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http://purl.uniprot.org/citations/25404403http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25404403http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25404403http://www.w3.org/2000/01/rdf-schema#comment"Ubiquitin-specific protease USP4 is emerging as an important regulator of cellular pathways, including the TGF-β response, NF-κB signalling and splicing, with possible roles in cancer. Here we show that USP4 has its catalytic triad arranged in a productive conformation. Nevertheless, it requires its N-terminal DUSP-Ubl domain to achieve full catalytic turnover. Pre-steady-state kinetics measurements reveal that USP4 catalytic domain activity is strongly inhibited by slow dissociation of ubiquitin after substrate hydrolysis. The DUSP-Ubl domain is able to enhance ubiquitin dissociation, hence promoting efficient turnover. In a mechanism that requires all USP4 domains, binding of the DUSP-Ubl domain promotes a change of a switching loop near the active site. This 'allosteric regulation of product discharge' provides a novel way of regulating deubiquitinating enzymes that may have relevance for other enzyme classes."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.org/dc/terms/identifier"doi:10.1038/ncomms6399"xsd:string
http://purl.uniprot.org/citations/25404403http://purl.org/dc/terms/identifier"doi:10.1038/ncomms6399"xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Sixma T.K."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Sixma T.K."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Clerici M."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Clerici M."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Faesen A.C."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Faesen A.C."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Luna-Vargas M.P."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/author"Luna-Vargas M.P."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/date"2014"xsd:gYear
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/name"Nat. Commun."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/name"Nat. Commun."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/pages"5399"xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/pages"5399"xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/title"The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/title"The DUSP-Ubl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange."xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/25404403http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/25404403http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25404403
http://purl.uniprot.org/citations/25404403http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25404403