Cathepsin G is aprotein that in humans is encoded by theCTSGgene. It is one of the threeserine proteases of thechymotrypsin family that are stored in theazurophil granules, and also a member of thepeptidase 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]
TheCTSG gene is located atchromosome 14q11.2, consisting of 5exons. Each residue of thecatalytic triad is located on a separate exon. Fivepolymorphisms have been identified by scanning the entirecoding region.[9] Cathepsin G homologs evolved from a common ancestor via gene duplication.[10]
Cathepsin G is a 255-amino-acid-residue protein including an 18-residue signal peptide, a two-residue activation peptide at theN-terminus and acarboxy terminal extension.[11] The activity of cathepsin G depends on a catalytic triad composed ofaspartate,histidine andserine residues which are widely separated in the primary sequence but close to each other at the active site of the enzyme in thetertiary structure.[12]
Cathepsin G has a specificity similar to that ofchymotrypsin C, but it is most closely related to other immune serine proteases, such asneutrophil elastase and thegranzymes.[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 ofECM components at inflammatory sites.[14] It localizes toNeutrophil extracellular traps (NETs), via its high affinity forDNA, 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 ofreceptors, conversion ofangiotensin I to angiotensin II,platelet activation, and induction of airway submucosal gland secretion.[17][18][19][20][21] Potential implications of the enzyme inblood-brain barrier breakdown was also found.[22]
Cathepsin G has been reported to play an important role in a variety of diseases, includingrheumatoid 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 withCTSG 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 ofkeratoconus.[32]
^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.ISBN978-0-470-72058-5.PMID399884.
^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.PMID1801740.
^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.
^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.PMID18021746.
^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.PMID11272269.S2CID30791872.
^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.PMID1892327.
^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.PMID9367256.S2CID40103486.
^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.PMID12223222.
^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.S2CID43571196.
^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.S2CID29489606.
^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.PMID24140156.
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.doi:10.2174/1381612023395376.PMID11945165.
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.doi:10.1152/ajplung.1992.263.2.L249.PMID1387511.
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.doi:10.1177/00220345920710120501.PMID1452887.S2CID27658837.
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.doi:10.1016/1043-4666(91)90499-4.PMID1873479.
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.
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.doi:10.1016/0003-2697(86)90612-3.PMID3799965.
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.doi:10.1016/0306-4522(94)90490-1.PMID7936190.S2CID24998185.
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.doi:10.1016/0378-1119(94)90802-8.PMID8125298.
