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Database: UniProt
Entry: P33587
LinkDB: P33587
Original site: P33587 
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   10-APR-2019, entry version 186.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ; TISSUE=Liver;
RX   PubMed=1618739;
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
RT   project: 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
RT   region 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.,
RA   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
CC       in the presence of calcium ions and phospholipids. Exerts a
CC       protective effect 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
CC       into a light chain and a heavy chain held together by a disulfide
CC       bond. The enzyme is then activated by thrombin, which cleaves a
CC       tetradecapeptide from the amino end of the heavy chain; this
CC       reaction, which occurs at the surface of endothelial cells, is
CC       strongly promoted by thrombomodulin.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P04070}.
CC       Golgi apparatus {ECO:0000250|UniProtKB:P04070}. Endoplasmic
CC       reticulum {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
CC       aspartate and asparagine is (R) stereospecific within EGF domains.
CC       {ECO:0000250}.
CC   -!- MISCELLANEOUS: Calcium also binds, with stronger affinity to
CC       another site, beyond the GLA domain. This GLA-independent binding
CC       site is necessary for the recognition of the thrombin-
CC       thrombomodulin complex.
CC   -!- SIMILARITY: Belongs to the peptidase S1 family.
CC       {ECO:0000255|PROSITE-ProRule:PRU00274}.
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   UniGene; Mm.2786; -.
DR   UniGene; Mm.489734; -.
DR   ProteinModelPortal; P33587; -.
DR   STRING; 10090.ENSMUSP00000132226; -.
DR   MEROPS; S01.218; -.
DR   iPTMnet; P33587; -.
DR   PhosphoSitePlus; P33587; -.
DR   jPOST; P33587; -.
DR   MaxQB; P33587; -.
DR   PaxDb; P33587; -.
DR   PeptideAtlas; P33587; -.
DR   PRIDE; P33587; -.
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   eggNOG; ENOG410IJRM; Eukaryota.
DR   eggNOG; COG5640; LUCA.
DR   GeneTree; ENSGT00940000154474; -.
DR   HOGENOM; HOG000251821; -.
DR   HOVERGEN; HBG013304; -.
DR   InParanoid; P33587; -.
DR   KO; K01344; -.
DR   OMA; LDWIHSH; -.
DR   OrthoDB; 1314811at2759; -.
DR   PhylomeDB; P33587; -.
DR   TreeFam; TF327329; -.
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   ChiTaRS; Proc; mouse.
DR   PRO; PR:P33587; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   Bgee; ENSMUSG00000024386; Expressed in 85 organ(s), highest expression level in liver.
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: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; IMP:MGI.
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: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; 4.10.740.10; -; 1.
DR   InterPro; IPR017857; Coagulation_fac-like_Gla_dom.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR013032; EGF-like_CS.
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; 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   Complete proteome; Disulfide bond; EGF-like domain;
KW   Endoplasmic reticulum; Gamma-carboxyglutamic acid; Glycoprotein;
KW   Golgi apparatus; Hemostasis; Hydrolase; Hydroxylation; Protease;
KW   Reference proteome; Repeat; Secreted; Serine protease; Signal;
KW   Zymogen.
FT   SIGNAL        1     18       {ECO:0000255}.
FT   PROPEP       19     41       {ECO:0000250}.
FT                                /FTId=PRO_0000028112.
FT   CHAIN        42    460       Vitamin K-dependent protein C.
FT                                /FTId=PRO_0000028113.
FT   CHAIN        42    196       Vitamin K-dependent protein C light
FT                                chain. {ECO:0000250}.
FT                                /FTId=PRO_0000028114.
FT   CHAIN       199    460       Vitamin K-dependent protein C heavy
FT                                chain. {ECO:0000250}.
FT                                /FTId=PRO_0000028115.
FT   PEPTIDE     199    212       Activation peptide. {ECO:0000250}.
FT                                /FTId=PRO_0000028116.
FT   DOMAIN       42     87       Gla. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   DOMAIN       96    131       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      135    175       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      213    449       Peptidase S1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00274}.
FT   ACT_SITE    253    253       Charge relay system.
FT   ACT_SITE    299    299       Charge relay system.
FT   ACT_SITE    401    401       Charge relay system.
FT   SITE        212    213       Cleavage; by thrombin. {ECO:0000250}.
FT   MOD_RES      47     47       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      48     48       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      55     55       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      57     57       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      60     60       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      61     61       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      66     66       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      67     67       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      70     70       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES      76     76       4-carboxyglutamate.
FT                                {ECO:0000250|UniProtKB:P00745,
FT                                ECO:0000255|PROSITE-ProRule:PRU00463}.
FT   MOD_RES     112    112       (3R)-3-hydroxyaspartate. {ECO:0000250}.
FT   CARBOHYD    214    214       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:16944957}.
FT   CARBOHYD    290    290       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    354    354       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID     58     63       {ECO:0000250}.
FT   DISULFID     91    110       {ECO:0000250}.
FT   DISULFID    100    105       {ECO:0000250}.
FT   DISULFID    104    119       {ECO:0000250}.
FT   DISULFID    121    130       {ECO:0000250}.
FT   DISULFID    139    150       {ECO:0000250}.
FT   DISULFID    146    159       {ECO:0000250}.
FT   DISULFID    161    174       {ECO:0000250}.
FT   DISULFID    182    319       Interchain (between light and heavy
FT                                chains). {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076, ECO:0000255|PROSITE-
FT                                ProRule:PRU00274, ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   DISULFID    238    254       {ECO:0000250}.
FT   DISULFID    372    386       {ECO:0000250}.
FT   DISULFID    397    425       {ECO:0000250}.
FT   VARIANT     327    327       Q -> QQ (in strain: BALB/c).
FT   VARIANT     392    392       D -> N (in strain: BALB/c).
FT   CONFLICT     65     65       F -> L (in Ref. 3; AAK07918).
FT                                {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
//
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