CN107176993A - 一种mmaf致病基因新突变及其应用 - Google Patents

一种mmaf致病基因新突变及其应用 Download PDF

Info

Publication number
CN107176993A
CN107176993A CN201710494668.XA CN201710494668A CN107176993A CN 107176993 A CN107176993 A CN 107176993A CN 201710494668 A CN201710494668 A CN 201710494668A CN 107176993 A CN107176993 A CN 107176993A
Authority
CN
China
Prior art keywords
leu
glu
ser
lys
val
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201710494668.XA
Other languages
English (en)
Inventor
沙艳伟
李萍
李琳
梅利斌
黄娴静
林绍彬
王旭
张庆
邱乒乒
龚秀芳
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BEIJING OBSTETRICS AND GYNECOLOGY HOSPITAL CAPITAL MEDICAL UNIVERSITY
Xiamen Maternity & Child Healthcare Hospital (xiamen City Family Planning Service Center)
Original Assignee
BEIJING OBSTETRICS AND GYNECOLOGY HOSPITAL CAPITAL MEDICAL UNIVERSITY
Xiamen Maternity & Child Healthcare Hospital (xiamen City Family Planning Service Center)
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by BEIJING OBSTETRICS AND GYNECOLOGY HOSPITAL CAPITAL MEDICAL UNIVERSITY, Xiamen Maternity & Child Healthcare Hospital (xiamen City Family Planning Service Center) filed Critical BEIJING OBSTETRICS AND GYNECOLOGY HOSPITAL CAPITAL MEDICAL UNIVERSITY
Priority to CN201710494668.XA priority Critical patent/CN107176993A/zh
Publication of CN107176993A publication Critical patent/CN107176993A/zh
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/34—Genitourinary disorders

Abstract

一种MMAF致病基因新突变及其应用，涉及致病基因，首次发现一种MMAF致病基因DNAH1的新突变。以MMAF多个患病家系及患病个体为研究对象，对家系中的患病个体进行了外显子组测序和比较，发现不同患者DNAH1基因存在不同的基因突变。利用这些突变可以对精子尾部多种形态异常(MMAF)进行检测。

