Alpha-ketoglutarate-dependent dioxygenase FTO

NameAlpha-ketoglutarate-dependent dioxygenase FTO
Synonyms
  • 1.14.11.-
  • Fat mass and obesity-associated protein
  • KIAA1752
Gene NameFTO
OrganismHuman
Amino acid sequence
>lcl|BSEQ0009822|Alpha-ketoglutarate-dependent dioxygenase FTO
MKRTPTAEEREREAKKLRLLEELEDTWLPYLTPKDDEFYQQWQLKYPKLILREASSVSEE
LHKEVQEAFLTLHKHGCLFRDLVRIQGKDLLTPVSRILIGNPGCTYKYLNTRLFTVPWPV
KGSNIKHTEAEIAAACETFLKLNDYLQIETIQALEELAAKEKANEDAVPLCMSADFPRVG
MGSSYNGQDEVDIKSRAAYNVTLLNFMDPQKMPYLKEEPYFGMGKMAVSWHHDENLVDRS
AVAVYSYSCEGPEEESEDDSHLEGRDPDIWHVGFKISWDIETPGLAIPLHQGDCYFMLDD
LNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQLALQNVCDDVDNDDVSLKSFE
PAVLKQGEEIHNEVEFEWLRQFWFQGNRYRKCTDWWCQPMAQLEALWKKMEGVTNAVLHE
VKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADQKPECRPYWEKDD
ASMPLPFDLTDIVSELRGQLLEAKP
Number of residues505
Molecular Weight58281.53
Theoretical pINot Available
GO Classification
Functions
  • ferrous iron binding
  • DNA-N1-methyladenine dioxygenase activity
  • oxidative DNA demethylase activity
  • oxidative RNA demethylase activity
Processes
  • RNA repair
  • regulation of multicellular organism growth
  • temperature homeostasis
  • adipose tissue development
  • DNA dealkylation involved in DNA repair
  • oxidative single-stranded DNA demethylation
  • DNA demethylation
  • oxidative demethylation
  • oxidative single-stranded RNA demethylation
  • regulation of lipid storage
  • regulation of respiratory system process
  • regulation of white fat cell proliferation
Components
  • nuclear speck
  • nucleus
General FunctionOxidative rna demethylase activity
Specific FunctionDioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. Has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. Has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:26458103). Has no activity towards 1-methylguanine. Has no detectable activity towards double-stranded DNA. Requires molecular oxygen, alpha-ketoglutarate and iron. Contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. Contributes to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein IDNot Available
UniProtKB IDQ9C0B1
UniProtKB Entry NameFTO_HUMAN
Cellular LocationNucleus
Gene sequence
>lcl|BSEQ0013935|Alpha-ketoglutarate-dependent dioxygenase FTO (FTO)
ATGAAGCGCACCCCGACTGCCGAGGAACGAGAGCGCGAAGCTAAGAAACTGAGGCTTCTT
GAAGAGCTTGAAGACACTTGGCTCCCTTATCTGACCCCCAAAGATGATGAATTCTATCAG
CAGTGGCAGCTGAAATATCCTAAACTAATTCTCCGAGAAGCCAGCAGTGTATCTGAGGAG
CTCCATAAAGAGGTTCAAGAAGCCTTTCTCACACTGCACAAGCATGGCTGCTTATTTCGG
GACCTGGTTAGGATCCAAGGCAAAGATCTGCTCACTCCGGTATCTCGCATCCTCATTGGT
AATCCAGGCTGCACCTACAAGTACCTGAACACCAGGCTCTTTACGGTCCCCTGGCCAGTG
AAAGGGTCTAATATAAAACACACCGAGGCTGAAATAGCCGCTGCTTGTGAGACCTTCCTC
AAGCTCAATGACTACCTGCAGATAGAAACCATCCAGGCTTTGGAAGAACTTGCTGCCAAA
GAGAAGGCTAATGAGGATGCTGTGCCATTGTGTATGTCTGCAGATTTCCCCAGGGTTGGG
ATGGGTTCATCCTACAACGGACAAGATGAAGTGGACATTAAGAGCAGAGCAGCATACAAC
GTAACTTTGCTGAATTTCATGGATCCTCAGAAAATGCCATACCTGAAAGAGGAACCTTAT
TTTGGCATGGGGAAAATGGCAGTGAGCTGGCATCATGATGAAAATCTGGTGGACAGGTCA
GCGGTGGCAGTGTACAGTTATAGCTGTGAAGGCCCTGAAGAGGAAAGTGAGGATGACTCT
CATCTCGAAGGCAGGGATCCTGATATTTGGCATGTTGGTTTTAAGATCTCATGGGACATA
GAGACACCTGGTTTGGCGATACCCCTTCACCAAGGAGACTGCTATTTCATGCTTGATGAT
CTCAATGCCACCCACCAACACTGTGTTTTGGCCGGTTCACAACCTCGGTTTAGTTCCACC
CACCGAGTGGCAGAGTGCTCAACAGGAACCTTGGATTATATTTTACAACGCTGTCAGTTG
GCTCTGCAGAATGTCTGTGACGATGTGGACAATGATGATGTCTCTTTGAAATCCTTTGAG
CCTGCAGTTTTGAAACAAGGAGAAGAAATTCATAATGAGGTCGAGTTTGAGTGGCTGAGG
CAGTTTTGGTTTCAAGGCAATCGATACAGAAAGTGCACTGACTGGTGGTGTCAACCCATG
GCTCAACTGGAAGCACTGTGGAAGAAGATGGAGGGTGTGACAAATGCTGTGCTTCATGAA
GTTAAAAGAGAGGGGCTCCCCGTGGAACAAAGGAATGAAATCTTGACTGCCATCCTTGCC
TCGCTCACTGCACGCCAGAACCTGAGGAGAGAATGGCATGCCAGGTGCCAGTCACGAATT
GCCCGAACATTACCTGCTGATCAGAAGCCAGAATGTCGGCCATACTGGGAAAAGGATGAT
