgga ggggggagcc 1620
atattttatt cttttattgt cagtatctgt atctctctct ctttttggag gtgcttaagc 1680
agaagcatta acttctctgg aaagggggga gctggggaaa ctcaaacttt tcccctgtcc 1740
tgatggtcag ctcccttctc tgtagggaac tctggggtcc cccatcccca tcctccagct 1800
tctggtactc tcctagagac agaagcaggc tggaggtaag gcctttgagc ccacaaagcc 1860
ttatcaagtg tcttccatca tggattcatt acagcttaat caaaataacg ccccagatac 1920
cagcccctgt atggcactgg cattgtccct gtgcctaaca ccagcgtttg aggggctggc 1980
cttcctgccc tacagaggtc tctgccggct ctttccttgc tcaaccatgg ctgaaggaaa 2040
ccagtgcaac agcactggct ctctccagga tccagaaggg gtttggtctg ggacttcctt 2100
gctctccctc ttctcaagtg ccttaatagt agggtaagtt gttaagagtg ggggagagca 2160
ggctggcagc tctccagtca ggaggcatag tttttactga acaatcaaag cacttggact 2220
cttgctcttt ctactctgaa ctaataaatc tgttgccaag ctggctagaa aaaaaaaaaa 2280
aaaaaa 2286
<210> 22
<211> 2341
<212> DNA
<213> 人
<400> 22
attccgggca gtgacgcgac ggcgggccgc gcggcgcatt tccgcctctg gcgaatggct 60
cgtctgtagt gcacgccgcg ggcccagctg cgaccccggc cccgcccccg ggaccccggc 120
catggacgaa ctgttccccc tcatcttccc ggcagagcca gcccaggcct ctggccccta 180
tgtggagatc attgagcagc ccaagcagcg gggcatgcgc ttccgctaca agtgcgaggg 240
gcgctccgcg ggcagcatcc caggcgagag gagcacagat accaccaaga cccaccccac 300
catcaagatc aatggctaca caggaccagg gacagtgcgc atctccctgg tcaccaagga 360
ccctcctcac cggcctcacc cccacgagct tgtaggaaag gactgccggg atggcttcta 420
tgaggctgag ctctgcccgg accgctgcat ccacagtttc cagaacctgg gaatccagtg 480
tgtgaagaag cgggacctgg agcaggctat cagtcagcgc atccagacca acaacaaccc 540
cttccaagtt cctatagaag agcagcgtgg ggactacgac ctgaatgctg tgcggctctg 600
cttccaggtg acagtgcggg acccatcagg caggcccctc cgcctgccgc ctgtcctttc 660
tcatcccatc tttgacaatc gtgcccccaa cactgccgag ctcaagatct gccgagtgaa 720
ccgaaactct ggcagctgcc tcggtgggga tgagatcttc ctactgtgtg acaaggtgca 780
gaaagacgat cgtcaccgga ttgaggagaa acgtaaaagg acatatgaga ccttcaagag 840
catcatgaag aagagtcctt tcagcggacc caccgacccc cggcctccac ctcgacgcat 900
tgctgtgcct tcccgcagct cagcttctgt ccccaagcca gcaccccagc cctatccctt 960
tacgtcatcc ctgagcacca tcaactatga tgagtttccc accatggtgt ttccttctgg 1020
gcagatcagc caggcctcgg ccttggcccc ggcccctccc caagtcctgc cccaggctcc 1080
agcccctgcc cctgctccag ccatggtatc agctctggcc caggccccag cccctgtccc 1140
agtcctagcc ccaggccctc ctcaggctgt ggccccacct gcccccaagc ccacccaggc 1200
tggggaagga acgctgtcag aggccctgct gcagctgcag tttgatgatg aagacctggg 1260
ggccttgctt ggcaacagca cagacccagc tgtgttcaca gacctggcat ccgtcgacaa 1320
ctccgagttt cagcagctgc tgaaccaggg catacctgtg gccccccaca caactgagcc 1380
catgctgatg gagtaccctg aggctataac tcgcctagtg acaggggccc agaggccccc 1440
cgacccagct cctgctccac tgggggcccc ggggctcccc aatggcctcc tttcaggaga 1500
tgaagacttc tcctccattg cggacatgga cttctcagcc ctgctgagtc agatcagctc 1560
ctaagggggt gacgcctgcc ctccccagag cactgggttg caggggattg aagccctcca 1620
aaagcactta cggattctgg tggggtgtgt tccaactgcc cccaactttg tggatgtctt 1680
ccttggaggg gggagccata ttttattctt ttattgtcag tatctgtatc tctctctctt 1740
tttggaggtg cttaagcaga agcattaact tctctggaaa ggggggagct ggggaaactc 1800
aaacttttcc cctgtcctga tggtcagctc ccttctctgt agggaactct ggggtccccc 1860
atccccatcc tccagcttct ggtactctcc tagagacaga agcaggctgg aggtaaggcc 1920
tttgagccca caaagcctta tcaagtgtct tccatcatgg attcattaca gcttaatcaa 1980
aataacgccc cagataccag cccctgtatg gcactggcat tgtccctgtg cctaacacca 2040
gcgtttgagg ggctggcctt cctgccctac agaggtctct gccggctctt tccttgctca 2100
accatggctg aaggaaacca gtgcaacagc actggctctc tccaggatcc agaaggggtt 2160
tggtctggga cttccttgct ctccctcttc tcaagtgcct taatagtagg gtaagttgtt 2220
aagagtgggg gagagcaggc tggcagctct ccagtcagga ggcatagttt ttactgaaca 2280
atcaaagcac ttggactctt gctctttcta ctctgaacta ataaatctgt tgccaagctg 2340
g 2341
<210> 23
<211> 2236
<212> DNA
<213> 人
<400> 23
attccgggca gtgacgcgac ggcgggccgc gcggcgcatt tccgcctctg gcgaatggct 60
cgtctgtagt gcacgccgcg ggcccagctg cgaccccggc cccgcccccg ggaccccggc 120
catggacgaa ctgttccccc tcatcttccc ggcagagcca gcccaggcct ctggccccta 180
tgtggagatc attgagcagc ccaagcagcg gggcatgcgc ttccgctaca agtgcgaggg 240
gcgctccgcg ggcagcatcc caggcgagag gagcacagat accaccaaga cccaccccac 300
catcaagatc aatggctaca caggaccagg gacagtgcgc atctccctgg tcaccaagga 360
ccctcctcac cggcctcacc cccacgagct tgtaggaaag gactgccggg atggcttcta 420
tgaggctgag ctctgcccgg accgctgcat ccacagtttc cagaacctgg gaatccagtg 480
tgtgaagaag cgggacctgg agcaggctat cagtcagcgc atccagacca acaacaaccc 540
cttccaagtt cctatagaag agcagcgtgg ggactacgac ctgaatgctg tgcggctctg 600
cttccaggtg acagtgcggg acccatcagg caggcccctc cgcctgccgc ctgtcctttc 660
tcatcccatc tttgacaatc acgatcgtca ccggattgag gagaaacgta aaaggacata 720
tgagaccttc aagagcatca tgaagaagag tcctttcagc ggacccaccg acccccggcc 780
tccacctcga cgcattgctg tgccttcccg cagctcagct tctgtcccca agccagcacc 840
ccagccctat ccctttacgt catccctgag caccatcaac tatgatgagt ttcccaccat 900
ggtgtttcct tctgggcaga tcagccaggc ctcggccttg gccccggccc ctccccaagt 960
cctgccccag gctccagccc ctgcccctgc tccagccatg gtatcagctc tggcccaggc 1020
cccagcccct gtcccagtcc tagccccagg ccctcctcag gctgtggccc cacctgcccc 1080
caagcccacc caggctgggg aaggaacgct gtcagaggcc ctgctgcagc tgcagtttga 1140
tgatgaagac ctgggggcct tgcttggcaa cagcacagac ccagctgtgt tcacagacct 1200
ggcatccgtc gacaactccg agtttcagca gctgctgaac cagggcatac ctgtggcccc 1260
ccacacaact gagcccatgc tgatggagta ccctgaggct ataactcgcc tagtgacagg 1320
ggcccagagg ccccccgacc cagctcctgc tccactgggg gccccggggc tccccaatgg 1380
cctcctttca ggagatgaag acttctcctc cattgcggac atggacttct cagccctgct 1440
gagtcagatc agctcctaag ggggtgacgc ctgccctccc cagagcactg ggttgcaggg 1500
gattgaagcc ctccaaaagc acttacggat tctggtgggg tgtgttccaa ctgcccccaa 1560
ctttgtggat gtcttccttg gaggggggag ccatatttta ttcttttatt gtcagtatct 1620
gtatctctct ctctttttgg aggtgcttaa gcagaagcat taacttctct ggaaaggggg 1680
gagctgggga aactcaaact tttcccctgt cctgatggtc agctcccttc tctgtaggga 1740
actctggggt cccccatccc catcctccag cttctggtac tctcctagag acagaagcag 1800
gctggaggta aggcctttga gcccacaaag ccttatcaag tgtcttccat catggattca 1860
ttacagctta atcaaaataa cgccccagat accagcccct gtatggcact ggcattgtcc 1920
ctgtgcctaa caccagcgtt tgaggggctg gccttcctgc cctacagagg tctctgccgg 1980
ctctttcctt gctcaaccat ggctgaagga aaccagtgca acagcactgg ctctctccag 2040
gatccagaag gggtttggtc tgggacttcc ttgctctccc tcttctcaag tgccttaata 2100
gtagggtaag ttgttaagag tgggggagag caggctggca gctctccagt caggaggcat 2160
agtttttact gaacaatcaa agcacttgga ctcttgctct ttctactctg aactaataaa 2220
tctgttgcca agctgg 2236
<210> 24
<211> 2555
<212> PRT
<213> 人
<400> 24
Met Pro Pro Leu Leu Ala Pro Leu Leu Cys Leu Ala Leu Leu Pro Ala
1 5 10 15
Leu Ala Ala Arg Gly Pro Arg Cys Ser Gln Pro Gly Glu Thr Cys Leu
20 25 30
Asn Gly Gly Lys Cys Glu Ala Ala Asn Gly Thr Glu Ala Cys Val Cys
35 40 45
Gly Gly Ala Phe Val Gly Pro Arg Cys Gln Asp Pro Asn Pro Cys Leu
50 55 60
Ser Thr Pro Cys Lys Asn Ala Gly Thr Cys His Val Val Asp Arg Arg
65 70 75 80
Gly Val Ala Asp Tyr Ala Cys Ser Cys Ala Leu Gly Phe Ser Gly Pro
85 90 95
Leu Cys Leu Thr Pro Leu Asp Asn Ala Cys Leu Thr Asn Pro Cys Arg
100 105 110
Asn Gly Gly Thr Cys Asp Leu Leu Thr Leu Thr Glu Tyr Lys Cys Arg
115 120 125
Cys Pro Pro Gly Trp Ser Gly Lys Ser Cys Gln Gln Ala Asp Pro Cys
130 135 140
Ala Ser Asn Pro Cys Ala Asn Gly Gly Gln Cys Leu Pro Phe Glu Ala
145 150 155 160
Ser Tyr Ile Cys His Cys Pro Pro Ser Phe His Gly Pro Thr Cys Arg
165 170 175
Gln Asp Val Asn Glu Cys Gly Gln Lys Pro Gly Leu Cys Arg His Gly
180 185 190
Gly Thr Cys His Asn Glu Val Gly Ser Tyr Arg Cys Val Cys Arg Ala
195 200 205
Thr His Thr Gly Pro Asn Cys Glu Arg Pro Tyr Val Pro Cys Ser Pro
210 215 220
Ser Pro Cys Gln Asn Gly Gly Thr Cys Arg Pro Thr Gly Asp Val Thr
225 230 235 240
His Glu Cys Ala Cys Leu Pro Gly Phe Thr Gly Gln Asn Cys Glu Glu
245 250 255
Asn Ile Asp Asp Cys Pro Gly Asn Asn Cys Lys Asn Gly Gly Ala Cys
260 265 270
Val Asp Gly Val Asn Thr Tyr Asn Cys Arg Cys Pro Pro Glu Trp Thr
275 280 285
Gly Gln Tyr Cys Thr Glu Asp Val Asp Glu Cys Gln Leu Met Pro Asn
290 295 300
Ala Cys Gln Asn Gly Gly Thr Cys His Asn Thr His Gly Gly Tyr Asn
305 310 315 320
Cys Val Cys Val Asn Gly Trp Thr Gly Glu Asp Cys Ser Glu Asn Ile
325 330 335
Asp Asp Cys Ala Ser Ala Ala Cys Phe His Gly Ala Thr Cys His Asp
340 345 350
Arg Val Ala Ser Phe Tyr Cys Glu Cys Pro His Gly Arg Thr Gly Leu
355 360 365
Leu Cys His Leu Asn Asp Ala Cys Ile Ser Asn Pro Cys Asn Glu Gly
370 375 380
Ser Asn Cys Asp Thr Asn Pro Val Asn Gly Lys Ala Ile Cys Thr Cys
385 390 395 400
Pro Ser Gly Tyr Thr Gly Pro Ala Cys Ser Gln Asp Val Asp Glu Cys
405 410 415
Ser Leu Gly Ala Asn Pro Cys Glu His Ala Gly Lys Cys Ile Asn Thr
420 425 430
Leu Gly Ser Phe Glu Cys Gln Cys Leu Gln Gly Tyr Thr Gly Pro Arg
435 440 445
Cys Glu Ile Asp Val Asn Glu Cys Val Ser Asn Pro Cys Gln Asn Asp
450 455 460
Ala Thr Cys Leu Asp Gln Ile Gly Glu Phe Gln Cys Ile Cys Met Pro
465 470 475 480
Gly Tyr Glu Gly Val His Cys Glu Val Asn Thr Asp Glu Cys Ala Ser
485 490 495
Ser Pro Cys Leu His Asn Gly Arg Cys Leu Asp Lys Ile Asn Glu Phe
500 505 510
Gln Cys Glu Cys Pro Thr Gly Phe Thr Gly His Leu Cys Gln Tyr Asp
515 520 525
Val Asp Glu Cys Ala Ser Thr Pro Cys Lys Asn Gly Ala Lys Cys Leu
530 535 540
Asp Gly Pro Asn Thr Tyr Thr Cys Val Cys Thr Glu Gly Tyr Thr Gly
545 550 555 560
Thr His Cys Glu Val Asp Ile Asp Glu Cys Asp Pro Asp Pro Cys His
565 570 575
Tyr Gly Ser Cys Lys Asp Gly Val Ala Thr Phe Thr Cys Leu Cys Arg
580 585 590
Pro Gly Tyr Thr Gly His His Cys Glu Thr Asn Ile Asn Glu Cys Ser
595 600 605
Ser Gln Pro Cys Arg His Gly Gly Thr Cys Gln Asp Arg Asp Asn Ala
610 615 620
Tyr Leu Cys Phe Cys Leu Lys Gly Thr Thr Gly Pro Asn Cys Glu Ile
625 630 635 640
Asn Leu Asp Asp Cys Ala Ser Ser Pro Cys Asp Ser Gly Thr Cys Leu
645 650 655
Asp Lys Ile Asp Gly Tyr Glu Cys Ala Cys Glu Pro Gly Tyr Thr Gly
660 665 670
Ser Met Cys Asn Ile Asn Ile Asp Glu Cys Ala Gly Asn Pro Cys His
675 680 685
Asn Gly Gly Thr Cys Glu Asp Gly Ile Asn Gly Phe Thr Cys Arg Cys
690 695 700
Pro Glu Gly Tyr His Asp Pro Thr Cys Leu Ser Glu Val Asn Glu Cys
705 710 715 720
Asn Ser Asn Pro Cys Val His Gly Ala Cys Arg Asp Ser Leu Asn Gly
725 730 735
Tyr Lys Cys Asp Cys Asp Pro Gly Trp Ser Gly Thr Asn Cys Asp Ile
740 745 750
Asn Asn Asn Glu Cys Glu Ser Asn Pro Cys Val Asn Gly Gly Thr Cys
755 760 765
Lys Asp Met Thr Ser Gly Tyr Val Cys Thr Cys Arg Glu Gly Phe Ser
770 775 780
Gly Pro Asn Cys Gln Thr Asn Ile Asn Glu Cys Ala Ser Asn Pro Cys
785 790 795 800
Leu Asn Gln Gly Thr Cys Ile Asp Asp Val Ala Gly Tyr Lys Cys Asn
805 810 815
Cys Leu Leu Pro Tyr Thr Gly Ala Thr Cys Glu Val Val Leu Ala Pro
820 825 830
Cys Ala Pro Ser Pro Cys Arg Asn Gly Gly Glu Cys Arg Gln Ser Glu
835 840 845
Asp Tyr Glu Ser Phe Ser Cys Val Cys Pro Thr Gly Trp Gln Gly Gln
850 855 860
Thr Cys Glu Val Asp Ile Asn Glu Cys Val Leu Ser Pro Cys Arg His
865 870 875 880
Gly Ala Ser Cys Gln Asn Thr His Gly Gly Tyr Arg Cys His Cys Gln
885 890 895
Ala Gly Tyr Ser Gly Arg Asn Cys Glu Thr Asp Ile Asp Asp Cys Arg
900 905 910
Pro Asn Pro Cys His Asn Gly Gly Ser Cys Thr Asp Gly Ile Asn Thr
915 920 925
Ala Phe Cys Asp Cys Leu Pro Gly Phe Arg Gly Thr Phe Cys Glu Glu
930 935 940
Asp Ile Asn Glu Cys Ala Ser Asp Pro Cys Arg Asn Gly Ala Asn Cys
945 950 955 960
Thr Asp Cys Val Asp Ser Tyr Thr Cys Thr Cys Pro Ala Gly Phe Ser
965 970 975
Gly Ile His Cys Glu Asn Asn Thr Pro Asp Cys Thr Glu Ser Ser Cys
980 985 990
Phe Asn Gly Gly Thr Cys Val Asp Gly Ile Asn Ser Phe Thr Cys Leu
995 1000 1005
Cys Pro Pro Gly Phe Thr Gly Ser Tyr Cys Gln His Asp Val Asn
1010 1015 1020
Glu Cys Asp Ser Gln Pro Cys Leu His Gly Gly Thr Cys Gln Asp
1025 1030 1035
Gly Cys Gly Ser Tyr Arg Cys Thr Cys Pro Gln Gly Tyr Thr Gly
1040 1045 1050
Pro Asn Cys Gln Asn Leu Val His Trp Cys Asp Ser Ser Pro Cys
1055 1060 1065
Lys Asn Gly Gly Lys Cys Trp Gln Thr His Thr Gln Tyr Arg Cys
1070 1075 1080
Glu Cys Pro Ser Gly Trp Thr Gly Leu Tyr Cys Asp Val Pro Ser
1085 1090 1095
Val Ser Cys Glu Val Ala Ala Gln Arg Gln Gly Val Asp Val Ala
1100 1105 1110
Arg Leu Cys Gln His Gly Gly Leu Cys Val Asp Ala Gly Asn Thr
1115 1120 1125
His His Cys Arg Cys Gln Ala Gly Tyr Thr Gly Ser Tyr Cys Glu
1130 1135 1140
Asp Leu Val Asp Glu Cys Ser Pro Ser Pro Cys Gln Asn Gly Ala
1145 1150 1155
Thr Cys Thr Asp Tyr Leu Gly Gly Tyr Ser Cys Lys Cys Val Ala
1160 1165 1170
Gly Tyr His Gly Val Asn Cys Ser Glu Glu Ile Asp Glu Cys Leu
1175 1180 1185
Ser His Pro Cys Gln Asn Gly Gly Thr Cys Leu Asp Leu Pro Asn
1190 1195 1200
Thr Tyr Lys Cys Ser Cys Pro Arg Gly Thr Gln Gly Val His Cys
1205 1210 1215
Glu Ile Asn Val Asp Asp Cys Asn Pro Pro Val Asp Pro Val Ser
1220 1225 1230
Arg Ser Pro Lys Cys Phe Asn Asn Gly Thr Cys Val Asp Gln Val
1235 1240 1245
Gly Gly Tyr Ser Cys Thr Cys Pro Pro Gly Phe Val Gly Glu Arg
1250 1255 1260
Cys Glu Gly Asp Val Asn Glu Cys Leu Ser Asn Pro Cys Asp Ala
1265 1270 1275
Arg Gly Thr Gln Asn Cys Val Gln Arg Val Asn Asp Phe His Cys
1280 1285 1290
Glu Cys Arg Ala Gly His Thr Gly Arg Arg Cys Glu Ser Val Ile
1295 1300 1305
Asn Gly Cys Lys Gly Lys Pro Cys Lys Asn Gly Gly Thr Cys Ala
1310 1315 1320
Val Ala Ser Asn Thr Ala Arg Gly Phe Ile Cys Lys Cys Pro Ala
1325 1330 1335
Gly Phe Glu Gly Ala Thr Cys Glu Asn Asp Ala Arg Thr Cys Gly
1340 1345 1350
Ser Leu Arg Cys Leu Asn Gly Gly Thr Cys Ile Ser Gly Pro Arg
1355 1360 1365
Ser Pro Thr Cys Leu Cys Leu Gly Pro Phe Thr Gly Pro Glu Cys
1370 1375 1380
Gln Phe Pro Ala Ser Ser Pro Cys Leu Gly Gly Asn Pro Cys Tyr
1385 1390 1395
Asn Gln Gly Thr Cys Glu Pro Thr Ser Glu Ser Pro Phe Tyr Arg
1400 1405 1410
Cys Leu Cys Pro Ala Lys Phe Asn Gly Leu Leu Cys His Ile Leu
1415 1420 1425
Asp Tyr Ser Phe Gly Gly Gly Ala Gly Arg Asp Ile Pro Pro Pro
1430 1435 1440
Leu Ile Glu Glu Ala Cys Glu Leu Pro Glu Cys Gln Glu Asp Ala
1445 1450 1455
