title: High incidence of ubiquitin-like domains in human ubiquitin-specific proteases.
abstract: Ubiquitin-specific proteases (USPs) emerge as key regulators of numerous cellular processes and account for the bulk of human deubiquitinating enzymes (DUBs). Their modular structure, mostly annotated by sequence homology, is believed to determine substrate recognition and subcellular localization. Currently, a large proportion of known human USP sequences are not annotated either structurally or functionally, including regions both within and flanking their catalytic cores. To extend the current understanding of human USPs, we applied consensus fold recognition to the unannotated content of the human USP family. The most interesting discovery was the marked presence of reliably predicted ubiquitin-like (UBL) domains in this family of enzymes. The UBL domain thus appears to be the most frequently occurring domain in the human USP family, after the characteristic catalytic domain. The presence of multiple UBL domains per USP protein, as well as of UBL domains embedded in the USP catalytic core, add to the structural complexity currently recognized for many DUBs. Possible functional roles of the newly uncovered UBL domains of human USPs, including proteasome binding, and substrate and protein target specificities, are discussed.
authors.affiliation: Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec H4P 2R2, Canada.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhu
authors.forename: Robert
authors.initials: R
authors.lastname: Ménard
authors.forename: Traian
authors.initials: T
authors.lastname: Sulea
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D019295:Computational Biology; D017076:Computer-Aided Design; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D064570:Ubiquitin-Specific Proteases; D014452:Ubiquitins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014452:Ubiquitins; D010450:Endopeptidases; D064570:Ubiquitin-Specific Proteases