Reactome: A Curated Pathway Database

Phosphorylation of IRF3 by TBK1 complexed with activated TLR3

Stable Identifier
Gallus gallus
Locations in the PathwayBrowser

IRF-3 is activated by two step phosphorylation. IKK related kinases TBK1 and/or IKKi mediate the phosphorylation of the residues Ser386 and/or Ser385 (site1) and a cluster of serine/threonine residues between Ser396 and Ser405 (site 2) [Panne et al 2007]. Phosphorylation of residues in site 2 alleviates autoinhibition to allow interaction with CBP (CREB-binding protein) and facilitates phosphorylation at site 1. Phosphorylation at site 1 is required for IRF-3 dimerization.

All serine residues mentioned above were empirically defined for human IRF3. Multiple sequence alignment of human, mouse and chicken IRF3 by ClustalW showed similarity in the C-terminal domain and the following chicken residues are predicted to be involved in chicken IRF3 activation:

  • Ser463 and/or Ser464 (site 1, corresponding to human Ser385 and Ser386)
  • Ser474 and Ser476 (site2,corresponding to human Ser396 and Ser398 from the cluster of Ser396-Ser405)

Literature References
Participant Of
This entity is regulated by:
Title Physical Entity Activity
protein serine/threonine kinase activity of ds viral RNA : TLR3 : TICAM1 : TBK1 complex [endosome membrane] ds viral RNA : TLR3 : TICAM1 : TBK1 complex [endosome membrane] protein serine/threonine kinase activity (0004674)
Inferred From