Otubains belong to the ovarian tumor (OTU) protein super-family present in eukaryotes, viruses and pathogenic bacterium. These proteins have no obvious homology to DUBs, however Otubain1 and Otubain2 were identified by affinity purification with the DUB-specific inhibitor Ub-aldehyde and both have an OTU domain (containing the active site), Ub-interacting motifs (UIMs) and Ub-associated domains (UBAs). Otubain1 exists in two isoforms with differential functions. The active Otubain1 transcript is implicated in immune cell clonal anergy via its interaction and destabilization (by promoting degradation) of GRAIL, an E3 ligase. Surprisingly, Otu1 has an indirect effect via its association with the C-terminal catalytic domain of another DUB USP8, forming a trimolecular complex with GRAIL. Otu1 has recently been identified as a substrate and is phosphorylated by the Yersinia protein kinase YpkA, suggesting that the regulation of T cell anergy is a mechanism for bacterial host survival. This recombinant protein is N-terminally tagged. Accession # NP_060140.