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Aliases for PROC Gene

Aliases for PROC Gene

  • Protein C, Inactivator Of Coagulation Factors Va And VIIIa 2 3 5
  • Blood Coagulation Factor XIV 3 4
  • Anticoagulant Protein C 3 4
  • Autoprothrombin IIA 3 4
  • Prepro-Protein C 2 3
  • EC 3.4.21.69 4 61
  • Protein C (Inactivator Of Coagulation Factors Va And VIIIa) 2
  • Vitamin K-Dependent Protein C 3
  • Type I Protein C 3
  • EC 3.4.21 61
  • PROC1 3
  • THPH3 3
  • THPH4 3
  • APC 3
  • PC 3

External Ids for PROC Gene

Previous GeneCards Identifiers for PROC Gene

  • GC02P125475
  • GC02P126102
  • GC02P128080
  • GC02P128269
  • GC02P127892
  • GC02P128176
  • GC02P120483

Summaries for PROC Gene

Entrez Gene Summary for PROC Gene

  • 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]

GeneCards Summary for PROC Gene

PROC (Protein C, Inactivator Of Coagulation Factors Va And VIIIa) is a Protein Coding gene. Diseases associated with PROC include Thrombophilia Due To Protein C Deficiency, Autosomal Recessive and Thrombophilia Due To Protein C Deficiency, Autosomal Dominant. Among its related pathways are Gamma carboxylation, hypusine formation and arylsulfatase activation and Formation of Fibrin Clot (Clotting Cascade). GO annotations related to this gene include calcium ion binding and peptidase activity. An important paralog of this gene is F7.

UniProtKB/Swiss-Prot for PROC Gene

  • 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 (PubMed:25618265). Exerts a protective effect on the endothelial cell barrier function (PubMed:25651845).

Gene Wiki entry for PROC Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for PROC Gene

Genomics for PROC Gene

Regulatory Elements for PROC Gene

Enhancers for PROC Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH02G127454 1.3 Ensembl ENCODE 12.3 +37.0 36956 2.6 FOXA2 MLX ZFP64 ARID4B SIN3A DMAP1 ZNF48 YY1 SLC30A9 SP5 PROC LIMS2 ERCC3 MAP3K2 ENSG00000236682 ENSG00000231731 MIR4783
GH02G127453 0.8 ENCODE 12.3 +35.1 35135 0.2 ELF3 PKNOX1 ARID4B DMAP1 ZNF48 RAD21 YY1 SLC30A9 GATA2 ZNF143 PROC ENSG00000231731 MIR4783
GH02G127455 0.8 ENCODE 12.3 +35.4 35355 0.2 ELF3 PKNOX1 ARID4B DMAP1 DNMT3B ZNF48 RAD21 YY1 SLC30A9 GATA2 PROC ENSG00000231731 MIR4783
GH02G127479 0.8 ENCODE 11.6 +61.0 61015 0.1 CTCF SAP130 AGO1 ARID4B RAD21 ZNF316 POLR2A ZNF143 SMC3 FOS PROC ERCC3 RNU4-48P GC02M127501
GH02G127348 0.7 Ensembl 11.7 -70.1 -70105 0.2 TAL1 ZNF10 ZNF394 ZNF507 OSR2 TCF12 ARID1B ATF3 NCOR1 IKZF1 ERCC3 MAP3K2 ENSG00000236682 PROC RNU4-48P LOC105373606 LOC100506922
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around PROC on UCSC Golden Path with GeneCards custom track

Genomic Location for PROC Gene

Chromosome:
2
Start:
127,418,405 bp from pter
End:
127,429,246 bp from pter
Size:
10,842 bases
Orientation:
Plus strand

Genomic View for PROC Gene

Genes around PROC on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
PROC Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for PROC Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for PROC Gene

Proteins for PROC Gene

  • Protein details for PROC Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P04070-PROC_HUMAN
    Recommended name:
    Vitamin K-dependent protein C
    Protein Accession:
    P04070
    Secondary Accessions:
    • B4DPQ7
    • Q15189
    • Q15190
    • Q16001
    • Q53S74
    • Q9UC55

