PROC_BOVIN
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 03-AUG-2022, entry version 166.
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; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC 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; GLU-55;
RP GLU-58; GLU-59; GLU-62; GLU-64; GLU-65; GLU-68 AND GLU-74.
RX PubMed=6896876; DOI=10.1016/s0021-9258(18)33696-2;
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; DOI=10.1016/s0021-9258(18)33697-4;
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; DOI=10.1016/s0021-9258(20)81925-5;
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; DOI=10.1016/s0021-9258(20)81926-7;
RA Johnson A.E., Esmon N.L., Laue T.M., Esmon C.T.;
RT "Structural changes required for activation of protein C are induced by
RT 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 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.
CC {ECO:0000269|PubMed:6896876}.
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; K02435; AAA30685.1; -; mRNA.
DR PIR; A26250; KXBO.
DR STRING; 9913.ENSBTAP00000005163; -.
DR MEROPS; S01.218; -.
DR iPTMnet; P00745; -.
DR PaxDb; P00745; -.
DR PRIDE; P00745; -.
DR eggNOG; ENOG502QQ3W; Eukaryota.
DR InParanoid; P00745; -.
DR OrthoDB; 1314811at2759; -.
DR BRENDA; 3.4.21.69; 908.
DR SABIO-RK; 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 GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
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; 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 Direct protein sequencing; 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; Zymogen.
FT SIGNAL <1..15
FT /evidence="ECO:0000255"
FT PROPEP 16..39
FT /evidence="ECO:0000269|PubMed:6896876"
FT /id="PRO_0000028098"
FT CHAIN 40..456
FT /note="Vitamin K-dependent protein C"
FT /id="PRO_0000028099"
FT CHAIN 40..194
FT /note="Vitamin K-dependent protein C light chain"
FT /id="PRO_0000028100"
FT CHAIN 197..456
FT /note="Vitamin K-dependent protein C heavy chain"
FT /id="PRO_0000028101"
FT PEPTIDE 197..210
FT /note="Activation peptide"
FT /id="PRO_0000028102"
FT DOMAIN 40..85
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 94..129
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 133..173
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 211..445
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 252
FT /note="Charge relay system"
FT ACT_SITE 298
FT /note="Charge relay system"
FT ACT_SITE 397
FT /note="Charge relay system"
FT MOD_RES 45
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 46
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 53
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 55
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 58
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 59
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 62
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 64
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 65
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 68
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 74
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463,
FT ECO:0000269|PubMed:6896876"
FT MOD_RES 110
FT /note="(3R)-3-hydroxyaspartate"
FT /evidence="ECO:0000269|PubMed:6896876"
FT CARBOHYD 136
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6896876"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6896877"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:6896877"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine; atypical; partial"
FT /evidence="ECO:0000269|PubMed:6896877"
FT DISULFID 56..61
FT /evidence="ECO:0000250"
FT DISULFID 89..108
FT /evidence="ECO:0000250"
FT DISULFID 98..103
FT /evidence="ECO:0000250"
FT DISULFID 102..117
FT /evidence="ECO:0000250"
FT DISULFID 119..128
FT /evidence="ECO:0000250"
FT DISULFID 137..148
FT /evidence="ECO:0000250"
FT DISULFID 144..157
FT /evidence="ECO:0000250"
FT DISULFID 159..172
FT /evidence="ECO:0000250"
FT DISULFID 180..318
FT /note="Interchain (between light and heavy chains)"
FT DISULFID 237..253
FT DISULFID 368..382
FT DISULFID 393..421
FT VARIANT 82
FT /note="F -> K"
FT CONFLICT 455..456
FT /note="VP -> PV (in Ref. 4; AA sequence)"
FT /evidence="ECO:0000305"
FT NON_TER 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