GCTTCGATGCCTCTGCCGTTTGACCTCACAGACATCGTTTCAGAACTCAGAGGTCAGCTT
CTGGAAGCAAAACCCTAG
GenBank Gene IDNot Available
GeneCard IDNot Available
GenAtlas IDNot Available
HGNC IDHGNC:24678
Chromosome Location16
LocusNot Available
References
  1. Nagase T, Kikuno R, Hattori A, Kondo Y, Okumura K, Ohara O: Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 2000 Dec 31;7(6):347-55. 11214970
  2. Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, Campbell CS, Campbell ML, Campbell EW, Caoile C, Challacombe JF, Chasteen LA, Chertkov O, Chi HC, Christensen M, Clark LM, Cohn JD, Denys M, Detter JC, Dickson M, Dimitrijevic-Bussod M, Escobar J, Fawcett JJ, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Goodwin LA, Grady DL, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Hildebrand CE, Huang W, Israni S, Jett J, Jewett PB, Kadner K, Kimball H, Kobayashi A, Krawczyk MC, Leyba T, Longmire JL, Lopez F, Lou Y, Lowry S, Ludeman T, Manohar CF, Mark GA, McMurray KL, Meincke LJ, Morgan J, Moyzis RK, Mundt MO, Munk AC, Nandkeshwar RD, Pitluck S, Pollard M, Predki P, Parson-Quintana B, Ramirez L, Rash S, Retterer J, Ricke DO, Robinson DL, Rodriguez A, Salamov A, Saunders EH, Scott D, Shough T, Stallings RL, Stalvey M, Sutherland RD, Tapia R, Tesmer JG, Thayer N, Thompson LS, Tice H, Torney DC, Tran-Gyamfi M, Tsai M, Ulanovsky LE, Ustaszewska A, Vo N, White PS, Williams AL, Wills PL, Wu JR, Wu K, Yang J, Dejong P, Bruce D, Doggett NA, Deaven L, Schmutz J, Grimwood J, Richardson P, Rokhsar DS, Eichler EE, Gilna P, Lucas SM, Myers RM, Rubin EM, Pennacchio LA: The sequence and analysis of duplication-rich human chromosome 16. Nature. 2004 Dec 23;432(7020):988-94. 15616553
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  4. Dina C, Meyre D, Gallina S, Durand E, Korner A, Jacobson P, Carlsson LM, Kiess W, Vatin V, Lecoeur C, Delplanque J, Vaillant E, Pattou F, Ruiz J, Weill J, Levy-Marchal C, Horber F, Potoczna N, Hercberg S, Le Stunff C, Bougneres P, Kovacs P, Marre M, Balkau B, Cauchi S, Chevre JC, Froguel P: Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007 Jun;39(6):724-6. Epub 2007 May 13. 17496892
  5. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI: A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007 May 11;316(5826):889-94. Epub 2007 Apr 12. 17434869
  6. Jia G, Yang CG, Yang S, Jian X, Yi C, Zhou Z, He C: Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO. FEBS Lett. 2008 Oct 15;582(23-24):3313-9. doi: 10.1016/j.febslet.2008.08.019. Epub 2008 Sep 5. 18775698
  7. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. 19608861
  8. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  9. Jia G, Fu Y, Zhao X, Dai Q, Zheng G, Yang Y, Yi C, Lindahl T, Pan T, Yang YG, He C: N6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO. Nat Chem Biol. 2011 Oct 16;7(12):885-7. doi: 10.1038/nchembio.687. 22002720
  10. Zhou J, Wan J, Gao X, Zhang X, Jaffrey SR, Qian SB: Dynamic m(6)A mRNA methylation directs translational control of heat shock response. Nature. 2015 Oct 22;526(7574):591-4. doi: 10.1038/nature15377. Epub 2015 Oct 12. 26458103
  11. Han Z, Niu T, Chang J, Lei X, Zhao M, Wang Q, Cheng W, Wang J, Feng Y, Chai J: Crystal structure of the FTO protein reveals basis for its substrate specificity. Nature. 2010 Apr 22;464(7292):1205-9. doi: 10.1038/nature08921. Epub 2010 Apr 7. 20376003
  12. Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, Meyre D, Golzio C, Molinari F, Kadhom N, Etchevers HC, Saudek V, Farooqi IS, Froguel P, Lindahl T, O'Rahilly S, Munnich A, Colleaux L: Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet. 2009 Jul;85(1):106-11. doi: 10.1016/j.ajhg.2009.06.002. Epub 2009 Jun 25. 19559399