Description

一种MMAF致病基因新突变及其应用
技术领域
本发明涉及致病基因，尤其是涉及一种MMAF致病基因新突变及其应用。
背景技术
精子尾部多种形态异常(multiple morphological abnormalities of thesperm flagella,MMAF)是一种隐性遗传的导致男性不育的畸形精子症，是一种很少见的遗传疾病，其主要临床特征是五种精子尾部异常的总和，包括短尾、无尾、卷尾、弯尾以及尾部宽度不规则。早期研究中也有文献称这个病为纤维鞘发育不良(dysplasia of thefibrous sheath，DFS)、短尾精子症(short tails，stump tails)。国外早期的分子方面发病机制研究发现DNAH1基因发生了突变(1.Ben Khelifa M,Coutton C,Zouari R,Karaouzene T,Rendu J,Bidart M,Yassine S,Pierre V,Delaroche J,Hennebicq S,Grunwald D,Escalier D,Pernet-Gallay K,Jouk PS,Thierry-Mieg N,Toure A,etal.Mutations in DNAH1,which encodes an inner arm heavy chain dynein,lead tomale infertility from multiple morphological abnormalities of the spermflagella.Am J Hum Genet.2014；94(1):95-104；2.Amiri-Yekta A,Coutton C,KherrafZE,Karaouzene T,Le Tanno P,Sanati MH,Sabbaghian M,Almadani N,Sadighi GilaniMA,Hosseini SH,Bahrami S,Daneshipour A,Bini M,Arnoult C,Colombo R,Gourabi H,et al.Whole-exome sequencing of familial cases of multiple morphologicalabnormalities of the sperm flagella(MMAF)reveals new DNAH1 mutations.HumReprod.2016；31(12):2872-2880)，该基因编码纤毛轴动力蛋白重链1(dynein axonemalheavy chain 1)蛋白。
目前MMAF的基因突变谱尚未完全发现，基因型和表现型的关系也不明确。目前单基因疾病的研究开始大量采用全外显子组测序(whole-exome sequencing)及全基因组测序(whole-genome sequencing)的方法，这两种方法被成功的应用于发现稀有单基因疾病的致病基因。全外显子组测序及全基因组测序技术已被证明为降低稀有单基因疾病候选基因甚至发现其致病基因的有力、有效手段。仅通过对几个很少的个体(包括患者及正常对照)的全外显子组或基因组进行测序来筛选与疾病相关的变异，其成功率大为提升。
因此本领域对MMAF的研究尚不清晰，对造成该疾病的原因更不明了，因此本领域迫切需要对MMAF的致病机理进行研究，找到新致病基因及突变位点。
发明内容
本发明的第一目的在于提供通过外显子组测序的方法确定MMAF的致病基因的新突变。
本发明的第二目的在于提供MMAF的生物标记物。
本发明的第三目的在于提供MMAF的生物标记物，具有突变的DNAH1基因或DNAH1蛋白。
本发明的第四目的在于提供MMAF的生物标记物的突变的DNAH1基因为SEQ ID NO:1的序列中突变。
本发明的第五目的在于提供MMAF的生物标记物的突变的DNAH1基因为SEQ ID NO:2的序列中突变。
本发明的第六目的在于提供突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子。
本发明的第七目的在于提供一种检测MMAF的方法。
本发明的第八目的在于提供通过PCR检测DNAH1基因或DNAH1蛋白突变中使用的引物对。
本发明的第九目的在于提供与突变DNAH1基因互补的核酸探针。
本发明的第十目的在于提供探针与突变DNAH1基因的互补区。
本发明的第十一目的在于提供检测突变DNAH1基因或DNAH1蛋白的试剂盒。
本发明的第十二目的在于提供检测突变DNAH1基因的试剂盒。
本发明的第十三目的在于提供一种MMAF致病基因新突变的应用。
所述通过外显子组测序的方法确定MMAF的致病基因的新突变。
所述MMAF的生物标记物，即突变的DNAH1基因或DNAH1蛋白，所述生物标记物是具有选自如下的突变的DNAH1基因或DNAH1蛋白：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)。
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)。
MMAF的生物标记物的突变的DNAH1基因为SEQ ID NO:1的序列中具有以下突变：
在外显子25中错义突变(c.4115C>T)；
在外显子73中移码突变(c.11726_11727del)；
在外显子43中错义突变(c.6822C>G)；
在外显子62中错义突变(c.9850G>A)；
在外显子39中错义突变(c.6212T>G)；
在外显子76中缺失突变(c.12200_12202del)；
在外显子22中错义突变(c.3836A>G)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A)；
在外显子37中无义突变(c.5864G>A)；
在外显子39中移码突变(c.6253_6254del)。
在外显子15中无义突变(c.2610G>A)；
在外显子76中错义突变(c.12287G>T)；
在外显子76中错义突变(c.12397C>T)；
在外显子45中错义突变(c.7066C>T)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T)。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有以下突变：
在外显子25中错义突变(p.T1372M)；
在外显子73中移码突变(p.P3909Rfs*33)；
在外显子43中错义突变(p.D2274E)；
在外显子62中错义突变(p.E3284K)；
在外显子39中错义突变(p.L2071R)；
在外显子76中缺失突变(p.N4068del)；
在外显子22中错义突变(p.K1279R)；
在外显子19中无义突变(p.W1036X)；
在外显子37中无义突变(p.W1955X)；
在外显子39中移码突变(p.E2086Gfs*8)。
在外显子15中无义突变(p.W870X)；
在外显子76中错义突变(p.R4096L)；
在外显子76中错义突变(p.R4133C)；
在外显子45中错义突变(p.R2356W)；
在外显子67中无义突变(p.E3544X)。
突变的DNAH1蛋白为SEQ ID NO:2的序列中，具有外显子19中无义突变(p.W1036X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:29。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子37中无义突变(p.W1955X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:30。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子15中无义突变(p.W870X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:31。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子67中无义突变(p.E3544X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:32。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子73中移码突变(p.P3909Rfs*33)，所述突变的DNAH1蛋白的序列是SEQ ID NO:33。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子39中移码突变(p.E2086Gfs*8)，所述突变的DNAH1蛋白的序列是SEQ ID NO:34。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子76中缺失突变(p.N4068del)，所述突变的DNAH1蛋白的序列是SEQ ID NO:35。
一种检测MMAF的方法，所述方法包括检测受试者的DNAH1基因或DNAH1蛋白中是否存在突变位点，若有突变位点，则所述受试者被鉴定为患有MMAF或易患MMAF，所述突变位点选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)。
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)。
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子。
DNAH1蛋白为SEQ ID NO:2的序列表示。
DNAH1基因为SEQ ID NO:1的序列表示。
一种检测MMAF的方法包括如下至少一组引物扩增的步骤：
SEQ ID NO:3和SEQ ID NO:4；
SEQ ID NO:5和SEQ ID NO:6；
SEQ ID NO:7和SEQ ID NO:8；
SEQ ID NO:9和SEQ ID NO:10；
SEQ ID NO:11和SEQ ID NO:12；
SEQ ID NO:13和SEQ ID NO:14；
SEQ ID NO:15和SEQ ID NO:16；
SEQ ID NO:17和SEQ ID NO:18；
SEQ ID NO:19和SEQ ID NO:20；
SEQ ID NO:21和SEQ ID NO:22；
SEQ ID NO:23和SEQ ID NO:24；
SEQ ID NO:25和SEQ ID NO:26；
SEQ ID NO:27和SEQ ID NO:28。
所述检测MMAF的方法中检测突变位点通过选自以下：测序、电泳、核酸杂交、原位杂交、PCR、逆转录酶链反应和变性高效液相色谱。
通过PCR检测DNAH1基因或DNAH1蛋白突变中使用的引物对，所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)。
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)，
其中所述引物对分别基于选自如下的位置前后设计，使得扩增该位置(编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变)：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
与突变DNAH1基因互补的核酸探针，所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)。
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)，
所述探针与突变DNAH1基因的互补区包括选自如下的位置(编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变)：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
检测突变DNAH1基因或DNAH1蛋白的试剂盒，包含一组或多组引物对，其中所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)。
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)，
其中所述引物对分别基于选自如下的位置前后设计，使得其扩增产物涵盖该位置(编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变)：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
所述检测突变DNAH1基因或DNAH1蛋白的试剂盒包含选自如下的至少一组引物：
SEQ ID NO:3和SEQ ID NO:4；
SEQ ID NO:5和SEQ ID NO:6；
SEQ ID NO:7和SEQ ID NO:8；
SEQ ID NO:9和SEQ ID NO:10；
SEQ ID NO:11和SEQ ID NO:12；
SEQ ID NO:13和SEQ ID NO:14；
SEQ ID NO:15和SEQ ID NO:16；
SEQ ID NO:17和SEQ ID NO:18；
SEQ ID NO:19和SEQ ID NO:20；
SEQ ID NO:21和SEQ ID NO:22；
SEQ ID NO:23和SEQ ID NO:24；
SEQ ID NO:25和SEQ ID NO:26；
SEQ ID NO:27和SEQ ID NO:28。
检测突变DNAH1基因的试剂盒，包含一个或多个核酸探针，所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)。
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)。
所述探针与突变DNAH1基因上包含选自如下的位置的区域互补(编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变)：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
一种MMAF致病基因新突变的应用。
本发明将为MMAF的发病机制研究奠定重要基础，有可能为MMAF的患者治疗提供全新的理论依据。
具体实施方式
在本发明中，采用本领域通用表示法表示突变。例如，突变(c.4115C>T；p.T1372M)中，c表示cDNA，p表示蛋白质，DNA水平的突变对应蛋白质水平的突变；移码突变(c.11726_11727del；p.P3909Rfs*33)中，c.11726_11727del表示DNA水平第11726至11727位缺失，p.P3909Rfs*33表示从第3909位起算的33个氨基酸的移码，形成的突变蛋白质仅有3940个氨基酸，如SEQ ID NO:33中所示；无义突变(c.3108G>A；p.W1036X)中，c.3108G>A表示cDNA水平第3108的G突变为A，p.W1036X表示第1036位的氨基酸W突变为终止密码子，形成的突变蛋白质仅有1035个氨基酸，如SEQ ID NO:29中所示；剪接位点突变(c.7377+1G>C)中，c.7377+1表示c.7377后面是内含子，+1表示该内含子的第1位，这位的G突变为C；同理在突变(c.5766-2A>G)中，c.5766-2表示c.5766前面是内含子，-2表示该内含子的第-2位，这位的A突变为G。
野生型DNAH1基因的cDNA序列如SEQ ID NO:1所示。
SEQ ID NO:2：野生型DNAH1蛋白的氨基酸序列。
在本发明中，提及基因序列，本领域技术人员应当理解，实际包括互补双链的任意一条，或者两条。为了方便，虽然多数情况下至给出了一条链，但实际上也公开了与之互补的另一条链。例如提及DNAH1基因的cDNA序列，实际上包括该序列以及其互补序列。例如，提及SEQ ID NO:1，实际包括其互补序列。本领域技术人员还可以理解，利用一条链可以检测另一条链，反之亦然。
本发明中的基因序列包括DNA形式或RNA形式，公开其中一种，意味着另一种也被公开。例如提及DNAH1基因的cDNA序列，实际也包括相应的RNA序列。
实施例1
确定MMAF的致病基因。
本发明收集到27例MMAF病例，所有患者均表现为不育，尾部畸形包括短尾、无尾、卷尾、弯尾以及尾部宽度不规则等典型的MMAF疾病特征。
本发明对所有患者进行了全外显子组测序，具体步骤如下：
样品制备：采集所述患者及其父母家人外周血，利用试剂盒抽提外周血白细胞中的基因组DNA(QIAamp DNA Mini Kit 51304.Qiagen,USA)，利用NanoDrop 2000测量DNA的浓度及纯度(Thermo Scientific,USA)，所得的每个标本基因组DNA的OD260/OD280均位于1.7-2.0之间，浓度不少于100ng/ul，总量不少于30ul。
然后，对上述27个样本的外显子组序列进行了测序。测序平台为Illumina Hiseq2000，依照Illumina标准建库说明书(参见http://www.illumina.com/)进行测序，简述如下：
1)使用Illumina公司试剂盒TruSeq DNA Library Prep Kit制作DNA文库。在外显子捕获过程中使用Agilent公司试剂盒SureSelect Human All Exon V5；
2)使用Illumina公司HiSeq2000测序平台对捕获的外显子区域进行平行测序读取长度为90bp，每个样本的平均测序深度最少为100；
3)使用Burrows-Wheeler Aligner(http://bio-bwa.sourceforge.net/)将测序结果比对到人参考基因组中(hg19)。使用SAMtools将重复读取结果去除，通过GATK(https://www.broadinstitute.org/gatk/)进行调整和校准。然后使用SAMtools(http://www.samtools.sourceforge.net/)挖掘出SNVs及InDels，并用ANNOVAR(http://www.openbioinformatics.org/annovar/)命名。
将等位基因频率大于1％的突变位点剔除(参考数据库包括dbSNP，1000Genomes，Exome Aggregation Consortium(ExAC))。
发现12个患者在基因DNAH1上具有纯合或复杂杂合突变：通过两个家系中3名患者和4位正常人SNP筛查共分离，这些位点可能是致病位点。
结果显示于表3。
本发明认为DNAH1基因为MMAF的致病基因。
实施例2
在其他病例中确认上述MMAF的致病基因。
接着，本发明纳入所有MMAF患者，对DNAH1基因为MMAF的致病基因进行验证。验证中利用Sanger法测序验证DNAH1基因的突变，其中考虑了家系内、家系外、散发等样本验证情况。
分别对12名患者、4名家系内正常人(即其中3名患者的父母，他们均为发病)基因进行检测。
具体方法步骤如下：
1.DNA提取：
分别提取12名患者、4名家系内正常人的外周静脉血，按照实施例1的方法提取基因组DNA和测定DNA含量。
2.引物设计及PCR反应
引物设计参考人类基因组序列数据库hg19，引物序列参见表1。
表1
PCR扩增体系如表2所示。
表2
PCR反应条件：
94℃变性5min，然后进入每个循环，即94℃变性30s，退火(通常为55℃，根据不同引物的退火温度设定)30s，72℃延伸1min，总共设定30个循环。所有循环结束，最终72℃延伸10min，并将PCR产物保存在4或-20℃。
3)将步骤2中获得的获自12名MMAF患者、4名家系内正常人(即该3例患者的父母，他们均未发病)的PCR扩征产物直接进行DNA测序，方法同实施例1。
本发明收集到的27例MMAF病例中有12例在DNAH1基因中检测到有意义的突变位点。同时所发现的突变位点在家族正常人中只携带一个等位基因变异位点。这些突变位点在ExAC数据库中的频率极低或无频率(见表3)，提示所检测到的位点很可能并非SNP。因此我们认为DNAH1基因为MMAF的致病基因。
表3
序列表说明：
SEQ ID NO:1：野生型DNAH1基因的cDNA序列
ATGGAGCAGCCTAACAGTAAAGGCTATAGCCTGGGAAGGACCCCTCAGGGCCCAGAGTGCAGCAGTGCTCCTGCAGTCCAAGTGGGGACCCACAGGGGCCTAGAGTATAACCCGGGGAAGATTCTTCCAGGATCAGACTATGGGTTGGGAAATCCTCCAGCCCTTGACCCCAAGCTCCCACATTTACCCCTGCCCCCGGCCCCACCCACACTCTCAGACTTGGGGCAGCCACGGAAGTCACCCCTGACAGGCACTGATAAGAAGTACCCGCTGATGAAGCAGCGTGGGTTCTACTCCGACATCCTCAGCCCTGGAACCTTAGATCAACTTGGGGAGGTATGTCGTGGCCCCCGAATGAGCCAGAACCTCCTGCGGCAGGCTGACCTTGACAAGTTCACCCCAAGAGTCGGAAGCTTTGAGGTTCCTGAAGACTTCCAGGAGCGCATGGAGCAGCAGTGCATCGGGTCCACCACCCGGCTGCTCGCCCAGACTGACTTCCCACTGCAGGCCTACGAGCCCAAGATGCAGGTGCCTTTCCAGGTGCTGCCAGGCCAGCATCCTCGCAAGATTGAGATCGAGAGGAGGAAACAGCAGTACCTGAGCCTGGACATTGAGCAGTTGCTGTTCAGCCAGGGCATCGACTCCAACAAGCTCATGCCCAGGCACCTGGACCACCAGCACCCCCAAACCATCGAACAGGGCCATGACCCAATCTTCCCCATCTACCTCCCACTGAAGGTATTTGACAATGAGGACTTTGACTGCCGGACTCCCAGAGAGTGGATCAACATGGGCTTGGAGCCAGGGTCTCTGGACAGGAAACCTGTCCCGGGAAAAGCCCTCTTGCCCACTGATGACTTCCTGGGGCATGAGGACCCCAAGAGTCAGAAGCTGAAGTACAAATGGTGCGAGGTCGGCGTCCTGGACTACGACGAGGAGAAGAAGCTATACCTGGTACACAAGACAGACGAGAAAGGCCTGGTGCGAGATGAGATGGGGAGGCCCATCCTGAATGCAGGGGTCACCACTGAAGGAAGGCCACCCCTTCAGGTCTGTCAGTACTGGGTGCCACGGATCCAGCTTCTCTTCTGCGCTGAGGACCCTTGCATGTTCGCACAACGTGTGGTCCAGGCCAACGCCCTGCGCAAGAACACGGAAGCACTGCTGCTCTACAACTTGTATGTGGACTGCATGCCCTCTGACGGCCAGCATGTCATCAGTGAACAGAGCCTGAGCAAGATCAAGCAGTGGGCCCTGAGCACGCCTCGGATGCGCAAAGGCCCCTCGGTTCTAGAGCACCTCAGCAGTCTTGCCAGAGAAGTGAGCCTGGACTATGAGCGCAGCATGAACAAGATCAACTTTGACCACGTTGTCTCTTCCAAGCCCGAGACCTTCTCCTACGTCACCCTCCCCAAGAAGGAGGAGGAGCAGGTGCCTGAGCGAGGGCTGGTGAGTGTCCCCAAGTACCACTTCTGGGAGCAGAAGGAGGACTTCACTTTCGTGTCCCTGCTCACACGGCCAGAGGTCATCACGGCCCTCAGCAAGGTGAGGGCCGAGTGCAACAAGGTGACCGCCATGTCCCTGTTCCACTCGAGCCTCTCCAAGTACAGCCACCTGGAGGAATTTGAGCAGATCCAGTCACAGACCTTCTCCCAGGTGCAGATGTTCCTCAAGGACAGCTGGATCAGCTCGCTAAAGGTGGCCATGCGCAGCAGCCTGCGCGACATGAGCAAGGGCTGGTACAACCTCTACGAGACCAACTGGGAGGTGTACCTCATGTCCAAGCTGCGCAAGCTGATGGAGCTGGTGAAGTACATGCTGCAGGACACACTGCGCTTCCTGGTGCAGGACTCACTTGCCAGCTTCTCACAGTTCATCAGCGACACCTGTTGCAGCGTGCTCAACTGCACCGATGACATGGTCTGGGGTGACGACTTAATTAACAGCCCCTACAGGCCCCGGAAGAATCCCCTGTTCATCATGGACCTGGTGCTGGACAGCTCTGGGGTGCACTATAGCACCCCACTGGAGCAGTTTGAGGCATCTCTGCTGAACCTCTTCGACAAGGGCATCCTGGCCACCCATGCCGTGCCCCAGCTGGAGAAGCTGGTGATGGAGGACATCTTCATCAGCGGTGACCCCCTGCTGGAGTCCGTGGGCCTTCATGAGCCACTGGTGGAAGAGCTACGGGCCACCATTGCCAGTGCCGTGTCCAAGGCCATGATCCCACTGCAGGCCTACGCCAAGGAGTACCGAAAGTACCTGGAGCTGAACAACAATGACATTGCCTCCTTTCTCAAAACCTACCAGACGCAGGGCCTGTTGGCCCAGGAGGTGCGGGAGGTAGTGCTCACCCACCTGCGGGAGAAGGAGATCCTGGACAGCTCGCTGCCCAGCAGCATCATCATTGGGCCTTTCTACATCAACACCGACAATGTCAAGCAGAGCCTGTCCAAGAAACGCAAGGCCCTGGCCACTTCCGTGCTGGACATCCTTGCCAAGAACCTGCATAAGGAGGTGGATAGCATCTGCGAGGAGTTCCGCAGCATCAGCCGCAAGATCTATGAGAAGCCCAACAGCATTGAGGAGCTGGCTGAGCTGCGAGAGTGGATGAAGGGCATCCCGGAGAGGCTGGTGGGCCTGGAGGAGCGGATTGTGAAGGTCATGGATGACTACCAGGTCATGGATGAATTCCTCTACAACCTCAGCTCAGATGACTTCAATGACAAATGGATTGCCAGCAACTGGCCTTCTAAGATCCTTGGGCAGATAGAGCTGGTGCAGCAGCAGCATGTGGAGGATGAGGAGAAGTTCCGCAAAATCCAGATCATGGATCAGAACAACTTCCAAGAGAAGCTGGAAGGGCTGCAGCTGGTAGTAGCTGGCTTCTCCATCCATGTGGAGATTTCACGTGCACACGAGATCGCCAACGAGGTGCGGCGTGTCAAGAAGCAGCTGAAGGACTGCCAGCAGCTGGCCATGCTCTACAACAACCGCGAGCGCATCTTCAGCTTGCCCATCACCAATTATGACAAGCTCTCCAGGATGGTGAAGGAGTTCCAACCCTACCTGGACCTTTGGACCACAGCGTCTGACTGGCTGCGCTGGTCGGAGAGCTGGATGAATGACCCCCTCTCTGCCATCGATGCTGAGCAGCTGGAGAAGAACGTGGTTGAAGCCTTCAAGACCATGCACAAGTGCGTGAAGCAGTTTAAGGACATGCCAGCCTGCCAGGAAGTGGCCTTGGACATCCGGGCCCGCATCGAGGAGTTCAAACCATACATCCCACTGATCCAGGGGCTGCGCAACCCTGGCATGCGGATCCGGCACTGGGAGACACTGTCCAACCAGATCAACATCAATGTCAGGCCCAAGGCCAACCTGACCTTTGCTCGCTGCCTGGAGATGAACCTGCAGGACCATATCGAGAGCATCAGCAAGGTGGCTGAGGTGGCTGGCAAGGAGTACGCCATCGAGCAGGCACTGGACAAGATGGAGAAGGAGTGGTCGACCATCCTGTTCAATGTACTGCCCTACAAGGCGACAGACACCTACATCCTGAAGAGCCCGGACGAGGCCTCACAGCTGCTGGACGACCACATCGTCATGACCCAGAATATGTCATTTTCACCCTACAAGAAGCCCTTTGAGCAGCGCATCAACTCCTGGGAGAACAAACTGAAGCTGACCCAGGAGGTTCTGGAGGAGTGGCTGAACTGTCAGCGGTCCTGGCTCTACCTGGAGCCCATCTTTAGCTCTGAGGACATCAACCAGCAGCTGCCTGTGGAGAGCAAGCGCTACCAGACCATGGAGCGGATCTGGAAGAAGATCATGAAGAATGCCTACGAGAACCGGGAGGTGATCAATGTGTGTTCCGACCTGAGAATGCTGGACAGCCTGCGGGACTGCAACAAGATTCTGGACCTGGTGCAGAAGGGCCTCAGCGAGTATCTGGAGACCAAGAGGAGCGCCTTCCCCAGATTCTACTTCCTGTCAGATGATGAACTACTAGAGATCTTGTCGCAGACAAAGGACCCCACGGCCGTGCAGCCACACCTGCGCAAGTGCTTCGAGAACATCGCTCGGCTGCTATTCCAGGAGGACCTGGAGATCACGCACATGTACTCAGCCGAGGGGGAGGAGGTACAGTTGTGCTTCTCCATCTACCCCTCCAGCAACGTGGAGGACTGGCTGCGGGAGGTGGAGCGCAGCATGAAGGCCAGTGTGCACGACATCATTGAGAAGGCCATCAGGGCCTACCCCACGATGCCCAGGACCCAGTGGGTTCTGAACTGGCCTGGCCAGGTGACCATCGCTGGGTGCCAGACCTACTGGACCATGGAGGTGGCAGAGGCTCTGGAGGCCGGCAACCTCAGAAGCCAACTGTTCCCCCAGCTCTGCCAGCAGCTCAGTGATCTGGTGGCCCTTGTGCGGGGGAAGCTGTCCCGCATGCAGCGGGCAGTGCTGTCAGCGCTAATCGTCATTGAGGTCCATGCCAAGGACGTGGTGAGCAAGCTAATCCAGGAGAACGTGGTCAGCGTGAATGACTTCCAGTGGATCTCACAGCTGAGGTACTACTGGACAAATAATGACCTGTATATCCGTGCTGTGAATGCTGAGTTCATCTATGGCTATGAGTACCTGGGCAACAGTGGGAGGCTGGTGATCACGCCCCTCACCGACAGGTGCTACCTGACACTGACCGGAGCTCTGCACCTCAAGTTTGGGGGTGCCCCAGCTGGCCCAGCTGGCACAGGCAAAACTGAGACCACCAAAGACCTGGGTAAGGCCTTGGCCATACAGACCGTTGTGTTCAACTGCTCTGACCAGCTCGACTTCATGGCCATGGGCAAGTTCTTCAAGGGCCTGGCCAGTGCTGGGGCCTGGGCCTGCTTCGACGAGTTCAATCGCATCGACATCGAGGTGCTGTCTGTGGTGGCGCAGCAGATCACCACCATCCAGAAGGCGCAGCAGCAGCGGGTGGAACGCTTCATGTTTGAGGGTGTGGAGATCCCACTGGTGCCATCCTGCGCAGTGTTTATCACCATGAACCCGGGCTACGCTGGCCGCACGGAGCTGCCTGACAATCTGAAGGCGCTCTTCCGACCCGTGGCCATGATGGTTCCAGATTACGCCATGATCACTGAGATCTCCCTCTATTCCTTTGGCTTTAATGAGGCCAGTGTGCTGGCTAAGAAGATCACAACCACCTTCAAGCTGTCTTCTGAGCAGCTCAGCTCCCAGGATCACTATGACTTCGGGATGAGAGCCGTGAAAACTGTGATCTCGGCTGCTGGGAACCTCAAGCGAGAAAACCCCAGCATGAATGAGGAGCTGATCTGCCTCCGGGCCATCCGTGATGTGAACGTGCCCAAGTTCCTGCAGGAGGACCTCAAGCTCTTCTCTGGCATCGTGTCCGACCTGTTTCCCACCATCAAGGAGGAGGACACGGACTACGGCATCCTGGATGAGGCCATCCGCGAGGCCTGCAGGAACAGCAACCTCAAGGATGTGGAGGGCTTCCTGACAAAGTGCATCCAGCTCTACGAGACCACGGTGGTACGACACGGCCTCATGCTCGTCGGGCCCACAGGCTCCGG
CAAGAGTACTTGTTACAGAGTCCTGGCAGCTGCCATGACGTCACTGAAAGGGCAGCCATCCATCAGTGGTGGCATGTACGAGGCTGTCAACTACTACGTGCTCAACCCCAAGTCCATCACGATGGGCCAGCTGTACGGGGAGTTTGACCTCCTCACCCATGAGTGGACAGACGGGATATTCTCCTCGTTCATCCGGGCGGGGGCCATCACCTCCGACACCAACAAGAAGTGGTACATGTTCGATGGGCCGGTGGATGCCATCTGGATTGAGAACATGAACACGGTGCTGGATGACAACAAGAAGCTGTGCCTCAGCTCTGGGGAGATCATCAAGCTCACAGAGGCAATGACCATGATGTTCGAGGTGCAAGACCTGGCGGTGGCTTCACCAGCTACAGTCTCCCGCTGTGGCATGGTGTACCTGGAGCCCAGCATCCTGGGGCTCATGCCCTTCATCGAGTGCTGGCTGAGGAAGCTGCCTCCCTTGCTGAAGCCCTATGAGGAGCATTTCAAGGCCCTCTTTGTCAGCTTCCTGGAGGAATCCATCTCCTTCGTTCGGTCCTCAGTGAAGGAGGTGATCGCCTCAACCAACTGCAACCTGACCATGAGCCTCCTCAAGCTGCTGGACTGCTTCTTCAAGCCCTTTCTGCCTAGAGAGGGCCTCAAGAAAATACCCTCTGAAAAGCTGAGTCGCATCGTAGAGTTGATCGAGCCCTGGTTCATCTTCTCCCTGATCTGGAGCGTGGGTGCCACTGGGGACAGCAGTGGCCGCACCAGTTTCAGCCACTGGCTAAGGCTCAAGATGGAGAACGAACAGCTGACTCTGCTTTTCCCAGAAGAGGGGCTGGTGTTCGATTACAGGCTGGAGGACGCGGGCATCAGTGGCACCAACGACAGTGAGGATGAAGAGGAGGAATACAAGCAGGTTGCCTGGGTGAAGTGGATGGACTCCTCAGCTCCATTCACCATGGTACCAGACACCAACTACTGCAACATCATTGTGCCCACCATGGACACCGTGCAGATGTCCCATTTACTGGACATGCTGCTCACCAACAAGAAGCCCGTGCTGTGCATTGGGCCAACAGGCACGGGGAAGACGCTCACCATCTCTGACAAGCTCCTCAAGAACCTGGCACTGGATTACATCAGCCACTTCCTCACCTTCTCAGCCCGCACTTCAGCCAACCAGACCCAGGACTTCATTGACAGCAAGCTGGACAAGAGGCGGAAGGGTGTGTTTGGACCACCTCTGGGGCGCAACTTTATCTTCTTCATCGATGACCTGAACATGCCGGCCCTGGAGACCTACGGTGCACAGCCACCCATCGAGCTGTTGCGCCAGTGGATGGACCACGGCGGCTGGTACGACCGCAAGATCATTGGTGCCTTCAAGAACCTAGTGGACATCAACTTTGTCTGTGCCATGGGCCCCCCGGGTGGAGGCAGGAACACCGTCACCCCGCGGCTGATGCGTCACTTCAACTACCTGTCTTTCGCTGAGATGGACGAGGTCAGCAAGAAACGCATCTTCTCCACCATCCTGGGCAACTGGTTGGATGGACTCCTTGGAGAAAAAAGCTACCGGGAGCGTGTGCCTGGGGCCCCCCACATTGCCCACTTCACGGAGCCCCTTGTGGAAGCCACCATCATGGTGTATGCAACCATCACCTCCCAGCTGCTGCCCACTCCAGCCAAGTCCCACTACACCTTCAACCTGAGGGACCTCTCCAAGGTCTTCCAAGGCATGCTCATGGCTGACCCGGCCAAGGTCGAGGACCAAGTGCAGCTGCTGCGACTGTGGTATCACGAGAACTGCCGCGTGTTCCGGGACCGACTGGTGAATGAGGAGGACCGCAGCTGGTTCGACCAGCTCCTCAAGCGCTGCATGGAGCAGTGGGAGGTGACCTTCAACAAGGTCTGCCCCTTCCAGCCCATTCTTTACGGGGACTTCATGTCACCAGGCTCCGATGTCAAGTCCTACGAGCTCATCACCAGTGAGAGTAAGATGATGCAGGTGATAGAGGAGTACATAGAGGACTACAACCAGATCAACACGGCCAAGCTGAAGCTGGTCCTCTTCATGGACGCCATGAGCCACATCTGTCGCATCAGCCGCACCCTACGCCAGGCGCTGGGCAATGCACTCCTGCTGGGCGTGGGTGGCAGCGGCCGCAGCTCCCTCACAAGGCTCGCCTCGCACATGGCCGAGTACGAGTGCTTCCAGATTGAACTATCCAAGAACTACGGCATGTCCGAGTGGCGAGATGATGTGAAGAAGGTCCTGCTCAAGGCGGGCCTACAGAACCTACCCATCACCTTCCTCTTCTCAGACACCCAGATCAAGAACGAATCCTTCCTGGAAGATATCAACAACGTCCTAAACTCTGGTGACATTCCCAATCTGTATACTGCGGACGAGCAGGACCAGATCGTCAGCACCATGCGGCCCTATATCCAGGAGCAGGGCCTACAGCCCACCAAGGCCAACCTCATGGCTGCTTACACAGGGCGTGTGCGCAGCAACATCCACATGGTGCTGTGCATGAGCCCCATCGGAGAGGTCTTCCGAGCTCGTCTGAGGCAGTTTCCCTCCCTGGTCAACTGCTGTACCATCGACTGGTTTAACGAGTGGCCGGCAGAAGCCCTGAAGTCTGTGGCCACCGTGTTCCTCAATGAGATCCCAGAACTGGAATCCTCCCAGGAAGAAATCCAAGGACTGATCCAGGTCTGTGTGTACATCCACCAGTCGGTGTCCAAGAAGTGCATCGAGTACCTGGCAGAGCTGACCCGCCACAACTATGTGACCCCCAAGAGCTACTTGGAGCTGCTTCATATTTTCTCCATCCTCATCGGGCAGAAGAAACTGGAGCTGAAAACTGCCAAGAACCGCATGAAGAGCGGCCTCGACAAGCTGCTGCGCACTTCTGAGGATGTAGCCAAGATGCAGGAGGACCTGGAGAGTATGCACCCCCTGCTGGAGGAGGCTGCCAAGGACACCATGCTCACCATGGAGCAGATCAAGGTGGATACGGCCATCGCCGAGGAGACCCGGAATTCAGTGCAGACAGAGGAGATCAAAGCCAATGAGAAGGCCAAGAAGGCACAAGCTATTGCTGACGATGCCCAGAAGGACCTGGACGAGGCGTTGCCAGCCCTGGATGCGGCTCTGGCCAGCCTGCGCAACCTCAACAAGAACGATGTGACCGAGGTACGTGCCATGCAGCGGCCACCCCCGGGTGTGAAACTGGTCATAGAAGCTGTGTGCATTATGAAAGGCATCAAGCCCAAGAAGGTGCCTGGAGAAAAGCCAGGCACCAAGGTGGATGACTACTGGGAGCCTGGCAAGGGGCTGCTGCAGGACCCGGGCCACTTCCTTGAGAGCCTCTTCAAGTTTGACAAGGACAACATTGGGGATGTGGTGATCAAAGCCATCCAGCCGTACATCGATAATGAAGAGTTCCAGCCAGCCACCATTGCCAAGGTGTCCAAGGCTTGCACCTCCATCTGCCAGTGGGTGCGCGCCATGCACAAGTACCACTTTGTGGCCAAGGCCGTGGAGCCCAAGCGGCAAGCCCTGCTGGAGGCCCAGGATGACCTGGGGGTGACACAGAGGATCCTGGATGAGGCAAAACAGCGCCTTCGTGAGGTGGAGGACGGCATCGCCACAATGCAGGCTAAGTACCGGGAATGCATTACCAAGAAGGAGGAGCTGGAGCTGAAGTGTGAGCAGTGTGAGCAGCGGCTGGGCCGAGCTGGCAAGCTCATCAACGGGCTGTCGGATGAGAAGGTGCGCTGGCAGGAGACGGTGGAGAACCTGCAGTACATGCTCAACAACATCTCCGGCGAT
GTCCTGGTGGCCGCTGGCTTTGTGGCCTACCTGGGCCCCTTCACGGGCCAGTACCGCACGGTGCTCTACGACAGCTGGGTCAAGCAGCTCAGGAGCCACAATGTCCCACACACCTCCGAGCCCACGCTAATCGGGACGCTGGGGAACCCTGTGAAGATCCGATCGTGGCAGATCGCTGGCCTCCCCAACGACACACTGTCAGTGGAGAACGGGGTCATCAACCAGTTTTCCCAGCGCTGGACCCACTTCATTGACCCTCAGAGCCAGGCCAACAAATGGATCAAGAACATGGAGAAGGACAATGGGCTGGATGTGTTCAAGTTGAGTGACCGCGACTTCCTGCGCAGCATGGAGAACGCCATCCGCTTTGGCAAGCCATGTCTCCTGGAGAACGTGGGCGAGGAGCTAGACCCAGCCCTGGAGCCAGTGCTGCTCAAGCAGACGTACAAGCAGCAGGGAAACACGGTGCTGAAGCTGGGGGACACGGTGATCCCCTACCATGAGGACTTCAGGATGTACATCACCACCAAGCTGCCCAACCCACACTACACGCCCGAGATCTCCACCAAACTCACCCTCATCAACTTCACCCTGTCGCCCAGTGGCCTAGAGGACCAGCTACTGGGCCAGGTAGTGGCAGAGGAGCGACCCGACCTGGAGGAGGCCAAGAACCAGCTGATTATCAGTAATGCCAAGATGCGCCAGGAGCTGAAGGACATTGAGGACCAGATCCTGTACCGGCTCAGCTCCTCCGAGGGCAACCCTGTAGATGACATGGAACTCATCAAGGTGCTGGAAGCCTCCAAGATGAAGGCTGCTGAGATCCAGGCCAAAGTCAGGATTGCAGAGCAGACGGAGAAGGACATCGACCTGACGCGCATGGAGTACATACCCGTGGCCATCCGCACCCAGATCCTCTTCTTCTGTGTGTCCGACCTGGCCAACGTGGACCCCATGTACCAGTACTCCCTTGAGTGGTTTCTCAACATCTTCCTCTCGGGCATCGCCAACTCAGAGAGAGCAGACAACCTGAAGAAGCGCATCTCCAACATCAACCGCTACCTGACCTACAGCCTCTACAGCAACGTCTGCCGCAGCCTCTTTGAGAAGCACAAGCTGATGTTTGCCTTCCTGCTGTGTGTTCGCATCATGATGAACGAGGGCAAAATCAACCAGAGTGAGTGGCGATACCTCCTGTCTGGGGGCTCCATCTCGATCATGACTGAGAATCCGGCACCGGACTGGCTGTCAGACCGGGCTTGGCGAGACATCCTAGCACTCTCGAACCTGCCAACCTTTTCCTCCTTCTCTTCCGACTTCGTGAAGCACCTCTCAGAATTCCGGGTCATCTTCGACAGCCTTGAGCCCCACCGGGAGCCTTTGCCTGGCATCTGGGACCAGTACCTAGACCAGTTCCAGAAGCTGCTAGTCCTCCGCTGCCTGCGTGGGGACAAGGTTACCAACGCCATGCAGGACTTTGTGGCCACCAACCTGGAGCCACGCTTCATTGAACCCCAGACAGCCAATCTGTCAGTGGTGTTCAAAGACTCCAACTCCACCACACCCCTCATCTTTGTGCTGTCACCCGGCACAGACCCTGCTGCCGACCTCTACAAGTTTGCCGAAGAAATGAAGTTCTCCAAAAAGCTCTCTGCCATCTCCCTGGGCCAGGGGCAGGGCCCTCGGGCAGAAGCCATGATGCGCAGCTCCATAGAGAGGGGCAAATGGGTCTTCTTCCAGAACTGCCACCTGGCACCAAGCTGGATGCCAGCCCTAGAACGCCTCATCGAGCACATCAACCCCGACAAGGTACACAGGGACTTCCGCCTCTGGCTCACCAGCCTGCCCAGCAACAAGTTCCCAGTGTCCATCCTGCAGAACGGCTCCAAGATGACCATTGAGCCGCCACGCGGTGTCAGGGCCAACCTGCTGAAGTCCTATAGTAGCCTTGGTGAAGACTTCCTCAACTCCTGCCACAAGGTGATGGAGTTCAAGTCTCTGCTGCTGTCTCTGTGCTTGTTCCATGGGAACGCCCTGGAGCGCCGTAAGTTTGGGCCCCTGGGCTTCAACATCCCCTATGAGTTCACGGATGGAGATCTGCGCATCTGCATCAGCCAGCTCAAGATGTTCCTGGACGAATATGATGACATCCCCTACAAGGTCCTCAAGTACACGGCAGGGGAGATCAATTACGGGGGCCGTGTCACTGATGACTGGGACCGGCGCTGCATCATGAACATCTTGGAGGACTTCTACAACCCTGACGTGCTCTCCCCTGAGCACAGCTACAGCGCCTCGGGCATCTACCACCAGATCCCGCCTACCTACGACCTCCACGGCTACCTCTCCTACATCAAGAGCCTCCCACTCAATGATATGCCTGAGATCTTTGGCCTGCATGACAATGCCAACATCACCTTTGCCCAGAACGAGACGTTCGCCCTCCTGGGCACCATCATCCAGCTGCAACCCAAATCATCTTCTGCAGGCAGCCAGGGCCGGGAGGAGATAGTGGAGGACGTCACCCAAAACATTCTGCTCAAGGTGCCTGAGCCTATCAACTTGCAATGGGTGATGGCCAAGTACCCAGTGCTGTATGAGGAATCAATGAACACAGTACTAGTACAAGAGGTCATTAGGTACAATCGGCTGCTGCAGGTGATCACACAGACACTGCAAGACCTACTCAAGGCACTCAAGGGGCTGGTAGTGATGTCCTCTCAGCTGGAGCTGATGGCTGCCAGCCTGTACAACAATACTGTGCCTGAGCTCTGGAGTGCCAAGGCCTACCCATCGCTCAAGCCTCTGTCATCATGGGTCATGGACCTGCTGCAACGCCTGGACTTTCTGCAGGCCTGGATCCAAGATGGCATCCCAGCTGTCTTCTGGATCAGTGGATTCTTCTTCCCCCAGGCTTTCTTAACAGGCACTCTGCAGAATTTTGCCCGCAAATTTGTCATCTCCATTGACACCATCTCCTTTGATTTCAAGGTGATGTTTGAGGCACCATCAGAGTTAACACAAAGACCCCAAGTAGGGTGCTATATCCATGGATTATTCCTGGAAGGTGCCCGCTGGGATCCAGAGGCCTTCCAGCTGGCTGAGTCTCAGCCCAAGGAGCTGTACACAGAGATGGCCGTTATCTGGCTCTTGCCAACACCCAACCGCAAGGCCCAGGACCAGGACTTTTACCTGTGCCCCATCTACAAGACACTGACTCGTGCTGGAACACTATCAACCACAGGACACTCTACCAACTATGTCATTGCTGTGGAGATCCCCACCCATCAGCCCCAGCGACACTGGATAAAGCGTGGTGTGGCCCTCATCTGTGCCCTGGACTACTAG
SEQ ID NO:2：野生型DNAH1蛋白的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELREWMKGIPERLVGLEERIVKVMDDYQVMDEFLYNLSSDDFNDKWIASNWPSKILGQIELVQQQHVEDEEKFRKIQIMDQNNFQEKLEGLQLVVAGFSIHVEISRAHEIANEVRRVKKQLKDCQQLAMLYNNRERIFSLPITNYDKLSRMVKEFQPYLDLWTTASDWLRWSESWMNDPLSAIDAEQLEKNVVEAFKTMHKCVKQFKDMPACQEVALDIRARIEEFKPYIPLIQGLRNPGMRIRHWETLSNQININVRPKANLTFARCLEMNLQDHIESISKVAEVAGKEYAIEQALDKMEKEWSTILFNVLPYKATDTYILKSPDEASQLLDDHIVMTQNMSFSPYKKPFEQRINSWENKLKLTQEVLEEWLNCQRSWLYLEPIFSSEDINQQLPVESKRYQTMERIWKKIMKNAYENREVINVCSDLRMLDSLRDCNKILDLVQKGLSEYLETKRSAFPRFYFLSDDELLEILSQTKDPTAVQPHLRKCFENIARLLFQEDLEITHMYSAEGEEVQLCFSIYPSSNVEDWLREVERSMKASVHDIIEKAIRAYPTMPRTQWVLNWPGQVTIAGCQTYWTMEVAEALEAGNLRSQLFPQLCQQLSDLVALVRGKLSRMQRAVLSALIVIEVHAKDVVSKLIQENVVSVNDFQWISQLRYYWTNNDLYIRAVNAEFIYGYEYLGNSGRLVITPLTDRCYLTLTGALHLKFGGAPAGPAGTGKTETTKDLGKALAIQTVVFNCSDQLDFMAMGKFFKGLASAGAWACFDEFNRIDIEVLSVVAQQITTIQKAQQQRVERFMFEGVEIPLVPSCAVFITMNPGYAGRTELPDNLKALFRPVAMMVPDYAMITEISLYSFGFNEASVLAKKITTTFKLSSEQLSSQDHYDFGMRAVKTVISAAGNLKRENPSMNEELICLRAIRDVNVPKFLQEDLKLFSGIVSDLFPTIKEEDTDYGILDEAIREACRNSNLKDVEGFLTKCIQLYETTVVRHGLMLVGPTGSGKSTCYRVLAAAMTSLKGQPSISGGMYEAVNYYVLNPKSITMGQLYGEFDLLTHEWTDGIFSSFIRAGAITSDTNKKWYMFDGPVDAIWIENMNTVLDDNKKLCLSSGEIIKLTEAMTMMFEVQDLAVASPATVSRCGMVYLEPSILGLMPFIECWLRKLPPLLKPYEEHFKALFVSFLEESISFVRSSVKEVIASTNCNLTMSLLKLLDCFFKPFLPREGLKKIPSEKLSRIVELIEPWFIFSLIWSVGATGDSSGRTSFSHWLRLKMENEQLTLLFPEEGLVFDYRLEDAGISGTNDSEDEEEEYKQVAWVKWMDSSAPFTMVPDTNYCNIIVPTMDTVQMSHLLDMLLTNKKPVLCIGPTGTGKTLTISDKLLKNLALDYISHFLTFSARTSANQTQDFIDSKLDKRRKGVFGPPLGRNFIFFIDDLNMPALETYGAQPPIELLRQWMDHGGWYDRKIIGAFKNLVDINFVCAMGPPGGGRNTVTPRLMRHFNYLSFAEMDEVSKKRIFSTILGNWLDGLLGEKSYRERVPGAPHIAHFTEPLVEATIMVYATITSQLLPTPAKSHYTFNLRDLSKVFQGMLMADPAKVEDQVQLLRLWYHENCRVFRDRLVNEEDRSWFDQLLKRCMEQWEVTFNKVCPFQPILYGDFMSPGSDVKSYELITSESKMMQVIEEYIEDYNQINTAKLKLVLFMDAMSHICRISRTLRQALGNALLLGVGGSGRSSLTRLASHMAEYECFQIELSKNYGMSEWRDDVKKVLLKAGLQNLPITFLFSDTQIKNESFLEDINNVLNSGDIPNLYTADEQDQIVSTMRPYIQEQGLQPTKANLMAAYTGRVRSNIHMVLCMSPIGEVFRARLRQFPSLVNCCTIDWFNEWPAEALKSVATVFLNEIPELESSQEEIQGLIQVCVYIHQSVSKKCIEYLAELTRHNYVTPKSYLELLHIFSILIGQKKLELKTAKNRMKSGLDKLLRTSEDVAKMQEDLESMHPLLEEAAKDTMLTMEQIKVDTAIAEETRNSVQTEEIKANEKAKKAQAIADDAQKDLDEALPALDAALASLRNLNKNDVTEVRAMQRPPPGVKLVIEAVCIMKGIKPKKVPGEKPGTKVDDYWEPGKGLLQDPGHFLESLFKFDKDNIGDVVIKAIQPYIDNEEFQPATIAKVSKACTSICQWVRAMHKYHFVAKAVEPKRQALLEAQDDLGVTQRILDEAKQRLREVEDGIATMQAKYRECITKKEELELKCEQCEQRLGRAGKLINGLSDEKVRWQETVENLQYMLNNISGDVLVAAGFVAYLGPFTGQYRTVLYDSWVKQLRSHNVPHTSEPTLIGTLGNPVKIRSWQIAGLPNDTLSVENGVINQFSQRWTHFIDPQSQANKWIKNMEKDNGLDVFKLSDRDFLRSMENAIRFGKPCLLENVGEELDPALEPVLLKQTYKQQGNTVLKLGDTVIPYHEDFRMYITTKLPNPHYTPEISTKLTLINFTLSPSGLEDQLLGQVVAEERPDLEEAKNQLIISNAKMRQELKDIEDQILYRLSSSEGNPVDDMELIKVLEASKMKAAEIQAKVRIAEQTEKDIDLTRMEYIPVAIRTQILFFCVSDLANVDPMYQYSLEWFLNIFLSGIANSERADNLKKRISNINRYLTYSLYSNVCRSLFEKHKLMFAFLLCVRIMMNEGKINQSEWRYLLSGGSISIMTENPAPDWLSDRAWRDILALSNLPTFSSFSSDFVKHLSEFRVIFDSLEPHREPLPGIWDQYLDQFQKLLVLRCLRGDKVTNAMQDFVATNLEPRFIEPQTANLSVVFKDSNSTTPLIFVLSPGTDPAADLYKFAEEMKFSKKLSAISLGQGQGPRAEAMMRSSIERGKWVFFQNCHLAPSWMPALERLIEHINPDKVHRDFRLWLTSLPSNKFPVSILQNGSKMTIEPPRGVRANLLKSYSSLGEDFLNSCHKVMEFKSLLLSLCLFHGNALERRKFGPLGFNIPYEFTDGDLRICISQLKMFLDEYDDIPYKVLKYTAGEINYGGRVTDDWDRRCIMNILEDFYNPDVLSPEHSYSASGIYHQIPPTYDLHGYLSYIKSLPLNDMPEIFGLHDNANITFAQNETFALLGTIIQLQPKSSSAGSQGREEIVEDVTQNILLKVPEPINLQWVMAKYPVLYEESMNTVLVQEVIRYNRLLQVITQTLQDLLKALKGLVVMSSQLELMAASLYNNTVPELWSAKAYPSLKPLSSWVMDLLQRLDFLQAWIQDGIPAVFWISGFFFPQAFLTGTLQNFARKFVISIDTISFDFKVMFEAPSELTQRPQVGCYIHGLFLEGARWDPEAFQLAESQPKELYTEMAVIWLLPTPNRKAQDQDFYLCPIYKTLTRAGTLSTTGHSTNYVIAVEIPTHQPQRHWIKRGVALICALDY
SEQ ID NO:29：突变DNAH1蛋白(p.W1036X)的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELREWMKGIPERLVGLEERIVKVMDDYQVMDEFLYNLSSDDFNDKWIASNWPSKILGQIELVQQQHVEDEEKFRKIQIMDQNNFQEKLEGLQLVVAGFSIHVEISRAHEIANEVRRVKKQLKDCQQLAMLYNNRERIFSLPITNYDKLSRMVKEFQPYLDLWTTASDWLR
SEQ ID NO:30：突变DNAH1蛋白(p.W1955X)的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELREWMKGIPERLVGLEERIVKVMDDYQVMDEFLYNLSSDDFNDKWIASNWPSKILGQIELVQQQHVEDEEKFRKIQIMDQNNFQEKLEGLQLVVAGFSIHVEISRAHEIANEVRRVKKQLKDCQQLAMLYNNRERIFSLPITNYDKLSRMVKEFQPYLDLWTTASDWLRWSESWMNDPLSAIDAEQLEKNVVEAFKTMHKCVKQFKDMPACQEVALDIRARIEEFKPYIPLIQGLRNPGMRIRHWETLSNQININVRPKANLTFARCLEMNLQDHIESISKVAEVAGKEYAIEQALDKMEKEWSTILFNVLPYKATDTYILKSPDEASQLLDDHIVMTQNMSFSPYKKPFEQRINSWENKLKLTQEVLEEWLNCQRSWLYLEPIFSSEDINQQLPVESKRYQTMERIWKKIMKNAYENREVINVCSDLRMLDSLRDCNKILDLVQKGLSEYLETKRSAFPRFYFLSDDELLEILSQTKDPTAVQPHLRKCFENIARLLFQEDLEITHMYSAEGEEVQLCFSIYPSSNVEDWLREVERSMKASVHDIIEKAIRAYPTMPRTQWVLNWPGQVTIAGCQTYWTMEVAEALEAGNLRSQLFPQLCQQLSDLVALVRGKLSRMQRAVLSALIVIEVHAKDVVSKLIQENVVSVNDFQWISQLRYYWTNNDLYIRAVNAEFIYGYEYLGNSGRLVITPLTDRCYLTLTGALHLKFGGAPAGPAGTGKTETTKDLGKALAIQTVVFNCSDQLDFMAMGKFFKGLASAGAWACFDEFNRIDIEVLSVVAQQITTIQKAQQQRVERFMFEGVEIPLVPSCAVFITMNPGYAGRTELPDNLKALFRPVAMMVPDYAMITEISLYSFGFNEASVLAKKITTTFKLSSEQLSSQDHYDFGMRAVKTVISAAGNLKRENPSMNEELICLRAIRDVNVPKFLQEDLKLFSGIVSDLFPTIKEEDTDYGILDEAIREACRNSNLKDVEGFLTKCIQLYETTVVRHGLMLVGPTGSGKSTCYRVLAAAMTSLKGQPSISGGMYEAVNYYVLNPKSITMGQLYGEFDLLTHEWTDGIFSSFIRAGAITSDTNKKWYMFDGPVDAI
SEQ ID NO:31：突变DNAH1蛋白(p.W870X)的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELRE
