ID CATG_MOUSE Reviewed; 261 AA. AC P28293; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 2. DT 24-JAN-2024, entry version 176. DE RecName: Full=Cathepsin G; DE EC=3.4.21.20 {ECO:0000250|UniProtKB:P08311}; DE AltName: Full=Vimentin-specific protease {ECO:0000303|PubMed:1577012}; DE Short=VSP {ECO:0000303|PubMed:1577012}; DE Flags: Precursor; GN Name=Ctsg; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY. RC STRAIN=Swiss Webster; TISSUE=Embryonic fibroblast; RX PubMed=8453108; RA Heusel J.W., Scarpati E.M., Jenkins N.A., Gilbert D.J., Copeland N.G., RA Shapiro S.D., Ley T.J.; RT "Molecular cloning, chromosomal location, and tissue-specific expression of RT the murine cathepsin G gene."; RL Blood 81:1614-1623(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Kulmburg P., Baumruker T., Werner F.; RL Submitted (DEC-1992) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=C57L/J; RX PubMed=9211743; DOI=10.1007/s002510050260; RA Aveskogh M., Lutzelschwab C., Huang M.R., Hellman L.; RT "Characterization of cDNA clones encoding mouse proteinase 3 RT (myeloblastine) and cathepsin G."; RL Immunogenetics 46:181-191(1997). RN [4] RP PROTEIN SEQUENCE OF 21-60, FUNCTION, AND ACTIVITY REGULATION. RX PubMed=1577012; DOI=10.1111/j.1432-1033.1992.tb16861.x; RA Nakamura N., Tsuru A., Hirayoshi K., Nagata K.; RT "Purification and characterization of a vimentin-specific protease in mouse RT myeloid leukemia cells. Regulation during differentiation and identity with RT cathepsin G."; RL Eur. J. Biochem. 205:947-954(1992). CC -!- FUNCTION: Serine protease with trypsin- and chymotrypsin-like CC specificity. Also displays antibacterial activity against Gram-negative CC and Gram-positive bacteria independent of its protease activity. CC Prefers Phe and Tyr residues in the P1 position of substrates but also CC cleaves efficiently after Trp and Leu. Shows a preference for CC negatively charged amino acids in the P2' position and for aliphatic CC amino acids both upstream and downstream of the cleavage site. Required CC for recruitment and activation of platelets which is mediated by the CC F2RL3/PAR4 platelet receptor. Binds reversibly to and stimulates B CC cells and CD4(+) and CD8(+) T cells. Also binds reversibly to natural CC killer (NK) cells and enhances NK cell cytotoxicity through its CC protease activity. Cleaves complement C3 (By similarity). Cleaves CC vimentin (PubMed:1577012). Cleaves thrombin receptor F2R/PAR1. Cleaves CC the synovial mucin-type protein PRG4/lubricin. Cleaves and activates CC IL36G which promotes expression of chemokines CXCL1 and CXLC8 in CC keratinocytes. Cleaves IL33 into mature forms which have greater CC activity than the unprocessed form. Cleaves coagulation factor F8 to CC produce a partially activated form. Also cleaves and activates CC coagulation factor F10. Cleaves leukocyte cell surface protein SPN/CD43 CC to releases its extracellular domain and trigger its intramembrane CC proteolysis by gamma-secretase, releasing the CD43 cytoplasmic tail CC chain (CD43-ct) which translocates to the nucleus. During apoptosis, CC cleaves SMARCA2/BRM to produce a 160 kDa cleavage product which CC localizes to the cytosol. Cleaves MBP in B cell lysosomes at '221- CC Phe-|-Lys-222', degrading the major immunogenic MBP epitope and CC preventing the activation of MBP-specific autoreactive T cells. Cleaves CC annexin ANXA1 and antimicrobial peptide CAMP to produce peptides which CC act on neutrophil N-formyl peptide receptors to enhance the release of CC CXCL2. Acts as a ligand for the N-formyl peptide receptor FPR1, CC enhancing phagocyte