[go: up one dir, main page]

CN100445300C - GLP-1 fusion protein and its preparation method and medical application - Google Patents

GLP-1 fusion protein and its preparation method and medical application Download PDF

Info

Publication number
CN100445300C
CN100445300C CNB2005100171754A CN200510017175A CN100445300C CN 100445300 C CN100445300 C CN 100445300C CN B2005100171754 A CNB2005100171754 A CN B2005100171754A CN 200510017175 A CN200510017175 A CN 200510017175A CN 100445300 C CN100445300 C CN 100445300C
Authority
CN
China
Prior art keywords
xaa
gly
misc
feature
leu
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.)
Expired - Fee Related
Application number
CNB2005100171754A
Other languages
Chinese (zh)
Other versions
CN1765931A (en
Inventor
魏洋
李玉新
刘霞
鲍永利
单保红
乌垠
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Priority to CNB2005100171754A priority Critical patent/CN100445300C/en
Publication of CN1765931A publication Critical patent/CN1765931A/en
Application granted granted Critical
Publication of CN100445300C publication Critical patent/CN100445300C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Landscapes

  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

本发明提供一种GLP-1融合蛋白及其制备方法,这些融合蛋白可用于胰岛素非依赖型糖尿病及肥胖等的治疗。The invention provides a GLP-1 fusion protein and a preparation method thereof. These fusion proteins can be used for the treatment of insulin-independent diabetes and obesity.

Description

GLP-1融合蛋白及其制备方法和医药用途 GLP-1 fusion protein and its preparation method and medical application

技术领域 technical field

本发明公开一种GLP-1融合蛋白及其制备方法,涉及GLP-1(7-37)与一些多肽的融合蛋白的制备,本发明还提供了这些融合蛋白在胰岛素非依赖型糖尿病及肥胖等疾病治疗中的医药用途,属于生物基因工程技术领域。The invention discloses a GLP-1 fusion protein and a preparation method thereof, and relates to the preparation of a fusion protein of GLP-1 (7-37) and some polypeptides. The invention also provides these fusion proteins in insulin-independent diabetes and obesity, etc. The medical application in disease treatment belongs to the technical field of biogenetic engineering.

背景技术 Background technique

本发明涉及的GLP-1(glucagon-like peptide-1,以下简称:GLP-1)主要是由小肠L-细胞分泌的一种37个氨基酸组成的多肽,其活性形式为GLP-1(7-37)OH和GLP-1(7-36)NH2(Mojsov S,J ClinInvest.1987Feb;79(2):616-9)。GLP-1 (glucagon-like peptide-1, hereinafter referred to as: GLP-1) involved in the present invention is mainly a polypeptide composed of 37 amino acids secreted by small intestinal L-cells, and its active form is GLP-1 (7- 37) OH and GLP-1(7-36)NH2 (Mojsov S, J Clin Invest. 1987 Feb; 79(2):616-9).

GLP-1类似物是当今治疗II型糖尿病的新一类药物。2005年4月,美国食品药物管理局批准了exenatide,一个可以注射的药物,以商品名Byetta出售,作为II型糖尿病患者的辅助治疗药物,Byetta是来自于蜥蜴唾液的GLP-1类似物,被Eli Lilly和Amylin医药公司所开发。GLP-1有明显降低病人在用餐后的血糖,能刺激胰岛素的生产,同时它还能起到一定减肥效应,并且不会引起低血糖症(Drucker DJ,Diabetes.1998 Feb;47(2):159-69.)。近期研究还表明GLP-1对胰腺有再生作用(Drucker DJ,Endocrinology.2003Dec;144(12):5145-8.)。由于天然GLP-1的N-端第2位Ala在体内很快被二肽酰基肽酶IV(DPP-IV)降解,大大限制了其临床应用。为了延长其体内生物半衰期,以使其作为治疗药物更好应用于临床,必须研制具有抗酶降解的长效GLP-1类似物或类同物。GLP-1 analogues are a new class of drugs in the treatment of type II diabetes today. In April 2005, the US Food and Drug Administration approved exenatide, an injectable drug sold under the trade name Byetta, as an adjunctive treatment for patients with type 2 diabetes. Byetta is a GLP-1 analogue derived from lizard saliva and is Developed by Eli Lilly and Amylin Pharmaceuticals. GLP-1 can significantly reduce the blood sugar of patients after meals, can stimulate the production of insulin, and it can also play a certain weight loss effect, and will not cause hypoglycemia (Drucker DJ, Diabetes.1998 Feb; 47 (2): 159-69.). Recent studies have also shown that GLP-1 has a regenerative effect on the pancreas (Drucker DJ, Endocrinology. 2003 Dec; 144(12): 5145-8.). Since the second Ala at the N-terminal of natural GLP-1 is quickly degraded by dipeptidyl peptidase IV (DPP-IV) in vivo, its clinical application is greatly limited. In order to prolong its biological half-life in vivo so that it can be better used as a therapeutic drug in clinic, it is necessary to develop long-acting GLP-1 analogues or analogues that are resistant to enzymatic degradation.

胰高血糖素是由胰腺A-细胞产生的29氨基酸的多肽,它与胰岛素作用相反,能增加血糖,抑制胰岛素的生产。研究表明,在II型糖尿病人中,血液胰高血糖素明显偏高,使用胰高血糖素拮抗物或抗胰高血糖素抗体可明显降低血糖(Shah P,J Clin EndocrinolMetab.2000 Nov;85(11):4053-9;及Johnson DG,Science.1982Feb 26;215(4536):1115-6)。因此,研制胰高血糖素拮抗物作为治疗II类糖尿病的新药具有一定前景(Djuric SW,Curr Opin InvestigDrugs.2002 Nov;3(11):1617-23)。Glucagon is a 29-amino acid polypeptide produced by pancreatic A-cells. It acts opposite to insulin, increasing blood sugar and inhibiting insulin production. Studies have shown that in people with type II diabetes, blood glucagon is significantly higher, and the use of glucagon antagonists or anti-glucagon antibodies can significantly reduce blood sugar (Shah P, J Clin Endocrinol Metab.2000 Nov; 85( 11): 4053-9; and Johnson DG, Science. 1982 Feb 26; 215(4536): 1115-6). Therefore, the development of glucagon antagonists as a new drug for the treatment of type II diabetes has certain prospects (Djuric SW, Curr Opin Investig Drugs. 2002 Nov; 3 (11): 1617-23).

发明内容 Contents of the invention

本发明提供了一种GLP-1融合蛋白,是GLP-1与人胰高血糖素受体或胰高血糖素家族中任何多肽受体及人免疫球蛋白Fc部分、免疫球蛋白Fc部分片段的融合蛋白。GLP-1的C末端可以直接或通过肽接头与免疫球蛋白Fc部分或人胰高血糖素家族受体的N末端融合。The invention provides a GLP-1 fusion protein, which is the combination of GLP-1, human glucagon receptor or any polypeptide receptor in the glucagon family, human immunoglobulin Fc part, and immunoglobulin Fc part fragment fusion protein. The C-terminus of GLP-1 can be fused directly or via a peptide linker to the Fc portion of an immunoglobulin or to the N-terminus of the human glucagon family receptors.

本发明公开了GLP-1融合蛋白的制备方法。The invention discloses a preparation method of GLP-1 fusion protein.

本发明还提供了将GLP-1与胰高血糖素家族受体或免疫球蛋白Fc部分融合在一起的接头,该接头由几个可自由伸展的氨基酸组成,可使被融合在一起的蛋白更好地折叠。The present invention also provides a linker for fusing GLP-1 with glucagon family receptors or the Fc part of immunoglobulin, the linker is composed of several amino acids that can be stretched freely, which can make the fused proteins more Nicely folded.

本发明的GLP-1融合蛋白包含两个多肽,其中,第一个多肽是GLP-1化合物,第二个是胰高血糖素家族受体,胰高血糖素家族受体选自:The GLP-1 fusion protein of the present invention comprises two polypeptides, wherein the first polypeptide is a GLP-1 compound, and the second is a glucagon family receptor, and the glucagon family receptor is selected from:

(1)整个胰高血糖素受体序列;(1) The entire glucagon receptor sequence;

(2)胰高血糖素受体功能区-1,主要由胰高血糖素受体第一膜外圈加上其两端的跨膜区组成;(2) Glucagon receptor functional region-1, which is mainly composed of the first outer ring of the glucagon receptor membrane and the transmembrane regions at both ends;

(3)胰高血糖素家族中任何多肽受体的功能区-1,主要由受体的第一膜外圈加上其两端的跨膜区组成;(3) Functional region-1 of any polypeptide receptor in the glucagon family, which is mainly composed of the first membrane outer ring of the receptor plus the transmembrane regions at both ends;

(4)胰高血糖素家族中任何多肽受体的功能区-2,主要由受体的第2膜外圈加上其两端的跨膜区组成;(4) Functional region-2 of any polypeptide receptor in the glucagon family, mainly composed of the second outer ring of the receptor plus the transmembrane regions at both ends;

(5)胰高血糖素家族中任何多肽受体的功能区-3,主要由受体的第3膜外圈加上其两端的跨膜区组成;(5) Functional region-3 of any polypeptide receptor in the glucagon family, mainly composed of the third outer ring of the receptor plus the transmembrane regions at both ends;

(6)GLP-1、GLP-2或葡萄糖依赖胰岛素营养多肽等属于胰高血糖素家族多肽的受体。(6) GLP-1, GLP-2, or glucose-dependent insulinotropic polypeptides, etc., belong to receptors of glucagon family polypeptides.

其中第一个多肽的C端与第二个多肽的N端融合或通过肽接头连接。Wherein the C-terminus of the first polypeptide is fused to the N-terminus of the second polypeptide or linked by a peptide linker.

肽接头优选自:The peptide linker is preferably selected from:

(1)具有(Gly-Thr-Gly)n的肽,其中n是1,2,3,4,5,6;(1) A peptide having (Gly-Thr-Gly)n, wherein n is 1, 2, 3, 4, 5, 6;

(2)具有(Gly-Ala-Pro)n的肽,其中n是1,2,3,4,5,6;(2) Peptides with (Gly-Ala-Pro)n, wherein n is 1, 2, 3, 4, 5, 6;

(3)具有(Gly-Pro-Gly)n的肽,其中n是1,2,3,4,5,6;(3) Peptides with (Gly-Pro-Gly)n, wherein n is 1, 2, 3, 4, 5, 6;

(4)具有(Gly-Gly-Gly-Gly-Ser)n的肽。其中n是1,2,3,4,5,6。(4) A peptide having (Gly-Gly-Gly-Gly-Ser)n. where n is 1, 2, 3, 4, 5, 6.

本发明的融合蛋白还可以是GLP-1化合物与人免疫球蛋白Fc段的融合,其中,人免疫球蛋白Fc段选自:The fusion protein of the present invention can also be a fusion of a GLP-1 compound and a human immunoglobulin Fc segment, wherein the human immunoglobulin Fc segment is selected from:

(1)人免疫球蛋白的Fc部分;(1) the Fc portion of a human immunoglobulin;

(2)人免疫球蛋白的Fc部分的类似物;(2) analogs of the Fc portion of human immunoglobulins;

(3)人免疫球蛋白的Fc部分的片段。(3) A fragment of the Fc portion of a human immunoglobulin.

上述两个多肽的融合可以为第一个多肽的C端与第二个多肽的N端融合或通过肽接头连接。肽接头优选自:The fusion of the above two polypeptides can be the fusion of the C-terminus of the first polypeptide with the N-terminus of the second polypeptide or connection through a peptide linker. The peptide linker is preferably selected from:

(1)具有(Gly-Thr-Gly)n的肽,其中n是1,2,3,4,5,6;(1) A peptide having (Gly-Thr-Gly)n, wherein n is 1, 2, 3, 4, 5, 6;

(2)具有(Gly-Ala-Pro)n的肽,其中n是1,2,3,4,5,6;(2) Peptides with (Gly-Ala-Pro)n, wherein n is 1, 2, 3, 4, 5, 6;

(3)具有(Gly-Pro-Gly)n的肽,其中n是1,2,3,4,5,6;(3) Peptides with (Gly-Pro-Gly)n, wherein n is 1, 2, 3, 4, 5, 6;

(4)Gly-Gly-Gly-Gly-Ser)n的肽。其中n是1,2,3,4,5,6。(4) Peptides of Gly-Gly-Gly-Gly-Ser)n. where n is 1, 2, 3, 4, 5, 6.

本发明融合蛋白也可以是三个多肽进行融合,其中,第一个多肽为GLP-1化合物,第二个多肽为人免疫球蛋白的Fc段或Fc段的片段,第三个多肽为人胰高血糖素受体或胰高血糖素家族中任何多肽的受体。The fusion protein of the present invention can also be a fusion of three polypeptides, wherein the first polypeptide is a GLP-1 compound, the second polypeptide is the Fc segment of human immunoglobulin or a fragment of the Fc segment, and the third polypeptide is human glucagon receptor for glucagon or any polypeptide in the glucagon family.

其中三个多肽直接相连或通过中间接头连接,中间接头优选自:Wherein the three polypeptides are directly connected or connected through an intermediate linker, and the intermediate linker is preferably selected from:

(1)具有(Gly-Thr-Gly)n的肽,其中n是1,2,3,4,5,6;(1) A peptide having (Gly-Thr-Gly)n, wherein n is 1, 2, 3, 4, 5, 6;

(2)具有(Gly-Ala-Pro)n的肽,其中n是1,2,3,4,5,6;(2) Peptides with (Gly-Ala-Pro)n, wherein n is 1, 2, 3, 4, 5, 6;

(3)具有(Gly-Pro-Gly)n的肽,其中n是1,2,3,4,5,6;(3) Peptides with (Gly-Pro-Gly)n, wherein n is 1, 2, 3, 4, 5, 6;

(4)具有(Gly-Gly-Gly-Gly-Ser)n的肽。其中n是1,2,3,4,5,6。(4) A peptide having (Gly-Gly-Gly-Gly-Ser)n. where n is 1, 2, 3, 4, 5, 6.

作为融合蛋白一部分的GLP-1一般优选具有不超过6个不同于GLP-1(7-37)OH,GLP-1(7-36)OH或Exendin-4中的相应氨基酸的氨基酸。GLP-1化合物甚至更优选具有不超过5个不同于GLP-1(7-37)OH,GLP-1(7-36)OH或Exendin-4中的相应氨基酸的氨基酸。GLP-1化合物最优选具有不超过4,3或2个不同于GLP-1(7-37)OH,GLP-1(7-36)OH或Exendin-4中的相应氨基酸的氨基酸。The GLP-1 that is part of the fusion protein generally preferably has no more than 6 amino acids that differ from the corresponding amino acids in GLP-1(7-37)OH, GLP-1(7-36)OH or Exendin-4. Even more preferably, the GLP-1 compound has no more than 5 amino acids that differ from the corresponding amino acids in GLP-1(7-37)OH, GLP-1(7-36)OH or Exendin-4. GLP-1 compounds most preferably have no more than 4, 3 or 2 amino acids that differ from the corresponding amino acids in GLP-1(7-37)OH, GLP-1(7-36)OH or Exendin-4.

本发明的GLP-1融合蛋白可以通过以下制备方法获得:基因重组技术或固相蛋白质合成技术。The GLP-1 fusion protein of the present invention can be obtained by the following preparation methods: gene recombination technology or solid-phase protein synthesis technology.

重组方法生产本发明融合蛋白的具体技术解决方案如下:The specific technical solution of recombinant method to produce fusion protein of the present invention is as follows:

一、构建编码本发明融合蛋白的重组载体1. Construction of the recombinant vector encoding the fusion protein of the present invention

(一)GLP-1的钓取(1) Fishing of GLP-1

根据公开的GLP-1序列设计PCR引物,以表达人GLP-1的cDNA,如胰腺,小肠,脑组织cDNA为模板,经PCR扩增获得GLP-1cDNA序列。PCR primers are designed according to the published GLP-1 sequence, and cDNA expressing human GLP-1, such as pancreas, small intestine, and brain tissue cDNA is used as a template, and the GLP-1 cDNA sequence is obtained by PCR amplification.

(二)胰高血糖素受体及其家族其它受体的钓取(2) Fishing of glucagon receptor and other receptors of its family

融合蛋白中胰高血糖素受体部分可以人肝组织cDNA为模板,使用相应受体的引物,经PCR扩增获得,然后克隆入TOPO TA载体(Invitrogen),重组的载体经Eco RI酶切及序列分析鉴定。所获得的质粒在此称为TOPO TA-胰高血糖素受体。The glucagon receptor part of the fusion protein can be obtained by PCR amplification using human liver tissue cDNA as a template, using the primers of the corresponding receptor, and then cloned into the TOPO TA vector (Invitrogen), and the recombinant vector is digested with Eco RI and digested. Identification by sequence analysis. The resulting plasmid is referred to herein as TOPO TA-glucagon receptor.

胰高血糖素受体N-端膜外功能区;功能区-1;功能区-2;功能区-3片段,可以上述TOPO TA-胰高血糖素受体为模板,以相应引物,经PCR扩增获得。Glucagon receptor N-terminal extramembrane functional region; functional region-1; functional region-2; functional region-3 fragments, the above-mentioned TOPO TA-glucagon receptor can be used as a template, and corresponding primers can be used for PCR Amplified obtained.

胰高血糖素家族的其它受体可用与胰高血糖素受体相同的方法钓取。Other receptors of the glucagon family can be fished in the same way as the glucagon receptor.

在获取了上述基因片断后,可用连接酶将相应基因连接,亦可用重叠PCR方法将之融合在一起,然后克隆入表达载体。After the above-mentioned gene fragments are obtained, the corresponding genes can be connected with ligase, and can also be fused together by overlapping PCR method, and then cloned into the expression vector.

(三)人IgG1 Fc段的钓取(3) Fishing of human IgG1 Fc segment

以表达IgG的人组织cDNA为模板经PCR扩增钓取编码人IgG1亚型的CH2和CH3功能区的cDNA序列,将之克隆入pV05载体(图6),所获得的质粒命名为pV05-人IgG1 Fc。Using the human tissue cDNA expressing IgG as a template, the cDNA sequences encoding the CH2 and CH3 functional regions of the human IgG1 subtype were amplified by PCR and cloned into the pV05 vector (Figure 6). The obtained plasmid was named pV05-human IgG1 Fc.

(四)重组表达载体的构建(4) Construction of recombinant expression vector

通过框内连接编码GLP-1的DNA与编码免疫球蛋白Fc部分或胰高血糖素及其类似物受体的DNA而构建编码融合蛋白的基因。也可以通过编码接头肽的基因框内连接编码GLP-1基因与编码免疫球蛋白Fc部分或胰高血糖素及其类似物受体的基因。The gene encoding the fusion protein is constructed by in-frame ligation of DNA encoding GLP-1 with DNA encoding the Fc portion of an immunoglobulin or the receptor for glucagon and its analogs. The gene encoding GLP-1 and the gene encoding the Fc part of an immunoglobulin or the receptor for glucagon and its analogues can also be linked in-frame via a gene encoding a linker peptide.

编码野生型GLP-1、胰高血糖素及其类似物受体、Fc多肽和片段的DNA可以在连接之前或在编码整个融合蛋白的cDNA的范围内进行突变。多种诱变技术是本领域公知的。例如,利用链重叠延伸以制备用于改变相应蛋白中的特定氨基酸序列的特定碱基突变的诱变PCR方法。DNA encoding wild-type GLP-1, glucagon and its analog receptors, Fc polypeptides and fragments can be mutated prior to ligation or within the cDNA encoding the entire fusion protein. Various mutagenesis techniques are well known in the art. For example, a mutagenesis PCR method that utilizes chain overlap extension to prepare a specific base mutation for changing a specific amino acid sequence in the corresponding protein.

当用哺乳动物细胞表达融合蛋白时,须有信号肽,以使表达的融合蛋白能被分泌到胞浆,信号肽被自动切除。本发明使用前胰高血糖素的信号肽,亦可使用其它信号肽,如:前副甲状腺激素的信号肽(Wiren,KM etc.The J of Bio.Chem.263(36):19771-19777(1988),或人IgG1Fc的信号肽。When the fusion protein is expressed in mammalian cells, a signal peptide is required so that the expressed fusion protein can be secreted into the cytoplasm, and the signal peptide is automatically excised. The present invention uses the signal peptide of preglucagon, and other signal peptides can also be used, such as: the signal peptide of preparathyroid hormone (Wiren, KM etc. The J of Bio. Chem. 263 (36): 19771-19777 ( 1988), or the signal peptide of human IgG1 Fc.

当用细菌表达融合蛋白时,可采用细菌融合蛋白表达方法,在N端加入蛋白酶切点及HA或6HIS标签用于吸附纯化,表达的融合蛋白经蛋白酶酶切后,得到含有正确切除位点的融合蛋白。还可使用最新的IMPACT细菌表达系统(New England,BioLabs Inc.)。这个IMPACT蛋白融合和纯化系统是利用可诱导的工程蛋白剪切元件的自身裂解活性来进行蛋白纯化和处理。通过pH和温度诱导裂解来纯化蛋白:使用pTWIN载体,这个intein标签是融合在目的蛋白的N-末端。此目的蛋白之后通过pH和温度诱导的裂解而被释放。When the fusion protein is expressed in bacteria, the bacterial fusion protein expression method can be used to add a protease cleavage point and HA or 6HIS tag to the N-terminus for adsorption and purification. fusion protein. The latest IMPACT bacterial expression system (New England, BioLabs Inc.) can also be used. The IMPACT protein fusion and purification system utilizes the self-cleavage activity of inducible engineered protein cleavage elements for protein purification and processing. Purify protein by pH and temperature induced cleavage: using the pTWIN vector, the intein tag is fused to the N-terminus of the protein of interest. The protein of interest is then released by pH and temperature induced cleavage.

一旦产生了编码完整融合蛋白的基因,它可以被克隆到适当的表达载体。Once the gene encoding the complete fusion protein has been generated, it can be cloned into an appropriate expression vector.

二、表达本发明的融合蛋白的一般方法Two, express the general method of fusion protein of the present invention

用此处描述的表达载体转染或转化宿主细胞,用于产生融合蛋白,此宿主细胞可以是真核或原核生物宿主细胞。用重组DNA载体转化或转染细胞的技术是本领域熟知的技术。Host cells transfected or transformed with the expression vectors described herein for the production of fusion proteins may be eukaryotic or prokaryotic host cells. Techniques for transforming or transfecting cells with recombinant DNA vectors are well known in the art.

三、回收并纯化重组产生的蛋白质3. Recovery and purification of recombinantly produced proteins

可通过在N-端或C-端加入的序列标签或融合蛋白的特性用相应的柱层析来纯化表达的融合蛋白。The expressed fusion protein can be purified by corresponding column chromatography through sequence tags added at the N-terminus or C-terminus or the identity of the fusion protein.

四、融合蛋白的活性检测4. Activity detection of fusion protein

(一)融合蛋白的体外结合活性测定(1) Determination of the binding activity of the fusion protein in vitro

125I标记的商品化的GLP-1(7-36)与本发明的融合蛋白竞争结合GLP-1受体,结果显示本发明的融合蛋白与GLP-1受体的结合活性略高于商品化的人GLP-1(7-36)。The commercialized GLP-1(7-36) labeled with 125 I competes with the fusion protein of the present invention for binding to the GLP-1 receptor, and the results show that the binding activity of the fusion protein of the present invention to the GLP-1 receptor is slightly higher than that of the commercial product Humanized GLP-1(7-36).

(二)融合蛋白在体外对cAMP水平的影响(2) Effect of fusion protein on cAMP level in vitro

将含GLP-1受体cDNA的重组载体转染到CHO细胞48小时后按文献所述方法测定cAMP(Wei and Mojsov,1996),结果显示本发明的融合蛋白在体外对cAMP水平的影响与商品化的人GLP-1(7-36)基本相同。After the recombinant vector containing GLP-1 receptor cDNA was transfected into CHO cells for 48 hours, cAMP was measured according to the method described in the literature (Wei and Mojsov, 1996). The results showed that the fusion protein of the present invention had the same impact on cAMP levels in vitro as commercial The normalized human GLP-1(7-36) is essentially the same.

(三)融合蛋白的药代动力学检测(3) Pharmacokinetic detection of fusion protein

给C57BL/6小鼠静脉内注射融合蛋白(50nM),分别于注射后0min,1hr,6hr,12hr,24hr,36hr,48hr,60hr和72hr后于尾静脉抽取血样。4℃离心分离血浆,用ELISA法检测融合蛋白水平。结果显示本发明的融合蛋白的生物半衰期较单纯的GLP-1明显延长。The fusion protein (50nM) was injected intravenously into C57BL/6 mice, and blood samples were drawn from the tail vein at 0min, 1hr, 6hr, 12hr, 24hr, 36hr, 48hr, 60hr and 72hr after injection. Plasma was separated by centrifugation at 4°C, and the level of fusion protein was detected by ELISA. The results show that the biological half-life of the fusion protein of the present invention is significantly longer than that of simple GLP-1.

(四)融合蛋白对小鼠耐糖能力的影响(4) Effect of fusion protein on glucose tolerance of mice

给过夜(16-18h)绝食的小鼠(C57BL/6)皮下注射不同剂量的融合蛋白(4μg/kg,16μg/kg,80μg/kg和1mg/kg)或生理盐水,注射30min和24h后,按1.5mg/g体重腹腔注射葡萄糖,并分别于注射后0,10,20,30,60,90,和120min后从尾尖采取血样。用葡萄糖表通过葡萄糖酶方法检测血中葡萄糖水平。结果显示给予本发明的融合蛋白后小鼠的耐糖能力明显提高,给予0.07nmol/kg本发明的融合蛋白即具有明显的降血糖作用,而且其降糖功能与融合蛋白的浓度呈正相关,当融合蛋白增加到18nmol/kg时,其降血糖功能变得更为明显。Subcutaneous injection of different doses of fusion protein (4μg/kg, 16μg/kg, 80μg/kg and 1mg/kg) or normal saline was given to mice (C57BL/6) fasted overnight (16-18h). After injection for 30min and 24h, Glucose was injected intraperitoneally at 1.5 mg/g body weight, and blood samples were collected from the tail tip at 0, 10, 20, 30, 60, 90, and 120 minutes after injection. Glucose levels in the blood were measured by the glucose enzymatic method with a glucose meter. The results show that the glucose tolerance of mice after the fusion protein of the present invention is significantly improved, and the fusion protein of the present invention at 0.07nmol/kg has an obvious hypoglycemic effect, and its hypoglycemic function is positively correlated with the concentration of the fusion protein. When the protein increased to 18nmol/kg, its hypoglycemic function became more obvious.

综上,体外及体内生物学活性检测结果表明本发明制备的融合蛋白不仅具有GLP-1正常的生物学活性,而且其生物半衰期较单独的GLP-1多肽明显延长。In conclusion, the test results of biological activity in vitro and in vivo show that the fusion protein prepared by the present invention not only has the normal biological activity of GLP-1, but also its biological half-life is significantly longer than that of the independent GLP-1 polypeptide.

融合蛋白药物组合物及用途Fusion protein pharmaceutical composition and use

本发明的融合蛋白可用于治疗胰岛素非依赖型糖尿病、胰岛素依赖型糖尿病、卒中、心肌梗塞、肥胖症、手术后分解代谢改变、功能性消化不良和肠激惹综合征。也包括需要利用GLP-1化合物进行预防性处理的患者,如具有发生胰岛素非依赖型糖尿病危险性的患者:葡萄糖耐受异常或空腹葡萄糖异常的受试者、体重超出相对于患者身高和体格来讲的正常体重25%的受试者、进行了部分胰切除手术的受试者、患有妊娠期糖尿病的受试者及患有急或慢性胰腺炎的受试者。本发明的融合蛋白既保持了GLP-1的生物学活性,同时又延长了GLP-1在体内的生物半衰期,因此本发明的融合蛋白可用于以上疾病的治疗。The fusion protein of the present invention can be used for treating insulin-independent diabetes, insulin-dependent diabetes, stroke, myocardial infarction, obesity, catabolic change after operation, functional dyspepsia and irritable bowel syndrome. Also included are patients requiring prophylactic treatment with GLP-1 compounds, such as patients at risk of developing insulin-independent diabetes mellitus: subjects with impaired glucose tolerance or abnormal fasting glucose, subjects with excess weight relative to the patient's height and build Subjects with 25% of normal body weight, subjects who underwent partial pancreatectomy, subjects with gestational diabetes mellitus, and subjects with acute or chronic pancreatitis. The fusion protein of the present invention not only maintains the biological activity of GLP-1, but also prolongs the biological half-life of GLP-1 in vivo, so the fusion protein of the present invention can be used for the treatment of the above diseases.

本发明还提供了一种药物组合物,它包括有效量的上述融合蛋白或药学上可接受的载体或稀释剂。The present invention also provides a pharmaceutical composition, which includes an effective amount of the above-mentioned fusion protein or a pharmaceutically acceptable carrier or diluent.

本发明组合物中的活性成分剂量可以不同,但是活性成分的量必须能获得适当的剂型。所选择的剂量根据所需治疗效果、给药途径和治疗周期而改变。一般说来,本发明活性成分的有效量为1×10-7-200mg/kg/天,1×10-4-100mg/kg/天,可以单剂量给药或分成多剂量给药。The dosage of the active ingredient in the compositions of the present invention may vary, but the amount of active ingredient must be such that a suitable dosage form will be obtained. The selected dosage will vary depending on the desired therapeutic effect, the route of administration and the duration of treatment. Generally, the effective dose of the active ingredient of the present invention is 1×10 -7 -200 mg/kg/day, 1×10 -4 -100 mg/kg/day, which can be administered in a single dose or divided into multiple doses.

本发明融合蛋白可以经口服、非肠道的(如肌肉、腹膜内、静脉内、皮下注射或植入)、鼻腔的、阴道的、直肠的、舌下的或局部的给药途径进行给药,并可与药学上可接受的载体进行配制以提供适合于每一种给药途径的剂型。The fusion protein of the present invention can be administered through oral, parenteral (such as intramuscular, intraperitoneal, intravenous, subcutaneous injection or implantation), nasal, vaginal, rectal, sublingual or topical routes of administration , and can be formulated with pharmaceutically acceptable carriers to provide dosage forms suitable for each route of administration.

口服的固体剂型包括胶囊、片剂、丸剂、粉剂和颗粒剂。在这些固体剂型中,将活性化合物与至少一种药学上可接受的惰性载体混合,该载体例如蔗糖、乳糖或淀粉。这些剂型可以正常使用也可包括除惰性稀释剂外的其它物质,例如润滑剂,如硬脂酸镁。在胶囊、片剂和丸剂中,这些剂型也可包括缓冲剂。片剂和丸剂可另外用肠衣制备。Solid dosage forms for oral administration include capsules, tablets, pills, powders and granules. In these solid dosage forms, the active compound is admixed with at least one inert pharmaceutically acceptable carrier such as sucrose, lactose or starch. These dosage forms can be used as usual and can also contain other substances besides inert diluents, for example lubricating agents, such as magnesium stearate. In capsules, tablets and pills, these dosage forms may also comprise buffering agents. Tablets and pills can additionally be prepared with enteric coatings.

口服的液体剂型包括药学上可接受的、含本领域通常使用的惰性稀释剂,如水的乳剂、溶液、悬浮液、糖浆剂。除了这些惰性稀释剂外,组合物也可包括辅助剂,例如润湿剂、乳化剂、悬浮剂、甜味剂、调味剂和香味剂。Oral liquid dosage forms include pharmaceutically acceptable emulsions, solutions, suspensions, and syrups containing inert diluents commonly used in the art, such as water. Besides such inert diluents, the composition can also include adjuvants, such as wetting agents, emulsifying agents, suspending agents, sweetening, flavoring, and perfuming agents.

本发明用于非肠道给药的制剂包括无菌水溶液或非水溶液、悬浮液或乳剂。非水溶剂或赋形剂,例如丙二醇、聚乙二醇、植物油(如橄榄油和玉米油)、明胶、可注射的有机酯(如油酸乙酯)。这些剂型也可包含诸如防腐剂、润湿剂、乳化剂和分散剂之类的辅助剂。可以通过以下方法进行灭菌,例如经细菌存留过滤器过滤,在组合物中加入灭菌剂、照射组合物或加热组合物。也可将它们制成无菌固体组合物的形式,使用前立即将其溶解在无菌水或其它可注射的无菌介质中。The preparations for parenteral administration of the present invention include sterile aqueous or non-aqueous solutions, suspensions or emulsions. Non-aqueous solvents or excipients such as propylene glycol, polyethylene glycol, vegetable oils such as olive oil and corn oil, gelatin, injectable organic esters such as ethyl oleate. These dosage forms may also contain adjuvants such as preserving, wetting, emulsifying and dispersing agents. Sterilization can be achieved by, for example, filtration through a bacteria-retaining filter, adding a sterilizing agent to the composition, irradiating the composition, or heating the composition. They can also be prepared in the form of sterile solid compositions which are dissolved in sterile water or other injectable sterile media immediately before use.

直肠或阴道给药的组合物优选栓剂,除了活性物质外,它可包含赋形剂,例如可可脂或栓剂蜡。Compositions for rectal or vaginal administration are preferably suppositories, which may contain, in addition to the active substance, excipients such as cocoa butter or a suppository wax.

