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Q8BGW1 (FTO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-ketoglutarate-dependent dioxygenase FTO

EC=1.14.11.-
Alternative name(s):
Fat mass and obesity-associated protein
Protein fatso
Gene names
Name:Fto
Synonyms:Kiaa1752
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length502 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. 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. Ref.5 Ref.6 Ref.7 Ref.8

Cofactor

Binds 1 Fe2+ ion per subunit. Ref.5

Enzyme regulation

Activated by ascorbate. Inhibited by N-oxalylglycine, fumarate and succinate. Ref.5

Subunit structure

Monomer. May also exist as homodimer. Ref.8

Subcellular location

Nucleus. Nucleus speckle By similarity Ref.5 Ref.7 Ref.8.

Tissue specificity

Ubiquitous. Detected in brain, brain cortex, hypothalamus, cerebellum, liver, pancreas, heart, kidney, white adipose tissue and skeletal muscle. Most abundant in the brain, particularly in hypothalamic nuclei governing energy balance. Ref.5 Ref.7

Induction

Down-regulated in fasting animals. Ref.5

Domain

The 3D-structure of the Fe2OG dioxygenase domain is similar to that of the Fe2OG dioxygenase domain found in the bacterial DNA repair dioxygenase alkB and its mammalian orthologs, but sequence similarity is very low. As a consequence, the domain is not detected by protein signature databases By similarity.

Disruption phenotype

Elevated perinatal mortality. Mice have normal body weight at birth, but show growth retardation from day 2 onwards, resulting in a weight reduction of 30-40% after 6 weeks, both in males and females. In addition, animals display reduced nose to anus length. Fat mass is reduced by 60% in males and by 23% in females. Lean body mass is reduced by 26% in males and 19% in females. White adipose tissue decreases more and more over time, while brown adipose tissue is not affected. Serum leptin levels are decreased, while serum levels of adiponectin are increased. Mice exhibit significant hyperphagia after correction for body weight. They show increased oxygen consumption, carbon dioxide production and heat generation, indicating increased energy expenditure, in spite of reduced spontaneous locomotor activity. Plasma adrenaline concentrations are significantly increased. Overall glucose metabolism appears normal. Ref.7

Sequence similarities

Belongs to the fto family.

Biophysicochemical properties

pH dependence:

Optimum pH is 5.5-6. Ref.6

Sequence caution

The sequence BAC98247.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Biological processDNA damage
DNA repair
RNA repair
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseObesity
   LigandIron
Metal-binding
   Molecular functionDioxygenase
Oxidoreductase
   PTMAcetylation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA dealkylation involved in DNA repair

Inferred from sequence or structural similarity. Source: UniProtKB

DNA demethylation

Inferred from direct assay Ref.5Ref.6. Source: BHF-UCL

RNA repair

Inferred from direct assay Ref.6. Source: BHF-UCL

adipose tissue development

Inferred from mutant phenotype Ref.7. Source: UniProtKB

oxidative demethylation

Inferred from direct assay Ref.6. Source: BHF-UCL

oxidative single-stranded DNA demethylation

Inferred from direct assay Ref.6. Source: BHF-UCL

oxidative single-stranded RNA demethylation

Inferred from direct assay Ref.6. Source: BHF-UCL

regulation of lipid storage

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of multicellular organism growth

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of respiratory system process

Inferred from mutant phenotype Ref.7. Source: UniProtKB

regulation of white fat cell proliferation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

temperature homeostasis

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentnuclear speck

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay Ref.7. Source: UniProtKB

   Molecular_functionDNA-N1-methyladenine dioxygenase activity

Inferred from direct assay Ref.5. Source: UniProtKB

ferrous iron binding

Inferred from sequence or structural similarity. Source: UniProtKB

oxidative DNA demethylase activity

Inferred from direct assay Ref.6. Source: BHF-UCL

oxidative RNA demethylase activity

Inferred from direct assay Ref.6. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8BGW1-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q8BGW1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     453-502: CQSRVVRTLP...LRGQLLEARS → FVLLRGGVWCPCPSSARPAQRTKVEDILS
Note: No experimental confirmation available.
Isoform 3 (identifier: Q8BGW1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     411-413: TNA → VSA
     414-502: Missing.
Note: No experimental confirmation available.
Isoform 4 (identifier: Q8BGW1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     296-316: DDLNATHQHCVLAGSQPRFSS → GNVGSLRVGHLWGFEIHFWIL
     317-502: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 502502Alpha-ketoglutarate-dependent dioxygenase FTO
PRO_0000286164

