FTO_XENLA
ID FTO_XENLA Reviewed; 501 AA.
AC Q68F54;
DT 01-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Alpha-ketoglutarate-dependent dioxygenase FTO;
DE AltName: Full=U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO;
DE EC=1.14.11.- {ECO:0000250|UniProtKB:Q9C0B1};
DE AltName: Full=U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO;
DE EC=1.14.11.- {ECO:0000250|UniProtKB:Q9C0B1};
DE AltName: Full=mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO;
DE Short=m6A(m)-demethylase FTO;
DE EC=1.14.11.- {ECO:0000250|UniProtKB:Q9C0B1};
DE AltName: Full=mRNA N(6)-methyladenosine demethylase FTO;
DE EC=1.14.11.53 {ECO:0000250|UniProtKB:Q9C0B1};
DE AltName: Full=tRNA N1-methyl adenine demethylase FTO;
DE EC=1.14.11.- {ECO:0000250|UniProtKB:Q9C0B1};
GN Name=fto;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: RNA demethylase that mediates oxidative demethylation of
CC different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a
CC regulator of fat mass, adipogenesis and energy homeostasis.
CC Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most
CC prevalent internal modification of messenger RNA (mRNA) in higher
CC eukaryotes. M6A demethylation by FTO affects mRNA expression and
CC stability. Also able to demethylate m6A in U6 small nuclear RNA
CC (snRNA). Mediates demethylation of N(6),2'-O-dimethyladenosine cap
CC (m6A(m)), by demethylating the N(6)-methyladenosine at the second
CC transcribed position of mRNAs and U6 snRNA. Demethylation of m6A(m) in
CC the 5'-cap by FTO affects mRNA stability by promoting susceptibility to
CC decapping. Also acts as a tRNA demethylase by removing N(1)-
CC methyladenine from various tRNAs. {ECO:0000250|UniProtKB:Q9C0B1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(N(6),2'-O-dimethyladenosine) in mRNA + O2 = a
CC 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenosine) in
CC mRNA + CO2 + formaldehyde + succinate; Xref=Rhea:RHEA:57896,
CC Rhea:RHEA-COMP:11518, Rhea:RHEA-COMP:11519, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:85958, ChEBI:CHEBI:85959;
CC Evidence={ECO:0000250|UniProtKB:Q9C0B1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + an N(6)-methyladenosine in mRNA + O2 = an
CC adenosine in mRNA + CO2 + formaldehyde + succinate;
CC Xref=Rhea:RHEA:49520, Rhea:RHEA-COMP:12414, Rhea:RHEA-COMP:12417,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:74411,
CC ChEBI:CHEBI:74449; EC=1.14.11.53;
CC Evidence={ECO:0000250|UniProtKB:Q9C0B1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + N(6)-methyladenosine in U6 snRNA + O2 =
CC adenosine in U6 snRNA + CO2 + formaldehyde + succinate;
CC Xref=Rhea:RHEA:57900, Rhea:RHEA-COMP:13573, Rhea:RHEA-COMP:13574,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:74411,
CC ChEBI:CHEBI:74449; Evidence={ECO:0000250|UniProtKB:Q9C0B1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(N(6),2'-O-dimethyladenosine) in U6 snRNA + O2 =
CC a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenosine)
CC in U6 snRNA + CO2 + formaldehyde + succinate; Xref=Rhea:RHEA:57904,
CC Rhea:RHEA-COMP:15030, Rhea:RHEA-COMP:15031, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:16842,
CC ChEBI:CHEBI:30031, ChEBI:CHEBI:85958, ChEBI:CHEBI:85959;
CC Evidence={ECO:0000250|UniProtKB:Q9C0B1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + an N(1)-methyladenosine in tRNA + O2 = an
CC adenosine in tRNA + CO2 + formaldehyde + succinate;
CC Xref=Rhea:RHEA:54576, Rhea:RHEA-COMP:10242, Rhea:RHEA-COMP:12312,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:74411,
CC ChEBI:CHEBI:74491; Evidence={ECO:0000250|UniProtKB:Q9C0B1};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000250|UniProtKB:Q9C0B1};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q9C0B1};
CC -!- ACTIVITY REGULATION: Activated by ascorbate. Inhibited by N-
CC oxalylglycine, fumarate and succinate. {ECO:0000250|UniProtKB:Q8BGW1}.
CC -!- SUBUNIT: Monomer. May also exist as homodimer.
CC {ECO:0000250|UniProtKB:Q8BGW1}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9C0B1}. Nucleus
CC speckle {ECO:0000250|UniProtKB:Q9C0B1}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9C0B1}. Note=Localizes mainly in the nucleus,
CC where it is able to demethylate N(6)-methyladenosine (m6A) and N(6),2'-
CC O-dimethyladenosine cap (m6A(m)) in U6 small nuclear RNA (snRNA), N(1)-
CC methyladenine from tRNAs and internal m6A in mRNAs. In the cytoplasm,
CC mediates demethylation of m6A and m6A(m) in mRNAs and N(1)-
CC methyladenine from tRNAs. {ECO:0000250|UniProtKB:Q9C0B1}.
