Cathepsin G

Details

Name
Cathepsin G
Kind
protein
Synonyms
  • 3.4.21.20
  • CG
Gene Name
CTSG
UniProtKB Entry
P08311Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0016283|Cathepsin G
MQPLLLLLAFLLPTGAEAGEIIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVL
TAAHCWGSNINVTLGAHNIQRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRR
NRNVNPVALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRQCLRIFGSYD
PRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVSSFLPWIRT
TMRSFKLLDQMETPL
Number of residues
255
Molecular Weight
28836.99
Theoretical pI
11.69
GO Classification
Functions
heparin binding / peptidase activity / serine-type endopeptidase activity
Processes
angiotensin maturation / defense response to fungus / extracellular matrix disassembly / immune response / positive regulation of immune response / protein phosphorylation / protein processing / proteolysis
Components
cytoplasm / extracellular exosome / extracellular region / extracellular space / nucleus / plasma membrane / secretory granule
General Function
Serine protease with trypsin- and chymotrypsin-like specificity (PubMed:29652924, PubMed:8194606). Also displays antibacterial activity against Gram-negative and Gram-positive bacteria independent of its protease activity (PubMed:2116408, PubMed:2117044). Prefers Phe and Tyr residues in the P1 position of substrates but also cleaves efficiently after Trp and Leu (PubMed:29652924). Shows a preference for negatively charged amino acids in the P2' position and for aliphatic amino acids both upstream and downstream of the cleavage site (PubMed:29652924). Required for recruitment and activation of platelets which is mediated by the F2RL3/PAR4 platelet receptor (PubMed:10702240, PubMed:3390156). Binds reversibly to and stimulates B cells and CD4(+) and CD8(+) T cells (PubMed:7842483, PubMed:9000539). Also binds reversibly to natural killer (NK) cells and enhances NK cell cytotoxicity through its protease activity (PubMed:9000539, PubMed:9536127). Cleaves complement C3 (PubMed:1861080). Cleaves vimentin (By similarity). Cleaves thrombin receptor F2R/PAR1 and acts as either an agonist or an inhibitor, depending on the F2R cleavage site (PubMed:10702240, PubMed:7744748). Cleavage of F2R at '41-Arg-|-Ser-42' results in receptor activation while cleavage at '55-Phe-|-Trp-56' results in inhibition of receptor activation (PubMed:7744748). Cleaves the synovial mucin-type protein PRG4/lubricin (PubMed:32144329). Cleaves and activates IL36G which promotes expression of chemokines CXCL1 and CXLC8 in keratinocytes (PubMed:30804664). Cleaves IL33 into mature forms which have greater activity than the unprocessed form (PubMed:22307629). Cleaves coagulation factor F8 to produce a partially activated form (PubMed:18217133). Also cleaves and activates coagulation factor F10 (PubMed:8920993). Cleaves leukocyte cell surface protein SPN/CD43 to releases its extracellular domain and trigger its intramembrane proteolysis by gamma-secretase, releasing the CD43 cytoplasmic tail chain (CD43-ct) which translocates to the nucleus (PubMed:18586676). Cleaves CCL5/RANTES to produce RANTES(4-68) lacking the N-terminal three amino acids which exhibits reduced chemotactic and antiviral activities (PubMed:16963625). During apoptosis, cleaves SMARCA2/BRM to produce a 160 kDa cleavage product which localizes to the cytosol (PubMed:11259672). Cleaves myelin basic protein MBP in B cell lysosomes at '224-Phe-|-Lys-225' and '248-Phe-|-Ser-249', degrading the major immunogenic MBP epitope and preventing the activation of MBP-specific autoreactive T cells (PubMed:15100291). Cleaves annexin ANXA1 and antimicrobial peptide CAMP to produce peptides which act on neutrophil N-formyl peptide receptors to enhance the release of CXCL2 (PubMed:22879591). Acts as a ligand for the N-formyl peptide receptor FPR1, enhancing phagocyte chemotaxis (PubMed:15210802). Has antibacterial activity against the Gram-negative bacteria N.gonorrhoeae and P.aeruginosa (PubMed:1937776, PubMed:2116408). Likely to act against N.gonorrhoeae by interacting with N.gonorrhoeae penA/PBP2 (PubMed:2126324). Exhibits potent antimicrobial activity against the Gram-positive bacterium L.monocytogenes (PubMed:2117044). Has antibacterial activity against the Gram-positive bacterium S.aureus and degrades S.aureus biofilms, allowing polymorphonuclear leukocytes to penetrate the biofilm and phagocytose bacteria (PubMed:2117044, PubMed:32995850). Has antibacterial activity against M.tuberculosis (PubMed:15385470). Mediates CASP4 activation induced by the Td92 surface protein of the periodontal pathogen T.denticola, causing production and secretion of IL1A and leading to pyroptosis of gingival fibroblasts (PubMed:29077095)