Regions

Region42 – 324283Fe2OG dioxygenase domain By similarity
Region210 – 22112Loop L1; predicted to block binding of double-stranded DNA or RNA By similarity
Region228 – 2314Substrate binding By similarity
Region313 – 3153Alpha-ketoglutarate binding By similarity

Sites

Metal binding2281Iron; catalytic By similarity
Metal binding2301Iron; catalytic By similarity
Metal binding3041Iron; catalytic By similarity
Binding site961Substrate By similarity
Binding site1081Substrate By similarity
Binding site2021Alpha-ketoglutarate By similarity
Binding site2921Alpha-ketoglutarate By similarity
Binding site3171Alpha-ketoglutarate By similarity
Binding site3191Alpha-ketoglutarate By similarity

Amino acid modifications

Modified residue2131N6-acetyllysine By similarity

Natural variations

Alternative sequence296 – 31621DDLNA…PRFSS → GNVGSLRVGHLWGFEIHFWI L in isoform 4.
VSP_025007
Alternative sequence317 – 502186Missing in isoform 4.
VSP_025008
Alternative sequence411 – 4133TNA → VSA in isoform 3.
VSP_025009
Alternative sequence414 – 50289Missing in isoform 3.
VSP_025010
Alternative sequence453 – 50250CQSRV…LEARS → FVLLRGGVWCPCPSSARPAQ RTKVEDILS in isoform 2.
VSP_025011

Experimental info

Mutagenesis3041H → A: Reduced enzyme activity. Ref.5
Mutagenesis3131R → A: Loss of enzyme activity. Ref.5
Mutagenesis3671I → A: Reduces enzyme activity by about 60%. Ref.8
Mutagenesis3671I → F: Alters protein structure and causes an increase in whole body metabolism, leading to a lean phenotype in adult males, but not in females. Ref.8
Sequence conflict1811G → R in BAC32382. Ref.3
Sequence conflict3841N → S in CAB59324. Ref.1
Sequence conflict3841N → S in BAC98247. Ref.2
Sequence conflict3841N → S in BAC40629. Ref.3
Sequence conflict3841N → S in AAH22222. Ref.4
Sequence conflict4101M → V in BAC98247. Ref.2
Sequence conflict4101M → V in BAC40629. Ref.3
Sequence conflict4101M → V in AAH22222. Ref.4
Sequence conflict4631V → A in BAC40629. Ref.3
Sequence conflict4631V → A in AAH22222. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 2003. Version 1.
Checksum: 69223B824028D872

FASTA50258,007
        10         20         30         40         50         60 
MKRVQTAEER EREAKKLRLL EELEDTWLPY LTPKDDEFYQ QWQLKYPKLV FREAGSIPEE 

        70         80         90        100        110        120 
LHKEVPEAFL TLHKHGCLFR DVVRIQGKDV LTPVSRILIG DPGCTYKYLN TRLFTVPWPV 

       130        140        150        160        170        180 
KGCTVKYTEA EIAAACQTFL KLNDYLQVET IQALEELAVR EKANEDAVPL CMAEFPRAGV 

       190        200        210        220        230        240 
GPSCDDEVDL KSRAAYNVTL LNFMDPQKMP YLKEEPYFGM GKMAVSWHHD ENLVDRSAVA 

       250        260        270        280        290        300 
VYSYSCEGSE DESEDESSFE GRDPDTWHVG FKISWDIETP GLTIPLHQGD CYFMLDDLNA 

       310        320        330        340        350        360 
THQHCVLAGS QPRFSSTHRV AECSTGTLDY ILERCQLALQ NVLNDSDDGD VSLKSFDPAV 

       370        380        390        400        410        420 
LKQGEEIHNE VEFEWLRQFW FQGNRYKLCT DWWCEPMTHL EGLWKKMESM TNAVLREVKR 

       430        440        450        460        470        480 
EGLPVEQRSE ILSAILVPLT VRQNLRKEWH ARCQSRVVRT LPVQQKPDCR PYWEKDDPSM 

       490        500 
PLPFDLTDVV SELRGQLLEA RS 

« Hide

Isoform 2 [UniParc].

Checksum: D79A1C3143BEF2D9
Show »

FASTA48155,393
Isoform 3 [UniParc].

Checksum: A3E62B85C8133963
Show »

FASTA41347,593
Isoform 4 [UniParc].

