RNA demethylase that mediates oxidative demethylation ofdifferent RNA species, such as mRNAs, tRNAs and snRNAs, and acts as aregulator of fat mass, adipogenesis and energy homeostasis. Specifically demethylates N (6) -methyladenosine (m6A) RNA, the most prevalent internal modification ofmessenger RNA (mRNA) in higher eukaryotes. M6A demethylation by FTO affects mRNA expression and stability. Also able to demethylate m6A in U6 small nuclear RNA (snRNA). Mediates demethylation of N (6), 2'-O-dimethyladenosine cap (m6A (m) ), by demethylating the N (6) -methyladenosine at the second transcribed position of mRNAs and U6snRNA. Demethylation of m6A (m) inthe 5'-cap by FTO affects mRNA stability by promoting susceptibility todecapping. Also acts as a tRNA demethylase byremoving N (1) -methyladenine from various tRNAs. Hasno activity towards 1-methylguanine. Has nodetectable activity towards double-stranded DNA. Alsoable to repair alkylated DNA and RNA by oxidative demethylation:demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylaseactivity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. Ability to repairalkylated DNA and RNA is however unsure in vivo. Involved in the regulation of fat mass, adipogenesisand body weight, thereby contributing to the regulation of body sizeand body fat accumulation. Involvedin the regulation of thermogenesis and the control of adipocytedifferentiation into brown or white fat cells. Regulates activity of the dopaminergic midbrain circuitry via itsability to demethylate m6A in mRNAs. Plays an oncogenicrole in a number of acute myeloid leukemias by enhancing leukemiconcogene-mediated cell transformation: acts by mediating m6Ademethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression. [1-6]

MKRTPTAEEREREAKKLRLLEELEDTWLPYLTPKDDEFYQQWQLKYPKLILREASSVSEELHKEVQEAFLTLHKHGCLFRDLVRIQGKDLLTPVSRILIGNPGCTYKYLNTRLFTVPWPVKGSNIKHTEAEIAAACETFLKLNDYLQIETIQALEELAAKEKANEDAVPLCMSADFPRVGMGSSYNGQDEVDIKSRAAYNVTLLNFMDPQKMPYLKEEPYFGMGKMAVSWHHDENLVDRSAVAVYSYSCEGPEEESEDDSHLEGRDPDIWHVGFKISWDIETPGLAIPLHQGDCYFMLDDLNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQLALQNVCDDVDNDDVSLKSFEPAVLKQGEEIHNEVEFEWLRQFWFQGNRYRKCTDWWCQPMAQLEALWKKMEGVTNAVLHEVKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADQKPECRPYWEKDDASMPLPFDLTDIVSELRGQLLEAKP