TTC3

TTC3 (Tetratricopeptide Repeat Domain 3) is a Protein Coding gene. Diseases related to TTC3 include Retinitis Pigmentosa 58 and Down Syndrome. Gene Ontology (GO) annotations related to TTC3 include ligase activity and ubiquitin-protein transferase activity. An important paralog of TTC3 is DZIP3.

Full Name

tetratricopeptide repeat domain 3

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).

Biological Process

Biological Process protein K48-linked ubiquitination Source:UniProtKB1 Publication
Biological Process ubiquitin-dependent protein catabolic process Source:UniProtKB1 Publication

Cellular Location

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).

PTM

Phosphorylation on Ser-378 by Akt is required for ubiquitin ligase activity.
Proteolytically cleaved into differently sized N- and C-terminal fragments.