CTSG
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCTSG, CATG, CG, cathepsin G
External IDsOMIM: 116830 MGI: 88563 HomoloGene: 105646 GeneCards: CTSG
Orthologs
SpeciesHumanMouse
Entrez

1511

13035

Ensembl

ENSG00000100448

ENSMUSG00000040314

UniProt

P08311

P28293

RefSeq (mRNA)

NM_001911

NM_007800

RefSeq (protein)

NP_001902

NP_031826

Location (UCSC)Chr 14: 24.57 – 24.58 MbChr 14: 56.34 – 56.34 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin G plays an important role in eliminating intracellular pathogens and breaking down tissues at inflammatory sites, as well as in anti-inflammatory response.[5][6][7][8]

Structure

Gene

The CTSG gene is located at chromosome 14q11.2, consisting of 5 exons. Each residue of the catalytic triad is located on a separate exon. Five polymorphisms have been identified by scanning the entire coding region.[9] Cathepsin G is one of those homologous protease that evolved from a common ancestor by gene duplication.[10]

Protein

Cathepsin G is a 255-amino-acid-residue protein including an 18-residue signal peptide, a two-residue activation peptide at the N-terminus and a carboxy terminal extension.[11] The activity of cathepsin G depends on a catalytic triad composed of aspartate, histidine and serine residues which are widely separated in the primary sequence but close to each other at the active site of the enzyme in the tertiary structure.[12]

Function

Cathepsin G has a specificity similar to that of chymotrypsin C, but it is most closely related to other immune serine proteases, such as neutrophil elastase and the granzymes.[13] As a neutrophil serine protease, was first identified as degradative enzyme that acts intracellularly to degrade ingested host pathogens and extracellularly in the breakdown of ECM components at inflammatory sites.[14] It localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.[13] Transcript variants utilizing alternative polyadenylation signals exist for this gene.[15] Cathepsin G was also found to exert broad-spectrum antibacterial action against Gram-negative and –positive bacteria independent of the function mentioned above.[16] Other functions of cathepsin G have been reported, including cleavage of receptors, conversion of angiotensin I to angiotensin II, platelet activation, and induction of airway submucosal gland secretion.[17][18][19][20][21] Potential implications of the enzyme in blood-brain barrier breakdown was also found.[22]

Clinical significance

Cathepsin G has been reported to play an important role in a variety of diseases, including rheumatoid arthritis, coronary artery disease, periodontitis, ischemic reperfusion injury, and bone metastasis.[23][24][25][26][27] It is also implicated in a variety of infectious inflammatory diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, and cystic fibrosis.[28][29][30] A recent study shows that patients with CTSG gene polymorphisms have higher risk of chronic postsurgical pain, suggesting cathepsin G may serve as a novel target for pain control and a potential marker to predict chronic postsurgical pain.[31] An upregulation of cathepsin G was reported in studies of keratoconus.[32]

Interactions

Cathepsin G has been found to interact with:

Cathepsin G is inhibited by:

  • [2-[3-[[(1-benzoyl-4-piperidinyl)methylamino]carbonyl]-2-naphthalenyl]-1-(1-naphthalenyl)-2-oxoethyl]-phosphonic acid (KPA) [34]
  • Caesalpinia echinata elastase inhibitor[35]
  • N-Arylacyl O-sulfonated aminoglycosides[36]

Cathepsin G lowers levels of:

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000100448 - Ensembl, May 2017
  2. 1 2 3 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 (November 1968). "Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes". The Journal of Experimental Medicine. 128 (5): 1137–55. doi:10.1084/jem.128.5.1137. PMC 2138566. PMID 5303065.
  6. Kao RC, Wehner NG, Skubitz KM, Gray BH, Hoidal JR (December 1988). "Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters". The Journal of Clinical Investigation. 82 (6): 1963–73. doi:10.1172/JCI113816. PMC 442778. PMID 3198760.
  7. Baggiolini M, Schnyder J, Bretz U, Dewald B, Ruch W (1979). "Cellular Mechanisms of Proteinase Release from Inflammatory Cells and the Degradation of Extracellular Proteins". In Evered D, Whelan J (eds.). Ciba Foundation Symposium 75 - Protein Degradation in Health and Disease. Novartis Foundation Symposia. Vol. 75. pp. 105–21. doi:10.1002/9780470720585.ch7. ISBN 9780470720585. PMID 399884.
  8. Virca GD, Metz G, Schnebli HP (October 1984). "Similarities between human and rat leukocyte elastase and cathepsin G". European Journal of Biochemistry. 144 (1): 1–9. doi:10.1111/j.1432-1033.1984.tb08423.x. PMID 6566611.
  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 (September 2001). "Characterization of polymorphic structure of cathepsin G gene: role in cardiovascular and cerebrovascular diseases". Arteriosclerosis, Thrombosis, and Vascular Biology. 21 (9): 1538–43. doi:10.1161/hq0901.095555. PMID 11557685.
  10. Salvesen G, Enghild JJ (1991). "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. 50 (4–6): 665–71. PMID 1801740.
  11. Salvesen G, Farley D, Shuman J, Przybyla A, Reilly C, Travis J (April 1987). "Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases". Biochemistry. 26 (8): 2289–93. doi:10.1021/bi00382a032. PMID 3304423.
  12. Korkmaz B, Moreau T, Gauthier F (February 2008). "Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions". Biochimie. 90 (2): 227–42. doi:10.1016/j.biochi.2007.10.009. PMID 18021746.
  13. 1 2 Thomas MP, Whangbo J, McCrossan G, Deutsch AJ, Martinod K, Walch M, Lieberman J (June 2014). "Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins". Journal of Immunology. 192 (11): 5390–7. doi:10.4049/jimmunol.1303296. PMC 4041364. PMID 24771851.
  14. Pham CT (July 2006). "Neutrophil serine proteases: specific regulators of inflammation". Nature Reviews. Immunology. 6 (7): 541–50. doi:10.1038/nri1841. PMID 16799473. S2CID 111538.
  15. "Entrez Gene: CTSG cathepsin G".
  16. Shafer WM, Pohl J, Onunka VC, Bangalore N, Travis J (January 1991). "Human lysosomal cathepsin G and granzyme B share a functionally conserved broad spectrum antibacterial peptide". The Journal of Biological Chemistry. 266 (1): 112–6. doi:10.1016/S0021-9258(18)52409-1. PMID 1985886.
  17. Beaufort N, Leduc D, Rousselle JC, Magdolen V, Luther T, Namane A, Chignard M, Pidard D (January 2004). "Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G". Journal of Immunology. 172 (1): 540–9. doi:10.4049/jimmunol.172.1.540. PMID 14688365.
  18. Bank U, Ansorge S (February 2001). "More than destructive: neutrophil-derived serine proteases in cytokine bioactivity control". Journal of Leukocyte Biology. 69 (2): 197–206. doi:10.1189/jlb.69.2.197. PMID 11272269. S2CID 30791872.
  19. Reilly CF, Tewksbury DA, Schechter NM, Travis J (August 1982). "Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases". The Journal of Biological Chemistry. 257 (15): 8619–22. doi:10.1016/S0021-9258(18)34171-1. PMID 6807977.
  20. Sambrano GR, Huang W, Faruqi T, Mahrus S, Craik C, Coughlin SR (March 2000). "Cathepsin G activates protease-activated receptor-4 in human platelets". The Journal of Biological Chemistry. 275 (10): 6819–23. doi:10.1074/jbc.275.10.6819. PMID 10702240.
  21. Nadel JA (September 1991). "Role of mast cell and neutrophil proteases in airway secretion". The American Review of Respiratory Disease. 144 (3 Pt 2): S48–51. doi:10.1164/ajrccm/144.3_pt_2.S48. PMID 1892327.
  22. Armao D, Kornfeld M, Estrada EY, Grossetete M, Rosenberg GA (September 1997). "Neutral proteases and disruption of the blood-brain barrier in rat". Brain Research. 767 (2): 259–64. doi:10.1016/S0006-8993(97)00567-2. PMID 9367256. S2CID 40103486.
  23. Szekanecz Z, Koch AE (May 2007). "Macrophages and their products in rheumatoid arthritis". Current Opinion in Rheumatology. 19 (3): 289–95. doi:10.1097/BOR.0b013e32805e87ae. PMID 17414958. S2CID 8096646.
  24. Takei T, Sakai S, Yokonuma T, Ijima H, Kawakami K (Jan–Feb 2007). "Fabrication of artificial endothelialized tubes with predetermined three-dimensional configuration from flexible cell-enclosing alginate fibers". Biotechnology Progress. 23 (1): 182–6. doi:10.1021/bp060152j. PMID 17269686. S2CID 40332839.
  25. Liu R, Chen L, Wu W, Chen H, Zhang S (January 2016). "Neutrophil serine proteases and their endogenous inhibitors in coronary artery ectasia patients". Anatolian Journal of Cardiology. 16 (1): 23–8. doi:10.5152/akd.2015.6072. PMC 5336701. PMID 26467359.
  26. Komine K, Kuroishi T, Ozawa A, Komine Y, Minami T, Shimauchi H, Sugawara S (March 2007). "Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis patients". Molecular Immunology. 44 (7): 1498–508. doi:10.1016/j.molimm.2006.09.003. PMID 17030385.
  27. Shimoda N, Fukazawa N, Nonomura K, Fairchild RL (March 2007). "Cathepsin g is required for sustained inflammation and tissue injury after reperfusion of ischemic kidneys". The American Journal of Pathology. 170 (3): 930–40. doi:10.2353/ajpath.2007.060486. PMC 1864870. PMID 17322378.
  28. Kawabata K, Hagio T, Matsuoka S (September 2002). "The role of neutrophil elastase in acute lung injury". European Journal of Pharmacology. 451 (1): 1–10. doi:10.1016/s0014-2999(02)02182-9. PMID 12223222.
  29. Moraes TJ, Chow CW, Downey GP (April 2003). "Proteases and lung injury". Critical Care Medicine. 31 (4 Suppl): S189–94. doi:10.1097/01.CCM.0000057842.90746.1E. PMID 12682439. S2CID 45296600.
  30. Twigg MS, Brockbank S, Lowry P, FitzGerald SP, Taggart C, Weldon S (2015). "The Role of Serine Proteases and Antiproteases in the Cystic Fibrosis Lung". Mediators of Inflammation. 2015: 293053. doi:10.1155/2015/293053. PMC 4491392. PMID 26185359.
  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 (October 2015). "Up-regulation of Cathepsin G in the Development of Chronic Postsurgical Pain: An Experimental and Clinical Genetic Study". Anesthesiology. 123 (4): 838–50. doi:10.1097/ALN.0000000000000828. PMID 26270939. S2CID 43571196.
  32. Whitelock RB, Fukuchi T, Zhou L, Twining SS, Sugar J, Feder RS, Yue BY (February 1997). "Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas". Investigative Ophthalmology & Visual Science. 38 (2): 529–34. PMID 9040486.
  33. Baumann M, Pham CT, Benarafa C (May 2013). "SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition of cathepsin G". Blood. 121 (19): 3900–7, S1–6. doi:10.1182/blood-2012-09-455022. PMC 3650706. PMID 23532733.
  34. Son ED, Shim JH, Choi H, Kim H, Lim KM, Chung JH, Byun SY, Lee TR (2012). "Cathepsin G inhibitor prevents ultraviolet B-induced photoaging in hairless mice via inhibition of fibronectin fragmentation". Dermatology. 224 (4): 352–60. doi:10.1159/000339337. PMID 22759782. S2CID 29489606.
  35. Cruz-Silva I, Neuhof C, Gozzo AJ, Nunes VA, Hirata IY, Sampaio MU, Figueiredo-Ribeiro Rde C, Neuhof H, Araújo Mda S (December 2013). "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. 96: 235–43. Bibcode:2013PChem..96..235C. doi:10.1016/j.phytochem.2013.09.025. PMID 24140156.
  36. Craciun I, Fenner AM, Kerns RJ (February 2016). "N-Arylacyl O-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3". Glycobiology. 26 (7): 701–9. doi:10.1093/glycob/cww011. PMC 4976519. PMID 26850997.
  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 (November 2014). "Cathepsin G activity lowers plasma LDL and reduces atherosclerosis". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1842 (11): 2174–83. doi:10.1016/j.bbadis.2014.07.026. PMC 4188792. PMID 25092171.

Further reading

  • The MEROPS online database for peptidases and their inhibitors: S01.133

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