Anti-Hypoxia Inducible Factor-3alpha (HIF-3a)

Protein function: Involved in adaptive response to hypoxia. Suppresses hypoxia-inducible expression of HIF1A and EPAS1. Binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters. The complex HIF3A-ARNT activates the transcription of reporter genes driven by HRE. Isoform 2 has a dominant-negative function of inactivating HIF1-mediated transcription. Isoform 2 attenuates the binding of HIF1 to hypoxia-responsive elements (HRE), thus inhibiting HRE-driven transcription. Hypoxia induces down-regulation of isoform 2, leading to activation of HIF1A in hypoxia. Conversely, upon restoring normoxia, the expression of isoform 2 increases and thereby secures an inhibition of HIF1A activity. May be a negative regulator of hypoxia-inducible gene expression in the kidney. May be involved in renal tumorigenesis. Functions as an inhibitor of angiogenesis in the cornea. [The UniProt Consortium]