Gly Asn Lys Val Cys Ser Leu Gln Cys Asn Asn His Ala Cys Gly
1460 1465 1470
Trp Asp Gly Gly Asp Cys Ser Leu Asn Phe Asn Asp Pro Trp Lys
1475 1480 1485
Asn Cys Thr Gln Ser Leu Gln Cys Trp Lys Tyr Phe Ser Asp Gly
1490 1495 1500
His Cys Asp Ser Gln Cys Asn Ser Ala Gly Cys Leu Phe Asp Gly
1505 1510 1515
Phe Asp Cys Gln Arg Ala Glu Gly Gln Cys Asn Pro Leu Tyr Asp
1520 1525 1530
Gln Tyr Cys Lys Asp His Phe Ser Asp Gly His Cys Asp Gln Gly
1535 1540 1545
Cys Asn Ser Ala Glu Cys Glu Trp Asp Gly Leu Asp Cys Ala Glu
1550 1555 1560
His Val Pro Glu Arg Leu Ala Ala Gly Thr Leu Val Val Val Val
1565 1570 1575
Leu Met Pro Pro Glu Gln Leu Arg Asn Ser Ser Phe His Phe Leu
1580 1585 1590
Arg Glu Leu Ser Arg Val Leu His Thr Asn Val Val Phe Lys Arg
1595 1600 1605
Asp Ala His Gly Gln Gln Met Ile Phe Pro Tyr Tyr Gly Arg Glu
1610 1615 1620
Glu Glu Leu Arg Lys His Pro Ile Lys Arg Ala Ala Glu Gly Trp
1625 1630 1635
Ala Ala Pro Asp Ala Leu Leu Gly Gln Val Lys Ala Ser Leu Leu
1640 1645 1650
Pro Gly Gly Ser Glu Gly Gly Arg Arg Arg Arg Glu Leu Asp Pro
1655 1660 1665
Met Asp Val Arg Gly Ser Ile Val Tyr Leu Glu Ile Asp Asn Arg
1670 1675 1680
Gln Cys Val Gln Ala Ser Ser Gln Cys Phe Gln Ser Ala Thr Asp
1685 1690 1695
Val Ala Ala Phe Leu Gly Ala Leu Ala Ser Leu Gly Ser Leu Asn
1700 1705 1710
Ile Pro Tyr Lys Ile Glu Ala Val Gln Ser Glu Thr Val Glu Pro
1715 1720 1725
Pro Pro Pro Ala Gln Leu His Phe Met Tyr Val Ala Ala Ala Ala
1730 1735 1740
Phe Val Leu Leu Phe Phe Val Gly Cys Gly Val Leu Leu Ser Arg
1745 1750 1755
Lys Arg Arg Arg Gln His Gly Gln Leu Trp Phe Pro Glu Gly Phe
1760 1765 1770
Lys Val Ser Glu Ala Ser Lys Lys Lys Arg Arg Glu Pro Leu Gly
1775 1780 1785
Glu Asp Ser Val Gly Leu Lys Pro Leu Lys Asn Ala Ser Asp Gly
1790 1795 1800
Ala Leu Met Asp Asp Asn Gln Asn Glu Trp Gly Asp Glu Asp Leu
1805 1810 1815
Glu Thr Lys Lys Phe Arg Phe Glu Glu Pro Val Val Leu Pro Asp
1820 1825 1830
Leu Asp Asp Gln Thr Asp His Arg Gln Trp Thr Gln Gln His Leu
1835 1840 1845
Asp Ala Ala Asp Leu Arg Met Ser Ala Met Ala Pro Thr Pro Pro
1850 1855 1860
Gln Gly Glu Val Asp Ala Asp Cys Met Asp Val Asn Val Arg Gly
1865 1870 1875
Pro Asp Gly Phe Thr Pro Leu Met Ile Ala Ser Cys Ser Gly Gly
1880 1885 1890
Gly Leu Glu Thr Gly Asn Ser Glu Glu Glu Glu Asp Ala Pro Ala
1895 1900 1905
Val Ile Ser Asp Phe Ile Tyr Gln Gly Ala Ser Leu His Asn Gln
1910 1915 1920
Thr Asp Arg Thr Gly Glu Thr Ala Leu His Leu Ala Ala Arg Tyr
1925 1930 1935
Ser Arg Ser Asp Ala Ala Lys Arg Leu Leu Glu Ala Ser Ala Asp
1940 1945 1950
Ala Asn Ile Gln Asp Asn Met Gly Arg Thr Pro Leu His Ala Ala
1955 1960 1965
Val Ser Ala Asp Ala Gln Gly Val Phe Gln Ile Leu Ile Arg Asn
1970 1975 1980
Arg Ala Thr Asp Leu Asp Ala Arg Met His Asp Gly Thr Thr Pro
1985 1990 1995
Leu Ile Leu Ala Ala Arg Leu Ala Val Glu Gly Met Leu Glu Asp
2000 2005 2010
Leu Ile Asn Ser His Ala Asp Val Asn Ala Val Asp Asp Leu Gly
2015 2020 2025
Lys Ser Ala Leu His Trp Ala Ala Ala Val Asn Asn Val Asp Ala
2030 2035 2040
Ala Val Val Leu Leu Lys Asn Gly Ala Asn Lys Asp Met Gln Asn
2045 2050 2055
Asn Arg Glu Glu Thr Pro Leu Phe Leu Ala Ala Arg Glu Gly Ser
2060 2065 2070
Tyr Glu Thr Ala Lys Val Leu Leu Asp His Phe Ala Asn Arg Asp
2075 2080 2085
Ile Thr Asp His Met Asp Arg Leu Pro Arg Asp Ile Ala Gln Glu
2090 2095 2100
Arg Met His His Asp Ile Val Arg Leu Leu Asp Glu Tyr Asn Leu
2105 2110 2115
Val Arg Ser Pro Gln Leu His Gly Ala Pro Leu Gly Gly Thr Pro
2120 2125 2130
Thr Leu Ser Pro Pro Leu Cys Ser Pro Asn Gly Tyr Leu Gly Ser
2135 2140 2145
Leu Lys Pro Gly Val Gln Gly Lys Lys Val Arg Lys Pro Ser Ser
2150 2155 2160
Lys Gly Leu Ala Cys Gly Ser Lys Glu Ala Lys Asp Leu Lys Ala
2165 2170 2175
Arg Arg Lys Lys Ser Gln Asp Gly Lys Gly Cys Leu Leu Asp Ser
2180 2185 2190
Ser Gly Met Leu Ser Pro Val Asp Ser Leu Glu Ser Pro His Gly
2195 2200 2205
Tyr Leu Ser Asp Val Ala Ser Pro Pro Leu Leu Pro Ser Pro Phe
2210 2215 2220
Gln Gln Ser Pro Ser Val Pro Leu Asn His Leu Pro Gly Met Pro
2225 2230 2235
Asp Thr His Leu Gly Ile Gly His Leu Asn Val Ala Ala Lys Pro
2240 2245 2250
Glu Met Ala Ala Leu Gly Gly Gly Gly Arg Leu Ala Phe Glu Thr
2255 2260 2265
Gly Pro Pro Arg Leu Ser His Leu Pro Val Ala Ser Gly Thr Ser
2270 2275 2280
Thr Val Leu Gly Ser Ser Ser Gly Gly Ala Leu Asn Phe Thr Val
2285 2290 2295
Gly Gly Ser Thr Ser Leu Asn Gly Gln Cys Glu Trp Leu Ser Arg
2300 2305 2310
Leu Gln Ser Gly Met Val Pro Asn Gln Tyr Asn Pro Leu Arg Gly
2315 2320 2325
Ser Val Ala Pro Gly Pro Leu Ser Thr Gln Ala Pro Ser Leu Gln
2330 2335 2340
His Gly Met Val Gly Pro Leu His Ser Ser Leu Ala Ala Ser Ala
2345 2350 2355
Leu Ser Gln Met Met Ser Tyr Gln Gly Leu Pro Ser Thr Arg Leu
2360 2365 2370
Ala Thr Gln Pro His Leu Val Gln Thr Gln Gln Val Gln Pro Gln
2375 2380 2385
Asn Leu Gln Met Gln Gln Gln Asn Leu Gln Pro Ala Asn Ile Gln
2390 2395 2400
Gln Gln Gln Ser Leu Gln Pro Pro Pro Pro Pro Pro Gln Pro His
2405 2410 2415
Leu Gly Val Ser Ser Ala Ala Ser Gly His Leu Gly Arg Ser Phe
2420 2425 2430
Leu Ser Gly Glu Pro Ser Gln Ala Asp Val Gln Pro Leu Gly Pro
2435 2440 2445
Ser Ser Leu Ala Val His Thr Ile Leu Pro Gln Glu Ser Pro Ala
2450 2455 2460
Leu Pro Thr Ser Leu Pro Ser Ser Leu Val Pro Pro Val Thr Ala
2465 2470 2475
Ala Gln Phe Leu Thr Pro Pro Ser Gln His Ser Tyr Ser Ser Pro
2480 2485 2490
Val Asp Asn Thr Pro Ser His Gln Leu Gln Val Pro Glu His Pro
2495 2500 2505
Phe Leu Thr Pro Ser Pro Glu Ser Pro Asp Gln Trp Ser Ser Ser
2510 2515 2520
Ser Pro His Ser Asn Val Ser Asp Trp Ser Glu Gly Val Ser Ser
2525 2530 2535
Pro Pro Thr Ser Met Gln Ser Gln Ile Ala Arg Ile Pro Glu Ala
2540 2545 2550
Phe Lys
2555
<210> 25
<211> 2471
<212> PRT
<213> 人
<400> 25
Met Pro Ala Leu Arg Pro Ala Leu Leu Trp Ala Leu Leu Ala Leu Trp
1 5 10 15
Leu Cys Cys Ala Ala Pro Ala His Ala Leu Gln Cys Arg Asp Gly Tyr
20 25 30
Glu Pro Cys Val Asn Glu Gly Met Cys Val Thr Tyr His Asn Gly Thr
35 40 45
Gly Tyr Cys Lys Cys Pro Glu Gly Phe Leu Gly Glu Tyr Cys Gln His
50 55 60
Arg Asp Pro Cys Glu Lys Asn Arg Cys Gln Asn Gly Gly Thr Cys Val
65 70 75 80
Ala Gln Ala Met Leu Gly Lys Ala Thr Cys Arg Cys Ala Ser Gly Phe
85 90 95
Thr Gly Glu Asp Cys Gln Tyr Ser Thr Ser His Pro Cys Phe Val Ser
100 105 110
Arg Pro Cys Leu Asn Gly Gly Thr Cys His Met Leu Ser Arg Asp Thr
115 120 125
Tyr Glu Cys Thr Cys Gln Val Gly Phe Thr Gly Lys Glu Cys Gln Trp
130 135 140
Thr Asp Ala Cys Leu Ser His Pro Cys Ala Asn Gly Ser Thr Cys Thr
145 150 155 160
Thr Val Ala Asn Gln Phe Ser Cys Lys Cys Leu Thr Gly Phe Thr Gly
165 170 175
Gln Lys Cys Glu Thr Asp Val Asn Glu Cys Asp Ile Pro Gly His Cys
180 185 190
Gln His Gly Gly Thr Cys Leu Asn Leu Pro Gly Ser Tyr Gln Cys Gln
195 200 205
Cys Pro Gln Gly Phe Thr Gly Gln Tyr Cys Asp Ser Leu Tyr Val Pro
210 215 220
Cys Ala Pro Ser Pro Cys Val Asn Gly Gly Thr Cys Arg Gln Thr Gly
225 230 235 240
Asp Phe Thr Phe Glu Cys Asn Cys Leu Pro Gly Phe Glu Gly Ser Thr
245 250 255
Cys Glu Arg Asn Ile Asp Asp Cys Pro Asn His Arg Cys Gln Asn Gly
260 265 270
Gly Val Cys Val Asp Gly Val Asn Thr Tyr Asn Cys Arg Cys Pro Pro
275 280 285
Gln Trp Thr Gly Gln Phe Cys Thr Glu Asp Val Asp Glu Cys Leu Leu
290 295 300
Gln Pro Asn Ala Cys Gln Asn Gly Gly Thr Cys Ala Asn Arg Asn Gly
305 310 315 320
Gly Tyr Gly Cys Val Cys Val Asn Gly Trp Ser Gly Asp Asp Cys Ser
325 330 335
Glu Asn Ile Asp Asp Cys Ala Phe Ala Ser Cys Thr Pro Gly Ser Thr
340 345 350
Cys Ile Asp Arg Val Ala Ser Phe Ser Cys Met Cys Pro Glu Gly Lys
355 360 365
Ala Gly Leu Leu Cys His Leu Asp Asp Ala Cys Ile Ser Asn Pro Cys
370 375 380
His Lys Gly Ala Leu Cys Asp Thr Asn Pro Leu Asn Gly Gln Tyr Ile
385 390 395 400
Cys Thr Cys Pro Gln Gly Tyr Lys Gly Ala Asp Cys Thr Glu Asp Val
405 410 415
Asp Glu Cys Ala Met Ala Asn Ser Asn Pro Cys Glu His Ala Gly Lys
420 425 430
Cys Val Asn Thr Asp Gly Ala Phe His Cys Glu Cys Leu Lys Gly Tyr
435 440 445
Ala Gly Pro Arg Cys Glu Met Asp Ile Asn Glu Cys His Ser Asp Pro
450 455 460
Cys Gln Asn Asp Ala Thr Cys Leu Asp Lys Ile Gly Gly Phe Thr Cys
465 470 475 480
Leu Cys Met Pro Gly Phe Lys Gly Val His Cys Glu Leu Glu Ile Asn
485 490 495
Glu Cys Gln Ser Asn Pro Cys Val Asn Asn Gly Gln Cys Val Asp Lys
500 505 510
Val Asn Arg Phe Gln Cys Leu Cys Pro Pro Gly Phe Thr Gly Pro Val
515 520 525
Cys Gln Ile Asp Ile Asp Asp Cys Ser Ser Thr Pro Cys Leu Asn Gly
530 535 540
Ala Lys Cys Ile Asp His Pro Asn Gly Tyr Glu Cys Gln Cys Ala Thr
545 550 555 560
Gly Phe Thr Gly Val Leu Cys Glu Glu Asn Ile Asp Asn Cys Asp Pro
565 570 575
Asp Pro Cys His His Gly Gln Cys Gln Asp Gly Ile Asp Ser Tyr Thr
580 585 590
Cys Ile Cys Asn Pro Gly Tyr Met Gly Ala Ile Cys Ser Asp Gln Ile
595 600 605
Asp Glu Cys Tyr Ser Ser Pro Cys Leu Asn Asp Gly Arg Cys Ile Asp
610 615 620
Leu Val Asn Gly Tyr Gln Cys Asn Cys Gln Pro Gly Thr Ser Gly Val
625 630 635 640
Asn Cys Glu Ile Asn Phe Asp Asp Cys Ala Ser Asn Pro Cys Ile His
645 650 655
Gly Ile Cys Met Asp Gly Ile Asn Arg Tyr Ser Cys Val Cys Ser Pro
660 665 670
Gly Phe Thr Gly Gln Arg Cys Asn Ile Asp Ile Asp Glu Cys Ala Ser
675 680 685
Asn Pro Cys Arg Lys Gly Ala Thr Cys Ile Asn Gly Val Asn Gly Phe
690 695 700
Arg Cys Ile Cys Pro Glu Gly Pro His His Pro Ser Cys Tyr Ser Gln
705 710 715 720
Val Asn Glu Cys Leu Ser Asn Pro Cys Ile His Gly Asn Cys Thr Gly
725 730 735
Gly Leu Ser Gly Tyr Lys Cys Leu Cys Asp Ala Gly Trp Val Gly Ile
740 745 750
Asn Cys Glu Val Asp Lys Asn Glu Cys Leu Ser Asn Pro Cys Gln Asn
755 760 765
Gly Gly Thr Cys Asp Asn Leu Val Asn Gly Tyr Arg Cys Thr Cys Lys
770 775 780
Lys Gly Phe Lys Gly Tyr Asn Cys Gln Val Asn Ile Asp Glu Cys Ala
785 790 795 800
Ser Asn Pro Cys Leu Asn Gln Gly Thr Cys Phe Asp Asp Ile Ser Gly
805 810 815
Tyr Thr Cys His Cys Val Leu Pro Tyr Thr Gly Lys Asn Cys Gln Thr
820 825 830
Val Leu Ala Pro Cys Ser Pro Asn Pro Cys Glu Asn Ala Ala Val Cys
835 840 845
Lys Glu Ser Pro Asn Phe Glu Ser Tyr Thr Cys Leu Cys Ala Pro Gly
850 855 860
Trp Gln Gly Gln Arg Cys Thr Ile Asp Ile Asp Glu Cys Ile Ser Lys
865 870 875 880
Pro Cys Met Asn His Gly Leu Cys His Asn Thr Gln Gly Ser Tyr Met
885 890 895
Cys Glu Cys Pro Pro Gly Phe Ser Gly Met Asp Cys Glu Glu Asp Ile
900 905 910
Asp Asp Cys Leu Ala Asn Pro Cys Gln Asn Gly Gly Ser Cys Met Asp
915 920 925
Gly Val Asn Thr Phe Ser Cys Leu Cys Leu Pro Gly Phe Thr Gly Asp
930 935 940
Lys Cys Gln Thr Asp Met Asn Glu Cys Leu Ser Glu Pro Cys Lys Asn
945 950 955 960
Gly Gly Thr Cys Ser Asp Tyr Val Asn Ser Tyr Thr Cys Lys Cys Gln
965 970 975
Ala Gly Phe Asp Gly Val His Cys Glu Asn Asn Ile Asn Glu Cys Thr
980 985 990
Glu Ser Ser Cys Phe Asn Gly Gly Thr Cys Val Asp Gly Ile Asn Ser
995 1000 1005
Phe Ser Cys Leu Cys Pro Val Gly Phe Thr Gly Ser Phe Cys Leu
1010 1015 1020
His Glu Ile Asn Glu Cys Ser Ser His Pro Cys Leu Asn Glu Gly
1025 1030 1035
Thr Cys Val Asp Gly Leu Gly Thr Tyr Arg Cys Ser Cys Pro Leu
1040 1045 1050
Gly Tyr Thr Gly Lys Asn Cys Gln Thr Leu Val Asn Leu Cys Ser
1055 1060 1065
Arg Ser Pro Cys Lys Asn Lys Gly Thr Cys Val Gln Lys Lys Ala
1070 1075 1080
Glu Ser Gln Cys Leu Cys Pro Ser Gly Trp Ala Gly Ala Tyr Cys
1085 1090 1095
Asp Val Pro Asn Val Ser Cys Asp Ile Ala Ala Ser Arg Arg Gly
1100 1105 1110
Val Leu Val Glu His Leu Cys Gln His Ser Gly Val Cys Ile Asn
1115 1120 1125
Ala Gly Asn Thr His Tyr Cys Gln Cys Pro Leu Gly Tyr Thr Gly
1130 1135 1140
Ser Tyr Cys Glu Glu Gln Leu Asp Glu Cys Ala Ser Asn Pro Cys
1145 1150 1155
Gln His Gly Ala Thr Cys Ser Asp Phe Ile Gly Gly Tyr Arg Cys
1160 1165 1170
Glu Cys Val Pro Gly Tyr Gln Gly Val Asn Cys Glu Tyr Glu Val
1175 1180 1185
Asp Glu Cys Gln Asn Gln Pro Cys Gln Asn Gly Gly Thr Cys Ile
1190 1195 1200
Asp Leu Val Asn His Phe Lys Cys Ser Cys Pro Pro Gly Thr Arg
1205 1210 1215
Gly Leu Leu Cys Glu Glu Asn Ile Asp Asp Cys Ala Arg Gly Pro
1220 1225 1230
His Cys Leu Asn Gly Gly Gln Cys Met Asp Arg Ile Gly Gly Tyr
1235 1240 1245
Ser Cys Arg Cys Leu Pro Gly Phe Ala Gly Glu Arg Cys Glu Gly
1250 1255 1260
Asp Ile Asn Glu Cys Leu Ser Asn Pro Cys Ser Ser Glu Gly Ser
1265 1270 1275
Leu Asp Cys Ile Gln Leu Thr Asn Asp Tyr Leu Cys Val Cys Arg
1280 1285 1290
Ser Ala Phe Thr Gly Arg His Cys Glu Thr Phe Val Asp Val Cys
1295 1300 1305
Pro Gln Met Pro Cys Leu Asn Gly Gly Thr Cys Ala Val Ala Ser
1310 1315 1320
Asn Met Pro Asp Gly Phe Ile Cys Arg Cys Pro Pro Gly Phe Ser
1325 1330 1335
Gly Ala Arg Cys Gln Ser Ser Cys Gly Gln Val Lys Cys Arg Lys
1340 1345 1350
Gly Glu Gln Cys Val His Thr Ala Ser Gly Pro Arg Cys Phe Cys
1355 1360 1365
Pro Ser Pro Arg Asp Cys Glu Ser Gly Cys Ala Ser Ser Pro Cys
1370 1375 1380
Gln His Gly Gly Ser Cys His Pro Gln Arg Gln Pro Pro Tyr Tyr
1385 1390 1395
Ser Cys Gln Cys Ala Pro Pro Phe Ser Gly Ser Arg Cys Glu Leu
1400 1405 1410
Tyr Thr Ala Pro Pro Ser Thr Pro Pro Ala Thr Cys Leu Ser Gln
1415 1420 1425
Tyr Cys Ala Asp Lys Ala Arg Asp Gly Val Cys Asp Glu Ala Cys
1430 1435 1440
Asn Ser His Ala Cys Gln Trp Asp Gly Gly Asp Cys Ser Leu Thr
1445 1450 1455
Met Glu Asn Pro Trp Ala Asn Cys Ser Ser Pro Leu Pro Cys Trp
1460 1465 1470
Asp Tyr Ile Asn Asn Gln Cys Asp Glu Leu Cys Asn Thr Val Glu
1475 1480 1485
Cys Leu Phe Asp Asn Phe Glu Cys Gln Gly Asn Ser Lys Thr Cys
1490 1495 1500
Lys Tyr Asp Lys Tyr Cys Ala Asp His Phe Lys Asp Asn His Cys
1505 1510 1515
Asp Gln Gly Cys Asn Ser Glu Glu Cys Gly Trp Asp Gly Leu Asp
1520 1525 1530
Cys Ala Ala Asp Gln Pro Glu Asn Leu Ala Glu Gly Thr Leu Val
1535 1540 1545
Ile Val Val Leu Met Pro Pro Glu Gln Leu Leu Gln Asp Ala Arg
1550 1555 1560
Ser Phe Leu Arg Ala Leu Gly Thr Leu Leu His Thr Asn Leu Arg
1565 1570 1575
Ile Lys Arg Asp Ser Gln Gly Glu Leu Met Val Tyr Pro Tyr Tyr
1580 1585 1590
Gly Glu Lys Ser Ala Ala Met Lys Lys Gln Arg Met Thr Arg Arg
1595 1600 1605
Ser Leu Pro Gly Glu Gln Glu Gln Glu Val Ala Gly Ser Lys Val
