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EPAS1 endothelial PAS domain protein 1 [ Homo sapiens (human) ]

Gene ID: 2034, updated on 3-Apr-2024

Summary

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Official Symbol
EPAS1provided by HGNC
Official Full Name
endothelial PAS domain protein 1provided by HGNC
Primary source
HGNC:HGNC:3374
See related
Ensembl:ENSG00000116016 MIM:603349; AllianceGenome:HGNC:3374
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
HLF; MOP2; ECYT4; HIF2A; PASD2; bHLHe73
Summary
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]
Expression
Broad expression in lung (RPKM 304.3), placenta (RPKM 244.1) and 22 other tissues See more
Orthologs
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Genomic context

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See EPAS1 in Genome Data Viewer
Location:
2p21
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (46297407..46386697)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (46302427..46391719)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (46524546..46613836)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene protein kinase C epsilon Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:46234481-46235680 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:46242352-46242990 Neighboring gene ribosomal protein L26 pseudogene 15 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:46294453-46295652 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:46344077-46345276 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_58540 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:46371061-46371560 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:46395156-46395343 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr2:46398401-46398983 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:46406387-46406887 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:46456039-46457023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15700 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15701 Neighboring gene uncharacterized LOC101926974 Neighboring gene uncharacterized LOC105374581 Neighboring gene Sharpr-MPRA regulatory region 5165 Neighboring gene Sharpr-MPRA regulatory region 3071 Neighboring gene ribosomal protein L36a pseudogene 14 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:46518393-46518894 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11446 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11447 Neighboring gene Sharpr-MPRA regulatory region 14137 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:46587586-46588785 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:46611587-46612086 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:46620302-46620802 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:46620803-46621303 Neighboring gene uncharacterized LOC124907762 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:46636005-46636579 Neighboring gene long intergenic non-protein coding RNA 1820

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. EPAS1 resistance to miRNA-based regulation contributes to prolonged expression of HIF-2 during hypoxia in human endothelial cells. Jaśkiewicz M, et al. Gene, 2023 Jun 5. PMID 36934786
  2. Endotyping COPD: hypoxia-inducible factor-2 as a molecular "switch" between the vascular and airway phenotypes? Myronenko O, et al. Eur Respir Rev, 2023 Mar 31. PMID 36631133, Free PMC Article
  3. Diagnosis and genetic analysis of polycythemia in children and a novel EPAS1 gene mutation. Cakmak HM, et al. Pediatr Neonatol, 2022 Nov. PMID 36002380
  4. [Hypoxia promotes erythroid differentiation of human K562 cells by upregulating endothelial PAS domain-containing protein 1 (EPAS1) expression]. Gao Z, et al. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, 2022 Jun. PMID 35732606
  5. The hypoxia-induced changes in miRNA-mRNA in RNA-induced silencing complexes and HIF-2 induced miRNAs in human endothelial cells. Moszyńska A, et al. FASEB J, 2022 Jul. PMID 35713587, Free PMC Article

See all (608) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Hypoxia-inducible factor-2alpha promotes fibrosis in non-alcoholic fatty liver disease by enhancing glutamine catabolism and inhibiting yes-associated protein phosphorylation in hepatic stellate cells.
    Title: Hypoxia-inducible factor-2α promotes fibrosis in non-alcoholic fatty liver disease by enhancing glutamine catabolism and inhibiting yes-associated protein phosphorylation in hepatic stellate cells.
  2. EPAS1-mutated paragangliomas associated with haemoglobin disorders.
    Title: EPAS1-mutated paragangliomas associated with haemoglobin disorders.
  3. Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.
    Title: Functional EPAS1/HIF2A missense variant is associated with hematocrit in Andean highlanders.
  4. HIF-2alpha-dependent TGFBI promotes ovarian cancer chemoresistance by activating PI3K/Akt pathway to inhibit apoptosis and facilitate DNA repair process.
    Title: HIF-2α-dependent TGFBI promotes ovarian cancer chemoresistance by activating PI3K/Akt pathway to inhibit apoptosis and facilitate DNA repair process.
  5. HIF-2alpha/LINC02609/APOL1-mediated lipid storage promotes endoplasmic reticulum homeostasis and regulates tumor progression in clear-cell renal cell carcinoma.
    Title: HIF-2α/LINC02609/APOL1-mediated lipid storage promotes endoplasmic reticulum homeostasis and regulates tumor progression in clear-cell renal cell carcinoma.
  6. A Case-Control Study of the Associations between EGLN1 Gene Polymorphisms and COPD.
    Title: A Case-Control Study of the Associations between EGLN1 Gene Polymorphisms and COPD.
  7. Somatic EPAS1 Variants in Pheochromocytoma and Paraganglioma in Patients With Sickle Cell Disease.
    Title: Somatic EPAS1 Variants in Pheochromocytoma and Paraganglioma in Patients With Sickle Cell Disease.
  8. Hypoxia-inducible factor 2alpha protein and mRNA expression correlate with histomorphological features in clear cell renal cell carcinoma.
    Title: Hypoxia-inducible factor 2α protein and mRNA expression correlate with histomorphological features in clear cell renal cell carcinoma.
  9. UBE3B promotes breast cancer progression by antagonizing HIF-2alpha degradation.
    Title: UBE3B promotes breast cancer progression by antagonizing HIF-2α degradation.
  10. Structural basis for binding of the renal carcinoma target hypoxia-inducible factor 2alpha to prolyl hydroxylase domain 2.
    Title: Structural basis for binding of the renal carcinoma target hypoxia-inducible factor 2α to prolyl hydroxylase domain 2.
Submit: New GeneRIF Correction See all GeneRIFs (527)

