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Description

Methylcytosine dioxygenase TET2 (EC 1.14.11.n2, UniProt Q4JK59, also known as Protein Ayu17-449) is encoded by the Tet2 (also known as Kiaa1546) gene (Gene ID 214133) in murine species. TET (ten-eleven translocation) proteins (TET1, TET2, and TET3) oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine, providing a means for active epigenetic DNA demethylation in mammals. TET proteins also modify genomic thymine residues to 5-hydroxyuracil. TET proteins depend on Fe(II) and 2-oxoglutarate as cofactors for activity, and 2-oxoglutarate is known to inhibit their activity, while ascorbate is shown to stimulate TET-mediated cytosine oxidation. In addition, post-translational modifications (PTMs), such as phosphorylation and O-GlcNAcylation, also play a role in regulating the activity of TET proteins. TET1 and TET2 are found highly expressed in mouse embryonic stem cells (mESCs) and TET3 is known to be upregulated in oocytes and oxidize the silenced paternal pronuclear DNA. High levels of TET proteins and genomic 5-hydroxymethylcytosine in neuronal tissues are also reported.