ID PROC_MOUSE Reviewed; 460 AA. AC P33587; O35498; Q91WN8; Q99PC6; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2004, sequence version 2. DT 04-NOV-2026, entry version 219. DE RecName: Full=Vitamin K-dependent protein C; DE EC=3.4.21.69; DE AltName: Full=Anticoagulant protein C; DE AltName: Full=Autoprothrombin IIA; DE AltName: Full=Blood coagulation factor XIV; DE Contains: DE RecName: Full=Vitamin K-dependent protein C light chain; DE Contains: DE RecName: Full=Vitamin K-dependent protein C heavy chain; DE Contains: DE RecName: Full=Activation peptide; DE Flags: Precursor; GN Name=Proc; 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 [MRNA]. RC STRAIN=BALB/cJ; TISSUE=Liver; RX PubMed=1618739; DOI=10.1093/oxfordjournals.jbchem.a123785; RA Tada N., Sato M., Tsujimura A., Iwase R., Hashimoto-Gotoh T.; RT "Isolation and characterization of a mouse protein C cDNA."; RL J. Biochem. 111:491-495(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=129/SvJ; RX PubMed=9493582; RA Jalbert L.R., Rosen E.D., Lissens A., Carmeliet P., Collen D., RA Castellino F.J.; RT "Nucleotide structure and characterization of the murine gene encoding RT anticoagulant protein C."; RL Thromb. Haemost. 79:310-316(1998). RN [3] RP NUCLEOTIDE SEQUENCE. RC STRAIN=C57BL/6J; RA Korf I.; RT "Complete sequence of UC72A01."; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 274-433. RC STRAIN=BALB/cJ; RX PubMed=8043441; DOI=10.1111/j.1365-2141.1994.tb04791.x; RA Murakawa M., Okamura T., Kamura T., Kuroiwa M., Harada M., Niho Y.; RT "A comparative study of partial primary structures of the catalytic region RT of mammalian protein C."; RL Br. J. Haematol. 86:590-600(1994). RN [6] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-214. RC STRAIN=C57BL/6J; TISSUE=Plasma; RX PubMed=16944957; DOI=10.1021/pr060186m; RA Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.; RT "Proteome-wide characterization of N-glycosylation events by diagonal RT chromatography."; RL J. Proteome Res. 5:2438-2447(2006). CC -!- FUNCTION: Protein C is a vitamin K-dependent serine protease that CC regulates blood coagulation by inactivating factors Va and VIIIa in the CC presence of calcium ions and phospholipids (By similarity). Exerts a CC protective effect on the endothelial cell barrier function (By CC similarity). {ECO:0000250|UniProtKB:P04070}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Degradation of blood coagulation factors Va and VIIIa.; CC EC=3.4.21.69; CC -!- SUBUNIT: Synthesized as a single chain precursor, which is cleaved into CC a light chain and a heavy chain held together by a disulfide bond. The CC enzyme is then activated by thrombin, which cleaves a tetradecapeptide CC from the amino end of the heavy chain; this reaction, which occurs at CC the surface of endothelial cells, is strongly promoted by CC thrombomodulin (By similarity). {ECO:0000250|UniProtKB:P04070}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P04070}. Golgi CC apparatus {ECO:0000250|UniProtKB:P04070}. Endoplasmic reticulum CC {ECO:0000250|UniProtKB:P04070}. CC -!- TISSUE SPECIFICITY: Plasma; synthesized in the liver. CC -!- PTM: Carboxylated by vitamin K-dependent GGCX to form gamma- CC carboxyglutamate; these residues are essential for the binding of CC calcium. {ECO:0000250|UniProtKB:P04070}. CC -!- PTM: N- and O-glycosylated (By similarity). CC {ECO:0000250|UniProtKB:P04070}. CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate CC and asparagine is (R) stereospecific within EGF domains. {ECO:0000250}. CC -!- MISCELLANEOUS: Calcium also binds, with stronger affinity to another CC site, beyond the GLA domain. This GLA-independent binding site is CC necessary for the recognition of the thrombin-thrombomodulin complex. 