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:Gene Ontology