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. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88- independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists 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 where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages. Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF3. Interacts with TICAM1 and TICAM2. Interacts with rotavirus A NSP1; this interaction leads to the proteasome- dependent degradation of IRF7. Interacts with Epstein-Barr virus LF2. Interacts with MYD88 AND TRAF6. By type I interferon (IFN) and viruses. Expressed predominantly in spleen, thymus and peripheral blood leukocytes. 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. Belongs to the IRF family. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: DNA binding protein; Transcription factor
Biological Process: transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; establishment of viral latency; toll-like receptor 3 signaling pathway; negative regulation of transcription from RNA polymerase II promoter; regulation of MyD88-independent toll-like receptor signaling pathway; regulation of adaptive immune response; positive regulation of interferon-beta production; positive regulation of interferon type I production; interferon type I biosynthetic process; toll-like receptor 4 signaling pathway; positive regulation of interferon-alpha production; regulation of interferon type I production; regulation of immune response; cytokine and chemokine mediated signaling pathway; MyD88-independent toll-like receptor signaling pathway; response to virus; interferon-alpha production; regulation of MyD88-dependent toll-like receptor signaling pathway; regulation of monocyte differentiation; toll-like receptor signaling pathway; innate immune response; positive regulation of transcription from RNA polymerase II promoter; toll-like receptor 9 signaling pathway; immunoglobulin mediated immune response; response to DNA damage stimulus; interferon-beta production
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.