Target intelligence / Profile preview

HemK methyltransferase family member 2 (HEMK2)

Target
HEMK2
Molecular classification
Enzyme, Protein methyltransferase, Histone methyltransferase, S-adenosyl-L-methionine-dependent methyltransferase
01

Overview

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.

Other names
N6AMT1N(6)-adenine-specific DNA methyltransferase 1Protein glutamine methyltransferaseKMT9 (for the H4K12 methyltransferase activity)N6AMT1/HEMK2
02

Mechanism of action

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)

03

Biological functions

Methylation of protein chain release factors (e.g., ETF1, also called eukaryotic release factor 1) which is important for translational terminationMonomethylation of lysine-12 on histone H4 (histone modification)Regulation of gene expression (through histone H4 methylation)Involvement in cell cycle controlModulation of translational fidelity and ribosome function
04

Disease associations

Cancer (dysregulation can alter translation termination, gene expression, and cell cycle regulation)Other (mutation/loss affects protein synthesis and potentially broad cell physiology)
05

Safety considerations

Potential for broad disruption of protein synthesis fidelity, gene expression, and cell proliferation, leading to possible cytotoxicity and off-target effects
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Interacting drugs

None clearly identified or clinically established; no FDA-approved drugs known to target HEMK2/N6AMT1 directly as of current knowledge
07

Biomarkers

Monomethylation of histone H4 at lysine-12 (H4K12me1)N5-methylglutamine on ETF1/release factors

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