N-terminal methyltransferase 1 (NTMT1)

N-terminal methyltransferase 1 (NTMT1) is a highly conserved S-adenosyl-L-methionine–dependent methyltransferase that specifically catalyzes the mono-, di-, or tri-methylation of the exposed α-amino group on proteins containing an [Ala/Gly/Ser]-Pro-Lys (XPK) motif at the N-terminus[1][2][5]. NTMT1 recognizes and modifies substrates such as RCC1, RB1, DDB2, CENP-A/B, and PARP3, influencing their DNA-binding capacity and other functions[2][3]. Through these activities, NTMT1 is implicated in the regulation of DNA damage response, genome stability, cancer progression, and aging[1][4]. NTMT1 is considered a promising therapeutic target, and several potent and selective small-molecule inhibitors, such as DC541 and BM30, have been developed in preclinical research[4].

Other names

Protein N-terminal methyltransferase 1N-terminal RCC1 methyltransferaseNRMT1METTL11A

Inhibition of methyl transfer from S-adenosyl-L-methionine to protein α-N-terminals blocks substrate modification. Prevents α-N-terminal methylation, impacting function of targeted proteins.