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. Cathepsin G is one of those homologous protease that evolved from a common ancestor by gene duplication.
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. 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.
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. 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. It localizes to Neutrophil extracellular traps (NETs), via its high affinity for DNA, an unusual property for serine proteases. Transcript variants utilizing alternative polyadenylation signals exist for this gene. Cathepsin G was also found to exert broad-spectrum antibacterial action against Gram-negative and –positive bacteria independent of the function mentioned above. 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. Potential implications of the enzyme in blood-brain barrier breakdown was also found.
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. It is also implicated in a variety of infectious inflammatory diseases, including chronic obstructive pulmonary disease, acute respiratory distress syndrome, and cystic fibrosis. 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. An upregulation of cathepsin G was reported in studies of keratoconus.
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↑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. PMID3304423.
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↑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. PMID26270939.
↑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. PMID22759782.
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↑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: 701–9. doi:10.1093/glycob/cww011. PMID26850997.
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The MEROPS online database for peptidases and their inhibitors: S01.133