IRF5 Protein, Human (His)

IRF5, a critical transcription factor, assumes a pivotal role in innate immunity by orchestrating the activation of type I interferon (IFN) genes, including IFNA and INFB, and inflammatory cytokines downstream of endolysosomal toll-like receptors (TLR7, TLR8, and TLR9). It functions as a key regulator in the transcription of type I IFN genes and IFN-stimulated genes (ISG) by binding to the interferon-stimulated response element (ISRE) in their promoters. Notably, IRF5 efficiently activates both IFN-beta (IFNB) and IFN-alpha (IFNA) genes, mediating their induction through the TLR-activated, MyD88-dependent pathway. Particularly relevant in the context of SARS-CoV-2 infection, IRF5 stands out as a significant transcriptional regulator of the IFN response. Maintained as a monomer in an autoinhibited state, its activation involves phosphorylation facilitated by the innate adapter protein TASL, which recruits IRF5, licensing it for phosphorylation by IKBKB. Subsequent steps involve the dissociation of phosphorylated IRF5 from adapter proteins, its dimerization, and nuclear entry to induce IFNs.