TTC3
Function
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).
Pathway
Protein modification; protein ubiquitination.
Post-translational modifications
Phosphorylation on Ser-378 by Akt is required for ubiquitin ligase activity.
Proteolytically cleaved into differently sized N- and C-terminal fragments.
Tissue Specificity
Found in all tissues examined.
Cellular localization
- Nucleus
- Cytoplasm
- Golgi apparatus
- 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).
Alternative names
DCRR1, RNF105, TPRD, TTC3, E3 ubiquitin-protein ligase TTC3, Protein DCRR1, RING finger protein 105, RING-type E3 ubiquitin transferase TTC3, TPR repeat protein D, Tetratricopeptide repeat protein 3, TPR repeat protein 3