UniProt Accession

 FTO_HUMAN; Q9C0B1; A2RUH1; B2RNS0; Q0P676; Q7Z785 

Genbank Protein ID

 AB051539; AC007347; AC007496; AC007909; BC003583; BC030798; BC132892; BC137091 

Genbank Nucleotide ID

 BAB21843.1; AAH03583.1; AAH30798.1; AAI32893.1; AAI37092.1 

Protein Name

 Alpha-ketoglutarate-dependent dioxygenase FTO 

Protein Synonyms/Alias

 Fat mass and obesity-associated protein 

Gene Name

 FTO 

Gene Synonyms/Alias

 KIAA1752 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
45	FYQQWQLKYPKLILR	ubiquitination	[1, 2]
48	QWQLKYPKLILREAS	ubiquitination	[1, 2]
88	DLVRIQGKDLLTPVS	ubiquitination	[1, 2, 3, 4]
107	GNPGCTYKYLNTRLF	ubiquitination	[1, 2, 3]
121	FTVPWPVKGSNIKHT	ubiquitination	[1, 2, 3]
126	PVKGSNIKHTEAEIA	ubiquitination	[3]
162	EELAAKEKANEDAVP	ubiquitination	[3]
194	GQDEVDIKSRAAYNV	ubiquitination	[3, 4, 5, 6]
211	LNFMDPQKMPYLKEE	ubiquitination	[1, 2]
216	PQKMPYLKEEPYFGM	acetylation	[7, 8, 9]
216	PQKMPYLKEEPYFGM	ubiquitination	[1, 2, 3]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [8] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 

Functional Description

 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. 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. 

Sequence Annotation

 REGION 32 327 Fe2OG dioxygenase domain.
 REGION 213 224 Loop L1; predicted to block binding of
 REGION 231 234 Substrate binding.
 REGION 316 318 Alpha-ketoglutarate binding.
 METAL 231 231 Iron; catalytic.
 METAL 233 233 Iron; catalytic.
 METAL 307 307 Iron; catalytic.
 BINDING 96 96 Substrate.
 BINDING 108 108 Substrate.
 BINDING 205 205 Alpha-ketoglutarate.
 BINDING 295 295 Alpha-ketoglutarate.
 BINDING 320 320 Alpha-ketoglutarate.
 BINDING 322 322 Alpha-ketoglutarate.
 MOD_RES 216 216 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; Alternative splicing; Complete proteome; Dioxygenase; Disease mutation; DNA damage; DNA repair; Iron; Metal-binding; Nucleus; Obesity; Oxidoreductase; Polymorphism; Reference proteome; RNA repair. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 505 AA 

Protein Sequence

Gene Ontology

 GO:0005634; C:nucleus; ISS:BHF-UCL.
 GO:0043734; F:DNA-N1-methyladenine dioxygenase activity; IDA:UniProtKB.
 GO:0008198; F:ferrous iron binding; IDA:UniProtKB.
 GO:0035516; F:oxidative DNA demethylase activity; IDA:UniProtKB.
 GO:0035515; F:oxidative RNA demethylase activity; IDA:BHF-UCL.
 GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:UniProtKB-KW.
 GO:0060612; P:adipose tissue development; IEA:Compara.
 GO:0006307; P:DNA dealkylation involved in DNA repair; IDA:UniProtKB.
 GO:0035552; P:oxidative single-stranded DNA demethylation; IDA:UniProtKB.
 GO:0035553; P:oxidative single-stranded RNA demethylation; IDA:BHF-UCL.
 GO:0010883; P:regulation of lipid storage; IEA:Compara.
 GO:0040014; P:regulation of multicellular organism growth; IEA:Compara.
 GO:0044065; P:regulation of respiratory system process; IEA:Compara.
 GO:0070350; P:regulation of white fat cell proliferation; IEA:Compara.
 GO:0042245; P:RNA repair; IDA:BHF-UCL.
 GO:0001659; P:temperature homeostasis; IEA:Compara. 

Interpro

 IPR024366; FTO_C.
 IPR024367; FTO_cat_dom. 

Pfam

 PF12934; FTO_CTD
 PF12933; FTO_NTD 

SMART

  

PROSITE

  

PRINTS