InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Irf3

Summary

InnateDB Protein

IDBP-265826.6

Last Modified

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

Gene Symbol

Irf3

Protein Name

interferon regulatory factor 3

Synonyms

C920001K05Rik; IRF-3;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000103466

InnateDB Gene

IDBG-181123 (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. {ECO:0000269PubMed:15800576}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. 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 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 41 experimentally validated interaction(s) in this database.
They are also associated with 79 interaction(s) predicted by orthology.

Experimentally validated
Total	41 [view]
Protein-Protein	27 [view]
Protein-DNA	12 [view]
Protein-RNA	2 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	79 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000975	regulatory region DNA binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0005515	protein binding
GO:0042803	protein homodimerization activity
GO:0044212	transcription regulatory region DNA binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0009617	response to bacterium
GO:0031663	lipopolysaccharide-mediated signaling pathway
GO:0032496	response to lipopolysaccharide
GO:0032727	positive regulation of interferon-alpha production
GO:0032728	positive regulation of interferon-beta production
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330	response to exogenous dsRNA
GO:0045087	innate immune response (InnateDB)
GO:0045351	type I interferon biosynthetic process
GO:0045358	negative regulation of interferon-beta biosynthetic process
GO:0050689	negative regulation of defense response to virus by host
GO:0050715	positive regulation of cytokine secretion
GO:0051607	defense response to virus
GO:0060340	positive regulation of type I interferon-mediated signaling pathway
GO:0071359	cellular response to dsRNA
GO:0097300	programmed necrotic cell death