SEQ ID NO:32：突变DNAH1蛋白(p.E3544X)的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELREWMKGIPERLVGLEERIVKVMDDYQVMDEFLYNLSSDDFNDKWIASNWPSKILGQIELVQQQHVEDEEKFRKIQIMDQNNFQEKLEGLQLVVAGFSIHVEISRAHEIANEVRRVKKQLKDCQQLAMLYNNRERIFSLPITNYDKLSRMVKEFQPYLDLWTTASDWLRWSESWMNDPLSAIDAEQLEKNVVEAFKTMHKCVKQFKDMPACQEVALDIRARIEEFKPYIPLIQGLRNPGMRIRHWETLSNQININVRPKANLTFARCLEMNLQDHIESISKVAEVAGKEYAIEQALDKMEKEWSTILFNVLPYKATDTYILKSPDEASQLLDDHIVMTQNMSFSPYKKPFEQRINSWENKLKLTQEVLEEWLNCQRSWLYLEPIFSSEDINQQLPVESKRYQTMERIWKKIMKNAYENREVINVCSDLRMLDSLRDCNKILDLVQKGLSEYLETKRSAFPRFYFLSDDELLEILSQTKDPTAVQPHLRKCFENIARLLFQEDLEITHMYSAEGEEVQLCFSIYPSSNVEDWLREVERSMKASVHDIIEKAIRAYPTMPRTQWVLNWPGQVTIAGCQTYWTMEVAEALEAGNLRSQLFPQLCQQLSDLVALVRGKLSRMQRAVLSALIVIEVHAKDVVSKLIQENVVSVNDFQWISQLRYYWTNNDLYIRAVNAEFIYGYEYLGNSGRLVITPLTDRCYLTLTGALHLKFGGAPAGPAGTGKTETTKDLGKALAIQTVVFNCSDQLDFMAMGKFFKGLASAGAWACFDEFNRIDIEVLSVVAQQITTIQKAQQQRVERFMFEGVEIPLVPSCAVFITMNPGYAGRTELPDNLKALFRPVAMMVPDYAMITEISLYSFGFNEASVLAKKITTTFKLSSEQLSSQDHYDFGMRAVKTVISAAGNLKRENPSMNEELICLRAIRDVNVPKFLQEDLKLFSGIVSDLFPTIKEEDTDYGILDEAIREACRNSNLKDVEGFLTKCIQLYETTVVRHGLMLVGPTGSGKSTCYRVLAAAMTSLKGQPSISGGMYEAVNYYVLNPKSITMGQLYGEFDLLTHEWTDGIFSSFIRAGAITSDTNKKWYMFDGPVDAIWIENMNTVLDDNKKLCLSSGEIIKLTEAMTMMFEVQDLAVASPATVSRCGMVYLEPSILGLMPFIECWLRKLPPLLKPYEEHFKALFVSFLEESISFVRSSVKEVIASTNCNLTMSLLKLLDCFFKPFLPREGLKKIPSEKLSRIVELIEPWFIFSLIWSVGATGDSSGRTSFSHWLRLKMENEQLTLLFPEEGLVFDYRLEDAGISGTNDSEDEEEEYKQVAWVKWMDSSAPFTMVPDTNYCNIIVPTMDTVQMSHLLDMLLTNKKPVLCIGPTGTGKTLTISDKLLKNLALDYISHFLTFSARTSANQTQDFIDSKLDKRRKGVFGPPLGRNFIFFIDDLNMPALETYGAQPPIELLRQWMDHGGWYDRKIIGAFKNLVDINFVCAMGPPGGGRNTVTPRLMRHFNYLSFAEMDEVSKKRIFSTILGNWLDGLLGEKSYRERVPGAPHIAHFTEPLVEATIMVYATITSQLLPTPAKSHYTFNLRDLSKVFQGMLMADPAKVEDQVQLLRLWYHENCRVFRDRLVNEEDRSWFDQLLKRCMEQWEVTFNKVCPFQPILYGDFMSPGSDVKSYELITSESKMMQVIEEYIEDYNQINTAKLKLVLFMDAMSHICRISRTLRQALGNALLLGVGGSGRSSLTRLASHMAEYECFQIELSKNYGMSEWRDDVKKVLLKAGLQNLPITFLFSDTQIKNESFLEDINNVLNSGDIPNLYTADEQDQIVSTMRPYIQEQGLQPTKANLMAAYTGRVRSNIHMVLCMSPIGEVFRARLRQFPSLVNCCTIDWFNEWPAEALKSVATVFLNEIPELESSQEEIQGLIQVCVYIHQSVSKKCIEYLAELTRHNYVTPKSYLELLHIFSILIGQKKLELKTAKNRMKSGLDKLLRTSEDVAKMQEDLESMHPLLEEAAKDTMLTMEQIKVDTAIAEETRNSVQTEEIKANEKAKKAQAIADDAQKDLDEALPALDAALASLRNLNKNDVTEVRAMQRPPPGVKLVIEAVCIMKGIKPKKVPGEKPGTKVDDYWEPGKGLLQDPGHFLESLFKFDKDNIGDVVIKAIQPYIDNEEFQPATIAKVSKACTSICQWVRAMHKYHFVAKAVEPKRQALLEAQDDLGVTQRILDEAKQRLREVEDGIATMQAKYRECITKKEELELKCEQCEQRLGRAGKLINGLSDEKVRWQETVENLQYMLNNISGDVLVAAGFVAYLGPFTGQYRTVLYDSWVKQLRSHNVPHTSEPTLIGTLGNPVKIRSWQIAGLPNDTLSVENGVINQFSQRWTHFIDPQSQANKWIKNMEKDNGLDVFKLSDRDFLRSMENAIRFGKPCLLENVGEELDPALEPVLLKQTYKQQGNTVLKLGDTVIPYHEDFRMYITTKLPNPHYTPEISTKLTLINFTLSPSGLEDQLLGQVVAEERPDLEEAKNQLIISNAKMRQELKDIEDQILYRLSSSEGNPVDDMELIKVLEASKMKAAEIQAKVRIAEQTEKDIDLTRMEYIPVAIRTQILFFCVSDLANVDPMYQYSLEWFLNIFLSGIANSERADNLKKRISNINRYLTYSLYSNVCRSLFEKHKLMFAFLLCVRIMMNEGKINQS
SEQ ID NO:33：突变DNAH1蛋白(p.P3909Rfs*33)的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELREWMKGIPERLVGLEERIVKVMDDYQVMDEFLYNLSSDDFNDKWIASNWPSKILGQIELVQQQHVEDEEKFRKIQIMDQNNFQEKLEGLQLVVAGFSIHVEISRAHEIANEVRRVKKQLKDCQQLAMLYNNRERIFSLPITNYDKLSRMVKEFQPYLDLWTTASDWLRWSESWMNDPLSAIDAEQLEKNVVEAFKTMHKCVKQFKDMPACQEVALDIRARIEEFKPYIPLIQGLRNPGMRIRHWETLSNQININVRPKANLTFARCLEMNLQDHIESISKVAEVAGKEYAIEQALDKMEKEWSTILFNVLPYKATDTYILKSPDEASQLLDDHIVMTQNMSFSPYKKPFEQRINSWENKLKLTQEVLEEWLNCQRSWLYLEPIFSSEDINQQLPVESKRYQTMERIWKKIMKNAYENREVINVCSDLRMLDSLRDCNKILDLVQKGLSEYLETKRSAFPRFYFLSDDELLEILSQTKDPTAVQPHLRKCFENIARLLFQEDLEITHMYSAEGEEVQLCFSIYPSSNVEDWLREVERSMKASVHDIIEKAIRAYPTMPRTQWVLNWPGQVTIAGCQTYWTMEVAEALEAGNLRSQLFPQLCQQLSDLVALVRGKLSRMQRAVLSALIVIEVHAKDVVSKLIQENVVSVNDFQWISQLRYYWTNNDLYIRAVNAEFIYGYEYLGNSGRLVITPLTDRCYLTLTGALHLKFGGAPAGPAGTGKTETTKDLGKALAIQTVVFNCSDQLDFMAMGKFFKGLASAGAWACFDEFNRIDIEVLSVVAQQITTIQKAQQQRVERFMFEGVEIPLVPSCAVFITMNPGYAGRTELPDNLKALFRPVAMMVPDYAMITEISLYSFGFNEASVLAKKITTTFKLSSEQLSSQDHYDFGMRAVKTVISAAGNLKRENPSMNEELICLRAIRDVNVPKFLQEDLKLFSGIVSDLFPTIKEEDTDYGILDEAIREACRNSNLKDVEGFLTKCIQLYETTVVRHGLMLVGPTGSGKSTCYRVLAAAMTSLKGQPSISGGMYEAVNYYVLNPKSITMGQLYGEFDLLTHEWTDGIFSSFIRAGAITSDTNKKWYMFDGPVDAIWIENMNTVLDDNKKLCLSSGEIIKLTEAMTMMFEVQDLAVASPATVSRCGMVYLEPSILGLMPFIECWLRKLPPLLKPYEEHFKALFVSFLEESISFVRSSVKEVIASTNCNLTMSLLKLLDCFFKPFLPREGLKKIPSEKLSRIVELIEPWFIFSLIWSVGATGDSSGRTSFSHWLRLKMENEQLTLLFPEEGLVFDYRLEDAGISGTNDSEDEEEEYKQVAWVKWMDSSAPFTMVPDTNYCNIIVPTMDTVQMSHLLDMLLTNKKPVLCIGPTGTGKTLTISDKLLKNLALDYISHFLTFSARTSANQTQDFIDSKLDKRRKGVFGPPLGRNFIFFIDDLNMPALETYGAQPPIELLRQWMDHGGWYDRKIIGAFKNLVDINFVCAMGPPGGGRNTVTPRLMRHFNYLSFAEMDEVSKKRIFSTILGNWLDGLLGEKSYRERVPGAPHIAHFTEPLVEATIMVYATITSQLLPTPAKSHYTFNLRDLSKVFQGMLMADPAKVEDQVQLLRLWYHENCRVFRDRLVNEEDRSWFDQLLKRCMEQWEVTFNKVCPFQPILYGDFMSPGSDVKSYELITSESKMMQVIEEYIEDYNQINTAKLKLVLFMDAMSHICRISRTLRQALGNALLLGVGGSGRSSLTRLASHMAEYECFQIELSKNYGMSEWRDDVKKVLLKAGLQNLPITFLFSDTQIKNESFLEDINNVLNSGDIPNLYTADEQDQIVSTMRPYIQEQGLQPTKANLMAAYTGRVRSNIHMVLCMSPIGEVFRARLRQFPSLVNCCTIDWFNEWPAEALKSVATVFLNEIPELESSQEEIQGLIQVCVYIHQSVSKKCIEYLAELTRHNYVTPKSYLELLHIFSILIGQKKLELKTAKNRMKSGLDKLLRTSEDVAKMQEDLESMHPLLEEAAKDTMLTMEQIKVDTAIAEETRNSVQTEEIKANEKAKKAQAIADDAQKDLDEALPALDAALASLRNLNKNDVTEVRAMQRPPPGVKLVIEAVCIMKGIKPKKVPGEKPGTKVDDYWEPGKGLLQDPGHFLESLFKFDKDNIGDVVIKAIQPYIDNEEFQPATIAKVSKACTSICQWVRAMHKYHFVAKAVEPKRQALLEAQDDLGVTQRILDEAKQRLREVEDGIATMQAKYRECITKKEELELKCEQCEQRLGRAGKLINGLSDEKVRWQETVENLQYMLNNISGDVLVAAGFVAYLGPFTGQYRTVLYDSWVKQLRSHNVPHTSEPTLIGTLGNPVKIRSWQIAGLPNDTLSVENGVINQFSQRWTHFIDPQSQANKWIKNMEKDNGLDVFKLSDRDFLRSMENAIRFGKPCLLENVGEELDPALEPVLLKQTYKQQGNTVLKLGDTVIPYHEDFRMYITTKLPNPHYTPEISTKLTLINFTLSPSGLEDQLLGQVVAEERPDLEEAKNQLIISNAKMRQELKDIEDQILYRLSSSEGNPVDDMELIKVLEASKMKAAEIQAKVRIAEQTEKDIDLTRMEYIPVAIRTQILFFCVSDLANVDPMYQYSLEWFLNIFLSGIANSERADNLKKRISNINRYLTYSLYSNVCRSLFEKHKLMFAFLLCVRIMMNEGKINQSEWRYLLSGGSISIMTENPAPDWLSDRAWRDILALSNLPTFSSFSSDFVKHLSEFRVIFDSLEPHREPLPGIWDQYLDQFQKLLVLRCLRGDKVTNAMQDFVATNLEPRFIEPQTANLSVVFKDSNSTTPLIFVLSPGTDPAADLYKFAEEMKFSKKLSAISLGQGQGPRAEAMMRSSIERGKWVFFQNCHLAPSWMPALERLIEHINPDKVHRDFRLWLTSLPSNKFPVSILQNGSKMTIEPPRGVRANLLKSYSSLGEDFLNSCHKVMEFKSLLLSLCLFHGNALERRKFGPLGFNIPYEFTDGDLRICISQLKMFLDEYDDIPYKVLKYTAGEINYGGRVTDDWDRRCIMNILEDFYNPDVLSRAQLQRLGHLPPDPAYLRPPRLPLLHQEPPTQ
SEQ ID NO:34：突变DNAH1蛋白(p.E2086Gfs*8)的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELREWMKGIPERLVGLEERIVKVMDDYQVMDEFLYNLSSDDFNDKWIASNWPSKILGQIELVQQQHVEDEEKFRKIQIMDQNNFQEKLEGLQLVVAGFSIHVEISRAHEIANEVRRVKKQLKDCQQLAMLYNNRERIFSLPITNYDKLSRMVKEFQPYLDLWTTASDWLRWSESWMNDPLSAIDAEQLEKNVVEAFKTMHKCVKQFKDMPACQEVALDIRARIEEFKPYIPLIQGLRNPGMRIRHWETLSNQININVRPKANLTFARCLEMNLQDHIESISKVAEVAGKEYAIEQALDKMEKEWSTILFNVLPYKATDTYILKSPDEASQLLDDHIVMTQNMSFSPYKKPFEQRINSWENKLKLTQEVLEEWLNCQRSWLYLEPIFSSEDINQQLPVESKRYQTMERIWKKIMKNAYENREVINVCSDLRMLDSLRDCNKILDLVQKGLSEYLETKRSAFPRFYFLSDDELLEILSQTKDPTAVQPHLRKCFENIARLLFQEDLEITHMYSAEGEEVQLCFSIYPSSNVEDWLREVERSMKASVHDIIEKAIRAYPTMPRTQWVLNWPGQVTIAGCQTYWTMEVAEALEAGNLRSQLFPQLCQQLSDLVALVRGKLSRMQRAVLSALIVIEVHAKDVVSKLIQENVVSVNDFQWISQLRYYWTNNDLYIRAVNAEFIYGYEYLGNSGRLVITPLTDRCYLTLTGALHLKFGGAPAGPAGTGKTETTKDLGKALAIQTVVFNCSDQLDFMAMGKFFKGLASAGAWACFDEFNRIDIEVLSVVAQQITTIQKAQQQRVERFMFEGVEIPLVPSCAVFITMNPGYAGRTELPDNLKALFRPVAMMVPDYAMITEISLYSFGFNEASVLAKKITTTFKLSSEQLSSQDHYDFGMRAVKTVISAAGNLKRENPSMNEELICLRAIRDVNVPKFLQEDLKLFSGIVSDLFPTIKEEDTDYGILDEAIREACRNSNLKDVEGFLTKCIQLYETTVVRHGLMLVGPTGSGKSTCYRVLAAAMTSLKGQPSISGGMYEAVNYYVLNPKSITMGQLYGEFDLLTHEWTDGIFSSFIRAGAITSDTNKKWYMFDGPVDAIWIENMNTVLDDNKKLCLSSGEIIKLTEAMTMMFEVQDLAVASPATVSRCGMVYLEPSILGLMPFIECWLRKLPPLLKPYEEHFKALFVSFLEESISFVRSSVKEVIASTNCNLTMSLLKLLDCFFKPFLPRGPQENTL
SEQ ID NO:35：突变DNAH1蛋白(p.N4068del)的氨基酸序列
MEQPNSKGYSLGRTPQGPECSSAPAVQVGTHRGLEYNPGKILPGSDYGLGNPPALDPKLPHLPLPPAPPTLSDLGQPRKSPLTGTDKKYPLMKQRGFYSDILSPGTLDQLGEVCRGPRMSQNLLRQADLDKFTPRVGSFEVPEDFQERMEQQCIGSTTRLLAQTDFPLQAYEPKMQVPFQVLPGQHPRKIEIERRKQQYLSLDIEQLLFSQGIDSNKLMPRHLDHQHPQTIEQGHDPIFPIYLPLKVFDNEDFDCRTPREWINMGLEPGSLDRKPVPGKALLPTDDFLGHEDPKSQKLKYKWCEVGVLDYDEEKKLYLVHKTDEKGLVRDEMGRPILNAGVTTEGRPPLQVCQYWVPRIQLLFCAEDPCMFAQRVVQANALRKNTEALLLYNLYVDCMPSDGQHVISEQSLSKIKQWALSTPRMRKGPSVLEHLSSLAREVSLDYERSMNKINFDHVVSSKPETFSYVTLPKKEEEQVPERGLVSVPKYHFWEQKEDFTFVSLLTRPEVITALSKVRAECNKVTAMSLFHSSLSKYSHLEEFEQIQSQTFSQVQMFLKDSWISSLKVAMRSSLRDMSKGWYNLYETNWEVYLMSKLRKLMELVKYMLQDTLRFLVQDSLASFSQFISDTCCSVLNCTDDMVWGDDLINSPYRPRKNPLFIMDLVLDSSGVHYSTPLEQFEASLLNLFDKGILATHAVPQLEKLVMEDIFISGDPLLESVGLHEPLVEELRATIASAVSKAMIPLQAYAKEYRKYLELNNNDIASFLKTYQTQGLLAQEVREVVLTHLREKEILDSSLPSSIIIGPFYINTDNVKQSLSKKRKALATSVLDILAKNLHKEVDSICEEFRSISRKIYEKPNSIEELAELREWMKGIPERLVGLEERIVKVMDDYQVMDEFLYNLSSDDFNDKWIASNWPSKILGQIELVQQQHVEDEEKFRKIQIMDQNNFQEKLEGLQLVVAGFSIHVEISRAHEIANEVRRVKKQLKDCQQLAMLYNNRERIFSLPITNYDKLSRMVKEFQPYLDLWTTASDWLRWSESWMNDPLSAIDAEQLEKNVVEAFKTMHKCVKQFKDMPACQEVALDIRARIEEFKPYIPLIQGLRNPGMRIRHWETLSNQININVRPKANLTFARCLEMNLQDHIESISKVAEVAGKEYAIEQALDKMEKEWSTILFNVLPYKATDTYILKSPDEASQLLDDHIVMTQNMSFSPYKKPFEQRINSWENKLKLTQEVLEEWLNCQRSWLYLEPIFSSEDINQQLPVESKRYQTMERIWKKIMKNAYENREVINVCSDLRMLDSLRDCNKILDLVQKGLSEYLETKRSAFPRFYFLSDDELLEILSQTKDPTAVQPHLRKCFENIARLLFQEDLEITHMYSAEGEEVQLCFSIYPSSNVEDWLREVERSMKASVHDIIEKAIRAYPTMPRTQWVLNWPGQVTIAGCQTYWTMEVAEALEAGNLRSQLFPQLCQQLSDLVALVRGKLSRMQRAVLSALIVIEVHAKDVVSKLIQENVVSVNDFQWISQLRYYWTNNDLYIRAVNAEFIYGYEYLGNSGRLVITPLTDRCYLTLTGALHLKFGGAPAGPAGTGKTETTKDLGKALAIQTVVFNCSDQLDFMAMGKFFKGLASAGAWACFDEFNRIDIEVLSVVAQQITTIQKAQQQRVERFMFEGVEIPLVPSCAVFITMNPGYAGRTELPDNLKALFRPVAMMVPDYAMITEISLYSFGFNEASVLAKKITTTFKLSSEQLSSQDHYDFGMRAVKTVISAAGNLKRENPSMNEELICLRAIRDVNVPKFLQEDLKLFSGIVSDLFPTIKEEDTDYGILDEAIREACRNSNLKDVEGFLTKCIQLYETTVVRHGLMLVGPTGSGKSTCYRVLAAAMTSLKGQPSISGGMYEAVNYYVLNPKSITMGQLYGEFDLLTHEWTDGIFSSFIRAGAITSDTNKKWYMFDGPVDAIWIENMNTVLDDNKKLCLSSGEIIKLTEAMTMMFEVQDLAVASPATVSRCGMVYLEPSILGLMPFIECWLRKLPPLLKPYEEHFKALFVSFLEESISFVRSSVKEVIASTNCNLTMSLLKLLDCFFKPFLPREGLKKIPSEKLSRIVELIEPWFIFSLIWSVGATGDSSGRTSFSHWLRLKMENEQLTLLFPEEGLVFDYRLEDAGISGTNDSEDEEEEYKQVAWVKWMDSSAPFTMVPDTNYCNIIVPTMDTVQMSHLLDMLLTNKKPVLCIGPTGTGKTLTISDKLLKNLALDYISHFLTFSARTSANQTQDFIDSKLDKRRKGVFGPPLGRNFIFFIDDLNMPALETYGAQPPIELLRQWMDHGGWYDRKIIGAFKNLVDINFVCAMGPPGGGRNTVTPRLMRHFNYLSFAEMDEVSKKRIFSTILGNWLDGLLGEKSYRERVPGAPHIAHFTEPLVEATIMVYATITSQLLPTPAKSHYTFNLRDLSKVFQGMLMADPAKVEDQVQLLRLWYHENCRVFRDRLVNEEDRSWFDQLLKRCMEQWEVTFNKVCPFQPILYGDFMSPGSDVKSYELITSESKMMQVIEEYIEDYNQINTAKLKLVLFMDAMSHICRISRTLRQALGNALLLGVGGSGRSSLTRLASHMAEYECFQIELSKNYGMSEWRDDVKKVLLKAGLQNLPITFLFSDTQIKNESFLEDINNVLNSGDIPNLYTADEQDQIVSTMRPYIQEQGLQPTKANLMAAYTGRVRSNIHMVLCMSPIGEVFRARLRQFPSLVNCCTIDWFNEWPAEALKSVATVFLNEIPELESSQEEIQGLIQVCVYIHQSVSKKCIEYLAELTRHNYVTPKSYLELLHIFSILIGQKKLELKTAKNRMKSGLDKLLRTSEDVAKMQEDLESMHPLLEEAAKDTMLTMEQIKVDTAIAEETRNSVQTEEIKANEKAKKAQAIADDAQKDLDEALPALDAALASLRNLNKNDVTEVRAMQRPPPGVKLVIEAVCIMKGIKPKKVPGEKPGTKVDDYWEPGKGLLQDPGHFLESLFKFDKDNIGDVVIKAIQPYIDNEEFQPATIAKVSKACTSICQWVRAMHKYHFVAKAVEPKRQALLEAQDDLGVTQRILDEAKQRLREVEDGIATMQAKYRECITKKEELELKCEQCEQRLGRAGKLINGLSDEKVRWQETVENLQYMLNNISGDVLVAAGFVAYLGPFTGQYRTVLYDSWVKQLRSHNVPHTSEPTLIGTLGNPVKIRSWQIAGLPNDTLSVENGVINQFSQRWTHFIDPQSQANKWIKNMEKDNGLDVFKLSDRDFLRSMENAIRFGKPCLLENVGEELDPALEPVLLKQTYKQQGNTVLKLGDTVIPYHEDFRMYITTKLPNPHYTPEISTKLTLINFTLSPSGLEDQLLGQVVAEERPDLEEAKNQLIISNAKMRQELKDIEDQILYRLSSSEGNPVDDMELIKVLEASKMKAAEIQAKVRIAEQTEKDIDLTRMEYIPVAIRTQILFFCVSDLANVDPMYQYSLEWFLNIFLSGIANSERADNLKKRISNINRYLTYSLYSNVCRSLFEKHKLMFAFLLCVRIMMNEGKINQSEWRYLLSGGSISIMTENPAPDWLSDRAWRDILALSNLPTFSSFSSDFVKHLSEFRVIFDSLEPHREPLPGIWDQYLDQFQKLLVLRCLRGDKVTNAMQDFVATNLEPRFIEPQTANLSVVFKDSNSTTPLIFVLSPGTDPAADLYKFAEEMKFSKKLSAISLGQGQGPRAEAMMRSSIERGKWVFFQNCHLAPSWMPALERLIEHINPDKVHRDFRLWLTSLPSNKFPVSILQNGSKMTIEPPRGVRANLLKSYSSLGEDFLNSCHKVMEFKSLLLSLCLFHGNALERRKFGPLGFNIPYEFTDGDLRICISQLKMFLDEYDDIPYKVLKYTAGEINYGGRVTDDWDRRCIMNILEDFYNPDVLSPEHSYSASGIYHQIPPTYDLHGYLSYIKSLPLNDMPEIFGLHDNANITFAQNETFALLGTIIQLQPKSSSAGSQGREEIVEDVTQNILLKVPEPINLQWVMAKYPVLYEESMNTVLVQEVIRYNRLLQVITQTLQDLLKALKGLVVMSSQLELMAASLYNTVPELWSAKAYPSLKPLSSWVMDLLQRLDFLQAWIQDGIPAVFWISGFFFPQAFLTGTLQNFARKFVISIDTISFDFKVMFEAPSELTQRPQVGCYIHGLFLEGARWDPEAFQLAESQPKELYTEMAVIWLLPTPNRKAQDQDFYLCPIYKTLTRAGTLSTTGHSTNYVIAVEIPTHQPQRHWIKRGVALICALDY。
序列表
<110>厦门市妇幼保健院（厦门市计划生育服务中心）；首都医科大学附属北京妇产医院
<120>一种MMAF致病基因新突变及其应用
<130> 2017
<160> 35
<170> PatentIn version 3.3
<210> 1
<211> 12798
<212> DNA
<213> Homo Sapiens
<400> 1
atggagcagc ctaacagtaa aggctatagc ctgggaagga cccctcaggg cccagagtgc 60
agcagtgctc ctgcagtcca agtggggacc cacaggggcc tagagtataa cccggggaag 120
attcttccag gatcagacta tgggttggga aatcctccag cccttgaccc caagctccca 180
catttacccc tgcccccggc cccacccaca ctctcagact tggggcagcc acggaagtca 240
cccctgacag gcactgataa gaagtacccg ctgatgaagc agcgtgggtt ctactccgac 300
atcctcagcc ctggaacctt agatcaactt ggggaggtat gtcgtggccc ccgaatgagc 360
cagaacctcc tgcggcaggc tgaccttgac aagttcaccc caagagtcgg aagctttgag 420
gttcctgaag acttccagga gcgcatggag cagcagtgca tcgggtccac cacccggctg 480
ctcgcccaga ctgacttccc actgcaggcc tacgagccca agatgcaggt gcctttccag 540
gtgctgccag gccagcatcc tcgcaagatt gagatcgaga ggaggaaaca gcagtacctg 600
agcctggaca ttgagcagtt gctgttcagc cagggcatcg actccaacaa gctcatgccc 660
aggcacctgg accaccagca cccccaaacc atcgaacagg gccatgaccc aatcttcccc 720
atctacctcc cactgaaggt atttgacaat gaggactttg actgccggac tcccagagag 780
tggatcaaca tgggcttgga gccagggtct ctggacagga aacctgtccc gggaaaagcc 840
ctcttgccca ctgatgactt cctggggcat gaggacccca agagtcagaa gctgaagtac 900
aaatggtgcg aggtcggcgt cctggactac gacgaggaga agaagctata cctggtacac 960
aagacagacg agaaaggcct ggtgcgagat gagatgggga ggcccatcct gaatgcaggg 1020
gtcaccactg aaggaaggcc accccttcag gtctgtcagt actgggtgcc acggatccag 1080
cttctcttct gcgctgagga cccttgcatg ttcgcacaac gtgtggtcca ggccaacgcc 1140
ctgcgcaaga acacggaagc actgctgctc tacaacttgt atgtggactg catgccctct 1200
gacggccagc atgtcatcag tgaacagagc ctgagcaaga tcaagcagtg ggccctgagc 1260
acgcctcgga tgcgcaaagg cccctcggtt ctagagcacc tcagcagtct tgccagagaa 1320
gtgagcctgg actatgagcg cagcatgaac aagatcaact ttgaccacgt tgtctcttcc 1380
aagcccgaga ccttctccta cgtcaccctc cccaagaagg aggaggagca ggtgcctgag 1440
cgagggctgg tgagtgtccc caagtaccac ttctgggagc agaaggagga cttcactttc 1500
gtgtccctgc tcacacggcc agaggtcatc acggccctca gcaaggtgag ggccgagtgc 1560
aacaaggtga ccgccatgtc cctgttccac tcgagcctct ccaagtacag ccacctggag 1620
gaatttgagc agatccagtc acagaccttc tcccaggtgc agatgttcct caaggacagc 1680
tggatcagct cgctaaaggt ggccatgcgc agcagcctgc gcgacatgag caagggctgg 1740
tacaacctct acgagaccaa ctgggaggtg tacctcatgt ccaagctgcg caagctgatg 1800
gagctggtga agtacatgct gcaggacaca ctgcgcttcc tggtgcagga ctcacttgcc 1860
agcttctcac agttcatcag cgacacctgt tgcagcgtgc tcaactgcac cgatgacatg 1920
gtctggggtg acgacttaat taacagcccc tacaggcccc ggaagaatcc cctgttcatc 1980
atggacctgg tgctggacag ctctggggtg cactatagca ccccactgga gcagtttgag 2040
gcatctctgc tgaacctctt cgacaagggc atcctggcca cccatgccgt gccccagctg 2100
gagaagctgg tgatggagga catcttcatc agcggtgacc ccctgctgga gtccgtgggc 2160
cttcatgagc cactggtgga agagctacgg gccaccattg ccagtgccgt gtccaaggcc 2220
atgatcccac tgcaggccta cgccaaggag taccgaaagt acctggagct gaacaacaat 2280
gacattgcct cctttctcaa aacctaccag acgcagggcc tgttggccca ggaggtgcgg 2340
gaggtagtgc tcacccacct gcgggagaag gagatcctgg acagctcgct gcccagcagc 2400
atcatcattg ggcctttcta catcaacacc gacaatgtca agcagagcct gtccaagaaa 2460
cgcaaggccc tggccacttc cgtgctggac atccttgcca agaacctgca taaggaggtg 2520
gatagcatct gcgaggagtt ccgcagcatc agccgcaaga tctatgagaa gcccaacagc 2580
attgaggagc tggctgagct gcgagagtgg atgaagggca tcccggagag gctggtgggc 2640
ctggaggagc ggattgtgaa ggtcatggat gactaccagg tcatggatga attcctctac 2700
aacctcagct cagatgactt caatgacaaa tggattgcca gcaactggcc ttctaagatc 2760
cttgggcaga tagagctggt gcagcagcag catgtggagg atgaggagaa gttccgcaaa 2820
atccagatca tggatcagaa caacttccaa gagaagctgg aagggctgca gctggtagta 2880
gctggcttct ccatccatgt ggagatttca cgtgcacacg agatcgccaa cgaggtgcgg 2940
cgtgtcaaga agcagctgaa ggactgccag cagctggcca tgctctacaa caaccgcgag 3000
cgcatcttca gcttgcccat caccaattat gacaagctct ccaggatggt gaaggagttc 3060
caaccctacc tggacctttg gaccacagcg tctgactggc tgcgctggtc ggagagctgg 3120
atgaatgacc ccctctctgc catcgatgct gagcagctgg agaagaacgt ggttgaagcc 3180
ttcaagacca tgcacaagtg cgtgaagcag tttaaggaca tgccagcctg ccaggaagtg 3240
gccttggaca tccgggcccg catcgaggag ttcaaaccat acatcccact gatccagggg 3300
ctgcgcaacc ctggcatgcg gatccggcac tgggagacac tgtccaacca gatcaacatc 3360
aatgtcaggc ccaaggccaa cctgaccttt gctcgctgcc tggagatgaa cctgcaggac 3420
catatcgaga gcatcagcaa ggtggctgag gtggctggca aggagtacgc catcgagcag 3480
gcactggaca agatggagaa ggagtggtcg accatcctgt tcaatgtact gccctacaag 3540
gcgacagaca cctacatcct gaagagcccg gacgaggcct cacagctgct ggacgaccac 3600
atcgtcatga cccagaatat gtcattttca ccctacaaga agccctttga gcagcgcatc 3660
aactcctggg agaacaaact gaagctgacc caggaggttc tggaggagtg gctgaactgt 3720
cagcggtcct ggctctacct ggagcccatc tttagctctg aggacatcaa ccagcagctg 3780
cctgtggaga gcaagcgcta ccagaccatg gagcggatct ggaagaagat catgaagaat 3840
gcctacgaga accgggaggt gatcaatgtg tgttccgacc tgagaatgct ggacagcctg 3900
cgggactgca acaagattct ggacctggtg cagaagggcc tcagcgagta tctggagacc 3960
aagaggagcg ccttccccag attctacttc ctgtcagatg atgaactact agagatcttg 4020
tcgcagacaa aggaccccac ggccgtgcag ccacacctgc gcaagtgctt cgagaacatc 4080
gctcggctgc tattccagga ggacctggag atcacgcaca tgtactcagc cgagggggag 4140
gaggtacagt tgtgcttctc catctacccc tccagcaacg tggaggactg gctgcgggag 4200
gtggagcgca gcatgaaggc cagtgtgcac gacatcattg agaaggccat cagggcctac 4260
cccacgatgc ccaggaccca gtgggttctg aactggcctg gccaggtgac catcgctggg 4320
tgccagacct actggaccat ggaggtggca gaggctctgg aggccggcaa cctcagaagc 4380
caactgttcc cccagctctg ccagcagctc agtgatctgg tggcccttgt gcgggggaag 4440
ctgtcccgca tgcagcgggc agtgctgtca gcgctaatcg tcattgaggt ccatgccaag 4500
gacgtggtga gcaagctaat ccaggagaac gtggtcagcg tgaatgactt ccagtggatc 4560
tcacagctga ggtactactg gacaaataat gacctgtata tccgtgctgt gaatgctgag 4620
ttcatctatg gctatgagta cctgggcaac agtgggaggc tggtgatcac gcccctcacc 4680
gacaggtgct acctgacact gaccggagct ctgcacctca agtttggggg tgccccagct 4740
ggcccagctg gcacaggcaa aactgagacc accaaagacc tgggtaaggc cttggccata 4800
cagaccgttg tgttcaactg ctctgaccag ctcgacttca tggccatggg caagttcttc 4860
aagggcctgg ccagtgctgg ggcctgggcc tgcttcgacg agttcaatcg catcgacatc 4920
gaggtgctgt ctgtggtggc gcagcagatc accaccatcc agaaggcgca gcagcagcgg 4980
gtggaacgct tcatgtttga gggtgtggag atcccactgg tgccatcctg cgcagtgttt 5040
atcaccatga acccgggcta cgctggccgc acggagctgc ctgacaatct gaaggcgctc 5100
ttccgacccg tggccatgat ggttccagat tacgccatga tcactgagat ctccctctat 5160
tcctttggct ttaatgaggc cagtgtgctg gctaagaaga tcacaaccac cttcaagctg 5220
tcttctgagc agctcagctc ccaggatcac tatgacttcg ggatgagagc cgtgaaaact 5280
gtgatctcgg ctgctgggaa cctcaagcga gaaaacccca gcatgaatga ggagctgatc 5340
tgcctccggg ccatccgtga tgtgaacgtg cccaagttcc tgcaggagga cctcaagctc 5400
ttctctggca tcgtgtccga cctgtttccc accatcaagg aggaggacac ggactacggc 5460
atcctggatg aggccatccg cgaggcctgc aggaacagca acctcaagga tgtggagggc 5520
ttcctgacaa agtgcatcca gctctacgag accacggtgg tacgacacgg cctcatgctc 5580
gtcgggccca caggctccgg caagagtact tgttacagag tcctggcagc tgccatgacg 5640
tcactgaaag ggcagccatc catcagtggt ggcatgtacg aggctgtcaa ctactacgtg 5700
ctcaacccca agtccatcac gatgggccag ctgtacgggg agtttgacct cctcacccat 5760
gagtggacag acgggatatt ctcctcgttc atccgggcgg gggccatcac ctccgacacc 5820
aacaagaagt ggtacatgtt cgatgggccg gtggatgcca tctggattga gaacatgaac 5880
acggtgctgg atgacaacaa gaagctgtgc ctcagctctg gggagatcat caagctcaca 5940
gaggcaatga ccatgatgtt cgaggtgcaa gacctggcgg tggcttcacc agctacagtc 6000
tcccgctgtg gcatggtgta cctggagccc agcatcctgg ggctcatgcc cttcatcgag 6060
tgctggctga ggaagctgcc tcccttgctg aagccctatg aggagcattt caaggccctc 6120
tttgtcagct tcctggagga atccatctcc ttcgttcggt cctcagtgaa ggaggtgatc 6180
gcctcaacca actgcaacct gaccatgagc ctcctcaagc tgctggactg cttcttcaag 6240
ccctttctgc ctagagaggg cctcaagaaa ataccctctg aaaagctgag tcgcatcgta 6300
gagttgatcg agccctggtt catcttctcc ctgatctgga gcgtgggtgc cactggggac 6360
agcagtggcc gcaccagttt cagccactgg ctaaggctca agatggagaa cgaacagctg 6420
actctgcttt tcccagaaga ggggctggtg ttcgattaca ggctggagga cgcgggcatc 6480
agtggcacca acgacagtga ggatgaagag gaggaataca agcaggttgc ctgggtgaag 6540
tggatggact cctcagctcc attcaccatg gtaccagaca ccaactactg caacatcatt 6600
gtgcccacca tggacaccgt gcagatgtcc catttactgg acatgctgct caccaacaag 6660
aagcccgtgc tgtgcattgg gccaacaggc acggggaaga cgctcaccat ctctgacaag 6720
ctcctcaaga acctggcact ggattacatc agccacttcc tcaccttctc agcccgcact 6780
tcagccaacc agacccagga cttcattgac agcaagctgg acaagaggcg gaagggtgtg 6840
tttggaccac ctctggggcg caactttatc ttcttcatcg atgacctgaa catgccggcc 6900
ctggagacct acggtgcaca gccacccatc gagctgttgc gccagtggat ggaccacggc 6960
ggctggtacg accgcaagat cattggtgcc ttcaagaacc tagtggacat caactttgtc 7020
tgtgccatgg gccccccggg tggaggcagg aacaccgtca ccccgcggct gatgcgtcac 7080
ttcaactacc tgtctttcgc tgagatggac gaggtcagca agaaacgcat cttctccacc 7140
atcctgggca actggttgga tggactcctt ggagaaaaaa gctaccggga gcgtgtgcct 7200
ggggcccccc acattgccca cttcacggag ccccttgtgg aagccaccat catggtgtat 7260
gcaaccatca cctcccagct gctgcccact ccagccaagt cccactacac cttcaacctg 7320
agggacctct ccaaggtctt ccaaggcatg ctcatggctg acccggccaa ggtcgaggac 7380
caagtgcagc tgctgcgact gtggtatcac gagaactgcc gcgtgttccg ggaccgactg 7440
gtgaatgagg aggaccgcag ctggttcgac cagctcctca agcgctgcat ggagcagtgg 7500
gaggtgacct tcaacaaggt ctgccccttc cagcccattc tttacgggga cttcatgtca 7560
ccaggctccg atgtcaagtc ctacgagctc atcaccagtg agagtaagat gatgcaggtg 7620
atagaggagt acatagagga ctacaaccag atcaacacgg ccaagctgaa gctggtcctc 7680
ttcatggacg ccatgagcca catctgtcgc atcagccgca ccctacgcca ggcgctgggc 7740
aatgcactcc tgctgggcgt gggtggcagc ggccgcagct ccctcacaag gctcgcctcg 7800
cacatggccg agtacgagtg cttccagatt gaactatcca agaactacgg catgtccgag 7860
tggcgagatg atgtgaagaa ggtcctgctc aaggcgggcc tacagaacct acccatcacc 7920
ttcctcttct cagacaccca gatcaagaac gaatccttcc tggaagatat caacaacgtc 7980
ctaaactctg gtgacattcc caatctgtat actgcggacg agcaggacca gatcgtcagc 8040
accatgcggc cctatatcca ggagcagggc ctacagccca ccaaggccaa cctcatggct 8100
gcttacacag ggcgtgtgcg cagcaacatc cacatggtgc tgtgcatgag ccccatcgga 8160
gaggtcttcc gagctcgtct gaggcagttt ccctccctgg tcaactgctg taccatcgac 8220
tggtttaacg agtggccggc agaagccctg aagtctgtgg ccaccgtgtt cctcaatgag 8280
atcccagaac tggaatcctc ccaggaagaa atccaaggac tgatccaggt ctgtgtgtac 8340
atccaccagt cggtgtccaa gaagtgcatc gagtacctgg cagagctgac ccgccacaac 8400
tatgtgaccc ccaagagcta cttggagctg cttcatattt tctccatcct catcgggcag 8460
aagaaactgg agctgaaaac tgccaagaac cgcatgaaga gcggcctcga caagctgctg 8520
cgcacttctg aggatgtagc caagatgcag gaggacctgg agagtatgca ccccctgctg 8580
gaggaggctg ccaaggacac catgctcacc atggagcaga tcaaggtgga tacggccatc 8640
gccgaggaga cccggaattc agtgcagaca gaggagatca aagccaatga gaaggccaag 8700
aaggcacaag ctattgctga cgatgcccag aaggacctgg acgaggcgtt gccagccctg 8760
gatgcggctc tggccagcct gcgcaacctc aacaagaacg atgtgaccga ggtacgtgcc 8820
atgcagcggc cacccccggg tgtgaaactg gtcatagaag ctgtgtgcat tatgaaaggc 8880
atcaagccca agaaggtgcc tggagaaaag ccaggcacca aggtggatga ctactgggag 8940
cctggcaagg ggctgctgca ggacccgggc cacttccttg agagcctctt caagtttgac 9000
aaggacaaca ttggggatgt ggtgatcaaa gccatccagc cgtacatcga taatgaagag 9060
ttccagccag ccaccattgc caaggtgtcc aaggcttgca cctccatctg ccagtgggtg 9120
cgcgccatgc acaagtacca ctttgtggcc aaggccgtgg agcccaagcg gcaagccctg 9180
ctggaggccc aggatgacct gggggtgaca cagaggatcc tggatgaggc aaaacagcgc 9240
cttcgtgagg tggaggacgg catcgccaca atgcaggcta agtaccggga atgcattacc 9300
aagaaggagg agctggagct gaagtgtgag cagtgtgagc agcggctggg ccgagctggc 9360
aagctcatca acgggctgtc ggatgagaag gtgcgctggc aggagacggt ggagaacctg 9420
cagtacatgc tcaacaacat ctccggcgat gtcctggtgg ccgctggctt tgtggcctac 9480
ctgggcccct tcacgggcca gtaccgcacg gtgctctacg acagctgggt caagcagctc 9540
aggagccaca atgtcccaca cacctccgag cccacgctaa tcgggacgct ggggaaccct 9600
gtgaagatcc gatcgtggca gatcgctggc ctccccaacg acacactgtc agtggagaac 9660
ggggtcatca accagttttc ccagcgctgg acccacttca ttgaccctca gagccaggcc 9720
aacaaatgga tcaagaacat ggagaaggac aatgggctgg atgtgttcaa gttgagtgac 9780
cgcgacttcc tgcgcagcat ggagaacgcc atccgctttg gcaagccatg tctcctggag 9840
aacgtgggcg aggagctaga cccagccctg gagccagtgc tgctcaagca gacgtacaag 9900
cagcagggaa acacggtgct gaagctgggg gacacggtga tcccctacca tgaggacttc 9960
aggatgtaca tcaccaccaa gctgcccaac ccacactaca cgcccgagat ctccaccaaa 10020
ctcaccctca tcaacttcac cctgtcgccc agtggcctag aggaccagct actgggccag 10080
gtagtggcag aggagcgacc cgacctggag gaggccaaga accagctgat tatcagtaat 10140
gccaagatgc gccaggagct gaaggacatt gaggaccaga tcctgtaccg gctcagctcc 10200
tccgagggca accctgtaga tgacatggaa ctcatcaagg tgctggaagc ctccaagatg 10260
aaggctgctg agatccaggc caaagtcagg attgcagagc agacggagaa ggacatcgac 10320
ctgacgcgca tggagtacat acccgtggcc atccgcaccc agatcctctt cttctgtgtg 10380
tccgacctgg ccaacgtgga ccccatgtac cagtactccc ttgagtggtt tctcaacatc 10440
ttcctctcgg gcatcgccaa ctcagagaga gcagacaacc tgaagaagcg catctccaac 10500
atcaaccgct acctgaccta cagcctctac agcaacgtct gccgcagcct ctttgagaag 10560
cacaagctga tgtttgcctt cctgctgtgt gttcgcatca tgatgaacga gggcaaaatc 10620
aaccagagtg agtggcgata cctcctgtct gggggctcca tctcgatcat gactgagaat 10680
ccggcaccgg actggctgtc agaccgggct tggcgagaca tcctagcact ctcgaacctg 10740
ccaacctttt cctccttctc ttccgacttc gtgaagcacc tctcagaatt ccgggtcatc 10800
ttcgacagcc ttgagcccca ccgggagcct ttgcctggca tctgggacca gtacctagac 10860
cagttccaga agctgctagt cctccgctgc ctgcgtgggg acaaggttac caacgccatg 10920
caggactttg tggccaccaa cctggagcca cgcttcattg aaccccagac agccaatctg 10980
tcagtggtgt tcaaagactc caactccacc acacccctca tctttgtgct gtcacccggc 11040
acagaccctg ctgccgacct ctacaagttt gccgaagaaa tgaagttctc caaaaagctc 11100
tctgccatct ccctgggcca ggggcagggc cctcgggcag aagccatgat gcgcagctcc 11160
atagagaggg gcaaatgggt cttcttccag aactgccacc tggcaccaag ctggatgcca 11220
gccctagaac gcctcatcga gcacatcaac cccgacaagg tacacaggga cttccgcctc 11280
tggctcacca gcctgcccag caacaagttc ccagtgtcca tcctgcagaa cggctccaag 11340
atgaccattg agccgccacg cggtgtcagg gccaacctgc tgaagtccta tagtagcctt 11400
ggtgaagact tcctcaactc ctgccacaag gtgatggagt tcaagtctct gctgctgtct 11460
ctgtgcttgt tccatgggaa cgccctggag cgccgtaagt ttgggcccct gggcttcaac 11520
atcccctatg agttcacgga tggagatctg cgcatctgca tcagccagct caagatgttc 11580
ctggacgaat atgatgacat cccctacaag gtcctcaagt acacggcagg ggagatcaat 11640
tacgggggcc gtgtcactga tgactgggac cggcgctgca tcatgaacat cttggaggac 11700
ttctacaacc ctgacgtgct ctcccctgag cacagctaca gcgcctcggg catctaccac 11760
cagatcccgc ctacctacga cctccacggc tacctctcct acatcaagag cctcccactc 11820
aatgatatgc ctgagatctt tggcctgcat gacaatgcca acatcacctt tgcccagaac 11880
gagacgttcg ccctcctggg caccatcatc cagctgcaac ccaaatcatc ttctgcaggc 11940
agccagggcc gggaggagat agtggaggac gtcacccaaa acattctgct caaggtgcct 12000
gagcctatca acttgcaatg ggtgatggcc aagtacccag tgctgtatga ggaatcaatg 12060
aacacagtac tagtacaaga ggtcattagg tacaatcggc tgctgcaggt gatcacacag 12120
acactgcaag acctactcaa ggcactcaag gggctggtag tgatgtcctc tcagctggag 12180
ctgatggctg ccagcctgta caacaatact gtgcctgagc tctggagtgc caaggcctac 12240
ccatcgctca agcctctgtc atcatgggtc atggacctgc tgcaacgcct ggactttctg 12300
caggcctgga tccaagatgg catcccagct gtcttctgga tcagtggatt cttcttcccc 12360
caggctttct taacaggcac tctgcagaat tttgcccgca aatttgtcat ctccattgac 12420
accatctcct ttgatttcaa ggtgatgttt gaggcaccat cagagttaac acaaagaccc 12480
caagtagggt gctatatcca tggattattc ctggaaggtg cccgctggga tccagaggcc 12540
ttccagctgg ctgagtctca gcccaaggag ctgtacacag agatggccgt tatctggctc 12600
ttgccaacac ccaaccgcaa ggcccaggac caggactttt acctgtgccc catctacaag 12660
acactgactc gtgctggaac actatcaacc acaggacact ctaccaacta tgtcattgct 12720
gtggagatcc ccacccatca gccccagcga cactggataa agcgtggtgt ggccctcatc 12780
tgtgccctgg actactag 12798
<210> 2
<211> 4265
<212> PRT
<213> Homo Sapiens
<400> 2
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu Trp Met Lys Gly Ile Pro Glu Arg Leu Val Gly
865 870 875 880
Leu Glu Glu Arg Ile Val Lys Val Met Asp Asp Tyr Gln Val Met Asp
885 890 895
Glu Phe Leu Tyr Asn Leu Ser Ser Asp Asp Phe Asn Asp Lys Trp Ile
900 905 910
Ala Ser Asn Trp Pro Ser Lys Ile Leu Gly Gln Ile Glu Leu Val Gln
915 920 925
Gln Gln His Val Glu Asp Glu Glu Lys Phe Arg Lys Ile Gln Ile Met
930 935 940
Asp Gln Asn Asn Phe Gln Glu Lys Leu Glu Gly Leu Gln Leu Val Val
945 950 955 960
Ala Gly Phe Ser Ile His Val Glu Ile Ser Arg Ala His Glu Ile Ala
965 970 975
