InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: IRF3

Summary

InnateDB Protein

IDBP-63229.6

Last Modified

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

Gene Symbol

IRF3

Protein Name

interferon regulatory factor 3

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000366344

InnateDB Gene

IDBG-63225 (IRF3)

Protein Structure

UniProt Annotation

Function

Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:10805757}. Nucleus {ECO:0000269PubMed:10805757}. Note=Shuttles between cytoplasmic and nuclear compartments, with export being the prevailing effect. When activated, IRF3 interaction with CREBBP prevents its export to the cytoplasm.

Disease Associations

Tissue Specificity

Expressed constitutively in a variety of tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 156 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	156 [view]
Protein-Protein	105 [view]
Protein-DNA	51 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000975	regulatory region DNA binding
GO:0003677	DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003712	transcription cofactor activity
GO:0005515	protein binding
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity

Biological Process

GO:0002224	toll-like receptor signaling pathway
GO:0002756	MyD88-independent toll-like receptor signaling pathway
GO:0006355	regulation of transcription, DNA-templated
GO:0006366	transcription from RNA polymerase II promoter
GO:0006915	apoptotic process
GO:0006974	cellular response to DNA damage stimulus
GO:0016032	viral process
GO:0019221	cytokine-mediated signaling pathway
GO:0032480	negative regulation of type I interferon production
GO:0032481	positive regulation of type I interferon production
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0034138	toll-like receptor 3 signaling pathway
GO:0034142	toll-like receptor 4 signaling pathway
GO:0035666	TRIF-dependent toll-like receptor signaling pathway
GO:0039530	MDA-5 signaling pathway
GO:0045087	innate immune response (InnateDB)
GO:0051607	defense response to virus
GO:0060333	interferon-gamma-mediated signaling pathway
GO:0060337	type I interferon signaling pathway
GO:0071888	macrophage apoptotic process