| IED ID | IndEnz0002018941 |
| Enzyme Type ID | protease018941 |
| Protein Name |
Cathepsin G CG EC 3.4.21.20 Cleaved into: Cathepsin G, C-terminal truncated form |
| Gene Name | CTSG |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MQPLLLLLAFLLPTGAEAGEIIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVLTAAHCWGSNINVTLGAHNIQRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRRNRNVNPVALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRQCLRIFGSYDPRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVSSFLPWIRTTMRSFKLLDQMETPL |
| Enzyme Length | 255 |
| Uniprot Accession Number | P08311 |
| Absorption | |
| Active Site | ACT_SITE 64; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU00274; ACT_SITE 108; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU00274; ACT_SITE 201; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU00274 |
| Activity Regulation | ACTIVITY REGULATION: Inhibited by soybean trypsin inhibitor, benzamidine, the synthetic peptide R13K, Z-Gly-Leu-Phe-CH2Cl, phenylmethylsulfonyl fluoride, 3,4-dichloroisocoumarin, DFP, SBTI and alpha-1-antitrypsin. Inhibited by LPS from P.aeruginosa but not by LPS from S.minnesota. Not inhibited by elastinal, CMK, TLCK, ETDA or leupeptin. {ECO:0000269|PubMed:1861080, ECO:0000269|PubMed:1937776, ECO:0000269|PubMed:3390156, ECO:0000269|PubMed:8194606}.; ACTIVITY REGULATION: (Microbial infection) Inhibited reversibly by S.aureus EapH1. {ECO:0000269|PubMed:32303641}.; ACTIVITY REGULATION: (Microbial infection) Activity is induced by the Td92 surface protein of the periodontal pathogen T.denticola. {ECO:0000269|PubMed:29077095}. |
| Binding Site | BINDING 57; /note="2-[3-({methyl[1-(2-naphthoyl)piperidin-4-Yl]amino}carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid; inhibitor"; /evidence="ECO:0000269|PubMed:15741158, ECO:0007744|PDB:1T32"; BINDING 57; /note="Bis-naphthyl beta-ketophosphonic acid; inhibitor"; /evidence="ECO:0000269|PubMed:11942800, ECO:0007744|PDB:1KYN"; BINDING 192; /note="2-[3-({methyl[1-(2-naphthoyl)piperidin-4-Yl]amino}carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid; inhibitor"; /evidence="ECO:0000269|PubMed:15741158, ECO:0007744|PDB:1T32"; BINDING 193; /note="2-[3-({methyl[1-(2-naphthoyl)piperidin-4-Yl]amino}carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid; inhibitor"; /evidence="ECO:0000269|PubMed:15741158, ECO:0007744|PDB:1T32"; BINDING 193; /note="Bis-naphthyl beta-ketophosphonic acid; inhibitor"; /evidence="ECO:0000269|PubMed:11942800, ECO:0007744|PDB:1KYN"; BINDING 195; /note="2-[3-({methyl[1-(2-naphthoyl)piperidin-4-Yl]amino}carbonyl)-2-naphthyl]-1-(1-naphthyl)-2-oxoethylphosphonic acid; inhibitor; via carbonyl oxygen"; /evidence="ECO:0000269|PubMed:15741158, ECO:0007744|PDB:1T32" |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Specificity similar to chymotrypsin C.; EC=3.4.21.20; Evidence={ECO:0000269|PubMed:15100291, ECO:0000269|PubMed:29077095, ECO:0000269|PubMed:29652924, ECO:0000269|PubMed:7744748, ECO:0000269|PubMed:7842483, ECO:0000269|PubMed:8194606}; |
| DNA Binding | |
| EC Number | 3.4.21.20 |
| Enzyme Function | FUNCTION: Serine protease with trypsin- and chymotrypsin-like specificity (PubMed:8194606, PubMed:29652924). 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:3390156, PubMed:10702240). 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:2116408, PubMed:1937776). 