1610 1615 1620
Phe Leu Glu Ile Asp Asn Arg Gln Cys Val Gln Asp Ser Asp His
1625 1630 1635
Cys Phe Lys Asn Thr Asp Ala Ala Ala Ala Leu Leu Ala Ser His
1640 1645 1650
Ala Ile Gln Gly Thr Leu Ser Tyr Pro Leu Val Ser Val Val Ser
1655 1660 1665
Glu Ser Leu Thr Pro Glu Arg Thr Gln Leu Leu Tyr Leu Leu Ala
1670 1675 1680
Val Ala Val Val Ile Ile Leu Phe Ile Ile Leu Leu Gly Val Ile
1685 1690 1695
Met Ala Lys Arg Lys Arg Lys His Gly Ser Leu Trp Leu Pro Glu
1700 1705 1710
Gly Phe Thr Leu Arg Arg Asp Ala Ser Asn His Lys Arg Arg Glu
1715 1720 1725
Pro Val Gly Gln Asp Ala Val Gly Leu Lys Asn Leu Ser Val Gln
1730 1735 1740
Val Ser Glu Ala Asn Leu Ile Gly Thr Gly Thr Ser Glu His Trp
1745 1750 1755
Val Asp Asp Glu Gly Pro Gln Pro Lys Lys Val Lys Ala Glu Asp
1760 1765 1770
Glu Ala Leu Leu Ser Glu Glu Asp Asp Pro Ile Asp Arg Arg Pro
1775 1780 1785
Trp Thr Gln Gln His Leu Glu Ala Ala Asp Ile Arg Arg Thr Pro
1790 1795 1800
Ser Leu Ala Leu Thr Pro Pro Gln Ala Glu Gln Glu Val Asp Val
1805 1810 1815
Leu Asp Val Asn Val Arg Gly Pro Asp Gly Cys Thr Pro Leu Met
1820 1825 1830
Leu Ala Ser Leu Arg Gly Gly Ser Ser Asp Leu Ser Asp Glu Asp
1835 1840 1845
Glu Asp Ala Glu Asp Ser Ser Ala Asn Ile Ile Thr Asp Leu Val
1850 1855 1860
Tyr Gln Gly Ala Ser Leu Gln Ala Gln Thr Asp Arg Thr Gly Glu
1865 1870 1875
Met Ala Leu His Leu Ala Ala Arg Tyr Ser Arg Ala Asp Ala Ala
1880 1885 1890
Lys Arg Leu Leu Asp Ala Gly Ala Asp Ala Asn Ala Gln Asp Asn
1895 1900 1905
Met Gly Arg Cys Pro Leu His Ala Ala Val Ala Ala Asp Ala Gln
1910 1915 1920
Gly Val Phe Gln Ile Leu Ile Arg Asn Arg Val Thr Asp Leu Asp
1925 1930 1935
Ala Arg Met Asn Asp Gly Thr Thr Pro Leu Ile Leu Ala Ala Arg
1940 1945 1950
Leu Ala Val Glu Gly Met Val Ala Glu Leu Ile Asn Cys Gln Ala
1955 1960 1965
Asp Val Asn Ala Val Asp Asp His Gly Lys Ser Ala Leu His Trp
1970 1975 1980
Ala Ala Ala Val Asn Asn Val Glu Ala Thr Leu Leu Leu Leu Lys
1985 1990 1995
Asn Gly Ala Asn Arg Asp Met Gln Asp Asn Lys Glu Glu Thr Pro
2000 2005 2010
Leu Phe Leu Ala Ala Arg Glu Gly Ser Tyr Glu Ala Ala Lys Ile
2015 2020 2025
Leu Leu Asp His Phe Ala Asn Arg Asp Ile Thr Asp His Met Asp
2030 2035 2040
Arg Leu Pro Arg Asp Val Ala Arg Asp Arg Met His His Asp Ile
2045 2050 2055
Val Arg Leu Leu Asp Glu Tyr Asn Val Thr Pro Ser Pro Pro Gly
2060 2065 2070
Thr Val Leu Thr Ser Ala Leu Ser Pro Val Ile Cys Gly Pro Asn
2075 2080 2085
Arg Ser Phe Leu Ser Leu Lys His Thr Pro Met Gly Lys Lys Ser
2090 2095 2100
Arg Arg Pro Ser Ala Lys Ser Thr Met Pro Thr Ser Leu Pro Asn
2105 2110 2115
Leu Ala Lys Glu Ala Lys Asp Ala Lys Gly Ser Arg Arg Lys Lys
2120 2125 2130
Ser Leu Ser Glu Lys Val Gln Leu Ser Glu Ser Ser Val Thr Leu
2135 2140 2145
Ser Pro Val Asp Ser Leu Glu Ser Pro His Thr Tyr Val Ser Asp
2150 2155 2160
Thr Thr Ser Ser Pro Met Ile Thr Ser Pro Gly Ile Leu Gln Ala
2165 2170 2175
Ser Pro Asn Pro Met Leu Ala Thr Ala Ala Pro Pro Ala Pro Val
2180 2185 2190
His Ala Gln His Ala Leu Ser Phe Ser Asn Leu His Glu Met Gln
2195 2200 2205
Pro Leu Ala His Gly Ala Ser Thr Val Leu Pro Ser Val Ser Gln
2210 2215 2220
Leu Leu Ser His His His Ile Val Ser Pro Gly Ser Gly Ser Ala
2225 2230 2235
Gly Ser Leu Ser Arg Leu His Pro Val Pro Val Pro Ala Asp Trp
2240 2245 2250
Met Asn Arg Met Glu Val Asn Glu Thr Gln Tyr Asn Glu Met Phe
2255 2260 2265
Gly Met Val Leu Ala Pro Ala Glu Gly Thr His Pro Gly Ile Ala
2270 2275 2280
Pro Gln Ser Arg Pro Pro Glu Gly Lys His Ile Thr Thr Pro Arg
2285 2290 2295
Glu Pro Leu Pro Pro Ile Val Thr Phe Gln Leu Ile Pro Lys Gly
2300 2305 2310
Ser Ile Ala Gln Pro Ala Gly Ala Pro Gln Pro Gln Ser Thr Cys
2315 2320 2325
Pro Pro Ala Val Ala Gly Pro Leu Pro Thr Met Tyr Gln Ile Pro
2330 2335 2340
Glu Met Ala Arg Leu Pro Ser Val Ala Phe Pro Thr Ala Met Met
2345 2350 2355
Pro Gln Gln Asp Gly Gln Val Ala Gln Thr Ile Leu Pro Ala Tyr
2360 2365 2370
His Pro Phe Pro Ala Ser Val Gly Lys Tyr Pro Thr Pro Pro Ser
2375 2380 2385
Gln His Ser Tyr Ala Ser Ser Asn Ala Ala Glu Arg Thr Pro Ser
2390 2395 2400
His Ser Gly His Leu Gln Gly Glu His Pro Tyr Leu Thr Pro Ser
2405 2410 2415
Pro Glu Ser Pro Asp Gln Trp Ser Ser Ser Ser Pro His Ser Ala
2420 2425 2430
Ser Asp Trp Ser Asp Val Thr Thr Ser Pro Thr Pro Gly Gly Ala
2435 2440 2445
Gly Gly Gly Gln Arg Gly Pro Gly Thr His Met Ser Glu Pro Pro
2450 2455 2460
His Asn Asn Met Gln Val Tyr Ala
2465 2470
<210> 26
<211> 1235
<212> PRT
<213> 人
<400> 26
Met Pro Ala Leu Arg Pro Ala Leu Leu Trp Ala Leu Leu Ala Leu Trp
1 5 10 15
Leu Cys Cys Ala Ala Pro Ala His Ala Leu Gln Cys Arg Asp Gly Tyr
20 25 30
Glu Pro Cys Val Asn Glu Gly Met Cys Val Thr Tyr His Asn Gly Thr
35 40 45
Gly Tyr Cys Lys Cys Pro Glu Gly Phe Leu Gly Glu Tyr Cys Gln His
50 55 60
Arg Asp Pro Cys Glu Lys Asn Arg Cys Gln Asn Gly Gly Thr Cys Val
65 70 75 80
Ala Gln Ala Met Leu Gly Lys Ala Thr Cys Arg Cys Ala Ser Gly Phe
85 90 95
Thr Gly Glu Asp Cys Gln Tyr Ser Thr Ser His Pro Cys Phe Val Ser
100 105 110
Arg Pro Cys Leu Asn Gly Gly Thr Cys His Met Leu Ser Arg Asp Thr
115 120 125
Tyr Glu Cys Thr Cys Gln Val Gly Phe Thr Gly Lys Glu Cys Gln Trp
130 135 140
Thr Asp Ala Cys Leu Ser His Pro Cys Ala Asn Gly Ser Thr Cys Thr
145 150 155 160
Thr Val Ala Asn Gln Phe Ser Cys Lys Cys Leu Thr Gly Phe Thr Gly
165 170 175
Gln Lys Cys Glu Thr Asp Val Asn Glu Cys Asp Ile Pro Gly His Cys
180 185 190
Gln His Gly Gly Thr Cys Leu Asn Leu Pro Gly Ser Tyr Gln Cys Gln
195 200 205
Cys Pro Gln Gly Phe Thr Gly Gln Tyr Cys Asp Ser Leu Tyr Val Pro
210 215 220
Cys Ala Pro Ser Pro Cys Val Asn Gly Gly Thr Cys Arg Gln Thr Gly
225 230 235 240
Asp Phe Thr Phe Glu Cys Asn Cys Leu Pro Gly Phe Glu Gly Ser Thr
245 250 255
Cys Glu Arg Asn Ile Asp Asp Cys Pro Asn His Arg Cys Gln Asn Gly
260 265 270
Gly Val Cys Val Asp Gly Val Asn Thr Tyr Asn Cys Arg Cys Pro Pro
275 280 285
Gln Trp Thr Gly Gln Phe Cys Thr Glu Asp Val Asp Glu Cys Leu Leu
290 295 300
Gln Pro Asn Ala Cys Gln Asn Gly Gly Thr Cys Ala Asn Arg Asn Gly
305 310 315 320
Gly Tyr Gly Cys Val Cys Val Asn Gly Trp Ser Gly Asp Asp Cys Ser
325 330 335
Glu Asn Ile Asp Asp Cys Ala Phe Ala Ser Cys Thr Pro Gly Ser Thr
340 345 350
Cys Ile Asp Arg Val Ala Ser Phe Ser Cys Met Cys Pro Glu Gly Lys
355 360 365
Ala Gly Leu Leu Cys His Leu Asp Asp Ala Cys Ile Ser Asn Pro Cys
370 375 380
His Lys Gly Ala Leu Cys Asp Thr Asn Pro Leu Asn Gly Gln Tyr Ile
385 390 395 400
Cys Thr Cys Pro Gln Gly Tyr Lys Gly Ala Asp Cys Thr Glu Asp Val
405 410 415
Asp Glu Cys Ala Met Ala Asn Ser Asn Pro Cys Glu His Ala Gly Lys
420 425 430
Cys Val Asn Thr Asp Gly Ala Phe His Cys Glu Cys Leu Lys Gly Tyr
435 440 445
Ala Gly Pro Arg Cys Glu Met Asp Ile Asn Glu Cys His Ser Asp Pro
450 455 460
Cys Gln Asn Asp Ala Thr Cys Leu Asp Lys Ile Gly Gly Phe Thr Cys
465 470 475 480
Leu Cys Met Pro Gly Phe Lys Gly Val His Cys Glu Leu Glu Ile Asn
485 490 495
Glu Cys Gln Ser Asn Pro Cys Val Asn Asn Gly Gln Cys Val Asp Lys
500 505 510
Val Asn Arg Phe Gln Cys Leu Cys Pro Pro Gly Phe Thr Gly Pro Val
515 520 525
Cys Gln Ile Asp Ile Asp Asp Cys Ser Ser Thr Pro Cys Leu Asn Gly
530 535 540
Ala Lys Cys Ile Asp His Pro Asn Gly Tyr Glu Cys Gln Cys Ala Thr
545 550 555 560
Gly Phe Thr Gly Val Leu Cys Glu Glu Asn Ile Asp Asn Cys Asp Pro
565 570 575
Asp Pro Cys His His Gly Gln Cys Gln Asp Gly Ile Asp Ser Tyr Thr
580 585 590
Cys Ile Cys Asn Pro Gly Tyr Met Gly Ala Ile Cys Ser Asp Gln Ile
595 600 605
Asp Glu Cys Tyr Ser Ser Pro Cys Leu Asn Asp Gly Arg Cys Ile Asp
610 615 620
Leu Val Asn Gly Tyr Gln Cys Asn Cys Gln Pro Gly Thr Ser Gly Val
625 630 635 640
Asn Cys Glu Ile Asn Phe Asp Asp Cys Ala Ser Asn Pro Cys Ile His
645 650 655
Gly Ile Cys Met Asp Gly Ile Asn Arg Tyr Ser Cys Val Cys Ser Pro
660 665 670
Gly Phe Thr Gly Gln Arg Cys Asn Ile Asp Ile Asp Glu Cys Ala Ser
675 680 685
Asn Pro Cys Arg Lys Gly Ala Thr Cys Ile Asn Gly Val Asn Gly Phe
690 695 700
Arg Cys Ile Cys Pro Glu Gly Pro His His Pro Ser Cys Tyr Ser Gln
705 710 715 720
Val Asn Glu Cys Leu Ser Asn Pro Cys Ile His Gly Asn Cys Thr Gly
725 730 735
Gly Leu Ser Gly Tyr Lys Cys Leu Cys Asp Ala Gly Trp Val Gly Ile
740 745 750
Asn Cys Glu Val Asp Lys Asn Glu Cys Leu Ser Asn Pro Cys Gln Asn
755 760 765
Gly Gly Thr Cys Asp Asn Leu Val Asn Gly Tyr Arg Cys Thr Cys Lys
770 775 780
Lys Gly Phe Lys Gly Tyr Asn Cys Gln Val Asn Ile Asp Glu Cys Ala
785 790 795 800
Ser Asn Pro Cys Leu Asn Gln Gly Thr Cys Phe Asp Asp Ile Ser Gly
805 810 815
Tyr Thr Cys His Cys Val Leu Pro Tyr Thr Gly Lys Asn Cys Gln Thr
820 825 830
Val Leu Ala Pro Cys Ser Pro Asn Pro Cys Glu Asn Ala Ala Val Cys
835 840 845
Lys Glu Ser Pro Asn Phe Glu Ser Tyr Thr Cys Leu Cys Ala Pro Gly
850 855 860
Trp Gln Gly Gln Arg Cys Thr Ile Asp Ile Asp Glu Cys Ile Ser Lys
865 870 875 880
Pro Cys Met Asn His Gly Leu Cys His Asn Thr Gln Gly Ser Tyr Met
885 890 895
Cys Glu Cys Pro Pro Gly Phe Ser Gly Met Asp Cys Glu Glu Asp Ile
900 905 910
Asp Asp Cys Leu Ala Asn Pro Cys Gln Asn Gly Gly Ser Cys Met Asp
915 920 925
Gly Val Asn Thr Phe Ser Cys Leu Cys Leu Pro Gly Phe Thr Gly Asp
930 935 940
Lys Cys Gln Thr Asp Met Asn Glu Cys Leu Ser Glu Pro Cys Lys Asn
945 950 955 960
Gly Gly Thr Cys Ser Asp Tyr Val Asn Ser Tyr Thr Cys Lys Cys Gln
965 970 975
Ala Gly Phe Asp Gly Val His Cys Glu Asn Asn Ile Asn Glu Cys Thr
980 985 990
Glu Ser Ser Cys Phe Asn Gly Gly Thr Cys Val Asp Gly Ile Asn Ser
995 1000 1005
Phe Ser Cys Leu Cys Pro Val Gly Phe Thr Gly Ser Phe Cys Leu
1010 1015 1020
His Glu Ile Asn Glu Cys Ser Ser His Pro Cys Leu Asn Glu Gly
1025 1030 1035
Thr Cys Val Asp Gly Leu Gly Thr Tyr Arg Cys Ser Cys Pro Leu
1040 1045 1050
Gly Tyr Thr Gly Lys Asn Cys Gln Thr Leu Val Asn Leu Cys Ser
1055 1060 1065
Arg Ser Pro Cys Lys Asn Lys Gly Thr Cys Val Gln Lys Lys Ala
1070 1075 1080
Glu Ser Gln Cys Leu Cys Pro Ser Gly Trp Ala Gly Ala Tyr Cys
1085 1090 1095
Asp Val Pro Asn Val Ser Cys Asp Ile Ala Ala Ser Arg Arg Gly
1100 1105 1110
Val Leu Val Glu His Leu Cys Gln His Ser Gly Val Cys Ile Asn
1115 1120 1125
Ala Gly Asn Thr His Tyr Cys Gln Cys Pro Leu Gly Tyr Thr Gly
1130 1135 1140
Ser Tyr Cys Glu Glu Gln Leu Asp Glu Cys Ala Ser Asn Pro Cys
1145 1150 1155
Gln His Gly Ala Thr Cys Ser Asp Phe Ile Gly Gly Tyr Arg Cys
1160 1165 1170
Glu Cys Val Pro Gly Tyr Gln Gly Val Asn Cys Glu Tyr Glu Val
1175 1180 1185
Asp Glu Cys Gln Asn Gln Pro Cys Gln Asn Gly Gly Thr Cys Ile
1190 1195 1200
Asp Leu Val Asn His Phe Lys Cys Ser Cys Pro Pro Gly Thr Arg
1205 1210 1215
Gly Met Lys Ser Ser Leu Ser Ile Phe His Pro Gly His Cys Leu
1220 1225 1230
Lys Leu
1235
<210> 27
<211> 2321
<212> PRT
<213> 人
<400> 27
Met Gly Pro Gly Ala Arg Gly Arg Arg Arg Arg Arg Arg Pro Met Ser
1 5 10 15
Pro Pro Pro Pro Pro Pro Pro Val Arg Ala Leu Pro Leu Leu Leu Leu
20 25 30
Leu Ala Gly Pro Gly Ala Ala Ala Pro Pro Cys Leu Asp Gly Ser Pro
35 40 45
Cys Ala Asn Gly Gly Arg Cys Thr Gln Leu Pro Ser Arg Glu Ala Ala
50 55 60
Cys Leu Cys Pro Pro Gly Trp Val Gly Glu Arg Cys Gln Leu Glu Asp
65 70 75 80
Pro Cys His Ser Gly Pro Cys Ala Gly Arg Gly Val Cys Gln Ser Ser
85 90 95
Val Val Ala Gly Thr Ala Arg Phe Ser Cys Arg Cys Pro Arg Gly Phe
100 105 110
Arg Gly Pro Asp Cys Ser Leu Pro Asp Pro Cys Leu Ser Ser Pro Cys
115 120 125
Ala His Gly Ala Arg Cys Ser Val Gly Pro Asp Gly Arg Phe Leu Cys
130 135 140
Ser Cys Pro Pro Gly Tyr Gln Gly Arg Ser Cys Arg Ser Asp Val Asp
145 150 155 160
Glu Cys Arg Val Gly Glu Pro Cys Arg His Gly Gly Thr Cys Leu Asn
165 170 175
Thr Pro Gly Ser Phe Arg Cys Gln Cys Pro Ala Gly Tyr Thr Gly Pro
180 185 190
Leu Cys Glu Asn Pro Ala Val Pro Cys Ala Pro Ser Pro Cys Arg Asn
195 200 205
Gly Gly Thr Cys Arg Gln Ser Gly Asp Leu Thr Tyr Asp Cys Ala Cys
210 215 220
Leu Pro Gly Phe Glu Gly Gln Asn Cys Glu Val Asn Val Asp Asp Cys
225 230 235 240
Pro Gly His Arg Cys Leu Asn Gly Gly Thr Cys Val Asp Gly Val Asn
245 250 255
Thr Tyr Asn Cys Gln Cys Pro Pro Glu Trp Thr Gly Gln Phe Cys Thr
260 265 270
Glu Asp Val Asp Glu Cys Gln Leu Gln Pro Asn Ala Cys His Asn Gly
275 280 285
Gly Thr Cys Phe Asn Thr Leu Gly Gly His Ser Cys Val Cys Val Asn
290 295 300
Gly Trp Thr Gly Glu Ser Cys Ser Gln Asn Ile Asp Asp Cys Ala Thr
305 310 315 320
Ala Val Cys Phe His Gly Ala Thr Cys His Asp Arg Val Ala Ser Phe
325 330 335
Tyr Cys Ala Cys Pro Met Gly Lys Thr Gly Leu Leu Cys His Leu Asp
340 345 350
Asp Ala Cys Val Ser Asn Pro Cys His Glu Asp Ala Ile Cys Asp Thr
355 360 365
Asn Pro Val Asn Gly Arg Ala Ile Cys Thr Cys Pro Pro Gly Phe Thr
370 375 380
Gly Gly Ala Cys Asp Gln Asp Val Asp Glu Cys Ser Ile Gly Ala Asn
385 390 395 400
Pro Cys Glu His Leu Gly Arg Cys Val Asn Thr Gln Gly Ser Phe Leu
405 410 415
Cys Gln Cys Gly Arg Gly Tyr Thr Gly Pro Arg Cys Glu Thr Asp Val
420 425 430
Asn Glu Cys Leu Ser Gly Pro Cys Arg Asn Gln Ala Thr Cys Leu Asp
435 440 445
Arg Ile Gly Gln Phe Thr Cys Ile Cys Met Ala Gly Phe Thr Gly Thr
450 455 460
Tyr Cys Glu Val Asp Ile Asp Glu Cys Gln Ser Ser Pro Cys Val Asn
465 470 475 480
Gly Gly Val Cys Lys Asp Arg Val Asn Gly Phe Ser Cys Thr Cys Pro
485 490 495
Ser Gly Phe Ser Gly Ser Thr Cys Gln Leu Asp Val Asp Glu Cys Ala
500 505 510
Ser Thr Pro Cys Arg Asn Gly Ala Lys Cys Val Asp Gln Pro Asp Gly
515 520 525
Tyr Glu Cys Arg Cys Ala Glu Gly Phe Glu Gly Thr Leu Cys Asp Arg
530 535 540
Asn Val Asp Asp Cys Ser Pro Asp Pro Cys His His Gly Arg Cys Val
545 550 555 560
Asp Gly Ile Ala Ser Phe Ser Cys Ala Cys Ala Pro Gly Tyr Thr Gly
565 570 575
Thr Arg Cys Glu Ser Gln Val Asp Glu Cys Arg Ser Gln Pro Cys Arg
580 585 590
His Gly Gly Lys Cys Leu Asp Leu Val Asp Lys Tyr Leu Cys Arg Cys
595 600 605
Pro Ser Gly Thr Thr Gly Val Asn Cys Glu Val Asn Ile Asp Asp Cys
610 615 620
Ala Ser Asn Pro Cys Thr Phe Gly Val Cys Arg Asp Gly Ile Asn Arg
625 630 635 640
Tyr Asp Cys Val Cys Gln Pro Gly Phe Thr Gly Pro Leu Cys Asn Val
