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

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Summary

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]

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Genomic context

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

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

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

We conclude that activated protein C generation and function can be modulated by changes in phospholipid occupancy of its endothelial cell receptor.
Title: sPLA2-V inhibits EPCR anticoagulant and antiapoptotic properties by accommodating lysophosphatidylcholine or PAF in the hydrophobic groove.
FVL and PROC mutations increase the risk of thrombosis in subjects with protein C deficiency, which could be considered as a 'variable' risk factor
Title: Hereditary protein C deficiency and thrombosis risk: genotype and phenotype relation in a large Italian family.
APC binding to endothelial protein C receptor (EPCR) allowing PAR1 activation, but activation of other PARS is also implicated in some cases. In addition to EPCR orchestrating these changes, CD11b is also capable of supporting APC signaling.
Title: Protein C anticoagulant system--anti-inflammatory effects.
Findings show that the protein C (PC) pathway is a unique system involved in controlling intestinal homeostasis and inflammation by regulating epithelial barrier function.
Title: Unexpected role of anticoagulant protein C in controlling epithelial barrier integrity and intestinal inflammation.
Studies suggest that for test-order policy of thrombophilia screening for PC, PS, and AT should be limited to outpatients.
Title: Inappropriate use of protein C, protein S, and antithrombin testing for hereditary thrombophilia screening: an experience from a large university hospital.
biologic function of APC in the control of coagulation and inflammation (Review)
Title: Multiple receptor-mediated functions of activated protein C.
Protein C deficiency is associated with short clot lysis time. CLT is partly genetically regulated. Suggestive QTLs were found on chromosomes 11 and 13.
Title: Genome scan of clot lysis time and its association with thrombosis in a protein C-deficient kindred.
These findings identify a role for beta-arrestin and Dvl-2 scaffolds in APC-activated PAR1 cytoprotective signaling in human endothelial cells.
Title: Activated protein C promotes protease-activated receptor-1 cytoprotective signaling through β-arrestin and dishevelled-2 scaffolds.
Increased serial protein C levels were found in severe sepsis patients treated with drotrecogin alfa (activated).
Title: Randomized trial evaluating serial protein C levels in severe sepsis patients treated with variable doses of drotrecogin alfa (activated).
higher age-adjusted activities for protein C and protein S in men than in women
Title: Normal ranges and genetic variants of antithrombin, protein C and protein S in the general Chinese population. Results of the Chinese Hemostasis Investigation on Natural Anticoagulants Study I Group.

Submit: New GeneRIF Correction See all (164)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

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.

Thrombophilia due to protein C deficiency, autosomal dominant

MIM: 176860

Thrombophilia due to protein C deficiency, autosomal recessive

MIM: 612304

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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

Function	Evidence Code	Pubs
calcium ion binding	IEA Inferred from Electronic Annotation more info
peptidase activity	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

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
extracellular space	IEA Inferred from Electronic Annotation more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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

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NCBI Reference Sequences (RefSeq)

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 ...

cl02449
Location:24 – 87
Blast Score: 180

Gla; Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p5 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)

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Related Sequences

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	AC068282.8	AAY15044.1
genomic	AF378903.2	AAK56377.1
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

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P04070.1	GenPept	UniProtKB/Swiss-Prot:P04070
Q6SPC0	GenPept	UniProtKB/TrEMBL:Q6SPC0
Q6V7X8	GenPept	UniProtKB/TrEMBL:Q6V7X8
Q6V7X9	GenPept	UniProtKB/TrEMBL:Q6V7X9
Q8IXB4	GenPept	UniProtKB/TrEMBL:Q8IXB4
Q8IXB5	GenPept	UniProtKB/TrEMBL:Q8IXB5
Q8IXB6	GenPept	UniProtKB/TrEMBL:Q8IXB6
Q8IXB7	GenPept	UniProtKB/TrEMBL:Q8IXB7
Q8J002	GenPept	UniProtKB/TrEMBL:Q8J002
Q8J003	GenPept	UniProtKB/TrEMBL:Q8J003
Q8J004	GenPept	UniProtKB/TrEMBL:Q8J004
Q8J005	GenPept	UniProtKB/TrEMBL:Q8J005
Q8J006	GenPept	UniProtKB/TrEMBL:Q8J006
Q8J007	GenPept	UniProtKB/TrEMBL:Q8J007
Q8J008	GenPept	UniProtKB/TrEMBL:Q8J008
Q8J009	GenPept	UniProtKB/TrEMBL:Q8J009