PROC_RAT
ID PROC_RAT Reviewed; 461 AA.
AC P31394;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 173.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=1627650; DOI=10.1016/0167-4781(92)90035-x;
RA Okafuji T., Maekawa K., Nawa K., Marumoto Y.;
RT "The cDNA cloning and mRNA expression of rat protein C.";
RL Biochim. Biophys. Acta 1131:329-332(1992).
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; X64336; CAA45617.1; -; mRNA.
DR PIR; S18994; S18994.
DR RefSeq; NP_036935.1; NM_012803.1.
DR AlphaFoldDB; P31394; -.
DR SMR; P31394; -.
DR STRING; 10116.ENSRNOP00000019596; -.
DR MEROPS; S01.218; -.
DR GlyGen; P31394; 3 sites.
DR PhosphoSitePlus; P31394; -.
DR PaxDb; P31394; -.
DR PRIDE; P31394; -.
DR GeneID; 25268; -.
DR KEGG; rno:25268; -.
DR UCSC; RGD:3411; rat.
DR CTD; 5624; -.
DR RGD; 3411; Proc.
DR eggNOG; ENOG502QQ3W; Eukaryota.
DR InParanoid; P31394; -.
DR PhylomeDB; P31394; -.
DR Reactome; R-RNO-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-RNO-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-RNO-159740; Gamma-carboxylation of protein precursors.
DR Reactome; R-RNO-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
DR Reactome; R-RNO-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR Reactome; R-RNO-202733; Cell surface interactions at the vascular wall.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:P31394; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:1905370; C:serine-type endopeptidase complex; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
DR GO; GO:0070012; F:oligopeptidase activity; IDA:RGD.
DR GO; GO:0008233; F:peptidase activity; ISO:RGD.
DR GO; GO:0043621; F:protein self-association; IDA:RGD.
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; IEP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030195; P:negative regulation of blood coagulation; IDA:RGD.
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; IDA:RGD.
DR GO; GO:0006508; P:proteolysis; ISO:RGD.
DR GO; GO:0044537; P:regulation of circulating fibrinogen levels; ISO:RGD.
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; 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; PS00134; TRYPSIN_HIS; 1.
DR PROSITE; PS00135; TRYPSIN_SER; 1.
PE 2: Evidence at transcript 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_0000028127"
FT CHAIN 42..461
FT /note="Vitamin K-dependent protein C"
FT /id="PRO_0000028128"
FT CHAIN 42..196
FT /note="Vitamin K-dependent protein C light chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028129"
FT CHAIN 199..461
FT /note="Vitamin K-dependent protein C heavy chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028130"
FT PEPTIDE 199..212
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028131"
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..450
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 254
FT /note="Charge relay system"
FT ACT_SITE 300
FT /note="Charge relay system"
FT ACT_SITE 402
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 215
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 291
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 355
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..320
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 239..255
FT /evidence="ECO:0000250"
FT DISULFID 373..387
FT /evidence="ECO:0000250"
FT DISULFID 398..426
FT /evidence="ECO:0000250"
SQ SEQUENCE 461 AA; 51912 MW; 8A4CF93664EDACD5 CRC64;
MWQFRIFLLF ASTWGISGVS AHPDPVFSSS EGAHQVLRVR RANSFLEEVR AGSLERECME
EICDFEEAQE IFQNVEDTLA FWIKYFDGDQ CSTPPLDHQC DSPCCGHGTC IDGLGGFSCS
CDKGWEGRFC QQEMGFQDCR VKNGGCYHYC LEETRGRRCR CAPGYELADD HMHCRPTVNF
PCGKLWKRTD KKRKNFKRDI DPEDEELELG PRIVNGTLTK QGDSPWQAIL LDSKKKLACG
GVLIHTSWVL TAAHCLESSK KLTVRLGEYD LRRRDPWELD LDIKEVLVHP NYTRSNSDND
IALLRLSQPA TLSKTIVPIC LPNSGLAQEL SQAGQETVVT GWGYQSDKVK DGRRNRTFIL
TFIRIPLAAR NDCMQVMNNV VSENMLCAGI IGDTRDACDG DSGGPMVVFF RGTWFLVGLV
SWGEGCGHLN NYGVYTKVGS YLKWIHSYIG ERDVSLKSPK L
