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Protein

Alpha-ketoglutarate-dependent dioxygenase FTO

Gene

Fto

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 N6-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

N6-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)DescriptionActionsGraphical viewLength
Binding sitei96SubstrateBy similarity1
Binding sitei108SubstrateBy similarity1
Binding sitei202Alpha-ketoglutarateBy similarity1
Metal bindingi228Iron; catalyticBy similarity1
Metal bindingi230Iron; catalyticBy similarity1
Binding sitei292Alpha-ketoglutarateBy similarity1
Metal bindingi304Iron; catalyticBy similarity1
Binding sitei317Alpha-ketoglutarateBy similarity1
Binding sitei319Alpha-ketoglutarateBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
Biological processDNA damage, DNA repair, RNA repair
LigandIron, Metal-binding

Enzyme and pathway databases

ReactomeiR-RNO-73943 Reversal of alkylation damage by DNA dioxygenases

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 19

Organism-specific databases

RGDi1305121 Fto

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Keywords - Diseasei

Obesity

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002861661 – 502Alpha-ketoglutarate-dependent dioxygenase FTOAdd BLAST502

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei213N6-acetyllysineBy similarity1

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

BgeeiENSRNOG00000011728
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
SMRiQ2A121
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni42 – 324Fe2OG dioxygenase domainBy similarityAdd BLAST283
Regioni210 – 221Loop L1; predicted to block binding of double-stranded DNA or RNABy similarityAdd BLAST12
Regioni228 – 231Substrate bindingBy similarity4
Regioni313 – 315Alpha-ketoglutarate bindingBy similarity3

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
PhylomeDBiQ2A121
TreeFamiTF333296

Family and domain databases

Gene3Di1.20.58.1470, 1 hit
2.60.120.590, 1 hit
InterProiView protein in InterPro
IPR037151 AlkB-like_sf
IPR032868 FTO
IPR024366 FTO_C
IPR038413 FTO_C_sf
IPR024367 FTO_cat_dom
PANTHERiPTHR31291 PTHR31291, 1 hit
PfamiView protein in Pfam
PF12934 FTO_CTD, 1 hit
PF12933 FTO_NTD, 1 hit
SMARTiView protein in SMART
SM01223 FTO_NTD, 1 hit

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

Similar proteinsi

Entry informationi

Entry nameiFTO_RAT
AccessioniPrimary (citable) accession number: Q2A121
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 2007
Last sequence update: April 4, 2006
Last modified: May 23, 2018
This is version 75 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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