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维基百科

组织蛋白酶B

行進 28, 2023

组织蛋白酶B（英文：Cathepsin B）属于溶酶体半胱氨酸蛋白酶家族，也叫半胱氨酸组织蛋白酶，在细胞内蛋白水解中起重要作用。[5]在人体内的组织蛋白酶B被编码为CTSB基因。[6][7]组织蛋白酶B的水平在某些癌症、癌前病变和各种其他病理状况中会上调。[8][9][10][11]

组织蛋白酶B
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名CTSB；, APPS, CPSB, cathepsin B, RECEUP
外部IDOMIM：116810 MGI：88561 HomoloGene：37550 GeneCards：CTSB
基因位置（人类）
染色体8號染色體[1]
基因座8p23.1起始11,842,524 bp[1]
终止11,869,448 bp[1]
RNA表达模式




查阅更多表达数据
直系同源
物種人類小鼠
Entrez

1508

13030

Ensembl

ENSG00000164733
​ENSG00000285132

ENSMUSG00000021939

UniProt

P07858

P10605

mRNA​序列

NM_007798

蛋白序列

NP_031824

基因位置​（UCSC）Chr 8: 11.84 – 11.87 MbChr 14: 63.36 – 63.38 Mb
PubMed​查找[3][4]
維基數據
檢視/編輯人類檢視/編輯小鼠

结构

基因

CTSB基因位于染色体8p22，由13个外显子组成。CTSB基因位于8p22染色体，由13个外显子组成。CTSB基因的启动子含有一个富含GC的区域，包含许多SP1位点，类似于管家基因。[12]已发现该基因至少有五个编码相同蛋白质的转录变体。[13]

蛋白质

组织蛋白酶B在粗面内质网上合成为339个氨基酸的前酶原，具有17个氨基酸的信号肽。[14][15]然后将43/46 kDa的组织蛋白酶原B转运到高尔基体，在那里将形成组织蛋白酶B。成熟的组织蛋白酶B由25-26 kDa的重链和5 kDa的轻链组成，它们通过二硫键的二聚体连接。

功能

组织蛋白酶B可增强其他蛋白酶的活性，包括基质金属蛋白酶、尿激酶（丝氨酸蛋白酶尿激酶纤溶酶原激活剂）和组织蛋白酶D。[16][17]因此，它在细胞外基质成分的蛋白水解、细胞间通讯中断和减少蛋白酶抑制剂的表达方面具有重要作用。[18]它还参与自噬和分解代谢，有造成肿瘤的恶性发展，并可能参与特异性免疫抵抗。[19]此外，它被确定为具有较小的连接酶活性，能够通过酰胺键连接肽片段。[20]

临床意义

组织蛋白酶B可以作为多种癌症的潜在有效生物标志物。.[16][21][22][23][24][25] 组织蛋白酶B的过度表达与侵袭性和转移性癌症有关。[26]组织蛋白酶B在新陈代谢过程中在肌肉组织中产生。它能够穿过血脑屏障[27]并且与神经发生有关，特别是在小鼠齿状回中。多种疾病导致组织蛋白酶B水平升高，从而导致许多病理过程，包括细胞死亡、炎症和有毒肽的产生。专注于神经系统疾病，在癫痫啮齿动物模型中的组织蛋白酶 B 基因敲除研究表明，组织蛋白酶B会导致大量因诱发癫痫而发生的凋亡细胞死亡。[28]

对诱发癫痫发作的老鼠进行组织蛋白酶B抑制剂治疗，可改善神经系统评分、学习能力，并大大减少神经元细胞死亡和促凋亡细胞死亡肽。[29]同样，在创伤性脑损伤老鼠模型中组织蛋白酶B基因敲除和组织蛋白酶B抑制剂治疗研究表明，组织蛋白酶B是导致神经肌肉功能障碍、记忆丧失、神经元细胞死亡以及增加促坏死与促凋亡细胞死亡肽的关键。[30][31]在缺血性非人类灵长类动物和啮齿动物模型中，组织蛋白酶B抑制剂治疗可防止脑神经元显着丧失，尤其是在海马体中的神经元。[32][33][34]在肺炎链球菌脑膜炎啮齿动物模型中，组织蛋白酶B抑制剂治疗极大地改善了感染的临床过程，并减少了脑部炎症和炎症性白细胞介素-1β （IL1-β）和肿瘤坏死因子-α（TNF-α）。[35]

