| Annotated protein: | Ubiquitin carboxyl-terminal hydrolase CYLD (EC 3.4.19.12) (Deubiquitinating enzyme CYLD) (Ubiquitin thioesterase CYLD) (Ubiquitin-specific-processing protease CYLD). Gene symbol: CYLD. Taxonomy: Rattus norvegicus (Rat). Uniprot ID: Q66H62 |
| antibody wiki: | |
| SynGO gene info: | SynGO data @ CYLD |
| Ontology domain: | Biological Process |
| SynGO term: | regulation protein catabolic process at postsynapse (GO:0140252) |
| Synapse type(s): | hippocampus, glutamatergic |
| Annotated paper: | Ma Q, et al. "Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity" Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8760-E8769 PMID:28973854 |
| Figure(s): | Figure 3, 7 |
| Annotation description: | "A DUB that selectively cleaves K63 chains is CYLD (PMID:19626045). ... We detected a markedly higher amount of CYLD in PSD compared with other fractions (Fig. 3A). In HEK293FT cells, CYLD inhibited TRAF6-induced K63 ubiquitination of PSD-95 (Fig. 3F). In vitro deubiquitination assays showed that WT CYLD, but not the C601A mutant lacking the DUB enzymatic activity, substantially diminished K63 ubiquitination of PSD-95 (Fig. 3G). These results suggest that CYLD is a PSD-enriched DUB that removes K63 chains on PSD- Additional experiments confirm that TRAF6 and CYLD are E3 ligases and DUBs for PSD-95, respectively, in neurons. Both TRAF6 and CYLD colocalized with PSD-95 on dendrites of cultured hippocampal neurons (Fig. S3A). Interactions between endogenous PSD-95 and TRAF6, Ubc13, Uev1A, or CYLD in mouse forebrain were also detected (Fig. S3 F-I). Importantly, overexpression of TRAF6, but not the E3 ligase-deficient mutant C70A, increased, but knockdown of TRAF6 decreased, K63 ubiquitination of PSD-95 in hippocampal neurons (Fig. 3 I, J, M, and N and Fig. S3C). In contrast, CYLD overexpression decreased, but knockdown increased, K63 ubiquitination of PSD-95 (Fig. 3 K-N). Thus, TRAF6-Ubc13/Uev1A-CYLD is a neuronal E2-E3-DUB complex regulating K63 ubiquitination of PSD-95." |
| Evidence tracking, Biological System: | Cultured neurons |
| Evidence tracking, Protein Targeting: | RNAi / shRNA Over-expression |
| Evidence tracking, Experiment Assay: | Western blot |
| 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: | 5361 |
| Dataset release (version): | 20231201 |
| View annotation as GO-CAM model: |  |