CC -!- DOMAIN: The 3D-structure of the Fe2OG dioxygenase domain is similar to
CC that of the Fe2OG dioxygenase domain found in the bacterial DNA repair
CC dioxygenase alkB and its mammalian orthologs, but sequence similarity
CC is very low. As a consequence, the domain is not detected by protein
CC signature databases. {ECO:0000250|UniProtKB:Q9C0B1}.
CC -!- SIMILARITY: Belongs to the fto family. {ECO:0000305}.
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DR EMBL; BC079990; AAH79990.1; -; mRNA.
DR RefSeq; NP_001087481.1; NM_001094012.1.
DR AlphaFoldDB; Q68F54; -.
DR SMR; Q68F54; -.
DR MaxQB; Q68F54; -.
DR GeneID; 447305; -.
DR KEGG; xla:447305; -.
DR CTD; 447305; -.
DR Xenbase; XB-GENE-972569; fto.L.
DR OrthoDB; 1300974at2759; -.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 447305; Expressed in ovary and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043734; F:DNA-N1-methyladenine dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1990931; F:mRNA N6-methyladenosine dioxygenase activity; ISS:UniProtKB.
DR GO; GO:0035516; F:oxidative DNA demethylase activity; ISS:UniProtKB.
DR GO; GO:0035515; F:oxidative RNA demethylase activity; ISS:UniProtKB.
DR GO; GO:1990984; F:tRNA demethylase activity; ISS:UniProtKB.
DR GO; GO:0006307; P:DNA dealkylation involved in DNA repair; IEA:InterPro.
DR GO; GO:0061157; P:mRNA destabilization; ISS:UniProtKB.
DR GO; GO:0035552; P:oxidative single-stranded DNA demethylation; ISS:UniProtKB.
DR GO; GO:0035553; P:oxidative single-stranded RNA demethylation; ISS:UniProtKB.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:InterPro.
DR GO; GO:0042245; P:RNA repair; IEA:InterPro.
DR Gene3D; 1.20.58.1470; -; 1.
DR Gene3D; 2.60.120.590; -; 1.
DR InterPro; IPR037151; AlkB-like_sf.
DR InterPro; IPR032868; FTO.
DR InterPro; IPR024366; FTO_C.
DR InterPro; IPR038413; FTO_C_sf.
DR InterPro; IPR024367; FTO_cat_dom.
DR PANTHER; PTHR31291; PTHR31291; 1.
DR Pfam; PF12934; FTO_CTD; 1.
DR Pfam; PF12933; FTO_NTD; 1.
DR SMART; SM01223; FTO_NTD; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Dioxygenase; Iron; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..501
FT /note="Alpha-ketoglutarate-dependent dioxygenase FTO"
FT /id="PRO_0000286167"
FT REGION 32..321
FT /note="Fe2OG dioxygenase domain"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT REGION 211..222
FT /note="Loop L1; predicted to block binding of double-
FT stranded DNA or RNA"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 96
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 108
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 203
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 229..232
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 229
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 231
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 289
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 301
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 310..312
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 314
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
FT BINDING 316
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250|UniProtKB:Q9C0B1"
SQ SEQUENCE 501 AA; 58527 MW; 25E3353EF37DBFC3 CRC64;
MKKRGVLCEE EKEVKKRKLL EQIGDGHLPY LSSKDDTFYD LWGSCYSKLT LLQAKHVPVD
LHHTVQNAFL SLLRNGCLFQ DLVRLKGKDI ITPVSRILIG RPGYTYKYLN TRLFAVPWIN
DELNTQYSTR NLLETYKAFS DLNDFLYSQT VNELQKLGKI HKDNFFQHSE YKEQIKSDQR
PSTSNYENVK LHSMESFNVT LINYMDPQNM SFLKEEPYFG MGKMAVSWHH DENLVEQSTV
AVYNYSYQES SNDVNGEDED PTRWHVGLKI AWDIETPGLL MPLSSGDCYL MLDDLNKTHQ
HCVIAGCQPR FSSTHRVAES STGTLQYIKS QCNSALQNLH MNPDTGAADL KNLEPNVLGQ
TEEIHNEVEF EWLRQFWFQG KRYNKCTTFW KEAMTELEIH WKQMETMTSL VLKAIENENL
TVDEKCNILK NILPPLVERQ DLRHDWRERC RSKLAKMLPP DQVPCFYPYW NDDNKTMPLP
FDLHNIISAL QKTLEENELK L
