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HemK methyltransferase family member 2 (HEMK2, also known as N6AMT1) is an enzyme with methyltransferase activity. It mainly catalyzes the methylation of glutamine residues within the GGQ motif of eukaryotic release factor 1 (ETF1) and monomethylates lysine-12 on histone H4 (H4K12me1) in a TRMT112-dependent heterodimer complex. These modifications are essential for proper translational termination and regulation of gene expression. The protein structure consists of an N-terminal substrate-binding domain and a C-terminal methyltransferase domain, characteristic of S-adenosyl-L-methionine (SAM)-dependent methyltransferases. HEMK2/N6AMT1 is highly conserved, present in all domains of life, and is essential for the fidelity of protein synthesis and epigenetic gene regulation. It has been implicated in cancer biology due to its role in cell cycle regulation and gene expression via histone methylation.
Drugs or inhibitors targeting HEMK2 would likely inhibit its methyltransferase activity on glutamine residues of protein release factors (affecting translation termination) or lysine-12 of histone H4 (affecting epigenetic regulation)
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