InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: HIF3A

Summary

InnateDB Protein

IDBP-58496.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

HIF3A

Protein Name

hypoxia inducible factor 3, alpha subunit

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000366898

InnateDB Gene

IDBG-58490 (HIF3A)

Protein Structure

UniProt Annotation

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). {ECO:0000250}.

Subcellular Localization

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). {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in kidney. Expressed abundantly in lung epithelial cells. Expression is regulated in an oxygen- dependent manner. {ECO:0000269PubMed:11573933}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 7 experimentally validated interaction(s) in this database.

Experimentally validated
Total	7 [view]
Protein-Protein	5 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003713	transcription coactivator activity
GO:0003714	transcription corepressor activity
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0046983	protein dimerization activity

Biological Process

GO:0001666	response to hypoxia
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:0007165	signal transduction
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0071456	cellular response to hypoxia

Cellular Component

GO:0005654	nucleoplasm
GO:0005829	cytosol

Protein Structure and Domains

PDB ID

InterPro

IPR000014 PAS domain
IPR001610 PAC motif
IPR011598 Myc-type, basic helix-loop-helix (bHLH) domain
IPR013655 PAS fold-3
IPR013767 PAS fold
IPR021537 Hypoxia-inducible factor, alpha subunit

PFAM

PF13188
PF13426
PF00010
PF08447
PF00989
PF11413

PRINTS

PIRSF

SMART

SM00091
SM00086
SM00353

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9Y2N7