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Showing Protein Alpha-ketoglutarate-dependent dioxygenase FTO (HMDBP12303)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP12303
Secondary Accession Numbers None
Name Alpha-ketoglutarate-dependent dioxygenase FTO
Synonyms
  1. Fat mass and obesity-associated protein
  2. Protein fatso
  3. U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO
  4. U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO
  5. mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO
  6. mRNA N(6)-methyladenosine demethylase FTO
  7. tRNA N1-methyl adenine demethylase FTO
  8. 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:17991826, PubMed:18775698, PubMed:28002401). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:28002401). M6A demethylation by FTO affects mRNA expression and stability (By similarity). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (By similarity). 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). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (By similarity). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (By similarity). Has no activity towards 1-methylguanine (By similarity). Has no detectable activity towards double-stranded DNA (By similarity). 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:17991826, PubMed:18775698). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:17991826, PubMed:18775698). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:19234441, PubMed:19680540, PubMed:21076408, PubMed:23817550, PubMed:23300482). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:19234441, PubMed:19680540). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (PubMed:23817550).
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
regulation of respiratory system process
regulation of white fat cell proliferation
DNA dealkylation involved in DNA repair
oxidative demethylation
RNA repair
adipose tissue development
regulation of multicellular organism growth
DNA demethylation
temperature homeostasis
Cellular Component
cytosol
cytoplasm
plasma membrane
nucleus
nuclear speck
intracellular membrane-bounded organelle
Molecular Function
ferrous iron binding
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 502
Molecular Weight 58006.365
Theoretical pI 5.117
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q8BGW1
UniProtKB/Swiss-Prot Entry Name FTO_MOUSE
PDB IDs Not Available
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. Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y: The transcriptional landscape of the mammalian genome. Science. 2005 Sep 2;309(5740):1559-63. [PubMed:16141072 ]
  3. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001. [PubMed:21183079 ]
  4. Peters T, Ausmeier K, Ruther U: Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation. Mamm Genome. 1999 Oct;10(10):983-6. doi: 10.1007/s003359901144. [PubMed:10501967 ]
  5. Okazaki N, Kikuno R, Ohara R, Inamoto S, Koseki H, Hiraoka S, Saga Y, Nagase T, Ohara O, Koga H: Prediction of the coding sequences of mouse homologues of KIAA gene: III. the complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries. DNA Res. 2003 Aug 31;10(4):167-80. doi: 10.1093/dnares/10.4.167. [PubMed:14621295 ]
  6. Gerken T, Girard CA, Tung YC, Webby CJ, Saudek V, Hewitson KS, Yeo GS, McDonough MA, Cunliffe S, McNeill LA, Galvanovskis J, Rorsman P, Robins P, Prieur X, Coll AP, Ma M, Jovanovic Z, Farooqi IS, Sedgwick B, Barroso I, Lindahl T, Ponting CP, Ashcroft FM, O'Rahilly S, Schofield CJ: The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science. 2007 Nov 30;318(5855):1469-72. doi: 10.1126/science.1151710. Epub 2007 Nov 8. [PubMed:17991826 ]
  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. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Bruning JC, Ruther U: Inactivation of the Fto gene protects from obesity. Nature. 2009 Apr 16;458(7240):894-8. doi: 10.1038/nature07848. Epub 2009 Feb 22. [PubMed:19234441 ]
  9. Church C, Lee S, Bagg EA, McTaggart JS, Deacon R, Gerken T, Lee A, Moir L, Mecinovic J, Quwailid MM, Schofield CJ, Ashcroft FM, Cox RD: A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene. PLoS Genet. 2009 Aug;5(8):e1000599. doi: 10.1371/journal.pgen.1000599. Epub 2009 Aug 14. [PubMed:19680540 ]
  10. Church C, Moir L, McMurray F, Girard C, Banks GT, Teboul L, Wells S, Bruning JC, Nolan PM, Ashcroft FM, Cox RD: Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet. 2010 Dec;42(12):1086-92. doi: 10.1038/ng.713. Epub 2010 Nov 14. [PubMed:21076408 ]
  11. Stratigopoulos G, Martin Carli JF, O'Day DR, Wang L, Leduc CA, Lanzano P, Chung WK, Rosenbaum M, Egli D, Doherty DA, Leibel RL: Hypomorphism for RPGRIP1L, a ciliary gene vicinal to the FTO locus, causes increased adiposity in mice. Cell Metab. 2014 May 6;19(5):767-79. doi: 10.1016/j.cmet.2014.04.009. [PubMed:24807221 ]
  12. Hess ME, Hess S, Meyer KD, Verhagen LA, Koch L, Bronneke HS, Dietrich MO, Jordan SD, Saletore Y, Elemento O, Belgardt BF, Franz T, Horvath TL, Ruther U, Jaffrey SR, Kloppenburg P, Bruning JC: The fat mass and obesity associated gene (Fto) regulates activity of the dopaminergic midbrain circuitry. Nat Neurosci. 2013 Aug;16(8):1042-8. doi: 10.1038/nn.3449. Epub 2013 Jun 30. [PubMed:23817550 ]
  13. McMurray F, Church CD, Larder R, Nicholson G, Wells S, Teboul L, Tung YC, Rimmington D, Bosch F, Jimenez V, Yeo GS, O'Rahilly S, Ashcroft FM, Coll AP, Cox RD: Adult onset global loss of the fto gene alters body composition and metabolism in the mouse. PLoS Genet. 2013;9(1):e1003166. doi: 10.1371/journal.pgen.1003166. Epub 2013 Jan 3. [PubMed:23300482 ]
  14. 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 ]