Asn Glu Val Arg Arg Val Lys Lys Gln Leu Lys Asp Cys Gln Gln Leu
980 985 990
Ala Met Leu Tyr Asn Asn Arg Glu Arg Ile Phe Ser Leu Pro Ile Thr
995 1000 1005
Asn Tyr Asp Lys Leu Ser Arg Met Val Lys Glu Phe Gln Pro Tyr
1010 1015 1020
Leu Asp Leu Trp Thr Thr Ala Ser Asp Trp Leu Arg Trp Ser Glu
1025 1030 1035
Ser Trp Met Asn Asp Pro Leu Ser Ala Ile Asp Ala Glu Gln Leu
1040 1045 1050
Glu Lys Asn Val Val Glu Ala Phe Lys Thr Met His Lys Cys Val
1055 1060 1065
Lys Gln Phe Lys Asp Met Pro Ala Cys Gln Glu Val Ala Leu Asp
1070 1075 1080
Ile Arg Ala Arg Ile Glu Glu Phe Lys Pro Tyr Ile Pro Leu Ile
1085 1090 1095
Gln Gly Leu Arg Asn Pro Gly Met Arg Ile Arg His Trp Glu Thr
1100 1105 1110
Leu Ser Asn Gln Ile Asn Ile Asn Val Arg Pro Lys Ala Asn Leu
1115 1120 1125
Thr Phe Ala Arg Cys Leu Glu Met Asn Leu Gln Asp His Ile Glu
1130 1135 1140
Ser Ile Ser Lys Val Ala Glu Val Ala Gly Lys Glu Tyr Ala Ile
1145 1150 1155
Glu Gln Ala Leu Asp Lys Met Glu Lys Glu Trp Ser Thr Ile Leu
1160 1165 1170
Phe Asn Val Leu Pro Tyr Lys Ala Thr Asp Thr Tyr Ile Leu Lys
1175 1180 1185
Ser Pro Asp Glu Ala Ser Gln Leu Leu Asp Asp His Ile Val Met
1190 1195 1200
Thr Gln Asn Met Ser Phe Ser Pro Tyr Lys Lys Pro Phe Glu Gln
1205 1210 1215
Arg Ile Asn Ser Trp Glu Asn Lys Leu Lys Leu Thr Gln Glu Val
1220 1225 1230
Leu Glu Glu Trp Leu Asn Cys Gln Arg Ser Trp Leu Tyr Leu Glu
1235 1240 1245
Pro Ile Phe Ser Ser Glu Asp Ile Asn Gln Gln Leu Pro Val Glu
1250 1255 1260
Ser Lys Arg Tyr Gln Thr Met Glu Arg Ile Trp Lys Lys Ile Met
1265 1270 1275
Lys Asn Ala Tyr Glu Asn Arg Glu Val Ile Asn Val Cys Ser Asp
1280 1285 1290
Leu Arg Met Leu Asp Ser Leu Arg Asp Cys Asn Lys Ile Leu Asp
1295 1300 1305
Leu Val Gln Lys Gly Leu Ser Glu Tyr Leu Glu Thr Lys Arg Ser
1310 1315 1320
Ala Phe Pro Arg Phe Tyr Phe Leu Ser Asp Asp Glu Leu Leu Glu
1325 1330 1335
Ile Leu Ser Gln Thr Lys Asp Pro Thr Ala Val Gln Pro His Leu
1340 1345 1350
Arg Lys Cys Phe Glu Asn Ile Ala Arg Leu Leu Phe Gln Glu Asp
1355 1360 1365
Leu Glu Ile Thr His Met Tyr Ser Ala Glu Gly Glu Glu Val Gln
1370 1375 1380
Leu Cys Phe Ser Ile Tyr Pro Ser Ser Asn Val Glu Asp Trp Leu
1385 1390 1395
Arg Glu Val Glu Arg Ser Met Lys Ala Ser Val His Asp Ile Ile
1400 1405 1410
Glu Lys Ala Ile Arg Ala Tyr Pro Thr Met Pro Arg Thr Gln Trp
1415 1420 1425
Val Leu Asn Trp Pro Gly Gln Val Thr Ile Ala Gly Cys Gln Thr
1430 1435 1440
Tyr Trp Thr Met Glu Val Ala Glu Ala Leu Glu Ala Gly Asn Leu
1445 1450 1455
Arg Ser Gln Leu Phe Pro Gln Leu Cys Gln Gln Leu Ser Asp Leu
1460 1465 1470
Val Ala Leu Val Arg Gly Lys Leu Ser Arg Met Gln Arg Ala Val
1475 1480 1485
Leu Ser Ala Leu Ile Val Ile Glu Val His Ala Lys Asp Val Val
1490 1495 1500
Ser Lys Leu Ile Gln Glu Asn Val Val Ser Val Asn Asp Phe Gln
1505 1510 1515
Trp Ile Ser Gln Leu Arg Tyr Tyr Trp Thr Asn Asn Asp Leu Tyr
1520 1525 1530
Ile Arg Ala Val Asn Ala Glu Phe Ile Tyr Gly Tyr Glu Tyr Leu
1535 1540 1545
Gly Asn Ser Gly Arg Leu Val Ile Thr Pro Leu Thr Asp Arg Cys
1550 1555 1560
Tyr Leu Thr Leu Thr Gly Ala Leu His Leu Lys Phe Gly Gly Ala
1565 1570 1575
Pro Ala Gly Pro Ala Gly Thr Gly Lys Thr Glu Thr Thr Lys Asp
1580 1585 1590
Leu Gly Lys Ala Leu Ala Ile Gln Thr Val Val Phe Asn Cys Ser
1595 1600 1605
Asp Gln Leu Asp Phe Met Ala Met Gly Lys Phe Phe Lys Gly Leu
1610 1615 1620
Ala Ser Ala Gly Ala Trp Ala Cys Phe Asp Glu Phe Asn Arg Ile
1625 1630 1635
Asp Ile Glu Val Leu Ser Val Val Ala Gln Gln Ile Thr Thr Ile
1640 1645 1650
Gln Lys Ala Gln Gln Gln Arg Val Glu Arg Phe Met Phe Glu Gly
1655 1660 1665
Val Glu Ile Pro Leu Val Pro Ser Cys Ala Val Phe Ile Thr Met
1670 1675 1680
Asn Pro Gly Tyr Ala Gly Arg Thr Glu Leu Pro Asp Asn Leu Lys
1685 1690 1695
Ala Leu Phe Arg Pro Val Ala Met Met Val Pro Asp Tyr Ala Met
1700 1705 1710
Ile Thr Glu Ile Ser Leu Tyr Ser Phe Gly Phe Asn Glu Ala Ser
1715 1720 1725
Val Leu Ala Lys Lys Ile Thr Thr Thr Phe Lys Leu Ser Ser Glu
1730 1735 1740
Gln Leu Ser Ser Gln Asp His Tyr Asp Phe Gly Met Arg Ala Val
1745 1750 1755
Lys Thr Val Ile Ser Ala Ala Gly Asn Leu Lys Arg Glu Asn Pro
1760 1765 1770
Ser Met Asn Glu Glu Leu Ile Cys Leu Arg Ala Ile Arg Asp Val
1775 1780 1785
Asn Val Pro Lys Phe Leu Gln Glu Asp Leu Lys Leu Phe Ser Gly
1790 1795 1800
Ile Val Ser Asp Leu Phe Pro Thr Ile Lys Glu Glu Asp Thr Asp
1805 1810 1815
Tyr Gly Ile Leu Asp Glu Ala Ile Arg Glu Ala Cys Arg Asn Ser
1820 1825 1830
Asn Leu Lys Asp Val Glu Gly Phe Leu Thr Lys Cys Ile Gln Leu
1835 1840 1845
Tyr Glu Thr Thr Val Val Arg His Gly Leu Met Leu Val Gly Pro
1850 1855 1860
Thr Gly Ser Gly Lys Ser Thr Cys Tyr Arg Val Leu Ala Ala Ala
1865 1870 1875
Met Thr Ser Leu Lys Gly Gln Pro Ser Ile Ser Gly Gly Met Tyr
1880 1885 1890
Glu Ala Val Asn Tyr Tyr Val Leu Asn Pro Lys Ser Ile Thr Met
1895 1900 1905
Gly Gln Leu Tyr Gly Glu Phe Asp Leu Leu Thr His Glu Trp Thr
1910 1915 1920
Asp Gly Ile Phe Ser Ser Phe Ile Arg Ala Gly Ala Ile Thr Ser
1925 1930 1935
Asp Thr Asn Lys Lys Trp Tyr Met Phe Asp Gly Pro Val Asp Ala
1940 1945 1950
Ile Trp Ile Glu Asn Met Asn Thr Val Leu Asp Asp Asn Lys Lys
1955 1960 1965
Leu Cys Leu Ser Ser Gly Glu Ile Ile Lys Leu Thr Glu Ala Met
1970 1975 1980
Thr Met Met Phe Glu Val Gln Asp Leu Ala Val Ala Ser Pro Ala
1985 1990 1995
Thr Val Ser Arg Cys Gly Met Val Tyr Leu Glu Pro Ser Ile Leu
2000 2005 2010
Gly Leu Met Pro Phe Ile Glu Cys Trp Leu Arg Lys Leu Pro Pro
2015 2020 2025
Leu Leu Lys Pro Tyr Glu Glu His Phe Lys Ala Leu Phe Val Ser
2030 2035 2040
Phe Leu Glu Glu Ser Ile Ser Phe Val Arg Ser Ser Val Lys Glu
2045 2050 2055
Val Ile Ala Ser Thr Asn Cys Asn Leu Thr Met Ser Leu Leu Lys
2060 2065 2070
Leu Leu Asp Cys Phe Phe Lys Pro Phe Leu Pro Arg Glu Gly Leu
2075 2080 2085
Lys Lys Ile Pro Ser Glu Lys Leu Ser Arg Ile Val Glu Leu Ile
2090 2095 2100
Glu Pro Trp Phe Ile Phe Ser Leu Ile Trp Ser Val Gly Ala Thr
2105 2110 2115
Gly Asp Ser Ser Gly Arg Thr Ser Phe Ser His Trp Leu Arg Leu
2120 2125 2130
Lys Met Glu Asn Glu Gln Leu Thr Leu Leu Phe Pro Glu Glu Gly
2135 2140 2145
Leu Val Phe Asp Tyr Arg Leu Glu Asp Ala Gly Ile Ser Gly Thr
2150 2155 2160
Asn Asp Ser Glu Asp Glu Glu Glu Glu Tyr Lys Gln Val Ala Trp
2165 2170 2175
Val Lys Trp Met Asp Ser Ser Ala Pro Phe Thr Met Val Pro Asp
2180 2185 2190
Thr Asn Tyr Cys Asn Ile Ile Val Pro Thr Met Asp Thr Val Gln
2195 2200 2205
Met Ser His Leu Leu Asp Met Leu Leu Thr Asn Lys Lys Pro Val
2210 2215 2220
Leu Cys Ile Gly Pro Thr Gly Thr Gly Lys Thr Leu Thr Ile Ser
2225 2230 2235
Asp Lys Leu Leu Lys Asn Leu Ala Leu Asp Tyr Ile Ser His Phe
2240 2245 2250
Leu Thr Phe Ser Ala Arg Thr Ser Ala Asn Gln Thr Gln Asp Phe
2255 2260 2265
Ile Asp Ser Lys Leu Asp Lys Arg Arg Lys Gly Val Phe Gly Pro
2270 2275 2280
Pro Leu Gly Arg Asn Phe Ile Phe Phe Ile Asp Asp Leu Asn Met
2285 2290 2295
Pro Ala Leu Glu Thr Tyr Gly Ala Gln Pro Pro Ile Glu Leu Leu
2300 2305 2310
Arg Gln Trp Met Asp His Gly Gly Trp Tyr Asp Arg Lys Ile Ile
2315 2320 2325
Gly Ala Phe Lys Asn Leu Val Asp Ile Asn Phe Val Cys Ala Met
2330 2335 2340
Gly Pro Pro Gly Gly Gly Arg Asn Thr Val Thr Pro Arg Leu Met
2345 2350 2355
Arg His Phe Asn Tyr Leu Ser Phe Ala Glu Met Asp Glu Val Ser
2360 2365 2370
Lys Lys Arg Ile Phe Ser Thr Ile Leu Gly Asn Trp Leu Asp Gly
2375 2380 2385
Leu Leu Gly Glu Lys Ser Tyr Arg Glu Arg Val Pro Gly Ala Pro
2390 2395 2400
His Ile Ala His Phe Thr Glu Pro Leu Val Glu Ala Thr Ile Met
2405 2410 2415
Val Tyr Ala Thr Ile Thr Ser Gln Leu Leu Pro Thr Pro Ala Lys
2420 2425 2430
Ser His Tyr Thr Phe Asn Leu Arg Asp Leu Ser Lys Val Phe Gln
2435 2440 2445
Gly Met Leu Met Ala Asp Pro Ala Lys Val Glu Asp Gln Val Gln
2450 2455 2460
Leu Leu Arg Leu Trp Tyr His Glu Asn Cys Arg Val Phe Arg Asp
2465 2470 2475
Arg Leu Val Asn Glu Glu Asp Arg Ser Trp Phe Asp Gln Leu Leu
2480 2485 2490
Lys Arg Cys Met Glu Gln Trp Glu Val Thr Phe Asn Lys Val Cys
2495 2500 2505
Pro Phe Gln Pro Ile Leu Tyr Gly Asp Phe Met Ser Pro Gly Ser
2510 2515 2520
Asp Val Lys Ser Tyr Glu Leu Ile Thr Ser Glu Ser Lys Met Met
2525 2530 2535
Gln Val Ile Glu Glu Tyr Ile Glu Asp Tyr Asn Gln Ile Asn Thr
2540 2545 2550
Ala Lys Leu Lys Leu Val Leu Phe Met Asp Ala Met Ser His Ile
2555 2560 2565
Cys Arg Ile Ser Arg Thr Leu Arg Gln Ala Leu Gly Asn Ala Leu
2570 2575 2580
Leu Leu Gly Val Gly Gly Ser Gly Arg Ser Ser Leu Thr Arg Leu
2585 2590 2595
Ala Ser His Met Ala Glu Tyr Glu Cys Phe Gln Ile Glu Leu Ser
2600 2605 2610
Lys Asn Tyr Gly Met Ser Glu Trp Arg Asp Asp Val Lys Lys Val
2615 2620 2625
Leu Leu Lys Ala Gly Leu Gln Asn Leu Pro Ile Thr Phe Leu Phe
2630 2635 2640
Ser Asp Thr Gln Ile Lys Asn Glu Ser Phe Leu Glu Asp Ile Asn
2645 2650 2655
Asn Val Leu Asn Ser Gly Asp Ile Pro Asn Leu Tyr Thr Ala Asp
2660 2665 2670
Glu Gln Asp Gln Ile Val Ser Thr Met Arg Pro Tyr Ile Gln Glu
2675 2680 2685
Gln Gly Leu Gln Pro Thr Lys Ala Asn Leu Met Ala Ala Tyr Thr
2690 2695 2700
Gly Arg Val Arg Ser Asn Ile His Met Val Leu Cys Met Ser Pro
2705 2710 2715
Ile Gly Glu Val Phe Arg Ala Arg Leu Arg Gln Phe Pro Ser Leu
2720 2725 2730
Val Asn Cys Cys Thr Ile Asp Trp Phe Asn Glu Trp Pro Ala Glu
2735 2740 2745
Ala Leu Lys Ser Val Ala Thr Val Phe Leu Asn Glu Ile Pro Glu
2750 2755 2760
Leu Glu Ser Ser Gln Glu Glu Ile Gln Gly Leu Ile Gln Val Cys
2765 2770 2775
Val Tyr Ile His Gln Ser Val Ser Lys Lys Cys Ile Glu Tyr Leu
2780 2785 2790
Ala Glu Leu Thr Arg His Asn Tyr Val Thr Pro Lys Ser Tyr Leu
2795 2800 2805
Glu Leu Leu His Ile Phe Ser Ile Leu Ile Gly Gln Lys Lys Leu
2810 2815 2820
Glu Leu Lys Thr Ala Lys Asn Arg Met Lys Ser Gly Leu Asp Lys
2825 2830 2835
Leu Leu Arg Thr Ser Glu Asp Val Ala Lys Met Gln Glu Asp Leu
2840 2845 2850
Glu Ser Met His Pro Leu Leu Glu Glu Ala Ala Lys Asp Thr Met
2855 2860 2865
Leu Thr Met Glu Gln Ile Lys Val Asp Thr Ala Ile Ala Glu Glu
2870 2875 2880
Thr Arg Asn Ser Val Gln Thr Glu Glu Ile Lys Ala Asn Glu Lys
2885 2890 2895
Ala Lys Lys Ala Gln Ala Ile Ala Asp Asp Ala Gln Lys Asp Leu
2900 2905 2910
Asp Glu Ala Leu Pro Ala Leu Asp Ala Ala Leu Ala Ser Leu Arg
2915 2920 2925
Asn Leu Asn Lys Asn Asp Val Thr Glu Val Arg Ala Met Gln Arg
2930 2935 2940
Pro Pro Pro Gly Val Lys Leu Val Ile Glu Ala Val Cys Ile Met
2945 2950 2955
Lys Gly Ile Lys Pro Lys Lys Val Pro Gly Glu Lys Pro Gly Thr
2960 2965 2970
Lys Val Asp Asp Tyr Trp Glu Pro Gly Lys Gly Leu Leu Gln Asp
2975 2980 2985
Pro Gly His Phe Leu Glu Ser Leu Phe Lys Phe Asp Lys Asp Asn
2990 2995 3000
Ile Gly Asp Val Val Ile Lys Ala Ile Gln Pro Tyr Ile Asp Asn
3005 3010 3015
Glu Glu Phe Gln Pro Ala Thr Ile Ala Lys Val Ser Lys Ala Cys
3020 3025 3030
Thr Ser Ile Cys Gln Trp Val Arg Ala Met His Lys Tyr His Phe
3035 3040 3045
Val Ala Lys Ala Val Glu Pro Lys Arg Gln Ala Leu Leu Glu Ala
3050 3055 3060
Gln Asp Asp Leu Gly Val Thr Gln Arg Ile Leu Asp Glu Ala Lys
3065 3070 3075
Gln Arg Leu Arg Glu Val Glu Asp Gly Ile Ala Thr Met Gln Ala
3080 3085 3090
Lys Tyr Arg Glu Cys Ile Thr Lys Lys Glu Glu Leu Glu Leu Lys
3095 3100 3105
Cys Glu Gln Cys Glu Gln Arg Leu Gly Arg Ala Gly Lys Leu Ile
3110 3115 3120
Asn Gly Leu Ser Asp Glu Lys Val Arg Trp Gln Glu Thr Val Glu
3125 3130 3135
Asn Leu Gln Tyr Met Leu Asn Asn Ile Ser Gly Asp Val Leu Val
3140 3145 3150
Ala Ala Gly Phe Val Ala Tyr Leu Gly Pro Phe Thr Gly Gln Tyr
3155 3160 3165
Arg Thr Val Leu Tyr Asp Ser Trp Val Lys Gln Leu Arg Ser His
3170 3175 3180
Asn Val Pro His Thr Ser Glu Pro Thr Leu Ile Gly Thr Leu Gly
3185 3190 3195
Asn Pro Val Lys Ile Arg Ser Trp Gln Ile Ala Gly Leu Pro Asn
3200 3205 3210
Asp Thr Leu Ser Val Glu Asn Gly Val Ile Asn Gln Phe Ser Gln
3215 3220 3225
Arg Trp Thr His Phe Ile Asp Pro Gln Ser Gln Ala Asn Lys Trp
3230 3235 3240
Ile Lys Asn Met Glu Lys Asp Asn Gly Leu Asp Val Phe Lys Leu
3245 3250 3255
Ser Asp Arg Asp Phe Leu Arg Ser Met Glu Asn Ala Ile Arg Phe
3260 3265 3270
Gly Lys Pro Cys Leu Leu Glu Asn Val Gly Glu Glu Leu Asp Pro
3275 3280 3285
Ala Leu Glu Pro Val Leu Leu Lys Gln Thr Tyr Lys Gln Gln Gly
3290 3295 3300
Asn Thr Val Leu Lys Leu Gly Asp Thr Val Ile Pro Tyr His Glu
3305 3310 3315
Asp Phe Arg Met Tyr Ile Thr Thr Lys Leu Pro Asn Pro His Tyr
3320 3325 3330
Thr Pro Glu Ile Ser Thr Lys Leu Thr Leu Ile Asn Phe Thr Leu
3335 3340 3345
Ser Pro Ser Gly Leu Glu Asp Gln Leu Leu Gly Gln Val Val Ala
3350 3355 3360
Glu Glu Arg Pro Asp Leu Glu Glu Ala Lys Asn Gln Leu Ile Ile
3365 3370 3375
Ser Asn Ala Lys Met Arg Gln Glu Leu Lys Asp Ile Glu Asp Gln
3380 3385 3390
Ile Leu Tyr Arg Leu Ser Ser Ser Glu Gly Asn Pro Val Asp Asp
3395 3400 3405
Met Glu Leu Ile Lys Val Leu Glu Ala Ser Lys Met Lys Ala Ala
3410 3415 3420
Glu Ile Gln Ala Lys Val Arg Ile Ala Glu Gln Thr Glu Lys Asp
3425 3430 3435
Ile Asp Leu Thr Arg Met Glu Tyr Ile Pro Val Ala Ile Arg Thr
3440 3445 3450
Gln Ile Leu Phe Phe Cys Val Ser Asp Leu Ala Asn Val Asp Pro
3455 3460 3465
Met Tyr Gln Tyr Ser Leu Glu Trp Phe Leu Asn Ile Phe Leu Ser
3470 3475 3480
Gly Ile Ala Asn Ser Glu Arg Ala Asp Asn Leu Lys Lys Arg Ile
3485 3490 3495
Ser Asn Ile Asn Arg Tyr Leu Thr Tyr Ser Leu Tyr Ser Asn Val
3500 3505 3510
Cys Arg Ser Leu Phe Glu Lys His Lys Leu Met Phe Ala Phe Leu
3515 3520 3525
Leu Cys Val Arg Ile Met Met Asn Glu Gly Lys Ile Asn Gln Ser
3530 3535 3540
Glu Trp Arg Tyr Leu Leu Ser Gly Gly Ser Ile Ser Ile Met Thr
3545 3550 3555
Glu Asn Pro Ala Pro Asp Trp Leu Ser Asp Arg Ala Trp Arg Asp
3560 3565 3570
Ile Leu Ala Leu Ser Asn Leu Pro Thr Phe Ser Ser Phe Ser Ser
3575 3580 3585
Asp Phe Val Lys His Leu Ser Glu Phe Arg Val Ile Phe Asp Ser
3590 3595 3600
Leu Glu Pro His Arg Glu Pro Leu Pro Gly Ile Trp Asp Gln Tyr
3605 3610 3615
Leu Asp Gln Phe Gln Lys Leu Leu Val Leu Arg Cys Leu Arg Gly
3620 3625 3630
Asp Lys Val Thr Asn Ala Met Gln Asp Phe Val Ala Thr Asn Leu
3635 3640 3645
Glu Pro Arg Phe Ile Glu Pro Gln Thr Ala Asn Leu Ser Val Val
3650 3655 3660
Phe Lys Asp Ser Asn Ser Thr Thr Pro Leu Ile Phe Val Leu Ser
3665 3670 3675
Pro Gly Thr Asp Pro Ala Ala Asp Leu Tyr Lys Phe Ala Glu Glu
3680 3685 3690
Met Lys Phe Ser Lys Lys Leu Ser Ala Ile Ser Leu Gly Gln Gly
3695 3700 3705
Gln Gly Pro Arg Ala Glu Ala Met Met Arg Ser Ser Ile Glu Arg
3710 3715 3720
Gly Lys Trp Val Phe Phe Gln Asn Cys His Leu Ala Pro Ser Trp
3725 3730 3735
Met Pro Ala Leu Glu Arg Leu Ile Glu His Ile Asn Pro Asp Lys
3740 3745 3750
Val His Arg Asp Phe Arg Leu Trp Leu Thr Ser Leu Pro Ser Asn
3755 3760 3765
Lys Phe Pro Val Ser Ile Leu Gln Asn Gly Ser Lys Met Thr Ile
3770 3775 3780
Glu Pro Pro Arg Gly Val Arg Ala Asn Leu Leu Lys Ser Tyr Ser
3785 3790 3795
Ser Leu Gly Glu Asp Phe Leu Asn Ser Cys His Lys Val Met Glu
3800 3805 3810
Phe Lys Ser Leu Leu Leu Ser Leu Cys Leu Phe His Gly Asn Ala
3815 3820 3825
Leu Glu Arg Arg Lys Phe Gly Pro Leu Gly Phe Asn Ile Pro Tyr
3830 3835 3840
Glu Phe Thr Asp Gly Asp Leu Arg Ile Cys Ile Ser Gln Leu Lys
3845 3850 3855
Met Phe Leu Asp Glu Tyr Asp Asp Ile Pro Tyr Lys Val Leu Lys
3860 3865 3870
Tyr Thr Ala Gly Glu Ile Asn Tyr Gly Gly Arg Val Thr Asp Asp
3875 3880 3885
Trp Asp Arg Arg Cys Ile Met Asn Ile Leu Glu Asp Phe Tyr Asn
3890 3895 3900
Pro Asp Val Leu Ser Pro Glu His Ser Tyr Ser Ala Ser Gly Ile
3905 3910 3915
Tyr His Gln Ile Pro Pro Thr Tyr Asp Leu His Gly Tyr Leu Ser
3920 3925 3930
Tyr Ile Lys Ser Leu Pro Leu Asn Asp Met Pro Glu Ile Phe Gly
3935 3940 3945
Leu His Asp Asn Ala Asn Ile Thr Phe Ala Gln Asn Glu Thr Phe
3950 3955 3960
Ala Leu Leu Gly Thr Ile Ile Gln Leu Gln Pro Lys Ser Ser Ser
3965 3970 3975
Ala Gly Ser Gln Gly Arg Glu Glu Ile Val Glu Asp Val Thr Gln
3980 3985 3990
Asn Ile Leu Leu Lys Val Pro Glu Pro Ile Asn Leu Gln Trp Val
3995 4000 4005
Met Ala Lys Tyr Pro Val Leu Tyr Glu Glu Ser Met Asn Thr Val
4010 4015 4020
Leu Val Gln Glu Val Ile Arg Tyr Asn Arg Leu Leu Gln Val Ile
4025 4030 4035
Thr Gln Thr Leu Gln Asp Leu Leu Lys Ala Leu Lys Gly Leu Val
4040 4045 4050
Val Met Ser Ser Gln Leu Glu Leu Met Ala Ala Ser Leu Tyr Asn
4055 4060 4065
Asn Thr Val Pro Glu Leu Trp Ser Ala Lys Ala Tyr Pro Ser Leu
4070 4075 4080
Lys Pro Leu Ser Ser Trp Val Met Asp Leu Leu Gln Arg Leu Asp
4085 4090 4095
Phe Leu Gln Ala Trp Ile Gln Asp Gly Ile Pro Ala Val Phe Trp
4100 4105 4110
Ile Ser Gly Phe Phe Phe Pro Gln Ala Phe Leu Thr Gly Thr Leu
4115 4120 4125
Gln Asn Phe Ala Arg Lys Phe Val Ile Ser Ile Asp Thr Ile Ser
4130 4135 4140
Phe Asp Phe Lys Val Met Phe Glu Ala Pro Ser Glu Leu Thr Gln
4145 4150 4155
Arg Pro Gln Val Gly Cys Tyr Ile His Gly Leu Phe Leu Glu Gly
4160 4165 4170
Ala Arg Trp Asp Pro Glu Ala Phe Gln Leu Ala Glu Ser Gln Pro
4175 4180 4185
Lys Glu Leu Tyr Thr Glu Met Ala Val Ile Trp Leu Leu Pro Thr
4190 4195 4200
Pro Asn Arg Lys Ala Gln Asp Gln Asp Phe Tyr Leu Cys Pro Ile
4205 4210 4215
Tyr Lys Thr Leu Thr Arg Ala Gly Thr Leu Ser Thr Thr Gly His
4220 4225 4230
Ser Thr Asn Tyr Val Ile Ala Val Glu Ile Pro Thr His Gln Pro
4235 4240 4245
Gln Arg His Trp Ile Lys Arg Gly Val Ala Leu Ile Cys Ala Leu
4250 4255 4260
Asp Tyr
4265
<210> 3
<211> 18
<212> DNA
<213>人工序列
<400> 3
gccttgtctt ccctcatc 18
<210> 4
<211> 21
<212> DNA
<213>人工序列
<400> 4
gaaaggaaag actccagaat c 21
<210> 5
<211> 20
<212> DNA
<213>人工序列
<400> 5
cctatgagtt cacggatgga 20
<210> 6
<211> 20
<212> DNA
<213>人工序列
<400> 6
ctgaccagga gttcactcac 20
<210> 7
<211> 18
<212> DNA
<213>人工序列
<400> 7
ttgaccagcc tcccacat 18
<210> 8
<211> 20
<212> DNA
<213>人工序列
<400> 8
atccttgttc tgagtgtcct 20
<210> 9
<211> 21
<212> DNA
<213>人工序列
<400> 9
atggatcaag aacatggtga g 21
<210> 10
<211> 18
<212> DNA
<213>人工序列
<400> 10
gaggcagagc tgatgctt 18
<210> 11
<211> 18
<212> DNA
<213>人工序列
<400> 11
ccttgctgaa gccctatg 18
<210> 12
<211> 18
<212> DNA
<213>人工序列
<400> 12
actctacgat gcgactca 18
<210> 13
<211> 21
<212> DNA
<213>人工序列
<400> 13
tctctgctct tagcctctat g 21
<210> 14
<211> 20
<212> DNA
<213>人工序列
<400> 14
ctcttctggc ttgggtcttt 20
<210> 15
<211> 18
<212> DNA
<213>人工序列
<400> 15
gggatgtggg acttctct 18
<210> 16
<211> 20
<212> DNA
<213>人工序列
<400> 16
cgttaatatg ggctgtggat 20
<210> 17
<211> 18
<212> DNA
<213>人工序列
<400> 17
aaggcaagga ggtcagga 18
<210> 18
<211> 18
<212> DNA
<213>人工序列
<400> 18
tggctccctg ctacactt 18
<210> 19
<211> 19
<212> DNA
<213>人工序列
<400> 19
tcaggtggga agagaagaa 19
<210> 20
<211> 18
<212> DNA
<213>人工序列
<400> 20
gagcaaaggt caggttgg 18
<210> 21
<211> 20
<212> DNA
<213>人工序列
<400> 21
attacaccat gtgacaccaa 20
<210> 22
<211> 18
<212> DNA
<213>人工序列
<400> 22
gaggcaagag gcatcatc 18
<210> 23
<211> 18
<212> DNA
<213>人工序列
<400> 23
caggatgttg tggtggag 18
<210> 24
<211> 18
<212> DNA
<213>人工序列
<400> 24
agggaggtgg tgggtaat 18
<210> 25
<211> 21
<212> DNA
<213>人工序列
<400> 25
agataggact atgtcttcac c 21
<210> 26
<211> 20
<212> DNA
<213>人工序列
<400> 26
tggaatggta ggtacagatg 20
<210> 27
<211> 18
<212> DNA
<213>人工序列
<400> 27
gctgtctctg tgcttgtt 18
<210> 28
<211> 18
<212> DNA
<213>人工序列
<400> 28
cctggttact gccttgga 18
<210> 29
<211> 1035
<212> PRT
<213> Homo Sapiens
<400> 29
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu Trp Met Lys Gly Ile Pro Glu Arg Leu Val Gly
865 870 875 880
Leu Glu Glu Arg Ile Val Lys Val Met Asp Asp Tyr Gln Val Met Asp
885 890 895
Glu Phe Leu Tyr Asn Leu Ser Ser Asp Asp Phe Asn Asp Lys Trp Ile
900 905 910
Ala Ser Asn Trp Pro Ser Lys Ile Leu Gly Gln Ile Glu Leu Val Gln
915 920 925
Gln Gln His Val Glu Asp Glu Glu Lys Phe Arg Lys Ile Gln Ile Met
930 935 940
Asp Gln Asn Asn Phe Gln Glu Lys Leu Glu Gly Leu Gln Leu Val Val
945 950 955 960
Ala Gly Phe Ser Ile His Val Glu Ile Ser Arg Ala His Glu Ile Ala
965 970 975
Asn Glu Val Arg Arg Val Lys Lys Gln Leu Lys Asp Cys Gln Gln Leu
980 985 990
Ala Met Leu Tyr Asn Asn Arg Glu Arg Ile Phe Ser Leu Pro Ile Thr
995 1000 1005
Asn Tyr Asp Lys Leu Ser Arg Met Val Lys Glu Phe Gln Pro Tyr
1010 1015 1020
Leu Asp Leu Trp Thr Thr Ala Ser Asp Trp Leu Arg
1025 1030 1035
<210> 30
<211> 1954
<212> PRT
<213> Homo Sapiens
<400> 30
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu Trp Met Lys Gly Ile Pro Glu Arg Leu Val Gly
865 870 875 880
Leu Glu Glu Arg Ile Val Lys Val Met Asp Asp Tyr Gln Val Met Asp
885 890 895
Glu Phe Leu Tyr Asn Leu Ser Ser Asp Asp Phe Asn Asp Lys Trp Ile
900 905 910
Ala Ser Asn Trp Pro Ser Lys Ile Leu Gly Gln Ile Glu Leu Val Gln
915 920 925
Gln Gln His Val Glu Asp Glu Glu Lys Phe Arg Lys Ile Gln Ile Met
930 935 940
Asp Gln Asn Asn Phe Gln Glu Lys Leu Glu Gly Leu Gln Leu Val Val
945 950 955 960
Ala Gly Phe Ser Ile His Val Glu Ile Ser Arg Ala His Glu Ile Ala
965 970 975
Asn Glu Val Arg Arg Val Lys Lys Gln Leu Lys Asp Cys Gln Gln Leu
980 985 990
Ala Met Leu Tyr Asn Asn Arg Glu Arg Ile Phe Ser Leu Pro Ile Thr
995 1000 1005
Asn Tyr Asp Lys Leu Ser Arg Met Val Lys Glu Phe Gln Pro Tyr
1010 1015 1020
Leu Asp Leu Trp Thr Thr Ala Ser Asp Trp Leu Arg Trp Ser Glu
1025 1030 1035
Ser Trp Met Asn Asp Pro Leu Ser Ala Ile Asp Ala Glu Gln Leu
1040 1045 1050
Glu Lys Asn Val Val Glu Ala Phe Lys Thr Met His Lys Cys Val
1055 1060 1065
Lys Gln Phe Lys Asp Met Pro Ala Cys Gln Glu Val Ala Leu Asp
1070 1075 1080
Ile Arg Ala Arg Ile Glu Glu Phe Lys Pro Tyr Ile Pro Leu Ile
1085 1090 1095
Gln Gly Leu Arg Asn Pro Gly Met Arg Ile Arg His Trp Glu Thr
1100 1105 1110
Leu Ser Asn Gln Ile Asn Ile Asn Val Arg Pro Lys Ala Asn Leu
1115 1120 1125
Thr Phe Ala Arg Cys Leu Glu Met Asn Leu Gln Asp His Ile Glu
1130 1135 1140
Ser Ile Ser Lys Val Ala Glu Val Ala Gly Lys Glu Tyr Ala Ile
1145 1150 1155
Glu Gln Ala Leu Asp Lys Met Glu Lys Glu Trp Ser Thr Ile Leu
1160 1165 1170
Phe Asn Val Leu Pro Tyr Lys Ala Thr Asp Thr Tyr Ile Leu Lys
1175 1180 1185
Ser Pro Asp Glu Ala Ser Gln Leu Leu Asp Asp His Ile Val Met
1190 1195 1200
Thr Gln Asn Met Ser Phe Ser Pro Tyr Lys Lys Pro Phe Glu Gln
1205 1210 1215
Arg Ile Asn Ser Trp Glu Asn Lys Leu Lys Leu Thr Gln Glu Val
1220 1225 1230
Leu Glu Glu Trp Leu Asn Cys Gln Arg Ser Trp Leu Tyr Leu Glu
1235 1240 1245
Pro Ile Phe Ser Ser Glu Asp Ile Asn Gln Gln Leu Pro Val Glu
1250 1255 1260
Ser Lys Arg Tyr Gln Thr Met Glu Arg Ile Trp Lys Lys Ile Met
1265 1270 1275
Lys Asn Ala Tyr Glu Asn Arg Glu Val Ile Asn Val Cys Ser Asp
1280 1285 1290
Leu Arg Met Leu Asp Ser Leu Arg Asp Cys Asn Lys Ile Leu Asp
1295 1300 1305
Leu Val Gln Lys Gly Leu Ser Glu Tyr Leu Glu Thr Lys Arg Ser
1310 1315 1320
Ala Phe Pro Arg Phe Tyr Phe Leu Ser Asp Asp Glu Leu Leu Glu
1325 1330 1335
Ile Leu Ser Gln Thr Lys Asp Pro Thr Ala Val Gln Pro His Leu
1340 1345 1350
Arg Lys Cys Phe Glu Asn Ile Ala Arg Leu Leu Phe Gln Glu Asp
1355 1360 1365
Leu Glu Ile Thr His Met Tyr Ser Ala Glu Gly Glu Glu Val Gln
1370 1375 1380
Leu Cys Phe Ser Ile Tyr Pro Ser Ser Asn Val Glu Asp Trp Leu
1385 1390 1395
Arg Glu Val Glu Arg Ser Met Lys Ala Ser Val His Asp Ile Ile
1400 1405 1410
Glu Lys Ala Ile Arg Ala Tyr Pro Thr Met Pro Arg Thr Gln Trp
1415 1420 1425
Val Leu Asn Trp Pro Gly Gln Val Thr Ile Ala Gly Cys Gln Thr
1430 1435 1440
Tyr Trp Thr Met Glu Val Ala Glu Ala Leu Glu Ala Gly Asn Leu
1445 1450 1455
Arg Ser Gln Leu Phe Pro Gln Leu Cys Gln Gln Leu Ser Asp Leu
1460 1465 1470
Val Ala Leu Val Arg Gly Lys Leu Ser Arg Met Gln Arg Ala Val
1475 1480 1485
Leu Ser Ala Leu Ile Val Ile Glu Val His Ala Lys Asp Val Val
1490 1495 1500
Ser Lys Leu Ile Gln Glu Asn Val Val Ser Val Asn Asp Phe Gln
1505 1510 1515
Trp Ile Ser Gln Leu Arg Tyr Tyr Trp Thr Asn Asn Asp Leu Tyr
1520 1525 1530
Ile Arg Ala Val Asn Ala Glu Phe Ile Tyr Gly Tyr Glu Tyr Leu
1535 1540 1545
Gly Asn Ser Gly Arg Leu Val Ile Thr Pro Leu Thr Asp Arg Cys
1550 1555 1560
Tyr Leu Thr Leu Thr Gly Ala Leu His Leu Lys Phe Gly Gly Ala
1565 1570 1575
Pro Ala Gly Pro Ala Gly Thr Gly Lys Thr Glu Thr Thr Lys Asp
1580 1585 1590
Leu Gly Lys Ala Leu Ala Ile Gln Thr Val Val Phe Asn Cys Ser
1595 1600 1605
Asp Gln Leu Asp Phe Met Ala Met Gly Lys Phe Phe Lys Gly Leu
1610 1615 1620
Ala Ser Ala Gly Ala Trp Ala Cys Phe Asp Glu Phe Asn Arg Ile
1625 1630 1635
Asp Ile Glu Val Leu Ser Val Val Ala Gln Gln Ile Thr Thr Ile
1640 1645 1650
Gln Lys Ala Gln Gln Gln Arg Val Glu Arg Phe Met Phe Glu Gly
1655 1660 1665
Val Glu Ile Pro Leu Val Pro Ser Cys Ala Val Phe Ile Thr Met
1670 1675 1680
Asn Pro Gly Tyr Ala Gly Arg Thr Glu Leu Pro Asp Asn Leu Lys
1685 1690 1695
Ala Leu Phe Arg Pro Val Ala Met Met Val Pro Asp Tyr Ala Met
1700 1705 1710
Ile Thr Glu Ile Ser Leu Tyr Ser Phe Gly Phe Asn Glu Ala Ser
1715 1720 1725
Val Leu Ala Lys Lys Ile Thr Thr Thr Phe Lys Leu Ser Ser Glu
1730 1735 1740
Gln Leu Ser Ser Gln Asp His Tyr Asp Phe Gly Met Arg Ala Val
1745 1750 1755
Lys Thr Val Ile Ser Ala Ala Gly Asn Leu Lys Arg Glu Asn Pro
1760 1765 1770
Ser Met Asn Glu Glu Leu Ile Cys Leu Arg Ala Ile Arg Asp Val
1775 1780 1785
Asn Val Pro Lys Phe Leu Gln Glu Asp Leu Lys Leu Phe Ser Gly
1790 1795 1800
Ile Val Ser Asp Leu Phe Pro Thr Ile Lys Glu Glu Asp Thr Asp
1805 1810 1815
Tyr Gly Ile Leu Asp Glu Ala Ile Arg Glu Ala Cys Arg Asn Ser
1820 1825 1830
Asn Leu Lys Asp Val Glu Gly Phe Leu Thr Lys Cys Ile Gln Leu
1835 1840 1845
Tyr Glu Thr Thr Val Val Arg His Gly Leu Met Leu Val Gly Pro
1850 1855 1860
Thr Gly Ser Gly Lys Ser Thr Cys Tyr Arg Val Leu Ala Ala Ala
1865 1870 1875
Met Thr Ser Leu Lys Gly Gln Pro Ser Ile Ser Gly Gly Met Tyr
1880 1885 1890
Glu Ala Val Asn Tyr Tyr Val Leu Asn Pro Lys Ser Ile Thr Met
1895 1900 1905
Gly Gln Leu Tyr Gly Glu Phe Asp Leu Leu Thr His Glu Trp Thr
1910 1915 1920
Asp Gly Ile Phe Ser Ser Phe Ile Arg Ala Gly Ala Ile Thr Ser
1925 1930 1935
Asp Thr Asn Lys Lys Trp Tyr Met Phe Asp Gly Pro Val Asp Ala
1940 1945 1950
Ile
<210> 31
<211> 869
<212> PRT
<213> Homo Sapiens
<400> 31
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu
865
<210> 32
<211> 3543
<212> PRT
<213> Homo Sapiens
<400> 32
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu Trp Met Lys Gly Ile Pro Glu Arg Leu Val Gly
865 870 875 880
Leu Glu Glu Arg Ile Val Lys Val Met Asp Asp Tyr Gln Val Met Asp
885 890 895
Glu Phe Leu Tyr Asn Leu Ser Ser Asp Asp Phe Asn Asp Lys Trp Ile
900 905 910
Ala Ser Asn Trp Pro Ser Lys Ile Leu Gly Gln Ile Glu Leu Val Gln
915 920 925
Gln Gln His Val Glu Asp Glu Glu Lys Phe Arg Lys Ile Gln Ile Met
930 935 940
Asp Gln Asn Asn Phe Gln Glu Lys Leu Glu Gly Leu Gln Leu Val Val
945 950 955 960
Ala Gly Phe Ser Ile His Val Glu Ile Ser Arg Ala His Glu Ile Ala
965 970 975
Asn Glu Val Arg Arg Val Lys Lys Gln Leu Lys Asp Cys Gln Gln Leu
980 985 990
Ala Met Leu Tyr Asn Asn Arg Glu Arg Ile Phe Ser Leu Pro Ile Thr
995 1000 1005
Asn Tyr Asp Lys Leu Ser Arg Met Val Lys Glu Phe Gln Pro Tyr
1010 1015 1020
Leu Asp Leu Trp Thr Thr Ala Ser Asp Trp Leu Arg Trp Ser Glu
1025 1030 1035
Ser Trp Met Asn Asp Pro Leu Ser Ala Ile Asp Ala Glu Gln Leu
1040 1045 1050
Glu Lys Asn Val Val Glu Ala Phe Lys Thr Met His Lys Cys Val
1055 1060 1065
Lys Gln Phe Lys Asp Met Pro Ala Cys Gln Glu Val Ala Leu Asp
1070 1075 1080
Ile Arg Ala Arg Ile Glu Glu Phe Lys Pro Tyr Ile Pro Leu Ile
1085 1090 1095
Gln Gly Leu Arg Asn Pro Gly Met Arg Ile Arg His Trp Glu Thr
1100 1105 1110
Leu Ser Asn Gln Ile Asn Ile Asn Val Arg Pro Lys Ala Asn Leu
1115 1120 1125
Thr Phe Ala Arg Cys Leu Glu Met Asn Leu Gln Asp His Ile Glu
1130 1135 1140
Ser Ile Ser Lys Val Ala Glu Val Ala Gly Lys Glu Tyr Ala Ile
1145 1150 1155
Glu Gln Ala Leu Asp Lys Met Glu Lys Glu Trp Ser Thr Ile Leu
1160 1165 1170
Phe Asn Val Leu Pro Tyr Lys Ala Thr Asp Thr Tyr Ile Leu Lys
1175 1180 1185
Ser Pro Asp Glu Ala Ser Gln Leu Leu Asp Asp His Ile Val Met
1190 1195 1200
Thr Gln Asn Met Ser Phe Ser Pro Tyr Lys Lys Pro Phe Glu Gln
1205 1210 1215
Arg Ile Asn Ser Trp Glu Asn Lys Leu Lys Leu Thr Gln Glu Val
1220 1225 1230
Leu Glu Glu Trp Leu Asn Cys Gln Arg Ser Trp Leu Tyr Leu Glu
1235 1240 1245
Pro Ile Phe Ser Ser Glu Asp Ile Asn Gln Gln Leu Pro Val Glu
1250 1255 1260
Ser Lys Arg Tyr Gln Thr Met Glu Arg Ile Trp Lys Lys Ile Met
1265 1270 1275
Lys Asn Ala Tyr Glu Asn Arg Glu Val Ile Asn Val Cys Ser Asp
1280 1285 1290
Leu Arg Met Leu Asp Ser Leu Arg Asp Cys Asn Lys Ile Leu Asp
1295 1300 1305
Leu Val Gln Lys Gly Leu Ser Glu Tyr Leu Glu Thr Lys Arg Ser
1310 1315 1320
Ala Phe Pro Arg Phe Tyr Phe Leu Ser Asp Asp Glu Leu Leu Glu
1325 1330 1335
Ile Leu Ser Gln Thr Lys Asp Pro Thr Ala Val Gln Pro His Leu
1340 1345 1350
Arg Lys Cys Phe Glu Asn Ile Ala Arg Leu Leu Phe Gln Glu Asp
1355 1360 1365
Leu Glu Ile Thr His Met Tyr Ser Ala Glu Gly Glu Glu Val Gln
1370 1375 1380
Leu Cys Phe Ser Ile Tyr Pro Ser Ser Asn Val Glu Asp Trp Leu
1385 1390 1395
Arg Glu Val Glu Arg Ser Met Lys Ala Ser Val His Asp Ile Ile
1400 1405 1410
Glu Lys Ala Ile Arg Ala Tyr Pro Thr Met Pro Arg Thr Gln Trp
1415 1420 1425
Val Leu Asn Trp Pro Gly Gln Val Thr Ile Ala Gly Cys Gln Thr
1430 1435 1440
Tyr Trp Thr Met Glu Val Ala Glu Ala Leu Glu Ala Gly Asn Leu
1445 1450 1455
Arg Ser Gln Leu Phe Pro Gln Leu Cys Gln Gln Leu Ser Asp Leu
1460 1465 1470
Val Ala Leu Val Arg Gly Lys Leu Ser Arg Met Gln Arg Ala Val
1475 1480 1485
Leu Ser Ala Leu Ile Val Ile Glu Val His Ala Lys Asp Val Val
1490 1495 1500
Ser Lys Leu Ile Gln Glu Asn Val Val Ser Val Asn Asp Phe Gln
1505 1510 1515
Trp Ile Ser Gln Leu Arg Tyr Tyr Trp Thr Asn Asn Asp Leu Tyr
1520 1525 1530
Ile Arg Ala Val Asn Ala Glu Phe Ile Tyr Gly Tyr Glu Tyr Leu
1535 1540 1545
Gly Asn Ser Gly Arg Leu Val Ile Thr Pro Leu Thr Asp Arg Cys
1550 1555 1560
Tyr Leu Thr Leu Thr Gly Ala Leu His Leu Lys Phe Gly Gly Ala
1565 1570 1575
Pro Ala Gly Pro Ala Gly Thr Gly Lys Thr Glu Thr Thr Lys Asp
1580 1585 1590
Leu Gly Lys Ala Leu Ala Ile Gln Thr Val Val Phe Asn Cys Ser
1595 1600 1605
Asp Gln Leu Asp Phe Met Ala Met Gly Lys Phe Phe Lys Gly Leu
1610 1615 1620
Ala Ser Ala Gly Ala Trp Ala Cys Phe Asp Glu Phe Asn Arg Ile
1625 1630 1635
Asp Ile Glu Val Leu Ser Val Val Ala Gln Gln Ile Thr Thr Ile
1640 1645 1650
Gln Lys Ala Gln Gln Gln Arg Val Glu Arg Phe Met Phe Glu Gly
1655 1660 1665
Val Glu Ile Pro Leu Val Pro Ser Cys Ala Val Phe Ile Thr Met
1670 1675 1680
Asn Pro Gly Tyr Ala Gly Arg Thr Glu Leu Pro Asp Asn Leu Lys
1685 1690 1695
Ala Leu Phe Arg Pro Val Ala Met Met Val Pro Asp Tyr Ala Met
1700 1705 1710
Ile Thr Glu Ile Ser Leu Tyr Ser Phe Gly Phe Asn Glu Ala Ser
1715 1720 1725
Val Leu Ala Lys Lys Ile Thr Thr Thr Phe Lys Leu Ser Ser Glu
1730 1735 1740
Gln Leu Ser Ser Gln Asp His Tyr Asp Phe Gly Met Arg Ala Val
1745 1750 1755
Lys Thr Val Ile Ser Ala Ala Gly Asn Leu Lys Arg Glu Asn Pro
1760 1765 1770
Ser Met Asn Glu Glu Leu Ile Cys Leu Arg Ala Ile Arg Asp Val
1775 1780 1785
Asn Val Pro Lys Phe Leu Gln Glu Asp Leu Lys Leu Phe Ser Gly
1790 1795 1800
Ile Val Ser Asp Leu Phe Pro Thr Ile Lys Glu Glu Asp Thr Asp
1805 1810 1815
Tyr Gly Ile Leu Asp Glu Ala Ile Arg Glu Ala Cys Arg Asn Ser
1820 1825 1830
Asn Leu Lys Asp Val Glu Gly Phe Leu Thr Lys Cys Ile Gln Leu
1835 1840 1845
Tyr Glu Thr Thr Val Val Arg His Gly Leu Met Leu Val Gly Pro
1850 1855 1860
Thr Gly Ser Gly Lys Ser Thr Cys Tyr Arg Val Leu Ala Ala Ala
1865 1870 1875
Met Thr Ser Leu Lys Gly Gln Pro Ser Ile Ser Gly Gly Met Tyr
1880 1885 1890
Glu Ala Val Asn Tyr Tyr Val Leu Asn Pro Lys Ser Ile Thr Met
1895 1900 1905
Gly Gln Leu Tyr Gly Glu Phe Asp Leu Leu Thr His Glu Trp Thr
1910 1915 1920
Asp Gly Ile Phe Ser Ser Phe Ile Arg Ala Gly Ala Ile Thr Ser
1925 1930 1935
Asp Thr Asn Lys Lys Trp Tyr Met Phe Asp Gly Pro Val Asp Ala
1940 1945 1950
Ile Trp Ile Glu Asn Met Asn Thr Val Leu Asp Asp Asn Lys Lys
1955 1960 1965
Leu Cys Leu Ser Ser Gly Glu Ile Ile Lys Leu Thr Glu Ala Met
1970 1975 1980
Thr Met Met Phe Glu Val Gln Asp Leu Ala Val Ala Ser Pro Ala
1985 1990 1995
Thr Val Ser Arg Cys Gly Met Val Tyr Leu Glu Pro Ser Ile Leu
2000 2005 2010
Gly Leu Met Pro Phe Ile Glu Cys Trp Leu Arg Lys Leu Pro Pro
2015 2020 2025
Leu Leu Lys Pro Tyr Glu Glu His Phe Lys Ala Leu Phe Val Ser
2030 2035 2040
Phe Leu Glu Glu Ser Ile Ser Phe Val Arg Ser Ser Val Lys Glu
2045 2050 2055
Val Ile Ala Ser Thr Asn Cys Asn Leu Thr Met Ser Leu Leu Lys
2060 2065 2070
Leu Leu Asp Cys Phe Phe Lys Pro Phe Leu Pro Arg Glu Gly Leu
2075 2080 2085
Lys Lys Ile Pro Ser Glu Lys Leu Ser Arg Ile Val Glu Leu Ile
2090 2095 2100
Glu Pro Trp Phe Ile Phe Ser Leu Ile Trp Ser Val Gly Ala Thr
2105 2110 2115
Gly Asp Ser Ser Gly Arg Thr Ser Phe Ser His Trp Leu Arg Leu
2120 2125 2130
Lys Met Glu Asn Glu Gln Leu Thr Leu Leu Phe Pro Glu Glu Gly
2135 2140 2145
Leu Val Phe Asp Tyr Arg Leu Glu Asp Ala Gly Ile Ser Gly Thr
2150 2155 2160
Asn Asp Ser Glu Asp Glu Glu Glu Glu Tyr Lys Gln Val Ala Trp
2165 2170 2175
Val Lys Trp Met Asp Ser Ser Ala Pro Phe Thr Met Val Pro Asp
2180 2185 2190
Thr Asn Tyr Cys Asn Ile Ile Val Pro Thr Met Asp Thr Val Gln
2195 2200 2205
Met Ser His Leu Leu Asp Met Leu Leu Thr Asn Lys Lys Pro Val
2210 2215 2220
Leu Cys Ile Gly Pro Thr Gly Thr Gly Lys Thr Leu Thr Ile Ser
2225 2230 2235
Asp Lys Leu Leu Lys Asn Leu Ala Leu Asp Tyr Ile Ser His Phe
2240 2245 2250
Leu Thr Phe Ser Ala Arg Thr Ser Ala Asn Gln Thr Gln Asp Phe
2255 2260 2265
Ile Asp Ser Lys Leu Asp Lys Arg Arg Lys Gly Val Phe Gly Pro
2270 2275 2280
Pro Leu Gly Arg Asn Phe Ile Phe Phe Ile Asp Asp Leu Asn Met
2285 2290 2295
Pro Ala Leu Glu Thr Tyr Gly Ala Gln Pro Pro Ile Glu Leu Leu
2300 2305 2310
Arg Gln Trp Met Asp His Gly Gly Trp Tyr Asp Arg Lys Ile Ile
2315 2320 2325
Gly Ala Phe Lys Asn Leu Val Asp Ile Asn Phe Val Cys Ala Met
2330 2335 2340
Gly Pro Pro Gly Gly Gly Arg Asn Thr Val Thr Pro Arg Leu Met
2345 2350 2355
Arg His Phe Asn Tyr Leu Ser Phe Ala Glu Met Asp Glu Val Ser
2360 2365 2370
Lys Lys Arg Ile Phe Ser Thr Ile Leu Gly Asn Trp Leu Asp Gly
2375 2380 2385
Leu Leu Gly Glu Lys Ser Tyr Arg Glu Arg Val Pro Gly Ala Pro
2390 2395 2400
His Ile Ala His Phe Thr Glu Pro Leu Val Glu Ala Thr Ile Met
2405 2410 2415
Val Tyr Ala Thr Ile Thr Ser Gln Leu Leu Pro Thr Pro Ala Lys
2420 2425 2430
Ser His Tyr Thr Phe Asn Leu Arg Asp Leu Ser Lys Val Phe Gln
2435 2440 2445
Gly Met Leu Met Ala Asp Pro Ala Lys Val Glu Asp Gln Val Gln
2450 2455 2460
Leu Leu Arg Leu Trp Tyr His Glu Asn Cys Arg Val Phe Arg Asp
2465 2470 2475
Arg Leu Val Asn Glu Glu Asp Arg Ser Trp Phe Asp Gln Leu Leu
2480 2485 2490
Lys Arg Cys Met Glu Gln Trp Glu Val Thr Phe Asn Lys Val Cys
2495 2500 2505
Pro Phe Gln Pro Ile Leu Tyr Gly Asp Phe Met Ser Pro Gly Ser
2510 2515 2520
Asp Val Lys Ser Tyr Glu Leu Ile Thr Ser Glu Ser Lys Met Met
2525 2530 2535
Gln Val Ile Glu Glu Tyr Ile Glu Asp Tyr Asn Gln Ile Asn Thr
2540 2545 2550
Ala Lys Leu Lys Leu Val Leu Phe Met Asp Ala Met Ser His Ile
2555 2560 2565
Cys Arg Ile Ser Arg Thr Leu Arg Gln Ala Leu Gly Asn Ala Leu
2570 2575 2580
Leu Leu Gly Val Gly Gly Ser Gly Arg Ser Ser Leu Thr Arg Leu
2585 2590 2595
Ala Ser His Met Ala Glu Tyr Glu Cys Phe Gln Ile Glu Leu Ser
2600 2605 2610
Lys Asn Tyr Gly Met Ser Glu Trp Arg Asp Asp Val Lys Lys Val
2615 2620 2625
Leu Leu Lys Ala Gly Leu Gln Asn Leu Pro Ile Thr Phe Leu Phe
2630 2635 2640
Ser Asp Thr Gln Ile Lys Asn Glu Ser Phe Leu Glu Asp Ile Asn
2645 2650 2655
Asn Val Leu Asn Ser Gly Asp Ile Pro Asn Leu Tyr Thr Ala Asp
2660 2665 2670
Glu Gln Asp Gln Ile Val Ser Thr Met Arg Pro Tyr Ile Gln Glu
2675 2680 2685
Gln Gly Leu Gln Pro Thr Lys Ala Asn Leu Met Ala Ala Tyr Thr
2690 2695 2700
Gly Arg Val Arg Ser Asn Ile His Met Val Leu Cys Met Ser Pro
2705 2710 2715
Ile Gly Glu Val Phe Arg Ala Arg Leu Arg Gln Phe Pro Ser Leu
2720 2725 2730
Val Asn Cys Cys Thr Ile Asp Trp Phe Asn Glu Trp Pro Ala Glu
2735 2740 2745
Ala Leu Lys Ser Val Ala Thr Val Phe Leu Asn Glu Ile Pro Glu
2750 2755 2760
Leu Glu Ser Ser Gln Glu Glu Ile Gln Gly Leu Ile Gln Val Cys
2765 2770 2775
Val Tyr Ile His Gln Ser Val Ser Lys Lys Cys Ile Glu Tyr Leu
2780 2785 2790
Ala Glu Leu Thr Arg His Asn Tyr Val Thr Pro Lys Ser Tyr Leu
2795 2800 2805
Glu Leu Leu His Ile Phe Ser Ile Leu Ile Gly Gln Lys Lys Leu
2810 2815 2820
Glu Leu Lys Thr Ala Lys Asn Arg Met Lys Ser Gly Leu Asp Lys
2825 2830 2835
Leu Leu Arg Thr Ser Glu Asp Val Ala Lys Met Gln Glu Asp Leu
2840 2845 2850
Glu Ser Met His Pro Leu Leu Glu Glu Ala Ala Lys Asp Thr Met
2855 2860 2865
Leu Thr Met Glu Gln Ile Lys Val Asp Thr Ala Ile Ala Glu Glu
2870 2875 2880
Thr Arg Asn Ser Val Gln Thr Glu Glu Ile Lys Ala Asn Glu Lys
2885 2890 2895
Ala Lys Lys Ala Gln Ala Ile Ala Asp Asp Ala Gln Lys Asp Leu
2900 2905 2910
Asp Glu Ala Leu Pro Ala Leu Asp Ala Ala Leu Ala Ser Leu Arg
2915 2920 2925
Asn Leu Asn Lys Asn Asp Val Thr Glu Val Arg Ala Met Gln Arg
2930 2935 2940
Pro Pro Pro Gly Val Lys Leu Val Ile Glu Ala Val Cys Ile Met
2945 2950 2955
Lys Gly Ile Lys Pro Lys Lys Val Pro Gly Glu Lys Pro Gly Thr
2960 2965 2970
Lys Val Asp Asp Tyr Trp Glu Pro Gly Lys Gly Leu Leu Gln Asp
2975 2980 2985
Pro Gly His Phe Leu Glu Ser Leu Phe Lys Phe Asp Lys Asp Asn
2990 2995 3000
Ile Gly Asp Val Val Ile Lys Ala Ile Gln Pro Tyr Ile Asp Asn
3005 3010 3015
Glu Glu Phe Gln Pro Ala Thr Ile Ala Lys Val Ser Lys Ala Cys
3020 3025 3030
Thr Ser Ile Cys Gln Trp Val Arg Ala Met His Lys Tyr His Phe
3035 3040 3045
Val Ala Lys Ala Val Glu Pro Lys Arg Gln Ala Leu Leu Glu Ala
3050 3055 3060
Gln Asp Asp Leu Gly Val Thr Gln Arg Ile Leu Asp Glu Ala Lys
3065 3070 3075
Gln Arg Leu Arg Glu Val Glu Asp Gly Ile Ala Thr Met Gln Ala
3080 3085 3090
Lys Tyr Arg Glu Cys Ile Thr Lys Lys Glu Glu Leu Glu Leu Lys
3095 3100 3105
Cys Glu Gln Cys Glu Gln Arg Leu Gly Arg Ala Gly Lys Leu Ile
3110 3115 3120
Asn Gly Leu Ser Asp Glu Lys Val Arg Trp Gln Glu Thr Val Glu
3125 3130 3135
Asn Leu Gln Tyr Met Leu Asn Asn Ile Ser Gly Asp Val Leu Val
3140 3145 3150
Ala Ala Gly Phe Val Ala Tyr Leu Gly Pro Phe Thr Gly Gln Tyr
3155 3160 3165
Arg Thr Val Leu Tyr Asp Ser Trp Val Lys Gln Leu Arg Ser His
3170 3175 3180
Asn Val Pro His Thr Ser Glu Pro Thr Leu Ile Gly Thr Leu Gly
3185 3190 3195
Asn Pro Val Lys Ile Arg Ser Trp Gln Ile Ala Gly Leu Pro Asn
3200 3205 3210
Asp Thr Leu Ser Val Glu Asn Gly Val Ile Asn Gln Phe Ser Gln
3215 3220 3225
Arg Trp Thr His Phe Ile Asp Pro Gln Ser Gln Ala Asn Lys Trp
3230 3235 3240
Ile Lys Asn Met Glu Lys Asp Asn Gly Leu Asp Val Phe Lys Leu
3245 3250 3255
Ser Asp Arg Asp Phe Leu Arg Ser Met Glu Asn Ala Ile Arg Phe
3260 3265 3270
Gly Lys Pro Cys Leu Leu Glu Asn Val Gly Glu Glu Leu Asp Pro
3275 3280 3285
Ala Leu Glu Pro Val Leu Leu Lys Gln Thr Tyr Lys Gln Gln Gly
3290 3295 3300
Asn Thr Val Leu Lys Leu Gly Asp Thr Val Ile Pro Tyr His Glu
3305 3310 3315
Asp Phe Arg Met Tyr Ile Thr Thr Lys Leu Pro Asn Pro His Tyr
3320 3325 3330
Thr Pro Glu Ile Ser Thr Lys Leu Thr Leu Ile Asn Phe Thr Leu
3335 3340 3345
Ser Pro Ser Gly Leu Glu Asp Gln Leu Leu Gly Gln Val Val Ala
3350 3355 3360
Glu Glu Arg Pro Asp Leu Glu Glu Ala Lys Asn Gln Leu Ile Ile
3365 3370 3375
Ser Asn Ala Lys Met Arg Gln Glu Leu Lys Asp Ile Glu Asp Gln
3380 3385 3390
Ile Leu Tyr Arg Leu Ser Ser Ser Glu Gly Asn Pro Val Asp Asp
3395 3400 3405
Met Glu Leu Ile Lys Val Leu Glu Ala Ser Lys Met Lys Ala Ala
3410 3415 3420
Glu Ile Gln Ala Lys Val Arg Ile Ala Glu Gln Thr Glu Lys Asp
3425 3430 3435
Ile Asp Leu Thr Arg Met Glu Tyr Ile Pro Val Ala Ile Arg Thr
3440 3445 3450
Gln Ile Leu Phe Phe Cys Val Ser Asp Leu Ala Asn Val Asp Pro
3455 3460 3465
Met Tyr Gln Tyr Ser Leu Glu Trp Phe Leu Asn Ile Phe Leu Ser
3470 3475 3480
Gly Ile Ala Asn Ser Glu Arg Ala Asp Asn Leu Lys Lys Arg Ile
3485 3490 3495
Ser Asn Ile Asn Arg Tyr Leu Thr Tyr Ser Leu Tyr Ser Asn Val
3500 3505 3510
Cys Arg Ser Leu Phe Glu Lys His Lys Leu Met Phe Ala Phe Leu
3515 3520 3525
Leu Cys Val Arg Ile Met Met Asn Glu Gly Lys Ile Asn Gln Ser
3530 3535 3540
<210> 33
<211> 3940
<212> PRT
<213> Homo Sapiens
<400> 33
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu Trp Met Lys Gly Ile Pro Glu Arg Leu Val Gly
865 870 875 880
Leu Glu Glu Arg Ile Val Lys Val Met Asp Asp Tyr Gln Val Met Asp
885 890 895
Glu Phe Leu Tyr Asn Leu Ser Ser Asp Asp Phe Asn Asp Lys Trp Ile
900 905 910
Ala Ser Asn Trp Pro Ser Lys Ile Leu Gly Gln Ile Glu Leu Val Gln
915 920 925
Gln Gln His Val Glu Asp Glu Glu Lys Phe Arg Lys Ile Gln Ile Met
930 935 940
Asp Gln Asn Asn Phe Gln Glu Lys Leu Glu Gly Leu Gln Leu Val Val
945 950 955 960
Ala Gly Phe Ser Ile His Val Glu Ile Ser Arg Ala His Glu Ile Ala
965 970 975
Asn Glu Val Arg Arg Val Lys Lys Gln Leu Lys Asp Cys Gln Gln Leu
980 985 990
Ala Met Leu Tyr Asn Asn Arg Glu Arg Ile Phe Ser Leu Pro Ile Thr
995 1000 1005
Asn Tyr Asp Lys Leu Ser Arg Met Val Lys Glu Phe Gln Pro Tyr
1010 1015 1020
Leu Asp Leu Trp Thr Thr Ala Ser Asp Trp Leu Arg Trp Ser Glu
1025 1030 1035
Ser Trp Met Asn Asp Pro Leu Ser Ala Ile Asp Ala Glu Gln Leu
1040 1045 1050
Glu Lys Asn Val Val Glu Ala Phe Lys Thr Met His Lys Cys Val
1055 1060 1065
Lys Gln Phe Lys Asp Met Pro Ala Cys Gln Glu Val Ala Leu Asp
1070 1075 1080
Ile Arg Ala Arg Ile Glu Glu Phe Lys Pro Tyr Ile Pro Leu Ile
1085 1090 1095
Gln Gly Leu Arg Asn Pro Gly Met Arg Ile Arg His Trp Glu Thr
1100 1105 1110
Leu Ser Asn Gln Ile Asn Ile Asn Val Arg Pro Lys Ala Asn Leu
1115 1120 1125
Thr Phe Ala Arg Cys Leu Glu Met Asn Leu Gln Asp His Ile Glu
1130 1135 1140
Ser Ile Ser Lys Val Ala Glu Val Ala Gly Lys Glu Tyr Ala Ile
1145 1150 1155
Glu Gln Ala Leu Asp Lys Met Glu Lys Glu Trp Ser Thr Ile Leu
1160 1165 1170
Phe Asn Val Leu Pro Tyr Lys Ala Thr Asp Thr Tyr Ile Leu Lys
1175 1180 1185
Ser Pro Asp Glu Ala Ser Gln Leu Leu Asp Asp His Ile Val Met
1190 1195 1200
Thr Gln Asn Met Ser Phe Ser Pro Tyr Lys Lys Pro Phe Glu Gln
1205 1210 1215
Arg Ile Asn Ser Trp Glu Asn Lys Leu Lys Leu Thr Gln Glu Val
1220 1225 1230
Leu Glu Glu Trp Leu Asn Cys Gln Arg Ser Trp Leu Tyr Leu Glu
1235 1240 1245
Pro Ile Phe Ser Ser Glu Asp Ile Asn Gln Gln Leu Pro Val Glu
1250 1255 1260
Ser Lys Arg Tyr Gln Thr Met Glu Arg Ile Trp Lys Lys Ile Met
1265 1270 1275
Lys Asn Ala Tyr Glu Asn Arg Glu Val Ile Asn Val Cys Ser Asp
1280 1285 1290
Leu Arg Met Leu Asp Ser Leu Arg Asp Cys Asn Lys Ile Leu Asp
1295 1300 1305
Leu Val Gln Lys Gly Leu Ser Glu Tyr Leu Glu Thr Lys Arg Ser
1310 1315 1320
Ala Phe Pro Arg Phe Tyr Phe Leu Ser Asp Asp Glu Leu Leu Glu
1325 1330 1335
Ile Leu Ser Gln Thr Lys Asp Pro Thr Ala Val Gln Pro His Leu
1340 1345 1350
Arg Lys Cys Phe Glu Asn Ile Ala Arg Leu Leu Phe Gln Glu Asp
1355 1360 1365
Leu Glu Ile Thr His Met Tyr Ser Ala Glu Gly Glu Glu Val Gln
1370 1375 1380
Leu Cys Phe Ser Ile Tyr Pro Ser Ser Asn Val Glu Asp Trp Leu
1385 1390 1395
Arg Glu Val Glu Arg Ser Met Lys Ala Ser Val His Asp Ile Ile
1400 1405 1410
Glu Lys Ala Ile Arg Ala Tyr Pro Thr Met Pro Arg Thr Gln Trp
1415 1420 1425
Val Leu Asn Trp Pro Gly Gln Val Thr Ile Ala Gly Cys Gln Thr
1430 1435 1440
Tyr Trp Thr Met Glu Val Ala Glu Ala Leu Glu Ala Gly Asn Leu
1445 1450 1455
Arg Ser Gln Leu Phe Pro Gln Leu Cys Gln Gln Leu Ser Asp Leu
1460 1465 1470
Val Ala Leu Val Arg Gly Lys Leu Ser Arg Met Gln Arg Ala Val
1475 1480 1485
Leu Ser Ala Leu Ile Val Ile Glu Val His Ala Lys Asp Val Val
1490 1495 1500
Ser Lys Leu Ile Gln Glu Asn Val Val Ser Val Asn Asp Phe Gln
1505 1510 1515
Trp Ile Ser Gln Leu Arg Tyr Tyr Trp Thr Asn Asn Asp Leu Tyr
1520 1525 1530
Ile Arg Ala Val Asn Ala Glu Phe Ile Tyr Gly Tyr Glu Tyr Leu
1535 1540 1545
Gly Asn Ser Gly Arg Leu Val Ile Thr Pro Leu Thr Asp Arg Cys
1550 1555 1560
Tyr Leu Thr Leu Thr Gly Ala Leu His Leu Lys Phe Gly Gly Ala
1565 1570 1575
Pro Ala Gly Pro Ala Gly Thr Gly Lys Thr Glu Thr Thr Lys Asp
1580 1585 1590
Leu Gly Lys Ala Leu Ala Ile Gln Thr Val Val Phe Asn Cys Ser
1595 1600 1605
Asp Gln Leu Asp Phe Met Ala Met Gly Lys Phe Phe Lys Gly Leu
1610 1615 1620
Ala Ser Ala Gly Ala Trp Ala Cys Phe Asp Glu Phe Asn Arg Ile
1625 1630 1635
Asp Ile Glu Val Leu Ser Val Val Ala Gln Gln Ile Thr Thr Ile
1640 1645 1650
Gln Lys Ala Gln Gln Gln Arg Val Glu Arg Phe Met Phe Glu Gly
1655 1660 1665
Val Glu Ile Pro Leu Val Pro Ser Cys Ala Val Phe Ile Thr Met
1670 1675 1680
Asn Pro Gly Tyr Ala Gly Arg Thr Glu Leu Pro Asp Asn Leu Lys
1685 1690 1695
Ala Leu Phe Arg Pro Val Ala Met Met Val Pro Asp Tyr Ala Met
1700 1705 1710
Ile Thr Glu Ile Ser Leu Tyr Ser Phe Gly Phe Asn Glu Ala Ser
1715 1720 1725
Val Leu Ala Lys Lys Ile Thr Thr Thr Phe Lys Leu Ser Ser Glu
1730 1735 1740
Gln Leu Ser Ser Gln Asp His Tyr Asp Phe Gly Met Arg Ala Val
1745 1750 1755
Lys Thr Val Ile Ser Ala Ala Gly Asn Leu Lys Arg Glu Asn Pro
1760 1765 1770
Ser Met Asn Glu Glu Leu Ile Cys Leu Arg Ala Ile Arg Asp Val
1775 1780 1785
Asn Val Pro Lys Phe Leu Gln Glu Asp Leu Lys Leu Phe Ser Gly
1790 1795 1800
Ile Val Ser Asp Leu Phe Pro Thr Ile Lys Glu Glu Asp Thr Asp
1805 1810 1815
Tyr Gly Ile Leu Asp Glu Ala Ile Arg Glu Ala Cys Arg Asn Ser
1820 1825 1830
Asn Leu Lys Asp Val Glu Gly Phe Leu Thr Lys Cys Ile Gln Leu
1835 1840 1845
Tyr Glu Thr Thr Val Val Arg His Gly Leu Met Leu Val Gly Pro
1850 1855 1860
Thr Gly Ser Gly Lys Ser Thr Cys Tyr Arg Val Leu Ala Ala Ala
1865 1870 1875
Met Thr Ser Leu Lys Gly Gln Pro Ser Ile Ser Gly Gly Met Tyr
1880 1885 1890
Glu Ala Val Asn Tyr Tyr Val Leu Asn Pro Lys Ser Ile Thr Met
1895 1900 1905
Gly Gln Leu Tyr Gly Glu Phe Asp Leu Leu Thr His Glu Trp Thr
1910 1915 1920
Asp Gly Ile Phe Ser Ser Phe Ile Arg Ala Gly Ala Ile Thr Ser
1925 1930 1935
Asp Thr Asn Lys Lys Trp Tyr Met Phe Asp Gly Pro Val Asp Ala
1940 1945 1950
Ile Trp Ile Glu Asn Met Asn Thr Val Leu Asp Asp Asn Lys Lys
1955 1960 1965
Leu Cys Leu Ser Ser Gly Glu Ile Ile Lys Leu Thr Glu Ala Met
1970 1975 1980
Thr Met Met Phe Glu Val Gln Asp Leu Ala Val Ala Ser Pro Ala
1985 1990 1995
Thr Val Ser Arg Cys Gly Met Val Tyr Leu Glu Pro Ser Ile Leu
2000 2005 2010
Gly Leu Met Pro Phe Ile Glu Cys Trp Leu Arg Lys Leu Pro Pro
2015 2020 2025
Leu Leu Lys Pro Tyr Glu Glu His Phe Lys Ala Leu Phe Val Ser
2030 2035 2040
Phe Leu Glu Glu Ser Ile Ser Phe Val Arg Ser Ser Val Lys Glu
2045 2050 2055
Val Ile Ala Ser Thr Asn Cys Asn Leu Thr Met Ser Leu Leu Lys
2060 2065 2070
Leu Leu Asp Cys Phe Phe Lys Pro Phe Leu Pro Arg Glu Gly Leu
2075 2080 2085
Lys Lys Ile Pro Ser Glu Lys Leu Ser Arg Ile Val Glu Leu Ile
2090 2095 2100
Glu Pro Trp Phe Ile Phe Ser Leu Ile Trp Ser Val Gly Ala Thr
2105 2110 2115
Gly Asp Ser Ser Gly Arg Thr Ser Phe Ser His Trp Leu Arg Leu
2120 2125 2130
Lys Met Glu Asn Glu Gln Leu Thr Leu Leu Phe Pro Glu Glu Gly
2135 2140 2145
Leu Val Phe Asp Tyr Arg Leu Glu Asp Ala Gly Ile Ser Gly Thr
2150 2155 2160
Asn Asp Ser Glu Asp Glu Glu Glu Glu Tyr Lys Gln Val Ala Trp
2165 2170 2175
Val Lys Trp Met Asp Ser Ser Ala Pro Phe Thr Met Val Pro Asp
2180 2185 2190
Thr Asn Tyr Cys Asn Ile Ile Val Pro Thr Met Asp Thr Val Gln
2195 2200 2205
Met Ser His Leu Leu Asp Met Leu Leu Thr Asn Lys Lys Pro Val
2210 2215 2220
Leu Cys Ile Gly Pro Thr Gly Thr Gly Lys Thr Leu Thr Ile Ser
2225 2230 2235
Asp Lys Leu Leu Lys Asn Leu Ala Leu Asp Tyr Ile Ser His Phe
2240 2245 2250
Leu Thr Phe Ser Ala Arg Thr Ser Ala Asn Gln Thr Gln Asp Phe
2255 2260 2265
Ile Asp Ser Lys Leu Asp Lys Arg Arg Lys Gly Val Phe Gly Pro
2270 2275 2280
Pro Leu Gly Arg Asn Phe Ile Phe Phe Ile Asp Asp Leu Asn Met
2285 2290 2295
Pro Ala Leu Glu Thr Tyr Gly Ala Gln Pro Pro Ile Glu Leu Leu
2300 2305 2310
Arg Gln Trp Met Asp His Gly Gly Trp Tyr Asp Arg Lys Ile Ile
2315 2320 2325
Gly Ala Phe Lys Asn Leu Val Asp Ile Asn Phe Val Cys Ala Met
2330 2335 2340
Gly Pro Pro Gly Gly Gly Arg Asn Thr Val Thr Pro Arg Leu Met
2345 2350 2355
Arg His Phe Asn Tyr Leu Ser Phe Ala Glu Met Asp Glu Val Ser
2360 2365 2370
Lys Lys Arg Ile Phe Ser Thr Ile Leu Gly Asn Trp Leu Asp Gly
2375 2380 2385
Leu Leu Gly Glu Lys Ser Tyr Arg Glu Arg Val Pro Gly Ala Pro
2390 2395 2400
His Ile Ala His Phe Thr Glu Pro Leu Val Glu Ala Thr Ile Met
2405 2410 2415
Val Tyr Ala Thr Ile Thr Ser Gln Leu Leu Pro Thr Pro Ala Lys
2420 2425 2430
Ser His Tyr Thr Phe Asn Leu Arg Asp Leu Ser Lys Val Phe Gln
2435 2440 2445
Gly Met Leu Met Ala Asp Pro Ala Lys Val Glu Asp Gln Val Gln
2450 2455 2460
Leu Leu Arg Leu Trp Tyr His Glu Asn Cys Arg Val Phe Arg Asp
2465 2470 2475
Arg Leu Val Asn Glu Glu Asp Arg Ser Trp Phe Asp Gln Leu Leu
2480 2485 2490
Lys Arg Cys Met Glu Gln Trp Glu Val Thr Phe Asn Lys Val Cys
2495 2500 2505
Pro Phe Gln Pro Ile Leu Tyr Gly Asp Phe Met Ser Pro Gly Ser
2510 2515 2520
Asp Val Lys Ser Tyr Glu Leu Ile Thr Ser Glu Ser Lys Met Met
2525 2530 2535
Gln Val Ile Glu Glu Tyr Ile Glu Asp Tyr Asn Gln Ile Asn Thr
2540 2545 2550
Ala Lys Leu Lys Leu Val Leu Phe Met Asp Ala Met Ser His Ile
2555 2560 2565
Cys Arg Ile Ser Arg Thr Leu Arg Gln Ala Leu Gly Asn Ala Leu
2570 2575 2580
Leu Leu Gly Val Gly Gly Ser Gly Arg Ser Ser Leu Thr Arg Leu
2585 2590 2595
Ala Ser His Met Ala Glu Tyr Glu Cys Phe Gln Ile Glu Leu Ser
2600 2605 2610
Lys Asn Tyr Gly Met Ser Glu Trp Arg Asp Asp Val Lys Lys Val
2615 2620 2625
Leu Leu Lys Ala Gly Leu Gln Asn Leu Pro Ile Thr Phe Leu Phe
2630 2635 2640
Ser Asp Thr Gln Ile Lys Asn Glu Ser Phe Leu Glu Asp Ile Asn
2645 2650 2655
Asn Val Leu Asn Ser Gly Asp Ile Pro Asn Leu Tyr Thr Ala Asp
2660 2665 2670
Glu Gln Asp Gln Ile Val Ser Thr Met Arg Pro Tyr Ile Gln Glu
2675 2680 2685
Gln Gly Leu Gln Pro Thr Lys Ala Asn Leu Met Ala Ala Tyr Thr
2690 2695 2700
Gly Arg Val Arg Ser Asn Ile His Met Val Leu Cys Met Ser Pro
2705 2710 2715
Ile Gly Glu Val Phe Arg Ala Arg Leu Arg Gln Phe Pro Ser Leu
2720 2725 2730
Val Asn Cys Cys Thr Ile Asp Trp Phe Asn Glu Trp Pro Ala Glu
2735 2740 2745
Ala Leu Lys Ser Val Ala Thr Val Phe Leu Asn Glu Ile Pro Glu
2750 2755 2760
Leu Glu Ser Ser Gln Glu Glu Ile Gln Gly Leu Ile Gln Val Cys
2765 2770 2775
Val Tyr Ile His Gln Ser Val Ser Lys Lys Cys Ile Glu Tyr Leu
2780 2785 2790
Ala Glu Leu Thr Arg His Asn Tyr Val Thr Pro Lys Ser Tyr Leu
2795 2800 2805
Glu Leu Leu His Ile Phe Ser Ile Leu Ile Gly Gln Lys Lys Leu
2810 2815 2820
Glu Leu Lys Thr Ala Lys Asn Arg Met Lys Ser Gly Leu Asp Lys
2825 2830 2835
Leu Leu Arg Thr Ser Glu Asp Val Ala Lys Met Gln Glu Asp Leu
2840 2845 2850
Glu Ser Met His Pro Leu Leu Glu Glu Ala Ala Lys Asp Thr Met
2855 2860 2865
Leu Thr Met Glu Gln Ile Lys Val Asp Thr Ala Ile Ala Glu Glu
2870 2875 2880
Thr Arg Asn Ser Val Gln Thr Glu Glu Ile Lys Ala Asn Glu Lys
2885 2890 2895
Ala Lys Lys Ala Gln Ala Ile Ala Asp Asp Ala Gln Lys Asp Leu
2900 2905 2910
Asp Glu Ala Leu Pro Ala Leu Asp Ala Ala Leu Ala Ser Leu Arg
2915 2920 2925
Asn Leu Asn Lys Asn Asp Val Thr Glu Val Arg Ala Met Gln Arg
2930 2935 2940
Pro Pro Pro Gly Val Lys Leu Val Ile Glu Ala Val Cys Ile Met
2945 2950 2955
Lys Gly Ile Lys Pro Lys Lys Val Pro Gly Glu Lys Pro Gly Thr
2960 2965 2970
Lys Val Asp Asp Tyr Trp Glu Pro Gly Lys Gly Leu Leu Gln Asp
2975 2980 2985
Pro Gly His Phe Leu Glu Ser Leu Phe Lys Phe Asp Lys Asp Asn
2990 2995 3000
Ile Gly Asp Val Val Ile Lys Ala Ile Gln Pro Tyr Ile Asp Asn
3005 3010 3015
Glu Glu Phe Gln Pro Ala Thr Ile Ala Lys Val Ser Lys Ala Cys
3020 3025 3030
Thr Ser Ile Cys Gln Trp Val Arg Ala Met His Lys Tyr His Phe
3035 3040 3045
Val Ala Lys Ala Val Glu Pro Lys Arg Gln Ala Leu Leu Glu Ala
3050 3055 3060
Gln Asp Asp Leu Gly Val Thr Gln Arg Ile Leu Asp Glu Ala Lys
3065 3070 3075
Gln Arg Leu Arg Glu Val Glu Asp Gly Ile Ala Thr Met Gln Ala
3080 3085 3090
Lys Tyr Arg Glu Cys Ile Thr Lys Lys Glu Glu Leu Glu Leu Lys
3095 3100 3105
Cys Glu Gln Cys Glu Gln Arg Leu Gly Arg Ala Gly Lys Leu Ile
3110 3115 3120
Asn Gly Leu Ser Asp Glu Lys Val Arg Trp Gln Glu Thr Val Glu
3125 3130 3135
Asn Leu Gln Tyr Met Leu Asn Asn Ile Ser Gly Asp Val Leu Val
3140 3145 3150
Ala Ala Gly Phe Val Ala Tyr Leu Gly Pro Phe Thr Gly Gln Tyr
3155 3160 3165
Arg Thr Val Leu Tyr Asp Ser Trp Val Lys Gln Leu Arg Ser His
3170 3175 3180
Asn Val Pro His Thr Ser Glu Pro Thr Leu Ile Gly Thr Leu Gly
3185 3190 3195
Asn Pro Val Lys Ile Arg Ser Trp Gln Ile Ala Gly Leu Pro Asn
3200 3205 3210
Asp Thr Leu Ser Val Glu Asn Gly Val Ile Asn Gln Phe Ser Gln
3215 3220 3225
Arg Trp Thr His Phe Ile Asp Pro Gln Ser Gln Ala Asn Lys Trp
3230 3235 3240
Ile Lys Asn Met Glu Lys Asp Asn Gly Leu Asp Val Phe Lys Leu
3245 3250 3255
Ser Asp Arg Asp Phe Leu Arg Ser Met Glu Asn Ala Ile Arg Phe
3260 3265 3270
Gly Lys Pro Cys Leu Leu Glu Asn Val Gly Glu Glu Leu Asp Pro
3275 3280 3285
Ala Leu Glu Pro Val Leu Leu Lys Gln Thr Tyr Lys Gln Gln Gly
3290 3295 3300
Asn Thr Val Leu Lys Leu Gly Asp Thr Val Ile Pro Tyr His Glu
3305 3310 3315
Asp Phe Arg Met Tyr Ile Thr Thr Lys Leu Pro Asn Pro His Tyr
3320 3325 3330
Thr Pro Glu Ile Ser Thr Lys Leu Thr Leu Ile Asn Phe Thr Leu
3335 3340 3345
Ser Pro Ser Gly Leu Glu Asp Gln Leu Leu Gly Gln Val Val Ala
3350 3355 3360
Glu Glu Arg Pro Asp Leu Glu Glu Ala Lys Asn Gln Leu Ile Ile
3365 3370 3375
Ser Asn Ala Lys Met Arg Gln Glu Leu Lys Asp Ile Glu Asp Gln
3380 3385 3390
Ile Leu Tyr Arg Leu Ser Ser Ser Glu Gly Asn Pro Val Asp Asp
3395 3400 3405
Met Glu Leu Ile Lys Val Leu Glu Ala Ser Lys Met Lys Ala Ala
3410 3415 3420
Glu Ile Gln Ala Lys Val Arg Ile Ala Glu Gln Thr Glu Lys Asp
3425 3430 3435
Ile Asp Leu Thr Arg Met Glu Tyr Ile Pro Val Ala Ile Arg Thr
3440 3445 3450
Gln Ile Leu Phe Phe Cys Val Ser Asp Leu Ala Asn Val Asp Pro
3455 3460 3465
Met Tyr Gln Tyr Ser Leu Glu Trp Phe Leu Asn Ile Phe Leu Ser
3470 3475 3480
Gly Ile Ala Asn Ser Glu Arg Ala Asp Asn Leu Lys Lys Arg Ile
3485 3490 3495
Ser Asn Ile Asn Arg Tyr Leu Thr Tyr Ser Leu Tyr Ser Asn Val
3500 3505 3510
Cys Arg Ser Leu Phe Glu Lys His Lys Leu Met Phe Ala Phe Leu
3515 3520 3525
Leu Cys Val Arg Ile Met Met Asn Glu Gly Lys Ile Asn Gln Ser
3530 3535 3540
Glu Trp Arg Tyr Leu Leu Ser Gly Gly Ser Ile Ser Ile Met Thr
3545 3550 3555
Glu Asn Pro Ala Pro Asp Trp Leu Ser Asp Arg Ala Trp Arg Asp
3560 3565 3570
Ile Leu Ala Leu Ser Asn Leu Pro Thr Phe Ser Ser Phe Ser Ser
3575 3580 3585
Asp Phe Val Lys His Leu Ser Glu Phe Arg Val Ile Phe Asp Ser
3590 3595 3600
Leu Glu Pro His Arg Glu Pro Leu Pro Gly Ile Trp Asp Gln Tyr
3605 3610 3615
Leu Asp Gln Phe Gln Lys Leu Leu Val Leu Arg Cys Leu Arg Gly
3620 3625 3630
Asp Lys Val Thr Asn Ala Met Gln Asp Phe Val Ala Thr Asn Leu
3635 3640 3645
Glu Pro Arg Phe Ile Glu Pro Gln Thr Ala Asn Leu Ser Val Val
3650 3655 3660
Phe Lys Asp Ser Asn Ser Thr Thr Pro Leu Ile Phe Val Leu Ser
3665 3670 3675
Pro Gly Thr Asp Pro Ala Ala Asp Leu Tyr Lys Phe Ala Glu Glu
3680 3685 3690
Met Lys Phe Ser Lys Lys Leu Ser Ala Ile Ser Leu Gly Gln Gly
3695 3700 3705
Gln Gly Pro Arg Ala Glu Ala Met Met Arg Ser Ser Ile Glu Arg
3710 3715 3720
Gly Lys Trp Val Phe Phe Gln Asn Cys His Leu Ala Pro Ser Trp
3725 3730 3735
Met Pro Ala Leu Glu Arg Leu Ile Glu His Ile Asn Pro Asp Lys
3740 3745 3750
Val His Arg Asp Phe Arg Leu Trp Leu Thr Ser Leu Pro Ser Asn
3755 3760 3765
Lys Phe Pro Val Ser Ile Leu Gln Asn Gly Ser Lys Met Thr Ile
3770 3775 3780
Glu Pro Pro Arg Gly Val Arg Ala Asn Leu Leu Lys Ser Tyr Ser
3785 3790 3795
Ser Leu Gly Glu Asp Phe Leu Asn Ser Cys His Lys Val Met Glu
3800 3805 3810
Phe Lys Ser Leu Leu Leu Ser Leu Cys Leu Phe His Gly Asn Ala
3815 3820 3825
Leu Glu Arg Arg Lys Phe Gly Pro Leu Gly Phe Asn Ile Pro Tyr
3830 3835 3840
Glu Phe Thr Asp Gly Asp Leu Arg Ile Cys Ile Ser Gln Leu Lys
3845 3850 3855
Met Phe Leu Asp Glu Tyr Asp Asp Ile Pro Tyr Lys Val Leu Lys
3860 3865 3870
Tyr Thr Ala Gly Glu Ile Asn Tyr Gly Gly Arg Val Thr Asp Asp
3875 3880 3885
Trp Asp Arg Arg Cys Ile Met Asn Ile Leu Glu Asp Phe Tyr Asn
3890 3895 3900
Pro Asp Val Leu Ser Arg Ala Gln Leu Gln Arg Leu Gly His Leu
3905 3910 3915
Pro Pro Asp Pro Ala Tyr Leu Arg Pro Pro Arg Leu Pro Leu Leu
3920 3925 3930
His Gln Glu Pro Pro Thr Gln
3935 3940
<210> 34
<211> 2092
<212> PRT
<213> Homo Sapiens
<400> 34
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu Trp Met Lys Gly Ile Pro Glu Arg Leu Val Gly
865 870 875 880
Leu Glu Glu Arg Ile Val Lys Val Met Asp Asp Tyr Gln Val Met Asp
885 890 895
Glu Phe Leu Tyr Asn Leu Ser Ser Asp Asp Phe Asn Asp Lys Trp Ile
900 905 910
