PROC_CANLF
ID PROC_CANLF Reviewed; 456 AA.
AC Q28278; Q9TTR0;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 157.
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 Flags: Precursor;
GN Name=PROC;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9922393; DOI=10.1007/s003359900958;
RA Leeb T., Kopp T., Deppe A., Breen M., Matis U., Brunnberg L., Brenig B.;
RT "Molecular characterization and chromosomal assignment of the canine
RT protein C gene.";
RL Mamm. Genome 10:134-139(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 273-429.
RX PubMed=8043441; DOI=10.1111/j.1365-2141.1994.tb04791.x;
RA Murakawa M., Okamura T., Kamura T., Kuroiwa M., Harada M., Niho Y.;
RT "A comparative study of partial primary structures of the catalytic region
RT of mammalian protein C.";
RL Br. J. Haematol. 86:590-600(1994).
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 (By similarity). {ECO:0000250}.
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}.
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; AJ001979; CAA05126.1; -; Genomic_DNA.
DR EMBL; D43751; BAA07808.1; -; Genomic_DNA.
DR RefSeq; NP_001013871.1; NM_001013849.1.
DR RefSeq; XP_013976844.1; XM_014121369.1.
DR AlphaFoldDB; Q28278; -.
DR SMR; Q28278; -.
DR STRING; 9615.ENSCAFP00000064602; -.
DR MEROPS; S01.218; -.
DR Ensembl; ENSCAFT00030009089; ENSCAFP00030007975; ENSCAFG00030004934.
DR Ensembl; ENSCAFT00040037166; ENSCAFP00040032380; ENSCAFG00040020095.
DR Ensembl; ENSCAFT00845039524; ENSCAFP00845030975; ENSCAFG00845022381.
DR GeneID; 476104; -.
DR KEGG; cfa:476104; -.
DR CTD; 5624; -.
DR VEuPathDB; HostDB:ENSCAFG00845022381; -.
DR eggNOG; ENOG502QQ3W; Eukaryota.
DR GeneTree; ENSGT00940000154505; -.
DR HOGENOM; CLU_006842_19_5_1; -.
DR InParanoid; Q28278; -.
DR OrthoDB; 1314811at2759; -.
DR Reactome; R-CFA-140875; Common Pathway of Fibrin Clot Formation.
DR Reactome; R-CFA-159740; Gamma-carboxylation of protein precursors.
DR Reactome; R-CFA-159763; Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
DR Reactome; R-CFA-159782; Removal of aminoterminal propeptides from gamma-carboxylated proteins.
DR Reactome; R-CFA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-CFA-8957275; Post-translational protein phosphorylation.
DR Proteomes; UP000002254; Chromosome 19.
DR Bgee; ENSCAFG00000004493; Expressed in liver and 21 other tissues.
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; IEA:Ensembl.
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; IPR009030; Growth_fac_rcpt_cys_sf.
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; 2.
DR SMART; SM00069; GLA; 1.
DR SMART; SM00020; Tryp_SPc; 1.
DR SUPFAM; SSF50494; SSF50494; 1.
DR SUPFAM; SSF57184; SSF57184; 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..20
FT /evidence="ECO:0000255"
FT PROPEP 21..42
FT /evidence="ECO:0000250"
FT /id="PRO_0000028103"
FT CHAIN 43..456
FT /note="Vitamin K-dependent protein C"
FT /id="PRO_0000028104"
FT CHAIN 43..197
FT /note="Vitamin K-dependent protein C light chain"
FT /id="PRO_0000028105"
FT CHAIN 200..456
FT /note="Vitamin K-dependent protein C heavy chain"
FT /id="PRO_0000028106"
FT DOMAIN 47..88
FT /note="Gla"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00463"
FT DOMAIN 97..132
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 136..176
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 /evidence="ECO:0000250"
FT ACT_SITE 298
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT ACT_SITE 397
FT /note="Charge relay system"
FT /evidence="ECO:0000250"
FT MOD_RES 48
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 49
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 56
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 58
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 62
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 68
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 71
FT /note="4-carboxyglutamate"
FT /evidence="ECO:0000250|UniProtKB:P00745,
FT ECO:0000255|PROSITE-ProRule:PRU00463"
FT MOD_RES 113
FT /note="(3R)-3-hydroxyaspartate"
FT /evidence="ECO:0000250"
FT CARBOHYD 139
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 350
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 59..64
FT /evidence="ECO:0000250"
FT DISULFID 92..111
FT /evidence="ECO:0000250"
FT DISULFID 101..106
FT /evidence="ECO:0000250"
FT DISULFID 105..120
FT /evidence="ECO:0000250"
FT DISULFID 122..131
FT /evidence="ECO:0000250"
FT DISULFID 140..151
FT /evidence="ECO:0000250"
FT DISULFID 147..160
FT /evidence="ECO:0000250"
FT DISULFID 162..175
FT /evidence="ECO:0000250"
FT DISULFID 183..318
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 237..253
FT /evidence="ECO:0000250"
FT DISULFID 368..382
FT /evidence="ECO:0000250"
FT DISULFID 393..421
FT /evidence="ECO:0000250"
SQ SEQUENCE 456 AA; 50814 MW; 7AD3A8C1C34E59FF CRC64;
MWQLASLSLL LTICGTCSTA APPGSVFSSS ESAHQVLRIR KRANSFLEEI RAGSLERECM
EEICDFEEAK EIFQNVDDTL AYWSKYVDGD QCAALPPEHA CDSPCCGHGS CIDGIGAFHC
DCGRGWEGRF CQHEVSYINC SLDNGGCSHY CLEEEGGRHC SCAPGYRLGD DHLQCQPAVK
FPCGRPGKQM EKKRKHLKRD TNQTDQIDPR LVNGKVTRRG ESPWQVVLLD SKKKLACGAV
LIHTSWVLTA AHCMEDSKKL IVRLGEYDLR RWEKGEMDVD IKEVLIHPNY SKSTTDNDIA
LLHLAQPAIF SQTIVPICLP DSGLAERELT QVGQETVVTG WGYRSETKRN RTFVLNFINI
PVAPHNECIQ AMYNMISENM LCAGILGDSR DACEGDSGGP MVTSFRGTWF LVGLVSWGEG
CGRLHNYGIY TKVSRYLDWI HSHIRGEEAS LENQVP