也可用本领域公知的标准赋形剂制备鼻腔或舌下给药的组合物。另外,本发明组合物可以以持续释放组合物的形式给药。Compositions for nasal or sublingual administration may also be prepared using standard excipients well known in the art. Additionally, the compositions of the present invention may be administered as sustained release compositions.

本发明的积极效果在于:融合蛋白中GLP-1可保持其天然功能,胰高血糖素家族受体部分及人IgG Fc片段部分则能够延长GLP-1半衰期,而且胰高血糖素家族受体具有中和胰高血糖素的作用,可起到双重降糖效果;人IgG Fc片段部分则有利于融合蛋白的纯化。The positive effects of the present invention are: GLP-1 in the fusion protein can maintain its natural function, the glucagon family receptor part and the human IgG Fc fragment part can prolong the half-life of GLP-1, and the glucagon family receptor has Neutralizing the effect of glucagon can play a double hypoglycemic effect; the human IgG Fc fragment is conducive to the purification of fusion proteins.

本发明中胰高血糖素家族受体部分延长GLP-1半衰期的原因如下:The reasons why the glucagon family receptor part prolongs the half-life of GLP-1 in the present invention are as follows:

胰高血糖素受体的第1和第3膜外圈,能与胰高血糖素的N-端结合。GLP-1的N-端与胰高血糖素几乎相同,因此GLP-1可与胰高血糖素受体(或胰高血糖素家族其它多肽的受体)微弱结合,此微弱结合可在某种程度上保护GLP-1免遭DPPIV的降解,故可延长GLP-1的半衰期。同样,当将GLP-1及GLP-1受体或部份功能区融合在一起时,GLP-1将和与之相连的受体部份微弱结合,以保护GLP-1,当融合蛋白遇上天然受体时,其结合力比融合蛋白的受体部分强,故融合蛋白中GLP-1倾向于与天然受体结合,发挥其生物学效应。The first and third outer rings of the glucagon receptor can bind to the N-terminus of glucagon. The N-terminus of GLP-1 is almost the same as that of glucagon, so GLP-1 can weakly bind to the glucagon receptor (or other polypeptide receptors of the glucagon family), and this weak binding can be in a certain Protect GLP-1 from the degradation of DPPIV to a certain extent, so it can prolong the half-life of GLP-1. Similarly, when GLP-1 and GLP-1 receptor or part of the functional region are fused together, GLP-1 will weakly bind to the part of the receptor connected to it to protect GLP-1. When the fusion protein meets When the natural receptor is used, its binding force is stronger than the receptor part of the fusion protein, so GLP-1 in the fusion protein tends to bind to the natural receptor and exert its biological effect.

除非另有说明,本文所用的所有技术和科学术语的含义与本发明所属领域的普通技术人员通常理解的相同。Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

附图说明 Description of drawings

图1显示了融合蛋白PPS 601免疫印迹结果Figure 1 shows the results of western blot of the fusion protein PPS 601

图2a显示了GLP-1受体序列Figure 2a shows the GLP-1 receptor sequence

图2b显示融合蛋白PPS601与人GLP-1(7-37)受体的结合结果Figure 2b shows the binding result of fusion protein PPS601 and human GLP-1(7-37) receptor

图3显示了融合蛋白PPS 601对cAMP水平的影响Figure 3 shows the effect of fusion protein PPS 601 on cAMP levels

图4显示了融合蛋白PPS 601的体内药代动力学结果Figure 4 shows the in vivo pharmacokinetic results of the fusion protein PPS 601

图5显示了融合蛋白PPS 601对小鼠耐糖能力的影响Figure 5 shows the effect of the fusion protein PPS 601 on the glucose tolerance of mice

图6显示了pV05载体图Figure 6 shows the pV05 vector map

图7显示了PPS 601重组载体图Figure 7 shows the PPS 601 recombinant vector map

具体实施方式: Detailed ways:

下列实施例用以帮助描述如何实施本发明的各种实施方案。这些实施例是为了举例说明,而不是以任何方式限定本发明的范围。The following examples are provided to help describe how various embodiments of the invention may be practiced. These examples are for illustration and are not intended to limit the scope of the invention in any way.

实施例1Example 1

融合蛋白载体的构建Construction of Fusion Protein Vector

融合蛋白中GLP-1部分可以任何表达人GLP-1的cDNA,如胰腺,小肠,脑组织cDNA为模板,经PCR扩增获得。小鼠与人有相同GLP-1氨基酸序列,故可取代人cDNA。The GLP-1 part of the fusion protein can be obtained by PCR amplification using any cDNA expressing human GLP-1, such as pancreas, small intestine, and brain tissue cDNA as a template. Mouse and human have the same GLP-1 amino acid sequence, so it can replace human cDNA.

可以通过各种不同的方法,包括上述的克隆方法和化学合成DNA的方法制备编码本发明的GLP-1的DNA。The DNA encoding the GLP-1 of the present invention can be prepared by various methods including the above-mentioned cloning method and the method of chemically synthesizing DNA.

融合蛋白中胰高血糖素受体部分可以人肝组织cDNA为模板,引物为5’-ATGCCCCCCTGCCAGCCACAG-3’及5’-TCAGAAGGGGCTCTCAGCCAATC-3’,经PCR扩增获得。所扩增的胰高血糖素受体为1431bp,将之克隆入TOPO TA载体(Invitrogen),重组的载体经EcoRI酶切及序列分析鉴定。所获得的质粒在此称为TOPO TA-胰高血糖素受体。The glucagon receptor part of the fusion protein can be obtained by PCR amplification using human liver tissue cDNA as a template, and primers 5'-ATGCCCCCCTGCCAGCCACAG-3' and 5'-TCAGAAGGGGCTCTCAGCCAATC-3'. The amplified glucagon receptor was 1431bp, which was cloned into TOPO TA vector (Invitrogen), and the recombinant vector was identified by EcoRI digestion and sequence analysis. The resulting plasmid is referred to herein as TOPO TA-glucagon receptor.

胰高血糖素受体N-端膜外功能区;功能区-1;功能区-2;功能区-3片段,可以上述TOPO TA-胰高血糖素受体为模板,以相应引物,经PCR扩增获得。在获取了上述基因片断后,可经联接酶将相应基因连接制备融合蛋白,亦可用重叠PCR方法将之融合在一起。然后克隆入表达载体。Glucagon receptor N-terminal extramembrane functional region; functional region-1; functional region-2; functional region-3 fragments, the above-mentioned TOPO TA-glucagon receptor can be used as a template, and corresponding primers can be used for PCR Amplified obtained. After the above-mentioned gene fragments are obtained, the corresponding genes can be connected by ligase to prepare a fusion protein, and the overlapping PCR method can also be used to fuse them together. Then cloned into the expression vector.

融合蛋白中GLP-1受体可以人肝组织cDNA为模板,使用引物5’-ATGGCCGGCGCCCCCGGC-3’及5’-TCAGCTGTAGGAGGCCTGGC-3’,经PCR扩增获得。所扩增的GLP-1受体为1392bp,将之克隆入TOPO TA载体(Invitrogen),重组的载体经EcoRI酶切及序列分析鉴定。所获得的质粒在此称为TOPO TA-GLP-1受体。The GLP-1 receptor in the fusion protein can be obtained by PCR amplification using human liver tissue cDNA as a template, using primers 5'-ATGGCCGGCGCCCCCGGC-3' and 5'-TCAGCTGTAGGAGGCCTGGC-3'. The amplified GLP-1 receptor is 1392bp, which is cloned into the TOPO TA vector (Invitrogen), and the recombinant vector is identified by EcoRI digestion and sequence analysis. The resulting plasmid is referred to herein as TOPO TA-GLP-1 receptor.

GLP-1受体N-端膜外功能区;功能区-1;功能区-2;功能区-3片段,可以上述TOPO TA-GLP-1受体为模板,以相应引物,经PCR扩增获得。在获取了上述基因片断后,可经联接酶将相应基因连接制备融合蛋白,亦可用重叠PCR方法将之融合在一起。然后克隆入表达载体。GLP-1 receptor N-terminal extramembrane functional region; functional region-1; functional region-2; functional region-3 fragments, the above-mentioned TOPO TA-GLP-1 receptor can be used as a template, and the corresponding primers can be amplified by PCR get. After the above-mentioned gene fragments are obtained, the corresponding genes can be connected by ligase to prepare a fusion protein, and the overlapping PCR method can also be used to fuse them together. Then cloned into the expression vector.

融合蛋白中GLP-2受体可以人肝组织cDNA为模板,使用引物5’-ATGAAGCTGGGATCGAGCAG-3’及5’-CTAGATCTCACTCTCTTCCAG-3’,经PCR扩增获得。所扩增的GLP-2受体为1162bp,将之克隆入TOPO TA载体(Invitrogen),重组的载体经EcoRI酶切及序列分析鉴定。所获得的质粒在此称为TOPO TA-GLP-2受体。The GLP-2 receptor in the fusion protein can be obtained by PCR amplification using human liver tissue cDNA as a template, using primers 5'-ATGAAGCTGGGATCGAGCAG-3' and 5'-CTAGATCTCACTCTCTTCCAG-3'. The amplified GLP-2 receptor is 1162bp, which is cloned into the TOPO TA vector (Invitrogen), and the recombinant vector is identified by EcoRI digestion and sequence analysis. The resulting plasmid is referred to herein as TOPO TA-GLP-2 receptor.

GLP-2受体N-端膜外功能区;功能区-1;功能区-2;功能区-3片段,可以上述TOPO TA-GLP-2受体为模板,以相应引物,经PCR扩增获得。在获取了上述基因片断后,可经联接酶将相应基因连接制备融合蛋白,亦可用重叠PCR方法将之融合在一起。然后克隆入表达载体。GLP-2 receptor N-terminal extramembrane functional region; functional region-1; functional region-2; functional region-3 fragments, the above-mentioned TOPO TA-GLP-2 receptor can be used as a template, and the corresponding primers can be amplified by PCR get. After the above-mentioned gene fragments are obtained, the corresponding genes can be connected by ligase to prepare a fusion protein, and the overlapping PCR method can also be used to fuse them together. Then cloned into the expression vector.

融合蛋白中人免疫球蛋白G1的Fc区段可使用任何有表达的人组织cDNA经PCR扩增获得。从人cDNA文库(GIBCO,BRL)中钓取人编码IgG1亚型的CH2和CH3功能区的cDNA序列。所用引物为:The Fc region of human immunoglobulin G1 in the fusion protein can be obtained by PCR amplification using any expressed human tissue cDNA. Human cDNA sequences encoding the CH2 and CH3 domains of the IgGl subtype were fished from a human cDNA library (GIBCO, BRL). The primers used are:

5’-AAAAGGCCCGGGCGACAAAACTCACACATGC-3’(含SrfI酶切位点)5'-AAAAGGCCCGGGCGACAAAACTCACACATGC-3' (with SrfI restriction site)

和5’-ATTTCGCCGGCGTTATTTACCCGGAGACAGGG-3’(含NotI酶切位点)And 5'-ATTTCGCCGGCGTTATTTACCCGGAGACAGGG-3' (with NotI restriction site)

此对引物用于扩增IgG1重链编码区的214-467bp区域,它包括铰链区、CH2和CH3功能区(Strausberg,R.L.etc.Proc.Natl.Acad.Sci.U.S.A.99(26),16899-16903(2002))。获得的人免疫球蛋白G1的Fc为759bp,在其5’-端含有中间接头GGCCCGGGC(SrfI酶切位点),在其3’-端含有TAA终止密码子及NotI酶切位点,将之克隆入pV05载体(图6),所获得的质粒命名为pV05-人免疫蛋白G1Fc。This pair of primers is used to amplify the 214-467bp region of the IgG1 heavy chain coding region, which includes the hinge region, CH2 and CH3 functional regions (Strausberg, R.L.etc.Proc.Natl.Acad.Sci.U.S.A.99(26), 16899- 16903 (2002)). The obtained Fc of human immunoglobulin G1 is 759bp, contains an intermediate linker GGCCCGGGC (SrfI restriction site) at its 5'-end, and contains a TAA stop codon and a NotI restriction site at its 3'-end. Cloned into the pV05 vector (Figure 6), the obtained plasmid was named pV05-human immune protein G1Fc.

当用哺乳动物细胞表达融合蛋白时,须有信号肽,以使表达的融合蛋白能被分泌到胞浆,信号肽被自动切除。本发明使用前胰高血糖素的信号肽,亦可使用其它信号肽,如:前副甲状腺激素的信号肽(Wiren,KM etc.The J of Bio.Chem.263(36):19771-19777(1988),或人IgG1Fc的信号肽。When the fusion protein is expressed in mammalian cells, a signal peptide is required so that the expressed fusion protein can be secreted into the cytoplasm, and the signal peptide is automatically excised. The present invention uses the signal peptide of preglucagon, and other signal peptides can also be used, such as: the signal peptide of preparathyroid hormone (Wiren, KM etc. The J of Bio. Chem. 263 (36): 19771-19777 ( 1988), or the signal peptide of human IgG1 Fc.

当用细菌表达融合蛋白时,可采用细菌融合蛋白表达方法,在N端加入蛋白酶切点及HA或6HIS TAG用于吸附纯化,表达的融合蛋白经蛋白酶酶切后,得到含有正确切除位点的融合蛋白。还可使用最新的IMPACT细菌表达系统(New England,BioLabs Inc.)。这个IMPACT蛋白融合和纯化系统是利用可诱导的工程蛋白剪切元件的自身裂解活性来进行蛋白纯化和处理。通过pH和温度诱导裂解来纯化蛋白:使用pTWIN载体,这个intein标签是融合在目的蛋白的N-末端。此目的蛋白之后通过pH和温度诱导的裂解而被释放。When the fusion protein is expressed in bacteria, the bacterial fusion protein expression method can be used, and a protease cleavage point and HA or 6HIS TAG are added to the N-terminus for adsorption and purification. fusion protein. The latest IMPACT bacterial expression system (New England, BioLabs Inc.) can also be used. The IMPACT protein fusion and purification system utilizes the self-cleavage activity of inducible engineered protein cleavage elements for protein purification and processing. Purify protein by pH and temperature induced cleavage: using the pTWIN vector, the intein tag is fused to the N-terminus of the protein of interest. The protein of interest is then released by pH and temperature induced cleavage.

实施例1aExample 1a

融合蛋白(第2位G取代A)GLP-1-中间接头-胰高血糖素受体N-端膜外功能区-人免疫蛋白G1Fc重组载体的构建:Construction of fusion protein (G in position 2 replacing A) GLP-1-middle linker-glucagon receptor N-terminal extramembrane domain-human immune protein G1Fc recombinant vector:

以小鼠脑组织cDNA为模板,使用下述引物:Using mouse brain tissue cDNA as a template, the following primers were used:

(a)5’-CCCAAGCTT ATGAAGACCATTTACTTTGT-3’(a) 5'-CCCAAGCTT ATGAAGACCATTTACTTTGT-3'

(b)5’-GGTCCCTTCAGCATGCTGCCAGCTGCCTTGCAC-3’(b) 5'-GGTCCCTTCAGCATGCTGCCAGCTGCCTTGCAC-3'

(c)5’-CATGCTGAAGGGACCTTTAC-3’(c) 5'-CATGCTGAAGGGACCTTTAC-3'

(d)5’-AAAAGGCGCGCCTTCCTCGGCCTTTCACCAGCC-3’(d) 5'-AAAAGGCGCGCCTTCCTCGGCCTTTCACCAGCC-3'

PCR扩增可分别获得胰高血糖素原信号肽及GLP-1编码序列。所获得信号肽的3’端经引物插入15bp GLP-15’端序列,再以引物(a),(d)经重叠PCR将信号肽与GLP-1融合在一起。在引物(b)及(c)中将Ala变Gly(GAA变成GCT),所获得的片段5‘及3’端分别插入HindIII及AscI酶切位点用于克隆。PCR amplification can obtain proglucagon signal peptide and GLP-1 coding sequence respectively. The 3' end of the obtained signal peptide was inserted into the 15bp GLP-15' end sequence through primers, and then the signal peptide and GLP-1 were fused together by overlapping PCR with primers (a) and (d). In primers (b) and (c), Ala was changed to Gly (GAA was changed to GCT), and the 5' and 3' ends of the obtained fragments were respectively inserted into HindIII and AscI restriction sites for cloning.

以TOPO TA-胰高血糖素受体为模板,使用下述引物:Using the TOPO TA-glucagon receptor as a template, the following primers were used:

(e)5’-AAGGCGCGCCTGCTCAGGTGATGGACTTC-3’(e) 5'-AAGGCGCGCCTGCTCAGGTGATGGACTTC-3'

(f)5’-AAAAGCCCGGGCCCTGGAAGCTGCTGTACATC-3’(f) 5'-AAAAGCCCGGGCCCTGGAAGCTGCTGTACATC-3'

经PCR扩增获得胰高血糖素受体N-端膜外功能区,其5’-端含GGCGCGCCT(AscI酶切位点),3’-端含GCCCGGGCC(SrfI酶切位点)。The N-terminal extramembrane domain of the glucagon receptor was amplified by PCR, its 5'-end contained GGCGCGCCT (AscI restriction site), and its 3'-end contained GCCCGGGCC (SrfI restriction site).

获得上述两片段后,可将其克隆入已经HindIII及SrfI酶切的载体pV05-人免疫蛋白G1的Fc中,然后转化入HB10D感受态细胞(invitrogen)。重组质粒经HindIII及NotI酶切及序列分析鉴定完全正确。After obtaining the above two fragments, they can be cloned into the Fc of the vector pV05-human immunoprotein G1 that has been digested with HindIII and SrfI, and then transformed into HB10D competent cells (invitrogen). The recombinant plasmid was identified completely correct by HindIII and NotI digestion and sequence analysis.

表达的融合蛋白序列为[序列ID NO:35]:The expressed fusion protein sequence is [Sequence ID NO: 35]:

HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-GAP-AQVMDFLFEKWKLYGDQCHHNLHGEGFTTSDVSSYLEGQAAKEFIAWLVKGRG-GAP-AQVMDFLFEKWKLYGDQCHHNL

SLLPPPTELVSLLPPPTELV

CNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPW

RDASQCQMDGEEI EVQKEVAKMYSSFQ-GPG-DKTHTCPPCPAPELLGGPSVFLFPPKRDASQCQMDGEEI EVQKEVAKMYSSFQ-GPG-DKTHTCPPCPAPELLGGPSVFLFPPK

PKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVS

VLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQ

VSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQG

NVFSCSVMHEALHNHYTQKSLSLSPGKNVFSCSVMHEALHNHYTQKSLSLSPGK

实施例1bExample 1b

融合蛋白(第2位G取代A)GLP-1-中间接头-胰高血糖素受体功能区-1-中间接头-人免疫蛋白G1Fc的重组载体的构建Construction of recombinant vector of fusion protein (G in position 2 replacing A) GLP-1-middle linker-glucagon receptor functional region-1-middle linker-human immune protein G1Fc

信号肽-(第2位G取代A)GLP-1片断的制备与方法1a相同。The preparation of the signal peptide-(G at position 2 replacing A) GLP-1 fragment was the same as method 1a.

胰高血糖素受体功能区-1可使用下述引物经PCR扩增获得:Glucagon receptor domain-1 can be obtained by PCR amplification using the following primers:

扩增胰高血糖素受体功能区-1引物为:The primers for amplifying the glucagon receptor functional domain-1 are:

5’-CCGGCGCGCCTGTCATTGATGGGCTGCTCAG-3’(含Asc I酶切位点)及5’-AAAAGCCCGGGCCAGCCACCGCTCCATCACT-3’(含Srf I酶切位点)。5'-CCGGCGCGCCTGTCATTGATGGGCTGCTCAG-3' (with Asc I restriction site) and 5'-AAAAGCCCGGGCCAGCCACCGCTCCATCACT-3' (with Srf I restriction site).

将上述PCR获得的片段用HindIII及SrfI酶切后克隆入已经HindIII及SrfI酶切的载体pV05-人免疫球蛋白G1的Fc中。重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The fragment obtained by the above PCR was digested with HindIII and SrfI and then cloned into the Fc of the vector pV05-human immunoglobulin G1 that had been digested with HindIII and SrfI. The inserted sequence of the recombinant plasmid was identified by nucleotide sequencing and its sequence was completely correct.

实施例1cExample 1c

融合蛋白(第2位G取代A)GLP-1-中间接头-胰高血糖素受体功能区-3-中间接头-人免疫蛋白G1Fc的重组载体的构建Construction of recombinant vector of fusion protein (G in position 2 replacing A) GLP-1-middle linker-glucagon receptor functional region-3-middle linker-human immune protein G1Fc

信号肽-(第2位G取代A)GLP-1片断的制备与方法1a相同。The preparation of the signal peptide-(G at position 2 replacing A) GLP-1 fragment was the same as method 1a.

胰高血糖素受体功能区-3可使用下述引物经PCR扩增获得:Glucagon receptor functional domain-3 can be obtained by PCR amplification using the following primers:

扩增胰高血糖素受体功能区-3引物为:The primers for amplifying the glucagon receptor functional domain-3 are:

5’-CCGGCGCGCCTGACGAGCACGCCCAGGGC-3’(含Asc I酶切位点)5'-CCGGCGCGCCTGACGAGCACGCCCAGGGC-3' (with Asc I restriction site)

5’-AAAAGCCCGGGCCGAGGTCGAAGAAGAGCTT-3’(含Srf I酶切位点)5'-AAAAGCCCGGGCCGAGGTCGAAGAAGAGCTT-3' (with Srf I restriction site)

将上述PCR获得的片段用HindIII及SrfI酶切后克隆入已经HindIII及SrfI酶切的载体pV05-人免疫球蛋白G1的Fc中。重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The fragment obtained by the above PCR was digested with HindIII and SrfI and then cloned into the Fc of the vector pV05-human immunoglobulin G1 that had been digested with HindIII and SrfI. The inserted sequence of the recombinant plasmid was identified by nucleotide sequencing and its sequence was completely correct.

实施例1dExample 1d

融合蛋白(第2位G取代A)GLP-1-中间接头-胰高血糖素受体功能区-1-中间接头-胰高血糖素受体功能区-3-中间接头-人免疫蛋白G1Fc的重组载体的构建:Fusion protein (2nd G replaces A) GLP-1-middle linker-glucagon receptor functional region-1-middle linker-glucagon receptor functional region-3-middle linker-human immune protein G1Fc Construction of recombinant vectors:

信号肽-(第2位G取代A)GLP-1片断的制备与方法1a相同。The preparation of the signal peptide-(G at position 2 replacing A) GLP-1 fragment was the same as method 1a.

胰高血糖素受体功能区-1及功能区-3可使用下述引物经PCR扩增分别获得:Glucagon receptor functional region-1 and functional region-3 can be respectively obtained by PCR amplification using the following primers:

扩增胰高血糖素受体功能区-1引物为:The primers for amplifying the glucagon receptor functional domain-1 are:

5’-CCGGCGCGCCTGTC ATT GAT GGG CTG CTC AG-3’(含Asc I酶切位点)及5’ACTTCCACCTCCGCCAGCCACCGCTCCATCACT-3’(含ACTTCCACCTCCGCC中间接头)。5'-CCGGCGCGCCTGTC ATT GAT GGG CTG CTC AG-3' (with Asc I restriction site) and 5'ACTTCCACCTCCGCCAGCCACCGCTCCATCACT-3' (with ACTTCCACCTCCGCC intermediate linker).

扩增胰高血糖素受体功能区-3引物为:The primers for amplifying the glucagon receptor functional domain-3 are:

5’-GGCGGAGGTGGAAGTGACGAGCACGCCCAGGGC-3’及5’-AAAAGCCCGGGCCGAGGTCGAAGAAGAGCTT-3’(含Srf I酶切位点)5'-GGCGGAGGTGGAAGTGACGAGCACGCCCAGGGC-3' and 5'-AAAAGCCCGGGCCGAGGTCGAAGAAGAGCTT-3' (with Srf I restriction site)

将上述PCR获得的两个片段经重叠PCR融合在一起,用HindIII及SrfI酶切后克隆入已经HindIII及SrfI酶切的载体pV05-人免疫球蛋白G1的Fc中,重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The two fragments obtained by the above PCR were fused together by overlapping PCR, digested with HindIII and SrfI, and then cloned into the Fc of the vector pV05-human immunoglobulin G1 that had been digested with HindIII and SrfI. Nucleotide sequencing identified that the sequence was completely correct.

表达的融合蛋白序列为[序列ID NO:36]:The expressed fusion protein sequence is [Sequence ID NO: 36]:

HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-

GAP-VIDGLLRTRYSQKIGDDLSVSTWLSDGAVAGGAP-VIDGLLRTRYSQKIGDDLSVSTWLSDGAVAG

-GGGS-DEHAQGTLRSAKLFFDL-GPG-DKTHTCPPCPAPELLGGPSVFLFPPKPK-GGGS-DEHAQGTLRSAKLFFDL-GPG-DKTHTCPPCPAPELLGGPSVFLFPPKPK

DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNST

YRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT

LPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDG

SFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

实施例1eExample 1e

融合蛋白(第2位G取代A)GLP-1-中间接头-人免疫蛋白G1Fc的构建:Construction of fusion protein (G in position 2 replacing A) GLP-1-intermediate linker-human immune protein G1Fc:

信号肽-(G8取代A)GLP-1片断的制备与实施例1a相同。只是引物(d)中用SrfI来代替AscI。获得后将其克隆入已经HindIII及SrfI酶切的载体pV05-人免疫蛋白G1的Fc中。重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The preparation of the signal peptide-(G8 substituting A) GLP-1 fragment was the same as in Example 1a. Just replace AscI with SrfI in primer (d). After obtaining it, clone it into the Fc of vector pV05-human immunoprotein G1 which has been digested with HindIII and SrfI. The inserted sequence of the recombinant plasmid was identified by nucleotide sequencing and its sequence was completely correct.

表达的融合蛋白序列为[序列ID NO:37]:The expressed fusion protein sequence is [Sequence ID NO: 37]:

HGEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-GAP-DKTHTCPPCPAPELLGGPHGEGTFTSDVSSYLEGQAAKEFIAWLVKGRG-GAP-DKTHTCPPCPAPELLGGP

SVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK

PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQ

PREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP

PVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSSLSPGK

实施例1fExample 1f

融合蛋白(第2位G取代A)GLP-1-中间接头-GLP-1受体-人免疫球蛋白G1Fc重组载体的构建Construction of Fusion Protein (Second G Replaces A) GLP-1-Middle Linker-GLP-1 Receptor-Human Immunoglobulin G1Fc Recombinant Vector

以小鼠脑组织cDNA为模板,使用下述引物:Using mouse brain tissue cDNA as a template, the following primers were used:

(a)5’-CCCAAGCTT ATGAAGACCATTTACTTTGT-3’(a) 5'-CCCAAGCTT ATGAAGACCATTTACTTTGT-3'

(b)5’-GGTCCCTTCAGCATGCTGCCAGCTGCCTTGCAC-3’(b) 5'-GGTCCCTTCAGCATGCTGCCAGCTGCCTTGCAC-3'

(c)5’-CATGCTGAAGGGACCTTTAC-3’(c) 5'-CATGCTGAAGGGACCTTTAC-3'

(d)5’-AAAAGGCGCGCCTTCCTCGGCCTTTCACCAGCC-3’(d) 5'-AAAAGGCGCGCCTTCCTCGGCCTTTCACCAGCC-3'

PCR扩增可分别获得胰高血糖素原信号肽及GLP-1编码序列。所获得信号肽的3’端经引物插入15bp GLP-15’端序列,再以引物(a),(d)经重叠PCR将信号肽与GLP-1融合在一起。在引物(b)及(c)中将Ala变Gly(GAA变成GCT),所获得的片段5‘及3’端分别插入HindIII及AscI酶切位点用于克隆。PCR amplification can obtain proglucagon signal peptide and GLP-1 coding sequence respectively. The 3' end of the obtained signal peptide was inserted into the 15bp GLP-15' end sequence through primers, and then the signal peptide and GLP-1 were fused together by overlapping PCR with primers (a) and (d). In primers (b) and (c), Ala was changed to Gly (GAA was changed to GCT), and the 5' and 3' ends of the obtained fragments were respectively inserted into HindIII and AscI restriction sites for cloning.

以TOPO TA-GLP-1受体为模板,使用下述引物:Using the TOPO TA-GLP-1 receptor as a template, the following primers were used:

(e)5’-AAGGCGCGCCTCGCCCCCAGGGTGCCAC-3’(e) 5'-AAGGCGCGCCTCGCCCCCAGGGTGCCAC-3'

(f)5’-AAAAGCCCGGGCCGCTGCAGGAGGCCTG-3’(f) 5'-AAAAGCCCGGGCCGCTGCAGGAGGCCTG-3'

经PCR扩增获得GLP-1受体,其5’-端含GGCGCGCCT(Asc I酶切位点),3’-端含GCCCGGGCC(SrfI酶切位点)。Obtain GLP-1 receptor through PCR amplification, and its 5'-end contains GGCGCGCCT (Asc I restriction site), and 3'-end contains GCCCGGGCC (SrfI restriction site).

获得上述两片段后,可将其克隆入已经HindIII及SrfI酶切的载体pV05-人免疫蛋白G1的Fc中,然后转化入HB10D感受态细胞(invitrogen)。重组质粒经HindIII及NotI酶切及序列分析鉴定其序列完全正确。After obtaining the above two fragments, they can be cloned into the Fc of the vector pV05-human immunoprotein G1 that has been digested with HindIII and SrfI, and then transformed into HB10D competent cells (invitrogen). The sequence of the recombinant plasmid was confirmed to be completely correct by HindIII and NotI digestion and sequence analysis.

实施例1gExample 1g

融合蛋白(第2位G取代A)GLP-1-中间接头-GLP-1受体N-端膜外功能区-人免疫球蛋白G1Fc重组载体的构建Construction of Fusion Protein (Second G Replaces A) GLP-1-Middle Linker-GLP-1 Receptor N-terminal Extramembrane Functional Region-Human Immunoglobulin G1Fc Recombinant Vector

以小鼠脑组织cDNA为模板,使用下述引物:Using mouse brain tissue cDNA as a template, the following primers were used:

(a)5’-CCCAAGCTT ATGAAGACCATTTACTTTGT-3’(a) 5'-CCCAAGCTT ATGAAGACCATTTACTTTGT-3'

(b)5’-GGTCCCTTCAGCATGCTGCCAGCTGCCTTGCAC-3’(b) 5'-GGTCCCTTCAGCATGCTGCCAGCTGCCTTGCAC-3'

(c)5’-CATGCTGAAGGGACCTTTAC-3’(c) 5'-CATGCTGAAGGGACCTTTAC-3'

(d)5’-AAAAGGCGCGCCTTCCTCGGCCTTTCACCAGCC-3’(d) 5'-AAAAGGCGCGCCTTCCTCGGCCTTTCACCAGCC-3'

PCR扩增可分别获得胰高血糖素原信号肽及GLP-1编码序列。所获得信号肽的3’端经引物插入15bp GLP-15’端序列,再以引物(a),(d)经重叠PCR将信号肽与GLP-1融合在一起。在引物(b)及(c)中将Ala变Gly(GAA变成GCT),所获得的片段5‘及3’端分别插入HindIII及AscI酶切位点用于克隆。PCR amplification can obtain proglucagon signal peptide and GLP-1 coding sequence respectively. The 3' end of the obtained signal peptide was inserted into the 15bp GLP-15' end sequence through primers, and then the signal peptide and GLP-1 were fused together by overlapping PCR with primers (a) and (d). In primers (b) and (c), Ala was changed to Gly (GAA was changed to GCT), and the 5' and 3' ends of the obtained fragments were respectively inserted into HindIII and AscI restriction sites for cloning.

以TOPO TA-GLP-1受体为模板,使用下述引物:Using the TOPO TA-GLP-1 receptor as a template, the following primers were used:

(e)5’-AAGGCGCGCCTCGCCCCCAGGGTGCCAC-3’(e) 5'-AAGGCGCGCCTCGCCCCCAGGGTGCCAC-3'

(f)5’-AAAAGCCCGGGCCGTAGAGGAACAGGAGCTG-3’(f) 5'-AAAAGCCCGGGCCGTAGAGGAACAGGAGCTG-3'

经PCR扩增获得GLP-1受体N-端膜外功能区,其5’-端含GGCGCGCCT(AscI酶切位点),3’-端含GCCCGGGCC(SrfI酶切位点)。获得上述两片段后,可将其克隆入已经HindIII及SrfI酶切的载体pV05-人免疫蛋白G1的Fc中,然后转化入HB10D感受态细胞(invitrogen)。重组质粒经HindIII及NotI酶切及序列分析鉴定其序列完全正确。The N-terminal extramembrane functional region of the GLP-1 receptor was amplified by PCR, its 5'-end contained GGCGCGCCT (AscI restriction site), and the 3'-end contained GCCCGGGCC (SrfI restriction site). After obtaining the above two fragments, they can be cloned into the Fc of the vector pV05-human immunoprotein G1 that has been digested with HindIII and SrfI, and then transformed into HB10D competent cells (invitrogen). The sequence of the recombinant plasmid was confirmed to be completely correct by HindIII and NotI digestion and sequence analysis.

实施例1hExample 1h

融合蛋白(第2位G取代A)GLP-1-中间接头-GLP-1受体功能区-1-中间接头-人免疫球蛋白G1Fc的重组载体的构建Construction of recombinant vector of fusion protein (G in position 2 replacing A) GLP-1-middle linker-GLP-1 receptor functional region-1-middle linker-human immunoglobulin G1Fc

信号肽-(第2位G取代A)GLP-1片断的制备与方法1a相同。The preparation of the signal peptide-(G at position 2 replacing A) GLP-1 fragment was the same as method 1a.

GLP-1受体功能区-1可使用下述引物经PCR扩增获得:GLP-1 receptor functional region-1 can be obtained by PCR amplification using the following primers:

扩增GLP-1受体功能区-1引物为:The primers for amplifying the GLP-1 receptor functional region-1 are:

5’-CCGGCGCGCCTAACTACATCCACCTGAAC-3’(含Asc I酶切位点)及5’-AAAAGCCCGGGCCCAGGTACACGCCCTCCAC-3’(含Srf I酶切位点)。5'-CCGGCGCGCCTAACTACATCCACCTGAAC-3' (with Asc I restriction site) and 5'-AAAAGCCCGGGCCCAGGTACACGCCCTCCAC-3' (with Srf I restriction site).

将上述PCR获得的片段用HindIII及SrfI酶切后克隆入已经HindIII及SrfI酶切的载体pV05-人免疫球蛋白G1的Fc中,重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The fragment obtained by the above PCR was digested with HindIII and SrfI and then cloned into the Fc of the vector pV05-human immunoglobulin G1 that had been digested with HindIII and SrfI. The inserted sequence of the recombinant plasmid was confirmed to be completely correct by nucleotide sequencing.

实施例1iExample 1i

融合蛋白(第2位G取代A)GLP-1-中间接头-GLP-1受体功能区-2-中间接头人免疫球蛋白G1Fc的重组载体的构建Construction of recombinant vector of fusion protein (G in position 2 replacing A) GLP-1-middle linker-GLP-1 receptor functional region-2-middle linker human immunoglobulin G1Fc

信号肽-(第2位G取代A)GLP-1片断的制备与方法1a相同。GLP-1受体功能区-2可使用下述引物经PCR扩增获得:The preparation of the signal peptide-(G at position 2 replacing A) GLP-1 fragment was the same as method 1a. GLP-1 receptor functional domain-2 can be obtained by PCR amplification using the following primers:

扩增GLP-1受体功能区-2引物为:The primers for amplifying the GLP-1 receptor functional domain-2 are:

5’-CCGGCGCGCCTTTCAGGCTCTACGTGAGC-3’(含Asc I酶切位点)及5’-AAAAGCCCGGGCCGCAGATGACCCGAACAAAG-3’(含含Srf I酶切位点)。5'-CCGGCGCGCCTTTCAGGCTCTACGTGAGC-3' (with Asc I restriction site) and 5'-AAAAGCCCGGGCCGCAGATGACCCGAACAAAG-3' (with Srf I restriction site).

将上述PCR获得的片段经HindIII及SrfI酶切后克隆入已经HindIII及SrfI酶切的载体pV05-人免疫球蛋白G1的Fc中。重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The fragment obtained by the above PCR was digested with HindIII and SrfI and then cloned into the Fc of the vector pV05-human immunoglobulin G1 that had been digested with HindIII and SrfI. The inserted sequence of the recombinant plasmid was identified by nucleotide sequencing and its sequence was completely correct.

实施例1jExample 1j

融合蛋白(第2位G取代A)GLP-1-中间接头-GLP-1受体功能区-3-中间接头-人免疫球蛋白G1Fc的重组载体的构建Construction of recombinant vector of fusion protein (G in position 2 replacing A) GLP-1-middle linker-GLP-1 receptor functional region-3-middle linker-human immunoglobulin G1Fc

信号肽-(第2位G取代A)GLP-1片断的制备与方法1a相同。The preparation of the signal peptide-(G at position 2 replacing A) GLP-1 fragment was the same as method 1a.

GLP-1受体功能区-3可使用下述引物经PCR扩增获得:GLP-1 receptor functional domain-3 can be obtained by PCR amplification using the following primers:

扩增GLP-1受体功能区-3引物为:The primers for amplifying the GLP-1 receptor functional region-3 are:

5’-CCGGCGCGCCTTCCACGCTGACACTCATC-3’(含Asc I酶切位点)及5’-AAAAGCCCGGGCCCTCATTGTTGACAAAGC-3’(含Srf I酶切位点)5'-CCGGCGCGCCTTCCACGCTGACACTCATC-3' (with Asc I restriction site) and 5'-AAAAGCCCGGGCCCCTCATTGTTGACAAAGC-3' (with Srf I restriction site)

将上述PCR获得的片段用HindIII及SrfI酶切后克隆入已经HindIII及SrfI酶切的载体pV05-人免疫球蛋白G1的Fc中。重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The fragment obtained by the above PCR was digested with HindIII and SrfI and then cloned into the Fc of the vector pV05-human immunoglobulin G1 that had been digested with HindIII and SrfI. The inserted sequence of the recombinant plasmid was identified by nucleotide sequencing and its sequence was completely correct.

实施例1kExample 1k

融合蛋白(第2位G取代A)GLP-1-中间接头-GLP-1受体功能区-1-中间接头-GLP-1受体功能区-3-中间接头-人免疫球蛋白G1Fc的重组载体的构建Recombination of Fusion Protein (Second G Replaces A) GLP-1-Middle Linker-GLP-1 Receptor Functional Region-1-Middle Linker-GLP-1 Receptor Functional Region-3-Middle Linker-Human Immunoglobulin G1Fc Vector construction

信号肽-(第2位G取代A)GLP-1片断的制备与方法1a相同。The preparation of the signal peptide-(G at position 2 replacing A) GLP-1 fragment was the same as method 1a.

GLP-1受体功能区-1及功能区-3可使用下述引物经PCR扩增分别获得:GLP-1 receptor functional region-1 and functional region-3 can be respectively obtained by PCR amplification using the following primers:

扩增GLP-1受体功能区-1引物为:The primers for amplifying the GLP-1 receptor functional region-1 are:

5’-CCGGCGCGCCTAACTACATCCACCTGAAC-3’(含Asc I酶切位点)及5’ACTTCCACCTCCGCCCAGGTACACGCCCTCCAC-3’(含ACTTCCACCTCCGCC中间接头)。5'-CCGGCGCGCCTAACTACATCCACCTGAAC-3' (containing the Asc I restriction site) and 5'ACTTCCACCTCCGCCCAGGTACACGCCCTCCAC-3' (containing the ACTTCCACCTCCGCC intermediate linker).

扩增GLP-1受体功能区-3引物为:The primers for amplifying the GLP-1 receptor functional domain-3 are:

5’-GGCGGAGGTGGAAGTTCCACGCTGACACTCATC-3’及5’-AAAAGCCCGGGCCCTCATTGTTGACAAAGC-3’(含Srf I酶切位点)5'-GGCGGAGGTGGAAGTTCCACGCTGACACTCATC-3' and 5'-AAAAGCCCGGGCCCTCATTGTTGACAAAGC-3' (with Srf I restriction site)

将上述PCR获得的两个片段经重叠PCR融合在一起,用HindIII及SrfI酶切后克隆入已经HindIII及SrfI酶切的载体pV05-人免疫球蛋白G1的Fc中。重组质粒的插入序列经核苷酸测序鉴定其序列完全正确。The two fragments obtained by the above PCR were fused together by overlapping PCR, digested with HindIII and SrfI, and then cloned into the Fc of the vector pV05-human immunoglobulin G1 that had been digested with HindIII and SrfI. The inserted sequence of the recombinant plasmid was identified by nucleotide sequencing and its sequence was completely correct.

实施例2Example 2

融合蛋白的表达Expression of fusion protein

实施例1中所构建的重组载体中融合蛋白的表达,可采用瞬时转染CHO方法。在10cm培养皿中接种CHO细胞106个,培养24小时后进行转染。将lipofectamine(Invitrogen)、OptiMEM及质粒混和后,室温保持30分钟,然后加入到经无血清OptiMEM洗涤过的CHO细胞中,共同培养5小时后,加入CHO-S-SFMII media(Gibco cat#31033-020)+1X谷氨酸盐(Gibco cat#25030-081)+10mM Na丁酸盐(Sigma cat#B5887),37度培养箱中培养48小时,收集含表达蛋白的上清液。The expression of the fusion protein in the recombinant vector constructed in Example 1 can adopt the method of transient transfection CHO. 106 CHO cells were inoculated in a 10 cm culture dish, and transfected after 24 hours of culture. After mixing lipofectamine (Invitrogen), OptiMEM and plasmid, keep it at room temperature for 30 minutes, then add it to CHO cells washed with serum-free OptiMEM, and after co-cultivating for 5 hours, add CHO-S-SFMII media (Gibco cat#31033- 020)+1X glutamate (Gibco cat#25030-081)+10mM Na butyrate (Sigma cat#B5887), cultivated in a 37 degree incubator for 48 hours, and collected the supernatant containing the expressed protein.

实施例3Example 3

融合蛋白的纯化Purification of fusion proteins

上述含表达蛋白的CHO上清液,经10K过滤膜浓缩10倍后,使用蛋白G柱去捕获含Fc的融合蛋白,用50mM柠檬酸(pH 3.3)洗脱,收集洗脱物(0.5ml),加入100μl 1M Tris pH 8.0中和酸性。经OD280nm测定蛋白含量后,合并所有含蛋白的收集管,经10K透析膜在PBS(pH7.4)中透析2次。The above-mentioned CHO supernatant containing the expressed protein was concentrated 10 times by a 10K filter membrane, and the protein G column was used to capture the fusion protein containing Fc, eluted with 50mM citric acid (pH 3.3), and the eluate (0.5ml) was collected , add 100μl 1M Tris pH 8.0 to neutralize the acidity. After the protein content was determined by OD280nm, all collection tubes containing protein were combined and dialyzed twice in PBS (pH7.4) through a 10K dialysis membrane.

实施例4Example 4

融合蛋白的免疫印迹鉴定Immunoblot identification of fusion proteins

用含1%SDS和2mg溴酚蓝的PBS稀释无诱导剂诱导条件下PPS601和血清样品的纯化材料。煮沸变性后,取20μl样品加至SDS-PAGE胶上,电泳后,将蛋白转至硝酸纤维素膜上。将膜用5%脱脂奶粉室温封闭2hr,加入HRP标记的羊抗人IgG(Sigma,USA),然后用ECL试剂盒发光显色(Amersham Pharmacia Biotech,USA),结果如图1所示本发明的融合蛋白得到了较好的表达。Purified material of PPS601 and serum samples under inducer-free induction conditions were diluted with PBS containing 1% SDS and 2 mg bromophenol blue. After boiling and denaturation, 20 μl of the sample was added to the SDS-PAGE gel, and after electrophoresis, the protein was transferred to the nitrocellulose membrane. Membrane was sealed with 5% skimmed milk powder at room temperature for 2hr, and HRP-labeled goat anti-human IgG (Sigma, USA) was added, and then the ECL kit was used for luminescent color development (Amersham Pharmacia Biotech, USA), and the results were shown in Figure 1. The fusion protein was well expressed.

实施例5Example 5

融合蛋白的体外结合活性测定In vitro binding activity assay of fusion protein

使用PCR扩增获得GLP-1受体cDNA(图2a),将之克隆入pcDNA3.1(Invitrogen,USA)。将GLP-1受体cDNA转染到CHO细胞48小时后按文献所示方法进行竞争结合试验(Wei and Mojsov,1996)。将CHO细胞与125I-GLP-1(7-36)(2200Ci/mmol,New England Nuclear,USA)在逐渐增加浓度(pM-uM)的hGLP-1(7-37)小肽(anaSPEC,USA)或GLP-1融合蛋白存在的情况下,4℃孵育15-18小时。反应在含有20mMHEPES,pH7.4,0.5%BSA and 0.1mM phenylmethylsulfonyl-fluoride(PMSF)的Hank’s平衡盐溶液中进行。孵育后将细胞用冰冷的PBS洗两次,用1NNaOH裂解,用γ计数仪检测放射活性,结果如图2b所示本发明的融合蛋白与GLP-1受体的结合活性略高于商品化的人GLP-1(7-36)。GLP-1 receptor cDNA was amplified by PCR (Fig. 2a), and cloned into pcDNA3.1 (Invitrogen, USA). 48 hours after the GLP-1 receptor cDNA was transfected into CHO cells, the competition binding assay was carried out according to the method described in the literature (Wei and Mojsov, 1996). CHO cells were treated with 125 I-GLP-1(7-36) (2200Ci/mmol, New England Nuclear, USA) in gradually increasing concentrations (pM-uM) of hGLP-1(7-37) small peptide (anaSPEC, USA ) or GLP-1 fusion protein, incubate at 4°C for 15-18 hours. The reaction was carried out in Hank's balanced salt solution containing 20 mM HEPES, pH 7.4, 0.5% BSA and 0.1 mM phenylmethylsulfonyl-fluoride (PMSF). After incubation, the cells were washed twice with ice-cold PBS, lysed with 1N NaOH, and radioactivity was detected with a gamma counter. As shown in Figure 2b, the binding activity of the fusion protein of the present invention to the GLP-1 receptor was slightly higher than that of the commercially available Human GLP-1(7-36).

实施例6Example 6

融合蛋白在体外对cAMP水平的影响Effect of fusion protein on cAMP level in vitro

将含GLP-1受体cDNA的重组载体转染到CHO细胞48小时后按文献所述方法测定cAMP(Wei and Mojsov,1996)。细胞被重新接种在24孔板上培养24小时,然后用缓冲液(Macy’s 5A pH 7.4,20mM HEPES,0.5%BSA,0.5mM IBMX)孵育。此细胞在没有任何小肽或者含不同浓度的hGLP-1或GLP-1融合蛋白(pM到μM)的条件下,37℃培养45分钟。在各个实验中均以forskolin(10μM,Sigma,USA)为阳性对照。弃去培养液,将细胞用PBS洗两次,用95%的乙醇裂解,13000rpm离心3分钟,将上清真空干燥后用0.05M醋酸缓冲液(0.5ml)溶解,用cAMPBiotrak SPA系统(Amersham,USA)检测cAMP水平,结果如图3所示本发明的融合蛋白在体外对cAMP水平的影响与商品化的人GLP-1(7-36)基本相同。After the recombinant vector containing GLP-1 receptor cDNA was transfected into CHO cells for 48 hours, cAMP was measured according to the method described in the literature (Wei and Mojsov, 1996). Cells were re-seeded on 24-well plates for 24 hours and then incubated with buffer (Macy’s 5A pH 7.4, 20mM HEPES, 0.5% BSA, 0.5mM IBMX). The cells were incubated at 37° C. for 45 minutes in the absence of any small peptide or with varying concentrations of hGLP-1 or GLP-1 fusion protein (pM to μM). Forskolin (10 μM, Sigma, USA) was used as a positive control in each experiment. Abandon culture medium, cell is washed twice with PBS, with 95% ethanol cracking, 13000rpm centrifugation 3 minutes, with 0.05M acetic acid buffer solution (0.5ml) dissolving after supernatant vacuum drying, with cAMPBiotrak SPA system (Amersham, USA) detected the level of cAMP, the result is shown in Figure 3. The influence of the fusion protein of the present invention on the level of cAMP in vitro is basically the same as that of commercialized human GLP-1 (7-36).

实施例7Example 7

融合蛋白的体内药代动力学In vivo pharmacokinetics of fusion proteins

融合蛋白的体内药代动力学:给C57BL/6小鼠静脉内注射融合蛋白(50nM),分别于注射后0min,1hr,6hr,12hr,24hr,36hr,48hr,60hr和72hr后于尾静脉抽取血样。4℃离心分离血浆,用ELISA法检测PPS601水平。融合蛋白(第2位G取代A)GLP-1-中间接头-胰高血糖素受体功能区-1-中间接头-胰高血糖素受体功能区-3-中间接头-人IgG1 Fc(PPS 601)的体内药代动力学结果见图4,本发明的融合蛋白在体内的半衰期较单独的GLP-1明显延长。In vivo pharmacokinetics of the fusion protein: C57BL/6 mice were injected intravenously with the fusion protein (50nM), and extracted from the tail vein at 0min, 1hr, 6hr, 12hr, 24hr, 36hr, 48hr, 60hr and 72hr after injection blood sample. Plasma was separated by centrifugation at 4°C, and the level of PPS601 was detected by ELISA. Fusion protein (2nd G replaces A) GLP-1-middle linker-glucagon receptor functional region-1-middle linker-glucagon receptor functional region-3-middle linker-human IgG1 Fc(PPS The in vivo pharmacokinetic results of 601) are shown in Figure 4, and the half-life of the fusion protein of the present invention is significantly longer than that of GLP-1 alone.

实施例8Example 8

ELISA法检测鼠血浆中融合蛋白的浓度Detection of Fusion Protein Concentration in Rat Plasma by ELISA

用ELISA方法鉴定鼠血浆中总融合蛋白的浓度。用PBS稀释的抗人IgG gamma链特异亲和提取的抗体(Sigma,USA)100μl(2μg/ml)包被96孔酶标板(Nunc-Immunoplate Maxisorp;Nalge NuncInternational,Demark),4℃过夜。洗涤4次后,用1%BSA-PBS 300μl室温封闭2hr。加入用0.5%BSA-PBS稀释的PPS601标准品及血清,室温作用2hr。洗涤四次后,加入HRP标记的羊抗人IgG(JacksonImmunoResearch,USA),室温作用1hr,然后加入TMB,室温作用20分钟。用硫酸中止反应后测定450-570nm值。The concentration of total fusion protein in mouse plasma was identified by ELISA method. 100 μl (2 μg/ml) of an anti-human IgG gamma chain-specific affinity-extracted antibody (Sigma, USA) diluted in PBS was used to coat a 96-well microtiter plate (Nunc-Immunoplate Maxisorp; Nalge Nunc International, Demark), overnight at 4°C. After washing 4 times, block with 300 μl of 1% BSA-PBS for 2 hr at room temperature. Add PPS601 standard substance and serum diluted with 0.5% BSA-PBS, and react at room temperature for 2 hours. After washing four times, HRP-labeled goat anti-human IgG (Jackson ImmunoResearch, USA) was added for 1 hr at room temperature, then TMB was added for 20 min at room temperature. The 450-570nm value was determined after quenching the reaction with sulfuric acid.

实施例9Example 9

融合蛋白对小鼠耐糖能力的影响Effect of Fusion Protein on Glucose Tolerance in Mice

给予融合蛋白的小鼠耐糖实验:给过夜(16-18h)绝食的小鼠(C57BL/6)皮下注射不同剂量的融合蛋白(4ug/kg,16ug/kg,80ug/kg和1mg/kg)或生理盐水,注射30min和24h后,按1.5mg/g体重腹腔注射葡萄糖,并分别于注射后0,10,20,30,60,90,和120min后从尾尖采取血样。用葡萄糖表通过葡萄糖酶方法检测血中葡萄糖水平。给予融合蛋白PPS 601的小鼠耐糖实验结果见图5,给予本发明的融合蛋白后,小鼠的耐糖能力明显增强。Glucose tolerance test of mice given fusion protein: subcutaneous injection of different doses of fusion protein (4ug/kg, 16ug/kg, 80ug/kg and 1mg/kg) to overnight (16-18h) fasted mice (C57BL/6) or 30min and 24h after normal saline injection, glucose was injected intraperitoneally at 1.5mg/g body weight, and blood samples were collected from the tail tip at 0, 10, 20, 30, 60, 90, and 120min after injection. Glucose levels in the blood were measured by the glucose enzymatic method with a glucose meter. The results of the glucose tolerance test of mice administered with the fusion protein PPS 601 are shown in Figure 5. After administration of the fusion protein of the present invention, the glucose tolerance of the mice was significantly enhanced.

序列表sequence listing

<110>东北师范大学<110>Northeast Normal University

<120>GLP-1融合蛋白及其制备方法和医药用途<120>GLP-1 fusion protein and its preparation method and medical application

<130>GLP-1<130>GLP-1

<160>37<160>37

<170>PatentIn version 3.3<170>PatentIn version 3.3

<210>1<210>1

<211>31<211>31

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(2)..(2)<222>(2)..(2)

<223>第2位的Xaa是Ala,Gly,Ser或Thr;<223> The second Xaa is Ala, Gly, Ser or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(3)..(3)<222>(3)..(3)

<223>第3位的Xaa是Glu,Asp,Gln或Asn;<223> The third Xaa is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(5)..(5)<222>(5)..(5)

<223>第5位的Xaa是Thr,Arg或Ile;<223> Xaa at position 5 is Thr, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(6)..(6)<222>(6)..(6)

<223>第6位的Xaa是Phe,Tyr或Leu;<223> The 6th Xaa is Phe, Tyr or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(8)..(8)<222>(8)..(8)

<223>第8位的Xaa是Ser或Asn;<223> the 8th Xaa is Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(9)..(9)<222>(9)..(9)

<223>第9位的Xaa是Asp或Asn;<223> The ninth Xaa is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(10)..(10)<222>(10)..(10)

<223>第10位的Xaa是Val,Ile,Met或Ala;<223> The 10th Xaa is Val, Ile, Met or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(11)..(11)<222>(11)..(11)

<223>第11位的Xaa是Ser,Thr,Ala或Asp;<223> The 11th Xaa is Ser, Thr, Ala or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(12)..(12)<222>(12)..(12)

<223>第12位的Xaa是Ser,Gln,Glu,Asn或Thr;<223> Xaa at position 12 is Ser, Gln, Glu, Asn or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(13)..(13)<222>(13)..(13)

<223>第13位的Xaa是Tyr,Phe,Gln,His或Leu;<223> The 13th Xaa is Tyr, Phe, Gln, His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(14)..(14)<222>(14)..(14)

<223>第14位的Xaa是Leu,Thr或Ser;<223> The 14th Xaa is Leu, Thr or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(15)..(15)<222>(15)..(15)

<223>第15位的Xaa是Glu,Gln,Asn,Asp,Arg或Lys;<223> Xaa at position 15 is Glu, Gln, Asn, Asp, Arg or Lys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(16)..(16)<222>(16)..(16)

<223>第16位的Xaa是Gly,Glu,Asp,Gln,Asn,Arg或Lys;<223> Xaa at position 16 is Gly, Glu, Asp, Gln, Asn, Arg or Lys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(17)..(17)<222>(17)..(17)

<223>第17位的Xaa是Gln,Lys,Leu或Phe;<223> Xaa at position 17 is Gln, Lys, Leu or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(18)..(18)<222>(18)..(18)

<223>第18位的Xaa是Ala或Lys;<223> Xaa at the 18th place is Ala or Lys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(19)..(19)<222>(19)..(19)

<223>第19位的Xaa是Ala,Thr,Ile或Ser;<223> Xaa at position 19 is Ala, Thr, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Lys,Arg或Gln;<223> Xaa at position 20 is Lys, Arg or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Glu,Asp,Asn,Ala,Ser,Lys或Arg;<223> Xaa at position 21 is Glu, Asp, Asn, Ala, Ser, Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(23)..(23)<222>(23)..(23)

<223>第23位的Xaa是Ile或Val;<223> Xaa at the 23rd position is Ile or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Ala,Ser,Asp,Glu,Gly或Thr;<223> Xaa at the 24th position is Ala, Ser, Asp, Glu, Gly or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(25)..(25)<222>(25)..(25)

<223>第25位的Xaa是Trp,Arg,Lys或Ser;<223> Xaa at position 25 is Trp, Arg, Lys or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(26)..(26)<222>(26)..(26)

<223>第26位的Xaa是Val,Lys,Ile,Ser或Ala;<223> Xaa at position 26 is Val, Lys, Ile, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(28)..(28)<222>(28)..(28)

<223>第28位的Xaa是Lys,Arg,Asn,Gln,Ser,Ala或Thr;<223> Xaa at position 28 is Lys, Arg, Asn, Gln, Ser, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(29)..(29)<222>(29)..(29)

<223>第29位的Xaa是Gly,Tyr或Ser;<223> Xaa at position 29 is Gly, Tyr or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Arg,Lys,Gln,Asp,Asn,Gly,Ala或Pro;<223> Xaa at position 30 is Arg, Lys, Gln, Asp, Asn, Gly, Ala or Pro;

<220><220>

<221>misc_feature<221>misc_feature

<222>(31)..(31)<222>(31)..(31)

<223>第31位的Xaa是Gly,Pro,Val,Arg,Lys或Ala或被去除;<223> Xaa at position 31 is Gly, Pro, Val, Arg, Lys or Ala or is removed;

<400>1<400>1

His Xaa Xaa Gly Xaa Xaa Thr Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa XaaHis Xaa Xaa Gly Xaa Xaa Thr Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa

1               5                   10                  151 5 10 15

Xaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Phe Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa

            20                  25                  3020 25 30

<210>2<210>2

<211>452<211>452

<212>PRT<212>PRT

<213>人<213> people

<400>2<400>2

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

                85                  90                  9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Val Met Tyr Thr Val Gly Tyr Ser Leu Ser LeuTyr Ser Ser Phe Gln Val Met Tyr Thr Val Gly Tyr Ser Leu Ser Leu

        115                 120                 125115 120 125

Gly Ala Leu Leu Leu Ala Leu Ala Ile Leu Gly Gly Leu Ser Lys LeuGly Ala Leu Leu Leu Ala Leu Ala Ile Leu Gly Gly Leu Ser Lys Leu

    130                 135                 140130 135 140

His Cys Thr Arg Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe ValHis Cys Thr Arg Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val

145                 150                 155                 160145 150 155 160

Leu Lys Ala Ser Ser Val Leu Val Ile Asp Gly Leu Leu Arg Thr ArgLeu Lys Ala Ser Ser Val Leu Val Ile Asp Gly Leu Leu Arg Thr Arg

                165                 170                 175165 170 175

Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu SerTyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu Ser

            180                 185                 190180 185 190

Asp Gly Ala Val Ala Gly Cys Arg Val Ala Ala Val Phe Met Gln TyrAsp Gly Ala Val Ala Gly Cys Arg Val Ala Ala Val Phe Met Gln Tyr

        195                 200                 205195 200 205

Gly Ile Val Ala Asn Tyr Cys Trp Leu Leu Val Glu Gly Leu Tyr LeuGly Ile Val Ala Asn Tyr Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu

    210                 215                 220210 215 220

His Asn Leu Leu Gly Leu Ala Thr Leu Pro Glu Arg Ser Phe Phe SerHis Asn Leu Leu Gly Leu Ala Thr Leu Pro Glu Arg Ser Phe Phe Ser

225                 230                 235                 240225 230 235 240

Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met Leu Phe Val Val ProLeu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met Leu Phe Val Val Pro

                245                 250                 255245 250 255

Trp Ala Val Val Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr SerTrp Ala Val Val Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser

            260                 265                 270260 265 270

Asn Asp Asn Met Gly Phe Trp Trp Ile Leu Arg Phe Pro Val Phe LeuAsn Asp Asn Met Gly Phe Trp Trp Ile Leu Arg Phe Pro Val Phe Leu

        275                 280                 285275 280 285

Ala Ile Leu Ile Asn Phe Phe Ile Phe Val Arg Ile Val Gln Leu LeuAla Ile Leu Ile Asn Phe Phe Ile Phe Val Arg Ile Val Gln Leu Leu

    290                 295                 300290 295 300

Val Ala Lys Leu Arg Ala Arg Gln Met His His Thr Asp Tyr Lys PheVal Ala Lys Leu Arg Ala Arg Gln Met His His Thr Asp Tyr Lys Phe

305                 310                 315                 320305 310 315 320

Arg Leu Ala Lys Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Val HisArg Leu Ala Lys Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Val His

                325                 330                 335325 330 335

Glu Val Val Phe Ala Phe Val Thr Asp Glu His Ala Gln Gly Thr LeuGlu Val Val Phe Ala Phe Val Thr Asp Glu His Ala Gln Gly Thr Leu

            340                 345                 350340 345 350

Arg Ser Ala Lys Leu Phe Phe Asp Leu Phe Leu Ser Ser Phe Gln GlyArg Ser Ala Lys Leu Phe Phe Asp Leu Phe Leu Ser Ser Phe Gln Gly

        355                 360                 365355 360 365

Leu Leu Val Ala Val Leu Tyr Cys Phe Leu Asn Lys Glu Val Gln SerLeu Leu Val Ala Val Leu Tyr Cys Phe Leu Asn Lys Glu Val Gln Ser

    370                 375                 380370 375 380

Glu Leu Arg Arg Arg Trp His Arg Trp Arg Leu Gly Lys Val Leu TrpGlu Leu Arg Arg Arg Trp His Arg Trp Arg Leu Gly Lys Val Leu Trp

385                 390                 395                 400385 390 395 400

Glu Glu Arg Asn Thr Ser Asn His Arg Ala Ser Ser Ser Pro Gly HisGlu Glu Arg Asn Thr Ser Asn His Arg Ala Ser Ser Ser Pro Gly His

                405                 410                 415405 410 415

Gly Pro Pro Ser Lys Glu Leu Gln Phe Gly Arg Gly Gly Gly Ser GlnGly Pro Pro Ser Lys Glu Leu Gln Phe Gly Arg Gly Gly Gly Ser Gln

            420                 425                 430420 425 430

Asp Ser Ser Ala Glu Thr Pro Leu Ala Gly Gly Leu Pro Arg Leu AlaAsp Ser Ser Ala Glu Thr Pro Leu Ala Gly Gly Leu Pro Arg Leu Ala

        435                 440                 445435 440 445

Glu Ser Pro PheGlu Ser Pro Phe

    450450

<210>3<210>3

<211>117<211>117

<212>PRT<212>PRT

<213>人<213> people

<400>3<400>3

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp ValArg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp ValArg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

               85                  90                  9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe GlnTyr Ser Ser Phe Gln

        115115

<210>4<210>4

<211>32<211>32

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(1)..(1)<222>(1)..(1)

<223>第1位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser<223> The first Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223>The 32nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<400>4<400>4

Xaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly AspXaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly Asp

1               5                   10                  151 5 10 15

Asp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly XaaAsp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly Xaa

            20                  25                  3020 25 30

<210>5<210>5

<211>20<211>20

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(1)..(1)<222>(1)..(1)

<223>第1位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223> The first Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 20th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>5<400>5

Xaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser Asn Asp AsnXaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser Asn Asp Asn

1               5                   10                  151 5 10 15

Met Gly Phe XaaMet Gly Phe Xaa

            2020

<210>6<210>6

<211>20<211>20

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(1)..(1)<222>(1)..(1)

<223>第1位的Xaa是Thr Leu Thr Leu Ile Pro Leu Leu Gly Val His Glu Val Val PheAla<223> The first Xaa is Thr Leu Thr Leu Ile Pro Leu Leu Gly Val His Glu Val Val PheAla

Phe Val Thr,从N-端起,所有氨基酸可被逐一去除;Phe Val Thr, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Leu Phe Leu Ser Ser Phe Gln Gly Leu Leu Val Ala Val LeuTyr Cys<223>The 20th Xaa is Leu Phe Leu Ser Ser Phe Gln Gly Leu Leu Val Ala Val LeuTyr Cys

Phe Leu Asn,从C-端起,所有氨基酸可被逐一去除;Phe Leu Asn, from the C-terminus, all amino acids can be removed one by one;

<400>6<400>6

Xaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser Asn Asp AsnXaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser Asn Asp Asn

1               5                   10                  151 5 10 15

Met Gly Phe XaaMet Gly Phe Xaa

            2020

<210>7<210>7

<211>55<211>55

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(1)..(1)<222>(1)..(1)

<223>第1位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu Lys AlaSer<223> The first Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu Lys AlaSer

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223>The 32nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer<223> The 33rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除<223> Xaa at position 34 is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除<223> The 35th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 36th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(55)..(55)<222>(55)..(55)

<223>第55位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223>The 55th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>7<400>7

Xaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly AspXaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly Asp

1               5                   10                  151 5 10 15

Asp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly XaaAsp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly Xaa

            20                  25                  3020 25 30

Xaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr SerXaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser

        35                  40                  4535 40 45

Asn Asp Asn Met Gly Phe XaaAsn Asp Asn Met Gly Phe Xaa

    50                  5550 55

<210>8<210>8

<211>53<211>53

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(1)..(1)<222>(1)..(1)

<223>第1位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu Lys AlaSer<223> The first Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu Lys AlaSer

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223>The 32nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer<223> The 33rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除<223> Xaa at position 34 is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除<223> The 35th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 36th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(53)..(53)<222>(53)..(53)

<223>第53位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223>The 53rd Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>8<400>8

Xaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly AspXaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly Asp

1               5                  10                  151 5 10 15

Asp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly XaaAsp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly Xaa

            20                  25                  3020 25 30

Xaa Xaa Xaa Xaa Asp Glu His Ala Gln Gly Thr Leu Arg Ser Ala LysXaa Xaa Xaa Xaa Asp Glu His Ala Gln Gly Thr Leu Arg Ser Ala Lys

        35                  40                  4535 40 45

Leu Phe Phe Asp XaaLeu Phe Phe Asp Xaa

    5050

<210>9<210>9

<211>41<211>41

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(1)..(1)<222>(1)..(1)

