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组织蛋白酶G

组织蛋白酶G
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
别名CTSG；, CATG, CG, cathepsin G
外部IDOMIM：116830 MGI：88563 HomoloGene：105646 GeneCards：CTSG
基因位置（人类）
14號染色體
染色体14號染色體[1]
14號染色體
组织蛋白酶G的基因位置
组织蛋白酶G的基因位置
基因座14q12起始24,573,518 bp[1]
终止24,576,250 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

1511

13035

Ensembl

ENSG00000100448

ENSMUSG00000040314

UniProt

P08311

P28293

mRNA​序列

​NM_001911

NM_007800

蛋白序列

NP_001902

NP_031826

基因位置​（UCSC）Chr 14: 24.57 – 24.58 MbChr 14: 56.34 – 56.34 Mb
PubMed​查找[3][4]
維基數據
檢視/編輯人類檢視/編輯小鼠

组织蛋白酶G（英文：Cathepsin G）是一种在人体中由CTSG基因编码的蛋白质。它是储存在嗜天青颗粒细胞中的糜蛋白酶家族的三种丝氨酸蛋白酶之一，也是肽酶S1蛋白家族的成员。组织蛋白酶G在消除细胞内病原体和分解炎症部位的组织以及抗炎反应中起重要作用。[5][6][7][8]

结构

基因

CTSG基因位于14号染色体q11.2，由5个外显子组成。催化三联体的每个残基都位于一个单独的外显子上。通过扫描整个编码区已鉴定出五个基因多态性。[9]组织蛋白酶G是通过基因复制从共同祖先进化而来的同源蛋白酶之一。[10]

蛋白质

组织蛋白酶G是一种255-氨基酸残基的蛋白质，包括一个18-残基信号肽、一个N端的两个残基活化肽和一个C端延伸。[11]组织蛋白酶G的活性依赖于由天冬氨酸、组氨酸和丝氨酸残基组成的催化三联体，这些残基在一级序列中广泛分离，但在三级结构中酶的活性位点彼此靠近。[12]

作用

组织蛋白酶G具有与胰凝乳蛋白酶C（英语：Chymotrypsin C）相似的特异性，但它与其他免疫丝氨酸蛋白酶如中性粒细胞弹性蛋白酶（英语：Neutrophil elastase）和颗粒酶的关系最为密切。[13]作为一种中性粒细胞丝氨酸蛋白酶，它首先被鉴定为降解酶，它在细胞内作用以降解摄入的宿主病原体，并在细胞外作用于炎症部位的细胞外基质成分的分解。[14]它定位于中性粒细胞胞外陷阱，通过其对DNA的高亲和力，这是丝氨酸蛋白酶的不寻常特性。[13]该基因存在利用替代多腺苷酸化信号的转录变体。[15]还发现组织蛋白酶G对革兰氏阴性菌和革兰氏阳性菌具有广谱抗菌作用，与上述功能无关。[16]组织蛋白酶G的其他功能已发现，包括切割受体、将血管紧张素I转化为血管紧张素II、血小板激活和诱导气道黏膜下腺分泌.[17][18][19][20][21]还发现了该酶在 血脑屏障 破坏中的潜在影响。[22]

临床意义

发现组织蛋白酶G在多种疾病中发挥重要作用，包括类风湿性关节炎、冠状动脉疾病、牙周炎、缺血再灌注损伤（英语：Reperfusion injury）和骨转移。[23][24][25][26][27]它还与多种感染性炎症疾病有关，包括慢性阻塞性肺病、急性呼吸窘迫综合征和囊腫性纖維化。[28][29][30]最近的一项研究表明，具有CTSG基因多态性的患者患慢性术后疼痛的风险更高，这表明组织蛋白酶G可能作为疼痛控制的新靶点和预测慢性术后疼痛的潜在标志物。[31]在圆锥角膜的研究中报告了组织蛋白酶G的上调。[32]

交互作用

已发现组织蛋白酶G与以下物质相互作用：

组织蛋白酶G受以下因素抑制：

  • [2-[3-[[(1-苯甲酰基-4-哌啶基)甲氨基]羰基]-2-萘基]-1-(1-萘基)-2-氧代乙基]-膦酸(KPA)[34]
  • Paubrasilia弹性蛋白酶抑制剂[35]
  • N-芳酰基O-磺化氨基糖苷类[36]

