PROC protein C (inactivator of coagulation factors Va and VIIIa) [Homo sapiens (human)] - Gene

Summary

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Official Symbol: PROCprovided by HGNC
Official Full Name: protein C (inactivator of coagulation factors Va and VIIIa)provided by HGNC
Primary source: HGNC:9451
See related: Ensembl:ENSG00000115718; HPRD:01466; MIM:612283; Vega:OTTHUMG00000131528
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PC; APC; PROC1; THPH3; THPH4
Summary: This gene encodes a vitamin K-dependent plasma glycoprotein. The encoded protein is cleaved to its activated form by the thrombin-thrombomodulin complex. This activated form contains a serine protease domain and functions in degradation of the activated forms of coagulation factors V and VIII. Mutations in this gene have been associated with thrombophilia due to protein C deficiency, neonatal purpura fulminans, and recurrent venous thrombosis.[provided by RefSeq, Dec 2009]

Genomic context

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Location :: 2q13-q14

Sequence :: Chromosome: 2; NC_000002.11 (128175996..128186822)

See PROC in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Complex genotypes of protein C or combined with protein S deficiency are primarily responsible for an increased risk of recurrent venous thromboembolism.
Title: Clinical and genetic features of protein C deficiency in 23 unrelated Chinese patients.
Protein C deficiency is the major inherited risk factor of VTE. The most common PROC mutation identified in this study was heterozygous c.565C > T missense mutation.
Title: [A survey of 20 inherited protein C deficiencies in the patients with venous thromboembolism].
Protein C allele frequency of the C2405T single nucleotide polymorphism was significantly different between the pulmonary thromboembolism patients and the control group.
Title: Protein C polymorphism and susceptibility to PTE in China.
effect of antithrombin (SERPINC1), protein C (PROC), thrombomodulin (THBD) and tissue factor pathway inhibitor (TFPI) single nucleotide polymorphisms (SNPs) on the risk of recurrent pregnancy loss
Title: Polymorphisms in antithrombin and in tissue factor pathway inhibitor genes are associated with recurrent pregnancy loss.
novel PROC c.574_576del variant is a possible genetic determinant of an increased risk of ischemic stroke and diminished anticoagulant activity of protein c
Title: Novel association of a PROC variant with ischemic stroke in a Chinese Han population.
PROC c.574_576del polymorphism identified as most common genetic risk factor for venous thrombosis in the Chinese population.
Title: PROC c.574_576del polymorphism: a common genetic risk factor for venous thrombosis in the Chinese population.
Differential transcription factor binding occurs for common SNPs in the 5' intronic regions of PROC which may contribute to PROC regulation and reported PROC SNP - phenotype associations
Title: A common polymorphism in the 5' region of the human protein c gene binds USF1.
analysis of deficiencies of antithrombin, protein C and protein S in a large patient cohort shows that genotyping for patients with AT deficiency is indicated for all subnormal activities, but not for PC activities >70% and for PS activities >55%
Title: Deficiencies of antithrombin, protein C and protein S - practical experience in genetic analysis of a large patient cohort.
Data indicate that protein C (PC) to activated protein C (APC) conversion is dependent upon Thrombomodulin (TM) concentration.
Title: Quantitative analysis of thrombomodulin-mediated conversion of protein C to APC: translation from in vitro to in vivo.
It discusses the potential of activated protein C as a novel target to reduce cancer progression, it points to several limitations of activated protein C administration in the setting of cancer cell metastasis.
Title: The protein C pathway in cancer metastasis.

Submit: New GeneRIF Correction See all (189)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Thrombophilia, hereditary, due to protein c deficiency, autosomal dominant

MIM: 176860

Genetic Testing Registry

Thrombophilia, hereditary, due to protein c deficiency, autosomal recessive

MIM: 612304

Genetic Testing Registry

NHGRI GWAS Catalog

A genome-wide association study of self-rated health.