Checksum: C6C1B6EB7E895140
Show »

FASTA31636,366

References

« Hide 'large scale' references
[1]"Cloning of Fatso (Fto), a novel gene deleted by the Fused toes (Ft) mouse mutation."
Peters T., Ausmeier K., Ruether U.
Mamm. Genome 10:983-986(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"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."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Nagase T., Ohara O., Koga H.
DNA Res. 10:167-180(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., 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 S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., 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 K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., 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 S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., 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.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
Strain: C57BL/6J and NOD.
Tissue: Aorta, Bone, Corpora quadrigemina, Skin, Thymus and Vein.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Strain: C57BL/6 and FVB/N.
Tissue: Brain and Kidney.
[5]"The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase."
Gerken T., Girard C.A., Tung Y.C., Webby C.J., Saudek V., Hewitson K.S., Yeo G.S., McDonough M.A., Cunliffe S., McNeill L.A., Galvanovskis J., Rorsman P., Robins P., Prieur X., Coll A.P., Ma M., Jovanovic Z., Farooqi I.S. expand/collapse author list , Sedgwick B., Barroso I., Lindahl T., Ponting C.P., Ashcroft F.M., O'Rahilly S., Schofield C.J.
Science 318:1469-1472(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, COFACTOR, ENZYME REGULATION, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-304 AND ARG-313, INDUCTION, TISSUE SPECIFICITY.
[6]"Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO."
Jia G., Yang C.G., Yang S., Jian X., Yi C., Zhou Z., He C.
FEBS Lett. 582:3313-3319(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[7]"Inactivation of the Fto gene protects from obesity."
Fischer J., Koch L., Emmerling C., Vierkotten J., Peters T., Bruning J.C., Ruther U.
Nature 458:894-898(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, FUNCTION, TISSUE SPECIFICITY.
[8]"A mouse model for the metabolic effects of the human fat mass and obesity associated FTO gene."
Church C., Lee S., Bagg E.A., McTaggart J.S., Deacon R., Gerken T., Lee A., Moir L., Mecinovic J., Quwailid M.M., Schofield C.J., Ashcroft F.M., Cox R.D.
PLoS Genet. 5:E1000599-E1000599(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, CIRCULAR DICHROISM, MUTAGENESIS OF ILE-367.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ237917 mRNA. Translation: CAB59324.1.
AK129437 mRNA. Translation: BAC98247.1. Different initiation.
AK036677 mRNA. Translation: BAC29533.1.
AK040866 mRNA. Translation: BAC30724.1.
AK045465 mRNA. Translation: BAC32382.1.
AK049502 mRNA. Translation: BAC33780.1.
AK088881 mRNA. Translation: BAC40629.1.
AK161060 mRNA. Translation: BAE36177.1.
BC022222 mRNA. Translation: AAH22222.1.
BC057008 mRNA. Translation: AAH57008.1.
CCDSCCDS22521.1. [Q8BGW1-1]
RefSeqNP_036066.2. NM_011936.2. [Q8BGW1-1]
UniGeneMm.4375.

3D structure databases

ProteinModelPortalQ8BGW1.
SMRQ8BGW1. Positions 30-500.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204941. 1 interaction.

PTM databases

PhosphoSiteQ8BGW1.

Proteomic databases

MaxQBQ8BGW1.
PaxDbQ8BGW1.
PRIDEQ8BGW1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000069718; ENSMUSP00000068380; ENSMUSG00000055932. [Q8BGW1-1]
GeneID26383.
KEGGmmu:26383.
UCSCuc009msq.2. mouse. [Q8BGW1-4]
uc009msr.2. mouse. [Q8BGW1-3]
uc009mss.2. mouse. [Q8BGW1-2]
uc009mst.2. mouse. [Q8BGW1-1]

Organism-specific databases

CTD79068.
MGIMGI:1347093. Fto.
RougeSearch...

Phylogenomic databases

eggNOGNOG45792.
GeneTreeENSGT00390000017730.
HOVERGENHBG101847.
InParanoidQ8BGW1.
OMAAVYNYSC.
OrthoDBEOG7CK36T.
PhylomeDBQ8BGW1.
TreeFamTF333296.

Gene expression databases

ArrayExpressQ8BGW1.
BgeeQ8BGW1.
CleanExMM_FTO.
GenevestigatorQ8BGW1.

Family and domain databases

InterProIPR024366. FTO_C.
IPR024367. FTO_cat_dom.
[Graphical view]
PfamPF12934. FTO_CTD. 1 hit.
PF12933. FTO_NTD. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFTO. mouse.
NextBio304305.
PROQ8BGW1.
SOURCESearch...

Entry information

Entry nameFTO_MOUSE
AccessionPrimary (citable) accession number: Q8BGW1
Secondary accession number(s): Q3TTZ5 expand/collapse secondary AC list , Q6ZPI7, Q8BR68, Q8CB66, Q8R250, Q9QZ13
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 87 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot