Human Gene EPAS1 (ENST00000263734.5) from GENCODE V44
Description: Homo sapiens endothelial PAS domain protein 1 (EPAS1), mRNA. (from RefSeq NM_001430) 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]. Gencode Transcript: ENST00000263734.5 Gencode Gene: ENSG00000116016.14 Transcript (Including UTRs) Position: hg38 chr2:46,297,407-46,386,697 Size: 89,291 Total Exon Count: 16 Strand: + Coding Region Position: hg38 chr2:46,297,912-46,384,660 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.
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.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0005515 protein binding GO:0008134 transcription factor binding GO:0035035 histone acetyltransferase binding GO:0046982 protein heterodimerization activity GO:0046983 protein dimerization activity GO:0043565 sequence-specific DNA binding
Biological Process: GO:0001525 angiogenesis GO:0001666 response to hypoxia GO:0001892 embryonic placenta development GO:0001974 blood vessel remodeling GO:0002027 regulation of heart rate GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006366 transcription from RNA polymerase II promoter GO:0006979 response to oxidative stress GO:0007005 mitochondrion organization GO:0007165 signal transduction GO:0007275 multicellular organism development GO:0007601 visual perception GO:0030097 hemopoiesis GO:0030154 cell differentiation GO:0030218 erythrocyte differentiation GO:0030324 lung development GO:0042415 norepinephrine metabolic process GO:0043129 surfactant homeostasis GO:0043619 regulation of transcription from RNA polymerase II promoter in response to oxidative stress GO:0043687 post-translational protein modification GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048469 cell maturation GO:0048625 myoblast fate commitment GO:0055072 iron ion homeostasis GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:0071456 cellular response to hypoxia
US Server