645 650 655
Glu Ile Asn Glu Cys Ala Ser Ser Pro Cys Gly Glu Gly Gly Ser Cys
660 665 670
Val Asp Gly Glu Asn Gly Phe Arg Cys Leu Cys Pro Pro Gly Ser Leu
675 680 685
Pro Pro Leu Cys Leu Pro Pro Ser His Pro Cys Ala His Glu Pro Cys
690 695 700
Ser His Gly Ile Cys Tyr Asp Ala Pro Gly Gly Phe Arg Cys Val Cys
705 710 715 720
Glu Pro Gly Trp Ser Gly Pro Arg Cys Ser Gln Ser Leu Ala Arg Asp
725 730 735
Ala Cys Glu Ser Gln Pro Cys Arg Ala Gly Gly Thr Cys Ser Ser Asp
740 745 750
Gly Met Gly Phe His Cys Thr Cys Pro Pro Gly Val Gln Gly Arg Gln
755 760 765
Cys Glu Leu Leu Ser Pro Cys Thr Pro Asn Pro Cys Glu His Gly Gly
770 775 780
Arg Cys Glu Ser Ala Pro Gly Gln Leu Pro Val Cys Ser Cys Pro Gln
785 790 795 800
Gly Trp Gln Gly Pro Arg Cys Gln Gln Asp Val Asp Glu Cys Ala Gly
805 810 815
Pro Ala Pro Cys Gly Pro His Gly Ile Cys Thr Asn Leu Ala Gly Ser
820 825 830
Phe Ser Cys Thr Cys His Gly Gly Tyr Thr Gly Pro Ser Cys Asp Gln
835 840 845
Asp Ile Asn Asp Cys Asp Pro Asn Pro Cys Leu Asn Gly Gly Ser Cys
850 855 860
Gln Asp Gly Val Gly Ser Phe Ser Cys Ser Cys Leu Pro Gly Phe Ala
865 870 875 880
Gly Pro Arg Cys Ala Arg Asp Val Asp Glu Cys Leu Ser Asn Pro Cys
885 890 895
Gly Pro Gly Thr Cys Thr Asp His Val Ala Ser Phe Thr Cys Thr Cys
900 905 910
Pro Pro Gly Tyr Gly Gly Phe His Cys Glu Gln Asp Leu Pro Asp Cys
915 920 925
Ser Pro Ser Ser Cys Phe Asn Gly Gly Thr Cys Val Asp Gly Val Asn
930 935 940
Ser Phe Ser Cys Leu Cys Arg Pro Gly Tyr Thr Gly Ala His Cys Gln
945 950 955 960
His Glu Ala Asp Pro Cys Leu Ser Arg Pro Cys Leu His Gly Gly Val
965 970 975
Cys Ser Ala Ala His Pro Gly Phe Arg Cys Thr Cys Leu Glu Ser Phe
980 985 990
Thr Gly Pro Gln Cys Gln Thr Leu Val Asp Trp Cys Ser Arg Gln Pro
995 1000 1005
Cys Gln Asn Gly Gly Arg Cys Val Gln Thr Gly Ala Tyr Cys Leu
1010 1015 1020
Cys Pro Pro Gly Trp Ser Gly Arg Leu Cys Asp Ile Arg Ser Leu
1025 1030 1035
Pro Cys Arg Glu Ala Ala Ala Gln Ile Gly Val Arg Leu Glu Gln
1040 1045 1050
Leu Cys Gln Ala Gly Gly Gln Cys Val Asp Glu Asp Ser Ser His
1055 1060 1065
Tyr Cys Val Cys Pro Glu Gly Arg Thr Gly Ser His Cys Glu Gln
1070 1075 1080
Glu Val Asp Pro Cys Leu Ala Gln Pro Cys Gln His Gly Gly Thr
1085 1090 1095
Cys Arg Gly Tyr Met Gly Gly Tyr Met Cys Glu Cys Leu Pro Gly
1100 1105 1110
Tyr Asn Gly Asp Asn Cys Glu Asp Asp Val Asp Glu Cys Ala Ser
1115 1120 1125
Gln Pro Cys Gln His Gly Gly Ser Cys Ile Asp Leu Val Ala Arg
1130 1135 1140
Tyr Leu Cys Ser Cys Pro Pro Gly Thr Leu Gly Val Leu Cys Glu
1145 1150 1155
Ile Asn Glu Asp Asp Cys Gly Pro Gly Pro Pro Leu Asp Ser Gly
1160 1165 1170
Pro Arg Cys Leu His Asn Gly Thr Cys Val Asp Leu Val Gly Gly
1175 1180 1185
Phe Arg Cys Thr Cys Pro Pro Gly Tyr Thr Gly Leu Arg Cys Glu
1190 1195 1200
Ala Asp Ile Asn Glu Cys Arg Ser Gly Ala Cys His Ala Ala His
1205 1210 1215
Thr Arg Asp Cys Leu Gln Asp Pro Gly Gly Gly Phe Arg Cys Leu
1220 1225 1230
Cys His Ala Gly Phe Ser Gly Pro Arg Cys Gln Thr Val Leu Ser
1235 1240 1245
Pro Cys Glu Ser Gln Pro Cys Gln His Gly Gly Gln Cys Arg Pro
1250 1255 1260
Ser Pro Gly Pro Gly Gly Gly Leu Thr Phe Thr Cys His Cys Ala
1265 1270 1275
Gln Pro Phe Trp Gly Pro Arg Cys Glu Arg Val Ala Arg Ser Cys
1280 1285 1290
Arg Glu Leu Gln Cys Pro Val Gly Val Pro Cys Gln Gln Thr Pro
1295 1300 1305
Arg Gly Pro Arg Cys Ala Cys Pro Pro Gly Leu Ser Gly Pro Ser
1310 1315 1320
Cys Arg Ser Phe Pro Gly Ser Pro Pro Gly Ala Ser Asn Ala Ser
1325 1330 1335
Cys Ala Ala Ala Pro Cys Leu His Gly Gly Ser Cys Arg Pro Ala
1340 1345 1350
Pro Leu Ala Pro Phe Phe Arg Cys Ala Cys Ala Gln Gly Trp Thr
1355 1360 1365
Gly Pro Arg Cys Glu Ala Pro Ala Ala Ala Pro Glu Val Ser Glu
1370 1375 1380
Glu Pro Arg Cys Pro Arg Ala Ala Cys Gln Ala Lys Arg Gly Asp
1385 1390 1395
Gln Arg Cys Asp Arg Glu Cys Asn Ser Pro Gly Cys Gly Trp Asp
1400 1405 1410
Gly Gly Asp Cys Ser Leu Ser Val Gly Asp Pro Trp Arg Gln Cys
1415 1420 1425
Glu Ala Leu Gln Cys Trp Arg Leu Phe Asn Asn Ser Arg Cys Asp
1430 1435 1440
Pro Ala Cys Ser Ser Pro Ala Cys Leu Tyr Asp Asn Phe Asp Cys
1445 1450 1455
His Ala Gly Gly Arg Glu Arg Thr Cys Asn Pro Val Tyr Glu Lys
1460 1465 1470
Tyr Cys Ala Asp His Phe Ala Asp Gly Arg Cys Asp Gln Gly Cys
1475 1480 1485
Asn Thr Glu Glu Cys Gly Trp Asp Gly Leu Asp Cys Ala Ser Glu
1490 1495 1500
Val Pro Ala Leu Leu Ala Arg Gly Val Leu Val Leu Thr Val Leu
1505 1510 1515
Leu Pro Pro Glu Glu Leu Leu Arg Ser Ser Ala Asp Phe Leu Gln
1520 1525 1530
Arg Leu Ser Ala Ile Leu Arg Thr Ser Leu Arg Phe Arg Leu Asp
1535 1540 1545
Ala His Gly Gln Ala Met Val Phe Pro Tyr His Arg Pro Ser Pro
1550 1555 1560
Gly Ser Glu Pro Arg Ala Arg Arg Glu Leu Ala Pro Glu Val Ile
1565 1570 1575
Gly Ser Val Val Met Leu Glu Ile Asp Asn Arg Leu Cys Leu Gln
1580 1585 1590
Ser Pro Glu Asn Asp His Cys Phe Pro Asp Ala Gln Ser Ala Ala
1595 1600 1605
Asp Tyr Leu Gly Ala Leu Ser Ala Val Glu Arg Leu Asp Phe Pro
1610 1615 1620
Tyr Pro Leu Arg Asp Val Arg Gly Glu Pro Leu Glu Pro Pro Glu
1625 1630 1635
Pro Ser Val Pro Leu Leu Pro Leu Leu Val Ala Gly Ala Val Leu
1640 1645 1650
Leu Leu Val Ile Leu Val Leu Gly Val Met Val Ala Arg Arg Lys
1655 1660 1665
Arg Glu His Ser Thr Leu Trp Phe Pro Glu Gly Phe Ser Leu His
1670 1675 1680
Lys Asp Val Ala Ser Gly His Lys Gly Arg Arg Glu Pro Val Gly
1685 1690 1695
Gln Asp Ala Leu Gly Met Lys Asn Met Ala Lys Gly Glu Ser Leu
1700 1705 1710
Met Gly Glu Val Ala Thr Asp Trp Met Asp Thr Glu Cys Pro Glu
1715 1720 1725
Ala Lys Arg Leu Lys Val Glu Glu Pro Gly Met Gly Ala Glu Glu
1730 1735 1740
Ala Val Asp Cys Arg Gln Trp Thr Gln His His Leu Val Ala Ala
1745 1750 1755
Asp Ile Arg Val Ala Pro Ala Met Ala Leu Thr Pro Pro Gln Gly
1760 1765 1770
Asp Ala Asp Ala Asp Gly Met Asp Val Asn Val Arg Gly Pro Asp
1775 1780 1785
Gly Phe Thr Pro Leu Met Leu Ala Ser Phe Cys Gly Gly Ala Leu
1790 1795 1800
Glu Pro Met Pro Thr Glu Glu Asp Glu Ala Asp Asp Thr Ser Ala
1805 1810 1815
Ser Ile Ile Ser Asp Leu Ile Cys Gln Gly Ala Gln Leu Gly Ala
1820 1825 1830
Arg Thr Asp Arg Thr Gly Glu Thr Ala Leu His Leu Ala Ala Arg
1835 1840 1845
Tyr Ala Arg Ala Asp Ala Ala Lys Arg Leu Leu Asp Ala Gly Ala
1850 1855 1860
Asp Thr Asn Ala Gln Asp His Ser Gly Arg Thr Pro Leu His Thr
1865 1870 1875
Ala Val Thr Ala Asp Ala Gln Gly Val Phe Gln Ile Leu Ile Arg
1880 1885 1890
Asn Arg Ser Thr Asp Leu Asp Ala Arg Met Ala Asp Gly Ser Thr
1895 1900 1905
Ala Leu Ile Leu Ala Ala Arg Leu Ala Val Glu Gly Met Val Glu
1910 1915 1920
Glu Leu Ile Ala Ser His Ala Asp Val Asn Ala Val Asp Glu Leu
1925 1930 1935
Gly Lys Ser Ala Leu His Trp Ala Ala Ala Val Asn Asn Val Glu
1940 1945 1950
Ala Thr Leu Ala Leu Leu Lys Asn Gly Ala Asn Lys Asp Met Gln
1955 1960 1965
Asp Ser Lys Glu Glu Thr Pro Leu Phe Leu Ala Ala Arg Glu Gly
1970 1975 1980
Ser Tyr Glu Ala Ala Lys Leu Leu Leu Asp His Phe Ala Asn Arg
1985 1990 1995
Glu Ile Thr Asp His Leu Asp Arg Leu Pro Arg Asp Val Ala Gln
2000 2005 2010
Glu Arg Leu His Gln Asp Ile Val Arg Leu Leu Asp Gln Pro Ser
2015 2020 2025
Gly Pro Arg Ser Pro Pro Gly Pro His Gly Leu Gly Pro Leu Leu
2030 2035 2040
Cys Pro Pro Gly Ala Phe Leu Pro Gly Leu Lys Ala Ala Gln Ser
2045 2050 2055
Gly Ser Lys Lys Ser Arg Arg Pro Pro Gly Lys Ala Gly Leu Gly
2060 2065 2070
Pro Gln Gly Pro Arg Gly Arg Gly Lys Lys Leu Thr Leu Ala Cys
2075 2080 2085
Pro Gly Pro Leu Ala Asp Ser Ser Val Thr Leu Ser Pro Val Asp
2090 2095 2100
Ser Leu Asp Ser Pro Arg Pro Phe Gly Gly Pro Pro Ala Ser Pro
2105 2110 2115
Gly Gly Phe Pro Leu Glu Gly Pro Tyr Ala Ala Ala Thr Ala Thr
2120 2125 2130
Ala Val Ser Leu Ala Gln Leu Gly Gly Pro Gly Arg Ala Gly Leu
2135 2140 2145
Gly Arg Gln Pro Pro Gly Gly Cys Val Leu Ser Leu Gly Leu Leu
2150 2155 2160
Asn Pro Val Ala Val Pro Leu Asp Trp Ala Arg Leu Pro Pro Pro
2165 2170 2175
Ala Pro Pro Gly Pro Ser Phe Leu Leu Pro Leu Ala Pro Gly Pro
2180 2185 2190
Gln Leu Leu Asn Pro Gly Thr Pro Val Ser Pro Gln Glu Arg Pro
2195 2200 2205
Pro Pro Tyr Leu Ala Val Pro Gly His Gly Glu Glu Tyr Pro Ala
2210 2215 2220
Ala Gly Ala His Ser Ser Pro Pro Lys Ala Arg Phe Leu Arg Val
2225 2230 2235
Pro Ser Glu His Pro Tyr Leu Thr Pro Ser Pro Glu Ser Pro Glu
2240 2245 2250
His Trp Ala Ser Pro Ser Pro Pro Ser Leu Ser Asp Trp Ser Glu
2255 2260 2265
Ser Thr Pro Ser Pro Ala Thr Ala Thr Gly Ala Met Ala Thr Thr
2270 2275 2280
Thr Gly Ala Leu Pro Ala Gln Pro Leu Pro Leu Ser Val Pro Ser
2285 2290 2295
Ser Leu Ala Gln Ala Gln Thr Gln Leu Gly Pro Gln Pro Glu Val
2300 2305 2310
Thr Pro Lys Arg Gln Val Leu Ala
2315 2320
<210> 28
<211> 2003
<212> PRT
<213> 人
<400> 28
Met Gln Pro Pro Ser Leu Leu Leu Leu Leu Leu Leu Leu Leu Leu Leu
1 5 10 15
Cys Val Ser Val Val Arg Pro Arg Gly Leu Leu Cys Gly Ser Phe Pro
20 25 30
Glu Pro Cys Ala Asn Gly Gly Thr Cys Leu Ser Leu Ser Leu Gly Gln
35 40 45
Gly Thr Cys Gln Cys Ala Pro Gly Phe Leu Gly Glu Thr Cys Gln Phe
50 55 60
Pro Asp Pro Cys Gln Asn Ala Gln Leu Cys Gln Asn Gly Gly Ser Cys
65 70 75 80
Gln Ala Leu Leu Pro Ala Pro Leu Gly Leu Pro Ser Ser Pro Ser Pro
85 90 95
Leu Thr Pro Ser Phe Leu Cys Thr Cys Leu Pro Gly Phe Thr Gly Glu
100 105 110
Arg Cys Gln Ala Lys Leu Glu Asp Pro Cys Pro Pro Ser Phe Cys Ser
115 120 125
Lys Arg Gly Arg Cys His Ile Gln Ala Ser Gly Arg Pro Gln Cys Ser
130 135 140
Cys Met Pro Gly Trp Thr Gly Glu Gln Cys Gln Leu Arg Asp Phe Cys
145 150 155 160
Ser Ala Asn Pro Cys Val Asn Gly Gly Val Cys Leu Ala Thr Tyr Pro
165 170 175
Gln Ile Gln Cys His Cys Pro Pro Gly Phe Glu Gly His Ala Cys Glu
180 185 190
Arg Asp Val Asn Glu Cys Phe Gln Asp Pro Gly Pro Cys Pro Lys Gly
195 200 205
Thr Ser Cys His Asn Thr Leu Gly Ser Phe Gln Cys Leu Cys Pro Val
210 215 220
Gly Gln Glu Gly Pro Arg Cys Glu Leu Arg Ala Gly Pro Cys Pro Pro
225 230 235 240
Arg Gly Cys Ser Asn Gly Gly Thr Cys Gln Leu Met Pro Glu Lys Asp
245 250 255
Ser Thr Phe His Leu Cys Leu Cys Pro Pro Gly Phe Ile Gly Pro Asp
260 265 270
Cys Glu Val Asn Pro Asp Asn Cys Val Ser His Gln Cys Gln Asn Gly
275 280 285
Gly Thr Cys Gln Asp Gly Leu Asp Thr Tyr Thr Cys Leu Cys Pro Glu
290 295 300
Thr Trp Thr Gly Trp Asp Cys Ser Glu Asp Val Asp Glu Cys Glu Thr
305 310 315 320
Gln Gly Pro Pro His Cys Arg Asn Gly Gly Thr Cys Gln Asn Ser Ala
325 330 335
Gly Ser Phe His Cys Val Cys Val Ser Gly Trp Gly Gly Thr Ser Cys
340 345 350
Glu Glu Asn Leu Asp Asp Cys Ile Ala Ala Thr Cys Ala Pro Gly Ser
355 360 365
Thr Cys Ile Asp Arg Val Gly Ser Phe Ser Cys Leu Cys Pro Pro Gly
370 375 380
Arg Thr Gly Leu Leu Cys His Leu Glu Asp Met Cys Leu Ser Gln Pro
385 390 395 400
Cys His Gly Asp Ala Gln Cys Ser Thr Asn Pro Leu Thr Gly Ser Thr
405 410 415
Leu Cys Leu Cys Gln Pro Gly Tyr Ser Gly Pro Thr Cys His Gln Asp
420 425 430
Leu Asp Glu Cys Leu Met Ala Gln Gln Gly Pro Ser Pro Cys Glu His
435 440 445
Gly Gly Ser Cys Leu Asn Thr Pro Gly Ser Phe Asn Cys Leu Cys Pro
450 455 460
Pro Gly Tyr Thr Gly Ser Arg Cys Glu Ala Asp His Asn Glu Cys Leu
465 470 475 480
Ser Gln Pro Cys His Pro Gly Ser Thr Cys Leu Asp Leu Leu Ala Thr
485 490 495
Phe His Cys Leu Cys Pro Pro Gly Leu Glu Gly Gln Leu Cys Glu Val
500 505 510
Glu Thr Asn Glu Cys Ala Ser Ala Pro Cys Leu Asn His Ala Asp Cys
515 520 525
His Asp Leu Leu Asn Gly Phe Gln Cys Ile Cys Leu Pro Gly Phe Ser
530 535 540
Gly Thr Arg Cys Glu Glu Asp Ile Asp Glu Cys Arg Ser Ser Pro Cys
545 550 555 560
Ala Asn Gly Gly Gln Cys Gln Asp Gln Pro Gly Ala Phe His Cys Lys
565 570 575
Cys Leu Pro Gly Phe Glu Gly Pro Arg Cys Gln Thr Glu Val Asp Glu
580 585 590
Cys Leu Ser Asp Pro Cys Pro Val Gly Ala Ser Cys Leu Asp Leu Pro
595 600 605
Gly Ala Phe Phe Cys Leu Cys Pro Ser Gly Phe Thr Gly Gln Leu Cys
610 615 620
Glu Val Pro Leu Cys Ala Pro Asn Leu Cys Gln Pro Lys Gln Ile Cys
625 630 635 640
Lys Asp Gln Lys Asp Lys Ala Asn Cys Leu Cys Pro Asp Gly Ser Pro
645 650 655
Gly Cys Ala Pro Pro Glu Asp Asn Cys Thr Cys His His Gly His Cys
660 665 670
Gln Arg Ser Ser Cys Val Cys Asp Val Gly Trp Thr Gly Pro Glu Cys
675 680 685
Glu Ala Glu Leu Gly Gly Cys Ile Ser Ala Pro Cys Ala His Gly Gly
690 695 700
Thr Cys Tyr Pro Gln Pro Ser Gly Tyr Asn Cys Thr Cys Pro Thr Gly
705 710 715 720
Tyr Thr Gly Pro Thr Cys Ser Glu Glu Met Thr Ala Cys His Ser Gly
725 730 735
Pro Cys Leu Asn Gly Gly Ser Cys Asn Pro Ser Pro Gly Gly Tyr Tyr
740 745 750
Cys Thr Cys Pro Pro Ser His Thr Gly Pro Gln Cys Gln Thr Ser Thr
755 760 765
Asp Tyr Cys Val Ser Ala Pro Cys Phe Asn Gly Gly Thr Cys Val Asn
770 775 780
Arg Pro Gly Thr Phe Ser Cys Leu Cys Ala Met Gly Phe Gln Gly Pro
785 790 795 800
Arg Cys Glu Gly Lys Leu Arg Pro Ser Cys Ala Asp Ser Pro Cys Arg
805 810 815
Asn Arg Ala Thr Cys Gln Asp Ser Pro Gln Gly Pro Arg Cys Leu Cys
820 825 830
Pro Thr Gly Tyr Thr Gly Gly Ser Cys Gln Thr Leu Met Asp Leu Cys
835 840 845
Ala Gln Lys Pro Cys Pro Arg Asn Ser His Cys Leu Gln Thr Gly Pro
850 855 860
Ser Phe His Cys Leu Cys Leu Gln Gly Trp Thr Gly Pro Leu Cys Asn
865 870 875 880
Leu Pro Leu Ser Ser Cys Gln Lys Ala Ala Leu Ser Gln Gly Ile Asp
885 890 895
Val Ser Ser Leu Cys His Asn Gly Gly Leu Cys Val Asp Ser Gly Pro
900 905 910
Ser Tyr Phe Cys His Cys Pro Pro Gly Phe Gln Gly Ser Leu Cys Gln
915 920 925
Asp His Val Asn Pro Cys Glu Ser Arg Pro Cys Gln Asn Gly Ala Thr
930 935 940
Cys Met Ala Gln Pro Ser Gly Tyr Leu Cys Gln Cys Ala Pro Gly Tyr
945 950 955 960
Asp Gly Gln Asn Cys Ser Lys Glu Leu Asp Ala Cys Gln Ser Gln Pro
965 970 975
Cys His Asn His Gly Thr Cys Thr Pro Lys Pro Gly Gly Phe His Cys
980 985 990
Ala Cys Pro Pro Gly Phe Val Gly Leu Arg Cys Glu Gly Asp Val Asp
995 1000 1005
Glu Cys Leu Asp Gln Pro Cys His Pro Thr Gly Thr Ala Ala Cys
1010 1015 1020
His Ser Leu Ala Asn Ala Phe Tyr Cys Gln Cys Leu Pro Gly His
1025 1030 1035
Thr Gly Gln Trp Cys Glu Val Glu Ile Asp Pro Cys His Ser Gln
1040 1045 1050
Pro Cys Phe His Gly Gly Thr Cys Glu Ala Thr Ala Gly Ser Pro
