Ovarian tumor domain proteases

Humans have 16 Ovarian 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). <br> <br>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).

人类拥有16个卵巢肿瘤领域（OTU）家族去泛素化酶（DUBs），这些酶可根据进化特征划分为三类：OTUs、Otubains（OTUBs）以及类似A20的OTUs（Komander et al. 2009）。OTU家族去泛素化酶在切割泛素交叉链接的类型上具有高度选择性。OTUB1特异性作用于K48链接的链，而OTUB2则能切割K11、K63和K48链接的多泛素（Wang et al. 2009, Edelmann et al. 2009, Mevissen et al. 2013）。A20偏好于K48链接的链，Cezanne特异性作用于K11链接的链，TRABID则作用于K29、K33和K63链接的多泛素（Licchesi et al. 2011, Komander & Barford 2008, Bremm et al. 2010, Mevissen et al. 2013）。OTU结构域的活性位点包含一个在其它硫醇-DUBs中未见过的非典型环状结构，且可能缺乏明显的催化天冬氨酸/天冬酰胺（Komander & Barford 2009, Messick et al. 2008, Lin et al. 2008）。A20和OTUB1具有不寻常的活性模式，它们直接结合E2酶（Nakada et al. 2010, Wertz et al. 2004）。