    Protein attributes for PROC Gene

    Size:
    461 amino acids
    Molecular mass:
    52071 Da
    Quaternary structure:
    • 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.
    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.
    SequenceCaution:
    • Sequence=S76088; Type=Erroneous termination; Positions=151; Note=Translated as Cys.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for PROC Gene

    Alternative splice isoforms for PROC Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for PROC Gene

Selected DME Specific Peptides for PROC Gene

P04070:
  • LLDSKKKL
  • RANSFLEE
  • DNDIALL
  • YTKVSRY
  • SENMLCAGI
  • VLTAAHC
  • VRLGEYDLRR
  • SQTIVPICLPDSGL
  • WVLTAAH
  • ERECIEE
  • GWEGRFC
  • DACEGDSGGP
  • DACEGDSGGPMV
  • GDSGGPMV

Post-translational modifications for PROC Gene

  • May be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide.
  • 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.
  • The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
  • The vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind calcium.
  • Glycosylation at isoforms=219, isoforms=2139, Asn290, Asn355, and Asn371
  • Modification sites at PhosphoSitePlus

Antibody Products

  • R&D Systems Antibodies for PROC (Coagulation Factor XIV/Protein C)

Protein Products

Assay Products

  • Cloud-Clone Corp Assay Kits for PROC

Domains & Families for PROC Gene

Gene Families for PROC Gene

Graphical View of Domain Structure for InterPro Entry

P04070

UniProtKB/Swiss-Prot:

PROC_HUMAN :
  • Belongs to the peptidase S1 family.
Family:
  • Belongs to the peptidase S1 family.
genes like me logo Genes that share domains with PROC: view

Function for PROC Gene

Molecular function for PROC Gene

GENATLAS Biochemistry:
protein C,coagulation factor (FVa and FVIIIa inactivator),vitamin K-dependent
UniProtKB/Swiss-Prot CatalyticActivity:
Degradation of blood coagulation factors Va and VIIIa.
UniProtKB/Swiss-Prot 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 (PubMed:25618265). Exerts a protective effect on the endothelial cell barrier function (PubMed:25651845).

Enzyme Numbers (IUBMB) for PROC Gene

Gene Ontology (GO) - Molecular Function for PROC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004252 serine-type endopeptidase activity IEA,TAS 15005336
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 15248212
GO:0008233 peptidase activity IEA --
GO:0008236 serine-type peptidase activity IEA --
genes like me logo Genes that share ontologies with PROC: view
genes like me logo Genes that share phenotypes with PROC: view

Human Phenotype Ontology for PROC Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for PROC Gene

MGI Knock Outs for PROC:

Animal Model Products

miRNA for PROC Gene

miRTarBase miRNAs that target PROC

Inhibitory RNA Products

Clone Products

No data available for Transcription Factor Targets and HOMER Transcription for PROC Gene

Localization for PROC Gene

Subcellular locations from UniProtKB/Swiss-Prot for PROC Gene

Secreted. Golgi apparatus. Endoplasmic reticulum.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for PROC gene
Compartment Confidence
extracellular 5
endoplasmic reticulum 5
golgi apparatus 5
plasma membrane 1
nucleus 1
cytosol 1
lysosome 1

Gene Ontology (GO) - Cellular Components for PROC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS,IEA --
GO:0005615 extracellular space IBA --
GO:0005783 endoplasmic reticulum IDA,IEA 25748729
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0005794 Golgi apparatus IEA,IDA 25748729
genes like me logo Genes that share ontologies with PROC: view

Pathways & Interactions for PROC Gene

genes like me logo Genes that share pathways with PROC: view

Gene Ontology (GO) - Biological Process for PROC Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001889 liver development IEA --
GO:0006465 signal peptide processing TAS --
GO:0006508 proteolysis NAS,IEA 12052963
GO:0006888 ER to Golgi vesicle-mediated transport TAS --
GO:0007596 blood coagulation TAS --
genes like me logo Genes that share ontologies with PROC: view