1055 1060 1065
Leu Gly Phe Ile Cys His Cys Pro Lys Gly Phe Glu Gly Pro Thr
1070 1075 1080
Cys Ser His Arg Ala Pro Ser Cys Gly Phe His His Cys His His
1085 1090 1095
Gly Gly Leu Cys Leu Pro Ser Pro Lys Pro Gly Phe Pro Pro Arg
1100 1105 1110
Cys Ala Cys Leu Ser Gly Tyr Gly Gly Pro Asp Cys Leu Thr Pro
1115 1120 1125
Pro Ala Pro Lys Gly Cys Gly Pro Pro Ser Pro Cys Leu Tyr Asn
1130 1135 1140
Gly Ser Cys Ser Glu Thr Thr Gly Leu Gly Gly Pro Gly Phe Arg
1145 1150 1155
Cys Ser Cys Pro His Ser Ser Pro Gly Pro Arg Cys Gln Lys Pro
1160 1165 1170
Gly Ala Lys Gly Cys Glu Gly Arg Ser Gly Asp Gly Ala Cys Asp
1175 1180 1185
Ala Gly Cys Ser Gly Pro Gly Gly Asn Trp Asp Gly Gly Asp Cys
1190 1195 1200
Ser Leu Gly Val Pro Asp Pro Trp Lys Gly Cys Pro Ser His Ser
1205 1210 1215
Arg Cys Trp Leu Leu Phe Arg Asp Gly Gln Cys His Pro Gln Cys
1220 1225 1230
Asp Ser Glu Glu Cys Leu Phe Asp Gly Tyr Asp Cys Glu Thr Pro
1235 1240 1245
Pro Ala Cys Thr Pro Ala Tyr Asp Gln Tyr Cys His Asp His Phe
1250 1255 1260
His Asn Gly His Cys Glu Lys Gly Cys Asn Thr Ala Glu Cys Gly
1265 1270 1275
Trp Asp Gly Gly Asp Cys Arg Pro Glu Asp Gly Asp Pro Glu Trp
1280 1285 1290
Gly Pro Ser Leu Ala Leu Leu Val Val Leu Ser Pro Pro Ala Leu
1295 1300 1305
Asp Gln Gln Leu Phe Ala Leu Ala Arg Val Leu Ser Leu Thr Leu
1310 1315 1320
Arg Val Gly Leu Trp Val Arg Lys Asp Arg Asp Gly Arg Asp Met
1325 1330 1335
Val Tyr Pro Tyr Pro Gly Ala Arg Ala Glu Glu Lys Leu Gly Gly
1340 1345 1350
Thr Arg Asp Pro Thr Tyr Gln Glu Arg Ala Ala Pro Gln Thr Gln
1355 1360 1365
Pro Leu Gly Lys Glu Thr Asp Ser Leu Ser Ala Gly Phe Val Val
1370 1375 1380
Val Met Gly Val Asp Leu Ser Arg Cys Gly Pro Asp His Pro Ala
1385 1390 1395
Ser Arg Cys Pro Trp Asp Pro Gly Leu Leu Leu Arg Phe Leu Ala
1400 1405 1410
Ala Met Ala Ala Val Gly Ala Leu Glu Pro Leu Leu Pro Gly Pro
1415 1420 1425
Leu Leu Ala Val His Pro His Ala Gly Thr Ala Pro Pro Ala Asn
1430 1435 1440
Gln Leu Pro Trp Pro Val Leu Cys Ser Pro Val Ala Gly Val Ile
1445 1450 1455
Leu Leu Ala Leu Gly Ala Leu Leu Val Leu Gln Leu Ile Arg Arg
1460 1465 1470
Arg Arg Arg Glu His Gly Ala Leu Trp Leu Pro Pro Gly Phe Thr
1475 1480 1485
Arg Arg Pro Arg Thr Gln Ser Ala Pro His Arg Arg Arg Pro Pro
1490 1495 1500
Leu Gly Glu Asp Ser Ile Gly Leu Lys Ala Leu Lys Pro Lys Ala
1505 1510 1515
Glu Val Asp Glu Asp Gly Val Val Met Cys Ser Gly Pro Glu Glu
1520 1525 1530
Gly Glu Glu Val Gly Gln Ala Glu Glu Thr Gly Pro Pro Ser Thr
1535 1540 1545
Cys Gln Leu Trp Ser Leu Ser Gly Gly Cys Gly Ala Leu Pro Gln
1550 1555 1560
Ala Ala Met Leu Thr Pro Pro Gln Glu Ser Glu Met Glu Ala Pro
1565 1570 1575
Asp Leu Asp Thr Arg Gly Pro Asp Gly Val Thr Pro Leu Met Ser
1580 1585 1590
Ala Val Cys Cys Gly Glu Val Gln Ser Gly Thr Phe Gln Gly Ala
1595 1600 1605
Trp Leu Gly Cys Pro Glu Pro Trp Glu Pro Leu Leu Asp Gly Gly
1610 1615 1620
Ala Cys Pro Gln Ala His Thr Val Gly Thr Gly Glu Thr Pro Leu
1625 1630 1635
His Leu Ala Ala Arg Phe Ser Arg Pro Thr Ala Ala Arg Arg Leu
1640 1645 1650
Leu Glu Ala Gly Ala Asn Pro Asn Gln Pro Asp Arg Ala Gly Arg
1655 1660 1665
Thr Pro Leu His Ala Ala Val Ala Ala Asp Ala Arg Glu Val Cys
1670 1675 1680
Gln Leu Leu Leu Arg Ser Arg Gln Thr Ala Val Asp Ala Arg Thr
1685 1690 1695
Glu Asp Gly Thr Thr Pro Leu Met Leu Ala Ala Arg Leu Ala Val
1700 1705 1710
Glu Asp Leu Val Glu Glu Leu Ile Ala Ala Gln Ala Asp Val Gly
1715 1720 1725
Ala Arg Asp Lys Trp Gly Lys Thr Ala Leu His Trp Ala Ala Ala
1730 1735 1740
Val Asn Asn Ala Arg Ala Ala Arg Ser Leu Leu Gln Ala Gly Ala
1745 1750 1755
Asp Lys Asp Ala Gln Asp Asn Arg Glu Gln Thr Pro Leu Phe Leu
1760 1765 1770
Ala Ala Arg Glu Gly Ala Val Glu Val Ala Gln Leu Leu Leu Gly
1775 1780 1785
Leu Gly Ala Ala Arg Glu Leu Arg Asp Gln Ala Gly Leu Ala Pro
1790 1795 1800
Ala Asp Val Ala His Gln Arg Asn His Trp Asp Leu Leu Thr Leu
1805 1810 1815
Leu Glu Gly Ala Gly Pro Pro Glu Ala Arg His Lys Ala Thr Pro
1820 1825 1830
Gly Arg Glu Ala Gly Pro Phe Pro Arg Ala Arg Thr Val Ser Val
1835 1840 1845
Ser Val Pro Pro His Gly Gly Gly Ala Leu Pro Arg Cys Arg Thr
1850 1855 1860
Leu Ser Ala Gly Ala Gly Pro Arg Gly Gly Gly Ala Cys Leu Gln
1865 1870 1875
Ala Arg Thr Trp Ser Val Asp Leu Ala Ala Arg Gly Gly Gly Ala
1880 1885 1890
Tyr Ser His Cys Arg Ser Leu Ser Gly Val Gly Ala Gly Gly Gly
1895 1900 1905
Pro Thr Pro Arg Gly Arg Arg Phe Ser Ala Gly Met Arg Gly Pro
1910 1915 1920
Arg Pro Asn Pro Ala Ile Met Arg Gly Arg Tyr Gly Val Ala Ala
1925 1930 1935
Gly Arg Gly Gly Arg Val Ser Thr Asp Asp Trp Pro Cys Asp Trp
1940 1945 1950
Val Ala Leu Gly Ala Cys Gly Ser Ala Ser Asn Ile Pro Ile Pro
1955 1960 1965
Pro Pro Cys Leu Thr Pro Ser Pro Glu Arg Gly Ser Pro Gln Leu
1970 1975 1980
Asp Cys Gly Pro Pro Ala Leu Gln Glu Met Pro Ile Asn Gln Gly
1985 1990 1995
Gly Glu Gly Lys Lys
2000
<210> 29
<211> 9322
<212> DNA
<213> 人
<400> 29
atgccgccgc tcctggcgcc cctgctctgc ctggcgctgc tgcccgcgct cgccgcacga 60
ggcccgcgat gctcccagcc cggtgagacc tgcctgaatg gcgggaagtg tgaagcggcc 120
aatggcacgg aggcctgcgt ctgtggcggg gccttcgtgg gcccgcgatg ccaggacccc 180
aacccgtgcc tcagcacccc ctgcaagaac gccgggacat gccacgtggt ggaccgcaga 240
ggcgtggcag actatgcctg cagctgtgcc ctgggcttct ctgggcccct ctgcctgaca 300
cccctggaca atgcctgcct caccaacccc tgccgcaacg ggggcacctg cgacctgctc 360
acgctgacgg agtacaagtg ccgctgcccg cccggctggt cagggaaatc gtgccagcag 420
gctgacccgt gcgcctccaa cccctgcgcc aacggtggcc agtgcctgcc cttcgaggcc 480
tcctacatct gccactgccc acccagcttc catggcccca cctgccggca ggatgtcaac 540
gagtgtggcc agaagcccgg gctttgccgc cacggaggca cctgccacaa cgaggtcggc 600
tcctaccgct gcgtctgccg cgccacccac actggcccca actgcgagcg gccctacgtg 660
ccctgcagcc cctcgccctg ccagaacggg ggcacctgcc gccccacggg cgacgtcacc 720
cacgagtgtg cctgcctgcc aggcttcacc ggccagaact gtgaggaaaa tatcgacgat 780
tgtccaggaa acaactgcaa gaacgggggt gcctgtgtgg acggcgtgaa cacctacaac 840
tgccgctgcc cgccagagtg gacaggtcag tactgtaccg aggatgtgga cgagtgccag 900
ctgatgccaa atgcctgcca gaacggcggg acctgccaca acacccacgg tggctacaac 960
tgcgtgtgtg tcaacggctg gactggtgag gactgcagcg agaacattga tgactgtgcc 1020
agcgccgcct gcttccacgg cgccacctgc catgaccgtg tggcctcctt ctactgcgag 1080
tgtccccatg gccgcacagg tctgctgtgc cacctcaacg acgcatgcat cagcaacccc 1140
tgtaacgagg gctccaactg cgacaccaac cctgtcaatg gcaaggccat ctgcacctgc 1200
ccctcggggt acacgggccc ggcctgcagc caggacgtgg atgagtgctc gctgggtgcc 1260
aacccctgcg agcatgcggg caagtgcatc aacacgctgg gctccttcga gtgccagtgt 1320
ctgcagggct acacgggccc ccgatgcgag atcgacgtca acgagtgcgt ctcgaacccg 1380
tgccagaacg acgccacctg cctggaccag attggggagt tccagtgcat ctgcatgccc 1440
ggctacgagg gtgtgcactg cgaggtcaac acagacgagt gtgccagcag cccctgcctg 1500
cacaatggcc gctgcctgga caagatcaat gagttccagt gcgagtgccc cacgggcttc 1560
actgggcatc tgtgccagta cgatgtggac gagtgtgcca gcaccccctg caagaatggt 1620
gccaagtgcc tggacggacc caacacttac acctgtgtgt gcacggaagg gtacacgggg 1680
acgcactgcg aggtggacat cgatgagtgc gaccccgacc cctgccacta cggctcctgc 1740
aaggacggcg tcgccacctt cacctgcctc tgccgcccag gctacacggg ccaccactgc 1800
gagaccaaca tcaacgagtg ctccagccag ccctgccgcc acgggggcac ctgccaggac 1860
cgcgacaacg cctacctctg cttctgcctg aaggggacca caggacccaa ctgcgagatc 1920
aacctggatg actgtgccag cagcccctgc gactcgggca cctgtctgga caagatcgat 1980
ggctacgagt gtgcctgtga gccgggctac acagggagca tgtgtaacat caacatcgat 2040
gagtgtgcgg gcaacccctg ccacaacggg ggcacctgcg aggacggcat caatggcttc 2100
acctgccgct gccccgaggg ctaccacgac cccacctgcc tgtctgaggt caatgagtgc 2160
aacagcaacc cctgcgtcca cggggcctgc cgggacagcc tcaacgggta caagtgcgac 2220
tgtgaccctg ggtggagtgg gaccaactgt gacatcaaca acaatgagtg tgaatccaac 2280
ccttgtgtca acggcggcac ctgcaaagac atgaccagtg gctacgtgtg cacctgccgg 2340
gagggcttca gcggtcccaa ctgccagacc aacatcaacg agtgtgcgtc caacccatgt 2400
ctgaaccagg gcacgtgtat tgacgacgtt gccgggtaca agtgcaactg cctgctgccc 2460
tacacaggtg ccacgtgtga ggtggtgctg gccccgtgtg cccccagccc ctgcagaaac 2520
ggcggggagt gcaggcaatc cgaggactat gagagcttct cctgtgtctg ccccacgggc 2580
tggcaagggc agacctgtga ggtcgacatc aacgagtgcg ttctgagccc gtgccggcac 2640
ggcgcatcct gccagaacac ccacggcggc taccgctgcc actgccaggc cggctacagt 2700
gggcgcaact gcgagaccga catcgacgac tgccggccca acccgtgtca caacgggggc 2760
tcctgcacag acggcatcaa cacggccttc tgcgactgcc tgcccggctt ccggggcact 2820
ttctgtgagg aggacatcaa cgagtgtgcc agtgacccct gccgcaacgg ggccaactgc 2880
acggactgcg tggacagcta cacgtgcacc tgccccgcag gcttcagcgg gatccactgt 2940
gagaacaaca cgcctgactg cacagagagc tcctgcttca acggtggcac ctgcgtggac 3000
ggcatcaact cgttcacctg cctgtgtcca cccggcttca cgggcagcta ctgccagcac 3060
gatgtcaatg agtgcgactc acagccctgc ctgcatggcg gcacctgtca ggacggctgc 3120
ggctcctaca ggtgcacctg cccccagggc tacactggcc ccaactgcca gaaccttgtg 3180
cactggtgtg actcctcgcc ctgcaagaac ggcggcaaat gctggcagac ccacacccag 3240
taccgctgcg agtgccccag cggctggacc ggcctttact gcgacgtgcc cagcgtgtcc 3300
tgtgaggtgg ctgcgcagcg acaaggtgtt gacgttgccc gcctgtgcca gcatggaggg 3360
ctctgtgtgg acgcgggcaa cacgcaccac tgccgctgcc aggcgggcta cacaggcagc 3420
tactgtgagg acctggtgga cgagtgctca cccagcccct gccagaacgg ggccacctgc 3480
acggactacc tgggcggcta ctcctgcaag tgcgtggccg gctaccacgg ggtgaactgc 3540
tctgaggaga tcgacgagtg cctctcccac ccctgccaga acgggggcac ctgcctcgac 3600
ctccccaaca cctacaagtg ctcctgccca cggggcactc agggtgtgca ctgtgagatc 3660
aacgtggacg actgcaatcc ccccgttgac cccgtgtccc ggagccccaa gtgctttaac 3720
aacggcacct gcgtggacca ggtgggcggc tacagctgca cctgcccgcc gggcttcgtg 3780
ggtgagcgct gtgaggggga tgtcaacgag tgcctgtcca atccctgcga cgcccgtggc 3840
acccagaact gcgtgcagcg cgtcaatgac ttccactgcg agtgccgtgc tggtcacacc 3900
gggcgccgct gcgagtccgt catcaatggc tgcaaaggca agccctgcaa gaatgggggc 3960
acctgcgccg tggcctccaa caccgcccgc gggttcatct gcaagtgccc tgcgggcttc 4020
gagggcgcca cgtgtgagaa tgacgctcgt acctgcggca gcctgcgctg cctcaacggc 4080
ggcacatgca tctccggccc gcgcagcccc acctgcctgt gcctgggccc cttcacgggc 4140
cccgaatgcc agttcccggc cagcagcccc tgcctgggcg gcaacccctg ctacaaccag 4200
gggacctgtg agcccacatc cgagagcccc ttctaccgtt gcctgtgccc cgccaaattc 4260
aacgggctct tgtgccacat cctggactac agcttcgggg gtggggccgg gcgcgacatc 4320
cccccgccgc tgatcgagga ggcgtgcgag ctgcccgagt gccaggagga cgcgggcaac 4380
aaggtctgca gcctgcagtg caacaaccac gcgtgcggct gggacggcgg tgactgctcc 4440
ctcaacttca atgacccctg gaagaactgc acgcagtctc tgcagtgctg gaagtacttc 4500
agtgacggcc actgtgacag ccagtgcaac tcagccggct gcctcttcga cggctttgac 4560
tgccagcgtg cggaaggcca gtgcaacccc ctgtacgacc agtactgcaa ggaccacttc 4620
agcgacgggc actgcgacca gggctgcaac agcgcggagt gcgagtggga cgggctggac 4680
tgtgcggagc atgtacccga gaggctggcg gccggcacgc tggtggtggt ggtgctgatg 4740
ccgccggagc agctgcgcaa cagctccttc cacttcctgc gggagctcag ccgcgtgctg 4800
cacaccaacg tggtcttcaa gcgtgacgca cacggccagc agatgatctt cccctactac 4860
ggccgcgagg aggagctgcg caagcacccc atcaagcgtg ccgccgaggg ctgggccgca 4920
cctgacgccc tgctgggcca ggtgaaggcc tcgctgctcc ctggtggcag cgagggtggg 4980
cggcggcgga gggagctgga ccccatggac gtccgcggct ccatcgtcta cctggagatt 5040
gacaaccggc agtgtgtgca ggcctcctcg cagtgcttcc agagtgccac cgacgtggcc 5100
gcattcctgg gagcgctcgc ctcgctgggc agcctcaaca tcccctacaa gatcgaggcc 5160
gtgcagagtg agaccgtgga gccgcccccg ccggcgcagc tgcacttcat gtacgtggcg 5220
gcggccgcct ttgtgcttct gttcttcgtg ggctgcgggg tgctgctgtc ccgcaagcgc 5280
cggcggcagc atggccagct ctggttccct gagggcttca aagtgtctga ggccagcaag 5340
aagaagcggc gggagcccct cggcgaggac tccgtgggcc tcaagcccct gaagaacgct 5400
tcagacggtg ccctcatgga cgacaaccag aatgagtggg gggacgagga cctggagacc 5460
aagaagttcc ggttcgagga gcccgtggtt ctgcctgacc tggacgacca gacagaccac 5520
cggcagtgga ctcagcagca cctggatgcc gctgacctgc gcatgtctgc catggccccc 5580
acaccgcccc agggtgaggt tgacgccgac tgcatggacg tcaatgtccg cgggcctgat 5640
ggcttcaccc cgctcatgat cgcctcctgc agcgggggcg gcctggagac gggcaacagc 5700
gaggaagagg aggacgcgcc ggccgtcatc tccgacttca tctaccaggg cgccagcctg 5760
cacaaccaga cagaccgcac gggcgagacc gccttgcacc tggccgcccg ctactcacgc 5820
tctgatgccg ccaagcgcct gctggaggcc agcgcagatg ccaacatcca ggacaacatg 5880
ggccgcaccc cgctgcatgc ggctgtgtct gccgacgcac aaggtgtctt ccagatcctg 5940
atccggaacc gagccacaga cctggatgcc cgcatgcatg atggcacgac gccactgatc 6000
ctggctgccc gcctggccgt ggagggcatg ctggaggacc tcatcaactc acacgccgac 6060
gtcaacgccg tagatgacct gggcaagtcc gccctgcact gggccgccgc cgtgaacaat 6120
gtggatgccg cagttgtgct cctgaagaac ggggctaaca aagatatgca gaacaacagg 6180
gaggagacac ccctgtttct ggccgcccgg gagggcagct acgagaccgc caaggtgctg 6240
ctggaccact ttgccaaccg ggacatcacg gatcatatgg accgcctgcc gcgcgacatc 6300
gcacaggagc gcatgcatca cgacatcgtg aggctgctgg acgagtacaa cctggtgcgc 6360
agcccgcagc tgcacggagc cccgctgggg ggcacgccca ccctgtcgcc cccgctctgc 6420
tcgcccaacg gctacctggg cagcctcaag cccggcgtgc agggcaagaa ggtccgcaag 6480
cccagcagca aaggcctggc ctgtggaagc aaggaggcca aggacctcaa ggcacggagg 6540
aagaagtccc aggacggcaa gggctgcctg ctggacagct ccggcatgct ctcgcccgtg 6600
gactccctgg agtcacccca tggctacctg tcagacgtgg cctcgccgcc actgctgccc 6660
tccccgttcc agcagtctcc gtccgtgccc ctcaaccacc tgcctgggat gcccgacacc 6720
cacctgggca tcgggcacct gaacgtggcg gccaagcccg agatggcggc gctgggtggg 6780
ggcggccggc tggcctttga gactggccca cctcgtctct cccacctgcc tgtggcctct 6840
ggcaccagca ccgtcctggg ctccagcagc ggaggggccc tgaatttcac tgtgggcggg 6900
tccaccagtt tgaatggtca atgcgagtgg ctgtcccggc tgcagagcgg catggtgccg 6960
aaccaataca accctctgcg ggggagtgtg gcaccaggcc ccctgagcac acaggccccc 7020
tccctgcagc atggcatggt aggcccgctg cacagtagcc ttgctgccag cgccctgtcc 7080
cagatgatga gctaccaggg cctgcccagc acccggctgg ccacccagcc tcacctggtg 7140
cagacccagc aggtgcagcc acaaaactta cagatgcagc agcagaacct gcagccagca 7200
aacatccagc agcagcaaag cctgcagccg ccaccaccac caccacagcc gcaccttggc 7260
gtgagctcag cagccagcgg ccacctgggc cggagcttcc tgagtggaga gccgagccag 7320
