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Database: UniProt
Entry: P00745
LinkDB: P00745
Original site: P00745 
ID   PROC_BOVIN              Reviewed;         456 AA.
AC   P00745;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   16-JAN-2019, entry version 158.
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; Fragment;
GN   Name=PROC;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC   Pecora; Bovidae; Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=6091100; DOI=10.1073/pnas.81.18.5653;
RA   Long G.L., Balagaje R.M., McGillivray R.T.A.;
RT   "Cloning and sequencing of liver cDNA coding for bovine protein C.";
RL   Proc. Natl. Acad. Sci. U.S.A. 81:5653-5656(1984).
RN   [2]
RP   PROTEIN SEQUENCE OF 40-194, GLYCOSYLATION AT ASN-136, HYDROXYLATION AT
RP   ASP-110, AND GAMMA-CARBOXYGLUTAMATION AT GLU-45; GLU-46; GLU-53;
RP   GLU-55; GLU-58; GLU-59; GLU-62; GLU-64; GLU-65; GLU-68 AND GLU-74.
RX   PubMed=6896876;
RA   Fernlund P., Stenflo J.;
RT   "Amino acid sequence of the light chain of bovine protein C.";
RL   J. Biol. Chem. 257:12170-12179(1982).
RN   [3]
RP   SEQUENCE REVISION TO 110.
RX   PubMed=6572939; DOI=10.1073/pnas.80.7.1802;
RA   Drakenberg T., Fernlund P., Roepstorff P., Stenflo J.;
RT   "Beta-hydroxyaspartic acid in vitamin K-dependent protein C.";
RL   Proc. Natl. Acad. Sci. U.S.A. 80:1802-1806(1983).
RN   [4]
RP   PROTEIN SEQUENCE OF 197-456, AND GLYCOSYLATION AT ASN-289; ASN-350 AND
RP   ASN-366.
RX   PubMed=6896877;
RA   Stenflo J., Fernlund P.;
RT   "Amino acid sequence of the heavy chain of bovine protein C.";
RL   J. Biol. Chem. 257:12180-12190(1982).
RN   [5]
RP   PROTEOLYTIC PROCESSING, AND CALCIUM-BINDING.
RX   PubMed=6304092;
RA   Esmon N.L., Debault L.E., Esmon C.T.;
RT   "Proteolytic formation and properties of gamma-carboxyglutamic acid-
RT   domainless protein C.";
RL   J. Biol. Chem. 258:5548-5553(1983).
RN   [6]
RP   PROTEOLYTIC PROCESSING, AND CALCIUM-BINDING DATA.
RX   PubMed=6406503;
RA   Johnson A.E., Esmon N.L., Laue T.M., Esmon C.T.;
RT   "Structural changes required for activation of protein C are induced
RT   by Ca2+ binding to a high affinity site that does not contain gamma-
RT   carboxyglutamic acid.";
RL   J. Biol. Chem. 258:5554-5560(1983).
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:0000269|PubMed:6896876}.
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; K02435; AAA30685.1; -; mRNA.
DR   PIR; A26250; KXBO.
DR   UniGene; Bt.49146; -.
DR   ProteinModelPortal; P00745; -.
DR   STRING; 9913.ENSBTAP00000005163; -.
DR   MEROPS; S01.218; -.
DR   iPTMnet; P00745; -.
DR   PaxDb; P00745; -.
DR   PRIDE; P00745; -.
DR   eggNOG; ENOG410IJRM; Eukaryota.
DR   eggNOG; COG5640; LUCA.
DR   HOGENOM; HOG000251821; -.
DR   HOVERGEN; HBG013304; -.
DR   InParanoid; P00745; -.
DR   OrthoDB; 1314811at2759; -.
DR   SABIO-RK; P00745; -.
DR   PMAP-CutDB; P00745; -.
DR   Proteomes; UP000009136; Unplaced.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0007596; P:blood coagulation; IEA:UniProtKB-KW.
DR   GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR   GO; GO:0030195; P:negative regulation of blood coagulation; IBA:GO_Central.
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   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; 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; 1.
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; PS00135; TRYPSIN_SER; 1.
