| Annotated protein: | Ubiquitin carboxyl-terminal hydrolase 46 (EC 3.4.19.12) (Deubiquitinating enzyme 46) (Ubiquitin thioesterase 46) (Ubiquitin-specific-processing protease 46). Gene symbol: USP46. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: F1M625 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ USP46 |
| Ontology domain: | Biological Process |
| SynGO term: | regulation of postsynaptic neurotransmitter receptor endocytosis (GO:0099149) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Huo Y, et al. "The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking" J Neurochem. 2015 Sep;134(6):1067-80 PMID:26077708 |
| Figure(s): | Fig.3, 5, 6, 7, 8 |
| Annotation description: | Fig.3: "USP46 deubiquitinates glutamate receptor subunit 1 (GluA1) in vivo and in vitro" Fig.5: "Knockdown of USP46 reduces both surface and total AMPARs in hippocampal neurons" Fig.6: "Over-expression of USP46 increases surface AMPAR expression" Fig.7: "Effect of USP46 on AMPAR internalization" Fig.8: "USP46 regulates AMPAR mediated synaptic currents" Notes: - The authors remark that "Ubiquitinated surface AMPARs are marked for efficient endocytosis, leading to inhibited synaptic transmission (Lin et al. 2011)." - In Fig.6 the authors show "We found that the surface GluA1 was significantly enhanced by USP46 over-expression. Quantification indicated a significant difference between EGFP control and cells with USP46 over-expression (Fig. 6a and b) (EGFP: 1 ± 0.05, n = 9 cells; USP46: 1.20 ± 0.05, n = 10 cells, p = 0.002). In contrast, no significant changes were detected in total GluA1 in neurons expressing either USP46 or USP12 (Fig. 6c and d) (EGFP: 1.0 ± 0.07, n = 9 cells; USP46: 1.08 ± 0.09, n = 9 cells, p = 0.20)." This argues for a role of USP46 in regulation of AMPAR endocytosis and not in protein degradation. I have refrained from making the annotation to term 'regulation of protein catabolic process at postsynapse, modulating synaptic transmission (GO:0099576)' because not sufficiently supported by the data. |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Whole-cell patch clamp Western blot |
| 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: | 2923 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |