Tet methylcytosine dioxygenase 3 (TET3) (TET3)

TET3 is a member of the TET (Ten-eleven translocation) family of dioxygenases that catalyzes the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), and further to 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC), facilitating active DNA demethylation in an Fe(II)/α-ketoglutarate-dependent manner. It contains a carboxy-terminal catalytic domain with cysteine-rich domain (CRD) and double-stranded β-helix (DSBH) regions, plus an amino-terminal CXXC domain for CpG binding. TET3 plays key roles in paternal pronucleus demethylation during zygote formation, embryogenesis, liver maturation, neuronal processes like axon regeneration and synaptic transmission, and immune regulation. It also recruits OGT to promote histone H2B GlcNAcylation and influences gene expression independently of catalysis via protein interactions. Dysregulation links TET3 to developmental disorders, metabolic issues like glucose intolerance, and cancers where it often shows upregulated expression promoting progression via pathways like PI3K/AKT/mTOR.

Other names

Ten-eleven translocation 3TET3 protein

Higher TET3 expression associated with increased sensitivity to sunitinib via regulation of PI3K/AKT and RTK pathways