ArticlePloS one2011
Lysine 92 amino acid residue of USP46, a gene associated with 'behavioral despair' in mice, influences the deubiquitinating enzyme activity.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Proximity-dependent biotinylation reveals an interaction between ubiquitin-specific peptidase 46 and centrosome-related proteins.FEBS open bio · 2025Article
- Structure, Inhibitors, and Biological Function in Nervous System and Cancer of Ubiquitin-Specific Protease 46.Bioinformatics and biology insights · 2024Review
- Possible Association of Polymorphisms in Ubiquitin Specific Peptidase 46 Gene With Post-traumatic Stress Disorder.Frontiers in psychiatry · 2021Article
- Identification of candidate substrates of ubiquitin-specific protease 13 using 2D-DIGE.International journal of molecular medicine · 2017Article
- Function of the Deubiquitinating Enzyme USP46 in the Nervous System and Its Regulation by WD40-Repeat Proteins.Frontiers in synaptic neuroscience · 2017Article
- A conserved two-step binding for the UAF1 regulator to the USP12 deubiquitinating enzyme.Journal of structural biology · 2016Article
- Identification of candidate genes for familial early-onset essential tremor.European journal of human genetics : EJHG · 2016Article
- E1-mediated recruitment of a UAF1-USP deubiquitinase complex facilitates human papillomavirus DNA replication.Journal of virology · 2014Article
- The WD40-repeat protein-containing deubiquitinase complex: catalysis, regulation, and potential for therapeutic intervention.Cell biochemistry and biophysics · 2013Review
- Article
- Ubiquitin-specific peptidase 46 (Usp46) regulates mouse immobile behavior in the tail suspension test through the GABAergic system.PloS one · 2012Article
- The role of deubiquitinating enzymes in synaptic function and nervous system diseases.Neural plasticity · 2012Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Deubiquitinating enzymes (DUBs) regulate diverse cellular functions by their activity of cleaving ubiquitin from specific protein substrates. Ubiquitin-Specific Protease 46 (USP46) has recently been identified as a quantitative trait gene responsible for immobility in the tail suspension test and forced swimming test in mice. Mice with a lysine codon (Lys 92) deletion in USP46 exhibited loss of 'behavioral despair' under inescapable stresses in addition to abnormalities in circadian behavioral rhythms and the GABAergic system. However, whether this deletion affects enzyme activity is unknown. Here we show that USP46 has deubiquitinating enzyme activity detected by USP cleavage assay using GST-Ub52 as a model substrate. Interestingly, compared to wild type, the Lys 92 deletion mutant resulted in a decreased deubiquitinating enzyme activity of 27.04%. We also determined the relative expression levels of Usp46 in rat tissues using real-time RT-PCR. Usp46 mRNA was expressed in various tissues examined including brain, with the highest expression in spleen. In addition, like rat USP46, both human and mouse USP46 are active toward to the model substrate, indicating the USP cleavage assay is a simple method for testing the deubiquitinating enzyme activity of USP46. These results suggest that the Lys 92 deletion of USP46 could influence enzyme activity and thereby provide a molecular clue how the enzyme regulating the pathogenesis of mental illnesses.
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