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Description

Endothelial PAS domain-containing protein 1 (UniProt: Q99814, also known as EPAS-1, Basic-helix-loop-helix-PAS protein MOP2, Class E basic helix-loop-helix protein 73, bHLHe73, HIF-1-alpha-like factor, HLF, Hypoxia-inducible factor 2-alpha, HIF-2-alpha, HIF2-alpha, Member of PAS protein 2, PAS domain-containing protein 2) is encoded by the EPAS1 (also known as BHLHE73, HIF2A, MOP2, PASD2) gene (Gene ID: 2034) in human. HIF-2a is a transcription factor that is involved in the induction of oxygen regulated genes. It displays about 48% identity to HIF-1a and is widely expressed with high expression observed in endothelial cells. Its levels are strongly induced by hypoxic conditions. HIF- 2a dimerizes with ARNT, via amino acid sequence 171-192, and this heterodimer binds to core DNA sequence 5&prime,-TACGTG-3&prime, within the hypoxia response element (HRE) of target gene promoters. Its DNA-binding region is localized to amino acids 26-53. It has two PAS (Per-Arnt-Sim) domains (aa 84-154 and 23-300). HIF-2a regulates the vascular endothelial growth factor (VEGF) expression and is implicated in the development of blood vessels and the tubular system of lung and is also involved in the formation of the endothelium that gives rise to the blood brain barrier. Under normoxic conditions it is hydroxylated on proline 405 and 531 prolyl hydroxylase 1 and 2 and the hydroxylated form undergoes rapid ubiquitination and proteasomal degradation. However, under hypoxic conditions, proline hydroxylation is impaired and HIF- 2a is stabilized. Mutations in EPAS1 gene are known to cause familial type erythrocytosis that is characterized by elevated serum hemoglobin and hematocrit with normal platelet and leukocyte counts. (Ref.: Strowitzki, MJ., et al. (2019). Cells. 8(5): 384, Wiesener, MS., et al. (1998). Blood. 92(7), 2260-2268).