dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi:IRF3/IRF7 dsRNA:RIG-1/MDA5:IPS-1:Ub-TRAF3:TBK1/IKKi phosphorylated IRF3/IRF7 Phosphorylation and release of IRF3/IRF7 Authored: Garapati, P V, 2010-08-02 Edited: Garapati, P V, 2010-08-02 Human IRF3 is activated through a two-step phosphorylation in the C-terminal domain mediated by TBK1 and/or IKKi, requiring Ser386 and/or Ser385- site 1; and a cluster of serine/threonine residues between Ser396 and Ser405- site 2 [Panne et al 2007]. Phosphorylated residues at site 2 (Ser396—Ser405) alleviate autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitate phosphorylation at site 1 (Ser385 or Ser386). Phosphorylation at site 1 is required for IRF3 dimerization.<br>IRF3 and IRF7 transcription factors possess distinct structural characteristics; IRF7 is phosphorylated on Ser477 and Ser479 residues [Lin R et al 2000]. <br>Since the number of serine residues involved into IRF activation remains unclear this reaction represents a minimum stoichiometry to achieve the phosphorylation of at least 3 Ser residues per each IRF transcription factor. [Lin et al 2000, Ning et al 2008] Pubmed10893229 Pubmed12692549 Pubmed14703513 Pubmed16914100 Pubmed17526488 Pubmed9463386 Reactome Database ID Release 43918229 Reactome, http://www.reactome.org ReactomeREACT_25368 Reviewed: Kawai, T, Akira, S, 2010-10-30 has a Stoichiometric coefficient of 6