ID:IRF3_HUMAN DESCRIPTION: RecName: Full=Interferon regulatory factor 3; Short=IRF-3; FUNCTION: Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and 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, becomes 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. ENZYME REGULATION: 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. SUBUNIT: Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF7. Interacts with CREBBP. May interact with MAVS. Interacts with IKBKE and TBK1. Interacts with TICAM1 and TICAM2. Interacts with rotavirus A NSP1 (via C-terminus); this interaction leads to the proteasome-dependent degradation of IRF3. Interacts with RBCK1. Interacts with TRIM21. Interacts with HERC5. INTERACTION: Self; NbExp=9; IntAct=EBI-2650369, EBI-2650369; Q92793:CREBBP; NbExp=3; IntAct=EBI-2650369, EBI-81215; Q9Y5Q3:MAFB; NbExp=4; IntAct=EBI-2650369, EBI-3649340; P06400:RB1; NbExp=2; IntAct=EBI-2650369, EBI-491274; P28749:RBL1; NbExp=2; IntAct=EBI-2650369, EBI-971402; O43765:SGTA; NbExp=3; IntAct=EBI-2650369, EBI-347996; Q9UHD2:TBK1; NbExp=4; IntAct=EBI-2650369, EBI-356402; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. 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. TISSUE SPECIFICITY: Expressed constitutively in a variety of tissues. PTM: Constitutively phosphorylated on many serines residues. C- terminal serine/threonine cluster is phosphorylated in response of induction by IKBKE and TBK1. Ser-385 and Ser-386 may be specifically phosphorylated in response to induction. An alternate model propose that the five serine/threonine residues between 396 and 405 are phosphorylated in response to a viral infection. Phosphorylation, and subsequent activation of IRF3 is inhibited by vaccinia virus protein E3. PTM: Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation. PTM: ISGylated by HERC5 resulting in sustained IRF3 activation and in the inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The phosphorylation state of IRF3 does not alter ISGylation. SIMILARITY: Belongs to the IRF family. SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding domain.
ModBase Predicted Comparative 3D Structure on Q14653
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Other Names for This Gene
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Methods, Credits, and Use Restrictions
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