在表达人类前类淀粉蛋白质（APP）的转基因阿尔茨海默症动物模型中，该模型含有在大多数阿尔茨海默症患者或豚鼠中发现的野生型β-分泌酶位点序列，这是人类野生型APP加工的自然模型, 遗传上删除组织蛋白酶B基因或化学上抑制组织蛋白酶B大脑活动导致此类小鼠的记忆缺陷得到显着改善并降低神经毒性全长β淀粉样蛋白(1-40/42)和特别有害的焦谷氨酸β淀粉样蛋白的水平(3-40/42)，这被认为是导致疾病的原因。[36][37][38][39][40][41][42]在一个非转基的因衰老加速的小鼠品系中，它也具有含有野生型β-分泌酶位点序列的APP，用银杏叶提取出的白果内酯，也可以通过组织蛋白酶B抑制剂降低了β淀粉样蛋白。[43]此外，siRNA 沉默或化学抑制具有人类野生型 β-分泌酶活性的原代啮齿动物海马细胞或牛嗜铬细胞中的组织蛋白酶B，可通过调节分泌途径减少β淀粉样蛋白的分泌。[44][45]CTSB基因的突变与热带胰腺炎（一种慢性胰腺炎）有关。[46]

相互作用

组织蛋白酶B可以与以下物质产生相互作用：

组织蛋白酶B可以被以下物质抑制：

参见

参考文献

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行進 28, 2023
组织蛋白酶b, 英文, cathepsin, 属于溶酶体半胱氨酸蛋白酶家族, 也叫半胱氨酸组织蛋白酶, 在细胞内蛋白水解中起重要作用, 在人体内的被编码为ctsb基因, 的水平在某些癌症, 癌前病变和各种其他病理状况中会上调, 已知的結構pdb直系同源搜索, pdbe, rcsbpdbid列表3pbh, 1csb, 1gmy, 1huc, 1pbh, 2ipp, 2pbh, 3ai8, 3cbj, 3cbk, 3k9m識別號别名ctsb, apps, cpsb, cathepsin, receup外部idomim,. 组织蛋白酶B 英文 Cathepsin B 属于溶酶体半胱氨酸蛋白酶家族 也叫半胱氨酸组织蛋白酶 在细胞内蛋白水解中起重要作用 5 在人体内的组织蛋白酶B被编码为CTSB基因 6 7 组织蛋白酶B的水平在某些癌症 癌前病变和各种其他病理状况中会上调 8 9 10 11 组织蛋白酶B已知的結構PDB直系同源搜索 PDBe RCSBPDBID列表3PBH 1CSB 1GMY 1HUC 1PBH 2IPP 2PBH 3AI8 3CBJ 3CBK 3K9M識別號别名CTSB APPS CPSB cathepsin B RECEUP外部IDOMIM 116810 MGI 88561 HomoloGene 37550 GeneCards CTSB基因位置 人类 染色体8號染色體 1 基因座8p23 1起始11 842 524 bp 1 终止11 869 448 bp 1 基因位置 小鼠 染色体小鼠14号染色体 2 基因座14 D1 14 33 24 cM起始63 359 911 bp 2 终止63 383 372 bp 2 RNA表达模式查阅更多表达数据基因本體分子功能 半胱氨酸型肽酶活性 collagen binding 肽酶活性 血浆蛋白结合 cysteine type endopeptidase activity 水解酶活性 proteoglycan binding serine type endopeptidase activity endopeptidase activity細胞組分 細胞內膜結合細胞器 黑色素体 胞內 細胞外區域 endolysosome lumen 核仁 線粒體 溶酶体 外排體 细胞质的核周区域 細胞外空間 ficolin 1 rich granule lumen collagen containing extracellular matrix生物學過程 regulation of apoptotic process epithelial cell differentiation 蛋白酶解 toll like receptor signaling pathway 蛻膜化 cellular response to thyroid hormone stimulus collagen catabolic process 病毒进入 regulation of catalytic activity proteolysis involved in cellular protein catabolic process neutrophil degranulationSources Amigo QuickGO直系同源物種人類小鼠Entrez150813030EnsemblENSG00000164733 ENSG00000285132ENSMUSG00000021939UniProtP07858P10605mRNA 序列 NM 001908 NM 147780 NM 147781 NM 147782 NM 147783 NM 001317237NM 007798蛋白序列NP 001304166 NP 001899 NP 680090 NP 680091 NP 680092 NP 680093NP 031824基因位置 