ID:PROC_HUMAN DESCRIPTION: RecName: Full=Vitamin K-dependent protein C; EC=3.4.21.69; AltName: Full=Anticoagulant protein C; AltName: Full=Autoprothrombin IIA; AltName: Full=Blood coagulation factor XIV; Contains: RecName: Full=Vitamin K-dependent protein C light chain; Contains: RecName: Full=Vitamin K-dependent protein C heavy chain; Contains: RecName: Full=Activation peptide; Flags: Precursor; FUNCTION: Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids. CATALYTIC ACTIVITY: Degradation of blood coagulation factors Va and VIIIa. SUBUNIT: Synthesized as a single chain precursor, which is cleaved into a light chain and a heavy chain held together by a disulfide bond. The enzyme is then activated by thrombin, which cleaves a tetradecapeptide from the amino end of the heavy chain; this reaction, which occurs at the surface of endothelial cells, is strongly promoted by thrombomodulin. INTERACTION: P51511:MMP15; NbExp=2; IntAct=EBI-1383018, EBI-1383043; TISSUE SPECIFICITY: Plasma; synthesized in the liver. PTM: The vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind calcium. PTM: N- and O-glycosylated. Partial (70%) N-glycosylation of Asn- 371 with an atypical N-X-C site produces a higher molecular weight form referred to as alpha. The lower molecular weight form, not N- glycosylated at Asn-371, is beta. O-glycosylated with core 1 or possibly core 8 glycans. PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains. PTM: May be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide. DISEASE: Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. However, many adults with heterozygous disease may be asymptomatic. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency. DISEASE: Defects in PROC are the cause of thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:612304]. A hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare. MISCELLANEOUS: Calcium also binds, with stronger affinity to another site, beyond the GLA domain. This GLA-independent binding site is necessary for the recognition of the thrombin- thrombomodulin complex. SIMILARITY: Belongs to the peptidase S1 family. SIMILARITY: Contains 2 EGF-like domains. SIMILARITY: Contains 1 Gla (gamma-carboxy-glutamate) domain. SIMILARITY: Contains 1 peptidase S1 domain. SEQUENCE CAUTION: Sequence=S76088; Type=Erroneous termination; Positions=151; Note=Translated as Cys; WEB RESOURCE: Name=Wikipedia; Note=Protein C entry; URL="http://en.wikipedia.org/wiki/Protein_C"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PROC"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/proc/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P04070
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0001889 liver development GO:0006508 proteolysis GO:0006888 ER to Golgi vesicle-mediated transport GO:0007596 blood coagulation GO:0007599 hemostasis GO:0030195 negative regulation of blood coagulation GO:0043066 negative regulation of apoptotic process GO:0043687 post-translational protein modification GO:0044267 cellular protein metabolic process GO:0044537 regulation of circulating fibrinogen levels GO:0050728 negative regulation of inflammatory response GO:0050819 negative regulation of coagulation GO:1903142 positive regulation of establishment of endothelial barrier
AK298449 - Homo sapiens cDNA FLJ51034 complete cds, highly similar to Vitamin K-dependent protein C precursor (EC 3.4.21.69). AK303773 - Homo sapiens cDNA FLJ51179 complete cds, highly similar to Vitamin K-dependent protein C precursor (EC 3.4.21.69). AK298280 - Homo sapiens cDNA FLJ51023 complete cds, highly similar to Vitamin K-dependent protein C precursor (EC 3.4.21.69). AK298454 - Homo sapiens cDNA FLJ51925 complete cds, highly similar to Vitamin K-dependent protein C precursor (EC 3.4.21.69). X02750 - Human liver mRNA for protein C. JD542122 - Sequence 523146 from Patent EP1572962. E01189 - cDNA encoding human protein C. BC034377 - Homo sapiens protein C (inactivator of coagulation factors Va and VIIIa), mRNA (cDNA clone MGC:34565 IMAGE:5188604), complete cds. JD318560 - Sequence 299584 from Patent EP1572962. DQ890791 - Synthetic construct clone IMAGE:100003421; FLH165973.01X; RZPDo839B0386D protein C (inactivator of coagulation factors Va and VIIIa) (PROC) gene, encodes complete protein. DQ893947 - Synthetic construct Homo sapiens clone IMAGE:100008407; FLH165969.01L; RZPDo839B0385D protein C (inactivator of coagulation factors Va and VIIIa) (PROC) gene, encodes complete protein. KJ897384 - Synthetic construct Homo sapiens clone ccsbBroadEn_06778 PROC gene, encodes complete protein. KR710712 - Synthetic construct Homo sapiens clone CCSBHm_00015810 PROC (PROC) mRNA, encodes complete protein. KR710713 - Synthetic construct Homo sapiens clone CCSBHm_00015834 PROC (PROC) mRNA, encodes complete protein. KR710714 - Synthetic construct Homo sapiens clone CCSBHm_00015897 PROC (PROC) mRNA, encodes complete protein. KR710715 - Synthetic construct Homo sapiens clone CCSBHm_00015959 PROC (PROC) mRNA, encodes complete protein. CU689868 - Synthetic construct Homo sapiens gateway clone IMAGE:100017316 5' read PROC mRNA. AB528552 - Synthetic construct DNA, clone: pF1KB5863, Homo sapiens PROC gene for protein C, without stop codon, in Flexi system. E00961 - cDNA encoding human protein C. K02059 - Human protein C, mRNA. S72338 - type I protein C {exon 5} [human, venous thromboembolism patient, peripheral blood, mRNA Partial Mutant, 136 nt]. S50739 - protein C [human, mRNA Partial Mutant, 315 nt]. JD429237 - Sequence 410261 from Patent EP1572962. JD056357 - Sequence 37381 from Patent EP1572962. JD291184 - Sequence 272208 from Patent EP1572962. JD233472 - Sequence 214496 from Patent EP1572962.
Protein P04070 (Reactome details) participates in the following event(s):
R-HSA-141040 Activated thrombin:thrombomodulin cleaves PROCR:Protein C to PROCR:Activated protein C R-HSA-159771 Furin cleaves pro-protein C to protein C R-HSA-5591052 PROCR binds Protein C R-HSA-5591086 SERPINA5 binds activated protein C R-HSA-5604929 Activated protein C binds Protein S R-HSA-5606996 Soluble PROCR binds activated protein C R-HSA-5603467 Activated protein C is released from PROCR R-HSA-159795 GGCX gamma-carboxylates 3D-PROC(33-197) (pro-protein C light chain) R-HSA-5607058 Activated protein C:PROCR binds F2R R-HSA-8952289 FAM20C phosphorylates FAM20C substrates R-HSA-141026 Activated protein C cleaves factor Va to factor Vi intermediate form R-HSA-5591040 Activated protein C cleaves Factor Va intermediate form for Factor Va R-HSA-5607002 Activated protein C cleaves factor VIIIa R-HSA-140875 Common Pathway of Fibrin Clot Formation R-HSA-202733 Cell surface interactions at the vascular wall R-HSA-159782 Removal of aminoterminal propeptides from gamma-carboxylated proteins R-HSA-140877 Formation of Fibrin Clot (Clotting Cascade) R-HSA-109582 Hemostasis R-HSA-159763 Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus R-HSA-159740 Gamma-carboxylation of protein precursors R-HSA-159854 Gamma-carboxylation, transport, and amino-terminal cleavage of proteins R-HSA-163841 Gamma carboxylation, hypusine formation and arylsulfatase activation R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-8957275 Post-translational protein phosphorylation R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins
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Common Gene Haplotype Alleles 