<223>第1位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met Leu PheVal<223> The first Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met Leu PheVal

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 20th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氮基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 21st Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(22)..(22)<222>(22)..(22)

<223>第22位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 22nd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(23)..(23)<222>(23)..(23)

<223>第23位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 23rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 24th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(41)..(41)<222>(41)..(41)

<223>第41位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 41st Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>9<400>9

Xaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser Asn Asp AsnXaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser Asn Asp Asn

1               5                   10                  151 5 10 15

Met Gly Phe Xaa Xaa Xaa Xaa Xaa Asp Glu His Ala Gln Gly Thr LeuMet Gly Phe Xaa Xaa Xaa Xaa Xaa Asp Glu His Ala Gln Gly Thr Leu

            20                  25                  3020 25 30

Arg Ser Ala Lys Leu Phe Phe Asp XaaArg Ser Ala Lys Leu Phe Phe Asp Xaa

        35                  4035 40

<210>10<210>10

<211>76<211>76

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(1)..(1)<222>(1)..(1)

<223>第1位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser<223> The first Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223>The 32nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 33rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 34th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 35th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 36th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(55)..(55)<222>(55)..(55)

<223>第55位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223>The 55th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(56)..(56)<222>(56)..(56)

<223>第56位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 56th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(57)..(57)<222>(57)..(57)

<223>第57位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 57th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(58)..(58)<222>(58)..(58)

<223>第58位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 58th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(59)..(59)<222>(59)..(59)

<223>第59位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 59th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(76)..(76)<222>(76)..(76)

<223>第76位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 76th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>10<400>10

Xaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly AspXaa Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile Gly Asp

1               5                   10                  151 5 10 15

Asp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly XaaAsp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala Gly Xaa

            20                  25                  3020 25 30

Xaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr SerXaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn Val Gln Cys Trp Thr Ser

        35                  40                  4535 40 45

Asn Asp Asn Met Gly Phe Xaa Xaa Xaa Xaa Xaa Asp Glu His Ala GlnAsn Asp Asn Met Gly Phe Xaa Xaa Xaa Xaa Xaa Asp Glu His Ala Gln

    50                  55                  6050 55 60

Gly Thr Leu Arg Ser Ala Lys Leu Phe Phe Asp XaaGly Thr Leu Arg Ser Ala Lys Leu Phe Phe Asp Xaa

65                  70                  7565 70 75

<210>11<210>11

<211>152<211>152

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(118)..(118)<222>(118)..(118)

<223>第118位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 118th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 119th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 120th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser<223> The 121st Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223> The 152nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<400>11<400>11

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                   151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

     50                  55                   6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                   75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

              85                   90                   9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg ThrTyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg Thr

        115                 120                 125115 120 125

Arg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp LeuArg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu

    130                 135                 140130 135 140

Ser Asp Gly Ala Val Ala Gly XaaSer Asp Gly Ala Val Ala Gly Xaa

145                 150145 150

<210>12<210>12

<211>140<211>140

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(118)..(118)<222>(118)..(118)

<223>第118位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 118th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 119th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 120th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 121st Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(140)..(140)<222>(140)..(140)

<223>第140位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 140th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>12<400>12

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

                85                  90                  9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn ValTyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn Val

        115                 120                 125115 120 125

Gln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe XaaGln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe Xaa

    130                 135                 140130 135 140

<210>13<210>13

<211>138<211>138

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(118)..(118)<222>(118)..(118)

<223>第118位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 118th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 119th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 120th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 121st Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(138)..(138)<222>(138)..(138)

<223>第138位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223>The 138th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>13<400>13

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

                85                  90                  9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Asp Glu His Ala Gln Gly ThrTyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Asp Glu His Ala Gln Gly Thr

      115                 120                 125115 120 125

Leu Arg Ser Ala Lys Leu Phe Phe Asp XaaLeu Arg Ser Ala Lys Leu Phe Phe Asp Xaa

  130                 135130 135

<210>14<210>14

<211>175<211>175

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(118)..(118)<222>(118)..(118)

<223>第118位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 118th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 119th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 120th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser<223> The 121st Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223> The 152nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 153rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly ProGly或Gly Gly Gly GlySer或被去除;<223> The 154th Xaa is Gly Thr Gly, Gly Ala Pro, Gly ProGly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 155th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223> The 156th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 175th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>14<400>14

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

                85                  90                  9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg ThrTyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg Thr

        115                 120                 125115 120 125

Arg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp LeuArg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu

    130                 135                 140130 135 140

Ser Asp Gly Ala Val Ala Gly Xaa Xaa Xaa Xaa Xaa Lys Cys Leu PheSer Asp Gly Ala Val Ala Gly Xaa Xaa Xaa Xaa Xaa Lys Cys Leu Phe

145                 150                 155                 160145 150 155 160

Glu Asn Val Gln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe XaaGlu Asn Val Gln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe Xaa

                165                 170                 175165 170 175

<210>15<210>15

<211>173<211>173

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(118)..(118)<222>(118)..(118)

<223>第118位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 118th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 119th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 120th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser<223> The 121st Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223> The 152nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 153rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或GlyGly Gly GlySer或被去除;<223> The 154th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or GlyGly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 155th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223> The 156th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 173rd Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>15<400>15

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

                85                  90                  9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg ThrTyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg Thr

        115                 120                 125115 120 125

Arg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp LeuArg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu

    130                 135                 140130 135 140

Ser Asp Gly Ala Val Ala Gly Xaa Xaa Xaa Xaa Xaa Asp Glu His AlaSer Asp Gly Ala Val Ala Gly Xaa Xaa Xaa Xaa Xaa Asp Glu His Ala

145                 150                 155                 160145 150 155 160

Gln Gly Thr Leu Arg Ser Ala Lys Leu Phe Phe Asp XaaGln Gly Thr Leu Arg Ser Ala Lys Leu Phe Phe Asp Xaa

                165                 170165 170

<210>16<210>16

<211>161<211>161

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(118)..(118)<222>(118)..(118)

<223>第118位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 118th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 119th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 120th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223>The 121st Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(140)..(140)<222>(140)..(140)

<223>第140位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 140th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(141)..(141)<222>(141)..(141)

<223>第141位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 141st Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(142)..(142)<222>(142)..(142)

<223>第142位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 142nd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(143)..(143)<222>(143)..(143)

<223>第143位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 143rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(144)..(144)<222>(144)..(144)

<223>第144位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223> The 144th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 161st Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>16<400>16

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

                85                  90                  9585 90 95

Gln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys MetGln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn ValTyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Lys Cys Leu Phe Glu Asn Val

        115                 120                 125115 120 125

Gln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe Xaa Xaa Xaa Xaa XaaGln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe Xaa Xaa Xaa Xaa Xaa

    130                 135                 140130 135 140

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

145                 150                 155                 160145 150 155 160

XaaXaa

<210>17<210>17

<211>196<211>196

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(118)..(118)<222>(118)..(118)

<223>第118位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 118th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 119th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 120th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser<223> The 121st Xaa is Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Ser

Ser Val Leu Val,从N-端起,所有氨基酸可被逐一去除;Ser Val Leu Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr<223> The 152nd Xaa is Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile Val AlaAsn Tyr

Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu,从C-端起,所有氨基酸可被逐一去除;Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 153rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 154th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 155th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223> The 156th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 175th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(176)..(176)<222>(176)..(176)

<223>第176位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 176th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(177)..(177)<222>(177)..(177)

<223>第177位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 177th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 178th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val<223> The 179th Xaa is Phe Ser Leu Tyr Leu Gly Ile Gly Trp Gly Ala Pro Met LeuPhe Val

Val Pro Trp Ala Val Val,从N-端起,所有氨基酸可被逐一去除;Val Pro Trp Ala Val Val, from the N-terminus, all amino acids can be removed one by one;

<220><220>

<221>misc_feature<221>misc_feature

<222>(196)..(196)<222>(196)..(196)

<223>第196位的Xaa是Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe<223> The 196th Xaa is Trp Trp Ile Leu Arg Phe Pro Val Phe Leu Ala Ile Leu IleAsn Phe

Phe Ile Phe Val Arg Ile Val,从C-端起,所有氨基酸可被逐一去除;Phe Ile Phe Val Arg Ile Val, from the C-terminus, all amino acids can be removed one by one;

<400>17<400>17

Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly AspAla Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr Gly Asp

1               5                   10                  151 5 10 15

Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu ValGln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu Leu Val

            20                  25                  3020 25 30

Cys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro AlaCys Asn Arg Thr Phe Asp Lys Tyr Ser Cys Trp Pro Asp Thr Pro Ala

        35                  40                  4535 40 45

Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His HisAsn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp His His

    50                  55                  6050 55 60

Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly GlnLys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp Gly Gln

65                  70                  75                  8065 70 75 80

Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln CysTrp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser Gln Cys

                85                  90                  9585 90 95

ln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Metln Met Asp Gly Glu Glu Ile Glu Val Gln Lys Glu Val Ala Lys Met

            100                 105                 110100 105 110

Tyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg ThrTyr Ser Ser Phe Gln Xaa Xaa Xaa Xaa Ile Asp Gly Leu Leu Arg Thr

        115                 120                 125115 120 125

Arg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp LeuArg Tyr Ser Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu

    130                 135                 140130 135 140

Ser Asp Gly Ala Val Ala Gly Xaa Xaa Xaa Xaa Xaa Lys Cys Leu PheSer Asp Gly Ala Val Ala Gly Xaa Xaa Xaa Xaa Xaa Lys Cys Leu Phe

145                 150                 155                 160145 150 155 160

Glu Asn Val Gln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe Xaa XaaGlu Asn Val Gln Cys Trp Thr Ser Asn Asp Asn Met Gly Phe Xaa Xaa

                165                 170                 175165 170 175

Xaa Xaa Xaa Asp Glu His Ala Gln Gly Thr Leu Arg Ser Ala Lys LeuXaa Xaa Xaa Asp Glu His Ala Gln Gly Thr Leu Arg Ser Ala Lys Leu

            180                 185                 190180 185 190

Phe Phe Asp XaaPhe Phe Asp Xaa

        195195

<210>18<210>18

<211>440<211>440

<212>PRT<212>PRT

<213>人<213> people

<400>18<400>18

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

            100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Ile Ile Tyr Thr Val GlySer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Ile Ile Tyr Thr Val Gly

        115                 120                 125115 120 125

Tyr Ala Leu Ser Phe Ser Ala Leu Val Ile Ala Ser Ala Ile Leu LeuTyr Ala Leu Ser Phe Ser Ala Leu Val Ile Ala Ser Ala Ile Leu Leu

    130                 135                 140130 135 140

Gly Phe Arg His Leu His Cys Thr Arg Asn Tyr Ile His Leu Asn LeuGly Phe Arg His Leu His Cys Thr Arg Asn Tyr Ile His Leu Asn Leu

145                 150                 155                 160145 150 155 160

Phe Ala Ser Phe Ile Leu Arg Ala Leu Ser Val Phe Ile Lys Asp AlaPhe Ala Ser Phe Ile Leu Arg Ala Leu Ser Val Phe Ile Lys Asp Ala

                165                 170                 175165 170 175

Ala Leu Lys Trp Met Tyr Ser Thr Ala Ala Gln Gln His Gln Trp AspAla Leu Lys Trp Met Tyr Ser Thr Ala Ala Gln Gln His Gln Trp Asp

            180                 185                 190180 185 190

Gly Leu Leu Ser Tyr Gln Asp Ser Leu Ser Cys Arg Leu Val Phe LeuGly Leu Leu Ser Tyr Gln Asp Ser Leu Ser Cys Arg Leu Val Phe Leu

        195                 200                 205195 200 205

Leu Met Gln Tyr Cys Val Ala Ala Asn Tyr Tyr Trp Leu Leu Val GluLeu Met Gln Tyr Cys Val Ala Ala Asn Tyr Tyr Trp Leu Leu Val Glu

    210                 215                 220210 215 220

Gly Val Tyr Leu Tyr Thr Leu Leu Ala Phe Ser Val Phe Ser Glu GlnGly Val Tyr Leu Tyr Thr Leu Leu Ala Phe Ser Val Phe Ser Glu Gln

225                 230                 235                 240225 230 235 240

Trp Ile Phe Arg Leu Tyr Val Ser Ile Gly Trp Gly Val Pro Leu LeuTrp Ile Phe Arg Leu Tyr Val Ser Ile Gly Trp Gly Val Pro Leu Leu

                245                 250                 255245 250 255

Phe Val Val Pro Trp Gly Ile Val Lys Tyr Leu Tyr Glu Asp Glu GlyPhe Val Val Pro Trp Gly Ile Val Lys Tyr Leu Tyr Glu Asp Glu Gly

            260                 265                 270260 265 270

Cys Trp Thr Arg Asn Ser Asn Met Asn Tyr Trp Leu Ile Ile Arg LeuCys Trp Thr Arg Asn Ser Asn Met Asn Tyr Trp Leu Ile Ile Arg Leu

        275                 280                 285275 280 285

Pro Ile Leu Phe Ala Ile Gly Val Asn Phe Leu Ile Phe Val Arg ValPro Ile Leu Phe Ala Ile Gly Val Asn Phe Leu Ile Phe Val Arg Val

    290                 295                 300290 295 300

Ile Cys Ile Val Val Ser Lys Leu Lys Ala Asn Leu Met Cys Lys ThrIle Cys Ile Val Val Ser Lys Leu Lys Ala Asn Leu Met Cys Lys Thr

305                 310                 315                 320305 310 315 320

Asp Ile Lys Cys Arg Leu Ala Lys Ser Thr Leu Thr Leu Ile Pro LeuAsp Ile Lys Cys Arg Leu Ala Lys Ser Thr Leu Thr Leu Ile Pro Leu

                325                 330                 335325 330 335

Leu Gly Thr His Glu Val Ile Phe Ala Phe Val Met Asp Glu His AlaLeu Gly Thr His Glu Val Ile Phe Ala Phe Val Met Asp Glu His Ala

            340                 345                 350340 345 350

Arg Gly Thr Leu Arg Phe Ile Lys Leu Phe Thr Glu Leu Ser Phe ThrArg Gly Thr Leu Arg Phe Ile Lys Leu Phe Thr Glu Leu Ser Phe Thr

        355                 360                 365355 360 365

Ser Phe Gln Gly Leu Met Val Ala Ile Leu Tyr Cys Phe Val Asn AsnSer Phe Gln Gly Leu Met Val Ala Ile Leu Tyr Cys Phe Val Asn Asn

    370                 375                 380370 375 380

Glu Val Gln Leu Glu Phe Arg Lys Ser Trp Glu Arg Trp Arg Leu GluGlu Val Gln Leu Glu Phe Arg Lys Ser Trp Glu Arg Trp Arg Leu Glu

385                 390                 395                 400385 390 395 400

His Leu His Ile Gln Arg Asp Ser Ser Met Lys Pro Leu Lys Cys ProHis Leu His Ile Gln Arg Asp Ser Ser Met Lys Pro Leu Lys Cys Pro

                405                 410                 415405 410 415

Thr Ser Ser Leu Ser Ser Gly Ala Thr Ala Gly Ser Ser Met Tyr ThrThr Ser Ser Leu Ser Ser Gly Ala Thr Ala Gly Ser Ser Met Tyr Thr

            420                 425                 430420 425 430

Ala Thr Cys Gln Ala Ser Cys SerAla Thr Cys Gln Ala Ser Cys Ser

        435                 440435 440

<210>19<210>19

<211>122<211>122

<212>PRT<212>PRT

<213>人<213> people

<400>19<400>19

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

yr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Pheyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

            100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu TyrSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr

        115                 120115 120

<210>20<210>20

<211>78<211>78

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(2)..(2)<222>(2)..(2)

<223>第2位的Xaa是Tyr,Ala或被去除;<223> The second Xaa is Tyr, Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(5)..(5)<222>(5)..(5)

<223>第5位的Xaa是Leu,Ala,Met或被去除;<223> The 5th Xaa is Leu, Ala, Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(9)..(9)<222>(9)..(9)

<223>第9位的Xaa是Ala,Gly或被去除;<223> The ninth Xaa is Ala, Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(12)..(12)<222>(12)..(12)

<223>第12位的Xaa是Ile,Val,Met或被去除;<223> The 12th Xaa is Ile, Val, Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(14)..(14)<222>(14)..(14)

<223>第14位的Xaa是Leu,Val或被去除;<223> The 14th Xaa is Leu, Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(15)..(15)<222>(15)..(15)

<223>第15位的Xaa是Arg,Lys或被去除;<223> Xaa at position 15 is Arg, Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(16)..(16)<222>(16)..(16)

<223>第16位的Xaa是Ala,Ser或被去除;<223> Xaa at the 16th position is Ala, Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(17)..(17)<222>(17)..(17)

<223>第17位的Xaa是Leu,Ser或被去除;<223> The 17th Xaa is Leu, Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(19)..(19)<222>(19)..(19)

<223>第19位的Xaa是Val,Leu或被去除;<223> The 19th Xaa is Val, Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Phe,Leu或被去除;<223> Xaa at the 20th place is Phe, Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Ile,Val或被去除;<223> Xaa at the 21st position is Ile, Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(22)..(22)<222>(22)..(22)

<223>第22位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 22 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 24 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(25)..(25)<222>(25)..(25)

<223>第25位的Xaa是Ala,Leu或Val;<223> The 25th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(27)..(27)<222>(27)..(27)

<223>第27位的Xaa是Lys,Arg或Asp;<223> Xaa at position 27 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(28)..(28)<222>(28)..(28)

<223>第28位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 28 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(29)..(29)<222>(29)..(29)

<223>第29位的Xaa是Met,Arg或Ser;<223> Xaa at the 29th position is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Tyr或Asn;<223> Xaa at the 30th place is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(31)..(31)<222>(31)..(31)

<223>第31位的Xaa是Ser或Arg;<223> Xaa at the 31st position is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Thr,Gln或Ala;<223> Xaa at position 32 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Lys,Arg或去除;<223> Xaa at position 33 is Lys, Arg or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Ala,Ile或Ser;<223> Xaa at position 34 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Ala,Gly或Ile;<223> Xaa at position 35 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 36 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(37)..(37)<222>(37)..(37)

<223>第37位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 37 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(38)..(38)<222>(38)..(38)

<223>第38位的Xaa是His或Leu;<223> Xaa at the 38th place is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(39)..(39)<222>(39)..(39)

<223>第39位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 39 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(40)..(40)<222>(40)..(40)

<223>第40位的Xaa是Trp,Val或Gln;<223> Xaa at position 40 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(41)..(41)<222>(41)..(41)

<223>第41位的Xaa是Asp或Ser;<223> Xaa at position 41 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(42)..(42)<222>(42)..(42)

<223>第42位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 42 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(43)..(43)<222>(43)..(43)

<223>第43位的Xaa是Arg或去除;<223> Xaa at position 43 is Arg or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(44)..(44)<222>(44)..(44)

<223>第44位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 44 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(46)..(46)<222>(46)..(46)

<223>第46位的Xaa是Ser或Asp;<223> Xaa at position 46 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(47)..(47)<222>(47)..(47)

<223>第47位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 47 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(48)..(48)<222>(48)..(48)

<223>第48位的Xaa是Gln,Glu或Gly;<223> Xaa at position 48 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(49)..(49)<222>(49)..(49)

<223>第49位的Xaa是Asp,Ala或Thr;<223> Xaa at position 49 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(50)..(50)<222>(50)..(50)

<223>第50位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 50 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(51)..(51)<222>(51)..(51)

<223>第51位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 51 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(52)..(52)<222>(52)..(52)

<223>第52位的Xaa是Ser,Gly或Ala;<223> Xaa at position 52 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(53)..(53)<222>(53)..(53)

<223>第53位的Xaa是Cys或被去除;<223> Xaa at position 53 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(54)..(54)<222>(54)..(54)

<223>第54位的Xaa是Arg或被去除;<223> Xaa at position 54 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(55)..(55)<222>(55)..(55)

<223>第55位的Xaa是Leu,Val,Ala,Ser或被去除;<223> Xaa at position 55 is Leu, Val, Ala, Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(56)..(56)<222>(56)..(56)

<223>第56位的Xaa是Val,Ala或被去除;<223> Xaa at position 56 is Val, Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(57)..(57)<222>(57)..(57)

<223>第57位的Xaa是Phe,Ala,Thr,Met或被去除;<223> Xaa at position 57 is Phe, Ala, Thr, Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(58)..(58)<222>(58)..(58)

<223>第58位的Xaa是Leu,Val或被去除;<223> Xaa at position 58 is Leu, Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(59)..(59)<222>(59)..(59)

<223>第59位的Xaa是Leu,Phe,Met或被去除;<223> The 59th Xaa is Leu, Phe, Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(63)..(63)<222>(63)..(63)

<223>第63位的Xaa是Cys,Gly,Ser或被去除;<223> Xaa at position 63 is Cys, Gly, Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(64)..(64)<222>(64)..(64)

<223>第64位的Xaa是Val,Ile,Met或被去除;<223> Xaa at position 64 is Val, Ile, Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(65)..(65)<222>(65)..(65)

<223>第65位的Xaa是Ala,Val,Met,Ile或被去除;<223> Xaa at position 65 is Ala, Val, Met, Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(69)..(69)<222>(69)..(69)

<223>第69位的Xaa是Tyr,Cys或被去除;<223> Xaa at position 69 is Tyr, Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(76)..(76)<222>(76)..(76)

<223>第76位的Xaa是Val或Leu或被去除;<223> Xaa at position 76 is Val or Leu or is removed;

<400>20<400>20

Asn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa XaaAsn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa

1               5                   10                  151 5 10 15

Xaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa XaaXaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

            20                  25                  3020 25 30

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa

        35                  40                  4535 40 45

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa

    50                  55                  6050 55 60

Xaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr LeuXaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu

65                  70                  7565 70 75

<210>21<210>21

<211>64<211>64

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(2)..(2)<222>(2)..(2)

<223>第2位的Xaa是Arg或Ser或被去除;<223> the second Xaa is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(5)..(5)<222>(5)..(5)

<223>第5位的Xaa是Val或Leu或被去除;<223> Xaa at position 5 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(6)..(6)<222>(6)..(6)

<223>第6位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 6 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(11)..(11)<222>(11)..(11)

<223>第11位的Xaa是Val或Ala或被去除;<223> Xaa at position 11 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(13)..(13)<222>(13)..(13)

<223>第13位的Xaa是Leu或Met或被去除;<223> The 13th Xaa is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(17)..(17)<222>(17)..(17)

<223>第17位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 17 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 20 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 21 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(22)..(22)<222>(22)..(22)

<223>第22位的Xaa是Val或被去除;<223> Xaa at the 22nd position is Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(23)..(23)<222>(23)..(23)

<223>第23位的Xaa是Lys或被去除;<223> Xaa at position 23 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<222>第24位的Xaa是Tyr或Cys;<222> Xaa at the 24th position is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(26)..(26)<222>(26)..(26)

<223>第26位的Xaa是Tyr或Phe;<223> Xaa at the 26th place is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(28)..(28)<222>(28)..(28)

<223>第28位的Xaa是Asp或Asn;<223> Xaa at the 28th position is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(29)..(29)<222>(29)..(29)

<223>第29位的Xaa是Glu或Val;<223> the 29th Xaa is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 30 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Thr,Glu或Ser;<223> Xaa at position 33 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Arg或Ser;<223> Xaa at the 34th position is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 36 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(39)..(39)<222>(39)..(39)

<223>第39位的Xaa是Asn或Gly或被去除;<223> Xaa at position 39 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(40)..(40)<222>(40)..(40)

<223>第40位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 40 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(42)..(42)<222>(42)..(42)

<223>第42位的Xaa是Leu或Trp或被去除;<223> Xaa at the 42nd position is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(44)..(44)<222>(44)..(44)

<223>第44位的Xaa是Ile或Leu或被去除;<223> Xaa at position 44 is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(46)..(46)<222>(46)..(46)

<223>第46位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 46 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(48)..(48)<222>(48)..(48)

<223>第48位的Xaa是Ile或Val或被去除;<223> Xaa at position 48 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(49)..(49)<222>(49)..(49)

<223>第49位的Xaa是Leu或Phe或被去除;<223> Xaa at the 49th position is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(50)..(50)<222>(50)..(50)

<223>第50位的Xaa是Phe或Leu或被去除;<223> Xaa at position 50 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(53)..(53)<222>(53)..(53)

<223>第53位的Xaa是Gly或Leu或被去除;<223> Xaa at position 53 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(54)..(54)<222>(54)..(54)

<223>第54位的Xaa是Val或Ile或被去除;<223> Xaa at position 54 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(57)..(57)<222>(57)..(57)

<223>第57位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 57 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(62)..(62)<222>(62)..(62)

<223>第62位的Xaa是Val或Ile或被去除;<223> Xaa at position 62 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(63)..(63)<222>(63)..(63)

<223>第63位的Xaa是Ile或Val或被去除;<223> Xaa at position 63 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(64)..(64)<222>(64)..(64)

<223>第64位的Xaa是Gln或Cys或被去除;<223> Xaa at position 64 is Gln or Cys or is removed;

<400>21<400>21

Phe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe ValPhe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val

1               5                   10                  151 5 10 15

Xaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys TrpXaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp

            20                  25                  3020 25 30

Xaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro XaaXaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa

        35                  40                  4535 40 45

Xaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa XaaXaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa

    50                  55                  6050 55 60

<210>22<210>22

<211>57<211>57

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(11)..(11)<222>(11)..(11)

<223>第11位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 11 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(15)..(15)<222>(15)..(15)

<223>第15位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 15 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Met,Thr,Ile,Ala或被去除;<223> The 20th Xaa is Met, Thr, Ile, Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(23)..(23)<222>(23)..(23)

<223>第23位的Xaa是His,Pro,Gln或Thr;<223> The 23rd Xaa is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 24 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(25)..(25)<222>(25)..(25)

<223>第25位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 25 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(26)..(26)<222>(26)..(26)

<223>第26位的Xaa是Gly或Ser;<223> Xaa at position 26 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(27)..(27)<222>(27)..(27)

<223>第27位的Xaa是Thr,Leu,Phe或Ala;<223> The 27th Xaa is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Phe,Ser或Leu;<223> Xaa at the 30th place is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(31)..(31)<222>(31)..(31)

<223>第31位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 31 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Lys或Arg;<223> Xaa at position 32 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 35 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 36 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(38)..(38)<222>(38)..(38)

<223>第38位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 38 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(39)..(39)<222>(39)..(39)

<223>第39位的Xaa是Phe或Leu或被去除;<223> Xaa at position 39 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(40)..(40)<222>(40)..(40)

<223>第40位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 40 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(45)..(45)<222>(45)..(45)

<223>第45位的Xaa是Leu或Met或被去除;<223> The 45th Xaa is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(46)..(46)<222>(46)..(46)

<223>第46位的Xaa是Met或Leu或被去除;<223> Xaa at position 46 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(49)..(49)<222>(49)..(49)

<223>第49位的Xaa是Ile或Val或被去除;<223> Xaa at position 49 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(54)..(54)<222>(54)..(54)

<223>第54位的Xaa是Val或Leu或被去除;<223> Xaa at position 54 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(56)..(56)<222>(56)..(56)

<223>第56位的Xaa是Asn或Lys或被去除;<223> Xaa at position 56 is Asn or Lys or is removed;

<400>22<400>22

Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa PheSer Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa Phe

1               5                   10                  151 5 10 15

Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa XaaAla Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa Xaa

             20                  25                  3020 25 30

Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val AlaLeu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val Ala

        35                  40                  4535 40 45

Xaa Leu Tyr Cys Phe Xaa Asn Xaa GluXaa Leu Tyr Cys Phe Xaa Asn Xaa Glu

    50                  5550 55

<210>23<210>23

<211>145<211>145

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(2)..(2)<222>(2)..(2)

<223>第2位的Xaa是Tyr或Ala或被去除;<223> the second Xaa is Tyr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(5)..(5)<222>(5)..(5)

<223>第5位的Xaa是Leu,Ala或Met或被去除;<223> The 5th Xaa is Leu, Ala or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(9)..(9)<222>(9)..(9)

<223>第9位的Xaa是Ala或Gly或被去除;<223> Xaa at position 9 is Ala or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(12)..(12)<222>(12)..(12)

<223>第12位的Xaa是Ile,Val或Met或被去除;<223> Xaa at position 12 is Ile, Val or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(14)..(14)<222>(14)..(14)

<223>第14位的Xaa是Leu或Val或被去除;<223> The 14th Xaa is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(15)..(15)<222>(15)..(15)

<223>第15位的Xaa是Arg或Lys或被去除;<223> Xaa at position 15 is Arg or Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(16)..(16)<222>(16)..(16)

<223>第16位的Xaa是Ala或Ser或被去除;<223> Xaa at position 16 is Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(17)..(17)<222>(17)..(17)

<223>第17位的Xaa是Leu或Ser或被去除;<223> The 17th Xaa is Leu or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(19)..(19)<222>(19)..(19)

<223>第19位的Xaa是Val或Leu或被去除;<223> the 19th Xaa is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Phe或Leu或被去除;<223> Xaa at the 20th place is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Ile或Val或被去除;<223> Xaa at position 21 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(22)..(22)<222>(22)..(22)

<223>第22位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 22 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 24 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(25)..(25)<222>(25)..(25)

<223>第25位的Xaa是Ala,Leu或Val;<223> The 25th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(27)..(27)<222>(27)..(27)

<223>第27位的Xaa是Lys,Arg或Asp;<223> Xaa at position 27 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(28)..(28)<222>(28)..(28)

<223>第28位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 28 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(29)..(29)<222>(29)..(29)

<223>第29位的Xaa是Met,Arg或Ser;<223> Xaa at the 29th position is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Tyr或Asn;<223> Xaa at the 30th place is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(31)..(31)<222>(31)..(31)

<223>第31位的Xaa是Ser或Arg;<223> Xaa at the 31st position is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Thr,Gln或Ala;<223> Xaa at position 32 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Lys或Arg或跳过;<223> Xaa at the 33rd position is Lys or Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Ala,Ile或Ser;<223> Xaa at position 34 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Ala,Gly或Ile;<223> Xaa at position 35 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 36 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(37)..(37)<222>(37)..(37)

<223>第37位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 37 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(38)..(38)<222>(38)..(38)

<223>第38位的Xaa是His或Leu;<223> Xaa at the 38th place is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(39)..(39)<222>(39)..(39)

<223>第39位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 39 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(40)..(40)<222>(40)..(40)

<223>第40位的Xaa是Trp,Val或Gln;<223> Xaa at position 40 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(41)..(41)<222>(41)..(41)

<223>第41位的Xaa是Asp或Ser;<223> Xaa at position 41 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(42)..(42)<222>(42)..(42)

<223>第42位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 42 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(43)..(43)<222>(43)..(43)

<223>第43位的Xaa是Arg或跳过;<223> Xaa at position 43 is Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(44)..(44)<222>(44)..(44)

<223>第44位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 44 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(46)..(46)<222>(46)..(46)

<223>第46位的Xaa是Ser或Asp;<223> Xaa at position 46 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(47)..(47)<222>(47)..(47)

<223>第47位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 47 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(48)..(48)<222>(48)..(48)

<223>第48位的Xaa是Gln,Glu或Gly;<223> Xaa at position 48 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(49)..(49)<222>(49)..(49)

<223>第49位的Xaa是Asp,Ala或Thr;<223> Xaa at position 49 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(50)..(50)<222>(50)..(50)

<223>第50位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 50 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(51)..(51)<222>(51)..(51)

<223>第51位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 51 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(52)..(52)<222>(52)..(52)

<223>第52位的Xaa是Ser,Gly或Ala;<223> Xaa at position 52 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(53)..(53)<222>(53)..(53)

<223>第53位的Xaa是Cys或被去除;<223> Xaa at position 53 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(54)..(54)<222>(54)..(54)

<223>第54位的Xaa是Arg或被去除;<223> Xaa at position 54 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(55)..(55)<222>(55)..(55)

<223>第55位的Xaa是Leu,Val,Ala或Ser或被去除;<223> Xaa at position 55 is Leu, Val, Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(56)..(56)<222>(56)..(56)

<223>第56位的Xaa是Val或Ala或被去除;<223> Xaa at position 56 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(57)..(57)<222>(57)..(57)

<223>第57位的Xaa是Phe,Ala,Thr或Met或被去除;<223> Xaa at position 57 is Phe, Ala, Thr or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(58)..(58)<222>(58)..(58)

<223>第58位的Xaa是Leu或Val或被去除;<223> Xaa at position 58 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(59)..(59)<222>(59)..(59)

<223>第59位的Xaa是Leu,Phe或Met或被去除;<223> Xaa at position 59 is Leu, Phe or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(63)..(63)<222>(63)..(63)

<223>第63位的Xaa是Cys,Gly或Ser或被去除;<223> Xaa at position 63 is Cys, Gly or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(64)..(64)<222>(64)..(64)

<223>第64位的Xaa是Val,Ile或Met或被去除;<223> Xaa at position 64 is Val, Ile or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(65)..(65)<222>(65)..(65)

<223>第65位的Xaa是Ala,Val,Met或Ile或被去除;<223> Xaa at position 65 is Ala, Val, Met or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(69)..(69)<222>(69)..(69)

<223>第69位的Xaa是Tyr或Cys或被去除;<223> Xaa at position 69 is Tyr or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(76)..(76)<222>(76)..(76)

