title: Cloning and enzymatic analysis of 22 novel human ubiquitin-specific proteases.
abstract: We have identified and cloned 22 human cDNAs encoding novel members of the ubiquitin-specific protease (USP) family. Eighteen of the identified proteins contain all structural features characteristic of these cysteine proteinases, whereas four of them have been classified as non-peptidase homologues. Northern blot analysis demonstrated that the identified USPs are broadly and differentially distributed in human tissues, some of them being especially abundant in skeletal muscle or testis. Enzymatic studies performed with the identified USPs revealed that at least twelve of them are deubiquitylating enzymes based on their ability to cleave ubiquitin from a ubiquitin-beta-galactosidase fusion protein. These results provide additional evidence of the extreme complexity and diversity of the USP proteolytic system in human tissues and open the possibility to explore the relevance of their multiple components in the regulation of ubiquitin-mediated pathways in normal and pathological functions.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Quesada
authors.forename: Araceli
authors.initials: A
authors.lastname: Díaz-Perales
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez-Fernández
authors.forename: Cecilia
authors.initials: C
authors.lastname: Garabaya
authors.forename: Santiago
authors.initials: S
authors.lastname: Cal
authors.forename: Carlos
authors.initials: C
authors.lastname: López-Otín
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular / Q000379:methods*; D046508:Culture Techniques; D010450:Endopeptidases / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D006801:Humans; D007527:Isoenzymes; D008969:Molecular Sequence Data; D009928:Organ Specificity; D016415:Sequence Alignment / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D064570:Ubiquitin-Specific Proteases
chemical_list: D007527:Isoenzymes; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases