CATG_MOUSE
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 03-AUG-2022, entry version 168.
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}.
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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; 6.
DR STRING; 10090.ENSMUSP00000015583; -.
DR BindingDB; P28293; -.
DR ChEMBL; CHEMBL5622; -.
DR MEROPS; S01.133; -.
DR GlyGen; P28293; 1 site.
DR PhosphoSitePlus; P28293; -.
DR PaxDb; P28293; -.
DR PeptideAtlas; P28293; -.
DR PRIDE; P28293; -.
DR ProteomicsDB; 281222; -.
DR Antibodypedia; 3597; 419 antibodies from 35 providers.
DR DNASU; 13035; -.
DR Ensembl; ENSMUST00000015583; ENSMUSP00000015583; ENSMUSG00000040314.
DR GeneID; 13035; -.
DR KEGG; mmu:13035; -.
DR UCSC; uc007ubn.1; mouse.
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; 1076876at2759; -.
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 73 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 tissues.
DR ExpressionAtlas; P28293; baseline and differential.
DR Genevisible; P28293; MM.
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:0006468; P:protein phosphorylation; ISO:MGI.
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; -; 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 Pfam; PF00089; Trypsin; 1.
DR PRINTS; PR00722; CHYMOTRYPSIN.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR PROSITE; PS50240; TRYPSIN_DOM; 1.
DR PROSITE; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
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
