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MGP000959

UniProt Annotations

Entry Information
Gene Nameendothelial PAS domain protein 1
Protein EntryEPAS1_HUMAN
UniProt IDQ99814
SpeciesHuman
Comments
Comment typeDescription
DiseaseErythrocytosis, 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.
FunctionTranscription 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.
InteractionQ96RK4:BBS4; NbExp=2; IntAct=EBI-447470, EBI-1805814; Q9GZT9:EGLN1; NbExp=2; IntAct=EBI-447470, EBI-1174818; P60228:EIF3E; NbExp=10; IntAct=EBI-447470, EBI-347740; P61244:MAX; NbExp=2; IntAct=EBI-447470, EBI-751711; P84022:SMAD3; NbExp=2; IntAct=EBI-447470, EBI-347161; P08047:SP1; NbExp=2; IntAct=EBI-447470, EBI-298336; P40818:USP8; NbExp=2; IntAct=EBI-447470, EBI-1050865;
PtmIn normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. {ECO:0000250}.
PtmIn 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). {ECO:0000250}.
PtmPhosphorylated on multiple sites in the CTAD. {ECO:0000250}.
PtmThe iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. {ECO:0000250}.
SimilarityContains 1 bHLH (basic helix-loop-helix) domain. {ECO:0000255|PROSITE-ProRule:PRU00981}.
SimilarityContains 1 PAC (PAS-associated C-terminal) domain. {ECO:0000305}.
SimilarityContains 2 PAS (PER-ARNT-SIM) domains. {ECO:0000255|PROSITE-ProRule:PRU00140}.
Subcellular LocationNucleus {ECO:0000255|PROSITE- ProRule:PRU00981}.
SubunitEfficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT. Interacts with CREBBP (By similarity). Interacts with EGLN1. Interacts with VHL. {ECO:0000250, ECO:0000269|PubMed:10202154, ECO:0000269|PubMed:19208626}.
Tissue SpecificityExpressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells.
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