FEATURES

FAMILY

DESCRIPTION

Also known as IRF3_HUMAN, IRF3. 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 (PubMed:22394562, PubMed:25636800, PubMed:27302953). 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 (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995). 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 (PubMed:16846591, PubMed:16979567, PubMed:20049431). 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 (PubMed:22394562, PubMed:25636800, PubMed:27302953). 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 (PubMed:16154084, PubMed:27302953, PubMed:33440148). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70:HSP90AA1:IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148). Monomer (PubMed:16846591, PubMed:16979567, PubMed:20049431). Homodimer; phosphorylation-induced (PubMed:22394562, PubMed:25636800, PubMed:26347139). Interacts (when phosphorylated) with CREBBP (PubMed:16154084, PubMed:27302953). Interacts with MAVS (via phosphorylated pLxIS motif) (PubMed:16153868, PubMed:25636800, PubMed:27302953). Interacts with TICAM1 (via phosphorylated pLxIS motif) (PubMed:12471095, PubMed:14739303, PubMed:25636800, PubMed:27302953). Interacts with STING1 (via phosphorylated pLxIS motif) (PubMed:22394562, PubMed:28331227, PubMed:25636800, PubMed:27302953). Interacts with IKBKE and TBK1 (PubMed:16281057, PubMed:23478265, PubMed:25636800). Interacts with TICAM2 (PubMed:14517278). Interacts with RBCK1 (PubMed:18711448). Interacts with HERC5 (PubMed:20308324). Interacts with DDX3X (phosphorylated at 'Ser-102'); the interaction allows the phosphorylation and activation of IRF3 by IKBKE (PubMed:23478265, PubMed:27980081). Interacts with TRIM21 and ULK1, in the presence of TRIM21; this interaction leads to IRF3 degradation by autophagy (PubMed:18641315, PubMed:26347139). Interacts with RIOK3; RIOK3 probably mediates the interaction of TBK1 with IRF3 (PubMed:19557502). Interacts with ILRUN; the interaction inhibits IRF3 binding to its DNA consensus sequence (PubMed:29802199). Interacts with LYAR; this interaction impairs IRF3 DNA-binding activity (PubMed:31413131). Interacts with TRAF3 (PubMed:27980081). Interacts with ZDHHC11; ZDHHC11 recruits IRF3 to STING1 upon DNA virus infection and thereby promotes IRF3 activation (PubMed:28331227). Interacts with HSP90AA1; the interaction mediates IRF3 association with TOMM70 (PubMed:20628368, PubMed:25609812). Interacts with BCL2; the interaction decreases upon Sendai virus infection (PubMed:25609812). Interacts with BAX; the interaction is direct, increases upon Sendai virus infection and mediates the formation of the apoptosis complex TOMM70:HSP90AA1:IRF3:BAX (PubMed:25609812).

EXTERNAL LINKS

IRF3

Mutations

Mutation(s) distribution

Mutations table