| Annotated protein: | E3 ubiquitin-protein ligase parkin (EC 2.3.2.31) (Parkin RBR E3 ubiquitin-protein ligase). Gene symbol: PRKN. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q9JK66 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ PRKN |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic membrane neurotransmitter receptor levels (GO:0099072) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Maraschi A, et al. "Parkin regulates kainate receptors by interacting with the GluK2 subunit" Nat Commun. 2014 Oct 15;5:5182 PMID:25316086 |
| Figure(s): | Fig.2, 3, 4 |
| Annotation description: | Fig.2: "Parkin interacts with GluK2" Fig.3: "Parkin ubiquitinates GluK2" Fig.4: "Loss of parkin function increases surface GluK2 levels, KAR currents and causes excitotoxicity" Note: - Parkin, PARK2 is a ubiquitin ligase that modifies the KAR thereby regulating its surface expression. - Data on synaptic KARs is not included in this paper but implied by the authors. However, the authors mention: "Parkin also mediates endophilin-A1 ubiquitination and some evidence suggests that endophilin-A-mediated parkin recruitment promotes synaptic protein ubiquitination9. The loss of endogenous parkin sensitizes in vitro midbrain dopaminergic neurons to kainate toxicity10, increases excitatory glutamatergic synapse numbers and increases vulnerability to synaptic excitotoxicity in cultured hippocampal neurons6. Hence, although current knowledge strongly suggests that parkin intervenes in modulating glutamatergic synapse function, the underlying molecular mechanism is unknown. We hypothesized that parkin may directly regulate ionotropic glutamate receptors of the N-methyl-d-aspartate (NMDAR), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPAR) or kainate receptor (KAR) types. Our results show that parkin regulates KAR function and suggest that KAR may have a pathogenetic role in parkin-related ARJP." |
| Evidence tracking, Biological System: | Cultured neurons Non-neuronal tissue |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp Western blot IP + WB/MSMS |
| Annotator(s): | Pim van Nierop (ORCID:0000-0003-0593-3443) 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: | 3783 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |