UNIPROT #

Q99814

PROTEIN NAME

Endothelial PAS domain-containing protein 1

GENE NAME

EPAS1

SYNONYMS

EPAS-1, bHLHe73, HLF, HIF-2-alpha, HIF2-alpha, EPAS1, BHLHE73, HIF2A, MOP2, PASD2

TISSUE SPECIFICITY

Expressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells.

POST-TRANSLATIONAL MODIFICATION

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).; 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.

SUBCELLULAR LOCATION

Nucleus. Nucleus speckle. Note=Colocalizes with HIF3A in the nucleus and speckles.

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 (By similarity). 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).