Ala Ser Asn Trp Pro Ser Lys Ile Leu Gly Gln Ile Glu Leu Val Gln
915 920 925
Gln Gln His Val Glu Asp Glu Glu Lys Phe Arg Lys Ile Gln Ile Met
930 935 940
Asp Gln Asn Asn Phe Gln Glu Lys Leu Glu Gly Leu Gln Leu Val Val
945 950 955 960
Ala Gly Phe Ser Ile His Val Glu Ile Ser Arg Ala His Glu Ile Ala
965 970 975
Asn Glu Val Arg Arg Val Lys Lys Gln Leu Lys Asp Cys Gln Gln Leu
980 985 990
Ala Met Leu Tyr Asn Asn Arg Glu Arg Ile Phe Ser Leu Pro Ile Thr
995 1000 1005
Asn Tyr Asp Lys Leu Ser Arg Met Val Lys Glu Phe Gln Pro Tyr
1010 1015 1020
Leu Asp Leu Trp Thr Thr Ala Ser Asp Trp Leu Arg Trp Ser Glu
1025 1030 1035
Ser Trp Met Asn Asp Pro Leu Ser Ala Ile Asp Ala Glu Gln Leu
1040 1045 1050
Glu Lys Asn Val Val Glu Ala Phe Lys Thr Met His Lys Cys Val
1055 1060 1065
Lys Gln Phe Lys Asp Met Pro Ala Cys Gln Glu Val Ala Leu Asp
1070 1075 1080
Ile Arg Ala Arg Ile Glu Glu Phe Lys Pro Tyr Ile Pro Leu Ile
1085 1090 1095
Gln Gly Leu Arg Asn Pro Gly Met Arg Ile Arg His Trp Glu Thr
1100 1105 1110
Leu Ser Asn Gln Ile Asn Ile Asn Val Arg Pro Lys Ala Asn Leu
1115 1120 1125
Thr Phe Ala Arg Cys Leu Glu Met Asn Leu Gln Asp His Ile Glu
1130 1135 1140
Ser Ile Ser Lys Val Ala Glu Val Ala Gly Lys Glu Tyr Ala Ile
1145 1150 1155
Glu Gln Ala Leu Asp Lys Met Glu Lys Glu Trp Ser Thr Ile Leu
1160 1165 1170
Phe Asn Val Leu Pro Tyr Lys Ala Thr Asp Thr Tyr Ile Leu Lys
1175 1180 1185
Ser Pro Asp Glu Ala Ser Gln Leu Leu Asp Asp His Ile Val Met
1190 1195 1200
Thr Gln Asn Met Ser Phe Ser Pro Tyr Lys Lys Pro Phe Glu Gln
1205 1210 1215
Arg Ile Asn Ser Trp Glu Asn Lys Leu Lys Leu Thr Gln Glu Val
1220 1225 1230
Leu Glu Glu Trp Leu Asn Cys Gln Arg Ser Trp Leu Tyr Leu Glu
1235 1240 1245
Pro Ile Phe Ser Ser Glu Asp Ile Asn Gln Gln Leu Pro Val Glu
1250 1255 1260
Ser Lys Arg Tyr Gln Thr Met Glu Arg Ile Trp Lys Lys Ile Met
1265 1270 1275
Lys Asn Ala Tyr Glu Asn Arg Glu Val Ile Asn Val Cys Ser Asp
1280 1285 1290
Leu Arg Met Leu Asp Ser Leu Arg Asp Cys Asn Lys Ile Leu Asp
1295 1300 1305
Leu Val Gln Lys Gly Leu Ser Glu Tyr Leu Glu Thr Lys Arg Ser
1310 1315 1320
Ala Phe Pro Arg Phe Tyr Phe Leu Ser Asp Asp Glu Leu Leu Glu
1325 1330 1335
Ile Leu Ser Gln Thr Lys Asp Pro Thr Ala Val Gln Pro His Leu
1340 1345 1350
Arg Lys Cys Phe Glu Asn Ile Ala Arg Leu Leu Phe Gln Glu Asp
1355 1360 1365
Leu Glu Ile Thr His Met Tyr Ser Ala Glu Gly Glu Glu Val Gln
1370 1375 1380
Leu Cys Phe Ser Ile Tyr Pro Ser Ser Asn Val Glu Asp Trp Leu
1385 1390 1395
Arg Glu Val Glu Arg Ser Met Lys Ala Ser Val His Asp Ile Ile
1400 1405 1410
Glu Lys Ala Ile Arg Ala Tyr Pro Thr Met Pro Arg Thr Gln Trp
1415 1420 1425
Val Leu Asn Trp Pro Gly Gln Val Thr Ile Ala Gly Cys Gln Thr
1430 1435 1440
Tyr Trp Thr Met Glu Val Ala Glu Ala Leu Glu Ala Gly Asn Leu
1445 1450 1455
Arg Ser Gln Leu Phe Pro Gln Leu Cys Gln Gln Leu Ser Asp Leu
1460 1465 1470
Val Ala Leu Val Arg Gly Lys Leu Ser Arg Met Gln Arg Ala Val
1475 1480 1485
Leu Ser Ala Leu Ile Val Ile Glu Val His Ala Lys Asp Val Val
1490 1495 1500
Ser Lys Leu Ile Gln Glu Asn Val Val Ser Val Asn Asp Phe Gln
1505 1510 1515
Trp Ile Ser Gln Leu Arg Tyr Tyr Trp Thr Asn Asn Asp Leu Tyr
1520 1525 1530
Ile Arg Ala Val Asn Ala Glu Phe Ile Tyr Gly Tyr Glu Tyr Leu
1535 1540 1545
Gly Asn Ser Gly Arg Leu Val Ile Thr Pro Leu Thr Asp Arg Cys
1550 1555 1560
Tyr Leu Thr Leu Thr Gly Ala Leu His Leu Lys Phe Gly Gly Ala
1565 1570 1575
Pro Ala Gly Pro Ala Gly Thr Gly Lys Thr Glu Thr Thr Lys Asp
1580 1585 1590
Leu Gly Lys Ala Leu Ala Ile Gln Thr Val Val Phe Asn Cys Ser
1595 1600 1605
Asp Gln Leu Asp Phe Met Ala Met Gly Lys Phe Phe Lys Gly Leu
1610 1615 1620
Ala Ser Ala Gly Ala Trp Ala Cys Phe Asp Glu Phe Asn Arg Ile
1625 1630 1635
Asp Ile Glu Val Leu Ser Val Val Ala Gln Gln Ile Thr Thr Ile
1640 1645 1650
Gln Lys Ala Gln Gln Gln Arg Val Glu Arg Phe Met Phe Glu Gly
1655 1660 1665
Val Glu Ile Pro Leu Val Pro Ser Cys Ala Val Phe Ile Thr Met
1670 1675 1680
Asn Pro Gly Tyr Ala Gly Arg Thr Glu Leu Pro Asp Asn Leu Lys
1685 1690 1695
Ala Leu Phe Arg Pro Val Ala Met Met Val Pro Asp Tyr Ala Met
1700 1705 1710
Ile Thr Glu Ile Ser Leu Tyr Ser Phe Gly Phe Asn Glu Ala Ser
1715 1720 1725
Val Leu Ala Lys Lys Ile Thr Thr Thr Phe Lys Leu Ser Ser Glu
1730 1735 1740
Gln Leu Ser Ser Gln Asp His Tyr Asp Phe Gly Met Arg Ala Val
1745 1750 1755
Lys Thr Val Ile Ser Ala Ala Gly Asn Leu Lys Arg Glu Asn Pro
1760 1765 1770
Ser Met Asn Glu Glu Leu Ile Cys Leu Arg Ala Ile Arg Asp Val
1775 1780 1785
Asn Val Pro Lys Phe Leu Gln Glu Asp Leu Lys Leu Phe Ser Gly
1790 1795 1800
Ile Val Ser Asp Leu Phe Pro Thr Ile Lys Glu Glu Asp Thr Asp
1805 1810 1815
Tyr Gly Ile Leu Asp Glu Ala Ile Arg Glu Ala Cys Arg Asn Ser
1820 1825 1830
Asn Leu Lys Asp Val Glu Gly Phe Leu Thr Lys Cys Ile Gln Leu
1835 1840 1845
Tyr Glu Thr Thr Val Val Arg His Gly Leu Met Leu Val Gly Pro
1850 1855 1860
Thr Gly Ser Gly Lys Ser Thr Cys Tyr Arg Val Leu Ala Ala Ala
1865 1870 1875
Met Thr Ser Leu Lys Gly Gln Pro Ser Ile Ser Gly Gly Met Tyr
1880 1885 1890
Glu Ala Val Asn Tyr Tyr Val Leu Asn Pro Lys Ser Ile Thr Met
1895 1900 1905
Gly Gln Leu Tyr Gly Glu Phe Asp Leu Leu Thr His Glu Trp Thr
1910 1915 1920
Asp Gly Ile Phe Ser Ser Phe Ile Arg Ala Gly Ala Ile Thr Ser
1925 1930 1935
Asp Thr Asn Lys Lys Trp Tyr Met Phe Asp Gly Pro Val Asp Ala
1940 1945 1950
Ile Trp Ile Glu Asn Met Asn Thr Val Leu Asp Asp Asn Lys Lys
1955 1960 1965
Leu Cys Leu Ser Ser Gly Glu Ile Ile Lys Leu Thr Glu Ala Met
1970 1975 1980
Thr Met Met Phe Glu Val Gln Asp Leu Ala Val Ala Ser Pro Ala
1985 1990 1995
Thr Val Ser Arg Cys Gly Met Val Tyr Leu Glu Pro Ser Ile Leu
2000 2005 2010
Gly Leu Met Pro Phe Ile Glu Cys Trp Leu Arg Lys Leu Pro Pro
2015 2020 2025
Leu Leu Lys Pro Tyr Glu Glu His Phe Lys Ala Leu Phe Val Ser
2030 2035 2040
Phe Leu Glu Glu Ser Ile Ser Phe Val Arg Ser Ser Val Lys Glu
2045 2050 2055
Val Ile Ala Ser Thr Asn Cys Asn Leu Thr Met Ser Leu Leu Lys
2060 2065 2070
Leu Leu Asp Cys Phe Phe Lys Pro Phe Leu Pro Arg Gly Pro Gln
2075 2080 2085
Glu Asn Thr Leu
2090
<210> 35
<211> 4264
<212> PRT
<213> Homo Sapiens
<400> 35
Met Glu Gln Pro Asn Ser Lys Gly Tyr Ser Leu Gly Arg Thr Pro Gln
1 5 10 15
Gly Pro Glu Cys Ser Ser Ala Pro Ala Val Gln Val Gly Thr His Arg
20 25 30
Gly Leu Glu Tyr Asn Pro Gly Lys Ile Leu Pro Gly Ser Asp Tyr Gly
35 40 45
Leu Gly Asn Pro Pro Ala Leu Asp Pro Lys Leu Pro His Leu Pro Leu
50 55 60
Pro Pro Ala Pro Pro Thr Leu Ser Asp Leu Gly Gln Pro Arg Lys Ser
65 70 75 80
Pro Leu Thr Gly Thr Asp Lys Lys Tyr Pro Leu Met Lys Gln Arg Gly
85 90 95
Phe Tyr Ser Asp Ile Leu Ser Pro Gly Thr Leu Asp Gln Leu Gly Glu
100 105 110
Val Cys Arg Gly Pro Arg Met Ser Gln Asn Leu Leu Arg Gln Ala Asp
115 120 125
Leu Asp Lys Phe Thr Pro Arg Val Gly Ser Phe Glu Val Pro Glu Asp
130 135 140
Phe Gln Glu Arg Met Glu Gln Gln Cys Ile Gly Ser Thr Thr Arg Leu
145 150 155 160
Leu Ala Gln Thr Asp Phe Pro Leu Gln Ala Tyr Glu Pro Lys Met Gln
165 170 175
Val Pro Phe Gln Val Leu Pro Gly Gln His Pro Arg Lys Ile Glu Ile
180 185 190
Glu Arg Arg Lys Gln Gln Tyr Leu Ser Leu Asp Ile Glu Gln Leu Leu
195 200 205
Phe Ser Gln Gly Ile Asp Ser Asn Lys Leu Met Pro Arg His Leu Asp
210 215 220
His Gln His Pro Gln Thr Ile Glu Gln Gly His Asp Pro Ile Phe Pro
225 230 235 240
Ile Tyr Leu Pro Leu Lys Val Phe Asp Asn Glu Asp Phe Asp Cys Arg
245 250 255
Thr Pro Arg Glu Trp Ile Asn Met Gly Leu Glu Pro Gly Ser Leu Asp
260 265 270
Arg Lys Pro Val Pro Gly Lys Ala Leu Leu Pro Thr Asp Asp Phe Leu
275 280 285
Gly His Glu Asp Pro Lys Ser Gln Lys Leu Lys Tyr Lys Trp Cys Glu
290 295 300
Val Gly Val Leu Asp Tyr Asp Glu Glu Lys Lys Leu Tyr Leu Val His
305 310 315 320
Lys Thr Asp Glu Lys Gly Leu Val Arg Asp Glu Met Gly Arg Pro Ile
325 330 335
Leu Asn Ala Gly Val Thr Thr Glu Gly Arg Pro Pro Leu Gln Val Cys
340 345 350
Gln Tyr Trp Val Pro Arg Ile Gln Leu Leu Phe Cys Ala Glu Asp Pro
355 360 365
Cys Met Phe Ala Gln Arg Val Val Gln Ala Asn Ala Leu Arg Lys Asn
370 375 380
Thr Glu Ala Leu Leu Leu Tyr Asn Leu Tyr Val Asp Cys Met Pro Ser
385 390 395 400
Asp Gly Gln His Val Ile Ser Glu Gln Ser Leu Ser Lys Ile Lys Gln
405 410 415
Trp Ala Leu Ser Thr Pro Arg Met Arg Lys Gly Pro Ser Val Leu Glu
420 425 430
His Leu Ser Ser Leu Ala Arg Glu Val Ser Leu Asp Tyr Glu Arg Ser
435 440 445
Met Asn Lys Ile Asn Phe Asp His Val Val Ser Ser Lys Pro Glu Thr
450 455 460
Phe Ser Tyr Val Thr Leu Pro Lys Lys Glu Glu Glu Gln Val Pro Glu
465 470 475 480
Arg Gly Leu Val Ser Val Pro Lys Tyr His Phe Trp Glu Gln Lys Glu
485 490 495
Asp Phe Thr Phe Val Ser Leu Leu Thr Arg Pro Glu Val Ile Thr Ala
500 505 510
Leu Ser Lys Val Arg Ala Glu Cys Asn Lys Val Thr Ala Met Ser Leu
515 520 525
Phe His Ser Ser Leu Ser Lys Tyr Ser His Leu Glu Glu Phe Glu Gln
530 535 540
Ile Gln Ser Gln Thr Phe Ser Gln Val Gln Met Phe Leu Lys Asp Ser
545 550 555 560
Trp Ile Ser Ser Leu Lys Val Ala Met Arg Ser Ser Leu Arg Asp Met
565 570 575
Ser Lys Gly Trp Tyr Asn Leu Tyr Glu Thr Asn Trp Glu Val Tyr Leu
580 585 590
Met Ser Lys Leu Arg Lys Leu Met Glu Leu Val Lys Tyr Met Leu Gln
595 600 605
Asp Thr Leu Arg Phe Leu Val Gln Asp Ser Leu Ala Ser Phe Ser Gln
610 615 620
Phe Ile Ser Asp Thr Cys Cys Ser Val Leu Asn Cys Thr Asp Asp Met
625 630 635 640
Val Trp Gly Asp Asp Leu Ile Asn Ser Pro Tyr Arg Pro Arg Lys Asn
645 650 655
Pro Leu Phe Ile Met Asp Leu Val Leu Asp Ser Ser Gly Val His Tyr
660 665 670
Ser Thr Pro Leu Glu Gln Phe Glu Ala Ser Leu Leu Asn Leu Phe Asp
675 680 685
Lys Gly Ile Leu Ala Thr His Ala Val Pro Gln Leu Glu Lys Leu Val
690 695 700
Met Glu Asp Ile Phe Ile Ser Gly Asp Pro Leu Leu Glu Ser Val Gly
705 710 715 720
Leu His Glu Pro Leu Val Glu Glu Leu Arg Ala Thr Ile Ala Ser Ala
725 730 735
Val Ser Lys Ala Met Ile Pro Leu Gln Ala Tyr Ala Lys Glu Tyr Arg
740 745 750
Lys Tyr Leu Glu Leu Asn Asn Asn Asp Ile Ala Ser Phe Leu Lys Thr
755 760 765
Tyr Gln Thr Gln Gly Leu Leu Ala Gln Glu Val Arg Glu Val Val Leu
770 775 780
Thr His Leu Arg Glu Lys Glu Ile Leu Asp Ser Ser Leu Pro Ser Ser
785 790 795 800
Ile Ile Ile Gly Pro Phe Tyr Ile Asn Thr Asp Asn Val Lys Gln Ser
805 810 815
Leu Ser Lys Lys Arg Lys Ala Leu Ala Thr Ser Val Leu Asp Ile Leu
820 825 830
Ala Lys Asn Leu His Lys Glu Val Asp Ser Ile Cys Glu Glu Phe Arg
835 840 845
Ser Ile Ser Arg Lys Ile Tyr Glu Lys Pro Asn Ser Ile Glu Glu Leu
850 855 860
Ala Glu Leu Arg Glu Trp Met Lys Gly Ile Pro Glu Arg Leu Val Gly
865 870 875 880
Leu Glu Glu Arg Ile Val Lys Val Met Asp Asp Tyr Gln Val Met Asp
885 890 895
Glu Phe Leu Tyr Asn Leu Ser Ser Asp Asp Phe Asn Asp Lys Trp Ile
900 905 910
Ala Ser Asn Trp Pro Ser Lys Ile Leu Gly Gln Ile Glu Leu Val Gln
915 920 925
Gln Gln His Val Glu Asp Glu Glu Lys Phe Arg Lys Ile Gln Ile Met
930 935 940
Asp Gln Asn Asn Phe Gln Glu Lys Leu Glu Gly Leu Gln Leu Val Val
945 950 955 960
Ala Gly Phe Ser Ile His Val Glu Ile Ser Arg Ala His Glu Ile Ala
965 970 975
Asn Glu Val Arg Arg Val Lys Lys Gln Leu Lys Asp Cys Gln Gln Leu
980 985 990
Ala Met Leu Tyr Asn Asn Arg Glu Arg Ile Phe Ser Leu Pro Ile Thr
995 1000 1005
Asn Tyr Asp Lys Leu Ser Arg Met Val Lys Glu Phe Gln Pro Tyr
1010 1015 1020
Leu Asp Leu Trp Thr Thr Ala Ser Asp Trp Leu Arg Trp Ser Glu
1025 1030 1035
Ser Trp Met Asn Asp Pro Leu Ser Ala Ile Asp Ala Glu Gln Leu
1040 1045 1050
Glu Lys Asn Val Val Glu Ala Phe Lys Thr Met His Lys Cys Val
1055 1060 1065
Lys Gln Phe Lys Asp Met Pro Ala Cys Gln Glu Val Ala Leu Asp
1070 1075 1080
Ile Arg Ala Arg Ile Glu Glu Phe Lys Pro Tyr Ile Pro Leu Ile
1085 1090 1095
Gln Gly Leu Arg Asn Pro Gly Met Arg Ile Arg His Trp Glu Thr
1100 1105 1110
Leu Ser Asn Gln Ile Asn Ile Asn Val Arg Pro Lys Ala Asn Leu
1115 1120 1125
Thr Phe Ala Arg Cys Leu Glu Met Asn Leu Gln Asp His Ile Glu
1130 1135 1140
Ser Ile Ser Lys Val Ala Glu Val Ala Gly Lys Glu Tyr Ala Ile
1145 1150 1155
Glu Gln Ala Leu Asp Lys Met Glu Lys Glu Trp Ser Thr Ile Leu
1160 1165 1170
Phe Asn Val Leu Pro Tyr Lys Ala Thr Asp Thr Tyr Ile Leu Lys
1175 1180 1185
Ser Pro Asp Glu Ala Ser Gln Leu Leu Asp Asp His Ile Val Met
1190 1195 1200
Thr Gln Asn Met Ser Phe Ser Pro Tyr Lys Lys Pro Phe Glu Gln
1205 1210 1215
Arg Ile Asn Ser Trp Glu Asn Lys Leu Lys Leu Thr Gln Glu Val
1220 1225 1230
Leu Glu Glu Trp Leu Asn Cys Gln Arg Ser Trp Leu Tyr Leu Glu
1235 1240 1245
Pro Ile Phe Ser Ser Glu Asp Ile Asn Gln Gln Leu Pro Val Glu
1250 1255 1260
Ser Lys Arg Tyr Gln Thr Met Glu Arg Ile Trp Lys Lys Ile Met
1265 1270 1275
Lys Asn Ala Tyr Glu Asn Arg Glu Val Ile Asn Val Cys Ser Asp
1280 1285 1290
Leu Arg Met Leu Asp Ser Leu Arg Asp Cys Asn Lys Ile Leu Asp
1295 1300 1305
Leu Val Gln Lys Gly Leu Ser Glu Tyr Leu Glu Thr Lys Arg Ser
1310 1315 1320
Ala Phe Pro Arg Phe Tyr Phe Leu Ser Asp Asp Glu Leu Leu Glu
1325 1330 1335
Ile Leu Ser Gln Thr Lys Asp Pro Thr Ala Val Gln Pro His Leu
1340 1345 1350
Arg Lys Cys Phe Glu Asn Ile Ala Arg Leu Leu Phe Gln Glu Asp
1355 1360 1365
Leu Glu Ile Thr His Met Tyr Ser Ala Glu Gly Glu Glu Val Gln
1370 1375 1380
Leu Cys Phe Ser Ile Tyr Pro Ser Ser Asn Val Glu Asp Trp Leu
1385 1390 1395
Arg Glu Val Glu Arg Ser Met Lys Ala Ser Val His Asp Ile Ile
1400 1405 1410
Glu Lys Ala Ile Arg Ala Tyr Pro Thr Met Pro Arg Thr Gln Trp
1415 1420 1425
Val Leu Asn Trp Pro Gly Gln Val Thr Ile Ala Gly Cys Gln Thr
1430 1435 1440
Tyr Trp Thr Met Glu Val Ala Glu Ala Leu Glu Ala Gly Asn Leu
1445 1450 1455
Arg Ser Gln Leu Phe Pro Gln Leu Cys Gln Gln Leu Ser Asp Leu
1460 1465 1470
Val Ala Leu Val Arg Gly Lys Leu Ser Arg Met Gln Arg Ala Val
1475 1480 1485
Leu Ser Ala Leu Ile Val Ile Glu Val His Ala Lys Asp Val Val
1490 1495 1500
Ser Lys Leu Ile Gln Glu Asn Val Val Ser Val Asn Asp Phe Gln
1505 1510 1515
Trp Ile Ser Gln Leu Arg Tyr Tyr Trp Thr Asn Asn Asp Leu Tyr
1520 1525 1530
Ile Arg Ala Val Asn Ala Glu Phe Ile Tyr Gly Tyr Glu Tyr Leu
1535 1540 1545
Gly Asn Ser Gly Arg Leu Val Ile Thr Pro Leu Thr Asp Arg Cys
1550 1555 1560
Tyr Leu Thr Leu Thr Gly Ala Leu His Leu Lys Phe Gly Gly Ala
1565 1570 1575
Pro Ala Gly Pro Ala Gly Thr Gly Lys Thr Glu Thr Thr Lys Asp
1580 1585 1590
Leu Gly Lys Ala Leu Ala Ile Gln Thr Val Val Phe Asn Cys Ser
1595 1600 1605
Asp Gln Leu Asp Phe Met Ala Met Gly Lys Phe Phe Lys Gly Leu
1610 1615 1620
Ala Ser Ala Gly Ala Trp Ala Cys Phe Asp Glu Phe Asn Arg Ile
1625 1630 1635
Asp Ile Glu Val Leu Ser Val Val Ala Gln Gln Ile Thr Thr Ile
1640 1645 1650
Gln Lys Ala Gln Gln Gln Arg Val Glu Arg Phe Met Phe Glu Gly
1655 1660 1665
Val Glu Ile Pro Leu Val Pro Ser Cys Ala Val Phe Ile Thr Met
1670 1675 1680
Asn Pro Gly Tyr Ala Gly Arg Thr Glu Leu Pro Asp Asn Leu Lys
1685 1690 1695
Ala Leu Phe Arg Pro Val Ala Met Met Val Pro Asp Tyr Ala Met
1700 1705 1710
Ile Thr Glu Ile Ser Leu Tyr Ser Phe Gly Phe Asn Glu Ala Ser
1715 1720 1725
Val Leu Ala Lys Lys Ile Thr Thr Thr Phe Lys Leu Ser Ser Glu
1730 1735 1740
Gln Leu Ser Ser Gln Asp His Tyr Asp Phe Gly Met Arg Ala Val
1745 1750 1755
Lys Thr Val Ile Ser Ala Ala Gly Asn Leu Lys Arg Glu Asn Pro
1760 1765 1770
Ser Met Asn Glu Glu Leu Ile Cys Leu Arg Ala Ile Arg Asp Val
1775 1780 1785
Asn Val Pro Lys Phe Leu Gln Glu Asp Leu Lys Leu Phe Ser Gly
1790 1795 1800
Ile Val Ser Asp Leu Phe Pro Thr Ile Lys Glu Glu Asp Thr Asp
1805 1810 1815
Tyr Gly Ile Leu Asp Glu Ala Ile Arg Glu Ala Cys Arg Asn Ser
1820 1825 1830
Asn Leu Lys Asp Val Glu Gly Phe Leu Thr Lys Cys Ile Gln Leu
1835 1840 1845
Tyr Glu Thr Thr Val Val Arg His Gly Leu Met Leu Val Gly Pro
1850 1855 1860
Thr Gly Ser Gly Lys Ser Thr Cys Tyr Arg Val Leu Ala Ala Ala
1865 1870 1875
Met Thr Ser Leu Lys Gly Gln Pro Ser Ile Ser Gly Gly Met Tyr
1880 1885 1890
Glu Ala Val Asn Tyr Tyr Val Leu Asn Pro Lys Ser Ile Thr Met
1895 1900 1905
Gly Gln Leu Tyr Gly Glu Phe Asp Leu Leu Thr His Glu Trp Thr
1910 1915 1920
Asp Gly Ile Phe Ser Ser Phe Ile Arg Ala Gly Ala Ile Thr Ser
1925 1930 1935
Asp Thr Asn Lys Lys Trp Tyr Met Phe Asp Gly Pro Val Asp Ala
1940 1945 1950
Ile Trp Ile Glu Asn Met Asn Thr Val Leu Asp Asp Asn Lys Lys
1955 1960 1965
Leu Cys Leu Ser Ser Gly Glu Ile Ile Lys Leu Thr Glu Ala Met
1970 1975 1980
Thr Met Met Phe Glu Val Gln Asp Leu Ala Val Ala Ser Pro Ala
1985 1990 1995
Thr Val Ser Arg Cys Gly Met Val Tyr Leu Glu Pro Ser Ile Leu
2000 2005 2010
Gly Leu Met Pro Phe Ile Glu Cys Trp Leu Arg Lys Leu Pro Pro
2015 2020 2025
Leu Leu Lys Pro Tyr Glu Glu His Phe Lys Ala Leu Phe Val Ser
2030 2035 2040
Phe Leu Glu Glu Ser Ile Ser Phe Val Arg Ser Ser Val Lys Glu
2045 2050 2055
Val Ile Ala Ser Thr Asn Cys Asn Leu Thr Met Ser Leu Leu Lys
2060 2065 2070
Leu Leu Asp Cys Phe Phe Lys Pro Phe Leu Pro Arg Glu Gly Leu
2075 2080 2085
Lys Lys Ile Pro Ser Glu Lys Leu Ser Arg Ile Val Glu Leu Ile
2090 2095 2100
Glu Pro Trp Phe Ile Phe Ser Leu Ile Trp Ser Val Gly Ala Thr
2105 2110 2115
Gly Asp Ser Ser Gly Arg Thr Ser Phe Ser His Trp Leu Arg Leu
2120 2125 2130
Lys Met Glu Asn Glu Gln Leu Thr Leu Leu Phe Pro Glu Glu Gly
2135 2140 2145
Leu Val Phe Asp Tyr Arg Leu Glu Asp Ala Gly Ile Ser Gly Thr
2150 2155 2160
Asn Asp Ser Glu Asp Glu Glu Glu Glu Tyr Lys Gln Val Ala Trp
2165 2170 2175
Val Lys Trp Met Asp Ser Ser Ala Pro Phe Thr Met Val Pro Asp
2180 2185 2190
Thr Asn Tyr Cys Asn Ile Ile Val Pro Thr Met Asp Thr Val Gln
2195 2200 2205
Met Ser His Leu Leu Asp Met Leu Leu Thr Asn Lys Lys Pro Val
2210 2215 2220
Leu Cys Ile Gly Pro Thr Gly Thr Gly Lys Thr Leu Thr Ile Ser
2225 2230 2235
Asp Lys Leu Leu Lys Asn Leu Ala Leu Asp Tyr Ile Ser His Phe
2240 2245 2250
Leu Thr Phe Ser Ala Arg Thr Ser Ala Asn Gln Thr Gln Asp Phe
2255 2260 2265
Ile Asp Ser Lys Leu Asp Lys Arg Arg Lys Gly Val Phe Gly Pro
2270 2275 2280
Pro Leu Gly Arg Asn Phe Ile Phe Phe Ile Asp Asp Leu Asn Met
2285 2290 2295
Pro Ala Leu Glu Thr Tyr Gly Ala Gln Pro Pro Ile Glu Leu Leu
2300 2305 2310
Arg Gln Trp Met Asp His Gly Gly Trp Tyr Asp Arg Lys Ile Ile
2315 2320 2325
Gly Ala Phe Lys Asn Leu Val Asp Ile Asn Phe Val Cys Ala Met
2330 2335 2340
Gly Pro Pro Gly Gly Gly Arg Asn Thr Val Thr Pro Arg Leu Met
2345 2350 2355
Arg His Phe Asn Tyr Leu Ser Phe Ala Glu Met Asp Glu Val Ser
2360 2365 2370
Lys Lys Arg Ile Phe Ser Thr Ile Leu Gly Asn Trp Leu Asp Gly
2375 2380 2385
Leu Leu Gly Glu Lys Ser Tyr Arg Glu Arg Val Pro Gly Ala Pro
2390 2395 2400
His Ile Ala His Phe Thr Glu Pro Leu Val Glu Ala Thr Ile Met
2405 2410 2415
Val Tyr Ala Thr Ile Thr Ser Gln Leu Leu Pro Thr Pro Ala Lys
2420 2425 2430
Ser His Tyr Thr Phe Asn Leu Arg Asp Leu Ser Lys Val Phe Gln
2435 2440 2445
Gly Met Leu Met Ala Asp Pro Ala Lys Val Glu Asp Gln Val Gln
2450 2455 2460
Leu Leu Arg Leu Trp Tyr His Glu Asn Cys Arg Val Phe Arg Asp
2465 2470 2475
Arg Leu Val Asn Glu Glu Asp Arg Ser Trp Phe Asp Gln Leu Leu
2480 2485 2490
Lys Arg Cys Met Glu Gln Trp Glu Val Thr Phe Asn Lys Val Cys
2495 2500 2505
Pro Phe Gln Pro Ile Leu Tyr Gly Asp Phe Met Ser Pro Gly Ser
2510 2515 2520
Asp Val Lys Ser Tyr Glu Leu Ile Thr Ser Glu Ser Lys Met Met
2525 2530 2535
Gln Val Ile Glu Glu Tyr Ile Glu Asp Tyr Asn Gln Ile Asn Thr
2540 2545 2550
Ala Lys Leu Lys Leu Val Leu Phe Met Asp Ala Met Ser His Ile
2555 2560 2565
Cys Arg Ile Ser Arg Thr Leu Arg Gln Ala Leu Gly Asn Ala Leu
2570 2575 2580
Leu Leu Gly Val Gly Gly Ser Gly Arg Ser Ser Leu Thr Arg Leu
2585 2590 2595
Ala Ser His Met Ala Glu Tyr Glu Cys Phe Gln Ile Glu Leu Ser
2600 2605 2610
Lys Asn Tyr Gly Met Ser Glu Trp Arg Asp Asp Val Lys Lys Val
2615 2620 2625
Leu Leu Lys Ala Gly Leu Gln Asn Leu Pro Ile Thr Phe Leu Phe
2630 2635 2640
Ser Asp Thr Gln Ile Lys Asn Glu Ser Phe Leu Glu Asp Ile Asn
2645 2650 2655
Asn Val Leu Asn Ser Gly Asp Ile Pro Asn Leu Tyr Thr Ala Asp
2660 2665 2670
Glu Gln Asp Gln Ile Val Ser Thr Met Arg Pro Tyr Ile Gln Glu
2675 2680 2685
Gln Gly Leu Gln Pro Thr Lys Ala Asn Leu Met Ala Ala Tyr Thr
2690 2695 2700
Gly Arg Val Arg Ser Asn Ile His Met Val Leu Cys Met Ser Pro
2705 2710 2715
Ile Gly Glu Val Phe Arg Ala Arg Leu Arg Gln Phe Pro Ser Leu
2720 2725 2730
Val Asn Cys Cys Thr Ile Asp Trp Phe Asn Glu Trp Pro Ala Glu
2735 2740 2745
Ala Leu Lys Ser Val Ala Thr Val Phe Leu Asn Glu Ile Pro Glu
2750 2755 2760
Leu Glu Ser Ser Gln Glu Glu Ile Gln Gly Leu Ile Gln Val Cys
2765 2770 2775
Val Tyr Ile His Gln Ser Val Ser Lys Lys Cys Ile Glu Tyr Leu
2780 2785 2790
Ala Glu Leu Thr Arg His Asn Tyr Val Thr Pro Lys Ser Tyr Leu
2795 2800 2805
Glu Leu Leu His Ile Phe Ser Ile Leu Ile Gly Gln Lys Lys Leu
2810 2815 2820
Glu Leu Lys Thr Ala Lys Asn Arg Met Lys Ser Gly Leu Asp Lys
2825 2830 2835
Leu Leu Arg Thr Ser Glu Asp Val Ala Lys Met Gln Glu Asp Leu
2840 2845 2850
Glu Ser Met His Pro Leu Leu Glu Glu Ala Ala Lys Asp Thr Met
2855 2860 2865
Leu Thr Met Glu Gln Ile Lys Val Asp Thr Ala Ile Ala Glu Glu
2870 2875 2880
Thr Arg Asn Ser Val Gln Thr Glu Glu Ile Lys Ala Asn Glu Lys
2885 2890 2895
Ala Lys Lys Ala Gln Ala Ile Ala Asp Asp Ala Gln Lys Asp Leu
2900 2905 2910
Asp Glu Ala Leu Pro Ala Leu Asp Ala Ala Leu Ala Ser Leu Arg
2915 2920 2925
Asn Leu Asn Lys Asn Asp Val Thr Glu Val Arg Ala Met Gln Arg
2930 2935 2940
Pro Pro Pro Gly Val Lys Leu Val Ile Glu Ala Val Cys Ile Met
2945 2950 2955
Lys Gly Ile Lys Pro Lys Lys Val Pro Gly Glu Lys Pro Gly Thr
2960 2965 2970
Lys Val Asp Asp Tyr Trp Glu Pro Gly Lys Gly Leu Leu Gln Asp
2975 2980 2985
Pro Gly His Phe Leu Glu Ser Leu Phe Lys Phe Asp Lys Asp Asn
2990 2995 3000
Ile Gly Asp Val Val Ile Lys Ala Ile Gln Pro Tyr Ile Asp Asn
3005 3010 3015
Glu Glu Phe Gln Pro Ala Thr Ile Ala Lys Val Ser Lys Ala Cys
3020 3025 3030
Thr Ser Ile Cys Gln Trp Val Arg Ala Met His Lys Tyr His Phe
3035 3040 3045
Val Ala Lys Ala Val Glu Pro Lys Arg Gln Ala Leu Leu Glu Ala
3050 3055 3060
Gln Asp Asp Leu Gly Val Thr Gln Arg Ile Leu Asp Glu Ala Lys
3065 3070 3075
Gln Arg Leu Arg Glu Val Glu Asp Gly Ile Ala Thr Met Gln Ala
3080 3085 3090
Lys Tyr Arg Glu Cys Ile Thr Lys Lys Glu Glu Leu Glu Leu Lys
3095 3100 3105
Cys Glu Gln Cys Glu Gln Arg Leu Gly Arg Ala Gly Lys Leu Ile
3110 3115 3120
Asn Gly Leu Ser Asp Glu Lys Val Arg Trp Gln Glu Thr Val Glu
3125 3130 3135
Asn Leu Gln Tyr Met Leu Asn Asn Ile Ser Gly Asp Val Leu Val
3140 3145 3150
Ala Ala Gly Phe Val Ala Tyr Leu Gly Pro Phe Thr Gly Gln Tyr
3155 3160 3165
Arg Thr Val Leu Tyr Asp Ser Trp Val Lys Gln Leu Arg Ser His
3170 3175 3180
Asn Val Pro His Thr Ser Glu Pro Thr Leu Ile Gly Thr Leu Gly
3185 3190 3195
Asn Pro Val Lys Ile Arg Ser Trp Gln Ile Ala Gly Leu Pro Asn
3200 3205 3210
Asp Thr Leu Ser Val Glu Asn Gly Val Ile Asn Gln Phe Ser Gln
3215 3220 3225
Arg Trp Thr His Phe Ile Asp Pro Gln Ser Gln Ala Asn Lys Trp
3230 3235 3240
Ile Lys Asn Met Glu Lys Asp Asn Gly Leu Asp Val Phe Lys Leu
3245 3250 3255
Ser Asp Arg Asp Phe Leu Arg Ser Met Glu Asn Ala Ile Arg Phe
3260 3265 3270
Gly Lys Pro Cys Leu Leu Glu Asn Val Gly Glu Glu Leu Asp Pro
3275 3280 3285
Ala Leu Glu Pro Val Leu Leu Lys Gln Thr Tyr Lys Gln Gln Gly
3290 3295 3300
Asn Thr Val Leu Lys Leu Gly Asp Thr Val Ile Pro Tyr His Glu
3305 3310 3315
Asp Phe Arg Met Tyr Ile Thr Thr Lys Leu Pro Asn Pro His Tyr
3320 3325 3330
Thr Pro Glu Ile Ser Thr Lys Leu Thr Leu Ile Asn Phe Thr Leu
3335 3340 3345
Ser Pro Ser Gly Leu Glu Asp Gln Leu Leu Gly Gln Val Val Ala
3350 3355 3360
Glu Glu Arg Pro Asp Leu Glu Glu Ala Lys Asn Gln Leu Ile Ile
3365 3370 3375
Ser Asn Ala Lys Met Arg Gln Glu Leu Lys Asp Ile Glu Asp Gln
3380 3385 3390
Ile Leu Tyr Arg Leu Ser Ser Ser Glu Gly Asn Pro Val Asp Asp
3395 3400 3405
Met Glu Leu Ile Lys Val Leu Glu Ala Ser Lys Met Lys Ala Ala
3410 3415 3420
Glu Ile Gln Ala Lys Val Arg Ile Ala Glu Gln Thr Glu Lys Asp
3425 3430 3435
Ile Asp Leu Thr Arg Met Glu Tyr Ile Pro Val Ala Ile Arg Thr
3440 3445 3450
Gln Ile Leu Phe Phe Cys Val Ser Asp Leu Ala Asn Val Asp Pro
3455 3460 3465
Met Tyr Gln Tyr Ser Leu Glu Trp Phe Leu Asn Ile Phe Leu Ser
3470 3475 3480
Gly Ile Ala Asn Ser Glu Arg Ala Asp Asn Leu Lys Lys Arg Ile
3485 3490 3495
Ser Asn Ile Asn Arg Tyr Leu Thr Tyr Ser Leu Tyr Ser Asn Val
3500 3505 3510
Cys Arg Ser Leu Phe Glu Lys His Lys Leu Met Phe Ala Phe Leu
3515 3520 3525
Leu Cys Val Arg Ile Met Met Asn Glu Gly Lys Ile Asn Gln Ser
3530 3535 3540
Glu Trp Arg Tyr Leu Leu Ser Gly Gly Ser Ile Ser Ile Met Thr
3545 3550 3555
Glu Asn Pro Ala Pro Asp Trp Leu Ser Asp Arg Ala Trp Arg Asp
3560 3565 3570
Ile Leu Ala Leu Ser Asn Leu Pro Thr Phe Ser Ser Phe Ser Ser
3575 3580 3585
Asp Phe Val Lys His Leu Ser Glu Phe Arg Val Ile Phe Asp Ser
3590 3595 3600
Leu Glu Pro His Arg Glu Pro Leu Pro Gly Ile Trp Asp Gln Tyr
3605 3610 3615
Leu Asp Gln Phe Gln Lys Leu Leu Val Leu Arg Cys Leu Arg Gly
3620 3625 3630
Asp Lys Val Thr Asn Ala Met Gln Asp Phe Val Ala Thr Asn Leu
3635 3640 3645
Glu Pro Arg Phe Ile Glu Pro Gln Thr Ala Asn Leu Ser Val Val
3650 3655 3660
Phe Lys Asp Ser Asn Ser Thr Thr Pro Leu Ile Phe Val Leu Ser
3665 3670 3675
Pro Gly Thr Asp Pro Ala Ala Asp Leu Tyr Lys Phe Ala Glu Glu
3680 3685 3690
Met Lys Phe Ser Lys Lys Leu Ser Ala Ile Ser Leu Gly Gln Gly
3695 3700 3705
Gln Gly Pro Arg Ala Glu Ala Met Met Arg Ser Ser Ile Glu Arg
3710 3715 3720
Gly Lys Trp Val Phe Phe Gln Asn Cys His Leu Ala Pro Ser Trp
3725 3730 3735
Met Pro Ala Leu Glu Arg Leu Ile Glu His Ile Asn Pro Asp Lys
3740 3745 3750
Val His Arg Asp Phe Arg Leu Trp Leu Thr Ser Leu Pro Ser Asn
3755 3760 3765
Lys Phe Pro Val Ser Ile Leu Gln Asn Gly Ser Lys Met Thr Ile
3770 3775 3780
Glu Pro Pro Arg Gly Val Arg Ala Asn Leu Leu Lys Ser Tyr Ser
3785 3790 3795
Ser Leu Gly Glu Asp Phe Leu Asn Ser Cys His Lys Val Met Glu
3800 3805 3810
Phe Lys Ser Leu Leu Leu Ser Leu Cys Leu Phe His Gly Asn Ala
3815 3820 3825
Leu Glu Arg Arg Lys Phe Gly Pro Leu Gly Phe Asn Ile Pro Tyr
3830 3835 3840
Glu Phe Thr Asp Gly Asp Leu Arg Ile Cys Ile Ser Gln Leu Lys
3845 3850 3855
Met Phe Leu Asp Glu Tyr Asp Asp Ile Pro Tyr Lys Val Leu Lys
3860 3865 3870
Tyr Thr Ala Gly Glu Ile Asn Tyr Gly Gly Arg Val Thr Asp Asp
3875 3880 3885
Trp Asp Arg Arg Cys Ile Met Asn Ile Leu Glu Asp Phe Tyr Asn
3890 3895 3900
Pro Asp Val Leu Ser Pro Glu His Ser Tyr Ser Ala Ser Gly Ile
3905 3910 3915
Tyr His Gln Ile Pro Pro Thr Tyr Asp Leu His Gly Tyr Leu Ser
3920 3925 3930
Tyr Ile Lys Ser Leu Pro Leu Asn Asp Met Pro Glu Ile Phe Gly
3935 3940 3945
Leu His Asp Asn Ala Asn Ile Thr Phe Ala Gln Asn Glu Thr Phe
3950 3955 3960
Ala Leu Leu Gly Thr Ile Ile Gln Leu Gln Pro Lys Ser Ser Ser
3965 3970 3975
Ala Gly Ser Gln Gly Arg Glu Glu Ile Val Glu Asp Val Thr Gln
3980 3985 3990
Asn Ile Leu Leu Lys Val Pro Glu Pro Ile Asn Leu Gln Trp Val
3995 4000 4005
Met Ala Lys Tyr Pro Val Leu Tyr Glu Glu Ser Met Asn Thr Val
4010 4015 4020
Leu Val Gln Glu Val Ile Arg Tyr Asn Arg Leu Leu Gln Val Ile
4025 4030 4035
Thr Gln Thr Leu Gln Asp Leu Leu Lys Ala Leu Lys Gly Leu Val
4040 4045 4050
Val Met Ser Ser Gln Leu Glu Leu Met Ala Ala Ser Leu Tyr Asn
4055 4060 4065
Thr Val Pro Glu Leu Trp Ser Ala Lys Ala Tyr Pro Ser Leu Lys
4070 4075 4080
Pro Leu Ser Ser Trp Val Met Asp Leu Leu Gln Arg Leu Asp Phe
4085 4090 4095
Leu Gln Ala Trp Ile Gln Asp Gly Ile Pro Ala Val Phe Trp Ile
4100 4105 4110
Ser Gly Phe Phe Phe Pro Gln Ala Phe Leu Thr Gly Thr Leu Gln
4115 4120 4125
Asn Phe Ala Arg Lys Phe Val Ile Ser Ile Asp Thr Ile Ser Phe
4130 4135 4140
Asp Phe Lys Val Met Phe Glu Ala Pro Ser Glu Leu Thr Gln Arg
4145 4150 4155
Pro Gln Val Gly Cys Tyr Ile His Gly Leu Phe Leu Glu Gly Ala
4160 4165 4170
Arg Trp Asp Pro Glu Ala Phe Gln Leu Ala Glu Ser Gln Pro Lys
4175 4180 4185
Glu Leu Tyr Thr Glu Met Ala Val Ile Trp Leu Leu Pro Thr Pro
4190 4195 4200
Asn Arg Lys Ala Gln Asp Gln Asp Phe Tyr Leu Cys Pro Ile Tyr
4205 4210 4215
Lys Thr Leu Thr Arg Ala Gly Thr Leu Ser Thr Thr Gly His Ser
4220 4225 4230
Thr Asn Tyr Val Ile Ala Val Glu Ile Pro Thr His Gln Pro Gln
4235 4240 4245
Arg His Trp Ile Lys Arg Gly Val Ala Leu Ile Cys Ala Leu Asp
4250 4255 4260
Tyr

