Alpha-ketoglutarate-dependent dioxygenase FTO

Details

Name

Alpha-ketoglutarate-dependent dioxygenase FTO

Synonyms

• 1.14.11.-
• Fat mass and obesity-associated protein
• KIAA1752

Gene Name

FTO

Organism

Humans

Amino acid sequence

>lcl|BSEQ0009822|Alpha-ketoglutarate-dependent dioxygenase FTO
MKRTPTAEEREREAKKLRLLEELEDTWLPYLTPKDDEFYQQWQLKYPKLILREASSVSEE
LHKEVQEAFLTLHKHGCLFRDLVRIQGKDLLTPVSRILIGNPGCTYKYLNTRLFTVPWPV
KGSNIKHTEAEIAAACETFLKLNDYLQIETIQALEELAAKEKANEDAVPLCMSADFPRVG
MGSSYNGQDEVDIKSRAAYNVTLLNFMDPQKMPYLKEEPYFGMGKMAVSWHHDENLVDRS
AVAVYSYSCEGPEEESEDDSHLEGRDPDIWHVGFKISWDIETPGLAIPLHQGDCYFMLDD
LNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQLALQNVCDDVDNDDVSLKSFE
PAVLKQGEEIHNEVEFEWLRQFWFQGNRYRKCTDWWCQPMAQLEALWKKMEGVTNAVLHE
VKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADQKPECRPYWEKDD
ASMPLPFDLTDIVSELRGQLLEAKP

Number of residues

505

Molecular Weight

58281.53

Theoretical pI

Not Available

GO Classification

Functions

DNA-N1-methyladenine dioxygenase activity / ferrous iron binding / oxidative DNA demethylase activity / oxidative RNA demethylase activity

Processes

adipose tissue development / DNA dealkylation involved in DNA repair / DNA demethylation / oxidative demethylation / oxidative single-stranded DNA demethylation / oxidative single-stranded RNA demethylation / regulation of lipid storage / regulation of multicellular organism growth / regulation of respiratory system process / regulation of white fat cell proliferation / RNA repair / temperature homeostasis

Components

nuclear speck / nucleus

General Function

Oxidative rna demethylase activity

Specific Function

Dioxygenase 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

• FTO_CTD (PF12934)
• FTO_NTD (PF12933)

Transmembrane Regions

Not Available

Cellular Location

Nucleus

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

Chromosome Location

16

Locus

Not Available

External Identifiers

Resource	Link
UniProtKB ID	Q9C0B1
UniProtKB Entry Name	FTO_HUMAN
HGNC ID	HGNC:24678

General 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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB11638	Artenimol	approved, experimental, investigational	unknown	ligand	Details