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.IRF3 and IRF7 transcription factors possess distinct structural characteristics; IRF7 is phosphorylated on Ser477 and Ser479 residues [Lin R et al 2000]. 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]
Coyle, AJ, Faia, KL, Fitzgerald, KA, Liao, SM, Rowe, DC, Latz, E, McWhirter, SM, Golenbock, DT, Maniatis, T
McWhirter, SM, Maniatis, T, Harrison, SC, Panne, D
Fujita, T, Inagaki, F, Takahashi, K, Yoneyama, M, Mori, M, Ito, T
Hiscott, J, Paz, S, Lin, R, Romieu-Mourez, R, Goubau, D, Nakhaei, P, Sun, Q, Julkunen, I
Nishida, E, Fukuda, M, Suhara, W, Fujita, T, Fukuhara, Y, Yoneyama, M
protein serine/threonine kinase activity of viral dsRNA:IFIH1, viral dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:2xTBK1,IKBKE:IRF3,IRF7 [mitochondrial outer membrane]
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