Cathepsin G
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| Location (UCSC) | Chr 14: 24.57 – 24.58 Mb | Chr 14: 56.34 – 56.34 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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Cathepsin G is a
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
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-
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
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
- ^ a b c GRCh38: Ensembl release 89: ENSG00000100448 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040314 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 5303065.
- PMID 3198760.
- PMID 399884.
- PMID 6566611.
- PMID 11557685.
- PMID 1801740.
- PMID 3304423.
- PMID 18021746.
- ^ PMID 24771851.
- S2CID 111538.
- ^ "Entrez Gene: CTSG cathepsin G".
- PMID 1985886.
- PMID 14688365.
- S2CID 30791872.
- PMID 6807977.
- PMID 10702240.
- PMID 1892327.
- S2CID 40103486.
- S2CID 8096646.
- S2CID 40332839.
- PMID 26467359.
- PMID 17030385.
- PMID 17322378.
- PMID 12223222.
- S2CID 45296600.
- PMID 26185359.
- S2CID 43571196.
- PMID 9040486.
- PMID 23532733.
- S2CID 29489606.
- PMID 24140156.
- PMID 26850997.
- PMID 25092171.
Further reading
- Shafer WM, Katzif S, Bowers S, Fallon M, Hubalek M, Reed MS, Veprek P, Pohl J (2002). "Tailoring an antibacterial peptide of human lysosomal cathepsin G to enhance its broad-spectrum action against antibiotic-resistant bacterial pathogens". Current Pharmaceutical Design. 8 (9): 695–702. PMID 11945165.
- Cohen AB, Stevens MD, Miller EJ, Atkinson MA, Mullenbach G (August 1992). "Generation of the neutrophil-activating peptide-2 by cathepsin G and cathepsin G-treated human platelets". The American Journal of Physiology. 263 (2 Pt 1): L249–56. PMID 1387511.
- Sasaki T, Ueno-Matsuda E (December 1992). "Immunocytochemical localization of cathepsins B and G in odontoclasts of human deciduous teeth". Journal of Dental Research. 71 (12): 1881–4. S2CID 27658837.
- Maison CM, Villiers CL, Colomb MG (August 1991). "Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G". Journal of Immunology. 147 (3): 921–6. PMID 1861080.
- Brandt E, Van Damme J, Flad HD (July 1991). "Neutrophils can generate their activator neutrophil-activating peptide 2 by proteolytic cleavage of platelet-derived connective tissue-activating peptide III". Cytokine. 3 (4): 311–21. PMID 1873479.
- Kargi HA, Campbell EJ, Kuhn C (August 1990). "Elastase and cathepsin G of human monocytes: heterogeneity and subcellular localization to peroxidase-positive granules". The Journal of Histochemistry and Cytochemistry. 38 (8): 1179–86. PMID 2164060.
- Pratt CW, Tobin RB, Church FC (April 1990). "Interaction of heparin cofactor II with neutrophil elastase and cathepsin G". The Journal of Biological Chemistry. 265 (11): 6092–7. PMID 2318847.
- Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF (July 1989). "Antibiotic proteins of human polymorphonuclear leukocytes". Proceedings of the National Academy of Sciences of the United States of America. 86 (14): 5610–4. PMID 2501794.
- Hohn PA, Popescu NC, Hanson RD, Salvesen G, Ley TJ (August 1989). "Genomic organization and chromosomal localization of the human cathepsin G gene". The Journal of Biological Chemistry. 264 (23): 13412–9. PMID 2569462.
- Livesey SA, Buescher ES, Krannig GL, Harrison DS, Linner JG, Chiovetti R (1989). "Human neutrophil granule heterogeneity: immunolocalization studies using cryofixed, dried and embedded specimens". Scanning Microscopy. Supplement. 3: 231–9, discussion 239–40. PMID 2616953.
- Campbell EJ, Silverman EK, Campbell MA (November 1989). "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. 143 (9): 2961–8. PMID 2681419.
- 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. PMID 3304423.
- Heck LW, Rostand KS, Hunter FA, Bhown A (October 1986). "Isolation, characterization, and amino-terminal amino acid sequence analysis of human neutrophil cathepsin G from normal donors". Analytical Biochemistry. 158 (1): 217–27. PMID 3799965.
- Crocker J, Jenkins R, Burnett D (May 1985). "Immunohistochemical localization of cathepsin G in human tissues". The American Journal of Surgical Pathology. 9 (5): 338–43. S2CID 23124253.
- Klickstein LB, Kaempfer CE, Wintroub BU (December 1982). "The granulocyte-angiotensin system. Angiotensin I-converting activity of cathepsin G". The Journal of Biological Chemistry. 257 (24): 15042–6. PMID 6294088.
- LaRosa CA, Rohrer MJ, Benoit SE, Barnard MR, Michelson AD (July 1994). "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. 84 (1): 158–68. PMID 7517206.
- Owen CA, Campbell MA, Sannes PL, Boukedes SS, Campbell EJ (November 1995). "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. 131 (3): 775–89. PMID 7593196.
- Savage MJ, Iqbal M, Loh T, Trusko SP, Scott R, Siman R (June 1994). "Cathepsin G: localization in human cerebral cortex and generation of amyloidogenic fragments from the beta-amyloid precursor protein". Neuroscience. 60 (3): 607–19. S2CID 24998185.
- Grisolano JL, Sclar GM, Ley TJ (September 1994). "Early myeloid cell-specific expression of the human cathepsin G gene in transgenic mice". Proceedings of the National Academy of Sciences of the United States of America. 91 (19): 8989–93. PMID 8090757.
- Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. PMID 8125298.
External links
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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