Homo sapiens Protein: IRF3
InnateDB Protein IDBP-63231.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IRF3
Protein Name interferon regulatory factor 3
Species Homo sapiens
Ensembl Protein ENSP00000366339
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.
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
Predicted by orthology
Total 21 [view]
Gene Ontology

Molecular Function
Accession GO Term
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
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
Protein Structure and Domains
InterPro IPR008984 SMAD/FHA domain
IPR019471 Interferon regulatory factor-3
PFAM PF10401
Post-translational Modifications
SwissProt Q14653
PhosphoSite PhosphoSite-Q14653
UniProt Splice Variant
Entrez Gene 3661
UniGene Hs.75254
RefSeq NP_001184054
OMIM 603734
HPRD 04769
EMBL AB102884 AB102886 AB102887 AC011495 AK292027 AK314421 BC000660 BC071721 CH471177 U86636 Z56281
GenPept AAC68818 AAH00660 AAH71721 BAD89413 BAD89415 BAD89416 BAF84716 BAG37040 CAA91227 EAW52510