gcagacgtgc agccactggg ccccagcagc ctggcggtgc acactattct gccccaggag 7380
agccccgccc tgcccacgtc gctgccatcc tcgctggtcc cacccgtgac cgcagcccag 7440
ttcctgacgc ccccctcgca gcacagctac tcctcgcctg tggacaacac ccccagccac 7500
cagctacagg tgcctgagca ccccttcctc accccgtccc ctgagtcccc tgaccagtgg 7560
tccagctcgt ccccgcattc caacgtctcc gactggtccg agggcgtctc cagccctccc 7620
accagcatgc agtcccagat cgcccgcatt ccggaggcct tcaagtaaac ggcgcgcccc 7680
acgagacccc ggcttccttt cccaagcctt cgggcgtctg tgtgcgctct gtggatgcca 7740
gggccgacca gaggagcctt tttaaaacac atgtttttat acaaaataag aacgaggatt 7800
ttaatttttt ttagtattta tttatgtact tttattttac acagaaacac tgccttttta 7860
tttatatgta ctgttttatc tggccccagg tagaaacttt tatctattct gagaaaacaa 7920
gcaagttctg agagccaggg ttttcctacg taggatgaaa agattcttct gtgtttataa 7980
aatataaaca aagattcatg atttataaat gccatttatt tattgattcc ttttttcaaa 8040
atccaaaaag aaatgatgtt ggagaaggga agttgaacga gcatagtcca aaaagctcct 8100
ggggcgtcca ggccgcgccc tttccccgac gcccacccaa ccccaagcca gcccggccgc 8160
tccaccagca tcacctgcct gttaggagaa gctgcatcca gaggcaaacg gaggcaaagc 8220
tggctcacct tccgcacgcg gattaatttg catctgaaat aggaaacaag tgaaagcata 8280
tgggttagat gttgccatgt gttttagatg gtttcttgca agcatgcttg tgaaaatgtg 8340
ttctcggagt gtgtatgcca agagtgcacc catggtacca atcatgaatc tttgtttcag 8400
gttcagtatt atgtagttgt tcgttggtta tacaagttct tggtccctcc agaaccaccc 8460
cggccccctg cccgttcttg aaatgtaggc atcatgcatg tcaaacatga gatgtgtgga 8520
ctgtggcact tgcctgggtc acacacggag gcatcctacc cttttctggg gaaagacact 8580
gcctgggctg accccggtgg cggccccagc acctcagcct gcacagtgtc ccccaggttc 8640
cgaagaagat gctccagcaa cacagcctgg gccccagctc gcgggacccg accccccgtg 8700
ggctcccgtg ttttgtagga gacttgccag agccgggcac attgagctgt gcaacgccgt 8760
gggctgcgtc ctttggtcct gtccccgcag ccctggcagg gggcatgcgg tcgggcaggg 8820
gctggaggga ggcgggggct gcccttgggc cacccctcct agtttgggag gagcagattt 8880
ttgcaatacc aagtatagcc tatggcagaa aaaatgtctg taaatatgtt tttaaaggtg 8940
gattttgttt aaaaaatctt aatgaatgag tctgttgtgt gtcatgccag tgagggacgt 9000
cagacttggc tcagctcggg gagccttagc cgcccatgca ctggggacgc tccgctgccg 9060
tgccgcctgc actcctcagg gcagcctccc ccggctctac gggggccgcg tggtgccatc 9120
cccagggggc atgaccagat gcgtcccaag atgttgattt ttactgtgtt ttataaaata 9180
gagtgtagtt tacagaaaaa gactttaaaa gtgatctaca tgaggaactg tagatgatgt 9240
atttttttca tcttttttgt taactgattt gcaataaaaa tgatactgat ggtgatctgg 9300
cttccaaaaa aaaaaaaaaa aa 9322
<210> 30
<211> 11474
<212> DNA
<213> 人
<400> 30
gcttgcggtg ggaggaggcg gctgaggcgg aaggacacac gaggctgctt cgttgcacac 60
ccgagaaagt ttcagccaaa cttcgggcgg cggctgaggc ggcggccgag gagcggcgga 120
ctcggggcgc ggggagtcga ggcatttgcg cctgggcttc ggagcgtagc gccagggcct 180
gagcctttga agcaggagga ggggaggaga gagtggggct cctctatcgg gaccccctcc 240
ccatgtggat ctgcccaggc ggcggcggcg gcggcggagg aggaggcgac cgagaagatg 300
cccgccctgc gccccgctct gctgtgggcg ctgctggcgc tctggctgtg ctgcgcggcc 360
cccgcgcatg cattgcagtg tcgagatggc tatgaaccct gtgtaaatga aggaatgtgt 420
gttacctacc acaatggcac aggatactgc aaatgtccag aaggcttctt gggggaatat 480
tgtcaacatc gagacccctg tgagaagaac cgctgccaga atggtgggac ttgtgtggcc 540
caggccatgc tggggaaagc cacgtgccga tgtgcctcag ggtttacagg agaggactgc 600
cagtactcaa catctcatcc atgctttgtg tctcgaccct gcctgaatgg cggcacatgc 660
catatgctca gccgggatac ctatgagtgc acctgtcaag tcgggtttac aggtaaggag 720
tgccaatgga cggatgcctg cctgtctcat ccctgtgcaa atggaagtac ctgtaccact 780
gtggccaacc agttctcctg caaatgcctc acaggcttca cagggcagaa atgtgagact 840
gatgtcaatg agtgtgacat tccaggacac tgccagcatg gtggcacctg cctcaacctg 900
cctggttcct accagtgcca gtgccctcag ggcttcacag gccagtactg tgacagcctg 960
tatgtgccct gtgcaccctc accttgtgtc aatggaggca cctgtcggca gactggtgac 1020
ttcacttttg agtgcaactg ccttccaggt tttgaaggga gcacctgtga gaggaatatt 1080
gatgactgcc ctaaccacag gtgtcagaat ggaggggttt gtgtggatgg ggtcaacact 1140
tacaactgcc gctgtccccc acaatggaca ggacagttct gcacagagga tgtggatgaa 1200
tgcctgctgc agcccaatgc ctgtcaaaat gggggcacct gtgccaaccg caatggaggc 1260
tatggctgtg tatgtgtcaa cggctggagt ggagatgact gcagtgagaa cattgatgat 1320
tgtgccttcg cctcctgtac tccaggctcc acctgcatcg accgtgtggc ctccttctct 1380
tgcatgtgcc cagaggggaa ggcaggtctc ctgtgtcatc tggatgatgc atgcatcagc 1440
aatccttgcc acaagggggc actgtgtgac accaaccccc taaatgggca atatatttgc 1500
acctgcccac aaggctacaa aggggctgac tgcacagaag atgtggatga atgtgccatg 1560
gccaatagca atccttgtga gcatgcagga aaatgtgtga acacggatgg cgccttccac 1620
tgtgagtgtc tgaagggtta tgcaggacct cgttgtgaga tggacatcaa tgagtgccat 1680
tcagacccct gccagaatga tgctacctgt ctggataaga ttggaggctt cacatgtctg 1740
tgcatgccag gtttcaaagg tgtgcattgt gaattagaaa taaatgaatg tcagagcaac 1800
ccttgtgtga acaatgggca gtgtgtggat aaagtcaatc gtttccagtg cctgtgtcct 1860
cctggtttca ctgggccagt ttgccagatt gatattgatg actgttccag tactccgtgt 1920
ctgaatgggg caaagtgtat cgatcacccg aatggctatg aatgccagtg tgccacaggt 1980
ttcactggtg tgttgtgtga ggagaacatt gacaactgtg accccgatcc ttgccaccat 2040
ggtcagtgtc aggatggtat tgattcctac acctgcatct gcaatcccgg gtacatgggc 2100
gccatctgca gtgaccagat tgatgaatgt tacagcagcc cttgcctgaa cgatggtcgc 2160
tgcattgacc tggtcaatgg ctaccagtgc aactgccagc caggcacgtc aggggttaat 2220
tgtgaaatta attttgatga ctgtgcaagt aacccttgta tccatggaat ctgtatggat 2280
ggcattaatc gctacagttg tgtctgctca ccaggattca cagggcagag atgtaacatt 2340
gacattgatg agtgtgcctc caatccctgt cgcaagggtg caacatgtat caacggtgtg 2400
aatggtttcc gctgtatatg ccccgaggga ccccatcacc ccagctgcta ctcacaggtg 2460
aacgaatgcc tgagcaatcc ctgcatccat ggaaactgta ctggaggtct cagtggatat 2520
aagtgtctct gtgatgcagg ctgggttggc atcaactgtg aagtggacaa aaatgaatgc 2580
ctttcgaatc catgccagaa tggaggaact tgtgacaatc tggtgaatgg atacaggtgt 2640
acttgcaaga agggctttaa aggctataac tgccaggtga atattgatga atgtgcctca 2700
aatccatgcc tgaaccaagg aacctgcttt gatgacataa gtggctacac ttgccactgt 2760
gtgctgccat acacaggcaa gaattgtcag acagtattgg ctccctgttc cccaaaccct 2820
tgtgagaatg ctgctgtttg caaagagtca ccaaattttg agagttatac ttgcttgtgt 2880
gctcctggct ggcaaggtca gcggtgtacc attgacattg acgagtgtat ctccaagccc 2940
tgcatgaacc atggtctctg ccataacacc cagggcagct acatgtgtga atgtccacca 3000
ggcttcagtg gtatggactg tgaggaggac attgatgact gccttgccaa tccttgccag 3060
aatggaggtt cctgtatgga tggagtgaat actttctcct gcctctgcct tccgggtttc 3120
actggggata agtgccagac agacatgaat gagtgtctga gtgaaccctg taagaatgga 3180
gggacctgct ctgactacgt caacagttac acttgcaagt gccaggcagg atttgatgga 3240
gtccattgtg agaacaacat caatgagtgc actgagagct cctgtttcaa tggtggcaca 3300
tgtgttgatg ggattaactc cttctcttgc ttgtgccctg tgggtttcac tggatccttc 3360
tgcctccatg agatcaatga atgcagctct catccatgcc tgaatgaggg aacgtgtgtt 3420
gatggcctgg gtacctaccg ctgcagctgc cccctgggct acactgggaa aaactgtcag 3480
accctggtga atctctgcag tcggtctcca tgtaaaaaca aaggtacttg cgttcagaaa 3540
aaagcagagt cccagtgcct atgtccatct ggatgggctg gtgcctattg tgacgtgccc 3600
aatgtctctt gtgacatagc agcctccagg agaggtgtgc ttgttgaaca cttgtgccag 3660
cactcaggtg tctgcatcaa tgctggcaac acgcattact gtcagtgccc cctgggctat 3720
actgggagct actgtgagga gcaactcgat gagtgtgcgt ccaacccctg ccagcacggg 3780
gcaacatgca gtgacttcat tggtggatac agatgcgagt gtgtcccagg ctatcagggt 3840
gtcaactgtg agtatgaagt ggatgagtgc cagaatcagc cctgccagaa tggaggcacc 3900
tgtattgacc ttgtgaacca tttcaagtgc tcttgcccac caggcactcg gggcctactc 3960
tgtgaagaga acattgatga ctgtgcccgg ggtccccatt gccttaatgg tggtcagtgc 4020
atggatagga ttggaggcta cagttgtcgc tgcttgcctg gctttgctgg ggagcgttgt 4080
gagggagaca tcaacgagtg cctctccaac ccctgcagct ctgagggcag cctggactgt 4140
atacagctca ccaatgacta cctgtgtgtt tgccgtagtg cctttactgg ccggcactgt 4200
gaaaccttcg tcgatgtgtg tccccagatg ccctgcctga atggagggac ttgtgctgtg 4260
gccagtaaca tgcctgatgg tttcatttgc cgttgtcccc cgggattttc cggggcaagg 4320
tgccagagca gctgtggaca agtgaaatgt aggaaggggg agcagtgtgt gcacaccgcc 4380
tctggacccc gctgcttctg ccccagtccc cgggactgcg agtcaggctg tgccagtagc 4440
ccctgccagc acgggggcag ctgccaccct cagcgccagc ctccttatta ctcctgccag 4500
tgtgccccac cattctcggg tagccgctgt gaactctaca cggcaccccc cagcacccct 4560
cctgccacct gtctgagcca gtattgtgcc gacaaagctc gggatggcgt ctgtgatgag 4620
gcctgcaaca gccatgcctg ccagtgggat gggggtgact gttctctcac catggagaac 4680
ccctgggcca actgctcctc cccacttccc tgctgggatt atatcaacaa ccagtgtgat 4740
gagctgtgca acacggtcga gtgcctgttt gacaactttg aatgccaggg gaacagcaag 4800
acatgcaagt atgacaaata ctgtgcagac cacttcaaag acaaccactg tgaccagggg 4860
tgcaacagtg aggagtgtgg ttgggatggg ctggactgtg ctgctgacca acctgagaac 4920
ctggcagaag gtaccctggt tattgtggta ttgatgccac ctgaacaact gctccaggat 4980
gctcgcagct tcttgcgggc actgggtacc ctgctccaca ccaacctgcg cattaagcgg 5040
gactcccagg gggaactcat ggtgtacccc tattatggtg agaagtcagc tgctatgaag 5100
aaacagagga tgacacgcag atcccttcct ggtgaacaag aacaggaggt ggctggctct 5160
aaagtctttc tggaaattga caaccgccag tgtgttcaag actcagacca ctgcttcaag 5220
aacacggatg cagcagcagc tctcctggcc tctcacgcca tacaggggac cctgtcatac 5280
cctcttgtgt ctgtcgtcag tgaatccctg actccagaac gcactcagct cctctatctc 5340
cttgctgttg ctgttgtcat cattctgttt attattctgc tgggggtaat catggcaaaa 5400
cgaaagcgta agcatggctc tctctggctg cctgaaggtt tcactcttcg ccgagatgca 5460
agcaatcaca agcgtcgtga gccagtggga caggatgctg tggggctgaa aaatctctca 5520
gtgcaagtct cagaagctaa cctaattggt actggaacaa gtgaacactg ggtcgatgat 5580
gaagggcccc agccaaagaa agtaaaggct gaagatgagg ccttactctc agaagaagat 5640
gaccccattg atcgacggcc atggacacag cagcaccttg aagctgcaga catccgtagg 5700
acaccatcgc tggctctcac ccctcctcag gcagagcagg aggtggatgt gttagatgtg 5760
aatgtccgtg gcccagatgg ctgcacccca ttgatgttgg cttctctccg aggaggcagc 5820
tcagatttga gtgatgaaga tgaagatgca gaggactctt ctgctaacat catcacagac 5880
ttggtctacc agggtgccag cctccaggcc cagacagacc ggactggtga gatggccctg 5940
caccttgcag cccgctactc acgggctgat gctgccaagc gtctcctgga tgcaggtgca 6000
gatgccaatg cccaggacaa catgggccgc tgtccactcc atgctgcagt ggcagctgat 6060
gcccaaggtg tcttccagat tctgattcgc aaccgagtaa ctgatctaga tgccaggatg 6120
aatgatggta ctacacccct gatcctggct gcccgcctgg ctgtggaggg aatggtggca 6180
gaactgatca actgccaagc ggatgtgaat gcagtggatg accatggaaa atctgctctt 6240
cactgggcag ctgctgtcaa taatgtggag gcaactcttt tgttgttgaa aaatggggcc 6300
aaccgagaca tgcaggacaa caaggaagag acacctctgt ttcttgctgc ccgggagggg 6360
agctatgaag cagccaagat cctgttagac cattttgcca atcgagacat cacagaccat 6420
atggatcgtc ttccccggga tgtggctcgg gatcgcatgc accatgacat tgtgcgcctt 6480
ctggatgaat acaatgtgac cccaagccct ccaggcaccg tgttgacttc tgctctctca 6540
cctgtcatct gtgggcccaa cagatctttc ctcagcctga agcacacccc aatgggcaag 6600
aagtctagac ggcccagtgc caagagtacc atgcctacta gcctccctaa ccttgccaag 6660
gaggcaaagg atgccaaggg tagtaggagg aagaagtctc tgagtgagaa ggtccaactg 6720
tctgagagtt cagtaacttt atcccctgtt gattccctag aatctcctca cacgtatgtt 6780
tccgacacca catcctctcc aatgattaca tcccctggga tcttacaggc ctcacccaac 6840
cctatgttgg ccactgccgc ccctcctgcc ccagtccatg cccagcatgc actatctttt 6900
tctaaccttc atgaaatgca gcctttggca catggggcca gcactgtgct tccctcagtg 6960
agccagttgc tatcccacca ccacattgtg tctccaggca gtggcagtgc tggaagcttg 7020
agtaggctcc atccagtccc agtcccagca gattggatga accgcatgga ggtgaatgag 7080
acccagtaca atgagatgtt tggtatggtc ctggctccag ctgagggcac ccatcctggc 7140
atagctcccc agagcaggcc acctgaaggg aagcacataa ccacccctcg ggagcccttg 7200
ccccccattg tgactttcca gctcatccct aaaggcagta ttgcccaacc agcgggggct 7260
ccccagcctc agtccacctg ccctccagct gttgcgggcc ccctgcccac catgtaccag 7320
attccagaaa tggcccgttt gcccagtgtg gctttcccca ctgccatgat gccccagcag 7380
gacgggcagg tagctcagac cattctccca gcctatcatc ctttcccagc ctctgtgggc 7440
aagtacccca cacccccttc acagcacagt tatgcttcct caaatgctgc tgagcgaaca 7500
cccagtcaca gtggtcacct ccagggtgag catccctacc tgacaccatc cccagagtct 7560
cctgaccagt ggtcaagttc atcaccccac tctgcttctg actggtcaga tgtgaccacc 7620
agccctaccc ctgggggtgc tggaggaggt cagcggggac ctgggacaca catgtctgag 7680
ccaccacaca acaacatgca ggtttatgcg tgagagagtc cacctccagt gtagagacat 7740
aactgacttt tgtaaatgct gctgaggaac aaatgaaggt catccgggag agaaatgaag 7800
aaatctctgg agccagcttc tagaggtagg aaagagaaga tgttcttatt cagataatgc 7860
aagagaagca attcgtcagt ttcactgggt atctgcaagg cttattgatt attctaatct 7920
aataagacaa gtttgtggaa atgcaagatg aatacaagcc ttgggtccat gtttactctc 7980
ttctatttgg agaataagat ggatgcttat tgaagcccag acattcttgc agcttggact 8040
gcattttaag ccctgcaggc ttctgccata tccatgagaa gattctacac tagcgtcctg 8100
ttgggaatta tgccctggaa ttctgcctga attgacctac gcatctcctc ctccttggac 8160
attcttttgt cttcatttgg tgcttttggt tttgcacctc tccgtgattg tagccctacc 8220
agcatgttat agggcaagac ctttgtgctt ttgatcattc tggcccatga aagcaacttt 8280
ggtctccttt cccctcctgt cttcccggta tcccttggag tctcacaagg tttactttgg 8340
tatggttctc agcacaaacc tttcaagtat gttgtttctt tggaaaatgg acatactgta 8400
ttgtgttctc ctgcatatat cattcctgga gagagaaggg gagaagaata cttttcttca 8460
acaaattttg ggggcaggag atcccttcaa gaggctgcac cttaattttt cttgtctgtg 8520
tgcaggtctt catataaact ttaccaggaa gaagggtgtg agtttgttgt ttttctgtgt 8580
atgggcctgg tcagtgtaaa gttttatcct tgatagtcta gttactatga ccctccccac 8640
ttttttaaaa ccagaaaaag gtttggaatg ttggaatgac caagagacaa gttaactcgt 8700
gcaagagcca gttacccacc cacaggtccc cctacttcct gccaagcatt ccattgactg 8760
cctgtatgga acacatttgt cccagatctg agcattctag gcctgtttca ctcactcacc 8820
cagcatatga aactagtctt aactgttgag cctttccttt catatccaca gaagacactg 8880
tctcaaatgt tgtacccttg ccatttagga ctgaactttc cttagcccaa gggacccagt 8940
gacagttgtc ttccgtttgt cagatgatca gtctctactg attatcttgc tgcttaaagg 9000
cctgctcacc aatctttctt tcacaccgtg tggtccgtgt tactggtata cccagtatgt 9060
tctcactgaa gacatggact ttatatgttc aagtgcagga attggaaagt tggacttgtt 9120
ttctatgatc caaaacagcc ctataagaag gttggaaaag gaggaactat atagcagcct 9180
ttgctatttt ctgctaccat ttcttttcct ctgaagcggc catgacattc cctttggcaa 9240
ctaacgtaga aactcaacag aacattttcc tttcctagag tcacctttta gatgataatg 9300
