Annotated protein:NEDD8-conjugating enzyme Ubc12 (EC 2.3.2.34) (NEDD8 carrier protein) (Ubiquitin-conjugating enzyme E2 M). Gene symbol: UBE2M. Taxonomy: Mus musculus (Mouse). Uniprot ID: P61082
antibody wiki:
SynGO gene info:SynGO data @ UBE2M
Ontology domain:Biological Process
SynGO term:regulation of postsynapse assembly (GO:0150052)
Synapse type(s):hippocampus, glutamatergic
Annotated paper:Vogl AM, et al. "Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition" Nat Neurosci. 2015 Feb;18(2):239-51 PMID:25581363
Figure(s):Figure 2, 3, 4, 6, 7
Annotation description:Similar to ubiquitylation, neddylation requires three sequential reaction steps accomplished by the heterodimeric E1-activating enzyme NAE (Nedd8 activating enzyme), the conjugating enzyme Ubc12 and an as yet incompletely characterized set of E3 ligases (PMID:18793140).

Figure 2: Inhibition of neddylation blocks spine maturation. shRNA knockdown of Ubc12 in DIV12 mouse hippocampal neurons strongly decreased dendritic spine density and increased the number of dendritic filopodia.

Figure 2,3: knockdown of Ubc12 and using NAE inhibitor MLN-4924 (Fig. S2c & PMID:19360080) also reduced dendritic spine maturation.

Figure 4: Neddylation is active in synapses, as demonstrated by live imaging experiments that quantified the rates of de novo growth and elimination of spines in mature cultured neurons (DIV19) treated for 8 h with vehicle or MLN-4924.

Figure 6, 7: molecular characterization of PSD95 (DLG4) neddylation further confirms this process takes place at the postsynapse.
Evidence tracking, Biological System:Cultured neurons
Evidence tracking, Protein Targeting:RNAi / shRNA
Antagonist / agonist
Evidence tracking, Experiment Assay:Confocal
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:5257
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology