The ubiquitination and deubiquitination of proteins can alter diverse cellular processes, such as proteolysis, trafficking, subcellular localisation, DNA repair, apoptosis and signal transduction. Deubiquitinating enzymes (DUBs) are responsible for removing ubiquitin from their target proteins. Previous reports have shown the presence of two subfamilies of DUBs inSchistosoma mansoni : Ub carboxyl-terminal hydrolase (UCH) and Ub-specific protease (USP). In this study, we analysed the ovarian tumour (OTU) and Machado-Josephdisease protein domain (MJD) proteases found in the Schistosoma mansoni genome database. An in silico analysis identified two different MJD subfamily members,Sm Ataxin-3 and Sm Josephin, and five distinct OTU proteases, Sm OTU1, Sm OTU3, Sm OTU5a, Sm OTU6b and Sm Otubain. The phylo genetic analysis showed the evolutionary conservation of these proteins. Furthermore, the 3D structures confirmed the similarity of these proteins with human proteins. In addition, we performed quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and observed distinct expression profiles for all of the investigated transcripts between the cercariae, schistosomula and adult worm stages. Taken together, our data suggest that MJD and OTU subfamily members contribute to regulating the activity of the Ub-proteasome system during the life cycle of this parasite.