Annotated protein:TNF receptor-associated factor 6 (EC 2.3.2.27) (E3 ubiquitin-protein ligase TRAF6) (RING-type E3 ubiquitin transferase TRAF6). Gene symbol: TRAF6. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: B5DF45
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SynGO gene info:SynGO data @ TRAF6
Ontology domain:Biological Process
SynGO term:regulation protein catabolic process at postsynapse (GO:0140252)
Synapse type(s):hippocampus, glutamatergic
Annotated paper:Ma Q, et al. "Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity" Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8760-E8769 PMID:28973854
Figure(s):Figure 3, 7
Annotation description:"TRAF6-facilitated K63 ubiquitination was diminished in K558R (Fig. S3B) and PSD-95ΔNT (Fig. 3D) mutants. In vitro ubiquitination assays using purified proteins showed that TRAF6, in conjunction with Ubc13/Uev1A, effectively delivered the ubiquitin moieties to PSD-95, which did not occur when TRAF6, UbK63, Ubc13, Uev1A, or PSD-95 was omitted from the reaction mix (Fig. 3E)."

"Knocking down TRAF6 prevented the AP5-elicited increase of PSD-95 ubiquitination (Fig. 7G), supporting the notion that TRAF6 mediates constitutive K63 ubiquitination of PSD-95."

"The activity-dependent assembly/disassembly of K63-polyUb chains may involve dynamic regulation of the E2-E3-substrate-DUB multiprotein complex we have identified in the PSD. The Ubc13/Uev1A dimer remains the only known K63-selective E2 that, together with the RING-domain family E3 ligase TRAF6, catalyzes the assembly of K63-polyUb chains on substrates. Our results suggest that the Ubc13/Uev1A-TRAF6 complex binds the PSD-95 NT and delivers ubiquitin moieties to cognate lysine sites."
Evidence tracking, Biological System:Cultured neurons
Evidence tracking, Protein Targeting:RNAi / shRNA
Evidence tracking, Experiment Assay:Western blot
Annotator(s):Frank Koopmans (ORCID:0000-0002-4973-5732)
Guus Smit (ORCID:0000-0002-2286-1587)
Matthijs Verhage (ORCID:0000-0002-2514-0216)
Lab:Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
SynGO annotation ID:5358
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology