hypoxia-inducible factor 3 alpha (HIF-3 alpha, HIF3 alpha 1, member of PAS protein 7, basic-helix-loop-helix-PAS protein MOP7, inhibitory PAS domain protein, IPAS, HIF3A, MOP7)

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Function

role in adaptive response to hypoxia
suppresses hypoxia-inducible expression of HIF1A & EPAS1
binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters
the complex HIF3A-ARNT activates transcription of reporter genes driven by HRE
isoform 4 has a dominant-negative function of inactivating HIF1A-mediated transcription
isoform 4 attenuates the binding of HIF1A to hypoxia-responsive elements (HRE), thus inhibiting HRE- driven transcription
hypoxia induces down-regulation of isoform 4,leading to activation of HIF1A in hypoxia
conversely, upon restoring normoxia, expression of isoform 4 increases thus restoring inhibition of HIF1A activity
isoform 4 may be a negative regulator of hypoxia-inducible gene expression in kidney
functions as an inhibitor of angiogenesis in cornea
heterodimerizes with ARNT
interacts via the oxygen-dependent degradation domain (ODD) with the beta domain of VHL

in normoxia, hydroxylated on Pro-492 in the O2-dependent degradation domain (ODD) by PHD; the hydroxylated Pro promotes interaction with VHL, initiating rapid ubiquitination & subsequent proteasomal degradation

expressed in kidney
expressed abundantly in lung epithelial cells
expression is regulated in an oxygen-dependent manner
strongly induced by hypoxia (1% O2, both at mRNA & protein level due to transcriptional activation & an increase in protein stability