UCSC Chr 8 11 84 11 87 MbChr 14 63 36 63 38 MbPubMed 查找 3 4 維基數據檢視 編輯人類檢視 編輯小鼠 目录 1 结构 1 1 基因 1 2 蛋白质 2 功能 3 临床意义 4 相互作用 5 参见 6 参考文献结构 编辑基因 编辑 CTSB基因位于染色体8p22 由13个外显子组成 CTSB基因位于8p22染色体 由13个外显子组成 CTSB基因的启动子含有一个富含GC的区域 包含许多SP1位点 类似于管家基因 12 已发现该基因至少有五个编码相同蛋白质的转录变体 13 蛋白质 编辑 组织蛋白酶B在粗面内质网上合成为339个氨基酸的前酶原 具有17个氨基酸的信号肽 14 15 然后将43 46 kDa的组织蛋白酶原B转运到高尔基体 在那里将形成组织蛋白酶B 成熟的组织蛋白酶B由25 26 kDa的重链和5 kDa的轻链组成 它们通过二硫键的二聚体连接 功能 编辑组织蛋白酶B可增强其他蛋白酶的活性 包括基质金属蛋白酶 尿激酶 丝氨酸蛋白酶尿激酶纤溶酶原激活剂 和组织蛋白酶D 16 17 因此 它在细胞外基质成分的蛋白水解 细胞间通讯中断和减少蛋白酶抑制剂的表达方面具有重要作用 18 它还参与自噬和分解代谢 有造成肿瘤的恶性发展 并可能参与特异性免疫抵抗 19 此外 它被确定为具有较小的连接酶活性 能够通过酰胺键连接肽片段 20 临床意义 编辑组织蛋白酶B可以作为多种癌症的潜在有效生物标志物 16 21 22 23 24 25 组织蛋白酶B的过度表达与侵袭性和转移性癌症有关 26 组织蛋白酶B在新陈代谢过程中在肌肉组织中产生 它能够穿过血脑屏障 27 并且与神经发生有关 特别是在小鼠齿状回中 多种疾病导致组织蛋白酶B水平升高 从而导致许多病理过程 包括细胞死亡 炎症和有毒肽的产生 专注于神经系统疾病 在癫痫啮齿动物模型中的组织蛋白酶 B 基因敲除研究表明 组织蛋白酶B会导致大量因诱发癫痫而发生的凋亡细胞死亡 28 对诱发癫痫发作的老鼠进行组织蛋白酶B抑制剂治疗 可改善神经系统评分 学习能力 并大大减少神经元细胞死亡和促凋亡细胞死亡肽 29 同样 在创伤性脑损伤老鼠模型中组织蛋白酶B基因敲除和组织蛋白酶B抑制剂治疗研究表明 组织蛋白酶B是导致神经肌肉功能障碍 记忆丧失 神经元细胞死亡以及增加促坏死与促凋亡细胞死亡肽的关键 30 31 在缺血性非人类灵长类动物和啮齿动物模型中 组织蛋白酶B抑制剂治疗可防止脑神经元显着丧失 尤其是在海马体中的神经元 32 33 34 在肺炎链球菌脑膜炎啮齿动物模型中 组织蛋白酶B抑制剂治疗极大地改善了感染的临床过程 并减少了脑部炎症和炎症性白细胞介素 1b IL1 b 和肿瘤坏死因子 a TNF a 35 在表达人类前类淀粉蛋白质 APP 的转基因阿尔茨海默症动物模型中 该模型含有在大多数阿尔茨海默症患者或豚鼠中发现的野生型b 分泌酶位点序列 这是人类野生型APP加工的自然模型 遗传上删除组织蛋白酶B基因或化学上抑制组织蛋白酶B大脑活动导致此类小鼠的记忆缺陷得到显着改善并降低神经毒性全长b淀粉样蛋白 1 40 42 和特别有害的焦谷氨酸b淀粉样蛋白的水平 3 40 42 这被认为是导致疾病的原因 36 37 38 39 40 41 42 在一个非转基的因衰老加速的小鼠品系中 它也具有含有野生型b 分泌酶位点序列的APP 用银杏叶提取出的白果内酯 也可以通过组织蛋白酶B抑制剂降低了b淀粉样蛋白 43 此外 siRNA 沉默或化学抑制具有人类野生型 b 分泌酶活性的原代啮齿动物海马细胞或牛嗜铬细胞中的组织蛋白酶B 可通过调节分泌途径减少b淀粉样蛋白的分泌 44 45 CTSB基因的突变与热带胰腺炎 一种慢性胰腺炎 有关 46 相互作用 编辑组织蛋白酶B可以与以下物质产生相互作用 组织蛋白酶D 47 胱抑素A 48 49 胱抑素B 48 50 S100A10 51 组织蛋白酶B可以被以下物质抑制 硝唑啉 52 CA 074 53 参见 编辑组织蛋白酶参考文献 编辑 1 0 1 1 1 2 GRCh38 Ensembl release 89 ENSG00000164733 ENSG00000285132 Ensembl May 2017 2 0 2 1 2 2 GRCm38 Ensembl release 89 ENSMUSG00000021939 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Sloane BF Cathepsin B and cystatins evidence for a role in cancer progression Seminars in Cancer Biology April 1990 1 2 137 52 PMID 2103490 Chan SJ San Segundo B McCormick MB Steiner DF Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs 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