Human Gene EPAS1 (uc002ruv.3) Description and Page Index
Description: Homo sapiens endothelial PAS domain protein 1 (EPAS1), mRNA. RefSeq Summary (NM_001430): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: SRR1660803.156330.1, SRR1660803.67820.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000263734.5/ ENSP00000263734.3 RefSeq Select criteria :: based on conservation, expression ##RefSeq-Attributes-END## Transcript (Including UTRs) Position: hg19 chr2:46,524,541-46,613,842 Size: 89,302 Total Exon Count: 16 Strand: + Coding Region Position: hg19 chr2:46,525,051-46,611,799 Size: 86,749 Coding Exon Count: 16
ID:EPAS1_HUMAN DESCRIPTION: RecName: Full=Endothelial PAS domain-containing protein 1; Short=EPAS-1; AltName: Full=Basic-helix-loop-helix-PAS protein MOP2; AltName: Full=Class E basic helix-loop-helix protein 73; Short=bHLHe73; AltName: Full=HIF-1-alpha-like factor; Short=HLF; AltName: Full=Hypoxia-inducible factor 2-alpha; Short=HIF-2-alpha; Short=HIF2-alpha; AltName: Full=Member of PAS protein 2; AltName: Full=PAS domain-containing protein 2; FUNCTION: Transcription 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. SUBUNIT: Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT. Interacts with CREBBP (By similarity). Interacts with EGLN1. Interacts with VHL. INTERACTION: Q96RK4:BBS4; NbExp=2; IntAct=EBI-447470, EBI-1805814; P60228:EIF3E; NbExp=10; IntAct=EBI-447470, EBI-347740; P61244:MAX; NbExp=2; IntAct=EBI-447470, EBI-751711; SUBCELLULAR LOCATION: Nucleus (Potential). TISSUE SPECIFICITY: Expressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells. 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). PTM: In normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation (By similarity). PTM: Phosphorylated on multiple sites in the CTAD (By similarity). PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains (By similarity). DISEASE: Defects in EPAS1 are the cause of familial erythrocytosis type 4 (ECYT4) [MIM:611783]. ECYT4 is an autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin concentration and hematocrit, and normal platelet and leukocyte counts. SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. SIMILARITY: Contains 1 PAC (PAS-associated C-terminal) domain. SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains.
Genetic Association Studies of Complex Diseases and Disorders
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q99814
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.