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組織蛋白酶G

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組織蛋白酶G
已知的結構
PDB直系同源搜索: PDBe RCSB
識別號
別名CTSG;, CATG, CG, cathepsin G
外部IDOMIM116830 MGI88563 HomoloGene105646 GeneCardsCTSG
基因位置(人類
14號染色體
染色體14號染色體[1]
14號染色體
組織蛋白酶G的基因位置
組織蛋白酶G的基因位置
基因座14q12起始24,573,518 bp[1]
終止24,576,250 bp[1]
RNA表達模式
查閱更多表達數據
直系同源
物種人類小鼠
Entrez
Ensembl
UniProt
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

組織蛋白酶G(英文:Cathepsin G)是一種在人體中由CTSG基因編碼的蛋白質。它是儲存在嗜天青顆粒細胞中的糜蛋白酶家族的三種絲氨酸蛋白酶之一,也是肽酶S1蛋白家族的成員。組織蛋白酶G在消除細胞內病原體和分解炎症部位的組織以及抗炎反應中起重要作用。[5][6][7][8]

結構

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基因

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CTSG基因位於14號染色體q11.2,由5個外顯子組成。催化三聯體的每個殘基都位於一個單獨的外顯子上。通過掃描整個編碼區已鑑定出五個基因多態性[9]組織蛋白酶G是通過基因複製從共同祖先進化而來的同源蛋白酶之一。[10]

蛋白質

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組織蛋白酶G是一種255-氨基酸殘基的蛋白質,包括一個18-殘基信號肽、一個N端的兩個殘基活化肽和一個C端延伸。[11]組織蛋白酶G的活性依賴於由天冬氨酸組氨酸絲氨酸殘基組成的催化三聯體,這些殘基在一級序列中廣泛分離,但在三級結構中酶的活性位點彼此靠近。[12]

作用

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組織蛋白酶G具有與胰凝乳蛋白酶C英語Chymotrypsin C相似的特異性,但它與其他免疫絲氨酸蛋白酶如中性粒細胞彈性蛋白酶英語Neutrophil elastase顆粒酶的關係最為密切。[13]作為一種中性粒細胞絲氨酸蛋白酶,它首先被鑑定為降解酶,它在細胞內作用以降解攝入的宿主病原體,並在細胞外作用於炎症部位的細胞外基質成分的分解。[14]它定位於中性粒細胞胞外陷阱,通過其對DNA的高親和力,這是絲氨酸蛋白酶的不尋常特性。[13]該基因存在利用替代多腺苷酸化信號的轉錄變體。[15]還發現組織蛋白酶G對革蘭氏陰性菌革蘭氏陽性菌具有廣譜抗菌作用,與上述功能無關。[16]組織蛋白酶G的其他功能已發現,包括切割受體、將血管緊張素I轉化為血管緊張素II、血小板激活和誘導氣道黏膜下腺分泌.[17][18][19][20][21]還發現了該酶在 血腦屏障 破壞中的潛在影響。[22]

臨床意義

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發現組織蛋白酶G在多種疾病中發揮重要作用,包括類風濕性關節炎冠狀動脈疾病牙周炎缺血再灌注損傷英語Reperfusion injury和骨轉移。[23][24][25][26][27]它還與多種感染性炎症疾病有關,包括慢性阻塞性肺病急性呼吸窘迫綜合症囊腫性纖維化[28][29][30]最近的一項研究表明,具有CTSG基因多態性的患者患慢性術後疼痛的風險更高,這表明組織蛋白酶G可能作為疼痛控制的新靶點和預測慢性術後疼痛的潛在標誌物。[31]圓錐角膜的研究中報告了組織蛋白酶G的上調。[32]

交互作用

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已發現組織蛋白酶G與以下物質相互作用

組織蛋白酶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彈性蛋白酶抑制劑[35]
  • N-芳酰基O-磺化氨基糖苷類[36]

組織蛋白酶G降低以下水平:

參見

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參考文獻

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  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可免費查閱. 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可免費查閱. 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可免費查閱. 
  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. 
  12. ^ Korkmaz B, Moreau T, Gauthier F. Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions. Biochimie. February 2008, 90 (2): 227–42. PMID 18021746. doi:10.1016/j.biochi.2007.10.009. 
  13. ^ 13.0 13.1 Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M, Lieberman J. Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins. Journal of Immunology. June 2014, 192 (11): 5390–7. PMC 4041364可免費查閱. PMID 24771851. doi:10.4049/jimmunol.1303296. 
  14. ^ Pham CT. Neutrophil serine proteases: specific regulators of inflammation. Nature Reviews. Immunology. July 2006, 6 (7): 541–50. PMID 16799473. S2CID 111538. doi:10.1038/nri1841. 
  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可免費查閱. 
  17. ^ Beaufort N, Leduc D, Rousselle JC, Magdolen V, Luther T, Namane A, Chignard M, Pidard D. Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G. Journal of Immunology. January 2004, 172 (1): 540–9. PMID 14688365. doi:10.4049/jimmunol.172.1.540可免費查閱. 
  18. ^ Bank U, Ansorge S. More than destructive: neutrophil-derived serine proteases in cytokine bioactivity control. Journal of Leukocyte Biology. February 2001, 69 (2): 197–206. PMID 11272269. S2CID 30791872. doi:10.1189/jlb.69.2.197. 
  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可免費查閱. 
  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可免費查閱. 
  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. 
  22. ^ Armao D, Kornfeld M, Estrada EY, Grossetete M, Rosenberg GA. Neutral proteases and disruption of the blood-brain barrier in rat. Brain Research. September 1997, 767 (2): 259–64. PMID 9367256. S2CID 40103486. doi:10.1016/S0006-8993(97)00567-2. 
  23. ^ Szekanecz Z, Koch AE. Macrophages and their products in rheumatoid arthritis. Current Opinion in Rheumatology. May 2007, 19 (3): 289–95. PMID 17414958. S2CID 8096646. doi:10.1097/BOR.0b013e32805e87ae. 
  24. ^ Takei T, Sakai S, Yokonuma T, Ijima H, Kawakami K. Fabrication of artificial endothelialized tubes with predetermined three-dimensional configuration from flexible cell-enclosing alginate fibers. Biotechnology Progress. Jan–Feb 2007, 23 (1): 182–6. PMID 17269686. S2CID 40332839. doi:10.1021/bp060152j. 
  25. ^ Liu R, Chen L, Wu W, Chen H, Zhang S. Neutrophil serine proteases and their endogenous inhibitors in coronary artery ectasia patients. Anatolian Journal of Cardiology. January 2016, 16 (1): 23–8. PMC 5336701可免費查閱. PMID 26467359. doi:10.5152/akd.2015.6072. 
  26. ^ Komine K, Kuroishi T, Ozawa A, Komine Y, Minami T, Shimauchi H, Sugawara S. Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis patients. Molecular Immunology. March 2007, 44 (7): 1498–508. PMID 17030385. doi:10.1016/j.molimm.2006.09.003. 
  27. ^ Shimoda N, Fukazawa N, Nonomura K, Fairchild RL. Cathepsin g is required for sustained inflammation and tissue injury after reperfusion of ischemic kidneys. The American Journal of Pathology. March 2007, 170 (3): 930–40. PMC 1864870可免費查閱. PMID 17322378. doi:10.2353/ajpath.2007.060486. 
  28. ^ Kawabata K, Hagio T, Matsuoka S. The role of neutrophil elastase in acute lung injury. European Journal of Pharmacology. September 2002, 451 (1): 1–10. PMID 12223222. doi:10.1016/s0014-2999(02)02182-9. 
  29. ^ Moraes TJ, Chow CW, Downey GP. Proteases and lung injury. Critical Care Medicine. April 2003, 31 (4 Suppl): S189–94. PMID 12682439. S2CID 45296600. doi:10.1097/01.CCM.0000057842.90746.1E. 
  30. ^ Twigg MS, Brockbank S, Lowry P, FitzGerald SP, Taggart C, Weldon S. The Role of Serine Proteases and Antiproteases in the Cystic Fibrosis Lung. Mediators of Inflammation. 2015, 2015: 293053. PMC 4491392可免費查閱. PMID 26185359. doi:10.1155/2015/293053可免費查閱. 
  31. ^ Liu X, Tian Y, Meng Z, Chen Y, Ho IH, Choy KW, Lichtner P, Wong SH, Yu J, Gin T, Wu WK, Cheng CH, Chan MT. Up-regulation of Cathepsin G in the Development of Chronic Postsurgical Pain: An Experimental and Clinical Genetic Study. Anesthesiology. October 2015, 123 (4): 838–50. PMID 26270939. S2CID 43571196. doi:10.1097/ALN.0000000000000828. 
  32. ^ Whitelock RB, Fukuchi T, Zhou L, Twining SS, Sugar J, Feder RS, Yue BY. Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas. Investigative Ophthalmology & Visual Science. February 1997, 38 (2): 529–34. PMID 9040486. 
  33. ^ Baumann M, Pham CT, Benarafa C. SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition of cathepsin G. Blood. May 2013, 121 (19): 3900–7, S1–6. PMC 3650706可免費查閱. PMID 23532733. doi:10.1182/blood-2012-09-455022. 
  34. ^ Son ED, Shim JH, Choi H, Kim H, Lim KM, Chung JH, Byun SY, Lee TR. Cathepsin G inhibitor prevents ultraviolet B-induced photoaging in hairless mice via inhibition of fibronectin fragmentation. Dermatology. 2012, 224 (4): 352–60. PMID 22759782. S2CID 29489606. doi:10.1159/000339337. 
  35. ^ Cruz-Silva I, Neuhof C, Gozzo AJ, Nunes VA, Hirata IY, Sampaio MU, Figueiredo-Ribeiro Rde C, Neuhof H, Araújo Mda S. Using a Caesalpinia echinata Lam. protease inhibitor as a tool for studying the roles of neutrophil elastase, cathepsin G and proteinase 3 in pulmonary edema. Phytochemistry. December 2013, 96: 235–43. PMID 24140156. doi:10.1016/j.phytochem.2013.09.025. 
  36. ^ Craciun I, Fenner AM, Kerns RJ. N-Arylacyl O-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3. Glycobiology. February 2016, 26 (7): 701–9. PMC 4976519可免費查閱. PMID 26850997. doi:10.1093/glycob/cww011. 
  37. ^ Wang J, Sjöberg S, Tang TT, Oörni K, Wu W, Liu C, Secco B, Tia V, Sukhova GK, Fernandes C, Lesner A, Kovanen PT, Libby P, Cheng X, Shi GP. Cathepsin G activity lowers plasma LDL and reduces atherosclerosis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. November 2014, 1842 (11): 2174–83. PMC 4188792可免費查閱. PMID 25092171. doi:10.1016/j.bbadis.2014.07.026. 

拓展閱讀

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外部連結

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組織蛋白酶G引用了美國國家醫學圖書館提供的資料,這些資料屬於公共領域