Claims (17)

1.通过外显子组测序的方法确定MMAF的致病基因的新突变。
2.MMAF的生物标记物，其特征在于即突变的DNAH1基因或DNAH1蛋白，所述生物标记物是具有选自如下的突变的DNAH1基因或DNAH1蛋白：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)；
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)。
3.MMAF的生物标记物的突变，其特征在于DNAH1基因为SEQ ID NO:1的序列中具有以下突变：
在外显子25中错义突变(c.4115C>T)；
在外显子73中移码突变(c.11726_11727del)；
在外显子43中错义突变(c.6822C>G)；
在外显子62中错义突变(c.9850G>A)；
在外显子39中错义突变(c.6212T>G)；
在外显子76中缺失突变(c.12200_12202del)；
在外显子22中错义突变(c.3836A>G)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A)；
在外显子37中无义突变(c.5864G>A)；
在外显子39中移码突变(c.6253_6254del)；
在外显子15中无义突变(c.2610G>A)；
在外显子76中错义突变(c.12287G>T)；
在外显子76中错义突变(c.12397C>T)；
在外显子45中错义突变(c.7066C>T)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T)。
4.如权利要求3所述MMAF的生物标记物的突变，其特征在于突变的DNAH1蛋白为SEQ IDNO:2的序列中具有以下突变：
在外显子25中错义突变(p.T1372M)；
在外显子73中移码突变(p.P3909Rfs*33)；
在外显子43中错义突变(p.D2274E)；
在外显子62中错义突变(p.E3284K)；
在外显子39中错义突变(p.L2071R)；
在外显子76中缺失突变(p.N4068del)；
在外显子22中错义突变(p.K1279R)；
在外显子19中无义突变(p.W1036X)；
在外显子37中无义突变(p.W1955X)；
在外显子39中移码突变(p.E2086Gfs*8)；
在外显子15中无义突变(p.W870X)；
在外显子76中错义突变(p.R4096L)；
在外显子76中错义突变(p.R4133C)；
在外显子45中错义突变(p.R2356W)；
在外显子67中无义突变(p.E3544X)。
5.突变的DNAH1蛋白，其特征在于为SEQ ID NO:2的序列中，具有外显子19中无义突变(p.W1036X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:29；
为SEQ ID NO:2的序列中具有外显子37中无义突变(p.W1955X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:30；
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子15中无义突变(p.W870X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:31；
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子67中无义突变(p.E3544X)，所述突变的DNAH1蛋白的序列是SEQ ID NO:32；
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子73中移码突变(p.P3909Rfs*33)，所述突变的DNAH1蛋白的序列是SEQ ID NO:33；
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子39中移码突变(p.E2086Gfs*8)，所述突变的DNAH1蛋白的序列是SEQ ID NO:34；
突变的DNAH1蛋白为SEQ ID NO:2的序列中具有外显子76中缺失突变(p.N4068del)，所述突变的DNAH1蛋白的序列是SEQ ID NO:35。
6.一种检测MMAF的方法，其特征在于所述方法包括检测受试者的DNAH1基因或DNAH1蛋白中是否存在突变位点，若有突变位点，则所述受试者被鉴定为患有MMAF或易患MMAF，所述突变位点选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)；
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)。
7.突变的DNAH1蛋白，其特征在于为SEQ ID NO:2的序列中具有外显子；DNAH1蛋白为SEQ ID NO:2的序列表示；DNAH1基因为SEQ ID NO:1的序列表示。
8.一种检测MMAF的方法，其特征在于包括如下至少一组引物扩增的步骤：
SEQ ID NO:3和SEQ ID NO:4；
SEQ ID NO:5和SEQ ID NO:6；
SEQ ID NO:7和SEQ ID NO:8；
SEQ ID NO:9和SEQ ID NO:10；
SEQ ID NO:11和SEQ ID NO:12；
SEQ ID NO:13和SEQ ID NO:14；
SEQ ID NO:15和SEQ ID NO:16；
SEQ ID NO:17和SEQ ID NO:18；
SEQ ID NO:19和SEQ ID NO:20；
SEQ ID NO:21和SEQ ID NO:22；
SEQ ID NO:23和SEQ ID NO:24；
SEQ ID NO:25和SEQ ID NO:26；
SEQ ID NO:27和SEQ ID NO:28。
9.检测MMAF的方法，其特征在于检测突变位点通过选自以下：测序、电泳、核酸杂交、原位杂交、PCR、逆转录酶链反应和变性高效液相色谱。
10.通过PCR检测DNAH1基因或DNAH1蛋白突变中使用的引物对，其特征在于所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)；
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)，
其中所述引物对分别基于选自如下的位置前后设计，使得扩增该位置，编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
11.突变DNAH1基因互补的核酸探针，其特征在于所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)；
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)。
12.探针与突变DNAH1基因的互补区包括选自如下的位置，编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
13.检测突变DNAH1基因或DNAH1蛋白的试剂盒，其特征在于包含一组或多组引物对，其中所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)；
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)；
其中所述引物对分别基于选自如下的位置前后设计，使得其扩增产物涵盖该位置，编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
14.检测突变DNAH1基因或DNAH1蛋白的试剂盒，其特征在于包含选自如下的至少一组引物：
SEQ ID NO:3和SEQ ID NO:4；
SEQ ID NO:5和SEQ ID NO:6；
SEQ ID NO:7和SEQ ID NO:8；
SEQ ID NO:9和SEQ ID NO:10；
SEQ ID NO:11和SEQ ID NO:12；
SEQ ID NO:13和SEQ ID NO:14；
SEQ ID NO:15和SEQ ID NO:16；
SEQ ID NO:17和SEQ ID NO:18；
SEQ ID NO:19和SEQ ID NO:20；
SEQ ID NO:21和SEQ ID NO:22；
SEQ ID NO:23和SEQ ID NO:24；
SEQ ID NO:25和SEQ ID NO:26；
SEQ ID NO:27和SEQ ID NO:28。
15.检测突变DNAH1基因的试剂盒，其特征在于包含一个或多个核酸探针，所述突变是选自如下任一种或其组合：
在外显子25中错义突变(c.4115C>T；p.T1372M)；
在外显子73中移码突变(c.11726_11727del；p.P3909Rfs*33)；
在外显子43中错义突变(c.6822C>G；p.D2274E)；
在外显子62中错义突变(c.9850G>A；p.E3284K)；
在外显子39中错义突变(c.6212T>G；p.L2071R)；
在外显子76中缺失突变(c.12200_12202del；p.N4068del)；
在外显子22中错义突变(c.3836A>G；p.K1279R)；
在外显子47-48剪接中剪接位点突变(c.7377+1G>C)；
在外显子19中无义突变(c.3108G>A；p.W1036X)；
在外显子37中无义突变(c.5864G>A；p.W1955X)；
在外显子39中移码突变(c.6253_6254del；p.E2086Gfs*8)；
在外显子15中无义突变(c.2610G>A；p.W870X)；
在外显子76中错义突变(c.12287G>T；p.R4096L)；
在外显子76中错义突变(c.12397C>T；p.R4133C)；
在外显子45中错义突变(c.7066C>T；p.R2356W)；
在外显子36-37剪接中剪接位点突变(c.5766-2A>G)；
在外显子67中无义突变(c.10630G>T；p.E3544X)。
16.探针与突变DNAH1基因上包含选自如下的位置的区域互补，编号基于DNAH1的cDNA序列，7377+1表示cDNA序列的7377位之后在基因组DNA中是内含子序列，该内含子序列的第一位发生突变，5766-2表示cDNA序列的5766位之前在基因组DNA中是内含子序列，该内含子序列的第2位发生突变：4115、11726_11727、6822、9850、6212、12200_12202、3836、7377+1、3108、5864、6253_6254、2610、12287、12397、7066、5766-2和10630。
17.一种MMAF致病基因新突变的应用。
CN201710494668.XA 2017-06-26 2017-06-26 一种mmaf致病基因新突变及其应用 Pending CN107176993A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710494668.XA CN107176993A (zh) 2017-06-26 2017-06-26 一种mmaf致病基因新突变及其应用

