PROC_MOUSE
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 03-AUG-2022, entry version 202.
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. Exerts a protective effect
CC on the endothelial cell barrier function.
CC {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.
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: The vitamin K-dependent, enzymatic carboxylation of some Glu
CC residues allows the modified protein to bind calcium.
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}.
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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; 9.
DR STRING; 10090.ENSMUSP00000132226; -.
DR MEROPS; S01.218; -.
DR GlyGen; P33587; 3 sites.
DR iPTMnet; P33587; -.
DR PhosphoSitePlus; P33587; -.
DR jPOST; P33587; -.
DR MaxQB; P33587; -.
DR PaxDb; P33587; -.
DR PeptideAtlas; P33587; -.
DR PRIDE; P33587; -.
DR ProteomicsDB; 291744; -.
DR DNASU; 19123; -.
DR Ensembl; ENSMUST00000171765; ENSMUSP00000132226; ENSMUSG00000024386.
DR Ensembl; ENSMUST00000234651; ENSMUSP00000157269; ENSMUSG00000024386.
DR GeneID; 19123; -.
DR KEGG; mmu:19123; -.
DR UCSC; uc008eiz.1; mouse.
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; VAPHNEC; -.
DR OrthoDB; 1314811at2759; -.
DR PhylomeDB; P33587; -.
DR TreeFam; TF327329; -.
DR BRENDA; 3.4.21.69; 3474.
DR Reactome; R-MMU-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-MMU-140875; Common Pathway of Fibrin Clot Formation.
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 BioGRID-ORCS; 19123; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Proc; mouse.
DR PRO; PR:P33587; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P33587; protein.
DR Bgee; ENSMUSG00000024386; Expressed in left lobe of liver and 61 other tissues.
DR ExpressionAtlas; P33587; baseline and differential.
DR Genevisible; P33587; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:1905370; C:serine-type endopeptidase complex; ISO:MGI.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0070012; F:oligopeptidase activity; ISO:MGI.
DR GO; GO:0008233; F:peptidase activity; IDA:MGI.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
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:MGI.
DR GO; GO:0006508; P:proteolysis; ISO:MGI.
DR GO; GO:0044537; P:regulation of circulating fibrinogen levels; IMP:MGI.
DR CDD; cd00190; Tryp_SPc; 1.
DR Gene3D; 2.40.10.10; -; 2.
DR Gene3D; 4.10.740.10; -; 1.
DR InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR InterPro; IPR000742; EGF-like_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; 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; PF00008; EGF; 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; SM00181; EGF; 2.
DR SMART; SM00179; EGF_CA; 2.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57630; SSF57630; 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
