组织蛋白酶G

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]

组织蛋白酶G
已知的结构 PDB 直系同源搜索: PDBe RCSB PDBID列表 1AU8、​1CGH、​1KYN、​1T32
识别号
别名	CTSG；, CATG, CG, cathepsin G
外部ID	OMIM：116830 MGI：88563 HomoloGene：105646 GeneCards：CTSG
基因位置（人类） 染色体 14号染色体[1] 基因座 14q12 起始 24,573,518 bp[1] 终止 24,576,250 bp[1]
基因位置（小鼠） 染色体 小鼠14号染色体[2] 基因座 14 C3|14 28.19 cM 起始 56,337,338 bp[2] 终止 56,340,031 bp[2]
RNA表达模式
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基因本体 分子功能 • heparin binding • 肽酶活性 • 血浆蛋白结合 • 水解酶活性 • serine-type endopeptidase activity • serine-type peptidase activity 细胞组分 • 细胞外间质 • 细胞膜 • secretory granule • cell surface • 外排体 • 细胞核 • 细胞外空间 • azurophil granule lumen • 应激颗粒 • 细胞外区域 • 细胞质 • collagen-containing extracellular matrix 生物学过程 • extracellular matrix disassembly • 蛋白酶解 • angiotensin maturation • protein phosphorylation • response to lipopolysaccharide • positive regulation of immune response • defense response to bacterium • 免疫反应 • defense response to Gram-positive bacterium • antimicrobial humoral response • neutrophil degranulation • defense response to fungus • neutrophil-mediated killing of gram-positive bacterium Sources:Amigo / QuickGO
直系同源
物种	人类	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 Mb	Chr 14: 56.34 – 56.34 Mb
PubMed​查找	[3]	[4]
维基数据
查看/编辑人类 查看/编辑小鼠

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肿性纤维化。^[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：

• SERPINB1（英语：SERPINB1）^[33]

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：

• 低密度脂蛋白^[37]

参见

• 组织蛋白酶

参考文献

1. GRCh38: Ensembl release 89: ENSG00000100448 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000040314 - Ensembl, May 2017
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4. Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
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拓展阅读

• Shafer WM, Katzif S, Bowers S, Fallon M, Hubalek M, Reed MS, Veprek P, Pohl J. Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens. Current Pharmaceutical Design. 2002, 8 (9): 695–702. PMID 11945165. doi:10.2174/1381612023395376.
• Cohen AB, Stevens MD, Miller EJ, Atkinson MA, Mullenbach G. Generation of the neutrophil-activating peptide-2 by cathepsin G and cathepsin G-treated human platelets. The American Journal of Physiology. August 1992, 263 (2 Pt 1): L249–56. PMID 1387511. doi:10.1152/ajplung.1992.263.2.L249.
• Sasaki T, Ueno-Matsuda E. Immunocytochemical localization of cathepsins B and G in odontoclasts of human deciduous teeth. Journal of Dental Research. December 1992, 71 (12): 1881–4. PMID 1452887. S2CID 27658837. doi:10.1177/00220345920710120501.
• Maison CM, Villiers CL, Colomb MG. Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G. Journal of Immunology. August 1991, 147 (3): 921–6. PMID 1861080.
• Brandt E, Van Damme J, Flad HD. Neutrophils can generate their activator neutrophil-activating peptide 2 by proteolytic cleavage of platelet-derived connective tissue-activating peptide III. Cytokine. July 1991, 3 (4): 311–21. PMID 1873479. doi:10.1016/1043-4666(91)90499-4.
• Kargi HA, Campbell EJ, Kuhn C. Elastase and cathepsin G of human monocytes: heterogeneity and subcellular localization to peroxidase-positive granules. The Journal of Histochemistry and Cytochemistry. August 1990, 38 (8): 1179–86. PMID 2164060. doi:10.1177/38.8.2164060 .
• Pratt CW, Tobin RB, Church FC. Interaction of heparin cofactor II with neutrophil elastase and cathepsin G. The Journal of Biological Chemistry. April 1990, 265 (11): 6092–7. PMID 2318847. doi:10.1016/S0021-9258(19)39296-8 .
• Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF. Antibiotic proteins of human polymorphonuclear leukocytes. Proceedings of the National Academy of Sciences of the United States of America. July 1989, 86 (14): 5610–4. Bibcode:1989PNAS...86.5610G. PMC 297672 . PMID 2501794. doi:10.1073/pnas.86.14.5610 .
• Hohn PA, Popescu NC, Hanson RD, Salvesen G, Ley TJ. Genomic organization and chromosomal localization of the human cathepsin G gene. The Journal of Biological Chemistry. August 1989, 264 (23): 13412–9. PMID 2569462. doi:10.1016/S0021-9258(18)80012-6 .
• Livesey SA, Buescher ES, Krannig GL, Harrison DS, Linner JG, Chiovetti R. Human neutrophil granule heterogeneity: immunolocalization studies using cryofixed, dried and embedded specimens. Scanning Microscopy. Supplement. 1989, 3: 231–9; discussion 239–40. PMID 2616953.
• Campbell EJ, Silverman EK, Campbell MA. Elastase and cathepsin G of human monocytes. Quantification of cellular content, release in response to stimuli, and heterogeneity in elastase-mediated proteolytic activity. Journal of Immunology. November 1989, 143 (9): 2961–8. PMID 2681419.
• 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.
• Heck LW, Rostand KS, Hunter FA, Bhown A. Isolation, characterization, and amino-terminal amino acid sequence analysis of human neutrophil cathepsin G from normal donors. Analytical Biochemistry. October 1986, 158 (1): 217–27. PMID 3799965. doi:10.1016/0003-2697(86)90612-3.
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• Klickstein LB, Kaempfer CE, Wintroub BU. The granulocyte-angiotensin system. Angiotensin I-converting activity of cathepsin G. The Journal of Biological Chemistry. December 1982, 257 (24): 15042–6. PMID 6294088. doi:10.1016/S0021-9258(18)33390-8 .
• LaRosa CA, Rohrer MJ, Benoit SE, Barnard MR, Michelson AD. Neutrophil cathepsin G modulates the platelet surface expression of the glycoprotein (GP) Ib-IX complex by proteolysis of the von Willebrand factor binding site on GPIb alpha and by a cytoskeletal-mediated redistribution of the remainder of the complex. Blood. July 1994, 84 (1): 158–68. PMID 7517206. doi:10.1182/blood.V84.1.158.158 .
• Owen CA, Campbell MA, Sannes PL, Boukedes SS, Campbell EJ. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. The Journal of Cell Biology. November 1995, 131 (3): 775–89. PMC 2120617 . PMID 7593196. doi:10.1083/jcb.131.3.775.
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• Maruyama K, Sugano S. Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. Gene. January 1994, 138 (1–2): 171–4. PMID 8125298. doi:10.1016/0378-1119(94)90802-8.

外部链接

• The MEROPS online database for peptidases and their inhibitors: S01.133 （页面存档备份，存于互联网档案馆）

组织蛋白酶G引用了美国国家医学图书馆提供的资料，这些资料属于公共领域。