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Showing Protein Alpha-ketoglutarate-dependent dioxygenase FTO (HMDBP12304)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP12304
Secondary Accession Numbers None
Name Alpha-ketoglutarate-dependent dioxygenase FTO
Synonyms
  1. Fat mass and obesity-associated protein
  2. U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO
  3. U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO
  4. mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO
  5. mRNA N(6)-methyladenosine demethylase FTO
  6. tRNA N1-methyl adenine demethylase FTO
  7. m6A(m)-demethylase FTO
Gene Name FTO
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:22002720, PubMed:26458103, PubMed:28002401, PubMed:30197295, PubMed:26457839, PubMed:25452335). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:26458103, PubMed:30197295, PubMed:26457839, PubMed:25452335). M6A demethylation by FTO affects mRNA expression and stability (PubMed:30197295). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (PubMed:30197295). 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 U6 snRNA (PubMed:28002401, PubMed:30197295). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (PubMed:28002401). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (PubMed:30197295). Has no activity towards 1-methylguanine (PubMed:20376003). Has no detectable activity towards double-stranded DNA (PubMed:20376003). Also able 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 demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:18775698, PubMed:20376003). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:26287746). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression (PubMed:28017614, PubMed:29249359).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
mRNA destabilization
oxidative single-stranded DNA demethylation
oxidative single-stranded RNA demethylation
regulation of brown fat cell differentiation
regulation of lipid storage
DNA dealkylation involved in DNA repair
oxidative demethylation
RNA repair
regulation of multicellular organism growth
DNA demethylation
Cellular Component
cytosol
cytoplasm
plasma membrane
nucleus
nucleoplasm
nuclear speck
intracellular membrane-bounded organelle
Molecular Function
ferrous iron binding
transferase activity
oxidative DNA demethylase activity
oxidative RNA demethylase activity
RNA N6-methyladenosine dioxygenase activity
tRNA demethylase activity
DNA-N1-methyladenine dioxygenase activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 505
Molecular Weight 58281.53
Theoretical pI 5.227
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9C0B1
UniProtKB/Swiss-Prot Entry Name FTO_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. 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. [PubMed:15489334 ]
  2. 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. [PubMed:19608861 ]
  3. 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. [PubMed:15616553 ]
  4. 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. [PubMed:11214970 ]
  5. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  6. 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. [PubMed:21269460 ]
  7. 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. [PubMed:18775698 ]
  8. Mauer J, Luo X, Blanjoie A, Jiao X, Grozhik AV, Patil DP, Linder B, Pickering BF, Vasseur JJ, Chen Q, Gross SS, Elemento O, Debart F, Kiledjian M, Jaffrey SR: Reversible methylation of m(6)Am in the 5' cap controls mRNA stability. Nature. 2017 Jan 19;541(7637):371-375. doi: 10.1038/nature21022. Epub 2016 Dec 21. [PubMed:28002401 ]