Specific Function
caspase binding
Pfam Domain Function
Signal Regions
1-18
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0016284|Cathepsin G (CTSG)
ATGCAGCCACTCCTGCTTCTGCTGGCCTTTCTCCTACCCACTGGGGCTGAGGCAGGGGAG
ATCATCGGAGGCCGGGAGAGCAGGCCCCACTCCCGCCCCTACATGGCGTATCTTCAGATC
CAGAGTCCAGCAGGTCAGAGCAGATGTGGAGGGTTCCTGGTGCGAGAAGACTTTGTGCTG
ACAGCAGCTCATTGCTGGGGAAGCAATATAAATGTCACCCTGGGCGCCCACAATATCCAG
AGACGGGAAAACACCCAGCAACACATCACTGCGCGCAGAGCCATCCGCCACCCTCAATAT
AATCAGCGGACCATCCAGAATGACATCATGTTATTGCAGCTGAGCAGAAGAGTCAGACGG
AATCGAAACGTGAACCCAGTGGCTCTGCCTAGAGCCCAGGAGGGACTGAGACCCGGGACG
CTGTGCACTGTGGCCGGCTGGGGCAGGGTCAGCATGAGGAGGGGAACAGATACACTCCGA
GAGGTGCAGCTGAGAGTGCAGAGGGATAGGCAGTGCCTCCGCATCTTCGGTTCCTACGAC
CCCCGAAGGCAGATTTGTGTGGGGGACCGGCGGGAACGGAAGGCTGCCTTCAAGGGGGAT
TCCGGAGGCCCCCTGCTGTGTAACAATGTGGCCCACGGCATCGTCTCCTATGGAAAGTCG
TCAGGGGTTCCTCCAGAAGTCTTCACCAGGGTCTCAAGTTTCCTGCCCTGGATAAGGACA
ACAATGAGAAGCTTCAAACTGCTGGATCAGATGGAGACCCCCCTGTGA
Chromosome Location
14
Locus
14q12
External Identifiers
ResourceLink
UniProtKB IDP08311
UniProtKB Entry NameCATG_HUMAN
GenBank Protein ID181182
GenBank Gene IDM16117
GeneCard IDCTSG
GenAtlas IDCTSG
HGNC IDHGNC:2532
PDB ID(s)1AU8, 1CGH, 1KYN, 1T32, 6VTM, 8D4S, 8D4V, 8D7I, 8D7K, 8G24, 8G25, 8G26
KEGG IDhsa:1511
IUPHAR/Guide To Pharmacology ID2348
NCBI Gene ID1511
General References
  1. Salvesen G, Farley D, Shuman J, Przybyla A, Reilly C, Travis J: Molecular cloning of human cathepsin G: structural similarity to mast cell and cytotoxic T lymphocyte proteinases. Biochemistry. 1987 Apr 21;26(8):2289-93. [Article]
  2. Hohn PA, Popescu NC, Hanson RD, Salvesen G, Ley TJ: Genomic organization and chromosomal localization of the human cathepsin G gene. J Biol Chem. 1989 Aug 15;264(23):13412-9. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Avril LE, Di Martino-Ferrer M, Pignede G, Seman M, Gauthier F: Identification of the U-937 membrane-associated proteinase interacting with the V3 loop of HIV-1 gp120 as cathepsin G. FEBS Lett. 1994 May 23;345(1):81-6. [Article]
  5. Heck LW, Rostand KS, Hunter FA, Bhown A: Isolation, characterization, and amino-terminal amino acid sequence analysis of human neutrophil cathepsin G from normal donors. Anal Biochem. 1986 Oct;158(1):217-27. [Article]
  6. Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF: Antibiotic proteins of human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5610-4. [Article]
  7. Maison CM, Villiers CL, Colomb MG: Proteolysis of C3 on U937 cell plasma membranes. Purification of cathepsin G. J Immunol. 1991 Aug 1;147(3):921-6. [Article]
  8. Gaskin G, Kendal H, Coulthart A, Turner N, Pusey CD: Use of proteinase 3 purified by reverse phase HPLC to detect autoantibodies in systemic vasculitis. J Immunol Methods. 1995 Mar 13;180(1):25-33. [Article]
  9. Wasiluk KR, Skubitz KM, Gray BH: Comparison of granule proteins from human polymorphonuclear leukocytes which are bactericidal toward Pseudomonas aeruginosa. Infect Immun. 1991 Nov;59(11):4193-200. [Article]
  10. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  11. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  12. Hof P, Mayr I, Huber R, Korzus E, Potempa J, Travis J, Powers JC, Bode W: The 1.8 A crystal structure of human cathepsin G in complex with Suc-Val-Pro-PheP-(OPh)2: a Janus-faced proteinase with two opposite specificities. EMBO J. 1996 Oct 15;15(20):5481-91. [Article]
  13. Ludecke B, Poller W, Olek K, Bartholome K: Sequence variant of the human cathepsin G gene. Hum Genet. 1993 Mar;91(1):83-4. [Article]

Associated Data

Drug Relations
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