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; D10445; BAA01235.1; -; mRNA. DR EMBL; AF034569; AAC33795.1; -; Genomic_DNA. DR EMBL; AF318182; AAK07918.1; -; mRNA. DR EMBL; BC013896; AAH13896.1; -; mRNA. DR EMBL; D43755; BAA07812.1; -; Genomic_DNA. DR CCDS; CCDS29116.1; -. DR PIR; JX0210; JX0210. DR RefSeq; NP_001036232.1; NM_001042767.3. DR RefSeq; NP_001300867.1; NM_001313938.1. DR RefSeq; XP_011245159.1; XM_011246857.2. DR AlphaFoldDB; P33587; -. DR SMR; P33587; -. DR BioGRID; 202390; 10. DR FunCoup; P33587; 79. DR STRING; 10090.ENSMUSP00000157269; -. DR MEROPS; S01.218; -. DR GlyCosmos; P33587; 3 sites, 1 glycan. DR GlyGen; P33587; 3 sites, 1 N-linked glycan (1 site). DR iPTMnet; P33587; -. DR PhosphoSitePlus; P33587; -. DR jPOST; P33587; -. DR PaxDb; 10090-ENSMUSP00000157269; -. DR PeptideAtlas; P33587; -. DR ProteomicsDB; 291744; -. DR DNASU; 19123; -. DR Ensembl; ENSMUST00000171765.2; ENSMUSP00000132226.2; ENSMUSG00000024386.10. DR Ensembl; ENSMUST00000234651.2; ENSMUSP00000157269.2; ENSMUSG00000024386.10. DR GeneID; 19123; -. DR KEGG; mmu:19123; -. DR UCSC; uc008eiz.1; mouse. DR AGR; MGI:97771; -. DR CTD; 5624; -. DR MGI; MGI:97771; Proc. DR VEuPathDB; HostDB:ENSMUSG00000024386; -. DR eggNOG; ENOG502QQ3W; Eukaryota. DR GeneTree; ENSGT00940000154474; -. DR HOGENOM; CLU_006842_19_5_1; -. DR InParanoid; P33587; -. DR OMA; AARNDCM; -. DR OrthoDB; 9028152at2759; -. DR PhylomeDB; P33587; -. DR BRENDA; 3.4.21.69; 3474. DR Reactome; R-MMU-159740; Gamma-carboxylation of protein precursors. DR Reactome; R-MMU-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus. DR Reactome; R-MMU-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins. DR Reactome; R-MMU-202733; Cell surface interactions at the vascular wall. DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation. DR Reactome; R-MMU-9769733; Fibrin formation. DR Reactome; R-MMU-9769739; Regulation of clotting cascade. DR Reactome; R-MMU-9769743; Amplification and propagation of coagulation cascade. DR BioGRID-ORCS; 19123; 2 hits in 81 CRISPR screens. DR PRO; PR:P33587; -. DR Proteomes; UP000000589; Chromosome 18. DR RNAct; P33587; protein. DR Bgee; ENSMUSG00000024386; Expressed in left lobe of liver and 63 other cell types or tissues. DR ExpressionAtlas; P33587; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0005576; C:extracellular region; ISO:GO_Central. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:1905370; C:serine-type endopeptidase complex; ISO:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0042802; F:identical protein binding; ISO:GO_Central. DR GO; GO:0070012; F:oligopeptidase activity; ISO:GO_Central. DR GO; GO:0008233; F:peptidase activity; IDA:MGI. DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB. DR GO; GO:0007596; P:blood coagulation; IEA:InterPro. DR GO; GO:0001889; P:liver development; IMP:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:MGI. DR GO; GO:0050819; P:negative regulation of coagulation; ISS:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:1903142; P:positive regulation of establishment of endothelial barrier; ISS:UniProtKB. DR GO; GO:0030163; P:protein catabolic process; ISO:GO_Central. DR GO; GO:0006508; P:proteolysis; ISO:GO_Central. DR GO; GO:0044537; P:regulation of circulating fibrinogen levels; IMP:MGI. DR CDD; cd00054; EGF_CA; 1. DR CDD; cd00190; Tryp_SPc; 1. DR FunFam; 2.40.10.10:FF:000365; -; 1. DR FunFam; 2.10.25.10:FF:000549; Vitamin K-dependent protein C; 1. DR FunFam; 2.10.25.10:FF:000567; Vitamin K-dependent protein C; 1. DR FunFam; 2.40.10.10:FF:000256; Vitamin K-dependent protein C; 1. DR FunFam; 4.10.740.10:FF:000001; vitamin K-dependent protein S; 1. DR Gene3D; 4.10.740.10; Coagulation Factor IX; 1. DR Gene3D; 2.10.25.10; Laminin; 2. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom. DR InterPro; IPR000742; EGF. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR035972; GLA-like_dom_SF. DR InterPro; IPR000294; GLA_domain. DR InterPro; IPR012224; Pept_S1A_FX. DR InterPro; IPR050442; Peptidase_S1_coag_factors. