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Aliases for EPAS1 Gene

Aliases for EPAS1 Gene

  • Endothelial PAS Domain Protein 1 2 3
  • HIF2A 3 4 6
  • MOP2 3 4 6
  • Class E Basic Helix-Loop-Helix Protein 73 3 4
  • Basic-Helix-Loop-Helix-PAS Protein MOP2 3 4
  • Hypoxia-Inducible Factor 2-Alpha 3 4
  • PAS Domain-Containing Protein 2 3 4
  • Member Of PAS Protein 2 3 4
  • HIF-1-Alpha-Like Factor 3 4
  • HIF-2-Alpha 3 4
  • HIF2-Alpha 3 4
  • BHLHe73 3 4
  • EPAS-1 3 4
  • ECYT4 3 6
  • PASD2 3 4
  • HLF 3 4
  • Endothelial PAS Domain-Containing Protein 1 3
  • Hypoxia-Inducible Factor 2 Alpha 3
  • HIF-1 Alpha-Like Factor 2
  • HIF-1alpha-Like Factor 3

External Ids for EPAS1 Gene

Summaries for EPAS1 Gene

Entrez Gene Summary for EPAS1 Gene

  • This gene encodes a transcription factor involved in the induction of genes regulated by oxygen, which is induced as oxygen levels fall. The encoded protein contains a basic-helix-loop-helix domain protein dimerization domain as well as a domain found in proteins in signal transduction pathways which respond to oxygen levels. Mutations in this gene are associated with erythrocytosis familial type 4. [provided by RefSeq, Nov 2009]

GeneCards Summary for EPAS1 Gene

EPAS1 (Endothelial PAS Domain Protein 1) is a Protein Coding gene. Diseases associated with EPAS1 include erythrocytosis, familial, 4 and sporadic pheochromocytoma. Among its related pathways are Pathways in cancer and Cellular Senescence. GO annotations related to this gene include sequence-specific DNA binding and transcription factor binding. An important paralog of this gene is AHRR.

UniProtKB/Swiss-Prot for EPAS1 Gene

  • Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5-[AG]CGTG-3 within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation seems to require recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD

Gene Wiki entry for EPAS1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for EPAS1 Gene

Genomics for EPAS1 Gene

Genomic Location for EPAS1 Gene

Start:
46,293,667 bp from pter
End:
46,386,703 bp from pter
Size:
93,037 bases
Orientation:
Plus strand

Genomic View for EPAS1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for EPAS1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for EPAS1 Gene

Regulatory Elements for EPAS1 Gene

Proteins for EPAS1 Gene

  • Protein details for EPAS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q99814-EPAS1_HUMAN
    Recommended name:
    Endothelial PAS domain-containing protein 1
    Protein Accession:
    Q99814
    Secondary Accessions:
    • Q86VA2
    • Q99630

    Protein attributes for EPAS1 Gene

    Size:
    870 amino acids
    Molecular mass:
    96459 Da
    Quaternary structure:
    • Interacts with HIF3A (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT. Interacts with CREBBP (By similarity). Interacts with EGLN1. Interacts with VHL.

    Three dimensional structures from OCA and Proteopedia for EPAS1 Gene

neXtProt entry for EPAS1 Gene

Proteomics data for EPAS1 Gene at MOPED

Post-translational modifications for EPAS1 Gene

  • In normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.
  • In normoxia, is probably hydroxylated on Pro-405 and Pro-531 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity).
  • Phosphorylated on multiple sites in the CTAD.
  • The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for EPAS1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for EPAS1 Gene

Domains for EPAS1 Gene

Gene Families for EPAS1 Gene

HGNC:
  • bHLH :Basic helix-loop-helix proteins

UniProtKB/Swiss-Prot:

EPAS1_HUMAN
Domain:
  • Contains 1 bHLH (basic helix-loop-helix) domain.:
    • Q99814
  • Contains 1 PAC (PAS-associated C-terminal) domain.:
    • Q99814
  • Contains 2 PAS (PER-ARNT-SIM) domains.:
    • Q99814
genes like me logo Genes that share domains with EPAS1: view

