Humans have 16 Overian tumour domain (OTU) family DUBs that can be evolutionally divided into three classes, the OTUs, the Otubains (OTUBs), and the A20-like OTUs (Komander et al. 2009).
OTU family DUBs can be highly selective in the type of ubiquitin crosslinks they cleave. OTUB1 is specific for K48-linked chains, whereas OTUB2 can cleave K11, K63 and K48-linked poly-Ub (Wang et al. 2009, Edelmann et al. 2009, Mevissen et al. 2013). A20 prefers K48-linked chains, Cezanne is specific for K11-linked chains, and TRABID acts on both K29, K33 and K63-linked poly-Ub (Licchesi et al. 2011, Komander & Barford 2008, Bremm et al. 2010, Mevissen et al. 2013). The active site of the OTU domain contains an unusual loop not seen in other thiol-DUBs and can lack an obvious catalytic Asp/Asn (Komander & Barford 2009, Messick et al. 2008, Lin et al. 2008). A20 and OTUB1 have an unusual mode of activity, binding directly to E2 enzymes (Nakada et al. 2010, Wertz et al. 2004).