gacaactata gacttgctca ttgttcagac tgattgcccc tcacctgaat ccactctctg 9360
tattcatgct cttggcaatt tctttgactt tcttttaagg gcagaagcat tttagttaat 9420
tgtagataaa gaatagtttt cttcctcttc tccttgggcc agttaataat tggtccatgg 9480
ctacactgca acttccgtcc agtgctgtga tgcccatgac acctgcaaaa taagttctgc 9540
ctgggcattt tgtagatatt aacaggtgaa ttcccgactc ttttggtttg aatgacagtt 9600
ctcattcctt ctatggctgc aagtatgcat cagtgcttcc cacttacctg atttgtctgt 9660
cggtggcccc atatggaaac cctgcgtgtc tgttggcata atagtttaca aatggttttt 9720
tcagtcctat ccaaatttat tgaaccaaca aaaataatta cttctgccct gagataagca 9780
gattaagttt gttcattctc tgctttattc tctccatgtg gcaacattct gtcagcctct 9840
ttcatagtgt gcaaacattt tatcattcta aatggtgact ctctgccctt ggacccattt 9900
attattcaca gatggggaga acctatctgc atggacctct gtggaccaca gcgtacctgc 9960
ccctttctgc cctcctgctc cagccccact tctgaaagta tcagctactg atccagccac 10020
tggatatttt atatcctccc ttttccttaa gcacaatgtc agaccaaatt gcttgtttct 10080
ttttcttgga ctactttaat ttggatcctt tgggtttgga gaaagggaat gtgaaagctg 10140
tcattacaga caacaggttt cagtgatgag gaggacaaca ctgcctttca aactttttac 10200
tgatctctta gattttaaga actcttgaat tgtgtggtat ctaataaaag ggaaggtaag 10260
atggataatc actttctcat ttgggttctg aattggagac tcagttttta tgagacacat 10320
cttttatgcc atgtatagat cctcccctgc tatttttggt ttatttttat tgttataaat 10380
gctttctttc tttgactcct cttctgcctg cctttgggga taggtttttt tgtttgttta 10440
tttgcttcct ctgttttgtt ttaagcatca ttttcttatg tgaggtgggg aagggaaagg 10500
tatgagggaa agagagtctg agaattaaaa tattttagta taagcaattg gctgtgatgc 10560
tcaaatccat tgcatcctct tattgaattt gccaatttgt aatttttgca taataaagaa 10620
ccaaaggtgt aatgttttgt tgagaggtgg tttagggatt ttggccctaa ccaatacatt 10680
gaatgtatga tgactatttg ggaggacaca tttatgtacc cagaggcccc cactaataag 10740
tggtactatg gttacttcct tgtgtacatt tctcttaaaa gtgatattat atctgtttgt 10800
atgagaaacc cagtaaccaa taaaatgacc gcatattcct gactaaacgt agtaaggaaa 10860
atgcacactt tgtttttact tttccgtttc attctaaagg tagttaagat gaaatttata 10920
tgaaagcatt tttatcacaa aataaaaaag gtttgccaag ctcagtggtg ttgtattttt 10980
tattttccaa tactgcatcc atggcctggc agtgttacct catgatgtca taatttgctg 11040
agagagcaaa ttttcttttc tttctgaatc ccacaaagcc tagcaccaaa cttctttttt 11100
tcttccttta attagatcat aaataaatga tcctggggaa aaagcatctg tcaaatagga 11160
aacatcacaa aactgagcac tcttctgtgc actagccata gctggtgaca aacagatggt 11220
tgctcaggga caaggtgcct tccaatggaa atgcgaagta gttgctatag caagaattgg 11280
gaactgggat ataagtcata atattaatta tgctgttatg taaatgattg gtttgtaaca 11340
ttccttaagt gaaatttgtg tagaacttaa tatacaggat tataaaataa tattttgtgt 11400
ataaatttgt tataagttca cattcataca tttatttata aagtcagtga gatatttgaa 11460
catgaaaaaa aaaa 11474
<210> 31
<211> 4326
<212> DNA
<213> 人
<400> 31
gcttgcggtg ggaggaggcg gctgaggcgg aaggacacac gaggctgctt cgttgcacac 60
ccgagaaagt ttcagccaaa cttcgggcgg cggctgaggc ggcggccgag gagcggcgga 120
ctcggggcgc ggggagtcga ggcatttgcg cctgggcttc ggagcgtagc gccagggcct 180
gagcctttga agcaggagga ggggaggaga gagtggggct cctctatcgg gaccccctcc 240
ccatgtggat ctgcccaggc ggcggcggcg gcggcggagg aggaggcgac cgagaagatg 300
cccgccctgc gccccgctct gctgtgggcg ctgctggcgc tctggctgtg ctgcgcggcc 360
cccgcgcatg cattgcagtg tcgagatggc tatgaaccct gtgtaaatga aggaatgtgt 420
gttacctacc acaatggcac aggatactgc aaatgtccag aaggcttctt gggggaatat 480
tgtcaacatc gagacccctg tgagaagaac cgctgccaga atggtgggac ttgtgtggcc 540
caggccatgc tggggaaagc cacgtgccga tgtgcctcag ggtttacagg agaggactgc 600
cagtactcaa catctcatcc atgctttgtg tctcgaccct gcctgaatgg cggcacatgc 660
catatgctca gccgggatac ctatgagtgc acctgtcaag tcgggtttac aggtaaggag 720
tgccaatgga cggatgcctg cctgtctcat ccctgtgcaa atggaagtac ctgtaccact 780
gtggccaacc agttctcctg caaatgcctc acaggcttca cagggcagaa atgtgagact 840
gatgtcaatg agtgtgacat tccaggacac tgccagcatg gtggcacctg cctcaacctg 900
cctggttcct accagtgcca gtgccctcag ggcttcacag gccagtactg tgacagcctg 960
tatgtgccct gtgcaccctc accttgtgtc aatggaggca cctgtcggca gactggtgac 1020
ttcacttttg agtgcaactg ccttccaggt tttgaaggga gcacctgtga gaggaatatt 1080
gatgactgcc ctaaccacag gtgtcagaat ggaggggttt gtgtggatgg ggtcaacact 1140
tacaactgcc gctgtccccc acaatggaca ggacagttct gcacagagga tgtggatgaa 1200
tgcctgctgc agcccaatgc ctgtcaaaat gggggcacct gtgccaaccg caatggaggc 1260
tatggctgtg tatgtgtcaa cggctggagt ggagatgact gcagtgagaa cattgatgat 1320
tgtgccttcg cctcctgtac tccaggctcc acctgcatcg accgtgtggc ctccttctct 1380
tgcatgtgcc cagaggggaa ggcaggtctc ctgtgtcatc tggatgatgc atgcatcagc 1440
aatccttgcc acaagggggc actgtgtgac accaaccccc taaatgggca atatatttgc 1500
acctgcccac aaggctacaa aggggctgac tgcacagaag atgtggatga atgtgccatg 1560
gccaatagca atccttgtga gcatgcagga aaatgtgtga acacggatgg cgccttccac 1620
tgtgagtgtc tgaagggtta tgcaggacct cgttgtgaga tggacatcaa tgagtgccat 1680
tcagacccct gccagaatga tgctacctgt ctggataaga ttggaggctt cacatgtctg 1740
tgcatgccag gtttcaaagg tgtgcattgt gaattagaaa taaatgaatg tcagagcaac 1800
ccttgtgtga acaatgggca gtgtgtggat aaagtcaatc gtttccagtg cctgtgtcct 1860
cctggtttca ctgggccagt ttgccagatt gatattgatg actgttccag tactccgtgt 1920
ctgaatgggg caaagtgtat cgatcacccg aatggctatg aatgccagtg tgccacaggt 1980
ttcactggtg tgttgtgtga ggagaacatt gacaactgtg accccgatcc ttgccaccat 2040
ggtcagtgtc aggatggtat tgattcctac acctgcatct gcaatcccgg gtacatgggc 2100
gccatctgca gtgaccagat tgatgaatgt tacagcagcc cttgcctgaa cgatggtcgc 2160
tgcattgacc tggtcaatgg ctaccagtgc aactgccagc caggcacgtc aggggttaat 2220
tgtgaaatta attttgatga ctgtgcaagt aacccttgta tccatggaat ctgtatggat 2280
ggcattaatc gctacagttg tgtctgctca ccaggattca cagggcagag atgtaacatt 2340
gacattgatg agtgtgcctc caatccctgt cgcaagggtg caacatgtat caacggtgtg 2400
aatggtttcc gctgtatatg ccccgaggga ccccatcacc ccagctgcta ctcacaggtg 2460
aacgaatgcc tgagcaatcc ctgcatccat ggaaactgta ctggaggtct cagtggatat 2520
aagtgtctct gtgatgcagg ctgggttggc atcaactgtg aagtggacaa aaatgaatgc 2580
ctttcgaatc catgccagaa tggaggaact tgtgacaatc tggtgaatgg atacaggtgt 2640
acttgcaaga agggctttaa aggctataac tgccaggtga atattgatga atgtgcctca 2700
aatccatgcc tgaaccaagg aacctgcttt gatgacataa gtggctacac ttgccactgt 2760
gtgctgccat acacaggcaa gaattgtcag acagtattgg ctccctgttc cccaaaccct 2820
tgtgagaatg ctgctgtttg caaagagtca ccaaattttg agagttatac ttgcttgtgt 2880
gctcctggct ggcaaggtca gcggtgtacc attgacattg acgagtgtat ctccaagccc 2940
tgcatgaacc atggtctctg ccataacacc cagggcagct acatgtgtga atgtccacca 3000
ggcttcagtg gtatggactg tgaggaggac attgatgact gccttgccaa tccttgccag 3060
aatggaggtt cctgtatgga tggagtgaat actttctcct gcctctgcct tccgggtttc 3120
actggggata agtgccagac agacatgaat gagtgtctga gtgaaccctg taagaatgga 3180
gggacctgct ctgactacgt caacagttac acttgcaagt gccaggcagg atttgatgga 3240
gtccattgtg agaacaacat caatgagtgc actgagagct cctgtttcaa tggtggcaca 3300
tgtgttgatg ggattaactc cttctcttgc ttgtgccctg tgggtttcac tggatccttc 3360
tgcctccatg agatcaatga atgcagctct catccatgcc tgaatgaggg aacgtgtgtt 3420
gatggcctgg gtacctaccg ctgcagctgc cccctgggct acactgggaa aaactgtcag 3480
accctggtga atctctgcag tcggtctcca tgtaaaaaca aaggtacttg cgttcagaaa 3540
aaagcagagt cccagtgcct atgtccatct ggatgggctg gtgcctattg tgacgtgccc 3600
aatgtctctt gtgacatagc agcctccagg agaggtgtgc ttgttgaaca cttgtgccag 3660
cactcaggtg tctgcatcaa tgctggcaac acgcattact gtcagtgccc cctgggctat 3720
actgggagct actgtgagga gcaactcgat gagtgtgcgt ccaacccctg ccagcacggg 3780
gcaacatgca gtgacttcat tggtggatac agatgcgagt gtgtcccagg ctatcagggt 3840
gtcaactgtg agtatgaagt ggatgagtgc cagaatcagc cctgccagaa tggaggcacc 3900
tgtattgacc ttgtgaacca tttcaagtgc tcttgcccac caggcactcg gggtatgaaa 3960
tcatccttat ccattttcca tccagggcat tgtcttaagt tataaatcca ttcttagtgt 4020
tcaggggatt ttataaaatt aaagatagga agactagctt cattccaagc atttagttct 4080
acatcctagt aattcaagcc attttattct cccatctctt gctagctctg atgttgtggt 4140
ttatgttgtc agttttatct ggttgtttgg catcttgata ttccatgaaa cacagaatat 4200
ggaagggata caacattagc ataacattaa aaaattagcc tggtcagtaa gatttcttgt 4260
tgcttcacag aaaagcaact aatggcctct aaaataaaca atttacattt aaaaaaaaaa 4320
aaaaaa 4326
<210> 32
<211> 8089
<212> DNA
<213> 人
<400> 32
gcggcgcgga ggctggcccg ggacgcgccc ggagcccagg gaaggaggga ggaggggagg 60
gtcgcggccg gccgccatgg ggccgggggc ccgtggccgc cgccgccgcc gtcgcccgat 120
gtcgccgcca ccgccaccgc cacccgtgcg ggcgctgccc ctgctgctgc tgctagcggg 180
gccgggggct gcagcccccc cttgcctgga cggaagcccg tgtgcaaatg gaggtcgttg 240
cacccagctg ccctcccggg aggctgcctg cctgtgcccg cctggctggg tgggtgagcg 300
gtgtcagctg gaggacccct gtcactcagg cccctgtgct ggccgtggtg tctgccagag 360
ttcagtggtg gctggcaccg cccgattctc atgccggtgc ccccgtggct tccgaggccc 420
tgactgctcc ctgccagatc cctgcctcag cagcccttgt gcccacggtg cccgctgctc 480
agtggggccc gatggacgct tcctctgctc ctgcccacct ggctaccagg gccgcagctg 540
ccgaagcgac gtggatgagt gccgggtggg tgagccctgc cgccatggtg gcacctgcct 600
caacacacct ggctccttcc gctgccagtg tccagctggc tacacagggc cactatgtga 660
gaaccccgcg gtgccctgtg caccctcacc atgccgtaac gggggcacct gcaggcagag 720
tggcgacctc acttacgact gtgcctgtct tcctgggttt gagggtcaga attgtgaagt 780
gaacgtggac gactgtccag gacaccgatg tctcaatggg gggacatgcg tggatggcgt 840
caacacctat aactgccagt gccctcctga gtggacaggc cagttctgca cggaggacgt 900
ggatgagtgt cagctgcagc ccaacgcctg ccacaatggg ggtacctgct tcaacacgct 960
gggtggccac agctgcgtgt gtgtcaatgg ctggacaggc gagagctgca gtcagaatat 1020
cgatgactgt gccacagccg tgtgcttcca tggggccacc tgccatgacc gcgtggcttc 1080
tttctactgt gcctgcccca tgggcaagac tggcctcctg tgtcacctgg atgacgcctg 1140
tgtcagcaac ccctgccacg aggatgctat ctgtgacaca aatccggtga acggccgggc 1200
catttgcacc tgtcctcccg gcttcacggg tggggcatgt gaccaggatg tggacgagtg 1260
ctctatcggc gccaacccct gcgagcactt gggcaggtgc gtgaacacgc agggctcctt 1320
cctgtgccag tgcggtcgtg gctacactgg acctcgctgt gagaccgatg tcaacgagtg 1380
tctgtcgggg ccctgccgaa accaggccac gtgcctcgac cgcataggcc agttcacctg 1440
tatctgtatg gcaggcttca caggaaccta ttgcgaggtg gacattgacg agtgtcagag 1500
tagcccctgt gtcaacggtg gggtctgcaa ggaccgagtc aatggcttca gctgcacctg 1560
cccctcgggc ttcagcggct ccacgtgtca gctggacgtg gacgaatgcg ccagcacgcc 1620
ctgcaggaat ggcgccaaat gcgtggacca gcccgatggc tacgagtgcc gctgtgccga 1680
gggctttgag ggcacgctgt gtgatcgcaa cgtggacgac tgctcccctg acccatgcca 1740
ccatggtcgc tgcgtggatg gcatcgccag cttctcatgt gcctgtgctc ctggctacac 1800
gggcacacgc tgcgagagcc aggtggacga atgccgcagc cagccctgcc gccatggcgg 1860
caaatgccta gacctggtgg acaagtacct ctgccgctgc ccttctggga ccacaggtgt 1920
gaactgcgaa gtgaacattg acgactgtgc cagcaacccc tgcacctttg gagtctgccg 1980
tgatggcatc aaccgctacg actgtgtctg ccaacctggc ttcacagggc ccctttgtaa 2040
cgtggagatc aatgagtgtg cttccagccc atgcggcgag ggaggttcct gtgtggatgg 2100
ggaaaatggc ttccgctgcc tctgcccgcc tggctccttg cccccactct gcctcccccc 2160
gagccatccc tgtgcccatg agccctgcag tcacggcatc tgctatgatg cacctggcgg 2220
gttccgctgt gtgtgtgagc ctggctggag tggcccccgc tgcagccaga gcctggcccg 2280
agacgcctgt gagtcccagc cgtgcagggc cggtgggaca tgcagcagcg atggaatggg 2340
tttccactgc acctgcccgc ctggtgtcca gggacgtcag tgtgaactcc tctccccctg 2400
caccccgaac ccctgtgagc atgggggccg ctgcgagtct gcccctggcc agctgcctgt 2460
ctgctcctgc ccccagggct ggcaaggccc acgatgccag caggatgtgg acgagtgtgc 2520
tggccccgca ccctgtggcc ctcatggtat ctgcaccaac ctggcaggga gtttcagctg 2580
cacctgccat ggagggtaca ctggcccttc ctgcgatcag gacatcaatg actgtgaccc 2640
caacccatgc ctgaacggtg gctcgtgcca agacggcgtg ggctcctttt cctgctcctg 2700
cctccctggt ttcgccggcc cacgatgcgc ccgcgatgtg gatgagtgcc tgagcaaccc 2760
ctgcggcccg ggcacctgta ccgaccacgt ggcctccttc acctgcacct gcccgccagg 2820
ctacggaggc ttccactgcg aacaggacct gcccgactgc agccccagct cctgcttcaa 2880
tggcgggacc tgtgtggacg gcgtgaactc gttcagctgc ctgtgccgtc ccggctacac 2940
aggagcccac tgccaacatg aggcagaccc ctgcctctcg cggccctgcc tacacggggg 3000
cgtctgcagc gccgcccacc ctggcttccg ctgcacctgc ctcgagagct tcacgggccc 3060
gcagtgccag acgctggtgg attggtgcag ccgccagcct tgtcaaaacg ggggtcgctg 3120
cgtccagact ggggcctatt gcctttgtcc ccctggatgg agcggacgcc tctgtgacat 3180
ccgaagcttg ccctgcaggg aggccgcagc ccagatcggg gtgcggctgg agcagctgtg 3240
tcaggcgggt gggcagtgtg tggatgaaga cagctcccac tactgcgtgt gcccagaggg 3300
ccgtactggt agccactgtg agcaggaggt ggacccctgc ttggcccagc cctgccagca 3360
tggggggacc tgccgtggct atatgggggg ctacatgtgt gagtgtcttc ctggctacaa 3420
tggtgataac tgtgaggacg acgtggacga gtgtgcctcc cagccctgcc agcacggggg 3480
ttcatgcatt gacctcgtgg cccgctatct ctgctcctgt cccccaggaa cgctgggggt 3540
gctctgcgag attaatgagg atgactgcgg cccaggccca ccgctggact cagggccccg 3600
gtgcctacac aatggcacct gcgtggacct ggtgggtggt ttccgctgca cctgtccccc 3660
aggatacact ggtttgcgct gcgaggcaga catcaatgag tgtcgctcag gtgcctgcca 3720
cgcggcacac acccgggact gcctgcagga cccaggcgga ggtttccgtt gcctttgtca 3780
tgctggcttc tcaggtcctc gctgtcagac tgtcctgtct ccctgcgagt cccagccatg 3840
ccagcatgga ggccagtgcc gtcctagccc gggtcctggg ggtgggctga ccttcacctg 3900
tcactgtgcc cagccgttct ggggtccgcg ttgcgagcgg gtggcgcgct cctgccggga 3960
gctgcagtgc ccggtgggcg tcccatgcca gcagacgccc cgcgggccgc gctgcgcctg 4020
ccccccaggg ttgtcgggac cctcctgccg cagcttcccg gggtcgccgc cgggggccag 4080
caacgccagc tgcgcggccg ccccctgtct ccacgggggc tcctgccgcc ccgcgccgct 4140
cgcgcccttc ttccgctgcg cttgcgcgca gggctggacc gggccgcgct gcgaggcgcc 4200
cgccgcggca cccgaggtct cggaggagcc gcggtgcccg cgcgccgcct gccaggccaa 4260
gcgcggggac cagcgctgcg accgcgagtg caacagccca ggctgcggct gggacggcgg 4320
cgactgctcg ctgagcgtgg gcgacccctg gcggcaatgc gaggcgctgc agtgctggcg 4380
cctcttcaac aacagccgct gcgaccccgc ctgcagctcg cccgcctgcc tctacgacaa 4440
cttcgactgc cacgccggtg gccgcgagcg cacttgcaac ccggtgtacg agaagtactg 4500
cgccgaccac tttgccgacg gccgctgcga ccagggctgc aacacggagg agtgcggctg 4560
ggatgggctg gattgtgcca gcgaggtgcc ggccctgctg gcccgcggcg tgctggtgct 4620
cacagtgctg ctgccgccag aggagctact gcgttccagc gccgactttc tgcagcggct 4680
cagcgccatc ctgcgcacct cgctgcgctt ccgcctggac gcgcacggcc aggccatggt 4740
