Post Translational Modifications | 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. In normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation. Phosphorylated on multiple sites in the CTAD. The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains. |
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. 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. |
Protein Name | Endothelial Pas Domain-Containing Protein 1Epas-1Basic-Helix-Loop-Helix-Pas Protein Mop2Class E Basic Helix-Loop-Helix Protein 73Bhlhe73Hif-1-Alpha-Like FactorHlfHypoxia-Inducible Factor 2-AlphaHif-2-AlphaHif2-AlphaMember Of Pas Protein 2Pas Domain-Containing Protein 2 |
Database Links | Reactome: R-HSA-1234158Reactome: R-HSA-1234174Reactome: R-HSA-1234176Reactome: R-HSA-452723Reactome: R-HSA-8849473Reactome: R-HSA-8951664Reactome: R-HSA-9664873 |
Cellular Localisation | NucleusNucleus SpeckleColocalizes With Hif3a In The Nucleus And Speckles |
Alternative Protein Names | Endothelial Pas Domain-Containing Protein 1 proteinEpas-1 proteinBasic-Helix-Loop-Helix-Pas Protein Mop2 proteinClass E Basic Helix-Loop-Helix Protein 73 proteinBhlhe73 proteinHif-1-Alpha-Like Factor proteinHlf proteinHypoxia-Inducible Factor 2-Alpha proteinHif-2-Alpha proteinHif2-Alpha proteinMember Of Pas Protein 2 proteinPas Domain-Containing Protein 2 proteinEPAS1 proteinBHLHE73 proteinHIF2A proteinMOP2 proteinPASD2 protein |
Information sourced from Uniprot.org