Deubiquitylases (DUBs) specifically cleave ubiquitin after the terminal carboxyl group of ubiquitin (Gly76) and can be divided into five groups in mammals. Four of the five subfamilies are cysteine proteases: ubiquitin specific proteases (USP/UBP), ubiquitin C-terminal hydrolases (UCH), Machado-Joseph Disease Domain (MJD) and ovarian tumor related (OTU). The fifth group is the Zn2+-containing JAMM motif metalloproteases.