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24278; COAGULATION FACTOR; 1. DR PANTHER; PTHR24278:SF0; VITAMIN K-DEPENDENT PROTEIN C; 1. DR Pfam; PF00008; EGF; 1. DR Pfam; PF14670; FXa_inhibition; 1. DR Pfam; PF00594; Gla; 1. DR Pfam; PF00089; Trypsin; 1. DR PIRSF; PIRSF001143; Factor_X; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR PRINTS; PR00001; GLABLOOD. DR SMART; SM00179; EGF_CA; 2. DR SMART; SM00069; GLA; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF57196; EGF/Laminin; 2. DR SUPFAM; SSF57630; GLA-domain; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS00010; ASX_HYDROXYL; 1. DR PROSITE; PS00022; EGF_1; 1. DR PROSITE; PS01186; EGF_2; 2. DR PROSITE; PS50026; EGF_3; 1. DR PROSITE; PS01187; EGF_CA; 1. DR PROSITE; PS00011; GLA_1; 1. DR PROSITE; PS50998; GLA_2; 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 Blood coagulation; Calcium; Cleavage on pair of basic residues; KW Disulfide bond; EGF-like domain; Endoplasmic reticulum; KW Gamma-carboxyglutamic acid; Glycoprotein; Golgi apparatus; Hemostasis; KW Hydrolase; Hydroxylation; Protease; Reference proteome; Repeat; Secreted; KW Serine protease; Signal; Zymogen. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT PROPEP 19..41 FT /evidence="ECO:0000250" FT /id="PRO_0000028112" FT CHAIN 42..460 FT /note="Vitamin K-dependent protein C" FT /id="PRO_0000028113" FT CHAIN 42..196 FT /note="Vitamin K-dependent protein C light chain" FT /evidence="ECO:0000250" FT /id="PRO_0000028114" FT CHAIN 199..460 FT /note="Vitamin K-dependent protein C heavy chain" FT /evidence="ECO:0000250" FT /id="PRO_0000028115" FT PEPTIDE 199..212 FT /note="Activation peptide" FT /evidence="ECO:0000250" FT /id="PRO_0000028116" FT DOMAIN 42..87 FT /note="Gla" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463" FT DOMAIN 96..131 FT /note="EGF-like 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 135..175 FT /note="EGF-like 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076" FT DOMAIN 213..449 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 253 FT /note="Charge relay system" FT ACT_SITE 299 FT /note="Charge relay system" FT ACT_SITE 401 FT /note="Charge relay system" FT SITE 212..213 FT /note="Cleavage; by thrombin" FT /evidence="ECO:0000250" FT MOD_RES 47 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 48 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 55 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 57 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 60 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 61 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 66 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 67 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 70 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 76 FT /note="4-carboxyglutamate" FT /evidence="ECO:0000250|UniProtKB:P00745, FT ECO:0000255|PROSITE-ProRule:PRU00463" FT MOD_RES 112 FT /note="(3R)-3-hydroxyaspartate" FT /evidence="ECO:0000250" FT CARBOHYD 214 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16944957" FT CARBOHYD 290 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 354 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 58..63 FT /evidence="ECO:0000250" FT DISULFID 91..110 FT /evidence="ECO:0000250" FT DISULFID 100..105 FT /evidence="ECO:0000250" FT DISULFID 104..119 FT /evidence="ECO:0000250" FT DISULFID 121..130 FT /evidence="ECO:0000250" FT DISULFID 139..150 FT /evidence="ECO:0000250" FT DISULFID 146..159 FT /evidence="ECO:0000250" FT DISULFID 161..174 FT /evidence="ECO:0000250" FT DISULFID 182..319 FT /note="Interchain (between light and heavy chains)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076, FT ECO:0000255|PROSITE-ProRule:PRU00274, ECO:0000255|PROSITE- FT ProRule:PRU00463" FT DISULFID 238..254 FT /evidence="ECO:0000250" FT DISULFID 372..386 FT /evidence="ECO:0000250" FT DISULFID 397..425 FT /evidence="ECO:0000250" FT VARIANT 327 FT /note="Q -> QQ (in strain: BALB/c)" FT VARIANT 392 FT /note="D -> N (in strain: BALB/c)" FT CONFLICT 65 FT /note="F -> L (in Ref. 3; AAK07918)" FT /evidence="ECO:0000305" SQ SEQUENCE 460 AA; 51818 MW; 0117F26E68FCC274 CRC64; MWQFRVFLLL MSTWGISSIP AHPDPVFSSS EHAHQVLRVR RANSFLEEMR PGSLERECME EICDFEEAQE IFQNVEDTLA FWIKYFDGDQ CSAPPLDHQC DSPCCGHGTC IDGIGSFSCS CDKGWEGKFC QQELRFQDCR VNNGGCLHYC LEESNGRRCA CAPGYELADD HMRCKSTVNF PCGKLGRWIE KKRKILKRDT DLEDELEPDP RIVNGTLTKQ GDSPWQAILL DSKKKLACGG VLIHTSWVLT AAHCVEGTKK LTVRLGEYDL RRRDHWELDL DIKEILVHPN YTRSSSDNDI ALLRLAQPAT LSKTIVPICL PNNGLAQELT QAGQETVVTG WGYQSDRIKD GRRNRTFILT FIRIPLVARN ECVEVMKNVV SENMLCAGII GDTRDACDGD SGGPMVVFFR GTWFLVGLVS WGEGCGHTNN YGIYTKVGSY LKWIHSYIGE KGVSLKSQKL //