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Protein

Alpha-ketoglutarate-dependent dioxygenase FTO

Gene

Fto

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript leveli

Functioni

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 (By similarity).By similarity

Catalytic activityi

N(6)-methyladenosine in mRNA + 2-oxoglutarate + O2 = adenosine in mRNA + formaldehyde + succinate + CO2.By similarity

Cofactori

Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity

Enzyme regulationi

Activated by ascorbate. Inhibited by N-oxalylglycine, fumarate and succinate (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei96 – 961SubstrateBy similarity
Binding sitei108 – 1081SubstrateBy similarity
Binding sitei202 – 2021Alpha-ketoglutarateBy similarity
Metal bindingi228 – 2281Iron; catalyticBy similarity
Metal bindingi230 – 2301Iron; catalyticBy similarity
Binding sitei292 – 2921Alpha-ketoglutarateBy similarity
Metal bindingi304 – 3041Iron; catalyticBy similarity
Binding sitei317 – 3171Alpha-ketoglutarateBy similarity
Binding sitei319 – 3191Alpha-ketoglutarateBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Oxidoreductase

Keywords - Biological processi

DNA damage, DNA repair, RNA repair

Keywords - Ligandi

Iron, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-ketoglutarate-dependent dioxygenase FTO (EC:1.14.11.-By similarity)
Alternative name(s):
Fat mass and obesity-associated protein
Gene namesi
Name:Fto
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 19

Organism-specific databases

RGDi1305121. Fto.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Keywords - Diseasei

Obesity

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 502502Alpha-ketoglutarate-dependent dioxygenase FTOPRO_0000286166Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei213 – 2131N6-acetyllysineBy similarity

Keywords - PTMi

Acetylation

Proteomic databases

PaxDbiQ2A121.
PRIDEiQ2A121.

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in teeth and weakly in bone.2 Publications

Inductioni

Up-regulated in the hypothalamus after 48 h fasting.1 Publication

Gene expression databases

ExpressionAtlasiQ2A121. baseline and differential.
GenevisibleiQ2A121. RN.

Interactioni

Subunit structurei

Monomer. may also exist as homodimer (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015718.

Structurei

3D structure databases

ProteinModelPortaliQ2A121.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni42 – 324283Fe2OG dioxygenase domainBy similarityAdd
BLAST
Regioni210 – 22112Loop L1; predicted to block binding of double-stranded DNA or RNABy similarityAdd
BLAST
Regioni228 – 2314Substrate bindingBy similarity
Regioni313 – 3153Alpha-ketoglutarate bindingBy similarity

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the fto family.Curated

Phylogenomic databases

eggNOGiENOG410IJ5C. Eukaryota.
ENOG4111PKJ. LUCA.
GeneTreeiENSGT00390000017730.
HOGENOMiHOG000273870.
HOVERGENiHBG101847.
InParanoidiQ2A121.
KOiK19469.
OMAiPVCIGPD.
OrthoDBiEOG7CK36T.
PhylomeDBiQ2A121.
TreeFamiTF333296.

Family and domain databases

InterProiIPR032868. FTO.
IPR024366. FTO_C.
IPR024367. FTO_cat_dom.
[Graphical view]
PANTHERiPTHR31291. PTHR31291. 1 hit.
PfamiPF12934. FTO_CTD. 1 hit.
PF12933. FTO_NTD. 1 hit.
[Graphical view]
SMARTiSM01223. FTO_NTD. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q2A121-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKRVQTAEER EREAKKLRLL EELEDTWLPY LTPKDDEFYQ QWQLKYPKLV
60 70 80 90 100
FREAGSIPEE LHKEVPEAFL TLHKHGCLFR DLVRIQGKDV LTPVSRILIG
110 120 130 140 150
DPGCTYKYLN TRLFTVPWPV KGCTINYTEA EIAAACQTFL KLNDYLQVET
160 170 180 190 200
IQALEELAIK EKANEDAVPL CMAEFPRAGV GPSCDDEVDL KSRAAYNVTL
210 220 230 240 250
LNFMDPQKMP YLKEEPYFGM GKMAVSWHHD ENLVDRSAVA VYSYSCEGSE
260 270 280 290 300
DESDDESSFE GRDPDTWHVG FKISWDIETP GLTIPLHQGD CYFMLDDLNA
310 320 330 340 350
THQHCVLAGS QPRFSSTHRV AECSTGTLDY ILQRCQLALQ NVLNDSDNGD
360 370 380 390 400
VSLKSFEPAV LKQGEEIHNE VEFEWLRQFW FQGNRYKICT DWWCEPMTQL
410 420 430 440 450
EGLWKKMESV TNAVLREVKR EGLSVEQRSE ILSAVLIPLT MRQNLRKEWH
460 470 480 490 500
ARCQARVVRT LPAQQKPDCR PYWEKDDPSM PLPFDLTDVV SEIRSQLLEA

RS
Length:502
Mass (Da):57,972
Last modified:April 4, 2006 - v1
Checksum:iDEF554159E312EA7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AM233906 mRNA. Translation: CAJ80872.1.
RefSeqiNP_001034802.1. NM_001039713.1.
UniGeneiRn.229320.

Genome annotation databases

EnsembliENSRNOT00000015718; ENSRNOP00000015718; ENSRNOG00000011728.
GeneIDi291905.
KEGGirno:291905.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AM233906 mRNA. Translation: CAJ80872.1.
RefSeqiNP_001034802.1. NM_001039713.1.
UniGeneiRn.229320.

3D structure databases

ProteinModelPortaliQ2A121.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000015718.

Proteomic databases

PaxDbiQ2A121.
PRIDEiQ2A121.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000015718; ENSRNOP00000015718; ENSRNOG00000011728.
GeneIDi291905.
KEGGirno:291905.

Organism-specific databases

CTDi79068.
RGDi1305121. Fto.

Phylogenomic databases

eggNOGiENOG410IJ5C. Eukaryota.
ENOG4111PKJ. LUCA.
GeneTreeiENSGT00390000017730.
HOGENOMiHOG000273870.
HOVERGENiHBG101847.
InParanoidiQ2A121.
KOiK19469.
OMAiPVCIGPD.
OrthoDBiEOG7CK36T.
PhylomeDBiQ2A121.
TreeFamiTF333296.

Miscellaneous databases

PROiQ2A121.

Gene expression databases

ExpressionAtlasiQ2A121. baseline and differential.
GenevisibleiQ2A121. RN.

Family and domain databases

InterProiIPR032868. FTO.
IPR024366. FTO_C.
IPR024367. FTO_cat_dom.
[Graphical view]
PANTHERiPTHR31291. PTHR31291. 1 hit.
PfamiPF12934. FTO_CTD. 1 hit.
PF12933. FTO_NTD. 1 hit.
[Graphical view]
SMARTiSM01223. FTO_NTD. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Expression of phosphoproteins and amelotin in teeth."
    Trueb B., Taeschler S., Schild C., Lang N.P.
    Int. J. Mol. Med. 19:49-54(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: Wistar.
  2. "The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain."
    Fredriksson R., Hagglund M., Olszewski P.K., Stephansson O., Jacobsson J.A., Olszewska A.M., Levine A.S., Lindblom J., Schioth H.B.
    Endocrinology 149:2062-2071(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY FASTING, TISSUE SPECIFICITY.

Entry informationi

Entry nameiFTO_RAT
AccessioniPrimary (citable) accession number: Q2A121
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: April 4, 2006
Last modified: July 6, 2016
This is version 66 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.