EPAS1

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]

Full Name

EPAS1

Research Area

Transcription factor involved in the induction of oxygen regulated genes. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity).

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 requires recruitment of transcriptional coactivators such as CREBBP and probably EP300. Interaction with redox regulatory protein APEX1 seems to activate CTAD (By similarity).

Biological Process

Angiogenesis Source: UniProtKB-KW
Blood vessel remodeling Source: Ensembl
Cell maturation Source: Ensembl
Cellular response to hypoxia Source: UniProtKB
Embryonic placenta development Source: Ensembl
Erythrocyte differentiation Source: Ensembl
Iron ion homeostasis Source: Ensembl
Lung development Source: Ensembl
Mitochondrion organization Source: Ensembl
Myoblast fate commitment Source: BHF-UCL
Norepinephrine metabolic process Source: Ensembl
Positive regulation of cold-induced thermogenesis Source: YuBioLab
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Regulation of heart rate Source: Ensembl
Regulation of protein neddylation Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central
Regulation of transcription from RNA polymerase II promoter in response to oxidative stress Source: Ensembl
Response to hypoxia Source: MGI
Signal transduction Source: ProtInc
Surfactant homeostasis Source: Ensembl
Visual perception Source: Ensembl

Cellular Location

Nucleus; Nucleus speckle. Colocalizes with HIF3A in the nucleus and speckles.

Involvement in disease

Erythrocytosis, familial, 4 (ECYT4):
An autosomal dominant disorder characterized by elevated serum hemoglobin and hematocrit, and normal platelet and leukocyte counts.

PTM

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).By similarity
In normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.By similarity
Phosphorylated on multiple sites in the CTAD.By similarity
The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.By similarity