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

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Summary

Official Symbol: EPAS1provided by HGNC
Official Full Name: endothelial PAS domain protein 1provided by HGNC
Primary source: HGNC:3374
See related: Ensembl:ENSG00000116016; HPRD:06787; MIM:603349; Vega:OTTHUMG00000128818
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]

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Genomic context

Location :: 2p21-p16

Sequence :: Chromosome: 2; NC_000002.11 (46524541..46613842)

See EPAS1 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?

Studies indicate that EPAS1, EGLN1 and PPARA genes subject to natural selection in native high-altitude Tibetans.
Title: Genetic determinants of Tibetan high-altitude adaptation.
in the first stages of clear cell renal cell carcinoma formation the stabilization of HIF-1alpha dominates, limiting proliferation, as the HIF-2alpha ratio increases, a more aggressive cell behavior emerges
Title: Epigenetic regulation of HIF-1α in renal cancer cells involves HIF-1α/2α binding to a reverse hypoxia-response element.
Results confirm that HIF-2alpha is tumor suppressive, and suggest that HIF-1alpha may also be tumor suppressive.
Title: Loss of either hypoxia inducible factor 1 or 2 promotes lung cancer cell colonization.
HIF-1alpha expression was an independent predictor of cancer-specific survival in clear cell RCC with sarcomatoid differentiation
Title: Expression of hypoxia inducible factor-1α and 2α in conventional renal cell carcinoma with or without sarcomatoid differentiation.
HIF-1alpha and HIF-2alpha induce transcription of Kaposi's sarcoma-associated herpesvirus LANA.
Title: Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen induction by hypoxia and hypoxia-inducible factors.
overexpression results in increased expression of IL-8 in endothelial cells
Title: Opposite effects of HIF-1α and HIF-2α on the regulation of IL-8 expression in endothelial cells.
Review of the role of mutation in EPAS-1 in human adaptation to high altitude hypobaric hypoxia.
Title: Hypoxia: adapting to high altitude by mutating EPAS-1, the gene encoding HIF-2α.
concluded that HIF2alpha plays an important role in the progression of uveal melanomas possibly by promoting the autocrine loop VEGF-pVEGFR2/KDR, and by enhancing the expression of LDHA gene
Title: Phosphorylated pVEGFR2/KDR receptor expression in uveal melanomas: relation with HIF2α and survival.
Elevated HIF-2alpha expression is associated with chondrosarcoma.
Title: Association of elevated HIF-2α levels with low Beclin 1 expression and poor prognosis in patients with chondrosarcoma.
These results indicate that KLHL20 is a novel player that regulates HIF-2alpha protein expression through mechanisms independent of hypoxia and pVHL.
Title: Kelch-like 20 up-regulates the expression of hypoxia-inducible factor-2α through hypoxia- and von Hippel-Lindau tumor suppressor protein-independent regulatory mechanisms.

Submit: New GeneRIF Correction See all (149)

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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

Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3.

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_001421.2	NP_001659.1	ARNT	BIND	PubMed	Arnt interacts with HLF. This interaction was modeled on a demonstrated interaction between human Arnt and mouse HLF.
NP_001421.2		ARNT	BIND	PubMed	HLF interacts with Arnt. This interaction was modeled on a demonstrated interaction between mouse HLF and human Arnt.
NP_001421.2	NP_000542.1	VHL	BIND	PubMed	The von Hippel-Lindau tumor suppressor protein (pVHL) interacts with Hypoxia inducible factor-2-alpha (HIF-2 alpha)
Q99814	P27540	ARNT	HPRD	PubMed
Q99814	O00327	ARNTL	HPRD	PubMed
Q99814	Q8WYA1	ARNTL2	HPRD	PubMed
Q99814	Q9GZT9	EGLN1	HPRD	PubMed
Q99814	Q96KS0	EGLN2	HPRD	PubMed
Q99814	Q9H6Z9	EGLN3	HPRD	PubMed
Q99814	P60228	EIF3E	HPRD	PubMed
Q99814	Q09472	EP300	HPRD	PubMed
Q99814	P61244	MAX	HPRD	PubMed
Q99814	Q15139	PRKD1	HPRD	PubMed
Q99814	P84022	SMAD3	HPRD	PubMed
Q99814	P40337	VHL	HPRD	PubMed
BioGRID:108348	BioGRID:106821	APC	BioGRID	PubMed	Two-hybrid
BioGRID:108348	BioGRID:106898	ARNT	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:108348	BioGRID:115244	ARNT2	BioGRID	PubMed	Two-hybrid
BioGRID:108348	BioGRID:106899	ARNTL	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:108348	BioGRID:120060	EGLN1	BioGRID	PubMed	Reconstituted Complex
BioGRID:108348	BioGRID:108459	F12	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:108348	BioGRID:109540	HSPA4	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:110319	MAX	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:110340	MCM3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:110344	MCM7	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:110372	MEF2C	BioGRID	PubMed	Two-hybrid
BioGRID:108348	BioGRID:111675	PSMC3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:208024	Ruvbl1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:115563	STUB1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:113188	SUMO1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:108348	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:108348	BioGRID:113269	VHL	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex

