Biology:Cathepsin G

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Short description: Protein-coding gene in the species Homo sapiens

Template:Cs1 config

A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.[1][2][3][4]

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.[5] Cathepsin G is one of those homologous protease that evolved from a common ancestor by gene duplication.[6]

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.[7] 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.[8]

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.[9] 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.[10] It localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases.[9] Transcript variants utilizing alternative polyadenylation signals exist for this gene.[11] Cathepsin G was also found to exert broad-spectrum antibacterial action against Gram-negative and –positive bacteria independent of the function mentioned above.[12] 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.[13][14][15][16][17] Potential implications of the enzyme in blood-brain barrier breakdown was also found.[18]

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.[19][20][21][22][23] It is also implicated in a variety of infectious inflammatory diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, and cystic fibrosis.[24][25][26] 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.[27] An upregulation of cathepsin G was reported in studies of keratoconus.[28]

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) [30]
  • Caesalpinia echinata elastase inhibitor[31]
  • N-Arylacyl O-sulfonated aminoglycosides[32]

Cathepsin G lowers levels of:

See also

References

  1. ↑ "Mediators of inflammation in leukocyte lysosomes. IX. Elastinolytic activity in granules of human polymorphonuclear leukocytes". The Journal of Experimental Medicine 128 (5): 1137–55. November 1968. doi:10.1084/jem.128.5.1137. PMID 5303065. 
  2. ↑ "Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters". The Journal of Clinical Investigation 82 (6): 1963–73. December 1988. doi:10.1172/JCI113816. PMID 3198760. 
  3. ↑ "Ciba Foundation Symposium 75 - Protein Degradation in Health and Disease". 75. 1979. pp. 105–21. doi:10.1002/9780470720585.ch7. ISBN 9780470720585. 
  4. ↑ "Similarities between human and rat leukocyte elastase and cathepsin G". European Journal of Biochemistry 144 (1): 1–9. October 1984. doi:10.1111/j.1432-1033.1984.tb08423.x. PMID 6566611. 
  5. ↑ "Characterization of polymorphic structure of cathepsin G gene: role in cardiovascular and cerebrovascular diseases". Arteriosclerosis, Thrombosis, and Vascular Biology 21 (9): 1538–43. September 2001. doi:10.1161/hq0901.095555. PMID 11557685. 
  6. ↑ "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. 1991. PMID 1801740. 
  7. ↑ "Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases". Biochemistry 26 (8): 2289–93. April 1987. doi:10.1021/bi00382a032. PMID 3304423. 
  8. ↑ "Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions". Biochimie 90 (2): 227–42. February 2008. doi:10.1016/j.biochi.2007.10.009. PMID 18021746. 
  9. ↑ 9.0 9.1 "Leukocyte protease binding to nucleic acids promotes nuclear localization and cleavage of nucleic acid binding proteins". Journal of Immunology 192 (11): 5390–7. June 2014. doi:10.4049/jimmunol.1303296. PMID 24771851. 
  10. ↑ "Neutrophil serine proteases: specific regulators of inflammation". Nature Reviews. Immunology 6 (7): 541–50. July 2006. doi:10.1038/nri1841. PMID 16799473. 
  11. ↑ "Entrez Gene: CTSG cathepsin G". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1511. 
  12. ↑ "Human lysosomal cathepsin G and granzyme B share a functionally conserved broad spectrum antibacterial peptide". The Journal of Biological Chemistry 266 (1): 112–6. January 1991. doi:10.1016/S0021-9258(18)52409-1. PMID 1985886. 
  13. ↑ "Proteolytic regulation of the urokinase receptor/CD87 on monocytic cells by neutrophil elastase and cathepsin G". Journal of Immunology 172 (1): 540–9. January 2004. doi:10.4049/jimmunol.172.1.540. PMID 14688365. 