<223>第76位的Xaa是Val或Leu或被去除;<223> Xaa at position 76 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(79)..(79)<222>(79)..(79)

<223>第79位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 79th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(80)..(80)<222>(80)..(80)

<223>第80位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 80th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(81)..(81)<222>(81)..(81)

<223>第81位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 81st Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(83)..(83)<222>(83)..(83)

<223>第83位的Xaa是Arg或Ser或被去除;<223> Xaa at position 83 is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(86)..(86)<222>(86)..(86)

<223>第86位的Xaa是Val或Leu或被去除;<223> Xaa at position 86 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(87)..(87)<222>(87)..(87)

<223>第87位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 87 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(92)..(92)<222>(92)..(92)

<223>第92位的Xaa是Val或Ala或被去除;<223> Xaa at position 92 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(94)..(94)<222>(94)..(94)

<223>第94位的Xaa是Leu或Met或被去除;<223> Xaa at position 94 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(98)..(98)<222>(98)..(98)

<223>第98位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 98 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(101)..(101)<222>(101)..(101)

<223>第101位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 101 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(102)..(102)<222>(102)..(102)

<223>第102位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 102 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(103)..(103)<222>(103)..(103)

<223>第103位的Xaa是Val或被去除;<223> Xaa at position 103 is Val or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(104)..(104)<222>(104)..(104)

<223>第104位的Xaa是Lys或被去除;<223> Xaa at position 104 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(105)..(105)<222>(105)..(105)

<223>第105位的Xaa是Tyr或Cys;<223> Xaa at position 105 is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(107)..(107)<222>(107)..(107)

<223>第107位的Xaa是Tyr或Phe;<223> The 107th Xaa is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(109)..(109)<222>(109)..(109)

<223>第109位的Xaa是Asp或Asn;<223> Xaa at position 109 is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(110)..(110)<222>(110)..(110)

<223>第110位的Xaa是Glu或Val;<223> the 110th Xaa is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(111)..(111)<222>(111)..(111)

<223>第111位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 111 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(114)..(114)<222>(114)..(114)

<223>第114位的Xaa是Thr,Glu或Ser;<223> Xaa at position 114 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(115)..(115)<222>(115)..(115)

<223>第115位的Xaa是Arg或Ser;<223> Xaa at position 115 is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(117)..(117)<222>(117)..(117)

<223>第117位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 117 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Asn或Gly或被去除;<223> Xaa at position 120 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 121 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Leu或Trp或被去除;<223> Xaa at position 123 is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Ile或Leu或被去除;<223> Xaa at position 125 is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 127 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(129)..(129)<222>(129)..(129)

<223>第129位的Xaa是Ile或Val或被去除;<223> Xaa at position 129 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Leu或Phe或被去除;<223> Xaa at position 130 is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(131)..(131)<222>(131)..(131)

<223>第131位的Xaa是Phe或Leu或被去除;<223> Xaa at position 131 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(134)..(134)<222>(134)..(134)

<223>第134位的Xaa是Gly或Leu或被去除;<223> Xaa at position 134 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(135)..(135)<222>(135)..(135)

<223>第135位的Xaa是Val或Ile或被去除;<223> Xaa at position 135 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(138)..(138)<222>(138)..(138)

<223>第138位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 138 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(143)..(143)<222>(143)..(143)

<223>第143位的Xaa是Val或Ile或被去除;<223> Xaa at position 143 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(144)..(144)<222>(144)..(144)

<223>第144位的Xaa是Ile或Val或被去除;<223> Xaa at position 144 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Gln或Cys或被去除;<223> Xaa at position 145 is Gln or Cys or is removed;

<400>23<400>23

Asn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa XaaAsn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa

1               5                   10                  151 5 10 15

Xaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa XaaXaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

            20                  25                  3020 25 30

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa

            35                  40                  4535 40 45

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa

    50                  55                  6050 55 60

Xaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa XaaXaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa

65                  70                  75                  8065 70 75 80

Xaa Phe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu PheXaa Phe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe

                85                  90                  9585 90 95

Val Xaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa CysVal Xaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys

            100                 105                 110100 105 110

Trp Xaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa ProTrp Xaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro

        115                 120                 125115 120 125

Xaa Xaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa XaaXaa Xaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa

    130                 135                 140130 135 140

XaaXaa

145145

<210>24<210>24

<211>138<211>138

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(2)..(2)<222>(2)..(2)

<223>第2位的Xaa是Tyr或Ala或被去除;<223> the second Xaa is Tyr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(5)..(5)<222>(5)..(5)

<223>第5位的Xaa是Leu,Ala或Met或被去除;<223> The 5th Xaa is Leu, Ala or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(9)..(9)<222>(9)..(9)

<223>第9位的Xaa是Ala或Gly或被去除;<223> Xaa at position 9 is Ala or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(12)..(12)<222>(12)..(12)

<223>第12位的Xaa是Ile,Val或Met或被去除;<223> Xaa at position 12 is Ile, Val or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(14)..(14)<222>(14)..(14)

<223>第14位的Xaa是Leu或Val或被去除;<223> The 14th Xaa is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(15)..(15)<222>(15)..(15)

<223>第15位的Xaa是Arg或Lys或被去除;<223> Xaa at position 15 is Arg or Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(16)..(16)<222>(16)..(16)

<223>第16位的Xaa是Ala或Ser或被去除;<223> Xaa at position 16 is Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(17)..(17)<222>(17)..(17)

<223>第17位的Xaa是Leu或Ser或被去除;<223> The 17th Xaa is Leu or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(19)..(19)<222>(19)..(19)

<223>第19位的Xaa是Val或Leu或被去除;<223> the 19th Xaa is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Phe或Leu或被去除;<223> Xaa at the 20th place is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Ile或Val或被去除;<223> Xaa at position 21 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(22)..(22)<222>(22)..(22)

<223>第22位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 22 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 24 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(25)..(25)<222>(25)..(25)

<223>第25位的Xaa是Ala,Leu或Val;<223> The 25th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(27)..(27)<222>(27)..(27)

<223>第27位的Xaa是Lys,Arg或Asp;<223> Xaa at position 27 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(28)..(28)<222>(28)..(28)

<223>第28位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 28 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(29)..(29)<222>(29)..(29)

<223>第29位的Xaa是Met,Arg或Ser;<223> Xaa at the 29th position is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Tyr或Asn;<223> Xaa at the 30th place is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(31)..(31)<222>(31)..(31)

<223>第31位的Xaa是Ser或Arg;<223> Xaa at the 31st position is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Thr,Gln或Ala;<223> Xaa at position 32 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Lys或Arg或跳过;<223> Xaa at the 33rd position is Lys or Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Ala,Ile或Ser;<223> Xaa at position 34 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Ala,Gly或Ile;<223> Xaa at position 35 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 36 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(37)..(37)<222>(37)..(37)

<223>第37位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 37 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(38)..(38)<222>(38)..(38)

<223>第38位的Xaa是His或Leu;<223> Xaa at the 38th place is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(39)..(39)<222>(39)..(39)

<223>第39位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 39 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(40)..(40)<222>(40)..(40)

<223>第40位的Xaa是Trp,Val或Gln;<223> Xaa at position 40 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(41)..(41)<222>(41)..(41)

<223>第41位的Xaa是Asp或Ser;<223> Xaa at position 41 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(42)..(42)<222>(42)..(42)

<223>第42位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 42 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(43)..(43)<222>(43)..(43)

<223>第43位的Xaa是Arg或跳过;<223> Xaa at position 43 is Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(44)..(44)<222>(44)..(44)

<223>第44位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 44 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(46)..(46)<222>(46)..(46)

<223>第46位的Xaa是Ser或Asp;<223> Xaa at position 46 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(47)..(47)<222>(47)..(47)

<223>第47位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 47 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(48)..(48)<222>(48)..(48)

<223>第48位的Xaa是Gln,Glu或Gly;<223> Xaa at position 48 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(49)..(49)<222>(49)..(49)

<223>第49位的Xaa是Asp,Ala或Thr;<223> Xaa at position 49 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(50)..(50)<222>(50)..(50)

<223>第50位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 50 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(51)..(51)<222>(51)..(51)

<223>第51位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 51 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(52)..(52)<222>(52)..(52)

<223>第52位的Xaa是Ser,Gly或Ala;<223> Xaa at position 52 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(53)..(53)<222>(53)..(53)

<223>第53位的Xaa是Cys或被去除;<223> Xaa at position 53 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(54)..(54)<222>(54)..(54)

<223>第54位的Xaa是Arg或被去除;<223> Xaa at position 54 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(55)..(55)<222>(55)..(55)

<223>第55位的Xaa是Leu,Val,Ala或Ser或被去除;<223> Xaa at position 55 is Leu, Val, Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(56)..(56)<222>(56)..(56)

<223>第56位的Xaa是Val或Ala或被去除;<223> Xaa at position 56 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(57)..(57)<222>(57)..(57)

<223>第57位的Xaa是Phe,Ala,Thr或Met或被去除;<223> Xaa at position 57 is Phe, Ala, Thr or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(58)..(58)<222>(58)..(58)

<223>第58位的Xaa是Leu或Val或被去除;<223> Xaa at position 58 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(59)..(59)<222>(59)..(59)

<223>第59位的Xaa是Leu,Phe或Met或被去除;<223> Xaa at position 59 is Leu, Phe or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(63)..(63)<222>(63)..(63)

<223>第63位的Xaa是Cys,Gly或Ser或被去除;<223> Xaa at position 63 is Cys, Gly or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(64)..(64)<222>(64)..(64)

<223>第64位的Xaa是Val,Ile或Met或被去除;<223> Xaa at position 64 is Val, Ile or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(65)..(65)<222>(65)..(65)

<223>第65位的Xaa是Ala,Val,Met或Ile或被去除;<223> Xaa at position 65 is Ala, Val, Met or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(69)..(69)<222>(69)..(69)

<223>第69位的Xaa是Tyr或Cys或被去除;<223> Xaa at position 69 is Tyr or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(76)..(76)<222>(76)..(76)

<223>第76位的Xaa是Val或Leu或被去除;<223> Xaa at position 76 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(79)..(79)<222>(79)..(79)

<223>第79位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 79th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(80)..(80)<222>(80)..(80)

<223>第80位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 80th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(81)..(81)<222>(81)..(81)

<223>第81位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 81st Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(92)..(92)<222>(92)..(92)

<223>第92位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 92 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(96)..(96)<222>(96)..(96)

<223>第96位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 96 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(101)..(101)<222>(101)..(101)

<223>第101位的Xaa是Met,Thr,Ile或Ala或被去除;<223> Xaa at position 101 is Met, Thr, Ile or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(104)..(104)<222>(104)..(104)

<223>第104位的Xaa是His,Pro,Gln或Thr;<223> Xaa at position 104 is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(105)..(105)<222>(105)..(105)

<223>第105位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 105 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(106)..(106)<222>(106)..(106)

<223>第106位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 106 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(107)..(107)<222>(107)..(107)

<223>第107位的Xaa是Gly或Ser;<223> Xaa at position 107 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(108)..(108)<222>(108)..(108)

<223>第108位的Xaa是Thr,Leu,Phe或Ala;<223> Xaa at position 108 is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(111)..(111)<222>(111)..(111)

<223>第11l位的Xaa是Phe,Ser或Leu;<223> Xaa at position 11l is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(112)..(112)<222>(112)..(112)

<223>第112位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 112 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(113)..(113)<222>(113)..(113)

<223>第113位的Xaa是Lys或Arg;<223> Xaa at position 113 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(116)..(116)<222>(116)..(116)

<223>第116位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 116 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(117)..(117)<222>(117)..(117)

<223>第117位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 117 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(119)..(119)<222>(119)..(119)

<223>第119位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 119 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Phe或Leu或被去除;<223> Xaa at position 120 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 121 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(126)..(126)<222>(126)..(126)

<223>第126位的Xaa是Leu或Met或被去除;<223> Xaa at position 126 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Met或Leu或被去除;<223> Xaa at position 127 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Ile或Val或被去除;<223> Xaa at position 130 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(135)..(135)<222>(135)..(135)

<223>第135位的Xaa是Val或Leu或被去除;<223> Xaa at position 135 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(137)..(137)<222>(137)..(137)

<223>第137位的Xaa是Asn或Lys或被去除;<223> Xaa at position 137 is Asn or Lys or is removed;

<400>24<400>24

Asn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa XaaAsn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa

1               5                   10                  151 5 10 15

Xaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa XaaXaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

            20                  25                  3020 25 30

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa

        35                  40                  4535 40 45

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa

    50                  55                  6050 55 60

Xaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa XaaXaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa

65                  70                  75                  8065 70 75 80

Xaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val XaaXaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa

                85                  90                  9585 90 95

Phe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa XaaPhe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa

            100                 105                 110100 105 110

Xaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa ValXaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val

        115                 120                 125115 120 125

Ala Xaa Leu Tyr Cys Phe Xaa Asn Xaa GluAla Xaa Leu Tyr Cys Phe Xaa Asn Xaa Glu

    130                 135130 135

<210>25<210>25

<211>124<211>124

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(2)..(2)<222>(2)..(2)

<223>第2位的Xaa是Arg或Ser或被去除;<223> the second Xaa is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(5)..(5)<222>(5)..(5)

<223>第5位的Xaa是Val或Leu或被去除;<223> Xaa at position 5 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(6)..(6)<222>(6)..(6)

<223>第6位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 6 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(11)..(11)<222>(11)..(11)

<223>第11位的Xaa是Val或Ala或被去除;<223> Xaa at position 11 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(13)..(13)<222>(13)..(13)

<223>第13位的Xaa是Leu或Met或被去除;<223> The 13th Xaa is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(17)..(17)<222>(17)..(17)

<223>第17位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 17 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 20 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 21 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(22)..(22)<222>(22)..(22)

<223>第22位的Xaa是Val或被去除;<223> Xaa at the 22nd position is Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(23)..(23)<222>(23)..(23)

<223>第23位的Xaa是Lys或被去除;<223> Xaa at position 23 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Tyr或Cys;<223> Xaa at the 24th position is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(26)..(26)<222>(26)..(26)

<223>第26位的Xaa是Tyr或Phe;<223> The 26th Xaa is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(28)..(28)<222>(28)..(28)

<223>第28位的Xaa是Asp或Asn;<223> Xaa at the 28th position is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(29)..(29)<222>(29)..(29)

<223>第29位的Xaa是Glu或Val;<223> the 29th Xaa is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 30 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Thr,Glu或Ser;<223> Xaa at position 33 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Arg或Ser;<223> Xaa at the 34th position is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 36 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(39)..(39)<222>(39)..(39)

<223>第39位的Xaa是Asn或Gly或被去除;<223> Xaa at position 39 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(40)..(40)<222>(40)..(40)

<223>第40位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 40 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(42)..(42)<222>(42)..(42)

<223>第42位的Xaa是Leu或Trp或被去除;<223> Xaa at the 42nd position is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(44)..(44)<222>(44)..(44)

<223>第44位的Xaa是Ile或Leu或被去除;<223> Xaa at position 44 is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(46)..(46)<222>(46)..(46)

<223>第46位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 46 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(48)..(48)<222>(48)..(48)

<223>第48位的Xaa是Ile或Val或被去除;<223> Xaa at position 48 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(49)..(49)<222>(49)..(49)

<223>第49位的Xaa是Leu或Phe或被去除;<223> Xaa at the 49th position is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(50)..(50)<222>(50)..(50)

<223>第50位的Xaa是Phe或Leu或被去除;<223> Xaa at position 50 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(53)..(53)<222>(53)..(53)

<223>第53位的Xaa是Gly或Leu或被去除;<223> Xaa at position 53 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(54)..(54)<222>(54)..(54)

<223>第54位的Xaa是Val或Ile或被去除;<223> Xaa at position 54 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(57)..(57)<222>(57)..(57)

<223>第57位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 57 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(62)..(62)<222>(62)..(62)

<223>第62位的Xaa是Val或Ile或被去除;<223> Xaa at position 62 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(63)..(63)<222>(63)..(63)

<223>第63位的Xaa是Ile或Val或被去除;<223> Xaa at position 63 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(64)..(64)<222>(64)..(64)

<223>第64位的Xaa是Gln或Cys或被去除;<223> Xaa at position 64 is Gln or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(65)..(65)<222>(65)..(65)

<223>第65位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 65th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(66)..(66)<222>(66)..(66)

<223>第66位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 66th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(67)..(67)<222>(67)..(67)

<223>第67位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 67th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(78)..(78)<222>(78)..(78)

<223>第78位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 78 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(82)..(82)<222>(82)..(82)

<223>第82位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 82 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(87)..(87)<222>(87)..(87)

<223>第87位的Xaa是Met,Thr,Ile或Ala或被去除;<223> Xaa at position 87 is Met, Thr, Ile or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(90)..(90)<222>(90)..(90)

<223>第90位的Xaa是His,Pro,Gln或Thr;<223> Xaa at position 90 is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(91)..(91)<222>(91)..(91)

<223>第91位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 91 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(92)..(92)<222>(92)..(92)

<223>第92位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 92 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(93)..(93)<222>(93)..(93)

<223>第93位的Xaa是Gly或Ser;<223> Xaa at position 93 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(94)..(94)<222>(94)..(94)

<223>第94位的Xaa是Thr,Leu,Phe或Ala;<223> Xaa at position 94 is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(97)..(97)<222>(97)..(97)

<223>第97位的Xaa是Phe,Ser或Leu;<223> The 97th Xaa is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(98)..(98)<222>(98)..(98)

<223>第98位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 98 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(99)..(99)<222>(99)..(99)

<223>第99位的Xaa是Lys或Arg;<223> Xaa at position 99 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(102)..(102)<222>(102)..(102)

<223>第102位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 102 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(103)..(103)<222>(103)..(103)

<223>第103位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 103 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(105)..(105)<222>(105)..(105)

<223>第105位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 105 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(106)..(106)<222>(106)..(106)

<223>第106位的Xaa是Phe或Leu或被去除;<223> Xaa at position 106 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(107)..(107)<222>(107)..(107)

<223>第107位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 107 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(112)..(112)<222>(112)..(112)

<223>第112位的Xaa是Leu或Met或被去除;<223> Xaa at position 112 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(113)..(113)<222>(113)..(113)

<223>第113位的Xaa是Met或Leu或被去除;<223> Xaa at position 113 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(116)..(116)<222>(116)..(116)

<223>第116位的Xaa是Ile或Val或被去除;<223> Xaa at position 116 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Val或Leu或被去除;<223> Xaa at position 121 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Asn或Lys或被去除;<223> Xaa at position 123 is Asn or Lys or is removed;

<400>25<400>25

Phe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe ValPhe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val

1               5                   10                  151 5 10 15

Xaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys TrpXaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp

            20                  25                  3020 25 30

Xaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro XaaXaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa

        35                  40                  4535 40 45

Xaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa XaaXaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa

    50                  55                  6050 55 60

Xaa Xaa Xaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His GluXaa Xaa Xaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu

65                  70                  75                  8065 70 75 80

Val Xaa Phe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu ArgVal Xaa Phe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg

                85                  90                  9585 90 95

Xaa Xaa Xaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly XaaXaa Xaa Xaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa

            100                 105                 110100 105 110

Xaa Val Ala Xaa Leu Tyr Cys Phe Xaa Asn Xaa GluXaa Val Ala Xaa Leu Tyr Cys Phe Xaa Asn Xaa Glu

        115                 120115 120

<210>26<210>26

<211>205<211>205

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(2)..(2)<222>(2)..(2)

<223>第2位的Xaa是Tyr或Ala或被去除;<223> the second Xaa is Tyr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(5)..(5)<222>(5)..(5)

<223>第5位的Xaa是Leu,Ala或Met或被去除;<223> The 5th Xaa is Leu, Ala or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(9)..(9)<222>(9)..(9)

<223>第9位的Xaa是Ala或Gly或被去除;<223> Xaa at position 9 is Ala or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(12)..(12)<222>(12)..(12)

<223>第12位的Xaa是Ile,Val或Met或被去除;<223> Xaa at position 12 is Ile, Val or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(14)..(14)<222>(14)..(14)

<223>第14位的Xaa是Leu或Val或被去除;<223> The 14th Xaa is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(15)..(15)<222>(15)..(15)

<223>第15位的Xaa是Arg或Lys或被去除;<223> Xaa at position 15 is Arg or Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(16)..(16)<222>(16)..(16)

<223>第16位的Xaa是Ala或Ser或被去除;<223> Xaa at position 16 is Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(17)..(17)<222>(17)..(17)

<223>第17位的Xaa是Leu或Ser或被去除;<223> The 17th Xaa is Leu or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(19)..(19)<222>(19)..(19)

<223>第19位的Xaa是Val或Leu或被去除;<223> the 19th Xaa is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(20)..(20)<222>(20)..(20)

<223>第20位的Xaa是Phe或Leu或被去除;<223> Xaa at the 20th place is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(21)..(21)<222>(21)..(21)

<223>第21位的Xaa是Ile或Val或被去除;<223> Xaa at position 21 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(22)..(22)<222>(22)..(22)

<223>第22位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 22 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(24)..(24)<222>(24)..(24)

<223>第24位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 24 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(25)..(25)<222>(25)..(25)

<223>第25位的Xaa是Ala,Leu或Val;<223> The 25th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(27)..(27)<222>(27)..(27)

<223>第27位的Xaa是Lys,Arg或Asp;<223> Xaa at position 27 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(28)..(28)<222>(28)..(28)

<223>第28位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 28 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(29)..(29)<222>(29)..(29)

<223>第29位的Xaa是Met,Arg或Ser;<223> Xaa at the 29th position is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(30)..(30)<222>(30)..(30)

<223>第30位的Xaa是Tyr或Asn;<223> Xaa at the 30th place is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(31)..(31)<222>(31)..(31)

<223>第31位的Xaa是Ser或Arg;<223> Xaa at the 31st position is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(32)..(32)<222>(32)..(32)

<223>第32位的Xaa是Thr,Gln或Ala;<223> Xaa at position 32 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(33)..(33)<222>(33)..(33)

<223>第33位的Xaa是Lys或Arg或跳过;<223> Xaa at the 33rd position is Lys or Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(34)..(34)<222>(34)..(34)

<223>第34位的Xaa是Ala,Ile或Ser;<223> Xaa at position 34 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(35)..(35)<222>(35)..(35)

<223>第35位的Xaa是Ala,Gly或Ile;<223> Xaa at position 35 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(36)..(36)<222>(36)..(36)

<223>第36位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 36 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(37)..(37)<222>(37)..(37)

<223>第37位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 37 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(38)..(38)<222>(38)..(38)

<223>第38位的Xaa是His或Leu;<223> Xaa at the 38th place is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(39)..(39)<222>(39)..(39)

<223>第39位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 39 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(40)..(40)<222>(40)..(40)

<223>第40位的Xaa是Trp,Val或Gln;<223> Xaa at position 40 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(41)..(41)<222>(41)..(41)

<223>第41位的Xaa是Asp或Ser;<223> Xaa at position 41 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(42)..(42)<222>(42)..(42)

<223>第42位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 42 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(43)..(43)<222>(43)..(43)

<223>第43位的Xaa是Arg或跳过;<223> Xaa at position 43 is Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(44)..(44)<222>(44)..(44)

<223>第44位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 44 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(46)..(46)<222>(46)..(46)

<223>第46位的Xaa是Ser或Asp;<223> Xaa at position 46 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(47)..(47)<222>(47)..(47)

<223>第47位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 47 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(48)..(48)<222>(48)..(48)

<223>第48位的Xaa是Gln,Glu或Gly;<223> Xaa at position 48 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(49)..(49)<222>(49)..(49)

<223>第49位的Xaa是Asp,Ala或Thr;<223> Xaa at position 49 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(50)..(50)<222>(50)..(50)

<223>第50位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 50 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(51)..(51)<222>(51)..(51)

<223>第51位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 51 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(52)..(52)<222>(52)..(52)

<223>第52位的Xaa是Ser,Gly或Ala;<223> Xaa at position 52 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(53)..(53)<222>(53)..(53)

<223>第53位的Xaa是Cys或被去除;<223> Xaa at position 53 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(54)..(54)<222>(54)..(54)

<223>第54位的Xaa是Arg或被去除;<223> Xaa at position 54 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(55)..(55)<222>(55)..(55)

<223>第55位的Xaa是Leu,Val,Ala或Ser或被去除;<223> Xaa at position 55 is Leu, Val, Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(56)..(56)<222>(56)..(56)

<223>第56位的Xaa是Val或Ala或被去除;<223> Xaa at position 56 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(57)..(57)<222>(57)..(57)

<223>第57位的Xaa是Phe,Ala,Thr或Met或被去除;<223> Xaa at position 57 is Phe, Ala, Thr or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(58)..(58)<222>(58)..(58)

<223>第58位的Xaa是Leu或Val或被去除;<223> Xaa at position 58 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(59)..(59)<222>(59)..(59)

<223>第59位的Xaa是Leu,Phe或Met或被去除;<223> Xaa at position 59 is Leu, Phe or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(63)..(63)<222>(63)..(63)

<223>第63位的Xaa是Cys,Gly或Ser或被去除;<223> Xaa at position 63 is Cys, Gly or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(64)..(64)<222>(64)..(64)

<223>第64位的Xaa是Val,Ile或Met或被去除;<223> Xaa at position 64 is Val, Ile or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(65)..(65)<222>(65)..(65)

<223>第65位的Xaa是Ala,Val,Met或Ile或被去除;<223> Xaa at position 65 is Ala, Val, Met or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(69)..(69)<222>(69)..(69)

<223>第69位的Xaa是Tyr或Cys或被去除;<223> Xaa at position 69 is Tyr or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(76)..(76)<222>(76)..(76)

<223>第76位的Xaa是Val或Leu或被去除;<223> Xaa at position 76 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(79)..(79)<222>(79)..(79)

<223>第79位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 79th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(80)..(80)<222>(80)..(80)

<223>第80位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 80th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(81)..(81)<222>(81)..(81)

<223>第81位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 81st Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(83)..(83)<222>(83)..(83)

<223>第83位的Xaa是Arg或Ser或被去除;<223> Xaa at position 83 is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(86)..(86)<222>(86)..(86)

<223>第86位的Xaa是Val或Leu或被去除;<223> Xaa at position 86 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(87)..(87)<222>(87)..(87)

<223>第87位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 87 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(92)..(92)<222>(92)..(92)

<223>第92位的Xaa是Val或Ala或被去除;<223> Xaa at position 92 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(94)..(94)<222>(94)..(94)

<223>第94位的Xaa是Leu或Met或被去除;<223> Xaa at position 94 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(98)..(98)<222>(98)..(98)

<223>第98位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 98 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(101)..(101)<222>(101)..(101)

<223>第101位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 101 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(102)..(102)<222>(102)..(102)

<223>第102位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 102 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(103)..(103)<222>(103)..(103)

<223>第103位的Xaa是Val或被去除;<223> Xaa at position 103 is Val or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(104)..(104)<222>(104)..(104)

<223>第104位的Xaa是Lys或被去除;<223> Xaa at position 104 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(105)..(105)<222>(105)..(105)

<223>第105位的Xaa是Tyr或Cys;<223> Xaa at position 105 is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(107)..(107)<222>(107)..(107)

<223>第107位的Xaa是Tyr或Phe;<223> The 107th Xaa is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(109)..(109)<222>(109)..(109)

<223>第109位的Xaa是Asp或Asn;<223> Xaa at position 109 is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(110)..(110)<222>(110)..(110)

<223>第110位的Xaa是Glu或Val;<223> the 110th Xaa is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(111)..(111)<222>(111)..(111)

<223>第111位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 111 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(114)..(114)<222>(114)..(114)

<223>第114位的Xaa是Thr,Glu或Ser;<223> Xaa at position 114 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(115)..(115)<222>(115)..(115)

<223>第115位的Xaa是Arg或Ser;<223> Xaa at position 115 is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(117)..(117)<222>(117)..(117)

<223>第117位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 117 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(120)..(120)<222>(120)..(120)

<223>第120位的Xaa是Asn或Gly或被去除;<223> Xaa at position 120 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(121)..(121)<222>(121)..(121)

<223>第121位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 121 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Leu或Trp或被去除;<223> Xaa at position 123 is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Ile或Leu或被去除;<223> Xaa at position 125 is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 127 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(129)..(129)<222>(129)..(129)

<223>第129位的Xaa是Ile或Val或被去除;<223> Xaa at position 129 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Leu或Phe或被去除;<223> Xaa at position 130 is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(131)..(131)<222>(131)..(131)

<223>第131位的Xaa是Phe或Leu或被去除;<223> Xaa at position 131 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(134)..(134)<222>(134)..(134)

<223>第134位的Xaa是Gly或Leu或被去除;<223> Xaa at position 134 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(135)..(135)<222>(135)..(135)

<223>第135位的Xaa是Val或Ile或被去除;<223> Xaa at position 135 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(138)..(138)<222>(138)..(138)

<223>第138位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 138 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(143)..(143)<222>(143)..(143)

<223>第143位的Xaa是Val或Ile或被去除;<223> Xaa at position 143 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(144)..(144)<222>(144)..(144)

<223>第144位的Xaa是Ile或Val或被去除;<223> Xaa at position 144 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Gln或Cys或被去除;<223> Xaa at position 145 is Gln or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(146)..(146)<222>(146)..(146)

<223>第146位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 146th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(147)..(147)<222>(147)..(147)

<223>第147位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 147th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(148)..(148)<222>(148)..(148)

<223>第148位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 148th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(159)..(159)<222>(159)..(159)

<223>第159位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 159 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(163)..(163)<222>(163)..(163)

<223>第163位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 163 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(168)..(168)<222>(168)..(168)

<223>第168位的Xaa是Met,Thr,Ile或Ala或被去除;<223> Xaa at position 168 is Met, Thr, Ile or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是His,Pro,Gln或Thr;<223> Xaa at position 171 is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(172)..(172)<222>(172)..(172)

<223>第172位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 172 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 173 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Gly或Ser;<223> Xaa at position 174 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Thr,Leu,Phe或Ala;<223> Xaa at position 175 is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Phe,Ser或Leu;<223> The 178th Xaa is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 179 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(180)..(180)<222>(180)..(180)

<223>第180位的Xaa是Lys或Arg;<223> Xaa at position 180 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(183)..(183)<222>(183)..(183)

<223>第183位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 183 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(184)..(184)<222>(184)..(184)

<223>第184位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 184 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(186)..(186)<222>(186)..(186)

<223>第186位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 186 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(187)..(187)<222>(187)..(187)

<223>第187位的Xaa是Phe或Leu或被去除;<223> Xaa at position 187 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(188)..(188)<222>(188)..(188)

<223>第188位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 188 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(193)..(193)<222>(193)..(193)

<223>第193位的Xaa是Leu或Met或被去除;<223> Xaa at position 193 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(194)..(194)<222>(194)..(194)

<223>第194位的Xaa是Met或Leu或被去除;<223> Xaa at position 194 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(197)..(197)<222>(197)..(197)

<223>第197位的Xaa是Ile或Val或被去除;<223> Xaa at position 197 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(202)..(202)<222>(202)..(202)

<223>第202位的Xaa是Val或Leu或被去除;<223> Xaa at position 202 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(204)..(204)<222>(204)..(204)

<223>第204位的Xaa是Asn或Lys或被去除;<223> Xaa at position 204 is Asn or Lys or is removed;

<400>26<400>26

Asn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa XaaAsn Xaa Ile His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa

1               5                   10                  151 5 10 15

Xaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa XaaXaa Ser Xaa Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

            20                  25                  3020 25 30

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa

        35                  40                  4535 40 45

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa

    50                  55                  6050 55 60

Xaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa XaaXaa Ala Asn Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa

65                  70                  75                  8065 70 75 80

Xaa Phe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu PheXaa Phe Xaa Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe

                85                  90                  9585 90 95

Val Xaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa CysVal Xaa Pro Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys

            100                 105                 110100 105 110

Trp Xaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa ProTrp Xaa Xaa Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro

        115                 120                 125115 120 125

Xaa Xaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa XaaXaa Xaa Xaa Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa

    130                 135                 140130 135 140

Xaa Xaa Xaa Xaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa HisXaa Xaa Xaa Xaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His

145                 150                 155                 160145 150 155 160

Glu Val Xaa Phe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa LeuGlu Val Xaa Phe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu

                165                 170                 175165 170 175

Arg Xaa Xaa Xaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln GlyArg Xaa Xaa Xaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly

            180                 185                 190180 185 190

Xaa Xaa Val Ala Xaa Leu Tyr Cys Phe Xaa Asn Xaa GluXaa Xaa Val Ala Xaa Leu Tyr Cys Phe Xaa Asn Xaa Glu

        195                 200                 205195 200 205

<210>27<210>27

<211>203<211>203

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 123rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(124)..(124)<222>(124)..(124)

<223>第124位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 124th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 125th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Tyr或Ala或被去除;<223> Xaa at position 127 is Tyr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Leu,Ala或Met或被去除;<223> Xaa at position 130 is Leu, Ala or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(134)..(134)<222>(134)..(134)

<223>第134位的Xaa是Ala或Gly或被去除;<223> Xaa at position 134 is Ala or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(137)..(137)<222>(137)..(137)

<223>第137位的Xaa是Ile,Val或Met或被去除;<223> Xaa at position 137 is Ile, Val or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(139)..(139)<222>(139)..(139)