Function for EPAS1 Gene

Molecular function for EPAS1 Gene

UniProtKB/Swiss-Prot Function: Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5-[AG]CGTG-3 within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation seems to require recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD

Gene Ontology (GO) - Molecular Function for EPAS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001077 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IEA --
GO:0003677 DNA binding IGI 9000051
GO:0003700 sequence-specific DNA binding transcription factor activity --
GO:0004871 signal transducer activity IEA --
GO:0005515 protein binding IPI 15231748
genes like me logo Genes that share ontologies with EPAS1: view
genes like me logo Genes that share phenotypes with EPAS1: view

Animal Models for EPAS1 Gene

MGI Knock Outs for EPAS1:

miRNA for EPAS1 Gene

miRTarBase miRNAs that target EPAS1

Transcription Factor Targeting for EPAS1 Gene

Selected GeneGlobe predicted Target genes for EPAS1

No data available for Enzyme Numbers (IUBMB) and HOMER Transcription for EPAS1 Gene

Localization for EPAS1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for EPAS1 Gene

Nucleus. Nucleus speckle. Note=Colocalizes with HIF3A in the nucleus and speckles. {ECO:0000250 UniProtKB:P97481}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for EPAS1 Gene COMPARTMENTS Subcellular localization image for EPAS1 gene
Compartment Confidence
nucleus 5
cytosol 4
extracellular 1

Gene Ontology (GO) - Cellular Components for EPAS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus --
GO:0005654 nucleoplasm TAS --
GO:0005667 transcription factor complex IPI 9576906
GO:0005737 cytoplasm --
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with EPAS1: view

Pathways for EPAS1 Gene

genes like me logo Genes that share pathways with EPAS1: view

Gene Ontology (GO) - Biological Process for EPAS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001525 angiogenesis IEA --
GO:0001666 response to hypoxia IDA 11782478
GO:0001892 embryonic placenta development IEA --
GO:0001974 blood vessel remodeling IEA --
GO:0002027 regulation of heart rate IEA --
genes like me logo Genes that share ontologies with EPAS1: view

Compounds for EPAS1 Gene

(9) Novoseek inferred chemical compound relationships for EPAS1 Gene

Compound -log(P) Hits PubMed IDs
vegf 60.2 53
glycyrrhizin 34.1 5
oxygen 29 10
pd 98,059 27.7 3
iron 20.8 9
genes like me logo Genes that share compounds with EPAS1: view

Transcripts for EPAS1 Gene

Unigene Clusters for EPAS1 Gene

Endothelial PAS domain protein 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for EPAS1 Gene

No ASD Table

Relevant External Links for EPAS1 Gene

GeneLoc Exon Structure for
EPAS1
ECgene alternative splicing isoforms for
EPAS1

Expression for EPAS1 Gene

mRNA expression in normal human tissues for EPAS1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for EPAS1 Gene

This gene is overexpressed in Lung (5.2).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for EPAS1 Gene

SOURCE GeneReport for Unigene cluster for EPAS1 Gene Hs.468410

mRNA Expression by UniProt/SwissProt for EPAS1 Gene

Q99814-EPAS1_HUMAN
Tissue specificity: Expressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells
genes like me logo Genes that share expressions with EPAS1: view

Orthologs for EPAS1 Gene

This gene was present in the common ancestor of animals.

