E3 ubiquitin-protein ligase which catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:20059950, PubMed:30696809). Mediates the ubiquitination and subsequent degradation of phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus (PubMed:20059950). 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 (PubMed:20059950). Positively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation by mediating the ubiquitination and subsequent degradation of SMURF2 (PubMed:30696809). Regulates neuronal differentiation by regulating actin remodeling and Golgi organization via a signaling cascade involving RHOA, CIT and ROCK (PubMed:17488780, PubMed:24695496). Inhibits cell proliferation (PubMed:30203323). 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-378) with AKT1, AKT2 and AKT3 (when phosphorylated) (PubMed:20059950). Interacts with CIT (PubMed:17488780). Interacts with POLG (PubMed:29290964). Interacts with HSP70 (PubMed:29290964). Interacts with SMURF2 (PubMed:30696809). Nuclear localization may be dependent on the proteolytic cleavage of full length protein in the cytoplasm (PubMed:30203323). This cleavage may reveal an N-terminal nuclear localization signal, allowing N-terminal fragments to enter the nucleus (PubMed:30203323). Found in all tissues examined. Up-regulated by TGFB1 signaling. Phosphorylation on Ser-378 by Akt is required for ubiquitin ligase activity. Proteolytically cleaved into differently sized N- and C-terminal fragments. Contaminating sequence. Potential poly-A sequence. Contaminating sequence. Potential poly-A sequence.