Reaction: Phosphorylation of IRF-3/IRF7 and their release from the activated TLR complex
- in pathway: Activation of IRF3, IRF7 mediated by TBK1, IKBKE
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.
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].
Reaction - small molecule participants:
ADP [cytosol]
ATP [cytosol]
Reactome.org reaction link: R-HSA-166245
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Reaction input - small molecules:
ATP(4-)
Reaction output - small molecules:
ADP(3-)
Reactome.org link: R-HSA-166245