E3 ubiquitin-protein ligase which catalyzes the formation of 'Lys-48'-polyubiquitin chains (, ). Mediates the ubiquitination and subsequent degradation of phosphorylated Akt (AKT1, AKT2 and AKT3) in the nucleus . 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 . Positively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation by mediating the ubiquitination and subsequent degradation of SMURF2 . Regulates neuronal differentiation by regulating actin remodeling and Golgi organization via a signaling cascade involving RHOA, CIT and ROCK (, ). Inhibits cell proliferation .
Subcellular locations: Nucleus, Cytoplasm, Golgi apparatus
Nuclear localization may be dependent on the proteolytic cleavage of full length protein in the cytoplasm . This cleavage may reveal an N-terminal nuclear localization signal, allowing N-terminal fragments to enter the nucleus .
Found in all tissues examined.