K63-polyubiquitin activated TLR4/TLR3:TRIF:K63-pUb-TRAF6 TAB1 : TAB2/TAB3 : TAK1 activated TLR4/TLR3:TRIF:K63-pUb-TRAF6:free K63-linked pUb:TAK1complex Activated TLR:TRIF:K63-pUb-TRAF6 recruits TAK1complex Authored: Shamovsky, V, 2010-06-01 Edited: Shamovsky, V, 2010-11-16 Pubmed10882101 Pubmed15327770 Pubmed19675569 Reactome Database ID Release 43936947 Reactome, http://www.reactome.org ReactomeREACT_25261 Reviewed: Fitzgerald, Katherine A, 2012-11-13 Reviewed: Gillespie, ME, 2010-11-30 TAK1-binding protein 2 (TAB2) and/or TAB3, as part of a complex that also contains TAK1 and TAB1, binds polyubiquitinated TRAF6. The TAB2 and TAB3 regulatory subunits of the TAK1 complex contain C-terminal Npl4 zinc finger (NZF) motifs that recognize with Lys63-pUb chains (Kanayama et al. 2004). The recognition mechanism is specific for Lys63-linked ubiquitin chains [Kulathu Y et al 2009]. TAK1 can be activated by unattached Lys63-polyubiquitinated chains when TRAF6 has no detectable polyubiquitination (Xia et al. 2009) and thus the synthesis of these chains by TRAF6 may be the signal transduction mechanism. has a Stoichiometric coefficient of 2