Tetratricopeptide repeat domain 3 (TTC3)

Tetratricopeptide repeat domain 3 (TTC3) is a protein encoded by the *TTC3* gene located on human chromosome 21q22.2, within the Down syndrome critical region. TTC3 contains multiple tetratricopeptide repeat (TPR) motifs and a RING finger domain, conferring its function as an E3 ubiquitin-protein ligase involved in protein ubiquitination and proteasomal degradation. It interacts with chaperones such as Hsp70 and targets substrates including phosphorylated Akt and DNA polymerase γ (POLG), affecting mitochondrial protein homeostasis. TTC3 is developmentally regulated and highly expressed in the nervous system; dysregulation or copy number variants have been linked to Down syndrome and may contribute to neurodegenerative pathologies through impaired protein homeostasis and aggregate formation[2][4].

Other names

TTC3

Poly-ubiquitination of substrate proteins (e.g., phosphorylated Akt); Regulation of protein degradation (DNA polymerase γ/POLG) via interaction and ubiquitination machinery; Potential co-chaperone activities with Hsp70