Protein: Cathepsin G (CG) (EC 3.4.21.20) [Cleaved into: Cathepsin G, C-terminal truncated form] (P08311)
Organism: Homo sapiens (Human)
Function: Serine protease with trypsin- and chymotrypsin-like specificity. Also displays antibacterial activity against Gram-negative and Gram-positive bacteria independent of its protease activity. Prefers Phe and Tyr residues in the P1 position of substrates but also cleaves efficiently after Trp and Leu. 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. Required for recruitment and activation of platelets which is mediated by the F2RL3/PAR4 platelet receptor. Binds reversibly to and stimulates B cells and CD4(+) and CD8(+) T cells. Also binds reversibly to natural killer (NK) cells and enhances NK cell cytotoxicity through its protease activity. Cleaves complement C3. Cleaves vimentin (By similarity). Cleaves thrombin receptor F2R/PAR1 and acts as either an agonist or an inhibitor, depending on the F2R cleavage site. 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. Cleaves the synovial mucin-type protein PRG4/lubricin. Cleaves and activates IL36G which promotes expression of chemokines CXCL1 and CXLC8 in keratinocytes. Cleaves IL33 into mature forms which have greater activity than the unprocessed form. Cleaves coagulation factor F8 to produce a partially activated form. Also cleaves and activates coagulation factor F10. 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. Cleaves CCL5/RANTES to produce RANTES(4-68) lacking the N-terminal three amino acids which exhibits reduced chemotactic and antiviral activities. During apoptosis, cleaves SMARCA2/BRM to produce a 160 kDa cleavage product which localizes to the cytosol. 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. Cleaves annexin ANXA1 and antimicrobial peptide CAMP to produce peptides which act on neutrophil N-formyl peptide receptors to enhance the release of CXCL2. Acts as a ligand for the N-formyl peptide receptor FPR1, enhancing phagocyte chemotaxis. Has antibacterial activity against the Gram-negative bacteria N.gonorrhoeae and P.aeruginosa. Likely to act against N.gonorrhoeae by interacting with N.gonorrhoeae penA/PBP2. Exhibits potent antimicrobial activity against the Gram-positive bacterium L.monocytogenes. 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. Has antibacterial activity against M.tuberculosis. 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.
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}.
InterPro domains:
- IPR001314: Peptidase S1A, chymotrypsin family (family) [50-206]
- IPR043504: Peptidase S1, PA clan, chymotrypsin-like fold (homologous_superfamily) [23-239]
- IPR018114: Serine proteases, trypsin family, histidine active site (active_site) [60-65]
- IPR033116: Serine proteases, trypsin family, serine active site (active_site) [195-206]
- IPR009003: Peptidase S1, PA clan (homologous_superfamily) [3-243]
- IPR001254: Serine proteases, trypsin domain (domain) [20-243]
Sequence:
MQPLLLLLAFLLPTGAEAGEIIGGRESRPHSRPYMAYLQIQSPAGQSRCGGFLVREDFVLTAAHCWGSNINVTLGAHNIQRRENTQQHITARRAIRHPQYNQRTIQNDIMLLQLSRRVRRNRNVNPVALPRAQEGLRPGTLCTVAGWGRVSMRRGTDTLREVQLRVQRDRQCLRIFGSYDPRRQICVGDRRERKAAFKGDSGGPLLCNNVAHGIVSYGKSSGVPPEVFTRVSSFLPWIRTTMRSFKLLDQMETPL
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0017171 (serine hydrolase activity), GO:0008233 (peptidase activity), GO:0008236 (serine-type peptidase activity), GO:0004175 (endopeptidase activity), GO:0004252 (serine-type endopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0002376 (immune system process), GO:0009987 (cellular process), GO:0009605 (response to external stimulus), GO:0042221 (response to chemical), GO:0048584 (positive regulation of response to stimulus), GO:0009607 (response to biotic stimulus), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0048583 (regulation of response to stimulus), GO:0002682 (regulation of immune system process), GO:0002252 (immune effector process), GO:0006950 (response to stress), GO:0002253 (activation of immune response), GO:0071704 (organic substance metabolic process), GO:0051707 (response to other organism), GO:0044238 (primary metabolic process), GO:0050776 (regulation of immune response), GO:1901564 (organonitrogen compound metabolic process), GO:0043207 (response to external biotic stimulus), GO:0019538 (protein metabolic process), GO:0006952 (defense response), GO:0050778 (positive regulation of immune response), GO:0043170 (macromolecule metabolic process), GO:0010033 (response to organic substance), GO:0009620 (response to fungus), GO:0098542 (defense response to other organism), GO:0034097 (response to cytokine), GO:0006508 (proteolysis), GO:0050832 (defense response to fungus), GO:0071310 (cellular response to organic substance), GO:0050832 (defense response to fungus), GO:0071346 (cellular response to type II interferon), GO:0071345 (cellular response to cytokine stimulus)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0071944 (cell periphery), GO:0001772 (immunological synapse), GO:0005773 (vacuole), GO:0005886 (plasma membrane), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0000323 (lytic vacuole), GO:0043231 (intracellular membrane-bounded organelle), GO:0005764 (lysosome), GO:0005634 (nucleus)