  9. 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. doi: 10.1038/ng2048. Epub 2007 May 13. [PubMed:17496892 ]
  10. 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. doi: 10.1126/science.1141634. Epub 2007 Apr 12. [PubMed:17434869 ]
  11. 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. [PubMed:22002720 ]
  12. Yang J, Loos RJ, Powell JE, Medland SE, Speliotes EK, Chasman DI, Rose LM, Thorleifsson G, Steinthorsdottir V, Magi R, Waite L, Smith AV, Yerges-Armstrong LM, Monda KL, Hadley D, Mahajan A, Li G, Kapur K, Vitart V, Huffman JE, Wang SR, Palmer C, Esko T, Fischer K, Zhao JH, Demirkan A, Isaacs A, Feitosa MF, Luan J, Heard-Costa NL, White C, Jackson AU, Preuss M, Ziegler A, Eriksson J, Kutalik Z, Frau F, Nolte IM, Van Vliet-Ostaptchouk JV, Hottenga JJ, Jacobs KB, Verweij N, Goel A, Medina-Gomez C, Estrada K, Bragg-Gresham JL, Sanna S, Sidore C, Tyrer J, Teumer A, Prokopenko I, Mangino M, Lindgren CM, Assimes TL, Shuldiner AR, Hui J, Beilby JP, McArdle WL, Hall P, Haritunians T, Zgaga L, Kolcic I, Polasek O, Zemunik T, Oostra BA, Junttila MJ, Gronberg H, Schreiber S, Peters A, Hicks AA, Stephens J, Foad NS, Laitinen J, Pouta A, Kaakinen M, Willemsen G, Vink JM, Wild SH, Navis G, Asselbergs FW, Homuth G, John U, Iribarren C, Harris T, Launer L, Gudnason V, O'Connell JR, Boerwinkle E, Cadby G, Palmer LJ, James AL, Musk AW, Ingelsson E, Psaty BM, Beckmann JS, Waeber G, Vollenweider P, Hayward C, Wright AF, Rudan I, Groop LC, Metspalu A, Khaw KT, van Duijn CM, Borecki IB, Province MA, Wareham NJ, Tardif JC, Huikuri HV, Cupples LA, Atwood LD, Fox CS, Boehnke M, Collins FS, Mohlke KL, Erdmann J, Schunkert H, Hengstenberg C, Stark K, Lorentzon M, Ohlsson C, Cusi D, Staessen JA, Van der Klauw MM, Pramstaller PP, Kathiresan S, Jolley JD, Ripatti S, Jarvelin MR, de Geus EJ, Boomsma DI, Penninx B, Wilson JF, Campbell H, Chanock SJ, van der Harst P, Hamsten A, Watkins H, Hofman A, Witteman JC, Zillikens MC, Uitterlinden AG, Rivadeneira F, Zillikens MC, Kiemeney LA, Vermeulen SH, Abecasis GR, Schlessinger D, Schipf S, Stumvoll M, Tonjes A, Spector TD, North KE, Lettre G, McCarthy MI, Berndt SI, Heath AC, Madden PA, Nyholt DR, Montgomery GW, Martin NG, McKnight B, Strachan DP, Hill WG, Snieder H, Ridker PM, Thorsteinsdottir U, Stefansson K, Frayling TM, Hirschhorn JN, Goddard ME, Visscher PM: FTO genotype is associated with phenotypic variability of body mass index. Nature. 2012 Oct 11;490(7419):267-72. doi: 10.1038/nature11401. Epub 2012 Sep 16. [PubMed:22982992 ]
  13. Smemo S, Tena JJ, Kim KH, Gamazon ER, Sakabe NJ, Gomez-Marin C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nobrega MA: Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature. 2014 Mar 20;507(7492):371-5. doi: 10.1038/nature13138. Epub 2014 Mar 12. [PubMed:24646999 ]
  14. Claussnitzer M, Dankel SN, Kim KH, Quon G, Meuleman W, Haugen C, Glunk V, Sousa IS, Beaudry JL, Puviindran V, Abdennur NA, Liu J, Svensson PA, Hsu YH, Drucker DJ, Mellgren G, Hui CC, Hauner H, Kellis M: FTO Obesity Variant Circuitry and Adipocyte Browning in Humans. N Engl J Med. 2015 Sep 3;373(10):895-907. doi: 10.1056/NEJMoa1502214. Epub 2015 Aug 19. [PubMed:26287746 ]
  15. 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. [PubMed:26458103 ]
  16. Li Z, Weng H, Su R, Weng X, Zuo Z, Li C, Huang H, Nachtergaele S, Dong L, Hu C, Qin X, Tang L, Wang Y, Hong GM, Huang H, Wang X, Chen P, Gurbuxani S, Arnovitz S, Li Y, Li S, Strong J, Neilly MB, Larson RA, Jiang X, Zhang P, Jin J, He C, Chen J: FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N(6)-Methyladenosine RNA Demethylase. Cancer Cell. 2017 Jan 9;31(1):127-141. doi: 10.1016/j.ccell.2016.11.017. Epub 2016 Dec 22. [PubMed:28017614 ]
  17. Su R, Dong L, Li C, Nachtergaele S, Wunderlich M, Qing Y, Deng X, Wang Y, Weng X, Hu C, Yu M, Skibbe J, Dai Q, Zou D, Wu T, Yu K, Weng H, Huang H, Ferchen K, Qin X, Zhang B, Qi J, Sasaki AT, Plas DR, Bradner JE, Wei M, Marcucci G, Jiang X, Mulloy JC, Jin J, He C, Chen J: R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m(6)A/MYC/CEBPA Signaling. Cell. 2018 Jan 11;172(1-2):90-105.e23. doi: 10.1016/j.cell.2017.11.031. Epub 2017 Dec 14. [PubMed:29249359 ]
  18. Wei J, Liu F, Lu Z, Fei Q, Ai Y, He PC, Shi H, Cui X, Su R, Klungland A, Jia G, Chen J, He C: Differential m(6)A, m(6)Am, and m(1)A Demethylation Mediated by FTO in the Cell Nucleus and Cytoplasm. Mol Cell. 2018 Sep 20;71(6):973-985.e5. doi: 10.1016/j.molcel.2018.08.011. Epub 2018 Sep 6. [PubMed:30197295 ]
  19. 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. [PubMed:20376003 ]
  20. Aik W, Demetriades M, Hamdan MK, Bagg EA, Yeoh KK, Lejeune C, Zhang Z, McDonough MA, Schofield CJ: Structural basis for inhibition of the fat mass and obesity associated protein (FTO). J Med Chem. 2013 May 9;56(9):3680-8. doi: 10.1021/jm400193d. Epub 2013 Apr 23. [PubMed:23547775 ]
  21. Toh JDW, Sun L, Lau LZM, Tan J, Low JJA, Tang CWQ, Cheong EJY, Tan MJH, Chen Y, Hong W, Gao YG, Woon ECY: A strategy based on nucleotide specificity leads to a subfamily-selective and cell-active inhibitor of N(6)-methyladenosine demethylase FTO. Chem Sci. 2015 Jan 1;6(1):112-122. doi: 10.1039/c4sc02554g. Epub 2014 Sep 22. [PubMed:28553460 ]
  22. Wang T, Hong T, Huang Y, Su H, Wu F, Chen Y, Wei L, Huang W, Hua X, Xia Y, Xu J, Gan J, Yuan B, Feng Y, Zhang X, Yang CG, Zhou X: Fluorescein Derivatives as Bifunctional Molecules for the Simultaneous Inhibiting and Labeling of FTO Protein. J Am Chem Soc. 2015 Nov 4;137(43):13736-9. doi: 10.1021/jacs.5b06690. Epub 2015 Oct 20. [PubMed:26457839 ]
  23. Huang Y, Yan J, Li Q, Li J, Gong S, Zhou H, Gan J, Jiang H, Jia GF, Luo C, Yang CG: Meclofenamic acid selectively inhibits FTO demethylation of m6A over ALKBH5. Nucleic Acids Res. 2015 Jan;43(1):373-84. doi: 10.1093/nar/gku1276. Epub 2014 Dec 1. [PubMed:25452335 ]
  24. 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. [PubMed:19559399 ]
  25. Rohena L, Lawson M, Guzman E, Ganapathi M, Cho MT, Haverfield E, Anyane-Yeboa K: FTO variant associated with malformation syndrome. Am J Med Genet A. 2016 Apr;170A(4):1023-8. doi: 10.1002/ajmg.a.37515. Epub 2015 Dec 24. [PubMed:26697951 ]
  26. Caglayan AO, Tuysuz B, Coskun S, Quon J, Harmanci AS, Baranoski JF, Baran B, Erson-Omay EZ, Henegariu O, Mane SM, Bilguvar K, Yasuno K, Gunel M: A patient with a novel homozygous missense mutation in FTO and concomitant nonsense mutation in CETP. J Hum Genet. 2016 May;61(5):395-403. doi: 10.1038/jhg.2015.160. Epub 2016 Jan 7. [PubMed:26740239 ]
  27. Daoud H, Zhang D, McMurray F, Yu A, Luco SM, Vanstone J, Jarinova O, Carson N, Wickens J, Shishodia S, Choi H, McDonough MA, Schofield CJ, Harper ME, Dyment DA, Armour CM: Identification of a pathogenic FTO mutation by next-generation sequencing in a newborn with growth retardation and developmental delay. J Med Genet. 2016 Mar;53(3):200-7. doi: 10.1136/jmedgenet-2015-103399. Epub 2015 Sep 16. [PubMed:26378117 ]