Orthologs for EPAS1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia EPAS1 36
  • 99.73 (n)
  • 99.89 (a)
EPAS1 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia EPAS1 36
  • 87.42 (n)
  • 87.69 (a)
EPAS1 37
  • 88 (a)
OneToOne
dog
(Canis familiaris)
Mammalia EPAS1 36
  • 88.63 (n)
  • 90.09 (a)
EPAS1 37
  • 90 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Epas1 36
  • 85.58 (n)
  • 88.03 (a)
Epas1 16
Epas1 37
  • 88 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia EPAS1 37
  • 81 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia EPAS1 37
  • 55 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Epas1 36
  • 84.62 (n)
  • 85.96 (a)
chicken
(Gallus gallus)
Aves EPAS1 36
  • 72.4 (n)
  • 76.31 (a)
EPAS1 37
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia EPAS1 37
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia epas1 36
  • 67.17 (n)
  • 67.13 (a)
zebrafish
(Danio rerio)
Actinopterygii epas1a 37
  • 56 (a)
OneToMany
epas1b 36
  • 64.79 (n)
  • 63.11 (a)
epas1b 37
  • 60 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta sima 37
  • 17 (a)
OneToMany
sima 38
  • 39 (a)
worm
(Caenorhabditis elegans)
Secernentea hif-1 37
  • 21 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 37
  • 28 (a)
OneToMany
Species with no ortholog for EPAS1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • 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)

Evolution for EPAS1 Gene

ENSEMBL:
Gene Tree for EPAS1 (if available)
TreeFam:
Gene Tree for EPAS1 (if available)

Paralogs for EPAS1 Gene

Paralogs for EPAS1 Gene

Selected SIMAP similar genes for EPAS1 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with EPAS1: view

Variants for EPAS1 Gene

Sequence variations from dbSNP and Humsavar for EPAS1 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs895436 -- 46,323,353(+) AGTAG(C/G)TGCCA intron-variant
rs1057773 -- 46,384,693(+) CTGCC(A/C/G)ACGCC utr-variant-3-prime
rs1114794 -- 46,327,566(+) CTGCA(A/G)AAAAA intron-variant
rs1190662 -- 46,313,526(+) agctc(A/C)ctgca intron-variant
rs1374748 -- 46,359,895(+) ATCGG(G/T)AGGCT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for EPAS1 Gene

Variant ID Type Subtype PubMed ID
dgv1181e1 CNV Complex 17122850
nsv2714 CNV Insertion 18451855
dgv149e55 CNV Loss 17911159

Relevant External Links for EPAS1 Gene

HapMap Linkage Disequilibrium report
EPAS1
Human Gene Mutation Database (HGMD)
EPAS1

Disorders for EPAS1 Gene

(1) OMIM Diseases for EPAS1 Gene (603349)

UniProtKB/Swiss-Prot

EPAS1_HUMAN
  • Erythrocytosis, familial, 4 (ECYT4) [MIM:611783]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts. {ECO:0000269 PubMed:18184961, ECO:0000269 PubMed:18378852, ECO:0000269 PubMed:19208626, ECO:0000269 PubMed:22367913}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(1) University of Copenhagen DISEASES for EPAS1 Gene

(17) Novoseek inferred disease relationships for EPAS1 Gene

Disease -log(P) Hits PubMed IDs
carcinoma renal cell 43.1 7
pheochromocytoma 35.7 2
tumors 28.8 13
bladder cancer 22.6 4
hepatocellular carcinoma 20.1 1

Relevant External Links for EPAS1

Genetic Association Database (GAD)
EPAS1
Human Genome Epidemiology (HuGE) Navigator
EPAS1
genes like me logo Genes that share disorders with EPAS1: view

Publications for EPAS1 Gene

  1. Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis. (PMID: 18378852) Percy M.J. … Lee F.S. (Blood 2008) 2 3 4 23 49
  2. Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. (PMID: 9079689) Hogenesch J.B. … Bradfield C.A. (J. Biol. Chem. 1997) 2 3 4 23
  3. The EPAS1 gene influences the aerobic-anaerobic contribution in elite endurance athletes. (PMID: 16208515) Henderson J. … Yu B. (Hum. Genet. 2005) 3 23 49
  4. Genetic contributions to the development of retinopathy of prematurity. (PMID: 18787502) Mohamed S. … Dagle J.M. (Pediatr. Res. 2009) 3 23 49
  5. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. (PMID: 9000051) Tian H. … Russell D.W. (Genes Dev. 1997) 2 3 4

Products for EPAS1 Gene

  • Addgene plasmids for EPAS1

Sources for EPAS1 Gene

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