PROC_PIG
ID PROC_PIG Reviewed; 459 AA.
AC Q9GLP2;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 135.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RX PubMed=11229814; DOI=10.1007/pl00000775;
RA Grimm D.R., Colter M.B., Braunschweig M., Alexander L.J., Neame P.J.,
RA Kim H.K.W.;
RT "Porcine factor V: cDNA cloning, gene mapping, three-dimensional protein
RT modeling of membrane binding sites and comparative anatomy of domains.";
RL Cell. Mol. Life Sci. 58:148-159(2001).
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; AF191307; AAG28380.1; -; mRNA.
DR RefSeq; NP_999083.1; NM_213918.1.
DR AlphaFoldDB; Q9GLP2; -.
DR SMR; Q9GLP2; -.
DR STRING; 9823.ENSSSCP00000026729; -.
DR MEROPS; S01.218; -.
DR PaxDb; Q9GLP2; -.
DR PeptideAtlas; Q9GLP2; -.
DR GeneID; 396954; -.
DR KEGG; ssc:396954; -.
DR CTD; 5624; -.
DR eggNOG; ENOG502QQ3W; Eukaryota.
DR InParanoid; Q9GLP2; -.
DR OrthoDB; 1314811at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
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: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; 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 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:0000250"
FT PROPEP 19..41
FT /evidence="ECO:0000250"
FT /id="PRO_0000028117"
FT CHAIN 42..459
FT /note="Vitamin K-dependent protein C"
FT /id="PRO_0000028118"
FT CHAIN 42..196
FT /note="Vitamin K-dependent protein C light chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028119"
FT CHAIN 199..459
FT /note="Vitamin K-dependent protein C heavy chain"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028120"
FT PEPTIDE 199..213
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000028121"
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 214..448
FT /note="Peptidase S1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274"
FT ACT_SITE 255
FT /note="Charge relay system"
FT ACT_SITE 301
FT /note="Charge relay system"
FT ACT_SITE 400
FT /note="Charge relay system"
FT SITE 213..214
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 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 292
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
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..321
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 240..256
FT /evidence="ECO:0000250"
FT DISULFID 371..385
FT /evidence="ECO:0000250"
FT DISULFID 396..424
FT /evidence="ECO:0000250"
SQ SEQUENCE 459 AA; 51867 MW; 8541AAC14CC16D09 CRC64;
MWQLASLLLL LIIWAVSSTP VPPDSVFSSS QRAHQMLRSK RANSFLEELR PSSLERECKE
ETCDFEEARE IFQNTENTMA FWSKYHDGDQ CAVSPPEHLC DSPCCGRGTC IDGLGGFRCD
CAQGWEGRFC LHEVRFSNCS TENGGCAHYC LEEEGGRRCA CAPGYRLGDD HLQCEPKVRS
PCGRLGNRME KKRKNLKRDT DQVDKKEDQI DPRLVNGKQS PWGESPWQVI LLDSKKKLAC
GAVLIHVSWV LTAAHCLDDY KKLTVRLGEY DLRRREKWEV DLDIKEFLVH PNYTRSTSDN
DIALLRLAEP ATFSQTIVPI CLPDSGLSER ELTRVGQETV VTGWGYRSEA KTNRSFILNF
IKVPVAPHNE CVQAMHNKIS ENMLCAGILG DSRDACEGDS GGPMVASFRG TWFLVGLVSW
GEGCGRLHNY GVYTKVSRYL DWIHGHIRME EAFHKNQVP
