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 predicted 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 enzymes. USP15 shares 60.5% sequence identity and 76% sequence similarity with the human homolog (UNP/Unph/USP4) of the mouse Unp proto-oncogene. Recombinant USP15 demonstrated ubiquitin-specific protease activity against engineered linear fusions of ubiquitin to beta-galactosidase and glutathione S-transferase. USP15 can also cleave the ubiquitin-proline bond, a property previously unique to Unp/UNP. Chromosomal mapping by fluorescence in situ hybridization and radiation hybrid analyses localized the USP15 gene to chromosome band 12q14, a different location than that of UNP (3p21.3). Analysis of expressed sequence tag databases reveals evidence of alternate polyadenylation 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 have descended from a common ancestor. A systematic nomenclature for the human USPs is proposed.
Baker
R T
RT
Division of Molecular Medicine, Australian National University, Canberra, ACT, 2601, Australia. Rohan.Baker@anu.edu.au
Wang
X W
XW
Woollatt
E
E
White
J A
JA
Sutherland
G R
GR
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D051258:MafB Transcription Factor; D051379:Mice; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000145:classification / Q000235:genetics*; D011392:Proline / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017386:Sequence Homology, Amino Acid; D009626:Terminology as Topic; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; D014452:Ubiquitins / Q000378:metabolism*
D030161:Avian Proteins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C490407:MAFB protein, human; C000715470:MAS1 protein, human; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D015513:Oncogene Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C486203:USP4 protein, human; D014452:Ubiquitins; C082325:Usp4 protein, mouse; D011392:Proline; D010450:Endopeptidases; C579226:USP15 protein, human; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases; C579225:Usp15 protein, mouse