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Methyltransferase-like protein 7A (METTL7A), also known as thiol methyltransferase 1A (TMT1A), is a poorly characterized S-methyltransferase enzyme that catalyzes the methylation of exogenous thiol-containing compounds, including certain drugs (notably thiol-based histone deacetylase inhibitors). Its enzymatic action can inactivate these drugs, leading to chemotherapeutic resistance in cancer cells. TMT1A is widely conserved across mammals, birds, and fish, and its overexpression has been documented to mediate resistance by directly methylating reactive drug thiol groups. Although originally hypothesized more than 60 years ago, it has only recently been molecularly identified as METTL7A. Beyond drug interactions, METTL7A is also reported to methylate hydrogen sulfide and may play a role in cell signaling related to sulfur metabolism. However, its normal physiological function in humans remains unclear, as it does not methylate major endogenous thiols like cysteine or glutathione
Drug inactivation via methylation: METTL7A methylates the thiol group of certain drugs (such as active romidepsin and other thiol-based HDAC inhibitors), inactivating them and thereby conferring drug resistance. Methylates hydrogen sulfide, converting it to methanethiol.
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