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hypoxia inducible factor 3 alpha subunit(HIF3A) Homo sapiens The protein encoded by this gene is the alpha-3 subunit of one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 subunits. It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2011],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 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, the expression of isoform 4 increases and thereby secure an inhibition of HIF1A activity. Isoform 4 may be a negative regulator of hypoxia-inducible gene expression in the kidney and may be involved in renal tumorigenesis. Functions as an inhibitor of angiogenesis in the cornea.,induction:Strongly induced by hypoxia (1% O(2)), both at the level of protein and mRNA due to an increase in protein stability and transcriptional activation.,online information:Hypoxia inducible factor entry,PTM:In normoxia, hydroxylated on Pro-492 in the oxygen-dependent degradation domain (ODD) by PHD. The hydroxylated proline promotes interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation.,similarity:Contains 1 basic helix-loop-helix (bHLH) domain.,similarity:Contains 2 PAS (PER-ARNT-SIM) domains.,subcellular location:In the nuclei of all periportal and perivenous hepatocytes. In the distal perivenous zone, detected in the cytoplasm of the hepatocytes.,subunit:Heterodimerizes with ARNT. Interacts via the oxygen-dependent degradation domain (ODD) with the beta domain of VHL.,tissue specificity:Expressed in kidney. Expressed abundantly in lung epithelial cells. Expression is regulated in an oxygen-dependent manner.,

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