The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily.
BACKGROUND
Genetic variants in the FTO (fat mass and obesity associated) gene have been associated with an increased risk of obesity. However, the function of its protein product has not been experimentally studied and previously reported sequence similarity analyses suggested the absence of homologs in existing protein databases. Here, we present the first detailed computational analysis of the sequence and predicted structure of the protein encoded by FTO.


RESULTS
We performed a sequence similarity search using the human FTO protein as query and then generated a profile using the multiple sequence alignment of the homologous sequences. Profile-to-sequence and profile-to-profile based comparisons identified remote homologs of the non-heme dioxygenase family.


CONCLUSIONS
Our analysis suggests that human FTO is a member of the non-heme dioxygenase (Fe(II)- and 2-oxoglutarate-dependent dioxygenases) superfamily. Amino acid conservation patterns support this hypothesis and indicate that both 2-oxoglutarate and iron should be important for FTO function. This computational prediction of the function of FTO should suggest further steps for its experimental characterization and help to formulate hypothesis about the mechanisms by which it relates to obesity in humans.
Sanchez-Pulido
Luis
L
Centro Nacional de Biotecnologia, CSIC, Madrid, Spain. sanchez@cnb.uam.es
Andrade-Navarro
Miguel A
MA
D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000595:Amino Acid Sequence; D049308:Dioxygenases / Q000032:analysis / Q000235:genetics*; D006418:Heme / Q000737:chemistry; D006801:Humans; D007656:Ketoglutaric Acids / Q000737:chemistry; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D019159:Nonheme Iron Proteins / Q000032:analysis / Q000235:genetics; D017433:Protein Structure, Secondary; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D007656:Ketoglutaric Acids; D019159:Nonheme Iron Proteins; D011506:Proteins; D006418:Heme; D049308:Dioxygenases; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human