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). {ECO:0000250|UniProtKB:P28293, ECO:0000269|PubMed:10702240, ECO:0000269|PubMed:11259672, ECO:0000269|PubMed:15100291, ECO:0000269|PubMed:15210802, ECO:0000269|PubMed:15385470, ECO:0000269|PubMed:16963625, ECO:0000269|PubMed:18217133, ECO:0000269|PubMed:18586676, ECO:0000269|PubMed:1861080, ECO:0000269|PubMed:1937776, ECO:0000269|PubMed:2116408, ECO:0000269|PubMed:2117044, ECO:0000269|PubMed:2126324, ECO:0000269|PubMed:22307629, ECO:0000269|PubMed:22879591, ECO:0000269|PubMed:29077095, ECO:0000269|PubMed:29652924, ECO:0000269|PubMed:30804664, ECO:0000269|PubMed:32144329, ECO:0000269|PubMed:32995850, ECO:0000269|PubMed:3390156, ECO:0000269|PubMed:7744748, ECO:0000269|PubMed:7842483, ECO:0000269|PubMed:8194606, ECO:0000269|PubMed:8920993, ECO:0000269|PubMed:9000539, ECO:0000269|PubMed:9536127}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (13); Binding site (6); Chain (2); Disulfide bond (3); Domain (1); Glycosylation (2); Helix (4); Mutagenesis (1); Natural variant (1); Propeptide (2); Region (2); Signal peptide (1); Turn (2) |
| Keywords | 3D-structure;Antibiotic;Antimicrobial;Cell membrane;Chemotaxis;Cytoplasm;Direct protein sequencing;Disulfide bond;Glycoprotein;Hydrolase;Lysosome;Membrane;Nucleus;Protease;Reference proteome;Secreted;Serine protease;Signal;Zymogen |
| Interact With | A8MQ03; Q15323; Q7Z3S9; Q9NRD5 |
| Induction | INDUCTION: Induced by the Td92 surface protein of the periodontal pathogen T.denticola (PubMed:29077095). Down-regulated in monocytes following M.tuberculosis infection and exposure to bacterial lipopolysaccharide which coincides with increased M.tuberculosis replication and intracellular survival (PubMed:15385470). {ECO:0000269|PubMed:15385470, ECO:0000269|PubMed:29077095}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15100291, ECO:0000269|PubMed:29077095, ECO:0000269|PubMed:8194606}; Peripheral membrane protein {ECO:0000305}. Cytoplasmic granule {ECO:0000269|PubMed:7499346}. Secreted {ECO:0000269|PubMed:29077095, ECO:0000269|PubMed:32144329, ECO:0000269|PubMed:3390156}. Cytoplasm, cytosol {ECO:0000269|PubMed:29077095}. Lysosome {ECO:0000269|PubMed:15100291, ECO:0000269|PubMed:29077095}. Nucleus {ECO:0000269|PubMed:11259672}. Note=Secreted by activated neutrophils (PubMed:3390156). Detected in synovial fluid (PubMed:32144329). Localizes to lysosomes in B cells where it is not endogenously synthesized but is internalized from the cell membrane (PubMed:15100291). Localizes to the nucleus during apoptosis (PubMed:11259672). {ECO:0000269|PubMed:11259672, ECO:0000269|PubMed:15100291, ECO:0000269|PubMed:32144329, ECO:0000269|PubMed:3390156}. |
| Modified Residue | |
| Post Translational Modification | PTM: Two C-terminal truncation variants have been identified, one which ends at Arg-243 and one which ends at Ser-244. {ECO:0000269|PubMed:26274980}. |
| Signal Peptide | SIGNAL 1..18; /evidence=ECO:0000255 |
| Structure 3D | X-ray crystallography (5) |
| Cross Reference PDB | 1AU8; 1CGH; 1KYN; 1T32; 6VTM; |
| Mapped Pubmed ID | 10512690; 11241273; 11502364; 11520793; 11557685; 11920276; 11928814; 11986950; 12524437; 12784398; 14688365; 14737102; 15131125; 15140022; 15967795; 16034099; 16317101; 16444434; 16799473; 16977463; 17174955; 17418861; 17653609; 18021746; 18835135; 19036358; 19250736; 19528350; 19578796; 19620298; 19910052; 19913121; 20056178; 20331476; 20589323; 20628086; 20800603; 20889553; 21193413; 21488974; 21543057; 2176865; 21850236; 22588119; 22641217; 22810585; 22915586; 23147993; 23454598; 23466190; 23902751; 23940756; 24532668; 24877096; 25248056; 25416956; 25461571; 2557753; 26270939; 2681419; 26837514; 26986619; 27666013; 28053237; 28544544; 28797985; 29703634; 29976772; 30017196; 30791695; 31647805; 32194574; 32813288; 33132312; 33245176; 4216367; 6263256; 6807977; 7075587; 8044845; 8692836; 9261109; 9570564; 9718313; |
| Motif | |
| Gene Encoded By | |
| Mass | 28,837 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=1.15 mM for Z-Lys-SBzl {ECO:0000269|PubMed:8194606}; KM=0.26 mM for Suc-Ala-Ala-Pro-Phe-SBzl {ECO:0000269|PubMed:8194606}; |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda | 3.4.21.20; |