组织蛋白酶G降低以下水平：

参见

参考文献

  1. ^ 1.0 1.1 1.2 GRCh38: Ensembl release 89: ENSG00000100448 - Ensembl, May 2017
  2. ^ 2.0 2.1 2.2 GRCm38: Ensembl release 89: ENSMUSG00000040314 - Ensembl, May 2017
  3. ^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  4. ^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine. 
  5. ^ Janoff A, Scherer J. Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes. The Journal of Experimental Medicine. November 1968, 128 (5): 1137–55. PMC 2138566 可免费查阅. PMID 5303065. doi:10.1084/jem.128.5.1137. 
  6. ^ Kao RC, Wehner NG, Skubitz KM, Gray BH, Hoidal JR. Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. The Journal of Clinical Investigation. December 1988, 82 (6): 1963–73. PMC 442778 可免费查阅. PMID 3198760. doi:10.1172/JCI113816. 
  7. ^ Baggiolini M, Schnyder J, Bretz U, Dewald B, Ruch W. Cellular mechanisms of proteinase release from inflammatory cells and the degradation of extracellular proteins. Ciba Foundation Symposium. Novartis Foundation Symposia. 1979, (75): 105–21. ISBN 9780470720585. PMID 399884. doi:10.1002/9780470720585.ch7. 
  8. ^ Virca GD, Metz G, Schnebli HP. Similarities between human and rat leukocyte elastase and cathepsin G. European Journal of Biochemistry. October 1984, 144 (1): 1–9. PMID 6566611. doi:10.1111/j.1432-1033.1984.tb08423.x. 
  9. ^ Herrmann SM, Funke-Kaiser H, Schmidt-Petersen K, Nicaud V, Gautier-Bertrand M, Evans A, Kee F, Arveiler D, Morrison C, Orzechowski HD, Elbaz A, Amarenco P, Cambien F, Paul M. Characterization of polymorphic structure of cathepsin G gene: role in cardiovascular and cerebrovascular diseases. Arteriosclerosis, Thrombosis, and Vascular Biology. September 2001, 21 (9): 1538–43. PMID 11557685. doi:10.1161/hq0901.095555 可免费查阅. 
  10. ^ Salvesen G, Enghild JJ. Zymogen activation specificity and genomic structures of human neutrophil elastase and cathepsin G reveal a new branch of the chymotrypsinogen superfamily of serine proteinases. Biomedica Biochimica Acta. 1991, 50 (4–6): 665–71. PMID 1801740. 
  11. ^ Salvesen G, Farley D, Shuman J, Przybyla A, Reilly C, Travis J. Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases. Biochemistry. April 1987, 26 (8): 2289–93. PMID 3304423. doi:10.1021/bi00382a032. 
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  15. ^ Entrez Gene: CTSG cathepsin G. 
  16. ^ Shafer WM, Pohl J, Onunka VC, Bangalore N, Travis J. Human lysosomal cathepsin G and granzyme B share a functionally conserved broad spectrum antibacterial peptide. The Journal of Biological Chemistry. January 1991, 266 (1): 112–6. PMID 1985886. doi:10.1016/S0021-9258(18)52409-1 可免费查阅. 
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  19. ^ Reilly CF, Tewksbury DA, Schechter NM, Travis J. Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. The Journal of Biological Chemistry. August 1982, 257 (15): 8619–22. PMID 6807977. doi:10.1016/S0021-9258(18)34171-1 可免费查阅. 
  20. ^ Sambrano GR, Huang W, Faruqi T, Mahrus S, Craik C, Coughlin SR. Cathepsin G activates protease-activated receptor-4 in human platelets. The Journal of Biological Chemistry. March 2000, 275 (10): 6819–23. PMID 10702240. doi:10.1074/jbc.275.10.6819 可免费查阅. 
  21. ^ Nadel JA. Role of mast cell and neutrophil proteases in airway secretion. The American Review of Respiratory Disease. September 1991, 144 (3 Pt 2): S48–51. PMID 1892327. doi:10.1164/ajrccm/144.3_pt_2.S48. 
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组织蛋白酶G引用了美国国家医学图书馆提供的資料，这些資料属于公共领域。

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