Protein ubiquitination requires the concerted action of the E1, E2, and E3 ubiquitin-conjugating enzymes. Ubiquitin is first activated through ATP-dependent formation of a thiol ester with ubiquitin-activating enzyme E1. The activated ubiquitin is then transferred to a thiol group of ubiquitin-carrier enzyme E2. The final step is the transfer of ubiquitin from E2 to an ε-amino group of the target protein lysine residue, which is mediated by ubiquitin-ligase enzyme E3.UBE2O is a unique member of the E2 family of ubiquitin-conjugating enzymes in that it functions as an E2-E3 hybrid enzyme. Research studies have demonstrated that UBE2O expression is regulated during erythroid differentiation, which suggests that its enzymatic activity participates in shaping the architecture of the erythrocyte proteome. UBE2O has also been implicated in BMP-7-induced adipocyte differentiation through its regulation of SMAD6 monoubiquitination.
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