Reaction: N6-methyladenine in mRNA + 2-oxoglutarate + O2 = adenine in mRNA + formaldehyde + succinate + CO2
Other name(s): ALKBH5; FTO
Systematic name: mRNA-N6-methyladenosine,2-oxoglutarate:oxygen oxidoreductase (formaldehyde-forming)
Comments: Contains iron(II). Catalyses oxidative demethylation of mRNA N6-methyladenine. The FTO enzyme from human can also demethylate N3-methylthymine from single stranded DNA and N3-methyluridine from single stranded RNA [1,2] with low activity [3].
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Jia, G., Yang, C.G., Yang, S., Jian, X., Yi, C., Zhou, Z. and He, C. Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 582 (2008) 3313-3319. [PMID: 18775698]
2. Han, Z., Niu, T., Chang, J., Lei, X., Zhao, M., Wang, Q., Cheng, W., Wang, J., Feng, Y. and Chai, J. Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature 464 (2010) 1205-1209. [PMID: 20376003]
3. Jia, G., Fu, Y., Zhao, X., Dai, Q., Zheng, G., Yang, Y., Yi, C., Lindahl, T., Pan, T., Yang, Y.G. and He, C. N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7 (2011) 885-887. [PMID: 22002720]
4. Zheng, G., Dahl, J.A., Niu, Y., Fedorcsak, P., Huang, C.M., Li, C.J., Vagbo, C.B., Shi, Y., Wang, W.L., Song, S.H., Lu, Z., Bosmans, R.P., Dai, Q., Hao, Y.J., Yang, X., Zhao, W.M., Tong, W.M., Wang, X.J., Bogdan, F., Furu, K., Fu, Y., Jia, G., Zhao, X., Liu, J., Krokan, H.E., Klungland, A., Yang, Y.G. and He, C. ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49 (2013) 18-29. [PMID: 23177736]
5. Feng, C., Liu, Y., Wang, G., Deng, Z., Zhang, Q., Wu, W., Tong, Y., Cheng, C. and Chen, Z. Crystal structures of the human RNA demethylase Alkbh5 reveal basis for substrate recognition. J. Biol. Chem. 289 (2014) 11571-11583. [PMID: 24616105]
6. Xu, C., Liu, K., Tempel, W., Demetriades, M., Aik, W., Schofield, C.J. and Min, J. Structures of human ALKBH5 demethylase reveal a unique binding mode for specific single-stranded N6-methyladenosine RNA demethylation. J. Biol. Chem. 289 (2014) 17299-17311. [PMID: 24778178]
7. Aik, W., Scotti, J.S., Choi, H., Gong, L., Demetriades, M., Schofield, C.J. and McDonough, M.A. Structure of human RNA N6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation. Nucleic Acids Res. 42 (2014) 4741-4754. [PMID: 24489119]