Phosphorylation and release of IRF3/IRF7

Stable Identifier
Reaction [transition]
Homo sapiens
Related Species
Influenza A virus, Human respiratory syncytial virus A, Rotavirus, Hepatitis C Virus, Measles virus
Locations in the PathwayBrowser
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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]

Literature References
PubMed ID Title Journal Year
12692549 IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway

Coyle, AJ, Faia, KL, Fitzgerald, KA, Liao, SM, Rowe, DC, Latz, E, McWhirter, SM, Golenbock, DT, Maniatis, T

Nat Immunol 2003
17526488 Interferon regulatory factor 3 is regulated by a dual phosphorylation-dependent switch

McWhirter, SM, Maniatis, T, Harrison, SC, Panne, D

J Biol Chem 2007
14703513 Identification of Ser-386 of interferon regulatory factor 3 as critical

Fujita, T, Inagaki, F, Takahashi, K, Yoneyama, M, Mori, M, Ito, T

J Biol Chem 2004
16914100 Induction of IRF-3 and IRF-7 phosphorylation following activation of the RIG-I pathway

Hiscott, J, Paz, S, Lin, R, Romieu-Mourez, R, Goubau, D, Nakhaei, P, Sun, Q, Julkunen, I

Cell Mol Biol (Noisy-le-grand) 2006
9463386 Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/p300

Nishida, E, Fukuda, M, Suhara, W, Fujita, T, Fukuhara, Y, Yoneyama, M

EMBO J 1998
Catalyst Activity

protein serine/threonine kinase activity of viral dsRNA:IFIH1, viral dsRNA:K63polyUb-DDX58:MAVS:K63polyUb-TRAF3:2xTBK1,IKBKE:IRF3,IRF7 [mitochondrial outer membrane]

Orthologous Events
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