<223>第139位的Xaa是Leu或Val或被去除;<223> Xaa at position 139 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(140)..(140)<222>(140)..(140)

<223>第140位的Xaa是Arg或Lys或被去除;<223> Xaa at position 140 is Arg or Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(141)..(141)<222>(141)..(141)

<223>第141位的Xaa是Ala或Ser或被去除;<223> Xaa at position 141 is Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(142)..(142)<222>(142)..(142)

<223>第142位的Xaa是Leu或Ser或被去除;<223> Xaa at position 142 is Leu or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(144)..(144)<222>(144)..(144)

<223>第144位的Xaa是Val或Leu或被去除;<223> Xaa at position 144 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Phe或Leu或被去除;<223> Xaa at position 145 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(146)..(146)<222>(146)..(146)

<223>第146位的Xaa是Ile或Val或被去除;<223> Xaa at position 146 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(147)..(147)<222>(147)..(147)

<223>第147位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 147 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(149)..(149)<222>(149)..(149)

<223>第149位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 149 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(150)..(150)<222>(150)..(150)

<223>第150位的Xaa是Ala,Leu或Val;<223> The 150th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Lys,Arg或Asp;<223> Xaa at position 152 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 153 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Met,Arg或Ser;<223> Xaa at position 154 is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Tyr或Asn;<223> Xaa at position 155 is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Ser或Arg;<223> Xaa at position 156 is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(157)..(157)<222>(157)..(157)

<223>第157位的Xaa是Thr,Gln或Ala;<223> Xaa at position 157 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(158)..(158)<222>(158)..(158)

<223>第158位的Xaa是Lys或Arg或跳过;<223> Xaa at position 158 is Lys or Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(159)..(159)<222>(159)..(159)

<223>第159位的Xaa是Ala,Ile或Ser;<223> Xaa at position 159 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(160)..(160)<222>(160)..(160)

<223>第160位的Xaa是Ala,Gly或Ile;<223> Xaa at position 160 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 161 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(162)..(162)<222>(162)..(162)

<223>第162位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 162 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(163)..(163)<222>(163)..(163)

<223>第163位的Xaa是His或Leu;<223> Xaa at position 163 is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(164)..(164)<222>(164)..(164)

<223>第164位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 164 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(165)..(165)<222>(165)..(165)

<223>第165位的Xaa是Trp,Val或Gln;<223> Xaa at position 165 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(166)..(166)<222>(166)..(166)

<223>第166位的Xaa是Asp或Ser;<223> Xaa at position 166 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(167)..(167)<222>(167)..(167)

<223>第167位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 167 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(168)..(168)<222>(168)..(168)

<223>第168位的Xaa是Arg或跳过;<223> The 168th Xaa is Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(169)..(169)<222>(169)..(169)

<223>第169位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 169 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是Ser或Asp;<223> Xaa at position 171 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(172)..(172)<222>(172)..(172)

<223>第172位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 172 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Gln,Glu或Gly;<223> Xaa at position 173 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Asp,Ala或Thr;<223> Xaa at position 174 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 175 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(176)..(176)<222>(176)..(176)

<223>第176位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 176 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(177)..(177)<222>(177)..(177)

<223>第177位的Xaa是Ser,Gly或Ala;<223> Xaa at position 177 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Cys或被去除;<223> Xaa at position 178 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Arg或被去除;<223> Xaa at position 179 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(180)..(180)<222>(180)..(180)

<223>第180位的Xaa是Leu,Val,Ala或Ser或被去除;<223> Xaa at position 180 is Leu, Val, Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(181)..(181)<222>(181)..(181)

<223>第181位的Xaa是Val或Ala或被去除;<223> Xaa at position 181 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(182)..(182)<222>(182)..(182)

<223>第182位的Xaa是Phe,Ala,Thr或Met或被去除;<223> Xaa at position 182 is Phe, Ala, Thr or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(183)..(183)<222>(183)..(183)

<223>第183位的Xaa是Leu或Val或被去除;<223> Xaa at position 183 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(184)..(184)<222>(184)..(184)

<223>第184位的Xaa是Leu,Phe或Met或被去除;<223> Xaa at position 184 is Leu, Phe or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(188)..(188)<222>(188)..(188)

<223>第188位的Xaa是Cys,Gly或Ser或被去除;<223> Xaa at position 188 is Cys, Gly or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(189)..(189)<222>(189)..(189)

<223>第189位的Xaa是Val,Ile或Met或被去除;<223> Xaa at position 189 is Val, Ile or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(190)..(190)<222>(190)..(190)

<223>第190位的Xaa是Ala,Val,Met或Ile或被去除;<223> Xaa at position 190 is Ala, Val, Met or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(194)..(194)<222>(194)..(194)

<223>第194位的Xaa是Tyr或Cys或被去除;<223> Xaa at position 194 is Tyr or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(201)..(201)<222>(201)..(201)

<223>第102位的Xaa是Val或Leu或被去除;<223> Xaa at position 102 is Val or Leu or is removed;

<400>27<400>27

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

            100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa IleSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa Ile

        115                 120                 125115 120 125

His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser XaaHis Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser Xaa

    130                 135                 140130 135 140

Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa

145                 150                 155                 160145 150 155 160

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

                165                 170                 175165 170 175

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa Xaa Ala AsnXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa Xaa Ala Asn

            180                 185                 190180 185 190

Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr LeuTyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu

        195                 200195 200

<210>28<210>28

<211>189<211>189

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 123rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(124)..(124)<222>(124)..(124)

<223>第124位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 124th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 125th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Arg或Ser或被去除;<223> Xaa at position 127 is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Val或Leu或被去除;<223> Xaa at position 130 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(131)..(131)<222>(131)..(131)

<223>第131位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 131 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(136)..(136)<222>(136)..(136)

<223>第136位的Xaa是Val或Ala或被去除;<223> Xaa at position 136 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(138)..(138)<222>(138)..(138)

<223>第138位的Xaa是Leu或Met或被去除;<223> Xaa at position 138 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(142)..(142)<222>(142)..(142)

<223>第142位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 142 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 145 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(146)..(146)<222>(146)..(146)

<223>第146位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 146 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(147)..(147)<222>(147)..(147)

<223>第147位的Xaa是Val或被去除;<223> Xaa at position 147 is Val or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(148)..(148)<222>(148)..(148)

<223>第148位的Xaa是Lys或被去除;<223> Xaa at position 148 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(149)..(149)<222>(149)..(149)

<223>第149位的Xaa是Tyr或Cys;<223> Xaa at position 149 is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(151)..(151)<222>(151)..(151)

<223>第151位的Xaa是Tyr或Phe;<223> Xaa at position 151 is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Asp或Asn;<223> Xaa at position 153 is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Glu或Val;<223> Xaa at position 154 is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 155 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(158)..(158)<222>(158)..(158)

<223>第158位的Xaa是Thr,Glu或Ser;<223> Xaa at position 158 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(159)..(159)<222>(159)..(159)

<223>第159位的Xaa是Arg或Ser;<223> Xaa at position 159 is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 161 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(164)..(164)<222>(164)..(164)

<223>第164位的Xaa是Asn或Gly或被去除;<223> Xaa at position 164 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(165)..(165)<222>(165)..(165)

<223>第165位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 165 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(167)..(167)<222>(167)..(167)

<223>第167位的Xaa是Leu或Trp或被去除;<223> Xaa at position 167 is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(169)..(169)<222>(169)..(169)

<223>第169位的Xaa是Ile或Leu或被去除;<223> Xaa at position 169 is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 171 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Ile或Val或被去除;<223> Xaa at position 173 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Leu或Phe或被去除;<223> Xaa at position 174 is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Phe或Leu或被去除;<223> Xaa at position 175 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Gly或Leu或被去除;<223> Xaa at position 178 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Val或Ile或被去除;<223> Xaa at position 179 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(182)..(182)<222>(182)..(182)

<223>第182位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 182 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(187)..(187)<222>(187)..(187)

<223>第187位的Xaa是Val或Ile或被去除;<223> Xaa at position 187 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(188)..(188)<222>(188)..(188)

<223>第188位的Xaa是Ile或Val或被去除;<223> Xaa at position 188 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(189)..(189)<222>(189)..(189)

<223>第189位的Xaa是Gln或Cys或被去除;<223> Xaa at position 189 is Gln or Cys or is removed;

<400>28<400>28

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

ro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cysro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

           100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Phe Xaa LeuSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Phe Xaa Leu

        115                 120                 125115 120 125

Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa Pro TrpTyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa Pro Trp

    130                 135                 140130 135 140

Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa Xaa AsnXaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa Xaa Asn

145                 150                 155                 160145 150 155 160

Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa Xaa AlaXaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa Xaa Ala

                165                 170                 175165 170 175

Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa XaaIle Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa

           180                 185180 185

<210>29<210>29

<211>182<211>182

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 123rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(124)..(124)<222>(124)..(124)

<223>第124位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 124th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 125th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(136)..(136)<222>(136)..(136)

<223>第136位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 136 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(140)..(140)<222>(140)..(140)

<223>第140位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 140 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Met,Thr,Ile或Ala或被去除;<223> Xaa at position 145 is Met, Thr, Ile or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(148)..(148)<222>(148)..(148)

<223>第148位的Xaa是His,Pro,Gln或Thr;<223> Xaa at position 148 is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(149)..(149)<222>(149)..(149)

<223>第149位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 149 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(150)..(150)<222>(150)..(150)

<223>第150位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 150 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(151)..(151)<222>(151)..(151)

<223>第151位的Xaa是Gly或Ser;<223> Xaa at position 151 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Thr,Leu,Phe或Ala;<223> Xaa at position 152 is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Phe,Ser或Leu;<223> The 155th Xaa is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 156 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(157)..(157)<222>(157)..(157)

<223>第157位的Xaa是Lys或Arg;<223> Xaa at position 157 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(160)..(160)<222>(160)..(160)

<223>第160位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 160 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 161 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(163)..(163)<222>(163)..(163)

<223>第163位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 163 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(164)..(164)<222>(164)..(164)

<223>第164位的Xaa是Phe或Leu或被去除;<223> Xaa at position 164 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(165)..(165)<222>(165)..(165)

<223>第165位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 165 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(170)..(170)<222>(170)..(170)

<223>第170位的Xaa是Leu或Met或被去除;<223> The 170th Xaa is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是Met或Leu或被去除;<223> Xaa at position 171 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Ile或Val或被去除;<223> Xaa at position 174 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Val或Leu或被去除;<223> Xaa at position 179 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(181)..(181)<222>(181)..(181)

<223>第181位的Xaa是Asn或Lys或被去除;<223> Xaa at position 181 is Asn or Lys or is removed;

<400>29<400>29

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

            100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Ser Thr LeuSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Ser Thr Leu

        115                 120                 125115 120 125

Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa Phe Ala Phe ValThr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa Phe Ala Phe Val

    130                 135                 140130 135 140

Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa Xaa Leu Phe XaaXaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa Xaa Leu Phe Xaa

145                 150                 155                 160145 150 155 160

Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val Ala Xaa Leu TyrXaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val Ala Xaa Leu Tyr

                165                 170                 175165 170 175

Cys Phe Xaa Asn Xaa GluCys Phe Xaa Asn Xaa Glu

            180                           

<210>30<210>30

<211>270<211>270

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 123rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(124)..(124)<222>(124)..(124)

<223>第124位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 124th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 125th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Tyr或Ala或被去除;<223> Xaa at position 127 is Tyr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Leu,Ala或Met或被去除;<223> Xaa at position 130 is Leu, Ala or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(134)..(134)<222>(134)..(134)

<223>第134位的Xaa是Ala或Gly或被去除;<223> Xaa at position 134 is Ala or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(137)..(137)<222>(137)..(137)

<223>第137位的Xaa是Ile,Val或Met或被去除;<223> Xaa at position 137 is Ile, Val or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(139)..(139)<222>(139)..(139)

<223>第139位的Xaa是Leu或Val或被去除;<223> Xaa at position 139 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(140)..(140)<222>(140)..(140)

<223>第140位的Xaa是Arg或Lys或被去除;<223> Xaa at position 140 is Arg or Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(141)..(141)<222>(141)..(141)

<223>第141位的Xaa是Ala或Ser或被去除;<223> Xaa at position 141 is Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(142)..(142)<222>(142)..(142)

<223>第142位的Xaa是Leu或Ser或被去除;<223> Xaa at position 142 is Leu or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(144)..(144)<222>(144)..(144)

<223>第144位的Xaa是Val或Leu或被去除;<223> Xaa at position 144 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Phe或Leu或被去除;<223> Xaa at position 145 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(146)..(146)<222>(146)..(146)

<223>第146位的Xaa是Ile或Val或被去除;<223> Xaa at position 146 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(147)..(147)<222>(147)..(147)

<223>第147位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 147 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(149)..(149)<222>(149)..(149)

<223>第149位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 149 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(150)..(150)<222>(150)..(150)

<223>第150位的Xaa是Ala,Leu或Val;<223> The 150th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Lys,Arg或Asp;<223> Xaa at position 152 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 153 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Met,Arg或Ser;<223> Xaa at position 154 is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Tyr或Asn;<223> Xaa at position 155 is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Ser或Arg;<223> Xaa at position 156 is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(157)..(157)<222>(157)..(157)

<223>第157位的Xaa是Thr,Gln或Ala;<223> Xaa at position 157 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(158)..(158)<222>(158)..(158)

<223>第158位的Xaa是Lys或Arg或跳过;<223> Xaa at position 158 is Lys or Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(159)..(159)<222>(159)..(159)

<223>第159位的Xaa是Ala,Ile或Ser;<223> Xaa at position 159 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(160)..(160)<222>(160)..(160)

<223>第160位的Xaa是Ala,Gly或Ile;<223> Xaa at position 160 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 161 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(162)..(162)<222>(162)..(162)

<223>第162位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 162 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(163)..(163)<222>(163)..(163)

<223>第163位的Xaa是His或Leu;<223> Xaa at position 163 is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(164)..(164)<222>(164)..(164)

<223>第164位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 164 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(165)..(165)<222>(165)..(165)

<223>第165位的Xaa是Trp,Val或Gln;<223> Xaa at position 165 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(166)..(166)<222>(166)..(166)

<223>第166位的Xaa是Asp或Ser;<223> Xaa at position 166 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(167)..(167)<222>(167)..(167)

<223>第167位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 167 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(168)..(168)<222>(168)..(168)

<223>第168位的Xaa是Arg或跳过;<223> The 168th Xaa is Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(169)..(169)<222>(169)..(169)

<223>第169位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 169 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是Ser或Asp;<223> Xaa at position 171 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(172)..(172)<222>(172)..(172)

<223>第172位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 172 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Gln,Glu或Gly;<223> Xaa at position 173 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Asp,Ala或Thr;<223> Xaa at position 174 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 175 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(176)..(176)<222>(176)..(176)

<223>第176位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 176 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(177)..(177)<222>(177)..(177)

<223>第177位的Xaa是Ser,Gly或Ala;<223> Xaa at position 177 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Cys或被去除;<223> Xaa at position 178 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Arg或被去除;<223> Xaa at position 179 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(180)..(180)<222>(180)..(180)

<223>第180位的Xaa是Leu,Val,Ala或Ser或被去除;<223> Xaa at position 180 is Leu, Val, Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(181)..(181)<222>(181)..(181)

<223>第181位的Xaa是Val或Ala或被去除;<223> Xaa at position 181 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(182)..(182)<222>(182)..(182)

<223>第182位的Xaa是Phe,Ala,Thr或Met或被去除;<223> Xaa at position 182 is Phe, Ala, Thr or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(183)..(183)<222>(183)..(183)

<223>第183位的Xaa是Leu或Val或被去除;<223> Xaa at position 183 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(184)..(184)<222>(184)..(184)

<223>第184位的Xaa是Leu,Phe或Met或被去除;<223> Xaa at position 184 is Leu, Phe or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(188)..(188)<222>(188)..(188)

<223>第188位的Xaa是Cys,Gly或Ser或被去除;<223> Xaa at position 188 is Cys, Gly or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(189)..(189)<222>(189)..(189)

<223>第189位的Xaa是Val,Ile或Met或被去除;<223> Xaa at position 189 is Val, Ile or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(190)..(190)<222>(190)..(190)

<223>第190位的Xaa是Ala,Val,Met或Ile或被去除;<223> Xaa at position 190 is Ala, Val, Met or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(194)..(194)<222>(194)..(194)

<223>第194位的Xaa是Tyr或Cys或被去除;<223> Xaa at position 194 is Tyr or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(201)..(201)<222>(201)..(201)

<223>第201位的Xaa是Val或Leu或被去除;<223> Xaa at position 201 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(204)..(204)<222>(204)..(204)

<223>第204位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 204th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(205)..(205)<222>(205)..(205)

<223>第205位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 205th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(206)..(206)<222>(206)..(206)

<223>第206位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 206th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(208)..(208)<222>(208)..(208)

<223>第208位的Xaa是Arg或Ser或被去除;<223> Xaa at position 208 is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(211)..(211)<222>(211)..(211)

<223>第211位的Xaa是Val或Leu或被去除;<223> Xaa at position 211 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(212)..(212)<222>(212)..(212)

<223>第212位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 212 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(217)..(217)<222>(217)..(217)

<223>第217位的Xaa是Val或Ala或被去除;<223> Xaa at position 217 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(219)..(219)<222>(219)..(219)

<223>第219位的Xaa是Leu或Met或被去除;<223> Xaa at position 219 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(223)..(223)<222>(223)..(223)

<223>第223位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 223 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(226)..(226)<222>(226)..(226)

<223>第226位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 226 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(227)..(227)<222>(227)..(227)

<223>第227位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 227 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(228)..(228)<222>(228)..(228)

<223>第228位的Xaa是Val或被去除;<223> Xaa at position 228 is Val or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(229)..(229)<222>(229)..(229)

<223>第229位的Xaa是Lys或被去除;<223> Xaa at position 229 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(230)..(230)<222>(230)..(230)

<223>第230位的Xaa是Tyr或Cys;<223> The 230th Xaa is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(232)..(232)<222>(232)..(232)

<223>第232位的Xaa是Tyr或Phe;<223> Xaa at position 232 is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(234)..(234)<222>(234)..(234)

<223>第234位的Xaa是Asp或Asn;<223> Xaa at the 234th position is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(235)..(235)<222>(235)..(235)

<223>第235位的Xaa是Glu或Val;<223> Xaa at position 235 is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(236)..(236)<222>(236)..(236)

<223>第236位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 236 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(239)..(239)<222>(239)..(239)

<223>第239位的Xaa是Thr,Glu或Ser;<223> Xaa at position 239 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(240)..(240)<222>(240)..(240)

<223>第240位的Xaa是Arg或Ser;<223> Xaa at the 240th position is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(242)..(242)<222>(242)..(242)

<223>第242位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 242 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(245)..(245)<222>(245)..(245)

<223>第245位的Xaa是Asn或Gly或被去除;<223> Xaa at position 245 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(246)..(246)<222>(246)..(246)

<223>第246位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 246 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(248)..(248)<222>(248)..(248)

<223>第248位的Xaa是Leu或Trp或被去除;<223> Xaa at position 248 is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(250)..(250)<222>(250)..(250)

<223>第250位的Xaa是Ile或Leu或被去除;<223> The 250th Xaa is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(252)..(252)<222>(252)..(252)

<223>第252位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 252 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(254)..(254)<222>(254)..(254)

<223>第254位的Xaa是Ile或Val或被去除;<223> Xaa at position 254 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(255)..(255)<222>(255)..(255)

<223>第255位的Xaa是Leu或Phe或被去除;<223> Xaa at position 255 is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(256)..(256)<222>(256)..(256)

<223>第256位的Xaa是Phe或Leu或被去除;<223> Xaa at position 256 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(259)..(259)<222>(259)..(259)

<223>第259位的Xaa是Gly或Leu或被去除;<223> Xaa at position 259 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(260)..(260)<222>(260)..(260)

<223>第260位的Xaa是Val或Ile或被去除;<223> Xaa at position 260 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(263)..(263)<222>(263)..(263)

<223>第263位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 263 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(268)..(268)<222>(268)..(268)

<223>第268位的Xaa是Val或Ile或被去除;<223> Xaa at position 268 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(269)..(269)<222>(269)..(269)

<223>第269位的Xaa是Ile或Val或被去除;<223> Xaa at position 269 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(270)..(270)<222>(270)..(270)

<223>第270位的Xaa是Gln或Cys或被去除;<223> Xaa at position 270 is Gln or Cys or is removed;

<400>30<400>30

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

            100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa IleSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa Ile

        115                 120                 125115 120 125

His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser XaaHis Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser Xaa

    130                 135                 140130 135 140

Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa

145                 150                 155                 160145 150 155 160

aa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaaaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

                165                 170                 175165 170 175

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa Xaa Ala AsnXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa Xaa Ala Asn

            180                 185                 190180 185 190

Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa Xaa Phe XaaTyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa Xaa Phe Xaa

        195                 200                 205195 200 205

Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa ProLeu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa Pro

    210                 215                 220210 215 220

Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa XaaTrp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa Xaa

225                 230                 235                 240225 230 235 240

Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa XaaAsn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa Xaa

                245                 250                 255245 250 255

Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa XaaAla Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa

            260                 265                 270260 265 270

<210>31<210>31

<211>263<211>263

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 123rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(124)..(124)<222>(124)..(124)

<223>第124位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 124th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 125th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Tyr或Ala或被去除;<223> Xaa at position 127 is Tyr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Leu,Ala或Met或被去除;<223> The 130th Xaa is Leu, Ala or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(134)..(134)<222>(134)..(134)

<223>第134位的Xaa是Ala或Gly或被去除;<223> Xaa at position 134 is Ala or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(137)..(137)<222>(137)..(137)

<223>第137位的Xaa是Ile,Val或Met或被去除;<223> Xaa at position 137 is Ile, Val or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(139)..(139)<222>(139)..(139)

<223>第139位的Xaa是Leu或Val或被去除;<223> Xaa at position 139 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(140)..(140)<222>(140)..(140)

<223>第140位的Xaa是Arg或Lys或被去除;<223> Xaa at position 140 is Arg or Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(141)..(141)<222>(141)..(141)

<223>第141位的Xaa是Ala或Ser或被去除;<223> Xaa at position 141 is Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(142)..(142)<222>(142)..(142)

<223>第142位的Xaa是Leu或Ser或被去除;<223> Xaa at position 142 is Leu or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(144)..(144)<222>(144)..(144)

<223>第144位的Xaa是Val或Leu或被去除;<223> Xaa at position 144 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Phe或Leu或被去除;<223> Xaa at position 145 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(146)..(146)<222>(146)..(146)

<223>第146位的Xaa是Ile或Val或被去除;<223> Xaa at position 146 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(147)..(147)<222>(147)..(147)

<223>第147位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 147 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(149)..(149)<222>(149)..(149)

<223>第149位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 149 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(150)..(150)<222>(150)..(150)

<223>第150位的Xaa是Ala,Leu或Val;<223> The 150th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Lys,Arg或Asp;<223> Xaa at position 152 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 153 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Met,Arg或Ser;<223> Xaa at position 154 is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Tyr或Asn;<223> Xaa at position 155 is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Ser或Arg;<223> Xaa at position 156 is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(157)..(157)<222>(157)..(157)

<223>第157位的Xaa是Thr,Gln或Ala;<223> Xaa at position 157 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(158)..(158)<222>(158)..(158)

<223>第158位的Xaa是Lys或Arg或跳过;<223> Xaa at position 158 is Lys or Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(159)..(159)<222>(159)..(159)

<223>第159位的Xaa是Ala,Ile或Ser;<223> Xaa at position 159 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(160)..(160)<222>(160)..(160)

<223>第160位的Xaa是Ala,Gly或Ile;<223> Xaa at position 160 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 161 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(162)..(162)<222>(162)..(162)

<223>第162位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 162 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(163)..(163)<222>(163)..(163)

<223>第163位的Xaa是His或Leu;<223> Xaa at position 163 is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(164)..(164)<222>(164)..(164)

<223>第164位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 164 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(165)..(165)<222>(165)..(165)

<223>第165位的Xaa是Trp,Val或Gln;<223> Xaa at position 165 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(166)..(166)<222>(166)..(166)

<223>第166位的Xaa是Asp或Ser;<223> Xaa at position 166 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(167)..(167)<222>(167)..(167)

<223>第167位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 167 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(168)..(168)<222>(168)..(168)

<223>第168位的Xaa是Arg或跳过;<223> The 168th Xaa is Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(169)..(169)<222>(169)..(169)

<223>第169位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 169 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是Ser或Asp;<223> Xaa at position 171 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(172)..(172)<222>(172)..(172)

<223>第172位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 172 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Gln,Glu或Gly;<223> Xaa at position 173 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Asp,Ala或Thr;<223> Xaa at position 174 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 175 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(176)..(176)<222>(176)..(176)

<223>第176位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 176 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(177)..(177)<222>(177)..(177)

<223>第177位的Xaa是Ser,Gly或Ala;<223> Xaa at position 177 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Cys或被去除;<223> Xaa at position 178 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Arg或被去除;<223> Xaa at position 179 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(180)..(180)<222>(180)..(180)

<223>第180位的Xaa是Leu,Val,Ala或Ser或被去除;<223> Xaa at position 180 is Leu, Val, Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(181)..(181)<222>(181)..(181)

<223>第181位的Xaa是Val或Ala或被去除;<223> Xaa at position 181 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(182)..(182)<222>(182)..(182)

<223>第182位的Xaa是Phe,Ala,Thr或Met或被去除;<223> Xaa at position 182 is Phe, Ala, Thr or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(183)..(183)<222>(183)..(183)

<223>第183位的Xaa是Leu或Val或被去除;<223> Xaa at position 183 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(184)..(184)<222>(184)..(184)

<223>第184位的Xaa是Leu,Phe或Met或被去除;<223> Xaa at position 184 is Leu, Phe or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(188)..(188)<222>(188)..(188)

<223>第188位的Xaa是Cys,Gly或Ser或被去除;<223> Xaa at position 188 is Cys, Gly or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(189)..(189)<222>(189)..(189)

<223>第189位的Xaa是Val,Ile或Met或被去除;<223> Xaa at position 189 is Val, Ile or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(190)..(190)<222>(190)..(190)

<223>第190位的Xaa是Ala,Val,Met或Ile或被去除;<223> Xaa at position 190 is Ala, Val, Met or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(194)..(194)<222>(194)..(194)

<223>第194位的Xaa是Tyr或Cys或被去除;<223> Xaa at position 194 is Tyr or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(201)..(201)<222>(201)..(201)

<223>第201位的Xaa是Val或Leu或被去除;<223> Xaa at position 201 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(204)..(204)<222>(204)..(204)

<223>第204位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 204th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(205)..(205)<222>(205)..(205)

<223>第205位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 205th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(206)..(206)<222>(206)..(206)

<223>第206位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 206th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(217)..(217)<222>(217)..(217)

<223>第217位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 217 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(221)..(221)<222>(221)..(221)

<223>第221位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 221 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(226)..(226)<222>(226)..(226)

<223>第226位的Xaa是Met,Thr,Ile或Ala或被去除;<223> Xaa at position 226 is Met, Thr, Ile or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(229)..(229)<222>(229)..(229)

<223>第229位的Xaa是His,Pro,Gln或Thr;<223> Xaa at position 229 is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(230)..(230)<222>(230)..(230)

<223>第230位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 230 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(231)..(231)<222>(231)..(231)

<223>第231位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 231 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(232)..(232)<222>(232)..(232)

<223>第232位的Xaa是Gly或Ser;<223> Xaa at position 232 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(233)..(233)<222>(233)..(233)

<223>第233位的Xaa是Thr,Leu,Phe或Ala;<223> Xaa at position 233 is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(236)..(236)<222>(236)..(236)

<223>第236位的Xaa是Phe,Ser或Leu;<223> Xaa at position 236 is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(237)..(237)<222>(237)..(237)

<223>第237位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 237 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(238)..(238)<222>(238)..(238)

<223>第238位的Xaa是Lys或Arg;<223> Xaa at position 238 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(241)..(241)<222>(241)..(241)

<223>第241位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 241 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(242)..(242)<222>(242)..(242)

<223>第242位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 242 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(244)..(244)<222>(244)..(244)

<223>第244位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 244 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(245)..(245)<222>(245)..(245)

<223>第245位的Xaa是Phe或Leu或被去除;<223> Xaa at position 245 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(246)..(246)<222>(246)..(246)

<223>第246位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 246 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(251)..(251)<222>(251)..(251)

<223>第251位的Xaa是Leu或Met或被去除;<223> Xaa at position 251 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(252)..(252)<222>(252)..(252)

<223>第252位的Xaa是Met或Leu或被去除;<223> Xaa at position 252 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(255)..(255)<222>(255)..(255)

<223>第255位的Xaa是Ile或Val或被去除;<223> Xaa at position 255 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(260)..(260)<222>(260)..(260)

<223>第260位的Xaa是Val或Leu或被去除;<223> Xaa at position 260 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(262)..(262)<222>(262)..(262)

<223>第262位的Xaa是Asn或Lys或被去除;<223> Xaa at position 262 is Asn or Lys or is removed;

<400>31<400>31

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

ys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Proys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

              85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

            100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa IleSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa Ile

        115                 120                 125115 120 125

His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser XaaHis Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser Xaa

    130                 135                 140130 135 140

Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa

145                 150                 155                 160145 150 155 160

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

                165                 170                 175165 170 175

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa XaaAla AsnXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa XaaAla Asn

            180                 185                 190180 185 190

Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa Xaa Ser ThrTyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa Xaa Ser Thr

        195                 200                 205195 200 205

Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa Phe Ala PheLeu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa Phe Ala Phe

    210                 215                 220210 215 220

Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa Xaa Leu PheVal Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa Xaa Leu Phe

225                 230                 235                 240225 230 235 240

Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val Ala Xaa LeuXaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val Ala Xaa Leu

            245                 250                 255245 250 255

Tyr Cys Phe Xaa Asn Xaa GluTyr Cys Phe Xaa Asn Xaa Glu

            260260

<210>32<210>32

<211>249<211>249

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 123rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(124)..(124)<222>(124)..(124)

<223>第124位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 124th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 125th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Arg或Ser或被去除;<223> Xaa at position 127 is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Val或Leu或被去除;<223> Xaa at position 130 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(131)..(131)<222>(131)..(131)

<223>第131位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 131 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(136)..(136)<222>(136)..(136)

<223>第136位的Xaa是Val或Ala或被去除;<223> Xaa at position 136 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(138)..(138)<222>(138)..(138)

<223>第138位的Xaa是Leu或Met或被去除;<223> Xaa at position 138 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(142)..(142)<222>(142)..(142)

<223>第142位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 142 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 145 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(146)..(146)<222>(146)..(146)

<223>第146位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 146 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(147)..(147)<222>(147)..(147)

<223>第147位的Xaa是Val或被去除;<223> Xaa at position 147 is Val or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(148)..(148)<222>(148)..(148)

<223>第148位的Xaa是Lys或被去除;<223> Xaa at position 148 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(149)..(149)<222>(149)..(149)

<223>第149位的Xaa是Tyr或Cys;<223> Xaa at position 149 is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(151)..(151)<222>(151)..(151)

<223>第151位的Xaa是Tyr或Phe;<223> Xaa at position 151 is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Asp或Asn;<223> Xaa at position 153 is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Glu或Val;<223> Xaa at position 154 is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 155 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(158)..(158)<222>(158)..(158)

<223>第158位的Xaa是Thr,Glu或Ser;<223> Xaa at position 158 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(159)..(159)<222>(159)..(159)

<223>第159位的Xaa是Arg或Ser;<223> Xaa at position 159 is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 161 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(164)..(164)<222>(164)..(164)

<223>第164位的Xaa是Asn或Gly或被去除;<223> Xaa at position 164 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(165)..(165)<222>(165)..(165)

<223>第165位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 165 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(167)..(167)<222>(167)..(167)

<223>第167位的Xaa是Leu或Trp或被去除;<223> Xaa at position 167 is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(169)..(169)<222>(169)..(169)

<223>第169位的Xaa是Ile或Leu或被去除;<223> Xaa at position 169 is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 171 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Ile或Val或被去除;<223> Xaa at position 173 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Leu或Phe或被去除;<223> Xaa at position 174 is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Phe或Leu或被去除;<223> Xaa at position 175 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Gly或Leu或被去除;<223> Xaa at position 178 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Val或Ile或被去除;<223> Xaa at position 179 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(182)..(182)<222>(182)..(182)

<223>第182位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 182 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(187)..(187)<222>(187)..(187)

<223>第187位的Xaa是Val或Ile或被去除;<223> Xaa at position 187 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(188)..(188)<222>(188)..(188)

<223>第188位的Xaa是Ile或Val或被去除;<223> Xaa at position 188 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(189)..(189)<222>(189)..(189)

<223>第189位的Xaa是Gln或Cys或被去除;<223> Xaa at position 189 is Gln or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(190)..(190)<222>(190)..(190)

<223>第190位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 190th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(191)..(191)<222>(191)..(191)

<223>第191位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 191st Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(192)..(192)<222>(192)..(192)

<223>第192位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 192nd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(203)..(203)<222>(203)..(203)

<223>第203位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 203 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(207)..(207)<222>(207)..(207)

<223>第207位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 207 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(212)..(212)<222>(212)..(212)