No data available for SIGNOR curated interactions for PROC Gene

Drugs & Compounds for PROC Gene

(11) Drugs for PROC Gene - From: DrugBank, PharmGKB, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Sodium Tetradecyl Sulfate Approved Pharma inhibitor, Target 6
Menadione Approved Nutra inhibitor, Target, activator 239
Warfarin Approved Pharma 470
Antihemophilic Factor (Recombinant) Approved, Investigational Pharma Enzyme, inactivator 0
Drospirenone Approved Pharma Antagonist 109

(4) Additional Compounds for PROC Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with PROC: view

Transcripts for PROC Gene

Unigene Clusters for PROC Gene

Protein C (inactivator of coagulation factors Va and VIIIa):
Representative Sequences:

Inhibitory RNA Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for PROC Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8 ^ 9a · 9b
SP1: - - -
SP2:
SP3:
SP4: - - -

Relevant External Links for PROC Gene

GeneLoc Exon Structure for
PROC
ECgene alternative splicing isoforms for
PROC

Expression for PROC Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for PROC Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for PROC Gene

This gene is overexpressed in Liver (x48.6).

Protein differential expression in normal tissues from HIPED for PROC Gene

This gene is overexpressed in Serum (42.3) and Plasma (12.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for PROC Gene



NURSA nuclear receptor signaling pathways regulating expression of PROC Gene:

PROC

SOURCE GeneReport for Unigene cluster for PROC Gene:

Hs.224698

mRNA Expression by UniProt/SwissProt for PROC Gene:

P04070-PROC_HUMAN
Tissue specificity: Plasma; synthesized in the liver.

Evidence on tissue expression from TISSUES for PROC Gene

  • Liver(4.6)
  • Blood(4.4)
  • Intestine(4.3)
  • Bone marrow(4)

Phenotype-based relationships between genes and organs from Gene ORGANizer for PROC Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • immune
  • integumentary
  • nervous
  • respiratory
Organs:
Head and neck:
  • brain
  • ear
  • eye
  • head
Thorax:
  • heart
  • lung
General:
  • blood
  • blood vessel
  • coagulation system
  • skin
genes like me logo Genes that share expression patterns with PROC: view

Primer Products

No data available for Protein tissue co-expression partners for PROC Gene

Orthologs for PROC Gene

This gene was present in the common ancestor of animals.

Orthologs for PROC Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia PROC 34 35
  • 99.64 (n)
dog
(Canis familiaris)
Mammalia LOC476104 34
  • 85.6 (n)
PROC 35
  • 71 (a)
OneToOne
cow
(Bos Taurus)
Mammalia PROC 34 35
  • 81.91 (n)
mouse
(Mus musculus)
Mammalia Proc 34 16 35
  • 78.1 (n)
rat
(Rattus norvegicus)
Mammalia Proc 34
  • 77.49 (n)
oppossum
(Monodelphis domestica)
Mammalia PROC 35
  • 58 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia PROC 35
  • 46 (a)
OneToOne
chicken
(Gallus gallus)
Aves PROC 34 35
  • 61.9 (n)
lizard
(Anolis carolinensis)
Reptilia PROC 35
  • 52 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia proc 34
  • 58.99 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.24334 34
zebrafish
(Danio rerio)
Actinopterygii proca 34 35
  • 54.58 (n)
PROC (2 of 2) 35
  • 47 (a)
OneToMany
zgc63987 34
fruit fly
(Drosophila melanogaster)
Insecta CG4998 36
  • 35 (a)
Tequila 36
  • 34 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 16 (a)
OneToMany
Species where no ortholog for PROC was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for PROC Gene

ENSEMBL:
Gene Tree for PROC (if available)
TreeFam:
Gene Tree for PROC (if available)

