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

Summary

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: mouse all
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Genomic context

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
EPAS1-mutated paragangliomas associated with haemoglobin disorders.
Title: EPAS1-mutated paragangliomas associated with haemoglobin disorders.
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.
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.
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.
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.
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.
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.
UBE3B promotes breast cancer progression by antagonizing HIF-2alpha degradation.
Title: UBE3B promotes breast cancer progression by antagonizing HIF-2α degradation.
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	Compare labs

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH71235 (e-PCR)
- UniSTS:28950

RH120495 (e-PCR)
- UniSTS:133660

D2S288 (e-PCR), detects polymorphism
- UniSTS:57394

RH16555 (e-PCR)
- UniSTS:82783

G20740 (e-PCR)
- UniSTS:59750

A006E13 (e-PCR)
- UniSTS:59751

RH122462 (e-PCR)
- UniSTS:135334

Epas1 (e-PCR), detects polymorphism
- UniSTS:499132

STS-M78744 (e-PCR)
- UniSTS:67522

SHGC-33342 (e-PCR)
- UniSTS:46788

D2S1715E (e-PCR)
- UniSTS:150744

D2S246E (e-PCR)
- UniSTS:473077

SGC34838 (e-PCR)
- UniSTS:31228

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

NG_016000.1 RefSeqGene

Range

5006..94296

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

46297407..46386697

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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