Methyltransferase N6AMT1

Definition:

Methyltransferase that can methylate proteins and, to a lower extent, arsenic. Catalytic subunit of a heterodimer with TRMT112, which monomethylates 'Lys-12' of histone H4 (H4K12me1), a modification present at the promoters of numerous genes encoding cell cycle regulators. Catalytic subunit of a heterodimer with TRMT112, which catalyzes N5-methylation of Glu residue of proteins with a Gly-Gln-Xaa-Xaa-Xaa-Arg motif. Methylates ETF1 on 'Gln-185'; ETF1 needs to be complexed to ERF3 in its GTP-bound form to be efficiently methylated. May also play a role in the modulation of arsenic-induced toxicity by mediating the conversion of monomethylarsonous acid (3+) into the less toxic dimethylarsonic acid. It however only plays a limited role in arsenic metabolism compared with AS3MT.

References:

[1]. Chuan-Le Xiao, et al. N6-Methyladenine DNA Modification in the Human Genome. Mol Cell. 2018 Jul 19;71(2):306-318.e7. [Content Brief]

[2]. Hao Zhang, et al. Interactive Effects of N6AMT1 and As3MT in Arsenic Biomethylation. Toxicol Sci. 2015 Aug;146(2):354-62. [Content Brief]

[3]. Wenjing Li, et al. Structural insight into human N6amt1-Trm112 complex functioning as a protein methyltransferase. Cell Discov. 2019 Sep 10;5:51. [Content Brief]

[4]. Sabine Figaro, et al. HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS Lett. 2008 Jul 9;582(16):2352-6. [Content Brief]

[5]. Eric Metzger, et al. KMT9 monomethylates histone H4 lysine 12 and controls proliferation of prostate cancer cells. Nat Struct Mol Biol. 2019 May;26(5):361-371. [Content Brief]

[6]. Peng Liu, et al. Deficiency in a glutamine-specific methyltransferase for release factor causes mouse embryonic lethality. Mol Cell Biol. 2010 Sep;30(17):4245-53. [Content Brief]

[7]. Clayton B Woodcock, et al. Human HemK2/KMT9/N6AMT1 is an active protein methyltransferase, but does not act on DNA in vitro, in the presence of Trm112. Cell Discov. 2019 Sep 10;5:50. [Content Brief]

[8]. Xuefeng Ren, et al. Involvement of N-6 adenine-specific DNA methyltransferase 1 (N6AMT1) in arsenic biomethylation and its role in arsenic-induced toxicity. Environ Health Perspect. 2011 Jun;119(6):771-7. [Content Brief]

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