FTO
entrez
79068
canonical
uniprot
Q9C0B1
canonical
ensembl
ENSG00000140718
resolver
ensp
ENSP00000418823
resolver
ensp
ENSP00000489641
resolver
ensp
ENSP00000489886
resolver
ensp
ENSP00000489936
resolver
ensp
ENSP00000666256
resolver
ensp
ENSP00000666257
resolver
ensp
ENSP00000666258
resolver
ensp
ENSP00000737692
resolver
ensp
ENSP00000737693
resolver
ensp
ENSP00000790778
resolver
ensp
ENSP00000790779
resolver
ensp
ENSP00000797037
resolver
ensp
ENSP00000797038
resolver
enst
ENST00000636218
resolver
genesymbol
FTO
resolver
genesymbol_syn
KIAA1752
resolver
hgnc
HGNC:24678
resolver
uniprot
A0A1B0GTC5
resolver
uniprot
A2RUH1
resolver
uniprot
B2RNS0
resolver
uniprot
B3KU60
resolver
uniprot
Q0P676
resolver
uniprot
Q7Z785
resolver
uniprot
Q99770
resolver
uniprot_entry
A0A1B0GTC5_HUMAN
resolver
uniprot_entry
B3KU60_HUMAN
resolver
uniprot_entry
FTO_HUMAN
resolver
uniprot_entry
Q99770_HUMAN
resolver
uniprot_sec
A2RUH1
resolver
uniprot_sec
B2RNS0
resolver
uniprot_sec
Q0P676
resolver
uniprot_sec
Q7Z785
resolver
activity_regulation
ACTIVITY REGULATION: Activated by ascorbate (By similarity). Inhibited by N-oxalylglycine, fumarate and succinate (By similarity). RNA N(6)-methyladenosine demethylase activity is inhibited by fluorescein derivatives (PubMed:26457839). RNA N(6)-methyladenosine demethylase activity is selectively inhibited by meclofenamic acid; inhibition is specific to FTO and meclofenamic acid does not inhibit ALKBH5 (PubMed:25452335). Specifically inhibited by R-2-hydroxyglutarate (R-2HG), an oncometabolite that also exerts a broad antileukemic activity (PubMed:29249359). Inhibition by R-2HG leads to increased level of N(6)-methyladenosine-containing transcripts, leading to down-regulate expression of MYC and CEBPA transcripts (PubMed:29249359). {ECO:0000250|UniProtKB:Q8BGW1, ECO:0000269|PubMed:25452335, ECO:0000269|PubMed:26457839, ECO:0000269|PubMed:29249359}.
uniprot
proteins
amino_acid_sequence
MKRTPTAEEREREAKKLRLLEELEDTWLPYLTPKDDEFYQQWQLKYPKLILREASSVSEELHKEVQEAFLTLHKHGCLFRDLVRIQGKDLLTPVSRILIGNPGCTYKYLNTRLFTVPWPVKGSNIKHTEAEIAAACETFLKLNDYLQIETIQALEELAAKEKANEDAVPLCMSADFPRVGMGSSYNGQDEVDIKSRAAYNVTLLNFMDPQKMPYLKEEPYFGMGKMAVSWHHDENLVDRSAVAVYSYSCEGPEEESEDDSHLEGRDPDIWHVGFKISWDIETPGLAIPLHQGDCYFMLDDLNATHQHCVLAGSQPRFSSTHRVAECSTGTLDYILQRCQLALQNVCDDVDNDDVSLKSFEPAVLKQGEEIHNEVEFEWLRQFWFQGNRYRKCTDWWCQPMAQLEALWKKMEGVTNAVLHEVKREGLPVEQRNEILTAILASLTARQNLRREWHARCQSRIARTLPADQKPECRPYWEKDDASMPLPFDLTDIVSELRGQLLEAKP
uniprot
proteins
disease_involvement
DISEASE: Growth retardation, developmental delay, and facial dysmorphism (GDFD) [MIM:612938]: A severe polymalformation syndrome characterized by postnatal growth retardation, microcephaly, severe psychomotor delay, functional brain deficits and characteristic facial dysmorphism. In some patients, structural brain malformations, cardiac defects, genital anomalies, and cleft palate are observed. Early death occurs by the age of 3 years. {ECO:0000269|PubMed:19559399, ECO:0000269|PubMed:22002720, ECO:0000269|PubMed:26378117, ECO:0000269|PubMed:26697951}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:24646999, ECO:0000269|PubMed:26287746}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. It is unclear whether variations associated with obesity directly affect FTO function or alter the expression of adjacent genes such as IRX3, rather than FTO itself (PubMed:24646999, PubMed:26287746). A pathogenic intronic FTO variation (rs1421085) disrupts an evolutionarily conserved motif for ARID5B binding (PubMed:26287746). Loss of ARID5B binding results in overexpression of two genes distal to FTO, IRX3 and IRX5. IRX3 and IRX5 overexpression shifts pre-adipocytes differentiation from brown to white fat cells, resulting in increased lipid storage and loss of mitochondrial thermogenesis (PubMed:26287746). {ECO:0000269|PubMed:24646999, ECO:0000269|PubMed:26287746}.