PE   1: Evidence at protein level;
KW   Blood coagulation; Calcium; Cleavage on pair of basic residues;
KW   Complete proteome; Direct protein sequencing; Disulfide bond;
KW   EGF-like domain; Endoplasmic reticulum; Gamma-carboxyglutamic acid;
KW   Glycoprotein; Golgi apparatus; Hemostasis; Hydrolase; Hydroxylation;
KW   Protease; Reference proteome; Repeat; Secreted; Serine protease;
KW   Signal; Zymogen.
FT   SIGNAL       <1     15       {ECO:0000255}.
FT   PROPEP       16     39       {ECO:0000269|PubMed:6896876}.
FT                                /FTId=PRO_0000028098.
FT   CHAIN        40    456       Vitamin K-dependent protein C.
FT                                /FTId=PRO_0000028099.
FT   CHAIN        40    194       Vitamin K-dependent protein C light
FT                                chain.
FT                                /FTId=PRO_0000028100.
FT   CHAIN       197    456       Vitamin K-dependent protein C heavy
FT                                chain.
FT                                /FTId=PRO_0000028101.
FT   PEPTIDE     197    210       Activation peptide.
FT                                /FTId=PRO_0000028102.
FT   DOMAIN       40     85       Gla. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463}.
FT   DOMAIN       94    129       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      133    173       EGF-like 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      211    445       Peptidase S1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00274}.
FT   ACT_SITE    252    252       Charge relay system.
FT   ACT_SITE    298    298       Charge relay system.
FT   ACT_SITE    397    397       Charge relay system.
FT   MOD_RES      45     45       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      46     46       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      53     53       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      55     55       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      58     58       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      59     59       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      62     62       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      64     64       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      65     65       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      68     68       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES      74     74       4-carboxyglutamate. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00463,
FT                                ECO:0000269|PubMed:6896876}.
FT   MOD_RES     110    110       (3R)-3-hydroxyaspartate.
FT                                {ECO:0000269|PubMed:6896876}.
FT   CARBOHYD    136    136       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:6896876}.
FT   CARBOHYD    289    289       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:6896877}.
FT   CARBOHYD    350    350       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000269|PubMed:6896877}.
FT   CARBOHYD    366    366       N-linked (GlcNAc...) asparagine;
FT                                atypical; partial.
FT                                {ECO:0000269|PubMed:6896877}.
FT   DISULFID     56     61       {ECO:0000250}.
FT   DISULFID     89    108       {ECO:0000250}.
FT   DISULFID     98    103       {ECO:0000250}.
FT   DISULFID    102    117       {ECO:0000250}.
FT   DISULFID    119    128       {ECO:0000250}.
FT   DISULFID    137    148       {ECO:0000250}.
FT   DISULFID    144    157       {ECO:0000250}.
FT   DISULFID    159    172       {ECO:0000250}.
FT   DISULFID    180    318       Interchain (between light and heavy
FT                                chains).
FT   DISULFID    237    253
FT   DISULFID    368    382
FT   DISULFID    393    421
FT   VARIANT      82     82       F -> K.
FT   CONFLICT    455    456       VP -> PV (in Ref. 4; AA sequence).
FT                                {ECO:0000305}.
FT   NON_TER       1      1
SQ   SEQUENCE   456 AA;  51409 MW;  CAAF6833F894C209 CRC64;
     XTSLLLFVTI WGISSTPAPP DSVFSSSQRA HQVLRIRKRA NSFLEELRPG NVERECSEEV
     CEFEEAREIF QNTEDTMAFW SFYSDGDQCE DRPSGSPCDL PCCGRGKCID GLGGFRCDCA
     EGWEGRFCLH EVRFSNCSAE NGGCAHYCME EEGRRHCSCA PGYRLEDDHQ LCVSKVTFPC
     GRLGKRMEKK RKTLKRDTNQ VDQKDQLDPR IVDGQEAGWG ESPWQAVLLD SKKKLVCGAV
     LIHVSWVLTV AHCLDSRKKL IVRLGEYDMR RWESWEVDLD IKEVIIHPNY TKSTSDNDIA
     LLRLAKPATL SQTIVPICLP DSGLSERKLT QVGQETVVTG WGYRDETKRN RTFVLSFIKV
     PVVPYNACVH AMENKISENM LCAGILGDPR DACEGDSGGP MVTFFRGTWF LVGLVSWGEG
     CGRLYNYGVY TKVSRYLDWI YGHIKAQEAP LESQVP
//
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