| Annotated protein: | E3 ubiquitin-protein ligase Mdm2 (EC 2.3.2.27). Gene symbol: MDM2. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: A0A8I6G5V3 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ MDM2 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of protein catabolic process at postsynapse, modulating synaptic transmission (GO:0099576) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Colledge M, et al. "Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression" Neuron. 2003 Oct 30;40(3):595-607 PMID:14642282 |
| Figure(s): | Figures 2-6 |
| Annotation description: | "PSD-95 (DLG4) interacts with and is ubiquitinated by the E3 ligase Mdm2. In response to NMDA receptor activation, PSD-95 is ubiquitinated and rapidly removed from synaptic sites by proteasome-dependent degradation. Mutations that block PSD-95 ubiquitination prevent NMDA-induced AMPA receptor endocytosis." Figure 2: NMDA treatment causes ubiquitination of PSD-95 that depends on a PEST motif. Figure 3: reverse-IP in synaptic plasma membrane extracts shows interaction between PSD-95 and Mdm2, a Ubiquitin E3 Ligase. Confocal imaging of cultured hippocampal neurons shows Mdm2 localized to synapses. Figure 4: Mdm2 ubiquitinates PSD-95 and regulates its expression levels and this depends on the PSD-95 PEST motif. Further, authors show that the proteasome regulates PSD-95 degradation and ubiquitination of PSD-95 via its PEST motif regulates endocytosis of AMPA receptors (Fig. 5, 6). This is a presumed consequence of Mdm2 ubiquitinating PSD-95. |
| Evidence tracking, Biological System: | Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | Over-expression Antibody (detection) Antagonist / agonist |
| Evidence tracking, Experiment Assay: | Confocal IP + WB/MSMS |
| 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: | 5199 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |