6ped

Structural highlights

Function

[N6MT1_HUMAN] Methyltransferase that can methylate both proteins and DNA, and to a lower extent, arsenic (PubMed:18539146, PubMed:21193388, PubMed:30017583). 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 (PubMed:18539146) (By similarity). Methylates ETF1 on 'Gln-185'; ETF1 needs to be complexed to ERF3 in its GTP-bound form to be efficiently methylated (PubMed:18539146, PubMed:20606008). Also acts as a N(6)-adenine-specific DNA methyltransferase by mediating methylation of DNA on the 6th position of adenine (N(6)-methyladenosine) (PubMed:30017583). N(6)-methyladenosine (m6A) DNA is significantly enriched in exonic regions and is associated with gene transcriptional activation (PubMed:30017583). 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 (PubMed:21193388, PubMed:25997655). It however only plays a limited role in arsenic metabolism compared with AS3MT (PubMed:25997655).[UniProtKB:Q6SKR2]^{[1] [2] [3] [4] [5]} [TR112_HUMAN] Acts as an activator of both rRNA/tRNA and protein methyltransferases (PubMed:25851604). Together with methyltransferase BUD23, methylates the N(7) position of a guanine in 18S rRNA (PubMed:25851604). The heterodimer with HEMK2/N6AMT1 catalyzes N5-methylation of ETF1 on 'Gln-185', using S-adenosyl L-methionine as methyl donor (PubMed:18539146). The heterodimer with ALKBH8 catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA species (PubMed:20308323). Involved in the pre-rRNA processing steps leading to small-subunit rRNA production (PubMed:25851604).^{[6] [7] [8]}

References

1. ↑ Figaro S, Scrima N, Buckingham RH, Heurgue-Hamard V. HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS Lett. 2008 Jul 9;582(16):2352-6. doi: 10.1016/j.febslet.2008.05.045. Epub, 2008 Jun 6. PMID:18539146 doi:http://dx.doi.org/10.1016/j.febslet.2008.05.045
2. ↑ Liu P, Nie S, Li B, Yang ZQ, Xu ZM, Fei J, Lin C, Zeng R, Xu GL. Deficiency in a glutamine-specific methyltransferase for release factor causes mouse embryonic lethality. Mol Cell Biol. 2010 Sep;30(17):4245-53. doi: 10.1128/MCB.00218-10. Epub 2010 Jul , 6. PMID:20606008 doi:http://dx.doi.org/10.1128/MCB.00218-10
3. ↑ Ren X, Aleshin M, Jo WJ, Dills R, Kalman DA, Vulpe CD, Smith MT, Zhang L. 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. doi: 10.1289/ehp.1002733. Epub, 2010 Dec 30. PMID:21193388 doi:http://dx.doi.org/10.1289/ehp.1002733
4. ↑ Zhang H, Ge Y, He P, Chen X, Carina A, Qiu Y, Aga DS, Ren X. Interactive Effects of N6AMT1 and As3MT in Arsenic Biomethylation. Toxicol Sci. 2015 Aug;146(2):354-62. doi: 10.1093/toxsci/kfv101. Epub 2015 May, 20. PMID:25997655 doi:http://dx.doi.org/10.1093/toxsci/kfv101
5. ↑ Xiao CL, Zhu S, He M, Chen, Zhang Q, Chen Y, Yu G, Liu J, Xie SQ, Luo F, Liang Z, Wang DP, Bo XC, Gu XF, Wang K, Yan GR. N(6)-Methyladenine DNA Modification in the Human Genome. Mol Cell. 2018 Jul 19;71(2):306-318.e7. doi: 10.1016/j.molcel.2018.06.015. Epub, 2018 Jul 12. PMID:30017583 doi:http://dx.doi.org/10.1016/j.molcel.2018.06.015
6. ↑ Figaro S, Scrima N, Buckingham RH, Heurgue-Hamard V. HemK2 protein, encoded on human chromosome 21, methylates translation termination factor eRF1. FEBS Lett. 2008 Jul 9;582(16):2352-6. doi: 10.1016/j.febslet.2008.05.045. Epub, 2008 Jun 6. PMID:18539146 doi:http://dx.doi.org/10.1016/j.febslet.2008.05.045
7. ↑ Fu D, Brophy JA, Chan CT, Atmore KA, Begley U, Paules RS, Dedon PC, Begley TJ, Samson LD. Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol Cell Biol. 2010 May;30(10):2449-59. doi: 10.1128/MCB.01604-09. Epub 2010 Mar , 22. PMID:20308323 doi:http://dx.doi.org/10.1128/MCB.01604-09
8. ↑ Zorbas C, Nicolas E, Wacheul L, Huvelle E, Heurgue-Hamard V, Lafontaine DL. The human 18S rRNA base methyltransferases DIMT1L and WBSCR22-TRMT112 but not rRNA modification are required for ribosome biogenesis. Mol Biol Cell. 2015 Jun 1;26(11):2080-95. doi: 10.1091/mbc.E15-02-0073. Epub 2015, Apr 7. PMID:25851604 doi:http://dx.doi.org/10.1091/mbc.E15-02-0073