Paralogs for PROC Gene

Paralogs for PROC Gene

genes like me logo Genes that share paralogs with PROC: view

Variants for PROC Gene

Sequence variations from dbSNP and Humsavar for PROC Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type
rs121918142 Pathogenic, Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860] 127,428,892(+) GACTG(C/G)ATCCA intron-variant, reference, missense
rs121918145 Pathogenic, Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860] 127,426,178(+) AGATC(C/T)GCGGC nc-transcript-variant, reference, missense
rs121918148 Pathogenic, Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860] 127,421,397(+) AGAGG(A/C)GATCT reference, missense
rs121918149 Pathogenic, Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860] 127,421,438(+) AAAAT(A/G)TGGAT reference, missense
rs121918150 Pathogenic, Thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:612304] 127,428,560(+) AGGCC(A/G)GCCAG intron-variant, reference, missense

Structural Variations from Database of Genomic Variants (DGV) for PROC Gene

Variant ID Type Subtype PubMed ID
nsv583036 CNV gain 21841781

Variation tolerance for PROC Gene

Residual Variation Intolerance Score: 12.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.91; 35.54% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for PROC Gene

Human Gene Mutation Database (HGMD)
PROC
SNPedia medical, phenotypic, and genealogical associations of SNPs for
PROC

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for PROC Gene

Disorders for PROC Gene

MalaCards: The human disease database

(15) MalaCards diseases for PROC Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
thrombophilia due to protein c deficiency, autosomal recessive
  • autosomal recessive protein c deficiency
thrombophilia due to protein c deficiency, autosomal dominant
  • proc deficiency autosomal dominant
protein c deficiency
  • hereditary thrombophilia due to congenital protein c deficiency
purpura fulminans
  • purpura gangrenosa
thrombophilia
  • hypercoagulability state
- elite association - COSMIC cancer census association via MalaCards
Search PROC in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

PROC_HUMAN
  • 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. 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. {ECO:0000269 PubMed:1301959, ECO:0000269 PubMed:1347706, ECO:0000269 PubMed:1511989, ECO:0000269 PubMed:1868249, ECO:0000269 PubMed:2437584, ECO:0000269 PubMed:25618265, ECO:0000269 PubMed:25748729, ECO:0000269 PubMed:2602169, ECO:0000269 PubMed:7792728, ECO:0000269 PubMed:7865674, ECO:0000269 PubMed:8292730, ECO:0000269 PubMed:8398832, ECO:0000269 PubMed:8499568, ECO:0000269 PubMed:8560401, ECO:0000269 PubMed:8829639, ECO:0000269 PubMed:9798967}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • 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. {ECO:0000269 PubMed:1511988, ECO:0000269 PubMed:1593215, ECO:0000269 PubMed:1611081, ECO:0000269 PubMed:25618265, ECO:0000269 PubMed:7841323, ECO:0000269 PubMed:7841324, ECO:0000269 PubMed:7878626}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Genatlas disease for PROC Gene

thrombosis,recurrent (pro-C type I and type II deficiency)

Relevant External Links for PROC

Genetic Association Database (GAD)
PROC
Human Genome Epidemiology (HuGE) Navigator
PROC
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
PROC
genes like me logo Genes that share disorders with PROC: view

Publications for PROC Gene

  1. Prevalence of genetic mutations in protein S, protein C and antithrombin genes in Japanese patients with deep vein thrombosis. (PMID: 18954896) Miyata T. … Ikeda Y. (Thromb. Res. 2009) 3 22 46 64
  2. Genetic determinants of warfarin dosing in the Han-Chinese population. (PMID: 19958090) Lee M.T. … Chen Y.T. (Pharmacogenomics 2009) 3 22 46 64
  3. PROC, PROCR and PROS1 polymorphisms, plasma anticoagulant phenotypes, and risk of cardiovascular disease and mortality in older adults: the Cardiovascular Health Study. (PMID: 18680534) Reiner A.P. … Lange L.A. (J. Thromb. Haemost. 2008) 3 22 46 64
  4. Association of warfarin dose with genes involved in its action and metabolism. (PMID: 17048007) Wadelius M. … Deloukas P. (Hum. Genet. 2007) 3 22 46 64
  5. R147W mutation of PROC gene is common in venous thrombotic patients in Taiwanese Chinese. (PMID: 15114590) Tsay W. … Shen M.C. (Am. J. Hematol. 2004) 3 22 46 64

Products for PROC Gene

Sources for PROC Gene

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