Identification, functional characterization, and chromosomal localization of USP15, a novel human ubiquitin-specific protease related to the UNP oncoprotein, and a systematic nomenclature for human ubiquitin-specific proteases

We have identified a novel gene, USP15, encoding a human ubiquitin-specific protease (USP), The USP15 protein consists of 952 amino acids with a predi cted molecular mass of 109.2 kDa and contains the highly conserved Cys and His boxes present in all members of the UBP family of deubiquitinating enzy mes. USP15 shares 60.5% sequence identity and 76% sequence similarity with the human homolog (UNP/Unph/USP4) of the mouse Unp proto-oncogene. Recombin ant USP15 demonstrated ubiquitin-specific protease activity against enginee red linear fusions of ubiquitin to beta-galactosidase and glutathione S-tra nsferase. USP15 can also cleave the ubiquitin-proline bond, a property prev iously unique to Unp/UNP. Chromosomal mapping by fluorescence in situ hybri dization and radiation hybrid analyses localized the USP15 gene to chromoso me band 12q14, a different location than that of UNP (3p21.3). Analysis of expressed sequence tag databases reveals evidence of alternate polyadenylat ion sites in the USP15 gene and also indicates that the gene may possess an exon/intron structure similar to that of the Unp gene, suggesting they hav e descended from a common ancestor. A systematic nomenclature for the human USPs is proposed. (C) 1999 Academic Press.