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: |