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These mutants cannot sustain ubiquitin-dependent proteolysis even though neither motif is essential for deubiquitylating activity. Ubiquitin-specific processing protease 5 (Ubp5), the closest paralogue of Doa4, has no functional overlap. Ubp5 concentrates at the bud neck; its N-terminal domain is critical for this. Importantly, substitution of the Ubp5 N-terminal domain with that of Doa4 relocalizes the Ubp5 enzyme to endosomes and provides Doa4 function. This is the first demonstration of a physiologically important DUB subcellular localization signal and provides a striking example of the functional diversification of DUB paralogues by the evolution of alternative spatial signals.<\/jats:p>","DOI":"10.1083\/jcb.200605134","type":"journal-article","created":{"date-parts":[[2006,12,4]],"date-time":"2006-12-04T20:01:32Z","timestamp":1165262492000},"page":"825-835","update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["A conserved late endosome\u2013targeting signal required for Doa4 deubiquitylating enzyme function"],"prefix":"10.1083","volume":"175","author":[{"given":"Alexander","family":"Amerik","sequence":"first","affiliation":[{"name":"1Department of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030"}]},{"given":"Nazia","family":"Sindhi","sequence":"additional","affiliation":[{"name":"1Department of Pharmacology, University of Connecticut Health Center, Farmington, CT 06030"}]},{"given":"Mark","family":"Hochstrasser","sequence":"additional","affiliation":[{"name":"2Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520"}]}],"member":"291","published-online":{"date-parts":[[2006,12,4]]},"reference":[{"key":"2023072908061654100_BIB1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.bbamcr.2004.10.003","volume":"1695","year":"2004","journal-title":"Biochim. 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