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FLASH GENE
Symbol IRF3 contributors: mct/pgu - updated : 19-10-2016
HGNC name interferon regulatory factor 3
HGNC id 6118
EXPRESSION
Type widely
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveintestinelarge intestinerectum  
Lymphoid/Immunespleen   highly
 thymus   highly
Nervousbrainbasal nucleicaudate nucleus  
 nervecranial nerve  highly
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text kidney
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a DNA-binding N-terminal domain
  • a domain of association with EP300 several phosphorylation sites controlling IRF3 dimer formation,
  • a C terminal transactivation domain that participates in the auto-inhibition of IRF3 activity
  • a tryptophan pentad repeat DNA-binding domain
  • conjugated PhosphoP
    mono polymer homomer , dimer
    HOMOLOGY
    interspecies homolog to murine Irf3
    Homologene
    FAMILY
  • interferon regulatory transcription factor (IRF) family
  • CATEGORY regulatory , transcription factor , signaling cytokine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,chromatin/chromosome
    text cytoplasmic translocated to nucleus after viral infection when activated by CREBBP
    basic FUNCTION
  • activating transcription by complex formation with other transcriptional factors (possibly members of the stat family)
  • mediating a specific gene program responsible for innate antiviral responses
  • plays a critical role in the activation of interferon genes upon virus infection
  • requirement for the TBK1-IRF3 pathway in host defense against a DNA virus infection
  • regulates expression of type I interferon-beta and plays an important role in antiviral immunity
  • plays a crucial role in host defense against viral and microbial infection as well as in cell growth regulation
  • plays a central role in the transcription of cellular antiviral genes, including IFNB
  • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the double stranded RNA, activated factor DRAF1 with CREBBP and EP300
  • complexing with TBK1 and playing a role in innate immune reactions
  • phosphorylated IRF3 forms a homodimer and translocates into the nucleus, recruiting coactivators such as EP300
  • phosphorylation of Ser/Thr residues which increases the negative charge of IRF3, resulting in its dimerization and association with DNA
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding IFNA by ISRE (IFN stimulated response element)
  • TAK1-JNK cascade is required for IRF3 function
  • TRIM21 (tripartite motif-containing 21) is significantly induced and interacts with IRF3 upon RNA virus infection
  • possible function for TRAF5 in mediating the activation of IRF3 and NF-kappaB downstream of MAVS through the recruitment of IKBKG
  • interaction with HERC5 (positive regulator of antiviral innate immune responses, which maintains IRF3 stability via catalyzing ISGylation of IRF3)
  • NR2C2 can stimulate IRF3 phosphorylation via JNK
  • requirement for IRF3, a master regulator of IFNB1 production, as a previously un-indentified interaction partner of IRF8
  • interaction with E2F1 (E2F1 negatively regulates IRF3 transcription through binding to the E2F consensus binding site)
  • interacting with CASP8 (CASP8 catalyzes an essential intermediate step in the ubiquitination and proteasome-mediated degradation of IRF3)
  • basal expression level of IRF3 is regulated by transcription factors SP1 and SP3
  • MRE11A physically interacted with dsDNA in the cytoplasm and was required for activation of TMEM173 and IRF3
  • DDX3X is a scaffolding adaptor that directly facilitates phosphorylation of IRF3 by IKBKE and might thus be involved in pathway-specific activation of IRF3
  • FOXO1 interacted with IRF3 in a viral infection-dependent manner and promoted K48-linked polyubiquitination and degradation of IRF3 in the cytosol
  • phosphorylation of TMEM173 on S366 strongly prevents the transcriptional activity of IRF3
  • CGAS-induced activation of TMEM173 also involves the activation of the NFKB1 and IRF3 pathways
  • endogenous optineurin is dispensable for NFKB activation but necessary for optimal IRF3 activation in immune cells
  • TBK1 is a downstream kinase controlling dsDNA-mediated IRF3 and NFKB1 signaling dependent on TMEM173
  • exerts its antiviral activity mainly through governing its downstream regulators DDX58 and IFIH1 by gene splicing to activate IRF3 and induce classical ISG expression independent of the JAT-STAT signaling pathway
  • HAVCR2-signaling inhibited phosphorylation of IRF3, a TLR4 downstream transcriptional factor regulating macrophage polarization
  • SNRNP200 promotes viral RNA sensing and IRF3 activation through the ability of its N-terminal Sec63 domain (Sec63-1) to bind RNA and to interact with TBK1
  • IRF3 is an important regulator of ORMDL3 induction following RSV infection by binding directly to the promoter of ORMDL3, which may be implicated in the inflammatory and immune reactions involved in bronchiolitis and wheezing diseases
  • IRF3 and IRF7 bind to many interferon-stimulated response element (ISRE)-type sites in the virus-response elements (VREs) of IFN promoters
  • ANKRD1 is involved in IRF3-mediated antiviral innate immune signaling pathways
  • TMEM173 promoted the transcriptional activity of ORMDL3, which was significantly associated with increased levels of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 6 (STAT6)
  • cell & other
    REGULATION
    activated by TLR3
    TLR4
    by phosphorylation of Ser/Thr residues clustered in its C-terminal domain
    the ribonucleic acid sensor DDX58 (activation restricted by caspase-8-mediated cleavage of the RIPK1 protein, which resulted in conversion of RIPK1 from a signaling enhancer to a signaling inhibitor)
    Other CASP8 catalyzes a specific cleavage of IRF3, a step that is required for its subsequent proteasome-mediated degradation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    aberrant expression in lung cancer
    tumoral     --other  
    aberrant splicing of IRF3 in hepatocellular carcinoma (HCC) contributes to the defect in IFN-mediated antiviral defenses
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Irf3(-/-) mice showed a pathogen-specific increase in acute mortality, bacterial burden, abscess formation and renal damage compared to wild type mice