uniprot
proteins
ec_number
1.14.11.-
uniprot
proteins
ec_number
1.14.11.53
uniprot
proteins
function
FUNCTION: RNA demethylase that mediates oxidative demethylation of different RNA species, such as mRNAs, tRNAs and snRNAs, and acts as a regulator of fat mass, adipogenesis and energy homeostasis (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:28002401, PubMed:30197295). Specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:22002720, PubMed:25452335, PubMed:26457839, PubMed:26458103, PubMed:30197295). M6A demethylation by FTO affects mRNA expression and stability (PubMed:30197295). Also able to demethylate m6A in U6 small nuclear RNA (snRNA) (PubMed:30197295). Mediates demethylation of N(6),2'-O-dimethyladenosine cap (m6A(m)), by demethylating the N(6)-methyladenosine at the second transcribed position of mRNAs and U6 snRNA (PubMed:28002401, PubMed:30197295). Demethylation of m6A(m) in the 5'-cap by FTO affects mRNA stability by promoting susceptibility to decapping (PubMed:28002401). Also acts as a tRNA demethylase by removing N(1)-methyladenine from various tRNAs (PubMed:30197295). Has no activity towards 1-methylguanine (PubMed:20376003). Has no detectable activity towards double-stranded DNA (PubMed:20376003). Also able to repair alkylated DNA and RNA by oxidative demethylation: demethylates single-stranded RNA containing 3-methyluracil, single-stranded DNA containing 3-methylthymine and has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine (PubMed:18775698, PubMed:20376003). Ability to repair alkylated DNA and RNA is however unsure in vivo (PubMed:18775698, PubMed:20376003). Involved in the regulation of fat mass, adipogenesis and body weight, thereby contributing to the regulation of body size and body fat accumulation (PubMed:18775698, PubMed:20376003). Involved in the regulation of thermogenesis and the control of adipocyte differentiation into brown or white fat cells (PubMed:26287746). Regulates activity of the dopaminergic midbrain circuitry via its ability to demethylate m6A in mRNAs (By similarity). Plays an oncogenic role in a number of acute myeloid leukemias by enhancing leukemic oncogene-mediated cell transformation: acts by mediating m6A demethylation of target transcripts such as MYC, CEBPA, ASB2 and RARA, leading to promote their expression (PubMed:28017614, PubMed:29249359). {ECO:0000250|UniProtKB:Q8BGW1, ECO:0000269|PubMed:18775698, ECO:0000269|PubMed:20376003, ECO:0000269|PubMed:22002720, ECO:0000269|PubMed:25452335, ECO:0000269|PubMed:26287746, ECO:0000269|PubMed:26457839, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:28002401, ECO:0000269|PubMed:28017614, ECO:0000269|PubMed:29249359, ECO:0000269|PubMed:30197295}.
uniprot
proteins
mass_dalton
58282
uniprot
proteins
mutagenesis
MUTAGEN 96; /note="R->M,W: Almost abolishes enzyme activity."; /evidence="ECO:0000269|PubMed:20376003"; MUTAGEN 108; /note="Y->A: Abolishes enzyme activity."; /evidence="ECO:0000269|PubMed:20376003"; MUTAGEN 114; /note="F->D: Perturbs interaction between N-terminal and C-terminal domains and strongly reduces enzyme activity."; /evidence="ECO:0000269|PubMed:20376003"; MUTAGEN 162; /note="K->R: Strong gain of stability and loss of ubiquitination."; /evidence="ECO:0000269|PubMed:39661064"; MUTAGEN 231..233; /note="HHD->AHA: Abolishes ability to demethylate N(6)-methyladenosine RNAs (m6A) RNAs."; /evidence="ECO:0000269|PubMed:22002720"; MUTAGEN 234; /note="E->P: Abolishes enzyme activity. Abolishes ability to demethylate N(6)-methyladenosine RNAs (m6A) RNAs; when associated with Q-322."; /evidence="ECO:0000269|PubMed:20376003"; MUTAGEN 392; /note="C->D: Perturbs interaction between N-terminal and C-terminal domains and strongly reduces enzyme activity."; /evidence="ECO:0000269|PubMed:20376003
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated by DTX2; leading to proteasomal degradation. {ECO:0000269|PubMed:39661064}.
uniprot
proteins
protein_family
Fto family
uniprot
proteins
pubmed
11214970
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616553
uniprot
proteins
pubmed
17434869
uniprot
proteins
pubmed
17496892
uniprot
proteins
pubmed
18775698
uniprot
proteins
pubmed
19559399
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20376003
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22002720
uniprot
proteins
pubmed
22982992
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23547775
uniprot
proteins
pubmed
24646999
uniprot
proteins
pubmed
25452335
uniprot
proteins
pubmed
26287746
uniprot
proteins
pubmed
26378117
uniprot
proteins
pubmed
26457839
uniprot
proteins
pubmed
26458103
uniprot
proteins
pubmed
26697951
uniprot
proteins
pubmed
26740239
uniprot
proteins
pubmed
28002401
uniprot
proteins
pubmed
28017614
uniprot
proteins
pubmed
28553460
uniprot
proteins
pubmed
29249359
uniprot
proteins
pubmed
30197295
uniprot
proteins
pubmed
39661064
uniprot
proteins
sequence_length
505
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22002720, ECO:0000269|PubMed:26458103, ECO:0000269|PubMed:28002401, ECO:0000269|PubMed:30197295}. Nucleus speckle {ECO:0000269|PubMed:22002720}. Cytoplasm {ECO:0000269|PubMed:30197295}. Note=Localizes mainly in the nucleus, where it is able to demethylate N(6)-methyladenosine (m6A) and N(6),2'-O-dimethyladenosine cap (m6A(m)) in U6 small nuclear RNA (snRNA), N(1)-methyladenine from tRNAs and internal m6A in mRNAs (PubMed:30197295). In the cytoplasm, mediates demethylation of m6A and m6A(m) in mRNAs and N(1)-methyladenine from tRNAs (PubMed:30197295). {ECO:0000269|PubMed:30197295}.
uniprot
proteins