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

Associated conditions

Description Tests
Erythrocytosis, familial, 4
MedGen: C2673187 OMIM: 611783 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.
EBI GWAS Catalog
Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of endothelial PAS domain protein 1 (EPAS1) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed
Knockdown of endothelial PAS domain protein 1 (EPAS1) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

Protein interactions

Protein Gene Interaction Pubs
Nef nef HIV-1 Nef increases expression of both VEGF and its transcriptional regulator, hypoxia-inducible factor 2alpha (HIF-2alpha), in a Src kinase-and Stat3-dependent manner PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA polymerase II-specific DNA-binding transcription factor binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein heterodimerization activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein heterodimerization activity IPI
Inferred from Physical Interaction
more info
 PubMed 
contributes_to sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables transcription coactivator binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in angiogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in blood vessel remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to hypoxia IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cellular response to hypoxia IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in embryonic placenta development IEA
Inferred from Electronic Annotation
more info
  
involved_in epithelial cell maturation IEA
Inferred from Electronic Annotation
more info
  
involved_in erythrocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in lung development IEA
Inferred from Electronic Annotation
more info
  
involved_in mRNA transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
involved_in mitochondrion organization IEA
Inferred from Electronic Annotation
more info
  
involved_in multicellular organismal-level iron ion homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in myoblast fate commitment ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in norepinephrine metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cold-induced thermogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of heart rate IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of protein neddylation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
acts_upstream_of_or_within response to hypoxia IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to oxidative stress IEA
Inferred from Electronic Annotation
more info
  
involved_in signal transduction TAS
Traceable Author Statement
more info
 PubMed 
involved_in surfactant homeostasis IEA
Inferred from Electronic Annotation
more info
  
involved_in visual perception IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nuclear speck IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
part_of transcription regulator complex IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
endothelial PAS domain-containing protein 1
Names
EPAS-1
HIF-1-alpha-like factor
HIF-1alpha-like factor
HIF-2-alpha
HIF2-alpha
PAS domain-containing protein 2
basic-helix-loop-helix-PAS protein MOP2
class E basic helix-loop-helix protein 73
hypoxia-inducible factor 2 alpha
member of PAS protein 2

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

  1. NG_016000.1 RefSeqGene

    Range
    5006..94296
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001430.5 → NP_001421.2  endothelial PAS domain-containing protein 1

    See identical proteins and their annotated locations for NP_001421.2

    Status: REVIEWED

    Source sequence(s)
    AC016696, AK123845, BC051338, CD109908
    Consensus CDS
    CCDS1825.1
    UniProtKB/Swiss-Prot
    Q86VA2, Q99630, Q99814
    UniProtKB/TrEMBL
    Q53SM6
    Related
    ENSP00000263734.3, ENST00000263734.5
    Conserved Domains (6) summary
    smart00091
    Location:86 → 147
    PAS; PAS domain
    cd00083
    Location:12 → 68
    HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
    cd00130
    Location:241 → 340
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    pfam08447
    Location:254 → 341
    PAS_3; PAS fold
    pfam08778
    Location:833 → 869
    HIF-1a_CTAD; HIF-1 alpha C terminal transactivation domain
    pfam11413
    Location:517 → 549
    HIF-1; Hypoxia-inducible factor-1

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    46297407..46386697
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011532698.3 → XP_011531000.1  endothelial PAS domain-containing protein 1 isoform X1

    UniProtKB/TrEMBL
    Q53SM6
    Conserved Domains (6) summary
    smart00091
    Location:99 → 160
    PAS; PAS domain
    cd00083
    Location:25 → 81
    HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...
    cd00130
    Location:254 → 353
    PAS; PAS domain; PAS motifs appear in archaea, eubacteria and eukarya. Probably the most surprising identification of a PAS domain was that in EAG-like K+-channels. PAS domains have been found to bind ligands, and to act as sensors for light and oxygen in ...
    pfam08447
    Location:267 → 354
    PAS_3; PAS fold
    pfam08778
    Location:846 → 882
    HIF-1a_CTAD; HIF-1 alpha C terminal transactivation domain
    pfam11413
    Location:530 → 562
    HIF-1; Hypoxia-inducible factor-1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    46302427..46391719
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341015.1 → XP_054196990.1  endothelial PAS domain-containing protein 1 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q99814.3 GenPept UniProtKB/Swiss-Prot:Q99814

Gene LinkOut

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