ID CATG_RAT Reviewed; 250 AA. AC P17977; G3V9Q7; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 29-SEP-2021, sequence version 2. DT 24-JAN-2024, entry version 124. DE RecName: Full=Cathepsin G; DE EC=3.4.21.20 {ECO:0000250|UniProtKB:P08311}; DE Flags: Precursor; GN Name=Ctsg; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] {ECO:0000312|Proteomes:UP000002494} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway {ECO:0000312|Proteomes:UP000002494}; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] {ECO:0000312|EMBL:EDM14312.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP PROTEIN SEQUENCE OF 21-46. RC STRAIN=Sprague-Dawley, and Wistar; RX PubMed=2222858; DOI=10.1515/bchm3.1990.371.2.595; RA Bjoerk P., Ohlsson K.; RT "Purification and N-terminal amino-acid sequence analysis of rat RT polymorphonuclear leukocyte cathepsin G."; RL Biol. Chem. Hoppe-Seyler 371:595-601(1990). 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 (By similarity). 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 '88-Phe-|- CC Lys-89' and '112-Phe-|-Ser-113', degrading the major immunogenic MBP CC epitope and preventing the activation of MBP-specific autoreactive T CC cells. Cleaves annexin ANXA1 and antimicrobial peptide CAMP to produce CC peptides which act on neutrophil N-formyl peptide receptors to enhance CC the release of CXCL2. Acts as a ligand for the N-formyl peptide CC receptor FPR1, enhancing phagocyte chemotaxis. Has antibacterial CC activity against the Gram-negative bacteria N.gonorrhoeae and CC P.aeruginosa. Likely to act against N.gonorrhoeae by interacting with CC N.gonorrhoeae penA/PBP2. Exhibits potent antimicrobial activity against CC the Gram-positive bacterium L.monocytogenes. Has antibacterial activity CC against the Gram-positive bacterium S.aureus and degrades S.aureus CC biofilms, allowing polymorphonuclear leukocytes to penetrate the CC biofilm and phagocytose bacteria. Has antibacterial activity against CC M.tuberculosis (By similarity). {ECO:0000250|UniProtKB:P08311, CC ECO:0000250|UniProtKB:P28293}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Specificity similar to chymotrypsin C.; EC=3.4.21.20; CC Evidence={ECO:0000250|UniProtKB:P08311}; 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 -!- 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; AABR07017957; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH474049; EDM14312.1; -; Genomic_DNA. DR PIR; S10608; S10608. DR RefSeq; NP_001099511.1; NM_001106041.1. DR AlphaFoldDB; P17977; -. DR SMR; P17977; -. DR STRING; 10116.ENSRNOP00000056429; -. DR MEROPS; S01.133; -. DR GlyCosmos; P17977; 1 site, No reported glycans. DR GlyGen; P17977; 1 site. DR PhosphoSitePlus; P17977; -. DR PaxDb; 10116-ENSRNOP00000056429; -. DR GeneID; 290257; -. DR KEGG; rno:290257; -. DR UCSC; RGD:1307681; rat. DR AGR; RGD:1307681; -. DR CTD; 1511; -. DR RGD; 1307681; Ctsg. DR VEuPathDB; HostDB:ENSRNOG00000020647; -. DR eggNOG; KOG3627; Eukaryota. DR HOGENOM; CLU_006842_1_0_1; -. DR InParanoid; P17977; -. DR OrthoDB; 2540265at2759; -. DR TreeFam; TF333630; -. DR PRO; PR:P17977; -. DR Proteomes; UP000002494; Chromosome 15. DR Proteomes; UP000234681; Chromosome 15. DR Bgee; ENSRNOG00000020647; Expressed in thymus and 3 other cell types or tissues. DR GO; GO:0010494; C:cytoplasmic stress granule; ISO:RGD. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB. 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:RGD. DR GO; GO:0030141; C:secretory granule; ISO:RGD. DR GO; GO:0089720; F:caspase binding; ISS:UniProtKB. DR GO; GO:0008201; F:heparin binding; ISO:RGD. DR GO; GO:0008233; F:peptidase activity; ISO:RGD. 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:RGD. DR GO; GO:0098786; P:biofilm matrix disassembly; ISS:UniProtKB. DR GO; GO:0050832; P:defense response to fungus; ISO:RGD. DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISS:UniProtKB. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISS:UniProtKB. 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; ISO:RGD. DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB. DR GO; GO:0050778; P:positive regulation of immune response; ISO:RGD. 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; ISO:RGD. 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. 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:0000250|UniProtKB:P08311" FT /id="PRO_0000453628" FT CHAIN 21..250 FT /note="Cathepsin G" FT /evidence="ECO:0000255" FT /id="PRO_0000453629" FT DOMAIN 21..244 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..112 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 109 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 202 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 143..208 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT DISULFID 173..187 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" SQ SEQUENCE 250 AA; 27804 MW; CCA0F0389C5BBF75 CRC64; MQPLLFLLIF VLFQEDEAGK IIGGREARPN SHPYMAFLLI QSPEGLSACG GFLVREDFVL TAGHCFGSSI NVTLGAHNIR RQEGTQQHIT VLRAIRHPDY NPPPVIQNDI MLLQLRSRAR RSRAVKPVAL PQATKRVQPG ALCTVAGWGL VSQRRGTNVL QEVKLRVQTD QTCANRFQFY NSQTQICVGN PRERKSAFKG DSGGPLVCNN VAQGIVSYGS SSGNPPAVFT RIQSFMPWIK RTMRRLSSRY //