cttcccttac caccggccta gtcctggctc cgaaccccgg gcccgtcggg agctggcccc 4800
cgaggtgatc ggctcggtag taatgctgga gattgacaac cggctctgcc tgcagtcgcc 4860
tgagaatgat cactgcttcc ccgatgccca gagcgccgct gactacctgg gagcgttgtc 4920
agcggtggag cgcctggact tcccgtaccc actgcgggac gtgcgggggg agccgctgga 4980
gcctccagaa cccagcgtcc cgctgctgcc actgctagtg gcgggcgctg tcttgctgct 5040
ggtcattctc gtcctgggtg tcatggtggc ccggcgcaag cgcgagcaca gcaccctctg 5100
gttccctgag ggcttctcac tgcacaagga cgtggcctct ggtcacaagg gccggcggga 5160
acccgtgggc caggacgcgc tgggcatgaa gaacatggcc aagggtgaga gcctgatggg 5220
ggaggtggcc acagactgga tggacacaga gtgcccagag gccaagcggc taaaggtaga 5280
ggagccaggc atgggggctg aggaggctgt ggattgccgt cagtggactc aacaccatct 5340
ggttgctgct gacatccgcg tggcaccagc catggcactg acaccaccac agggcgacgc 5400
agatgctgat ggcatggatg tcaatgtgcg tggcccagat ggcttcaccc cgctaatgct 5460
ggcttccttc tgtggggggg ctctggagcc aatgccaact gaagaggatg aggcagatga 5520
cacatcagct agcatcatct ccgacctgat ctgccagggg gctcagcttg gggcacggac 5580
tgaccgtact ggcgagactg ctttgcacct ggctgcccgt tatgcccgtg ctgatgcagc 5640
caagcggctg ctggatgctg gggcagacac caatgcccag gaccactcag gccgcactcc 5700
cctgcacaca gctgtcacag ccgatgccca gggtgtcttc cagattctca tccgaaaccg 5760
ctctacagac ttggatgccc gcatggcaga tggctcaacg gcactgatcc tggcggcccg 5820
cctggcagta gagggcatgg tggaagagct catcgccagc catgctgatg tcaatgctgt 5880
ggatgagctt gggaaatcag ccttacactg ggctgcggct gtgaacaacg tggaagccac 5940
tttggccctg ctcaaaaatg gagccaataa ggacatgcag gatagcaagg aggagacccc 6000
cctattcctg gccgcccgcg agggcagcta tgaggctgcc aagctgctgt tggaccactt 6060
tgccaaccgt gagatcaccg accacctgga caggctgccg cgggacgtag cccaggagag 6120
actgcaccag gacatcgtgc gcttgctgga tcaacccagt gggccccgca gcccccccgg 6180
tccccacggc ctggggcctc tgctctgtcc tccaggggcc ttcctccctg gcctcaaagc 6240
ggcacagtcg gggtccaaga agagcaggag gccccccggg aaggcggggc tggggccgca 6300
ggggccccgg gggcggggca agaagctgac gctggcctgc ccgggccccc tggctgacag 6360
ctcggtcacg ctgtcgcccg tggactcgct ggactccccg cggcctttcg gtgggccccc 6420
tgcttcccct ggtggcttcc cccttgaggg gccctatgca gctgccactg ccactgcagt 6480
gtctctggca cagcttggtg gcccaggccg ggcgggtcta gggcgccagc cccctggagg 6540
atgtgtactc agcctgggcc tgctgaaccc tgtggctgtg cccctcgatt gggcccggct 6600
gcccccacct gcccctccag gcccctcgtt cctgctgcca ctggcgccgg gaccccagct 6660
gctcaaccca gggacccccg tctccccgca ggagcggccc ccgccttacc tggcagtccc 6720
aggacatggc gaggagtacc cggcggctgg ggcacacagc agccccccaa aggcccgctt 6780
cctgcgggtt cccagtgagc acccttacct gaccccatcc cccgaatccc ctgagcactg 6840
ggccagcccc tcacctccct ccctctcaga ctggtccgaa tccacgccta gcccagccac 6900
tgccactggg gccatggcca ccaccactgg ggcactgcct gcccagccac ttcccttgtc 6960
tgttcccagc tcccttgctc aggcccagac ccagctgggg ccccagccgg aagttacccc 7020
caagaggcaa gtgttggcct gagacgctcg tcagttctta gatcttgggg gcctaaagag 7080
acccccgtcc tgcctccttt ctttctctgt ctcttccttc cttttagtct ttttcatcct 7140
cttctctttc caccaaccct cctgcatcct tgccttgcag cgtgaccgag ataggtcatc 7200
agcccagggc ttcagtcttc ctttatttat aatgggtggg ggctaccacc caccctctca 7260
gtcttgtgaa gagtctggga cctccttctt ccccacttct ctcttccctc attcctttct 7320
ctctccttct ggcctctcat ttccttacac tctgacatga atgaattatt attattttta 7380
tttttctttt tttttttaca ttttgtatag aaacaaattc atttaaacaa acttattatt 7440
attatttttt acaaaatata tatatggaga tgctccctcc ccctgtgaac cccccagtgc 7500
ccccgtgggg ctgagtctgt gggcccattc ggccaagctg gattctgtgt acctagtaca 7560
caggcatgac tgggatcccg tgtaccgagt acacgaccca ggtatgtacc aagtaggcac 7620
ccttgggcgc acccactggg gccaggggtc gggggagtgt tgggagcctc ctccccaccc 7680
cacctccctc acttcactgc attccagatg ggacatgttc catagccttg ctggggaagg 7740
gcccactgcc aactccctct gccccagccc cacccttggc catctccctt tgggaactag 7800
ggggctgctg gtgggaaatg ggagccaggg cagatgtatg cattcctttg tgtccctgta 7860
aatgtgggac tacaagaaga ggagctgcct gagtggtact ttctcttcct ggtaatcctc 7920
tggcccagcc tcatggcaga atagaggtat ttttaggcta tttttgtaat atggcttctg 7980
gtcaaaatcc ctgtgtagct gaattcccaa gccctgcatt gtacagcccc ccactcccct 8040
caccacctaa taaaggaata gttaacactc aaaaaaaaaa aaaaaaaaa 8089
<210> 33
<211> 6762
<212> DNA
<213> 人
<400> 33
agacgtgagg cttgcagcag gccgaggagg aagaagaggg gcagtgggag cagaggaggt 60
ggctcctgcc ccagtgagag ctctgagggt ccctgcctga agagggacag ggaccggggc 120
ttggagaagg ggctgtggaa tgcagccccc ttcactgctg ctgctgctgc tgctgctgct 180
gctgctatgt gtctcagtgg tcagacccag agggctgctg tgtgggagtt tcccagaacc 240
ctgtgccaat ggaggcacct gcctgagcct gtctctggga caagggacct gccagtgtgc 300
ccctggcttc ctgggtgaga cgtgccagtt tcctgacccc tgccagaacg cccagctctg 360
ccaaaatgga ggcagctgcc aagccctgct tcccgctccc ctagggctcc ccagctctcc 420
ctctccattg acacccagct tcttgtgcac ttgcctccct ggcttcactg gtgagagatg 480
ccaggccaag cttgaagacc cttgtcctcc ctccttctgt tccaaaaggg gccgctgcca 540
catccaggcc tcgggccgcc cacagtgctc ctgcatgcct ggatggacag gtgagcagtg 600
ccagcttcgg gacttctgtt cagccaaccc atgtgttaat ggaggggtgt gtctggccac 660
atacccccag atccagtgcc actgcccacc gggcttcgag ggccatgcct gtgaacgtga 720
tgtcaacgag tgcttccagg acccaggacc ctgccccaaa ggcacctcct gccataacac 780
cctgggctcc ttccagtgcc tctgccctgt ggggcaggag ggtccacgtt gtgagctgcg 840
ggcaggaccc tgccctccta ggggctgttc gaatgggggc acctgccagc tgatgccaga 900
gaaagactcc acctttcacc tctgcctctg tcccccaggt ttcataggcc cagactgtga 960
ggtgaatcca gacaactgtg tcagccacca gtgtcagaat gggggcactt gccaggatgg 1020
gctggacacc tacacctgcc tctgcccaga aacctggaca ggctgggact gctccgaaga 1080
tgtggatgag tgtgagaccc agggtccccc tcactgcaga aacgggggca cctgccagaa 1140
ctctgctggt agctttcact gcgtgtgtgt gagtggctgg ggcggcacaa gctgtgagga 1200
gaacctggat gactgtattg ctgccacctg tgccccggga tccacctgca ttgaccgggt 1260
gggctctttc tcctgcctct gcccacctgg acgcacagga ctcctgtgcc acttggaaga 1320
catgtgtctg agccagccgt gccatgggga tgcccaatgc agcaccaacc ccctcacagg 1380
ctccacactc tgcctgtgtc agcctggcta ttcggggccc acctgccacc aggacctgga 1440
cgagtgtctg atggcccagc aaggcccaag tccctgtgaa catggcggtt cctgcctcaa 1500
cactcctggc tccttcaact gcctctgtcc acctggctac acaggctccc gttgtgaggc 1560
tgatcacaat gagtgcctct cccagccctg ccacccagga agcacctgtc tggacctact 1620
tgccaccttc cactgcctct gcccgccagg cttagaaggg cagctctgtg aggtggagac 1680
caacgagtgt gcctcagctc cctgcctgaa ccacgcggat tgccatgacc tgctcaacgg 1740
cttccagtgc atctgcctgc ctggattctc cggcacccga tgtgaggagg atatcgatga 1800
gtgcagaagc tctccctgtg ccaatggtgg gcagtgccag gaccagcctg gagccttcca 1860
ctgcaagtgt ctcccaggct ttgaagggcc acgctgtcaa acagaggtgg atgagtgcct 1920
gagtgaccca tgtcccgttg gagccagctg ccttgatctt ccaggagcct tcttttgcct 1980
ctgcccctct ggtttcacag gccagctctg tgaggttccc ctgtgtgctc ccaacctgtg 2040
ccagcccaag cagatatgta aggaccagaa agacaaggcc aactgcctct gtcctgatgg 2100
aagccctggc tgtgccccac ctgaggacaa ctgcacctgc caccacgggc actgccagag 2160
atcctcatgt gtgtgtgacg tgggttggac ggggccagag tgtgaggcag agctaggggg 2220
ctgcatctct gcaccctgtg cccatggggg gacctgctac ccccagccct ctggctacaa 2280
ctgcacctgc cctacaggct acacaggacc cacctgtagt gaggagatga cagcttgtca 2340
ctcagggcca tgtctcaatg gcggctcctg caaccctagc cctggaggct actactgcac 2400
ctgccctcca agccacacag ggccccagtg ccaaaccagc actgactact gtgtgtctgc 2460
cccgtgcttc aatgggggta cctgtgtgaa caggcctggc accttctcct gcctctgtgc 2520
catgggcttc cagggcccgc gctgtgaggg aaagctccgc cccagctgtg cagacagccc 2580
ctgtaggaat agggcaacct gccaggacag ccctcagggt ccccgctgcc tctgccccac 2640
tggctacacc ggaggcagct gccagactct gatggactta tgtgcccaga agccctgccc 2700
acgcaattcc cactgcctcc agactgggcc ctccttccac tgcttgtgcc tccagggatg 2760
gaccgggcct ctctgcaacc ttccactgtc ctcctgccag aaggctgcac tgagccaagg 2820
catagacgtc tcttcccttt gccacaatgg aggcctctgt gtcgacagcg gcccctccta 2880
tttctgccac tgcccccctg gattccaagg cagcctgtgc caggatcacg tgaacccatg 2940
tgagtccagg ccttgccaga acggggccac ctgcatggcc cagcccagtg ggtatctctg 3000
ccagtgtgcc ccaggctacg atggacagaa ctgctcaaag gaactcgatg cttgtcagtc 3060
ccaaccctgt cacaaccatg gaacctgtac tcccaaacct ggaggattcc actgtgcctg 3120
ccctccaggc tttgtggggc tacgctgtga gggagacgtg gacgagtgtc tggaccagcc 3180
ctgccacccc acaggcactg cagcctgcca ctctctggcc aatgccttct actgccagtg 3240
tctgcctgga cacacaggcc agtggtgtga ggtggagata gacccctgcc acagccaacc 3300
ctgctttcat ggagggacct gtgaggccac agcaggatca cccctgggtt tcatctgcca 3360
ctgccccaag ggttttgaag gccccacctg cagccacagg gccccttcct gcggcttcca 3420
tcactgccac cacggaggcc tgtgtctgcc ctcccctaag ccaggcttcc caccacgctg 3480
tgcctgcctc agtggctatg ggggtcctga ctgcctgacc ccaccagctc ctaaaggctg 3540
tggccctccc tccccatgcc tatacaatgg cagctgctca gagaccacgg gcttgggggg 3600
cccaggcttt cgatgctcct gccctcacag ctctccaggg ccccggtgtc agaaacccgg 3660
agccaagggg tgtgagggca gaagtggaga tggggcctgc gatgctggct gcagtggccc 3720
gggaggaaac tgggatggag gggactgctc tctgggagtc ccagacccct ggaagggctg 3780
cccctcccac tctcggtgct ggcttctctt ccgggacggg cagtgccacc cacagtgtga 3840
ctctgaagag tgtctgtttg atggctacga ctgtgagacc cctccagcct gcactccagc 3900
ctatgaccag tactgccatg atcacttcca caacgggcac tgtgagaaag gctgcaacac 3960
tgcagagtgt ggctgggatg gaggtgactg caggcctgaa gatggggacc cagagtgggg 4020
gccctccctg gccctgctgg tggtactgag ccccccagcc ctagaccagc agctgtttgc 4080
cctggcccgg gtgctgtccc tgactctgag ggtaggactc tgggtaagga aggatcgtga 4140
tggcagggac atggtgtacc cctatcctgg ggcccgggct gaagaaaagc taggaggaac 4200
tcgggacccc acctatcagg agagagcagc ccctcaaacg cagcccctgg gcaaggagac 4260
cgactccctc agtgctgggt ttgtggtggt catgggtgtg gatttgtccc gctgtggccc 4320
tgaccacccg gcatcccgct gtccctggga ccctgggctt ctactccgct tccttgctgc 4380
gatggctgca gtgggagccc tggagcccct gctgcctgga ccactgctgg ctgtccaccc 4440
tcatgcaggg accgcacccc ctgccaacca gcttccctgg cctgtgctgt gctccccagt 4500
ggccggggtg attctcctgg ccctaggggc tcttctcgtc ctccagctca tccggcgtcg 4560
acgccgagag catggagctc tctggctgcc ccctggtttc actcgacggc ctcggactca 4620
gtcagctccc caccgacgcc ggcccccact aggcgaggac agcattggtc tcaaggcact 4680
gaagccaaag gcagaagttg atgaggatgg agttgtgatg tgctcaggcc ctgaggaggg 4740
agaggaggtg ggccaggctg aagaaacagg cccaccctcc acgtgccagc tctggtctct 4800
gagtggtggc tgtggggcgc tccctcaggc agccatgcta actcctcccc aggaatctga 4860
gatggaagcc cctgacctgg acacccgtgg acctgatggg gtgacacccc tgatgtcagc 4920
agtttgctgt ggggaagtac agtccgggac cttccaaggg gcatggttgg gatgtcctga 4980
gccctgggaa cctctgctgg atggaggggc ctgtccccag gctcacaccg tgggcactgg 5040
ggagaccccc ctgcacctgg ctgcccgatt ctcccggcca accgctgccc gccgcctcct 5100
tgaggctgga gccaacccca accagccaga ccgggcaggg cgcacacccc ttcatgctgc 5160
tgtggctgct gatgctcggg aggtctgcca gcttctgctc cgtagcagac aaactgcagt 5220
ggacgctcgc acagaggacg ggaccacacc cttgatgctg gctgccaggc tggcggtgga 5280
agacctggtt gaagaactga ttgcagccca agcagacgtg ggggccagag ataaatgggg 5340
gaaaactgcg ctgcactggg ctgctgccgt gaacaacgcc cgagccgccc gctcgcttct 5400
ccaggccgga gccgataaag atgcccagga caacagggag cagacgccgc tattcctggc 5460
ggcgcgggaa ggagcggtgg aagtagccca gctactgctg gggctggggg cagcccgaga 5520
gctgcgggac caggctgggc tagcgccggc ggacgtcgct caccaacgta accactggga 5580
tctgctgacg ctgctggaag gggctgggcc accagaggcc cgtcacaaag ccacgccggg 5640
ccgcgaggct gggcccttcc cgcgcgcacg gacggtgtca gtaagcgtgc ccccgcatgg 5700
gggcggggct ctgccgcgct gccggacgct gtcagccgga gcaggccctc gtgggggcgg 5760
agcttgtctg caggctcgga cttggtccgt agacttggct gcgcgggggg gcggggccta 5820
ttctcattgc cggagcctct cgggagtagg agcaggagga ggcccgaccc ctcgcggccg 5880
taggttttct gcaggcatgc gcgggcctcg gcccaaccct gcgataatgc gaggaagata 5940
cggagtggct gccgggcgcg gaggcagggt ctcaacggat gactggccct gtgattgggt 6000
ggccctggga gcttgcggtt ctgcctccaa cattccgatc ccgcctcctt gccttactcc 6060
gtccccggag cggggatcac ctcaacttga ctgtggtccc ccagccctcc aagaaatgcc 6120
cataaaccaa ggaggagagg gtaaaaaata gaagaataca tggtagggag gaattccaaa 6180
aatgattacc cattaaaagg caggctggaa ggccttcctg gttttaagat ggatccccca 6240
aaatgaaggg ttgtgagttt agtttctctc ctaaaatgaa tgtatgccca ccagagcaga 6300
catcttccac gtggagaagc tgcagctctg gaaagagggt ttaagatgct aggatgaggc 6360
aggcccagtc ctcctccaga aaataagaca ggccacagga gggcagagtg gagtggaaat 6420
acccctaagt tggaaccaag aattgcaggc atatgggatg taagatgttc tttcctatat 6480
atggtttcca aagggtgccc ctatgatcca ttgtccccac tgcccacaaa tggctgacaa 6540
atatttattg ggcacctact atgtgccagg cactgtgtag gtgctgaaaa gtggccaagg 6600
gccacccccg ctgatgactc cttgcattcc ctcccctcac aacaaagaac tccactgtgg 6660
ggatgaagcg cttcttctag ccactgctat cgctatttaa gaaccctaaa tctgtcaccc 6720
ataataaagc tgatttgaag tgttaaaaaa aaaaaaaaaa aa 6762
<210> 34
<211> 200
<212> DNA
<213> 人工序列
<220>
<223> CMV启动子
<400> 34
atcgatgtta ataattaaca tatatgttaa tcattaacta tatagttaat tattaaccgc 60
tatgttaatg attaacacta gttaggcgtg tacggtggga ggcctatata agcagagctc 120
gtttagtgaa ccgtcagatc gcctggagac gccatccacg ctgttttgac ctccatagaa 180
gacaccggga ccgatccagc 200
<210> 35
<211> 9
<212> DNA
<213> 人工序列
<220>
<223> Kozak序列
<400> 35
gccgccacc 9

Claims (20)

1.包含编码嵌合Notch多肽的核苷酸序列的核酸，所述嵌合Notch多肽从N末端到C末端并以共价连接的方式包含：a)包含特异性结合抗原的结合剂的细胞外结构域；b)包含一个或多个蛋白水解切割位点的所述受体多肽；c)包含转录调节物的细胞内结构域，其中所述结合剂与所述抗原的结合诱导在所述一个或多个蛋白水解切割位点的所述Notch受体多肽的切割，由此释放所述细胞内结构域和所述转录调节物，并且其中所述转录调节物包含人源的DNA结合结构域和人源的转录激活结构域。
2.如权利要求1中所述的核酸，其中所述结合剂包含抗体。
3.如权利要求2中所述的核酸，其中所述抗体选自下组：scFv、双特异性抗体、纳米抗体或bite。
4.如权利要求3中所述的核酸，其中所述转录调节物为转录激活物。
5.如权利要求3中所述的核酸，其中所述转录调节物为转录阻遏物。
6.如权利要求1中所述的核酸，其中所述转录调节物来自HNF转录调节物家族。
7.如权利要求6中所述的核酸，其中所述转录调节物为HNF1 alpha或HNF1 beta。
8.如权利要求7中所述的核酸，其中所述转录激活结构域选自下组：RelA(p65)、YAP、WWTR1(TAZ)、CREB3(LZIP)和MyoD。
9.包含权利要求1的核酸的重组载体。
10.包含权利要求8的核酸的重组载体。
11.用权利要求1的核酸转化的宿主细胞。
12.权利要求11的宿主细胞，其中所述细胞为巨噬细胞。
13.权利要求12的宿主细胞，其中所述巨噬细胞衍生自单核细胞。
14.制备包含转录调节物的嵌合Notch多肽的方法，其中所述转录调节物包含人源的DNA结合结构域，所述方法包括培养权利要求11的宿主细胞。
15.包含人源化转录调节物的嵌合Notch多肽。
16.权利要求15的嵌合Notch多肽，其中所述人源化转录调节物来自HNF转录调节物家族。
17.权利要求16的嵌合Notch多肽，其中所述人源化转录调节物包含HNF1 alpha或HNF1beta。
18.治疗患者的疾病的方法，所述患者需要所述治疗，所述方法包括用包含人源化转录调节物的嵌合Notch多肽治疗所述患者。
19.如权利要求18中所述的治疗患者的疾病的方法，包括选自HNF1转录调节物家族的人源化转录调节物。
20.如权利要求19中所述的治疗疾病的方法，其中所述疾病为癌症。
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