Identifiers
HUGO:TRAF6
TNF receptor associated factor 6
HUGO:TRAF6 hgnc_id:HGNC:12036 HGNC:12036 ENTREZ:7189 UNIPROT:Q9Y4K3
TNF receptor-associated factor 6, E3 ubiquitin protein ligase
HUGO:TRAF6, HGNC:12036, ENTREZ:7189, UNIPROT:Q9Y4K3, GENECARDS:GC11M036467
HUGO:TRAF6 HGNC:12036 ENTREZ:7189 UNIPROT:Q9Y4K3
"TNF receptor-associated factor 6"
Maps_Modules
HMC:AVOIDING_IMMUNE_DESTRUCTION
Adaptive Immune Response / TCR_SIGNALING
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
Cancer Associated Fibroblasts / INFLAMMATORY_SIGNALING_PATHWAYS
EMT Senescence / EMT_REGULATORS
HMC:RESISTING_CELL_DEATH
Regulated Cell Death / DEATH_RECEPTOR_PATHWAYS
Regulated Cell Death / DEPENDANCE_RECEPTORS
Innate Immunity / IMMUNOSTIMULATORY_CORE_PATHWAYS
HMC:EVADING_GROWTH_SUPPRESSORS
Survival / MAPK
References
PMID:15125833
MALT1 oligomers is critical for activation of the IKK complex17, 18, most likely by MALT1-dependent recruitment of the ubiquitin ligase TRAF6 (refs. 17,19) and subsequent lysine 63???mediated ubiquitination of IKK(also called NEMO)18.
PMID:17948050
TRAF6 associates with Malt1 in response to T-cell activation and can function as an E3 ligase for Malt1 in vitro and in vivo, mediating lysine 63-linked ubiquitination of Malt1.
Ubiquitin chains on Malt1 provide a docking surface for the recruitment of the IKK regulatory subunit NEMO/IKKgamma.
http://link.springer.com/chapter/10.1007/978-1-4419-6676-6_7#page-2
PMID:19161412 , PMID:12620219
IRAK-1 interacts with the downstream adaptor TRAF6,
resulting in formation of a complex that also includes TAK1 and TAB2.
IRAK-1 mediates the translocation of TRAF6, TAK1 and TAB2 to the cytosol,
where they form a multiprotein complex with other cytosolic proteins,
which are needed for stimulation of TAK1 kinase activity.
PMID:18758450
The ubiquitin ligase (E3) TRAF6 interacts with a consensus motif present in TGFBR1.
The TGFBR1???TRAF6 interaction is required for TGFB-induced autoubiquitylation of TRAF6 and subsequent activation of the TAK1???p38/JNK pathway
TGFB specifically activates TAK1 (MAP3K7) through interaction of TGFBRI with TRAF6.
The kinase activity of TGFBRI is not required for activation of TAK1 and p38.
Model in which TGFB - induced activation of TAK1 is initiated by ligand-induced oligomerization of TGFBreceptors. This in turn cause dimerization of TRAF6, followed by auto-ubiquitylation and activation.
This possibility is consistent with the observation that artifical dimerization of TRAF6 causes its auto-ubiquitylation.
Activated TRAF6 then causes Lys 63-linked ubiquitylation and activation of TAK1 (MAP3K7). TAK1 may be further activated by juxtaposition-induced autophosphorylation.
The recruitment of TAK1 may be facilitated by Smad7, which has been shown to have an adaptor function in the pathway
PMID:18922473
TRAF6 is specifically required for the Smad-independent activation of JNK and p38.
The carboxyl TRAF homology domain physically interacts with TGFB receptors.
TGFB induces K63-linked ubiquitination of TRAF6 and promotes association between TRAF6 and TAK1 (MAP3K7).
TGFB activates JNK and p38 through a mechanism similar to that operating in the interleukin1B/Toll- like receptor pathway.
PMID:16252010
PMID:14660645, PMID:18264787, PMID:12620219
Upon recruitment to the IL-1R complex IRAK1 binds TRAF6 forming a MyD88-IRAK1-TRAF6 complex analogous to the TNFR-associated complex of TRADD RIP and TRAF2.
PMID:11274345
References
in_re695( Innate Immunity ):
PMID:14660645, PMID:18264787, PMID:12620219
IRAK-1 interacts with the downstream adaptor TRAF6,
resulting in formation of a complex that also includes TAK1 and TAB2.
IRAK-1 mediates the translocation of TRAF6, TAK1, and TAB2 to the cytosol,
where they form a multiprotein complex with other cytosolic proteins,
which are needed for stimulation of TAK1 kinase activity.
PMID:12150927
IRAK3 (IRAK-M) is a negative regulator of Toll-like receptor signaling
in macrophages. It prevented dissociation of IRAK and IRAK-4 from MyD88 and formation of IRAK-TRAF6 complexes.