IRF3

IRF3 ;
Interferon regulatory factor 3 ;
IRF-3

function:Mediates interferon-stimulated response element (ISRE) promoter activation. Functions as a molecular switch for antiviral activity. DsRNA generated during the course of an viral infection leads to IRF3 phosphorylation on the C-terminal serine/threonine cluster. This induces a conformational change , leading to its dimerization , nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1) , a complex which activates the transcription of genes under the control of ISRE. The complex binds to the IE and PRDIII regions on the IFN-alpha and IFN-beta promoters respectively. IRF-3 does not have any transcription activation domains. ,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. ,similarity:Belongs to the IRF family. ,similarity:Contains 1 tryptophan pentad repeat DNA-binding domain. ,subcellular location:Shuttles between cytoplasmic and nuclear compartments , with export being the prevailing effect. When activated , IRF3 interaction with CREBBP prevents its export to the cytoplasm. ,subunit:Homodimer; phosphorylation-induced. 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. ,tissue specificity:Expressed constitutively in a variety of tissues. ,

cytokine production , response to molecule of bacterial origin , transcription , transcription , DNA-dependent , regulation of transcription , DNA-dependent , transcription from RNA polymerase II promoter , cell surface receptor linked signal transduction , intracellular signaling cascade , protein kinase cascade , I-kappaB kinase/NF-kappaB cascade , response to virus , response to bacterium , response to organic substance , lipopolysaccharide-mediated signaling pathway ,response to lipopolysaccharide , type I interferon production , RNA biosynthetic process , cytokine biosynthetic process ,cytokine metabolic process , response to exogenous dsRNA , response to dsRNA , type I interferon biosynthetic process ,regulation of transcription , regulation of RNA metabolic process ,

Cytoplasm . Nucleus . Mitochondrion . Shuttles between cytoplasmic and nuclear compartments , with export being the prevailing effect (PubMed:10805757) . When activated , IRF3 interaction with CREBBP prevents its export to the cytoplasm (PubMed:10805757) . Recruited to mitochondria via TOMM70:HSP90AA1 upon Sendai virus infection (PubMed:25609812) . .