E3 ubiquitin-protein ligase which catalyzes the formation of 'Lys-48'-polyubiquitin chains (By similarity). Mediates the ubiquitination and subsequent degradation of phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus (By similarity). Acts as a terminal regulator of Akt signaling after activation; its phosphorylation by Akt, which is a prerequisite for ubiquitin ligase activity, suggests the existence of a regulation mechanism required to control Akt levels after activation (By similarity). Positively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation by mediating the ubiquitination and subsequent degradation of SMURF2 (By similarity). Regulates neuronal differentiation by regulating actin remodeling and Golgi organization via a signaling cascade involving RHOA, CIT and ROCK (PubMed:24695496). Inhibits cell proliferation (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts (when phosphorylated on Ser-397) with AKT1, AKT2 and AKT3 (when phosphorylated) (By similarity). Interacts with CIT (By similarity). Interacts with POLG (By similarity). Interacts with HSP70 (By similarity). Interacts with SMURF2 (By similarity). Nuclear localization may be dependent on the proteolytic cleavage of full length protein in the cytoplasm (By similarity). This cleavage may reveal an N-terminal nuclear localization signal, allowing N-terminal fragments to enter the nucleus (By similarity). Phosphorylation on Ser-397 by Akt is required for ubiquitin ligase activity. Proteolytically cleaved into differently sized N- and C-terminal fragments.