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Details on Person UniProt:P97481 Epas1
| Class:Id | ReferenceGeneProduct:97788 |
|---|---|
| _chainChangeLog | chain:1-874 added on Fri February 6 2015 |
| _displayName | UniProt:P97481 Epas1 |
| _timestamp | 2023-11-03 18:28:55 |
| chain | chain:1-874 |
| checksum | A6FFA490AE43640C |
| comment | FUNCTION 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 (PubMed:26245371). 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 APEX seems to activate CTAD (By similarity).SUBUNIT Interacts with HIF3A isoform 2 (PubMed:21546903). Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:26245371). Interacts with CREBBP (PubMed:11983697). Interacts with EGLN1. Interacts with VHL (By similarity).INTERACTION Colocalizes with HIF3A isoform 2 in the nucleus and speckles.TISSUE SPECIFICITY Expressed in most tissues, with highest levels in lung, followed by heart, kidney, brain and liver. Predominantly expressed in endothelial cells. Also found in smooth muscle cells of the uterus, neurons, and brown adipose tissue. High expression in embryonic choroid plexus and kidney glomeruli.DEVELOPMENTAL STAGE In day 11 embryo, expression is almost exclusively seen in endothelial cells of the intersegmental blood vessels separating the somites, the atrial and ventricular chambers of the heart, and the dorsal aorta. High expression also occurs in extraembryonic membranes. In the developing brain of day 13 embryo, endothelial cells of the highly vascularized choroid plexus contain high levels of EPAS1.PTM In normoxia, is probably hydroxylated on Pro-405 and Pro-530 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-851 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.PTM Phosphorylated on multiple sites in the CTAD.PTM The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. |
| description | recommendedName: Endothelial PAS domain-containing protein 1 shortName: EPAS-1 alternativeName: HIF-1-alpha-like factor shortName: HLF shortName: mHLF alternativeName: HIF-related factor shortName: HRF alternativeName: Hypoxia-inducible factor 2-alpha shortName: HIF-2-alpha shortName: HIF2-alpha |
| geneName | Epas1 Hif2a |
| identifier | P97481 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Activator Angiogenesis Developmental protein Differentiation Direct protein sequencing DNA-binding Hydroxylation Nucleus Phosphoprotein Reference proteome Repeat Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:6807888] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 |
| name | Epas1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | EPAS1_MOUSE O08787 O55046 |
| sequenceLength | 874 |
| species | [Species:48892] Mus musculus |
| (referenceEntity) | [EntityWithAccessionedSequence:9666411] Epas1 [cytosol] [Mus musculus] |
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No pathways have been reviewed or authored by UniProt:P97481 Epas1 (97788)
