phosphorylated IRF3/IRF7 activated TLR3/4:TRIF:K63-poly-Ub-TRAF3:p-TBK1/p-IKKE:IRF3/IRF7 activated TLR3/4:TRIF:K63-poly-Ub-TRAF3:p-TBK1/p-IKK epsilon Phosphorylation of IRF-3/IRF7 and their release from the activated TLR complex Authored: de Bono, B, 2005-08-16 10:54:15 EC Number: 2.7.11 Edited: Shamovsky, V, 2011-08-12 Human IRF-3 is activated through a two step phosphorylation in the C-terminal domain mediated by TBK1 and/or IKK-i. It requires 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 alleviate autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitate phosphorylation at site 1. Phosphorylation at site 1 is required for IRF-3 dimerization.<p>IRF-3 and IRF-7 transcription factors possess distinct structural characteristics; IRF-7 is phosphorylated on Ser477 and Ser479 residues [Lin R et al 2000]. TRAF6 mediated ubiquitination of IRF7 is also required and essential for IRF7 phosphorylation and activation. The K-63 linked ubiquitination occurs on the last three C-terminal lysine sites (positions 444, 446, and 452) of human IRF7 independently of its C-terminal functional phosphorylation sites.[Ning et al 2008]. Pubmed10893229 Pubmed12692549 Pubmed14703513 Pubmed17526488 Pubmed18710948 Reactome Database ID Release 43166245 Reactome, http://www.reactome.org ReactomeREACT_6728 Reviewed: Fitzgerald, Katherine A, 2012-11-13 Reviewed: Gay, NJ, 2006-04-24 16:48:17 Reviewed: Gillespie, ME, 2010-11-30 has a Stoichiometric coefficient of 2 has a Stoichiometric coefficient of 6