Structure
The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.[2] The DSBH domain contains three Fe2+ binding sites and an α-ketoglutarate binding site.[2] This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases.
In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.[3] Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.[3]
Function
Common Function
All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).[4] Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.[4]
Disease
Relevance
Structural highlights
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