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710494668.XA CN107176993A (zh) 2017-06-26 2017-06-26 一种mmaf致病基因新突变及其应用

Publications (1)

Publication Number Publication Date
CN107176993A true CN107176993A (zh) 2017-09-19

Family

ID=59844378

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710494668.XA Pending CN107176993A (zh) 2017-06-26 2017-06-26 一种mmaf致病基因新突变及其应用

Country Status (1)

Country Link
CN (1) CN107176993A (zh)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107523629A (zh) * 2017-09-22 2017-12-29 厦门市妇幼保健院（厦门市计划生育服务中心） 无头精子症致病基因新突变及其应用
CN107523628A (zh) * 2017-09-22 2017-12-29 厦门市妇幼保健院（厦门市计划生育服务中心） 一种mmaf致病新基因及其应用

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104268515A (zh) * 2014-09-18 2015-01-07 山东大学 一种精子形态异常检测方法
WO2015120075A3 (en) * 2014-02-04 2015-12-23 Genentech, Inc. Mutant smoothened and methods of using the same

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015120075A3 (en) * 2014-02-04 2015-12-23 Genentech, Inc. Mutant smoothened and methods of using the same
CN104268515A (zh) * 2014-09-18 2015-01-07 山东大学 一种精子形态异常检测方法

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
AMIRI-YEKTA A等: "Whole-exome sequencing of familial cases of multiple morphological abnormalities of the sperm flagella (MMAF) reveals new DNAH1 mutations", 《HUMAN REPRODUCTION》 *
WANG X 等: "Homo sapiens dynein axonemal heavy chain 1 (DNAH1), mRNA", 《GENBANK》 *
WANG X.等: "Homozygous DNAH1 frameshift mutation causes multiple morphological anomalies of the sperm flagella in Chinese", 《CLINICAL GENETICS》 *
YANWEI SHA等: "DNAH1 gene mutations and their potential association with dysplasia of the sperm fibrous sheath and infertility in the Han Chinese population", 《FERTILITY AND STERILITY》 *
杨慎敏: "精子鞭毛多发形态异常的形态学研究和致病基因鉴定", 《中国博士学位论文全文数据库 医药卫生科技辑》 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107523629A (zh) * 2017-09-22 2017-12-29 厦门市妇幼保健院（厦门市计划生育服务中心） 无头精子症致病基因新突变及其应用
CN107523628A (zh) * 2017-09-22 2017-12-29 厦门市妇幼保健院（厦门市计划生育服务中心） 一种mmaf致病新基因及其应用
CN107523628B (zh) * 2017-09-22 2020-02-14 厦门市妇幼保健院（厦门市计划生育服务中心） 一种mmaf致病新基因及其应用

Similar Documents

Publication Publication Date Title
Lamnidis et al. Ancient Fennoscandian genomes reveal origin and spread of Siberian ancestry in Europe
Jones et al. Comprehensive mutation analysis of TSC1 and TSC2—and phenotypic correlations in 150 families with tuberous sclerosis
Groves et al. Mutation cluster region, association between germline and somatic mutations and genotype-phenotype correlation in upper gastrointestinal familial adenomatous polyposis
Clevenger et al. Single nucleotide polymorphism identification in polyploids: a review, example, and recommendations
Rickards et al. mtDNA history of the Cayapa Amerinds of Ecuador: detection of additional founding lineages for the Native American populations
Benjafield et al. No association of angiotensin-converting enzyme 2 gene (ACE2) polymorphisms with essential hypertension
Carpten et al. HRPT2, encoding parafibromin, is mutated in hyperparathyroidism–jaw tumor syndrome
Aveyard et al. Somatic mutation of PTEN in bladder carcinoma
Björk et al. Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: cumulative risks and APC gene mutations
Templeton A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping or DNA sequencing. V. Analysis of case/control sampling designs: Alzheimer's disease and the apoprotein E locus.
Góngora-Castillo et al. Genomic approaches for interrogating the biochemistry of medicinal plant species
Margres et al. Selection to increase expression, not sequence diversity, precedes gene family origin and expansion in rattlesnake venom
Watkins et al. Multiple origins of the mtDNA 9‐bp deletion in populations of South India
US20110008773A1 (en) Method for the determination of data for the preparation of the diagnosis of phakomatosis
AU2016275186A1 (en) Methods and compositions for cannabis characterization
Hunt et al. Linkage of body mass index to chromosome 20 in Utah pedigrees
Pons et al. Evolutionary dynamics of satellite DNA family PIM357 in species of the genus Pimelia (Tenebrionidae, Coleoptera)
Uyar et al. Human leukocyte antigen‐A,‐B and‐C alleles and human leukocyte antigen haplotypes in Turkey: relationship to other populations
CN107164520A (zh) 一种严重弱精子症新致病基因及其应用
Scott et al. Familial adenomatous polyposis: more evidence for disease diversity and genetic heterogeneity
Valoroso et al. Transcriptome-wide identification and expression analysis of DIVARICATA-and RADIALIS-like genes of the mediterranean orchid Orchis italica
CN107176993A (zh) 一种mmaf致病基因新突变及其应用
CN107176994A (zh) 一种mmaf新致病基因及其应用
Viginier et al. Very low genetic variability in the Indian queenless ant Diacamma indicum
Vargas-Alarcón et al. Distribution of HLA class II alleles and haplotypes in Mexican Mestizo population: comparison with other populations

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20170919