Genome-wide association study identifies novel loci for plasma levels of protein C: the ARIC study.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P04070	P00450	CP	HPRD	PubMed
P04070	P00734	F2	HPRD	PubMed
P04070	P12259	F5	HPRD	PubMed
P04070	P00451	F8	HPRD	PubMed
P04070	P38435	GGCX	HPRD	PubMed
P04070	P02776	PF4	HPRD	PubMed
P04070	P04070	PROC	HPRD	PubMed
P04070	Q9UNN8	PROCR	HPRD	PubMed
P04070	P07225	PROS1	HPRD	PubMed
P04070	P05154	SERPINA5	HPRD	PubMed
P04070	P35237	SERPINB6	HPRD	PubMed
P04070	P07204	THBD	HPRD	PubMed
BioGRID:111608	BioGRID:107843	CSNK2B	BioGRID	PubMed	Two-hybrid
BioGRID:111608	BioGRID:111219	PF4	BioGRID	PubMed	Reconstituted Complex
BioGRID:111608	BioGRID:115797	PROCR	BioGRID	PubMed	Reconstituted Complex
BioGRID:111608	BioGRID:111135	SERPINA5	BioGRID	PubMed	Co-purification; Reconstituted Complex
BioGRID:111608	BioGRID:112938	TK1	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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Cell surface interactions at the vascular wall, organism-specific biosystem (from REACTOME)
Cell surface interactions at the vascular wall, organism-specific biosystemLeukocyte extravasation is a rigorously controlled process that guides white cell movement from the vascular lumen to sites of tissue inflammation. The powerful adhesive interactions that are require...
Common Pathway, organism-specific biosystem (from REACTOME)
Common Pathway, organism-specific biosystemThe common pathway consists of the cascade of activation events leading from the formation of activated factor X to the formation of active thrombin, the cleavage of fibrinogen by thrombin, and the f...
Complement and Coagulation Cascades, organism-specific biosystem (from WikiPathways)
Complement and Coagulation Cascades, organism-specific biosystemBlood coagulation is a series of coordinated and calcium-dependent proenzyme-to-serine protease conversions likely to be localized on the surfaces of activated cells in vivo. It culminates in the for...
Complement and coagulation cascades, organism-specific biosystem (from KEGG)
Complement and coagulation cascades, organism-specific biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Complement and coagulation cascades, conserved biosystem (from KEGG)
Complement and coagulation cascades, conserved biosystemThe complement system is a proteolytic cascade in blood plasma and a mediator of innate immunity, a nonspecific defense mechanism against pathogens. There are three pathways of complement activation:...
Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystem (from REACTOME)
Formation of Fibrin Clot (Clotting Cascade), organism-specific biosystemThe formation of a fibrin clot at the site of an injury to the wall of a normal blood vessel is an essential part of the process to stop blood loss after vascular injury. The reactions that lead to ...
Gamma-carboxylation of protein precursors, organism-specific biosystem (from REACTOME)
Gamma-carboxylation of protein precursors, organism-specific biosystemGamma-carboxylation of a cluster of glutamate residues near the amino termini of thrombin, factor VII, factor IX, factor X, protein C, protein S, protein Z, and Gas 6 is required for these proteins t...
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins, organism-specific biosystem (from REACTOME)
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins, organism-specific biosystemA number of proteins, including eight required for normal blood clot formation and its regulation (Prothrombin (factor II), factor VII, factor IX, factor X, protein C, protein S, protein Z, and Gas6)...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
PTM: gamma carboxylation, hypusine formation and arylsulfatase activation, organism-specific biosystem (from REACTOME)
PTM: gamma carboxylation, hypusine formation and arylsulfatase activation, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
Post-translational protein modification, organism-specific biosystem (from REACTOME)
Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
Removal of aminoterminal propeptides from gamma-carboxylated proteins, organism-specific biosystem (from REACTOME)
Removal of aminoterminal propeptides from gamma-carboxylated proteins, organism-specific biosystemFurin is an endopeptidase localized to the Golgi membrane that cleaves many proteins on the carboxyterminal side of the sequence motif Arg-[any residue]-(Lys or Arg)-Arg (Jones et al. 1995; Leduc et ...
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus, organism-specific biosystem (from REACTOME)
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus, organism-specific biosystemThe details of the vesicle-mediated transport of proteins from the endoplasmic reticulum to the Golgi apparatus will be annotated in a future release of Reactome.

