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 04-NOV-2026, entry version 178. 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 (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. 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}. 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; K02435; AAA30685.1; -; mRNA. DR PIR; A26250; KXBO. DR FunCoup; P00745; 123. DR STRING; 9913.ENSBTAP00000065381; -. DR MEROPS; S01.218; -. DR GlyCosmos; P00745; 4 sites, No reported glycans. DR GlyGen; P00745; 5 sites. DR iPTMnet; P00745; -. DR PaxDb; 9913-ENSBTAP00000065381; -. DR eggNOG; ENOG502QQ3W; Eukaryota. DR InParanoid; P00745; -. DR OMA; AARNDCM; -. DR OrthoDB; 9028152at2759; -. 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:0005576; C:extracellular region; 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:InterPro. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0030195; P:negative regulation of blood coagulation; IEA:UniProtKB-ARBA. 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; IBA:GO_Central. 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; 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; 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; 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; 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 //