IRF3 - Interferon regulatory factor 3 - human protein (Function)
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IRF3 »  Interferon regulatory factor 3  (IRF-3)
Gene name:  IRF3
Family name: IRF
Entry whose protein(s) existence is based on evidence at protein level
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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.  
  • CuratedUniProtKB
GO molecular function 
DNA bindingdefinition[GO:0003677]  
Identical protein bindingdefinition[GO:0042802]  
  • IPIIntAct
Protein bindingdefinition[GO:0005515]  
  • IPIUniProtKB
  • IPIIntAct
Protein homodimerization activitydefinition[GO:0042803]  
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700] silver  
  • IEAInterPro 2 GO
Transcription cofactor activitydefinition[GO:0003712]  
Transcription regulatory region DNA bindingdefinition[GO:0044212] silver  
  • IEAOrtholog Compara
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • TASUniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
  • TASUniProtKB
Cellular response to dsRNAdefinition[GO:0071359] silver  
  • IEAOrtholog Compara
Defense response to virusdefinition[GO:0051607]  
  • ISSOrtholog Curator
Lipopolysaccharide-mediated signaling pathwaydefinition[GO:0031663] silver  
  • IEAOrtholog Compara
Macrophage apoptotic processdefinition[GO:0071888]  
  • TASUniProtKB
MDA-5 signaling pathwaydefinition[GO:0039530]  
  • TASUniProtKB
Negative regulation of defense response to virus by hostdefinition[GO:0050689] silver  
  • IEAOrtholog Compara
Negative regulation of interferon-beta biosynthetic processdefinition[GO:0045358] silver  
  • IEAOrtholog Compara
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122] silver  
  • IEAOrtholog Compara
Positive regulation of cytokine secretiondefinition[GO:0050715] silver  
  • IEAOrtholog Compara
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123] silver  
  • IEAOrtholog Compara
Positive regulation of interferon-alpha productiondefinition[GO:0032727]  
  • ISSOrtholog Curator
Positive regulation of interferon-beta productiondefinition[GO:0032728]  
  • TASUniProtKB
  • ISSOrtholog Curator
Positive regulation of type I interferon-mediated signaling pathwaydefinition[GO:0060340] silver  
  • IEAOrtholog Compara
Response to exogenous dsRNAdefinition[GO:0043330] silver  
  • IEAOrtholog Compara
Transcription from RNA polymerase II promoterdefinition[GO:0006366]  
Type I interferon biosynthetic processdefinition[GO:0045351] silver  
  • IEAOrtholog Compara
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB KW
Enzymatic activity 
It is regulated in the following manner
In the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes.  
  • CuratedUniProtKB
According to KEGG, this protein belongs to the following pathways:
Cytosolic DNA-sensing pathway  hsa04623+3661  
Hepatitis C  hsa05160+3661  
Herpes simplex infection  hsa05168+3661  
Influenza A  hsa05164+3661  
Measles  hsa05162+3661  
Pertussis  hsa05133+3661  
RIG-I-like receptor signaling pathway  hsa04622+3661  
Toll-like receptor signaling pathway  hsa04620+3661  
According to Reactome, this protein belongs to the following pathways:
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon  REACT_25148  
Factors involved in megakaryocyte development and platelet production  REACT_24970  
Interferon alpha/beta signaling  REACT_25162  
Interferon gamma signaling  REACT_25078  
IRF3 mediated activation of type 1 IFN  REACT_118811  
IRF3-mediated induction of type I IFN  REACT_163993  
ISG15 antiviral mechanism  REACT_115831  
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production  REACT_163743  
Negative regulators of RIG-I/MDA5 signaling  REACT_25271  
Regulation of innate immune responses to cytosolic DNA  REACT_163977  
TRAF3-dependent IRF activation pathway  REACT_25026  
TRAF6 mediated IRF7 activation  REACT_24938  


Biological process 
Antiviral defense  definition   [KW-0051]
Host-virus interaction  definition   [KW-0945]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Technical term 
Reference proteome  definition   [KW-1185]

Further external links

GeneWiki: IRF3
GenomeRNAi: 3661
PRO: PR:Q14653