OTU domain-containing protein 3 (UniProt: Q5T2D3; also known as EC: 3.4.19.12, OTUD3) is encoded by the OTUD3 (also known as KIAA0459) gene (Gene ID: 23252) in human. OTUD3 is a cytoplasmic deubiquitinating enzyme that hydrolyzes Lys-6- and Lys-11-linked polyubiquitin and is reported to hydrolyze heterotypic (mixed and branched) and homotypic chains. It has an OUT domain (aa 65-189) and a UBA-like domain (aa 230-270). Its specificity is given by the S1' ubiquitin-binding site within the OTU domain composed of the Cys-, His- and Variable-loops. The UBA-like domain has no effect on ubiquitin hydrolysis. It displays a thiol-dependent ubiquitin-specific protease activity. It is reported to regulate PTEN stability and suppresses tumorigenesis. OTUD3 transgenic mice exhibit higher levels of the PTEN and are shown to be less prone to tumorigenesis. OTUD3 is believed to regulate PTEN in a manner, which is dependent on its DUB activity. The catalytically inactive mutant C76A does not upregulate PTEN and may even have a downregulating effect. It can remove Lys-6, Lys-11, Lys-27, and Lys-48 types of ubiquitin chain on PTEN. (Ref.: Yuan, L., et al (2015). Nat. Cell Biol. 17(9); 1169-1181).