<223>第212位的Xaa是Met,Thr,Ile或Ala或被去除;<223> Xaa at position 212 is Met, Thr, Ile or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(215)..(215)<222>(215)..(215)

<223>第215位的Xaa是His,Pro,Gln或Thr;<223> Xaa at position 215 is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(216)..(216)<222>(216)..(216)

<223>第216位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 216 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(217)..(217)<222>(217)..(217)

<223>第217位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 217 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(218)..(218)<222>(218)..(218)

<223>第218位的Xaa是Gly或Ser;<223> Xaa at position 218 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(219)..(219)<222>(219)..(219)

<223>第219位的Xaa是Thr,Leu,Phe或Ala;<223> The 219th Xaa is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(222)..(222)<222>(222)..(222)

<223>第222位的Xaa是Phe,Ser或Leu;<223> Xaa at the 222nd position is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(223)..(223)<222>(223)..(223)

<223>第223位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 223 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(224)..(224)<222>(224)..(224)

<223>第224位的Xaa是Lys或Arg;<223> Xaa at position 224 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(227)..(227)<222>(227)..(227)

<223>第227位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 227 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(228)..(228)<222>(228)..(228)

<223>第228位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 228 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(230)..(230)<222>(230)..(230)

<223>第230位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 230 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(231)..(231)<222>(231)..(231)

<223>第231位的Xaa是Phe或Leu或被去除;<223> Xaa at position 231 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(232)..(232)<222>(232)..(232)

<223>第232位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 232 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(237)..(237)<222>(237)..(237)

<223>第237位的Xaa是Leu或Met或被去除;<223> Xaa at position 237 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(238)..(238)<222>(238)..(238)

<223>第238位的Xaa是Met或Leu或被去除;<223> Xaa at position 238 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(241)..(241)<222>(241)..(241)

<223>第241位的Xaa是Ile或Val或被去除;<223> Xaa at position 241 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(246)..(246)<222>(246)..(246)

<223>第246位的Xaa是Val或Leu或被去除;<223> Xaa at position 246 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(248)..(248)<222>(248)..(248)

<223>第248位的Xaa是Asn或Lys或被去除;<223> Xaa at position 248 is Asn or Lys or is removed;

<400>32<400>32

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

TrpArg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrpArg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

           100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Phe Xaa LeuSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Phe Xaa Leu

        115                 120                 125115 120 125

Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa Pro TrpTyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa Pro Trp

    130                 135                 140130 135 140

Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa Xaa AsnXaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa Xaa Asn

145                 150                 155                 160145 150 155 160

Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa Xaa AlaXaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa Xaa Ala

                165                 170                 175165 170 175

Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa Xaa Xaa XaaIle Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa Xaa Xaa Xaa

            180                 185                 190180 185 190

Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa PheSer Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa Phe

        195                 200                 205195 200 205

Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa LeuArg Xaa Xaa XaaAla Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa LeuArg Xaa Xaa Xaa

    210                 215                 220210 215 220

Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val AlaLeu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val Ala

225                 230                 235                 240225 230 235 240

Xaa Leu Tyr Cys Phe Xaa Asn Xaa GluXaa Leu Tyr Cys Phe Xaa Asn Xaa Glu

                245245

<210>33<210>33

<211>330<211>330

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<220><220>

<221>misc_feature<221>misc_feature

<222>(123)..(123)<222>(123)..(123)

<223>第123位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 123rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(124)..(124)<222>(124)..(124)

<223>第124位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 124th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(125)..(125)<222>(125)..(125)

<223>第125位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 125th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(127)..(127)<222>(127)..(127)

<223>第127位的Xaa是Tyr或Ala或被去除;<223> Xaa at position 127 is Tyr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(130)..(130)<222>(130)..(130)

<223>第130位的Xaa是Leu,Ala或Met或被去除;<223> Xaa at position 130 is Leu, Ala or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(134)..(134)<222>(134)..(134)

<223>第134位的Xaa是Ala或Gly或被去除;<223> Xaa at position 134 is Ala or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(137)..(137)<222>(137)..(137)

<223>第137位的Xaa是Ile,Val或Met或被去除;<223> Xaa at position 137 is Ile, Val or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(139)..(139)<222>(139)..(139)

<223>第139位的Xaa是Leu或Val或被去除;<223> Xaa at position 139 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(140)..(140)<222>(140)..(140)

<223>第140位的Xaa是Arg或Lys或被去除;<223> Xaa at position 140 is Arg or Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(141)..(141)<222>(141)..(141)

<223>第141位的Xaa是Ala或Ser或被去除;<223> Xaa at position 141 is Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(142)..(142)<222>(142)..(142)

<223>第142位的Xaa是Leu或Ser或被去除;<223> Xaa at position 142 is Leu or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(144)..(144)<222>(144)..(144)

<223>第144位的Xaa是Val或Leu或被去除;<223> Xaa at position 144 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(145)..(145)<222>(145)..(145)

<223>第145位的Xaa是Phe或Leu或被去除;<223> Xaa at position 145 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(146)..(146)<222>(146)..(146)

<223>第146位的Xaa是Ile或Val或被去除;<223> Xaa at position 146 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(147)..(147)<222>(147)..(147)

<223>第147位的Xaa是Lys,Arg,Gln,Asp,Glu,Asn或Ile;<223> Xaa at position 147 is Lys, Arg, Gln, Asp, Glu, Asn or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(149)..(149)<222>(149)..(149)

<223>第149位的Xaa是Ala,Gly,Thr,Trp,Val,Arg或Ile;<223> Xaa at position 149 is Ala, Gly, Thr, Trp, Val, Arg or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(150)..(150)<222>(150)..(150)

<223>第150位的Xaa是Ala,Leu或Val;<223> The 150th Xaa is Ala, Leu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(152)..(152)<222>(152)..(152)

<223>第152位的Xaa是Lys,Arg或Asp;<223> Xaa at position 152 is Lys, Arg or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(153)..(153)<222>(153)..(153)

<223>第153位的Xaa是Trp,Thr,Gln或Asn;<223> Xaa at position 153 is Trp, Thr, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(154)..(154)<222>(154)..(154)

<223>第154位的Xaa是Met,Arg或Ser;<223> Xaa at position 154 is Met, Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(155)..(155)<222>(155)..(155)

<223>第155位的Xaa是Tyr或Asn;<223> Xaa at position 155 is Tyr or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(156)..(156)<222>(156)..(156)

<223>第156位的Xaa是Ser或Arg;<223> Xaa at position 156 is Ser or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(157)..(157)<222>(157)..(157)

<223>第157位的Xaa是Thr,Gln或Ala;<223> Xaa at position 157 is Thr, Gln or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(158)..(158)<222>(158)..(158)

<223>第158位的Xaa是Lys或Arg或跳过;<223> Xaa at position 158 is Lys or Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(159)..(159)<222>(159)..(159)

<223>第159位的Xaa是Ala,Ile或Ser;<223> Xaa at position 159 is Ala, Ile or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(160)..(160)<222>(160)..(160)

<223>第160位的Xaa是Ala,Gly或Ile;<223> Xaa at position 160 is Ala, Gly or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(161)..(161)<222>(161)..(161)

<223>第161位的Xaa是Gln,Asp,Pro,Glu或Ile;<223> Xaa at position 161 is Gln, Asp, Pro, Glu or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(162)..(162)<222>(162)..(162)

<223>第162位的Xaa是Gln,Asp,Glu,Ser或Asn;<223> Xaa at position 162 is Gln, Asp, Glu, Ser or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(163)..(163)<222>(163)..(163)

<223>第163位的Xaa是His或Leu;<223> Xaa at position 163 is His or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(164)..(164)<222>(164)..(164)

<223>第164位的Xaa是Gln,Ser,Tyr或Glu;<223> Xaa at position 164 is Gln, Ser, Tyr or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(165)..(165)<222>(165)..(165)

<223>第165位的Xaa是Trp,Val或Gln;<223> Xaa at position 165 is Trp, Val or Gln;

<220><220>

<221>misc_feature<221>misc_feature

<222>(166)..(166)<222>(166)..(166)

<223>第166位的Xaa是Asp或Ser;<223> Xaa at position 166 is Asp or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(167)..(167)<222>(167)..(167)

<223>第167位的Xaa是Gly,Thr,Val,Ser或Ala;<223> Xaa at position 167 is Gly, Thr, Val, Ser or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(168)..(168)<222>(168)..(168)

<223>第168位的Xaa是Arg或跳过;<223> The 168th Xaa is Arg or skipped;

<220><220>

<221>misc_feature<221>misc_feature

<222>(169)..(169)<222>(169)..(169)

<223>第169位的Xaa是Leu,Trp,Arg,Thr或Tyr;<223> Xaa at position 169 is Leu, Trp, Arg, Thr or Tyr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(171)..(171)<222>(171)..(171)

<223>第171位的Xaa是Ser或Asp;<223> Xaa at position 171 is Ser or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(172)..(172)<222>(172)..(172)

<223>第172位的Xaa是Tyr,Asp或Thr;<223> Xaa at position 172 is Tyr, Asp or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(173)..(173)<222>(173)..(173)

<223>第173位的Xaa是Gln,Glu或Gly;<223> Xaa at position 173 is Gln, Glu or Gly;

<220><220>

<221>misc_feature<221>misc_feature

<222>(174)..(174)<222>(174)..(174)

<223>第174位的Xaa是Asp,Ala或Thr;<223> Xaa at position 174 is Asp, Ala or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(175)..(175)<222>(175)..(175)

<223>第175位的Xaa是Ser,Val,Leu或Met;<223> Xaa at position 175 is Ser, Val, Leu or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(176)..(176)<222>(176)..(176)

<223>第176位的Xaa是Leu,Ala,Thr或Val;<223> Xaa at position 176 is Leu, Ala, Thr or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(177)..(177)<222>(177)..(177)

<223>第177位的Xaa是Ser,Gly或Ala;<223> Xaa at position 177 is Ser, Gly or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(178)..(178)<222>(178)..(178)

<223>第178位的Xaa是Cys或被去除;<223> Xaa at position 178 is Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(179)..(179)<222>(179)..(179)

<223>第179位的Xaa是Arg或被去除;<223> Xaa at position 179 is Arg or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(180)..(180)<222>(180)..(180)

<223>第180位的Xaa是Leu,Val,Ala或Ser或被去除;<223> Xaa at position 180 is Leu, Val, Ala or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(181)..(181)<222>(181)..(181)

<223>第181位的Xaa是Val或Ala或被去除;<223> Xaa at position 181 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(182)..(182)<222>(182)..(182)

<223>第182位的Xaa是Phe,Ala,Thr或Met或被去除;<223> Xaa at position 182 is Phe, Ala, Thr or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(183)..(183)<222>(183)..(183)

<223>第183位的Xaa是Leu或Val或被去除;<223> Xaa at position 183 is Leu or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(184)..(184)<222>(184)..(184)

<223>第184位的Xaa是Leu,Phe或Met或被去除;<223> Xaa at position 184 is Leu, Phe or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(188)..(188)<222>(188)..(188)

<223>第188位的Xaa是Cys,Gly或Ser或被去除;<223> Xaa at position 188 is Cys, Gly or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(189)..(189)<222>(189)..(189)

<223>第189位的Xaa是Val,Ile或Met或被去除;<223> Xaa at position 189 is Val, Ile or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(190)..(190)<222>(190)..(190)

<223>第190位的Xaa是Ala,Val,Met或Ile或被去除;<223> Xaa at position 190 is Ala, Val, Met or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(194)..(194)<222>(194)..(194)

<223>第194位的Xaa是Tyr或Cys或被去除;<223> Xaa at position 194 is Tyr or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(201)..(201)<222>(201)..(201)

<223>第201位的Xaa是Val或Leu或被去除;<223> Xaa at position 201 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(204)..(204)<222>(204)..(204)

<223>第204位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 204th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(205)..(205)<222>(205)..(205)

<223>第205位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 205th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(206)..(206)<222>(206)..(206)

<223>第206位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 206th Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(208)..(208)<222>(208)..(208)

<223>第208位的Xaa是Arg或Ser或被去除;<223> Xaa at position 208 is Arg or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(211)..(211)<222>(211)..(211)

<223>第211位的Xaa是Val或Leu或被去除;<223> Xaa at position 211 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(212)..(212)<222>(212)..(212)

<223>第212位的Xaa是Ser,Gly或Cys或被去除;<223> Xaa at position 212 is Ser, Gly or Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(217)..(217)<222>(217)..(217)

<223>第217位的Xaa是Val或Ala或被去除;<223> Xaa at position 217 is Val or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(219)..(219)<222>(219)..(219)

<223>第219位的Xaa是Leu或Met或被去除;<223> Xaa at position 219 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(223)..(223)<222>(223)..(223)

<223>第223位的Xaa是Val,Leu或Ile或被去除;<223> Xaa at position 223 is Val, Leu or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(226)..(226)<222>(226)..(226)

<223>第226位的Xaa是Gly,Ala,Met或Val或被去除;<223> Xaa at position 226 is Gly, Ala, Met or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(227)..(227)<222>(227)..(227)

<223>第227位的Xaa是Ile,Val,Thr或Ala或被去除;<223> Xaa at position 227 is Ile, Val, Thr or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(228)..(228)<222>(228)..(228)

<223>第228位的Xaa是Val或被去除;<223> Xaa at position 228 is Val or removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(229)..(229)<222>(229)..(229)

<223>第229位的Xaa是Lys或被去除;<223> Xaa at position 229 is Lys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(230)..(230)<222>(230)..(230)

<223>第230位的Xaa是Tyr或Cys;<223> The 230th Xaa is Tyr or Cys;

<220><220>

<221>misc_feature<221>misc_feature

<222>(232)..(232)<222>(232)..(232)

<223>第232位的Xaa是Tyr或Phe;<223> Xaa at position 232 is Tyr or Phe;

<220><220>

<221>misc_feature<221>misc_feature

<222>(234)..(234)<222>(234)..(234)

<223>第234位的Xaa是Asp或Asn;<223> Xaa at the 234th position is Asp or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(235)..(235)<222>(235)..(235)

<223>第235位的Xaa是Glu或Val;<223> Xaa at position 235 is Glu or Val;

<220><220>

<221>misc_feature<221>misc_feature

<222>(236)..(236)<222>(236)..(236)

<223>第236位的Xaa是Gly,Gln,Glu或Asp;<223> Xaa at position 236 is Gly, Gln, Glu or Asp;

<220><220>

<221>misc_feature<221>misc_feature

<222>(239)..(239)<222>(239)..(239)

<223>第239位的Xaa是Thr,Glu或Ser;<223> Xaa at position 239 is Thr, Glu or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(240)..(240)<222>(240)..(240)

<223>第240位的Xaa是Arg或Ser;<223> Xaa at the 240th position is Arg or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(242)..(242)<222>(242)..(242)

<223>第242位的Xaa是Ser,Asp,Asn或Met;<223> Xaa at position 242 is Ser, Asp, Asn or Met;

<220><220>

<221>misc_feature<221>misc_feature

<222>(245)..(245)<222>(245)..(245)

<223>第245位的Xaa是Asn或Gly或被去除;<223> Xaa at position 245 is Asn or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(246)..(246)<222>(246)..(246)

<223>第246位的Xaa是Tyr或Phe或被去除;<223> Xaa at position 246 is Tyr or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(248)..(248)<222>(248)..(248)

<223>第248位的Xaa是Leu或Trp或被去除;<223> Xaa at position 248 is Leu or Trp or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(250)..(250)<222>(250)..(250)

<223>第250位的Xaa是Ile或Leu或被去除;<223> The 250th Xaa is Ile or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(252)..(252)<222>(252)..(252)

<223>第252位的Xaa是Leu,Phe,Ile或Ser或被去除;<223> Xaa at position 252 is Leu, Phe, Ile or Ser or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(254)..(254)<222>(254)..(254)

<223>第254位的Xaa是Ile或Val或被去除;<223> Xaa at position 254 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(255)..(255)<222>(255)..(255)

<223>第255位的Xaa是Leu或Phe或被去除;<223> Xaa at position 255 is Leu or Phe or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(256)..(256)<222>(256)..(256)

<223>第256位的Xaa是Phe或Leu或被去除;<223> Xaa at position 256 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(259)..(259)<222>(259)..(259)

<223>第259位的Xaa是Gly或Leu或被去除;<223> Xaa at position 259 is Gly or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(260)..(260)<222>(260)..(260)

<223>第260位的Xaa是Val或Ile或被去除;<223> Xaa at position 260 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(263)..(263)<222>(263)..(263)

<223>第263位的Xaa是Leu,Phe或Ile或被去除;<223> Xaa at position 263 is Leu, Phe or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(268)..(268)<222>(268)..(268)

<223>第268位的Xaa是Val或Ile或被去除;<223> Xaa at position 268 is Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(269)..(269)<222>(269)..(269)

<223>第269位的Xaa是Ile或Val或被去除;<223> Xaa at position 269 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(270)..(270)<222>(270)..(270)

<223>第270位的Xaa是Gln,Cys或被去除;<223> Xaa at position 270 is Gln, Cys or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(271)..(271)<222>(271)..(271)

<223>第271位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer;<223> The 271st Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer;

<220><220>

<221>misc_feature<221>misc_feature

<222>(272)..(272)<222>(272)..(272)

<223>第272位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 272nd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(273)..(273)<222>(273)..(273)

<223>第273位的Xaa是Gly Thr Gly,Gly Ala Pro,Gly Pro Gly或Gly Gly Gly GlySer或被去除;<223> The 273rd Xaa is Gly Thr Gly, Gly Ala Pro, Gly Pro Gly or Gly Gly Gly GlySer or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(284)..(284)<222>(284)..(284)

<223>第284位的Xaa是Thr,Val或Ile或被去除;<223> Xaa at position 284 is Thr, Val or Ile or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(288)..(288)<222>(288)..(288)

<223>第288位的Xaa是Ile,Val,Leu或Ala或被去除;<223> Xaa at position 288 is Ile, Val, Leu or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(293)..(293)<222>(293)..(293)

<223>第293位的Xaa是Met,Thr,Ile或Ala或被去除;<223> Xaa at position 293 is Met, Thr, Ile or Ala or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(296)..(296)<222>(296)..(296)

<223>第296位的Xaa是His,Pro,Gln或Thr;<223> Xaa at position 296 is His, Pro, Gln or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(297)..(297)<222>(297)..(297)

<223>第297位的Xaa是Ala,Lys,Val或Thr;<223> Xaa at position 297 is Ala, Lys, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(298)..(298)<222>(298)..(298)

<223>第298位的Xaa是Arg,Lys,Gln或Glu;<223> Xaa at position 298 is Arg, Lys, Gln or Glu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(299)..(299)<222>(299)..(299)

<223>第299位的Xaa是Gly或Ser;<223> Xaa at position 299 is Gly or Ser;

<220><220>

<221>misc_feature<221>misc_feature

<222>(300)..(300)<222>(300)..(300)

<223>第300位的Xaa是Thr,Leu,Phe或Ala;<223> The 300th Xaa is Thr, Leu, Phe or Ala;

<220><220>

<221>misc_feature<221>misc_feature

<222>(303)..(303)<222>(303)..(303)

<223>第303位的Xaa是Phe,Ser或Leu;<223> Xaa at the 303rd position is Phe, Ser or Leu;

<220><220>

<221>misc_feature<221>misc_feature

<222>(304)..(304)<222>(304)..(304)

<223>第304位的Xaa是Ile,Ala,Val或Thr;<223> Xaa at position 304 is Ile, Ala, Val or Thr;

<220><220>

<221>misc_feature<221>misc_feature

<222>(305)..(305)<222>(305)..(305)

<223>第305位的Xaa是Lys或Arg;<223> Xaa at position 305 is Lys or Arg;

<220><220>

<221>misc_feature<221>misc_feature

<222>(308)..(308)<222>(308)..(308)

<223>第308位的Xaa是Thr,Phe,Tyr或Ile;<223> Xaa at position 308 is Thr, Phe, Tyr or Ile;

<220><220>

<221>misc_feature<221>misc_feature

<222>(309)..(309)<222>(309)..(309)

<223>第309位的Xaa是Glu,Asp,Gln或Asn;<223> Xaa at position 309 is Glu, Asp, Gln or Asn;

<220><220>

<221>misc_feature<221>misc_feature

<222>(311)..(311)<222>(311)..(311)

<223>第311位的Xaa是Ser,Phe或Leu或去除Leu;<223> Xaa at position 311 is Ser, Phe or Leu or Leu is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(312)..(312)<222>(312)..(312)

<223>第312位的Xaa是Phe或Leu或被去除;<223> Xaa at position 312 is Phe or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(313)..(313)<222>(313)..(313)

<223>第313位的Xaa是Thr,Ser或Gly或被去除;<223> Xaa at position 313 is Thr, Ser or Gly or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(318)..(318)<222>(318)..(318)

<223>第318位的Xaa是Leu或Met或被去除;<223> Xaa at position 318 is Leu or Met or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(319)..(319)<222>(319)..(319)

<223>第319位的Xaa是Met或Leu或被去除;<223> Xaa at position 319 is Met or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(322)..(322)<222>(322)..(322)

<223>第322位的Xaa是Ile或Val或被去除;<223> Xaa at position 322 is Ile or Val or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(327)..(327)<222>(327)..(327)

<223>第327位的Xaa是Val或Leu或被去除;<223> Xaa at position 327 is Val or Leu or is removed;

<220><220>

<221>misc_feature<221>misc_feature

<222>(329)..(329)<222>(329)..(329)

<223>第329位的Xaa是Asn或Lys或被去除;<223> Xaa at position 329 is Asn or Lys or is removed;

<400>33<400>33

Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys TrpArg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln Lys Trp

1               5                   10                  151 5 10 15

Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro ProArg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp Pro Pro

            20                  25                  3020 25 30

Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala CysPro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr Ala Cys

        35                  40                  4535 40 45

Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro TrpTrp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys Pro Trp

    50                  55                  6050 55 60

Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg PheTyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val Tyr Arg Phe

65                  70                  75                  8065 70 75 80

Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu ProCys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser Leu Pro

                85                  90                  9585 90 95

Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg SerTrp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu Arg Ser

            100                 105                 110100 105 110

Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa IleSer Pro Glu Glu Gln Leu Leu Phe Leu Tyr Xaa Xaa Xaa Asn Xaa Ile

        115                 120                 125115 120 125

His Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser XaaHis Xaa Asn Leu Phe Xaa Ser Phe Xaa Leu Xaa Xaa Xaa Xaa Ser Xaa

    130                 135                 140130 135 140

Xaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Asp Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa

145                 150                 155                 160145 150 155 160

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Leu Xaa Xaa Xaa Xaa Xaa Xaa

                165                 170                 175165 170 175

Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa Xaa Ala AsnXaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Met Gln Tyr Xaa Xaa Xaa Ala Asn

        180                 185                 190180 185 190

Tyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa Xaa Phe XaaTyr Xaa Trp Leu Leu Val Glu Gly Xaa Tyr Leu Xaa Xaa Xaa Phe Xaa

        195                 200                 205195 200 205

Leu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa ProLeu Tyr Xaa Xaa Ile Gly Trp Gly Xaa Pro Xaa Leu Phe Val Xaa Pro

    210                 215                 220210 215 220

Trp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa XaaTrp Xaa Xaa Xaa Xaa Xaa Leu Xaa Glu Xaa Xaa Xaa Cys Trp Xaa Xaa

225                 230                 235                 240225 230 235 240

Asn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa XaaAsn Xaa Asn Met Xaa Xaa Trp Xaa Ile Xaa Arg Xaa Pro Xaa Xaa Xaa

                245                 250                 255245 250 255

Ala Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa Xaa XaaAla Ile Xaa Xaa Asn Phe Xaa Ile Phe Val Arg Xaa Xaa Xaa Xaa Xaa

            260                 265                 270260 265 270

Xaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val XaaXaa Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Xaa His Glu Val Xaa

        275                 280                 285275 280 285

Phe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa XaaPhe Ala Phe Val Xaa Asp Glu Xaa Xaa Xaa Xaa Xaa Leu Arg Xaa Xaa

    290                 295                 300290 295 300

Xaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa ValXaa Leu Phe Xaa Xaa Leu Xaa Xaa Xaa Ser Phe Gln Gly Xaa Xaa Val

305                 310                 315                 320305 310 315 320

Ala Xaa Leu Tyr Cys Phe Xaa Asn Xaa GluAla Xaa Leu Tyr Cys Phe Xaa Asn Xaa Glu

                325                 330325 330

<210>34<210>34

<211>227<211>227

<212>PRT<212>PRT

<213>人<213> people

<400>34<400>34

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu GlyAsp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

1               5                   10                  151 5 10 15

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu MetGly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

            20                  25                  3020 25 30

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser HisIle Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

        35                  40                  4535 40 45

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu ValGlu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

    50                  55                  6050 55 60

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr TyrHis Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

65                  70                  75                  8065 70 75 80

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn GlyArg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

                85                  90                  9585 90 95

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro IleLys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

            100                 105                 110100 105 110

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln ValGlu Lys Thr Ile Ser Lys Ala Lys Gly Gly Gln Pro Arg Glu Pro Gln Val

        115                 120                 125115 120 125

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val SerTyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

    130                 135                 140130 135 140

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

145                 150                 155                 160145 150 155 160

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro ProTrp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

                165                 170                 175165 170 175

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr ValVal Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

            180                 185                 190180 185 190

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val MetAsp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

        195                 200                 205195 200 205

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu SerHis Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

    210                 215                 220210 215 220

Pro Gly LysPro Gly Lys

225225

<210>35<210>35

<211>381<211>381

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>35<400>35

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu TyrAla Pro Ala Gln Val Met Asp Phe Leu Phe Glu Lys Trp Lys Leu Tyr

        35                  40                  4535 40 45

Gly Asp Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr GluGly Asp Gln Cys His His Asn Leu Ser Leu Leu Pro Pro Pro Thr Glu

    50                  55                  6050 55 60

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

65                  70                  75                  8065 70 75 80

Pro Ala Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro TrpPro Ala Asn Thr Thr Ala Asn Ile Ser Cys Pro Trp Tyr Leu Pro Trp

                85                  90                  9585 90 95

His His Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro AspHis His Lys Val Gln His Arg Phe Val Phe Lys Arg Cys Gly Pro Asp

            100                 105                 110100 105 110

Gly Gln Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala SerGly Gln Trp Val Arg Gly Pro Arg Gly Gln Pro Trp Arg Asp Ala Ser

        115                 120                 125115 120 125

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

    130                 135                 140130 135 140

Lys Met Tyr Ser Ser Phe Gln Gly Pro Gly Asp Lys Thr His Thr CysLys Met Tyr Ser Ser Phe Gln Gly Pro Gly Asp Lys Thr His Thr Cys

145                 150                 155                 160145 150 155 160

Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe LeuPro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu

                165                 170                 175165 170 175

Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro GluPhe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu

            180                 185                 190180 185 190

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

        195                 200                 205195 200 205

Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr LysPhe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys

    210                 215                 220210 215 220

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

225                 230                 235                 240225 230 235 240

Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys LysThr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys

                245                 250                 255245 250 255

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

            260                 265                 270260 265 270

Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro SerAla Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser

        275                 280                 285275 280 285

Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val LysArg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys

    290                 295                 300290 295 300

Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly GlnGly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln

305                 310                 315                 320305 310 315 320

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

                325                 330                 335325 330 335

Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp GlnSer Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln

            340                 345                 350340 345 350

Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His AsnGln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn

        355                 360                 365355 360 365

His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly LysHis Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

    370                 375                 380370 375 380

<210>36<210>36

<211>340<211>340

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>36<400>36

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu LysAla Pro Asn Ala Ile His Ala Asn Leu Phe Ala Ser Phe Val Leu Lys

        35                  40                  4535 40 45

Ala Ser Ser Val Leu Val Ile Asp Gly Leu Leu Arg Thr Arg Tyr SerAla Ser Ser Val Leu Val Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser

    50                  55                  6050 55 60

Gln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu Ser Asp GlyGln Lys Ile Gly Asp Asp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly

65                  70                  75                  8065 70 75 80

Ala Val Ala Gly Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly IleAla Val Ala Gly Cys Arg Val Ala Ala Val Phe Met Gln Tyr Gly Ile

                85                  90                  9585 90 95

Val Ala Asn Tyr Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu Gly ProVal Ala Asn Tyr Cys Trp Leu Leu Val Glu Gly Leu Tyr Leu Gly Pro

            100                 105                 110100 105 110

Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu LeuGly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu

        115                 120                 125115 120 125

Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr LeuGly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu

    130                 135                 140130 135 140

Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val SerMet Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser

145                 150                 155                 160145 150 155 160

His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val GluHis Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu

                165                 170                 175165 170 175

Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ash Ser ThrVal His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Ash Ser Thr

            180                 185                 190180 185 190

Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu AsnTyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn

        195                 200                 205195 200 205

Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala ProGly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro

    210                 215                 220210 215 220

Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro GlnIle Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln

225                 230                 235                 240225 230 235 240

Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln ValVal Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val

                245                 250                 255245 250 255

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

            260                 265                 270260 265 270

Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr ProGlu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro

        275                 280                 285275 280 285

Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu ThrPro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr

    290                 295                 300290 295 300

Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser ValVal Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val

305                 310                 315                 320305 310 315 320

Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser LeuMet His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu

                325                 330                 335325 330 335

Ser Pro Gly LysSer Pro Gly Lys

            340340

<210>37<210>37

<211>318<211>318

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>37<400>37

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

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

        35                  40                  4535 40 45

Phe Ala Phe Val Thr Asp Glu His Ala Gln Gly Thr Leu Arg Ser AlaPhe Ala Phe Val Thr Asp Glu His Ala Gln Gly Thr Leu Arg Ser Ala

    50                  55                  6050 55 60

Lys Leu Phe Phe Asp Leu Phe Leu Ser Ser Phe Gln Gly Leu Leu ValLys Leu Phe Phe Asp Leu Phe Leu Ser Ser Phe Gln Gly Leu Leu Val

65                  70                  75                  8065 70 75 80

Ala Val Leu Tyr Cys Phe Leu Asn Gly Pro Gly Asp Lys Thr His ThrAla Val Leu Tyr Cys Phe Leu Asn Gly Pro Gly Asp Lys Thr His Thr

                85                  90                  9585 90 95

Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val PheCys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe

            100                 105                 110100 105 110

Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr ProLeu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro

        115                 120                 125115 120 125

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

    130                 135                 140130 135 140

Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys ThrLys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr

145                 150                 155                 160145 150 155 160

Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser ValLys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val

                165                 170                 175165 170 175

Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys CysLeu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys

            180                 185                 190180 185 190

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

        195                 200                 205195 200 205

Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro ProLys Ala Lys Gly Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro

    210                 215                 220210 215 220

Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu ValSer Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val

225                 230                 235                 240225 230 235 240

Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn GlyLys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly

                245                 250                 255245 250 255

Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser AspGln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp

            260                 265                 270260 265 270

Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg TrpGly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp

        275                 280                 285275 280 285

Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu HisGln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His

    290                 295                 300290 295 300

Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly LysAsn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

305                 310                 315305 310 315

<210>38<210>38

<211>316<211>316

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>38<400>38

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Val Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys IleAla Pro Val Ile Asp Gly Leu Leu Arg Thr Arg Tyr Ser Gln Lys Ile

        35                  40                  4535 40 45

Gly Asp Asp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val AlaGly Asp Asp Leu Ser Val Ser Thr Trp Leu Ser Asp Gly Ala Val Ala

        50                  55                  6050 55 60

Gly Gly Gly Gly Ser Asp Glu His Ala Gln Gly Thr Leu Arg Ser AlaGly Gly Gly Gly Ser Asp Glu His Ala Gln Gly Thr Leu Arg Ser Ala

65                  70                  75                  8065 70 75 80

Lys Leu Phe Phe Asp Leu Gly Pro Gly Asp Lys Thr His Thr Cys ProLys Leu Phe Phe Asp Leu Gly Pro Gly Asp Lys Thr His Thr Cys Pro

                85                  90                  9585 90 95

Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu PhePro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe

            100                 105                 110100 105 110

Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu ValPro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val

        115                 120                 125115 120 125

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

    130                 135                 140130 135 140

Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys ProAsn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro

145                 150                 155                 160145 150 155 160

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

                165                 170                 175165 170 175

Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys ValVal Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val

            180                 185                 190180 185 190

Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys AlaSer Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala

      195                 200                 205195 200 205

Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser ArgLys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg

    210                 215                 220210 215 220

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

225                 230                 235                 240225 230 235 240

Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln ProPhe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro

                245                 250                 255245 250 255

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

            260                 265                 270260 265 270

Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln GlnPhe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln

        275                 280                 285275 280 285

Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn HisGly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His

    290                 295                 300290 295 300

Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly LysTyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

305                 310                 315305 310 315

<210>39<210>39

<211>261<211>261

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>39<400>39

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu LeuAla Pro Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu

        35                  40                  4535 40 45

Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp ThrLeu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr

    50                  55                  6050 55 60

Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp ValLeu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val

65                  70                  75                  8065 70 75 80

Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly ValSer His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val

                85                  90                  9585 90 95

Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn SerGlu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser

            100                 105                 110100 105 110

Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp LeuThr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu

        115                 120                 125115 120 125

Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro AlaAsn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala

    130                 135                 140130 135 140

Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu ProPro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro

145                 150                 155                 160145 150 155 160

Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn GlnGln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln

                165                 170                 175165 170 175

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

            180                 185                 190180 185 190

Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr ThrVal Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr

        195                 200                 205195 200 205

Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys LeuPro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu

    210                 215                 220210 215 220

Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys SerThr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser

225                 230                 235                 240225 230 235 240

Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu SerVal Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser

                245                 250                 255245 250 255

Leu Ser Pro Gly LysLeu Ser Pro Gly Lys

            260260

<210>40<210>40

<211>704<211>704

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>40<400>40

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

           20                  25                  3020 25 30

Ala Pro Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val GlnAla Pro Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln

        35                  40                  4535 40 45

Lys Trp Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu AspLys Trp Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp

    50                  55                  6050 55 60

Pro Pro Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu TyrPro Pro Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr

65                  70                  75                  8065 70 75 80

Ala Cys Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser CysAla Cys Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys

                85                  90                  9585 90 95

Pro Trp Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val TyrPro Trp Tyr Leu Pro Trp Ala Ser Ser Ser Val Pro Gln Gly His Val Tyr

            100                 105                 110100 105 110

Arg Phe Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser SerArg Phe Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser

        115                 120                 125115 120 125

Leu Pro Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly GluLeu Pro Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu

    130                 135                 140130 135 140

Arg Ser Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Ile Ile Tyr ThrArg Ser Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Ile Ile Tyr Thr

145                 150                 155                 160145 150 155 160

Val Gly Tyr Ala Leu Ser Phe Ser Ala Leu Val Ile Ala Ser Ala IleVal Gly Tyr Ala Leu Ser Phe Ser Ala Leu Val Ile Ala Ser Ala Ile

                165                 170                 175165 170 175

Leu Leu Gly Phe Arg His Leu His Cys Thr Arg Asn Tyr Ile His LeuLeu Leu Gly Phe Arg His Leu His Cys Thr Arg Asn Tyr Ile His Leu

            180                 185                 190180 185 190

Asn Leu Phe Ala Ser Phe Ile Leu Arg Ala Leu Ser Val Phe Ile LysAsn Leu Phe Ala Ser Phe Ile Leu Arg Ala Leu Ser Val Phe Ile Lys

        195                 200                 205195 200 205

Asp Ala Ala Leu Lys Trp Met Tyr Ser Thr Ala Ala Gln Gln His GlnAsp Ala Ala Leu Lys Trp Met Tyr Ser Thr Ala Ala Gln Gln His Gln

    210                 215                 220210 215 220

Trp Asp Gly Leu Leu Ser Tyr Gln Asp Ser Leu Ser Cys Arg Leu ValTrp Asp Gly Leu Leu Ser Tyr Gln Asp Ser Leu Ser Cys Arg Leu Val

225                 230                 235                 240225 230 235 240

Phe Leu Leu Met Gln Tyr Cys Val Ala Ala Asn Tyr Tyr Trp Leu LeuPhe Leu Leu Met Gln Tyr Cys Val Ala Ala Asn Tyr Tyr Trp Leu Leu

                245                 250                 255245 250 255

Val Glu Gly Val Tyr Leu Tyr Thr Leu Leu Ala Phe Ser Val Phe SerVal Glu Gly Val Tyr Leu Tyr Thr Leu Leu Ala Phe Ser Val Phe Ser

          260                 265                 270260 265 270

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

        275                 280                 285275 280 285

Leu Leu Phe Val Val Pro Trp Gly Ile Val Lys Tyr Leu Tyr Glu AspLeu Leu Phe Val Val Pro Trp Gly Ile Val Lys Tyr Leu Tyr Glu Asp

    290                 295                 300290 295 300

Glu Gly Cys Trp Thr Arg Asn Ser Asn Met Asn Tyr Trp Leu Ile IleGlu Gly Cys Trp Thr Arg Asn Ser Asn Met Asn Tyr Trp Leu Ile Ile

305                 310                 315                 320305 310 315 320

Arg Leu Pro Ile Leu Phe Ala Ile Gly Val Asn Phe Leu Ile Phe ValArg Leu Pro Ile Leu Phe Ala Ile Gly Val Asn Phe Leu Ile Phe Val

                325                 330                 335325 330 335

Arg Val Ile Cys Ile Val Val Ser Lys Leu Lys Ala Asn Leu Met CysArg Val Ile Cys Ile Val Val Ser Lys Leu Lys Ala Asn Leu Met Cys

            340                 345                 350340 345 350

Lys Thr Asp Ile Lys Cys Arg Leu Ala Lys Ser Thr Leu Thr Leu IleLys Thr Asp Ile Lys Cys Arg Leu Ala Lys Ser Thr Leu Thr Leu Ile

        355                 360                 365355 360 365

Pro Leu Leu Gly Thr His Glu Val Ile Phe Ala Phe Val Met Asp GluPro Leu Leu Gly Thr His Glu Val Ile Phe Ala Phe Val Met Asp Glu

    370                 375                 380370 375 380

His Ala Arg Gly Thr Leu Arg Phe Ile Lys Leu Phe Thr Glu Leu SerHis Ala Arg Gly Thr Leu Arg Phe Ile Lys Leu Phe Thr Glu Leu Ser

385                 390                 395                 400385 390 395 400

Phe Thr Ser Phe Gln Gly Leu Met Val Ala Ile Leu Tyr Cys Phe ValPhe Thr Ser Phe Gln Gly Leu Met Val Ala Ile Leu Tyr Cys Phe Val

                405                 410                 415405 410 415

Asn Asn Glu Val Gln Leu Glu Phe Arg Lys Ser Trp Glu Arg Trp ArgAsn Asn Glu Val Gln Leu Glu Phe Arg Lys Ser Trp Glu Arg Trp Arg

            420                 425                 430420 425 430

Leu Glu His Leu His Ile Gln Arg Asp Ser Ser Met Lys Pro Leu LysLeu Glu His Leu His Ile Gln Arg Asp Ser Ser Met Lys Pro Leu Lys

        435                 440                 445435 440 445

Cys Pro Thr Ser Ser Leu Ser Ser Gly Ala Thr Ala Gly Ser Ser MetCys Pro Thr Ser Ser Leu Ser Ser Ser Gly Ala Thr Ala Gly Ser Ser Ser Met

    450                 455                 460450 455 460

Tyr Thr Ala Thr Cys Gln Ala Ser Cys Ser Gly Pro Gly Asp Lys ThrTyr Thr Ala Thr Cys Gln Ala Ser Cys Ser Gly Pro Gly Asp Lys Thr

465                 470                 475                 480465 470 475 480

His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro SerHis Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser

                485                 490                 495485 490 495

Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser ArgVal Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg

            500                 505                 510500 505 510

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

        515                 520                 525515 520 525

Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn AlaGlu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala

    530                 535                 540530 535 540

Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val ValLys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val

545                 550                 555                 560545 550 555 560

Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu TyrSer Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr

                565                 570                 575565 570 575

Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys ThrLys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr

            580                 585                 590580 585 590

Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr LeuIle Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu

        595                 600                 605595 600 605

Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr CysPro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys

    610                 615                 620610 615 620

Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu SerLeu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser

625                 630                 635                 640625 630 635 640

Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu AspAsn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp

                645                 650                 655645 650 655

Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys SerSer Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser

            660                 665                 670660 665 670

Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu AlaArg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala

        675                 680                 685675 680 685

Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly LysLeu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

    690                 695                 700690 695 700

<210>41<210>41

<211>386<211>386

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>41<400>41

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val GlnAla Pro Arg Pro Gln Gly Ala Thr Val Ser Leu Trp Glu Thr Val Gln

        35                  40                  4535 40 45

Lys Trp Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu AspLys Trp Arg Glu Tyr Arg Arg Gln Cys Gln Arg Ser Leu Thr Glu Asp

    50                  55                  6050 55 60

Pro Pro Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu TyrPro Pro Pro Ala Thr Asp Leu Phe Cys Asn Arg Thr Phe Asp Glu Tyr

65                  70                  75                  8065 70 75 80

Ala Cys Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser CysAla Cys Trp Pro Asp Gly Glu Pro Gly Ser Phe Val Asn Val Ser Cys

                85                  90                  9585 90 95

Pro Trp Tyr Leu Pro Trp Ala Ser Ser Val Pro Gln Gly His Val TyrPro Trp Tyr Leu Pro Trp Ala Ser Ser Ser Val Pro Gln Gly His Val Tyr

            100                 105                 110100 105 110

Arg Phe Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser SerArg Phe Cys Thr Ala Glu Gly Leu Trp Leu Gln Lys Asp Asn Ser Ser

        115                 120                 125115 120 125

Leu Pro Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly GluLeu Pro Trp Arg Asp Leu Ser Glu Cys Glu Glu Ser Lys Arg Gly Glu

    130                 135                 140130 135 140

Arg Ser Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Gly Pro Gly AspArg Ser Ser Pro Glu Glu Gln Leu Leu Phe Leu Tyr Gly Pro Gly Asp

145                 150                 155                 160145 150 155 160

Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly GlyLys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly

                165                 170                 175165 170 175

Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met IlePro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile

           180                 185                 190180 185 190

Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His GluSer Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu

        195                 200                 205195 200 205

Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val HisAsp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His

    210                 215                 220210 215 220

Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr ArgAsn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg

225                 230                 235                 240225 230 235 240

Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly LysVal Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys

                245                 250                 255245 250 255

Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile GluGlu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu

            260                 265                 270260 265 270

Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val TyrLys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr

        275                 280                 285275 280 285

Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser LeuThr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu

    290                 295                 300290 295 300

Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu TrpThr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp

305                 310                 315                 320305 310 315 320

Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro ValGlu Ser Asn Gly Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val

                325                 330                 335325 330 335

Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val AspLeu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp

            340                 345                 350340 345 350

Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met HisLys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His

        355                 360                 365355 360 365

Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser ProGlu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro

    370                 375                 380370 375 380

Gly LysGly Lys

385385

<210>42<210>42

<211>339<211>339

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>42<400>42

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Asn Tyr Ile His Leu Asn Leu Phe Ala Ser Phe Ile Leu ArgAla Pro Asn Tyr Ile His Leu Asn Leu Phe Ala Ser Phe Ile Leu Arg

        35                  40                  4535 40 45

Ala Leu Ser Val Phe Ile Lys Asp Ala Ala Leu Lys Trp Met Tyr SerAla Leu Ser Val Phe Ile Lys Asp Ala Ala Leu Lys Trp Met Tyr Ser

    50                  55                  6050 55 60

Thr Ala Ala Gln Gln His Gln Trp Asp Gly Leu Leu Ser Tyr Gln AspThr Ala Ala Gln Gln His Gln Trp Asp Gly Leu Leu Ser Tyr Gln Asp

65                  70                  75                  8065 70 75 80

Ser Leu Ser Cys Arg Leu Val Phe Leu Leu Met Gln Tyr Cys Val AlaSer Leu Ser Cys Arg Leu Val Phe Leu Leu Met Gln Tyr Cys Val Ala

                85                  90                  9585 90 95

Ala Asn Tyr Tyr Trp Leu Leu Val Glu Gly Val Tyr Leu Gly Pro GlyAla Asn Tyr Tyr Trp Leu Leu Val Glu Gly Val Tyr Leu Gly Pro Gly

            100                 105                 110100 105 110

Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu GlyAsp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly

        115                 120                 125115 120 125

Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu MetGly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met

    130                 135                 140130 135 140

Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser HisIle Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His

145                 150                 155                 160145 150 155 160

Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu ValGlu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val

                165                 170                 175165 170 175

His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr TyrHis Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr

            180                 185                 190180 185 190

Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn GlyArg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly

        195                 200                 205195 200 205

Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro IleLys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile

    210                 215                 220210 215 220

Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln ValGlu Lys Thr Ile Ser Lys Ala Lys Gly Gly Gln Pro Arg Glu Pro Gln Val

225                 230                 235                 240225 230 235 240

Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val SerTyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser

                245                 250                 255245 250 255

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

            260                 265                 270260 265 270

Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro ProTrp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro

        275                 280                 285275 280 285

Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr ValVal Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val

    290                 295                 300290 295 300

Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val MetAsp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met

305                 310                 315                 320305 310 315 320

His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu SerHis Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser

                325                 330                 335325 330 335

Pro Gly LysPro Gly Lys

<210>43<210>43

<211>328<211>328

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>43<400>43

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Phe Arg Leu Tyr Val Ser Ile Gly Trp Gly Val Pro Leu LeuAla Pro Phe Arg Leu Tyr Val Ser Ile Gly Trp Gly Val Pro Leu Leu

        35                  40                  4535 40 45

Phe Val Val Pro Trp Gly Ile Val Lys Tyr Leu Tyr Glu Asp Glu GlyPhe Val Val Pro Trp Gly Ile Val Lys Tyr Leu Tyr Glu Asp Glu Gly

    50                  55                  6050 55 60

Cys Trp Thr Arg Asn Ser Asn Met Asn Tyr Trp Leu Ile Ile Arg LeuCys Trp Thr Arg Asn Ser Asn Met Asn Tyr Trp Leu Ile Ile Arg Leu

65                  70                  75                  8065 70 75 80

Pro Ile Leu Phe Gly Ile Gly Val Asn Phe Leu Ile Phe Val Arg ValPro Ile Leu Phe Gly Ile Gly Val Asn Phe Leu Ile Phe Val Arg Val

                85                  90                  9585 90 95

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

            100                 105                 110100 105 110

Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys ProPro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro

        115                 120                 125115 120 125

Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val ValLys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val

    130                 135                 140130 135 140

Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr ValVal Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val

145                 150                 155                 160145 150 155 160

Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu GlnAsp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln

                165                 170                 175165 170 175

Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His GlnTyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln

            180                 185                 190180 185 190

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

        195                 200                 205195 200 205

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

    210                 215                 220210 215 220

Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu ThrArg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr

225                 230                 235                 240225 230 235 240

Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro SerLys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser

                245                 250                 255245 250 255

Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn TyrAsp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr

            260                 265                 270260 265 270

Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu TyrLys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr

        275                 280                 285275 280 285

Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val PheSer Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe

    290                 295                 300290 295 300

Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln LysSer Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys

305                 310                 315                 320305 310 315 320

Ser Leu Ser Leu Ser Pro Gly LysSer Leu Ser Leu Ser Pro Gly Lys

                325325

<210>44<210>44

<211>321<211>321

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>44<400>44

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Thr His Glu ValAla Pro Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Thr His Glu Val

        35                  40                  4535 40 45

Ile Phe Ala Phe Val Met Asp Glu His Ala Arg Gly Thr Leu Arg PheIle Phe Ala Phe Val Met Asp Glu His Ala Arg Gly Thr Leu Arg Phe

    50                  55                  6050 55 60

Ile Lys Leu Phe Thr Glu Leu Ser Phe Thr Ser Phe Gln Gly Leu MetIle Lys Leu Phe Thr Glu Leu Ser Phe Thr Ser Phe Gln Gly Leu Met

65                  70                  75                  8065 70 75 80

Val Ala Ile Leu Tyr Cys Phe Val Asn Asn Glu Gly Pro Gly Asp LysVal Ala Ile Leu Tyr Cys Phe Val Asn Asn Glu Gly Pro Gly Asp Lys

                85                  90                  9585 90 95

Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly ProThr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro

            100                 105                 110100 105 110

Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile SerSer Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser

        115                 120                 125115 120 125

Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu AspArg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp

    130                 135                 140130 135 140

Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His AsnPro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn

145                 150                 155                 160145 150 155 160

Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg ValAla Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val

                165                 170                 175165 170 175

Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys GluVal Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu

            180                 185                 190180 185 190

Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu LysTyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys

        195                 200                 205195 200 205

Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr ThrThr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr

    210                 215                 220210 215 220

Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu ThrLeu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr

225                 230                 235                 240225 230 235 240

Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp GluCys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu

                245                 250                 255245 250 255

Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val LeuSer Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu

            260                 265                 270260 265 270

Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp LysAsp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys

        275                 280                 285275 280 285

Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His GluSer Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu

    290                 295                 300290 295 300

Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro GlyAla Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly

305                 310                 315                 320305 310 315 320

LysLys

<210>45<210>45

<211>399<211>399

<212>PRT<212>PRT

<213>人工序列<213> Artificial sequence

<400>45<400>45

His Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu GlyHis Gly Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly

1               5                   10                  151 5 10 15

Gln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly GlyGln Ala Ala Lys Glu Phe Ile Ala Trp Leu Val Lys Gly Arg Gly Gly

            20                  25                  3020 25 30

Ala Pro Asn Tyr Ile His Leu Asn Leu Phe Ala Ser Phe Ile Leu ArgAla Pro Asn Tyr Ile His Leu Asn Leu Phe Ala Ser Phe Ile Leu Arg

        35                  40                  4535 40 45

Ala Leu Ser Val Phe Ile Lys Asp Ala Ala Leu Lys Trp Met Tyr SerAla Leu Ser Val Phe Ile Lys Asp Ala Ala Leu Lys Trp Met Tyr Ser

    50                  55                  6050 55 60

Thr Ala Ala Gln Gln His Gln Trp Asp Gly Leu Leu Ser Tyr Gln AspThr Ala Ala Gln Gln His Gln Trp Asp Gly Leu Leu Ser Tyr Gln Asp

65                  70                  75                  8065 70 75 80

Ser Leu Ser Cys Arg Leu Val Phe Leu Leu Met Gln Tyr Cys Val AlaSer Leu Ser Cys Arg Leu Val Phe Leu Leu Met Gln Tyr Cys Val Ala

                85                  90                  9585 90 95

Ala Asn Tyr Tyr Trp Leu Leu Val Glu Gly Val Tyr Leu Gly Pro GlyAla Asn Tyr Tyr Trp Leu Leu Val Glu Gly Val Tyr Leu Gly Pro Gly

            100                 105                 110100 105 110

Ser Thr Leu Thr Leu Ile Pro Leu Leu Gly Thr His Glu Val Ile PheSer Thr Leu Thr Leu Ile Pro Leu Leu Gly Thr His His Glu Val Ile Phe

        115                 120                 125115 120 125

Ala Phe Val Met Asp Glu His Ala Arg Gly Thr Leu Arg Phe Ile LysAla Phe Val Met Asp Glu His Ala Arg Gly Thr Leu Arg Phe Ile Lys

    130                 135                 140130 135 140

Leu Phe Thr Glu Leu Ser Phe Thr Ser Phe Gln Gly Leu Met Val AlaLeu Phe Thr Glu Leu Ser Phe Thr Ser Phe Gln Gly Leu Met Val Ala

145                 150                 155                 160145 150 155 160

Ile Leu Tyr Cys Phe Val Asn Asn Glu Gly Pro Gly Asp Lys Thr HisIle Leu Tyr Cys Phe Val Asn Asn Glu Gly Pro Gly Asp Lys Thr His

                165                 170                 175165 170 175

Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser ValThr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val

            180                 185                 190180 185 190

Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg ThrPhe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr

        195                 200                 205195 200 205

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

    210                 215                 220210 215 220

Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala LysVal Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys

225                 230                 235                 240225 230 235 240

Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val SerThr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser

                245                 250                 255245 250 255

Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr LysVal Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys

          260                 265                 270260 265 270

Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr IleCys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile

        275                 280                 285275 280 285

Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu ProSer Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro

    290                 295                 300290 295 300

Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys LeuPro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu

305                 310                 315                 320305 310 315 320

Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser AsnVal Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn

                325                 330                 335325 330 335

Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp SerGly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser

            340                 345                 350340 345 350

Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser ArgAsp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg

        355                 360                 365355 360 365

Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala LeuTrp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu

    370                 375                 380370 375 380

His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly LysHis Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys

385                 390                 395385 390 395

Claims (6)

1. A glucagon-like peptide-1 (GLP-1) fusion protein, the amino acid sequence general formula of which is: polypeptide a-linker-polypeptide B, polypeptide a-linker-polypeptide B-linker-polypeptide C or polypeptide a-linker-polypeptide C-linker-polypeptide B; wherein,
the polypeptide A is GLP-1(7-37) [ sequence ID: n0: 1] having the sequence:
His-Xaa2-Xaa3-Gly-Xaa5-Xaa6-Thr-Xaa8-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21-Phe-Xaa23-Xaa24-Xaa25-Xaa26-Leu-Xaa28-Xaa29-Xaa30-Xaa31
xaa2 is: ala, Gly, Ser, Thr; xaa3 is: glu, Asp, Gln, Asn; xaa5 is: thr, Arg, Ile; xaa6 is: phe, Tyr, Leu; xaa8 is: ser, Asn; xaa9 is: asp, Asn; xaa10 is: val, Ile, Met, Ala; xaa11 is: ser, Thr, Ala, Asp; xaa12 is: ser, Gln, Glu, Asn, Thr; xaa13 is: tyr, Phe, Gln, His, Leu; xaa14 is: leu, Thr, Ser; xaa15 is: glu, Gln, Asn, Asp, Arg, Lys; xaa16 is: gly, Glu, Asp, Gln, Asn, Arg, Lys; xaa17 is: gln, Lys, Leu, Phe; xaa18 is: ala, Lys; xaa19 is: ala, Thr, Ile, Ser; xaa20 is: lys, Arg, Gln; xaa21 is: glu, Asp, Asn, Ala, Ser, Lys, Arg; xaa23 is: ile, Val; xaa24 is: ala, Ser, Asp, Glu, Gly, Thr; xaa25 is: trp, Arg, Lys, Ser; xaa27 is: val, Lys, Ile, Ser, Ala; xaa28 is: lys, Arg, Asn, Gln, Ser, Ala, Thr; xaa29 is: gly, Tyr, Ser; xaa30 is: arg, Lys, Gln, Asp, Asn, Gly, Ala, Pro; xaa31 is: gly, Pro, Val, Arg, Lys, Ala or deleted;
polypeptide B is the full-length sequence of human glucagon receptor, N-terminal extramembranous functional region, glucagon receptor functional region-1, glucagon receptor functional region-2, glucagon receptor functional region-3 or the combined sequence of the glucagon receptor functional regions;
the polypeptide C is a CH2-CH3 segment of human immunoglobulin G1 Fc.
2. The fusion protein according to claim 1, characterized in that: a linker between polypeptide a, polypeptide B and polypeptide C selected from the group consisting of:
(Gly-Thr-Gly) n, (Gly-Ala-Pro) n, (Gly-Pro-Gly) n, or (GIy-Gly-Gly-Gly-Ser) n;
wherein n is 1, 2, 3, 4, 5, 6.
3. The fusion protein of claim 1, characterized in that the glucagon receptor is any one of the following sequences:
(1) the entire glucagon receptor sequence [ sequence ID NO: 2] having the sequence:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQVMYTVGYSLSLGALLLALAILGGLSKLHCTRNAIHANLFASFVLKASSVLVIDGLLRTRYSQKIGDDLSVSTWLSDGAVAGCRVAAVFMQYGIVANYCWLLVEGLYLHNLLGLATLPERSFFSLYLGIGWGAPMLFVVPWAVVKCLFENVQCWTSNDNMGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMHHTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEHAQGTLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELRRRWHRWRLGKVLWEERNTSNHRASSSPGHGPPSKELQFGRGGGSQDSSAETPLAGGLPRLAESPF
(2) the N-terminal extramembranous domain of the glucagon receptor [ sequence ID NO: 3] having the sequence:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ
(3) glucagon receptor functional region-1, which is composed of the outer ring of the first membrane of glucagon receptor and the transmembrane regions at both ends [ sequence ID NO: 4] having the sequence:
Xaa1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa2
wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
(4) glucagon receptor functional domain-2, which is composed of the membrane outer loop of glucagon receptor 2 and transmembrane domains at both ends thereof [ sequence ID NO: 5] having the sequence:
Xaa3-KCLFENVQCWTSNDNMGF-Xaa4
wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
(5) glucagon receptor functional region-3, which is composed of glucagon receptor 3 rd membrane outer ring and transmembrane regions at two ends [ sequence ID NO: 6] having the sequence:
Xaa5-DEHAQGTLRSAKLFFD-Xaa6
wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
(6) glucagon receptor domain 1-linker-glucagon receptor domain 2, having the sequence structure [ sequence ID NO: 7]:
xaa1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa 2-intermediate joint-Xaa 3-KCLFENVQCWTSNDNMGF-Xaa4
Wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
(7) glucagon receptor domain 1-linker-glucagon receptor domain 3, having the sequence structure [ sequence ID NO: 8]:
xaa1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa 2-intermediate joint-Xaa 5-DEHAQGTLRSAKLFFD-Xaa6
Wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
(8) glucagon receptor domain 2-linker-glucagon receptor domain 3, having the sequence structure [ sequence ID NO: 9]:
xaa3-KCLFENVQCWTSNDNMGF-Xaa 4-intermediate linker-Xaa 5-DEHAQGTLRSAKLFFD-Xaa 6.
Wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
(9) glucagon receptor functional region 1-intermediate linker-glucagon receptor functional region 2-intermediate linker-glucagon receptor functional region 3, the sequence structure of which is as follows [ sequence ID NO: 10]:
xaa1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa 2-intermediate joint-Xaa 3-KCLFENVQCWTSNDNMGF-Xaa 4-intermediate joint-Xaa 5-DEHAQGTLRSAKLFFD-Xaa6
Wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
(10) the glucagon receptor N-terminal extramembranous functional region-intermediate connector-glucagon receptor functional region 1 has the following sequence structure [ sequence ID NO: 11]:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ-intermediate joint-Xaa 1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa2
Wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
(11) the glucagon receptor N-terminal extramembranous functional region-intermediate connector-glucagon receptor functional region 2 has the following sequence structure [ sequence ID NO: 12]:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ-intermediate joint-Xaa 3-KCLFENVQCWTSNDNMGF-Xaa4
Wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
(12) the glucagon receptor N-terminal extramembranous functional region-intermediate linker-glucagon receptor functional region 3 has the following sequence structure [ sequence ID NO: 13]:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ-intermediate joint-Xaa 5-DEHAQGTLRSAKLFFD-Xaa6
Wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
(13) the glucagon receptor N-end extramembranous functional region-intermediate connector-glucagon receptor functional region 1-intermediate connector-glucagon receptor functional region 2 has the following sequence structure [ sequence ID NO: 14]:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTAN I SCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ-intermediate joint-Xaa 1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa 2-intermediate joint-Xaa 3-KCLFENVQCWTSNDNMGF-Xaa4
Wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
(14) the glucagon receptor N-end extramembranous functional region-intermediate connector-glucagon receptor functional region 1-intermediate connector-glucagon receptor functional region 3 has the following sequence structure [ sequence ID NO: 15]:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ-intermediate joint-Xaa 1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa 2-intermediate joint-Xaa 5-DEHAQGTLRSAKLFFD-Xaa 6.
Wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
(15) the glucagon receptor N-end extramembranous functional region-intermediate connector-glucagon receptor functional region 2-intermediate connector-glucagon receptor functional region 3 has the following sequence structure [ sequence ID NO: 16]:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ-intermediate joint-Xaa 3-KCLFENVQCWTSNDNMGF-Xaa 4-intermediate joint-Xaa 5-DEHAQGTLRSAKLFFD-Xaa6
Wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
(16) the glucagon receptor N-terminal extramembranous functional region-intermediate connector-glucagon receptor functional region 1-intermediate connector-glucagon receptor functional region 2-intermediate connector-glucagon receptor functional region 3 has the following sequence structure [ sequence ID NO: 17]:
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQ-intermediate joint-Xaa 1-IDGLLRTRYSQKIGDDLSVSTWLSDGAVAG-Xaa 2-intermediate joint-Xaa 3-KCLFENVQCWTSNDNMGF-Xaa 4-intermediate joint-Xaa 5-DEHAQGTLRSAKLFFD-Xaa 6.
Wherein Xaa1 is the following sequence: NAIHANLFASFVLKASSVLV
From the N-terminus of Xaa1, all amino acids can be removed one by one;
wherein Xaa2 is the following sequence: CRVAAVFMQYGIVANYCWLLVEGLYL
From the C-terminus of Xaa2, all amino acids can be removed one by one;
wherein Xaa3 is the following sequence: FSLYLGIGWGAPMLFVVPWAVV
From the N-terminus of Xaa3, all amino acids can be removed one by one;
wherein Xaa4 is the following sequence: WWILRFPVFLAILINFFIFVRIV
From the C-terminus of Xaa4, all amino acids can be removed one by one;
wherein Xaa5 is the following sequence: TLTLIPLLGVHEVVFAFVT
From the N-terminus of Xaa5, all amino acids can be removed one by one;
wherein Xaa6 is the following sequence: LFLSSFQGLLVAVLYCFLN
From the C-terminus of Xaa6, all amino acids can be removed one by one;
4. the fusion protein of GLP-1 of claim 1, wherein polypeptide C is the CH2-CH3 segment of human immunoglobulin G1Fc, the sequence of which is [ SEQ ID NO: 34]:
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK。
5. a pharmaceutical composition for treating non-insulin dependent diabetes mellitus or obesity, comprising the fusion protein of any one of claims 1 to 4.
6. Use of a fusion protein of GLP-1 as defined in claims 1-4 for the preparation of a medicament for the treatment of type I diabetes, type II diabetes, obesity, stroke.
CNB2005100171754A 2005-09-30 2005-09-30 GLP-1 fusion protein and its preparation method and medical application Expired - Fee Related CN100445300C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CNB2005100171754A CN100445300C (en) 2005-09-30 2005-09-30 GLP-1 fusion protein and its preparation method and medical application

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CNB2005100171754A CN100445300C (en) 2005-09-30 2005-09-30 GLP-1 fusion protein and its preparation method and medical application

Publications (2)

Publication Number Publication Date
CN1765931A CN1765931A (en) 2006-05-03
CN100445300C true CN100445300C (en) 2008-12-24

Family

ID=36742066

Family Applications (1)

Application Number Title Priority Date Filing Date
CNB2005100171754A Expired - Fee Related CN100445300C (en) 2005-09-30 2005-09-30 GLP-1 fusion protein and its preparation method and medical application

Country Status (1)

Country Link
CN (1) CN100445300C (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101294187B (en) * 2008-06-06 2013-07-31 暨南大学 Method for sustained-releasing polypeptide with biological activity and application thereof
WO2010020767A2 (en) * 2008-08-21 2010-02-25 Asterion Limited Glp-1 fusion polypeptides
CN102532323B (en) * 2010-12-09 2014-07-23 天津药物研究院 Polypeptide complex, pharmaceutical composition, as well as preparation method and application of polypeptide complex
WO2020184941A1 (en) * 2019-03-08 2020-09-17 Genexine, Inc. Glp-1 fusion proteins and uses thereof
EP4458863A1 (en) * 2021-12-31 2024-11-06 Sunshine Lake Pharma Co., Ltd. Fusion protein of glp-1 and gdf15 and use thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004094461A2 (en) * 2003-04-21 2004-11-04 Bristol-Myers Squibb Company Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions
CN1564829A (en) * 2001-01-05 2005-01-12 辉瑞大药厂 Antibodies to insulin-like growth factor I receptor

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1564829A (en) * 2001-01-05 2005-01-12 辉瑞大药厂 Antibodies to insulin-like growth factor I receptor
WO2004094461A2 (en) * 2003-04-21 2004-11-04 Bristol-Myers Squibb Company Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions

Also Published As

Publication number Publication date
CN1765931A (en) 2006-05-03

Similar Documents

Publication Publication Date Title
JP7211712B2 (en) glucagon receptor agonist
JP6006309B2 (en) Engineered polypeptides with increased duration of action and reduced immunogenicity
JP6012684B2 (en) Extended recombinant polypeptide and composition comprising extended recombinant polypeptide
RU2269354C2 (en) Agonists of hypophysis adenylate cyclase peptide-activator receptor-3(r3)(pacap) and methods for their pharmacological using
JP7268202B2 (en) Fusion proteins for treating metabolic diseases
CN109836488B (en) Glucagon analogues for treating metabolic diseases
US11911443B2 (en) Fusion proteins with extended serum half life
WO2005035761A1 (en) Splice variants of preproglucagon, glucagon-like peptide-1 and oxyntomodulin
WO2011153965A1 (en) Fusion protein of exendin-4 and its analog, preparation method and use thereof
WO2014031420A1 (en) Homodimeric proteins
TW201100104A (en) Drug fusions and conjugates
CN103370083A (en) Engineered polypeptides having enhanced duration of action
JP2020505029A (en) Relaxin fusion polypeptides and uses thereof
CN102558362A (en) A fusion protein for treating diabetes and its preparation method
CN110678550B (en) Long-acting adrenomedullin derivative
JP2008546816A (en) Exendin 4 polypeptide fragments and uses thereof
WO2022117044A1 (en) Glp-1/gcg dual receptor agonist polypeptide and fusion protein thereof
CN100445300C (en) GLP-1 fusion protein and its preparation method and medical application
CN113150172B (en) GLP-1R/GIPR double-target agonist fusion protein and preparation method and application thereof
JP6612360B2 (en) Fusion protein complex and fusion protein having medicinal action
KR102349718B1 (en) A novel bispecific protein and use thereof
CN101220088A (en) Fusion protein of human glucagon-like peptide-1 analog and application thereof
WO2015000413A1 (en) Long-acting blood sugar decreasing fusion protein
CN106146667B (en) A kind of Exendin-4 fusion protein and its preparation method and use
WO2021083306A1 (en) Glp-1/gcg dual-acceptor agonist polypeptide

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20081224

Termination date: 20150930

EXPY Termination of patent right or utility model