Characterization and chromosomal localization of USP3, a novel human ubiquitin-specific protease

Conjugation to the small eukaryotic protein ubiquitin can functionally modi fy or target proteins for degradation by the proteasome. Removal of the ubi quitin modification, or deubiquitination, is performed by ubiquitin-specifi c proteases and is an important mechanism regulating this pathway. Here we describe a novel human ubiquitin-specific protease, USP3, initially identif ied as a partial cDNA clone similar to one of two highly conserved sequence regions common to all ubiquitin-specific proteases. We have isolated a com plete USP3 cDNA clone containing both of these conserved sequence regions. The USP3 gone appears to be single copy and maps to human chromosome 15q22. 3. A USP3 probe detects two mRNA transcripts, one of which corresponds in l ength to the cDNA. Both are expressed at low levels in all tissues examined , with highest expression in pancreas, The USP3 protein is a functional ubi quitin-specific protease in vitro, and is able to inhibit ubiquitin-depende nt degradation of both an N-end Rule substrate and abnormal endogenous prot eins in yeast. USP3 is also only the second known ubiquitin-specific protea se capable of efficiently cleaving a ubiquitin-proline bond.