  14. ↑ "More than destructive: neutrophil-derived serine proteases in cytokine bioactivity control". Journal of Leukocyte Biology 69 (2): 197–206. February 2001. doi:10.1189/jlb.69.2.197. PMID 11272269. 
  15. ↑ "Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases". The Journal of Biological Chemistry 257 (15): 8619–22. August 1982. doi:10.1016/S0021-9258(18)34171-1. PMID 6807977. 
  16. ↑ "Cathepsin G activates protease-activated receptor-4 in human platelets". The Journal of Biological Chemistry 275 (10): 6819–23. March 2000. doi:10.1074/jbc.275.10.6819. PMID 10702240. 
  17. ↑ "Role of mast cell and neutrophil proteases in airway secretion". The American Review of Respiratory Disease 144 (3 Pt 2): S48–51. September 1991. doi:10.1164/ajrccm/144.3_pt_2.S48. PMID 1892327. 
  18. ↑ "Neutral proteases and disruption of the blood-brain barrier in rat". Brain Research 767 (2): 259–64. September 1997. doi:10.1016/S0006-8993(97)00567-2. PMID 9367256. 
  19. ↑ "Macrophages and their products in rheumatoid arthritis". Current Opinion in Rheumatology 19 (3): 289–95. May 2007. doi:10.1097/BOR.0b013e32805e87ae. PMID 17414958. 
  20. ↑ "Fabrication of artificial endothelialized tubes with predetermined three-dimensional configuration from flexible cell-enclosing alginate fibers". Biotechnology Progress 23 (1): 182–6. Jan–Feb 2007. doi:10.1021/bp060152j. PMID 17269686. 
  21. ↑ "Neutrophil serine proteases and their endogenous inhibitors in coronary artery ectasia patients". Anatolian Journal of Cardiology 16 (1): 23–8. January 2016. doi:10.5152/akd.2015.6072. PMID 26467359. 
  22. ↑ "Cleaved inflammatory lactoferrin peptides in parotid saliva of periodontitis patients". Molecular Immunology 44 (7): 1498–508. March 2007. doi:10.1016/j.molimm.2006.09.003. PMID 17030385. 
  23. ↑ "Cathepsin g is required for sustained inflammation and tissue injury after reperfusion of ischemic kidneys". The American Journal of Pathology 170 (3): 930–40. March 2007. doi:10.2353/ajpath.2007.060486. PMID 17322378. 
  24. ↑ "The role of neutrophil elastase in acute lung injury". European Journal of Pharmacology 451 (1): 1–10. September 2002. doi:10.1016/s0014-2999(02)02182-9. PMID 12223222. 
  25. ↑ "Proteases and lung injury". Critical Care Medicine 31 (4 Suppl): S189–94. April 2003. doi:10.1097/01.CCM.0000057842.90746.1E. PMID 12682439. 
  26. ↑ "The Role of Serine Proteases and Antiproteases in the Cystic Fibrosis Lung". Mediators of Inflammation 2015: 293053. 2015. doi:10.1155/2015/293053. PMID 26185359. 
  27. ↑ "Up-regulation of Cathepsin G in the Development of Chronic Postsurgical Pain: An Experimental and Clinical Genetic Study". Anesthesiology 123 (4): 838–50. October 2015. doi:10.1097/ALN.0000000000000828. PMID 26270939. 
  28. ↑ "Cathepsin G, acid phosphatase, and alpha 1-proteinase inhibitor messenger RNA levels in keratoconus corneas". Investigative Ophthalmology & Visual Science 38 (2): 529–34. February 1997. PMID 9040486. 
  29. ↑ "SerpinB1 is critical for neutrophil survival through cell-autonomous inhibition of cathepsin G". Blood 121 (19): 3900–7, S1–6. May 2013. doi:10.1182/blood-2012-09-455022. PMID 23532733. 
  30. ↑ "Cathepsin G inhibitor prevents ultraviolet B-induced photoaging in hairless mice via inhibition of fibronectin fragmentation". Dermatology 224 (4): 352–60. 2012. doi:10.1159/000339337. PMID 22759782. 
  31. ↑ "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. December 2013. doi:10.1016/j.phytochem.2013.09.025. PMID 24140156. Bibcode: 2013PChem..96..235C. 
  32. ↑ "N-Arylacyl O-sulfonated aminoglycosides as novel inhibitors of human neutrophil elastase, cathepsin G and proteinase 3". Glycobiology 26 (7): 701–9. February 2016. doi:10.1093/glycob/cww011. PMID 26850997. 
  33. ↑ "Cathepsin G activity lowers plasma LDL and reduces atherosclerosis". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1842 (11): 2174–83. November 2014. doi:10.1016/j.bbadis.2014.07.026. PMID 25092171. 

Further reading

External links

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

This article incorporates text from the United States National Library of Medicine, which is in the public domain.



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