ID:HIF3A_HUMAN DESCRIPTION: RecName: Full=Hypoxia-inducible factor 3-alpha; Short=HIF-3-alpha; Short=HIF3-alpha; AltName: Full=Basic-helix-loop-helix-PAS protein MOP7; AltName: Full=Class E basic helix-loop-helix protein 17; Short=bHLHe17; AltName: Full=HIF3-alpha-1; AltName: Full=Inhibitory PAS domain protein; Short=IPAS; AltName: Full=Member of PAS protein 7; AltName: Full=PAS domain-containing protein 7; 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 (By similarity). SUBUNIT: Heterodimerizes with ARNT. Interacts via the oxygen- dependent degradation domain (ODD) with the beta domain of VHL. SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=In the nuclei of all periportal and perivenous hepatocytes. In the distal perivenous zone, detected in the cytoplasm of the hepatocytes (By similarity). TISSUE SPECIFICITY: Expressed in kidney. Expressed abundantly in lung epithelial cells. Expression is regulated in an oxygen- dependent manner. 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. 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 bHLH (basic helix-loop-helix) domain. SIMILARITY: Contains 2 PAS (PER-ARNT-SIM) domains. WEB RESOURCE: Name=Wikipedia; Note=Hypoxia inducible factor entry; URL="http://en.wikipedia.org/wiki/Hypoxia_inducible_factor";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9Y2N7
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0003677 DNA binding GO:0003700 transcription factor activity, sequence-specific DNA binding GO:0003713 transcription coactivator activity GO:0003714 transcription corepressor activity GO:0046983 protein dimerization activity
Biological Process: GO:0001525 angiogenesis GO:0001666 response to hypoxia GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006915 apoptotic process GO:0007275 multicellular organism development GO:0043687 post-translational protein modification GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0061418 regulation of transcription from RNA polymerase II promoter in response to hypoxia GO:1903507 negative regulation of nucleic acid-templated transcription GO:0071456 cellular response to hypoxia
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