Function	Evidence Code	Pubs
DNA binding	IGI Inferred from Genetic Interaction more info	PubMed
histone acetyltransferase binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
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
sequence-specific DNA binding transcription factor activity	IEA Inferred from Electronic Annotation more info
signal transducer activity	IEA Inferred from Electronic Annotation more info
transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
angiogenesis	IEA Inferred from Electronic Annotation more info
blood vessel remodeling	IEA Inferred from Electronic Annotation more info
cell differentiation	IEA Inferred from Electronic Annotation more info
cell maturation	IEA Inferred from Electronic Annotation more info
embryonic placenta development	IEA Inferred from Electronic Annotation more info
erythrocyte differentiation	IEA Inferred from Electronic Annotation more info
hemopoiesis	IEA Inferred from Electronic Annotation more info
lung development	IEA Inferred from Electronic Annotation more info
mitochondrion organization	IEA Inferred from Electronic Annotation more info
multicellular organismal development	IEA Inferred from Electronic Annotation more info
myoblast cell fate commitment	ISS Inferred from Sequence or Structural Similarity more info
norepinephrine metabolic process	IEA Inferred from Electronic Annotation more info
positive regulation of transcription from RNA polymerase II promoter	IGI Inferred from Genetic Interaction more info	PubMed
regulation of heart rate	IEA Inferred from Electronic Annotation more info
regulation of transcription from RNA polymerase II promoter in response to oxidative stress	IEA Inferred from Electronic Annotation more info
response to hypoxia	IDA Inferred from Direct Assay more info	PubMed
response to oxidative stress	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed
surfactant homeostasis	IEA Inferred from Electronic Annotation more info
transcription from RNA polymerase II promoter	TAS Traceable Author Statement more info	PubMed
visual perception	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
nucleus	IEA Inferred from Electronic Annotation more info
transcription factor complex	IDA Inferred from Direct Assay more info	PubMed
transcription factor complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

Preferred Names: endothelial PAS domain-containing protein 1

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

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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_016000.1 RefSeqGene

Range

5001..94302

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001430.4 → NP_001421.2 endothelial PAS domain-containing protein 1

Status: REVIEWED

Source sequence(s)

AC016696, AK123845, BC051338, BM671511, CD109908

Consensus CDS

CCDS1825.1

UniProtKB/TrEMBL

B3KW07

UniProtKB/Swiss-Prot

Q99814

Related

ENSP00000263734, OTTHUMP00000159033, ENST00000263734, OTTHUMT00000250752

Conserved Domains (5) summary

cd00083
Location:21 – 68
Blast Score: 106

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
Blast Score: 183

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 ...

pfam08778
Location:831 – 870
Blast Score: 185

HIF-1a_CTAD; HIF-1 alpha C terminal transactivation domain

pfam08447
Location:254 – 341
Blast Score: 199

PAS_3; PAS fold

pfam11413
Location:516 – 550
Blast Score: 145

HIF-1; Hypoxia-inducible factor-1

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

46524541..46613842

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

46262570..46351445

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC016696.8	AAX93237.1
genomic	AC016912.7	AAY14704.1
genomic	CH471053.2	EAX00255.1
mRNA	AF052094.1	None
mRNA	AK123845.1	BAG53969.1
mRNA	BC015869.1	None
mRNA	BC051338.1	AAH51338.1
mRNA	BM671511.1	None
mRNA	CD109908.1	None
mRNA	U51626.1	AAC51212.1
mRNA	U81984.1	AAB41495.1