General gene information

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Markers

GDB:181257 (e-PCR)
- UniSTS:155225

GDB:178362 (e-PCR)
- UniSTS:154988

GDB:186843 (e-PCR)
- UniSTS:155512

GDB:181584 (e-PCR)
- UniSTS:155295

GDB:176978 (e-PCR)
- UniSTS:154817

D2S2639 (e-PCR)
- UniSTS:60395

RH70647 (e-PCR)
- UniSTS:34047

Genotypes

See PROC SNP Geneview Report
See PROC SNP Genotype Report
See PROC SNP Variation Viewer Report

Homology

Homologs of the PROC gene: The PROC gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
serine-type endopeptidase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
blood coagulation	TAS Traceable Author Statement more info
cellular protein metabolic process	TAS Traceable Author Statement more info
leukocyte migration	TAS Traceable Author Statement more info
negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of blood coagulation	TAS Traceable Author Statement more info	PubMed
peptidyl-glutamic acid carboxylation	TAS Traceable Author Statement more info
post-translational protein modification	TAS Traceable Author Statement more info
proteolysis	NAS Non-traceable Author Statement more info	PubMed
proteolysis	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
Golgi lumen	TAS Traceable Author Statement more info
endoplasmic reticulum lumen	TAS Traceable Author Statement more info
extracellular region	NAS Non-traceable Author Statement more info	PubMed
extracellular region	TAS Traceable Author Statement more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: vitamin K-dependent protein C

Names: vitamin K-dependent protein C; autoprothrombin IIA; anticoagulant protein C; blood coagulation factor XIV

NP_000303.1

EC 3.4.21.69

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016323.1 RefSeqGene

Range

5001..15827

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000312.3 → NP_000303.1 vitamin K-dependent protein C preproprotein

Status: REVIEWED

Source sequence(s)

BC034377, BM975043, DA642156

Consensus CDS

CCDS2145.1

UniProtKB/Swiss-Prot

P04070

Related

ENSP00000234071, OTTHUMP00000162263, ENST00000234071, OTTHUMT00000254385

Conserved Domains (3) summary

cd00054
Location:100 – 132
Blast Score: 108

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

cd00190
Location:213 – 448
Blast Score: 641

Tryp_SPc; Trypsin-like serine protease; Many of these are synthesized as inactive precursor zymogens that are cleaved during limited proteolysis to generate their active forms. Alignment contains also inactive enzymes that have substitutions of the catalytic triad ...

smart00069
Location:24 – 87
Blast Score: 180

GLA; Domain containing Gla (gamma-carboxyglutamate) residues.

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p10 Primary Assembly

Range

128175996..128186822

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

120483060..120493885

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018913.1 Alternate CHM1_1.0

Range

127675258..127686083

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AB083690.1	BAC21165.1
genomic	AB083693.1	BAC21166.1
genomic	AB083695.1	BAC21167.1
genomic	AB083696.1	BAC21168.1
genomic	AB083697.1	BAC21169.1
genomic	AB083698.1	BAC21170.1
genomic	AB083699.1	BAC21171.1
genomic	AB083700.1	BAC21172.1
genomic	AB086849.1	BAC53629.1
genomic	AB086850.1	BAC53630.1
genomic	AB086851.1	BAC53631.1
genomic	AB086852.1	BAC54280.1
genomic	ABBA01040207.1 (1230..12055)	None
genomic	AC068282.8	AAY15044.1
genomic	AF378903.2	AAK56377.1
genomic	AMYH01011018.1 (298252..309077)	None
genomic	AY348553.1	AAQ24849.1
genomic	AY348554.1	AAQ24850.1
genomic	AY454079.1	AAR23427.1
genomic	CH471103.1	EAW95320.1
genomic	CQ757487.1	CAF32600.1
genomic	CQ821348.1	CAG34344.1
genomic	CS355172.1	CAL24228.1
genomic	GM997828.1	CAX30697.1
genomic	GM997830.1	CAX30698.1
genomic	M11228.1	AAA60166.1
genomic	M12712.1	AAA60165.1
genomic	S55227.1	AAB25410.1
genomic	S58668.1	AAB26335.1
mRNA	AK298280.1	BAG60540.1
mRNA	AK298449.1	BAG60665.1
mRNA	AK298454.1	BAG60669.1
mRNA	AK303773.1	BAG64736.1
mRNA	BC034377.1	AAH34377.1
mRNA	BM975043.1	None
mRNA	CB113383.1	None
mRNA	DA642156.1	None
mRNA	K02059.1	AAA60164.1
mRNA	S50739.1	AAB24150.1
mRNA	X02750.1	CAA26528.1
other-genetic	DQ890791.2	ABM81717.1
other-genetic	DQ893947.2	ABM84873.1