chemotaxis. Has antibacterial activity against the CC Gram-negative bacteria N.gonorrhoeae and P.aeruginosa. Likely to act CC against N.gonorrhoeae by interacting with N.gonorrhoeae penA/PBP2. CC Exhibits potent antimicrobial activity against the Gram-positive CC bacterium L.monocytogenes. Has antibacterial activity against the Gram- CC positive bacterium S.aureus and degrades S.aureus biofilms, allowing CC polymorphonuclear leukocytes to penetrate the biofilm and phagocytose CC bacteria. Has antibacterial activity against M.tuberculosis (By CC similarity). {ECO:0000250|UniProtKB:P08311, CC ECO:0000269|PubMed:1577012}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Specificity similar to chymotrypsin C.; EC=3.4.21.20; CC Evidence={ECO:0000250|UniProtKB:P08311}; CC -!- ACTIVITY REGULATION: Inhibited by chymostatin, phenylmethanesulfonyl CC fluoride and diisopropyl fluorophosphate. {ECO:0000269|PubMed:1577012}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P08311}; CC Peripheral membrane protein {ECO:0000305}. Cytoplasmic granule CC {ECO:0000250|UniProtKB:P08311}. Secreted CC {ECO:0000250|UniProtKB:P08311}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P08311}. Lysosome CC {ECO:0000250|UniProtKB:P08311}. Nucleus {ECO:0000250|UniProtKB:P08311}. CC Note=Secreted by activated neutrophils. Detected in synovial fluid. CC Localizes to lysosomes in B cells where it is not endogenously CC synthesized but is internalized from the cell membrane. Localizes to CC the nucleus during apoptosis. {ECO:0000250|UniProtKB:P08311}. CC -!- TISSUE SPECIFICITY: In adult, detected only in bone marrow where CC expression is restricted to a small population of early myeloid cells. CC {ECO:0000269|PubMed:8453108}. CC -!- SIMILARITY: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- CC ProRule:PRU00274}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M96801; AAA37376.1; -; Genomic_DNA. DR EMBL; X70057; CAA49661.1; -; Genomic_DNA. DR EMBL; X78544; CAA55290.1; -; mRNA. DR CCDS; CCDS27142.1; -. DR PIR; S40162; S40162. DR RefSeq; NP_031826.1; NM_007800.2. DR AlphaFoldDB; P28293; -. DR SMR; P28293; -. DR BioGRID; 198972; 7. DR STRING; 10090.ENSMUSP00000015583; -. DR BindingDB; P28293; -. DR ChEMBL; CHEMBL5622; -. DR MEROPS; S01.133; -. DR GlyCosmos; P28293; 1 site, No reported glycans. DR GlyGen; P28293; 2 sites, 1 O-linked glycan (1 site). DR PhosphoSitePlus; P28293; -. DR PaxDb; 10090-ENSMUSP00000015583; -. DR PeptideAtlas; P28293; -. DR ProteomicsDB; 281222; -. DR Antibodypedia; 3597; 457 antibodies from 35 providers. DR DNASU; 13035; -. DR Ensembl; ENSMUST00000015583.2; ENSMUSP00000015583.2; ENSMUSG00000040314.3. DR GeneID; 13035; -. DR KEGG; mmu:13035; -. DR UCSC; uc007ubn.1; mouse. DR AGR; MGI:88563; -. DR CTD; 1511; -. DR MGI; MGI:88563; Ctsg. DR VEuPathDB; HostDB:ENSMUSG00000040314; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT01030000234551; -. DR HOGENOM; CLU_006842_1_0_1; -. DR InParanoid; P28293; -. DR OMA; QLDQMEI; -. DR OrthoDB; 2540265at2759; -. DR PhylomeDB; P28293; -. DR TreeFam; TF333630; -. DR BRENDA; 3.4.21.20; 3474. DR Reactome; R-MMU-1474228; Degradation of the extracellular matrix. DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases. DR Reactome; R-MMU-2022377; Metabolism of Angiotensinogen to Angiotensins. DR Reactome; R-MMU-448706; Interleukin-1 processing. DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR Reactome; R-MMU-6803157; Antimicrobial peptides. DR BioGRID-ORCS; 13035; 1 hit in 78 CRISPR screens. DR PRO; PR:P28293; -. DR Proteomes; UP000000589; Chromosome 14. DR RNAct; P28293; Protein. DR Bgee; ENSMUSG00000040314; Expressed in femorotibial joint and 35 other cell types or tissues. DR ExpressionAtlas; P28293; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0010494; C:cytoplasmic stress granule; ISO:MGI. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central. DR GO; GO:0005764; C:lysosome; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISO:MGI. DR GO; GO:0030141; C:secretory granule; ISO:MGI. DR GO; GO:0089720; F:caspase binding; ISS:UniProtKB. DR GO; GO:0008201; F:heparin binding; ISO:MGI. DR GO; GO:0008233; F:peptidase activity; ISO:MGI. DR GO; GO:0048018; F:receptor ligand activity; ISS:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB. DR GO; GO:0008236; F:serine-type peptidase activity; ISO:MGI. DR GO; GO:0019731; P:antibacterial humoral response; ISO:MGI. DR GO; GO:0098786; P:biofilm matrix disassembly; ISS:UniProtKB. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISO:MGI. DR GO; GO:0050832; P:defense response to fungus; IMP:MGI. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI. DR GO; GO:0002548; P:monocyte chemotaxis; ISS:UniProtKB. DR GO; GO:0050868; P:negative regulation of T cell activation; ISS:UniProtKB. DR GO; GO:0042119; P:neutrophil activation; ISS:UniProtKB. DR GO; GO:0070946; P:neutrophil-mediated killing of gram-positive bacterium; IMP:MGI. DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB. DR GO; GO:0050778; P:positive regulation of immune response; IMP:MGI. DR GO; GO:1901731; P:positive regulation of platelet aggregation; ISS:UniProtKB. DR GO; GO:0016485; P:protein processing; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB. DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:MGI. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24271:SF13; CATHEPSIN G; 1. DR PANTHER; PTHR24271; KALLIKREIN-RELATED; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. DR Genevisible; P28293; MM. PE 1: Evidence at protein level; KW Antibiotic; Antimicrobial; Cell membrane; Chemotaxis; Cytoplasm; KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase; KW Lysosome; Membrane; Nucleus; Protease; Reference proteome; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT PROPEP 19..20 FT /note="Activation peptide" FT /evidence="ECO:0000269|PubMed:1577012" FT /id="PRO_0000027514" FT CHAIN 21..261 FT /note="Cathepsin G" FT /id="PRO_0000027515" FT DOMAIN 21..243 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT REGION 21..25 FT /note="Important for antimicrobial activity" FT /evidence="ECO:0000250|UniProtKB:P08311" FT REGION 97..111 FT /note="Important for antimicrobial activity" FT /evidence="ECO:0000250|UniProtKB:P08311" FT ACT_SITE 64 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 108 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 201 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT CARBOHYD 71 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 49..65 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 142..207 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 172..186 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT CONFLICT 51 FT /note="G -> S (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 56 FT /note="E -> G (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 60 FT /note="L -> P (in Ref. 4; AA sequence)" FT /evidence="ECO:0000305" SQ SEQUENCE 261 AA; 29096 MW; 5EFA1A6E10E1D7FC CRC64; MQPLLLLLTF ILLQGDEAGK IIGGREARPH SYPYMAFLLI QSPEGLSACG GFLVREDFVL TAAHCLGSSI NVTLGAHNIQ MRERTQQLIT VLRAIRHPDY NPQNIRNDIM LLQLRRRARR SGSVKPVALP QASKKLQPGD LCTVAGWGRV SQSRGTNVLQ EVQLRVQMDQ MCANRFQFYN SQTQICVGNP RERKSAFRGD SGGPLVCSNV AQGIVSYGSN NGNPPAVFTK IQSFMPWIKR TMRRFAPRYQ RPANSLSQAQ T //