InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Hif3a

Summary

InnateDB Protein

IDBP-147496.6

Last Modified

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

Gene Symbol

Hif3a

Protein Name

hypoxia inducible factor 3, alpha subunit

Synonyms

bHLHe17; Ipas; MOP7; NEPAS;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000048248

InnateDB Gene

IDBG-147492 (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 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 (By similarity). 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. {ECO:0000250, ECO:0000269PubMed:9840812}.

Subcellular Localization

Nucleus {ECO:0000255PROSITE- ProRule:PRU00981}. Cytoplasm {ECO:0000250}.

Disease Associations

Tissue Specificity

Expressed in lung, brain, heart and kidney. Isoform 2 is expressed predominantly in the eye and at lower levels in the cerebellum and the cerebrum. Highly expressed in the epithelial cell layer of the cornea with lower expression in the layers of ganglion cells, inner nuclear cells, and rods and cones of the retina. In the cerebellum expressed only the Purkinje cell layer. {ECO:0000269PubMed:11734856, ECO:0000269PubMed:9840812}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 1 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	1 [view]
Protein-Protein	1 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

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:0006366	transcription from RNA polymerase II promoter
GO:0007165	signal transduction

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

MGI:1859778

InterPro

IPR000014 PAS domain
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
SM00353

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q0VBL6