Fat mass and obesity associated (FTO)

Fat mass and obesity associated (FTO) is dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. FTO has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. FTO has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. FTO has no activity towards 1-methylguanine. FTO has no detectable activity towards double-stranded DNA. FTO requires molecular oxygen, alpha-ketoglutarate and iron. FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. FTO contributes to the regulation of body size and body fat accumulation.

Fat mass and obesity associated (FTO) Related Areas

Cardiovascular>>Lipid Metabolism>>FTO

Fat mass and obesity associated (FTO) Alternative Names

Fat mass and obesity associated, FTO, KIAA1752, MGC5149 [Homo sapiens]

Fat mass and obesity associated, Fto, AW743446, mKIAA1752 [Mus musculus]

Summaries for Fat mass and obesity associated (FTO)

Entrez Gene summary for FTO:

This FTO gene is a nuclear protein of the AlkB related non-haem iron and 2-oxoglutarate-dependent oxygenase superfamily but the exact physiological function of this gene is not known. Other non-heme iron enzymes function to reverse alkylated DNA and RNA damage by oxidative demethylation. Studies in mice and humans indicate a role in nervous and cardiovascular systems and a strong association with body mass index, obesity risk, and type 2 diabetes. [provided by RefSeq, Jul 2011]

Wikipedia summary for FTO:

Fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16. As one homolog in the AlkB family proteins, it is the first mRNA demethylase that has been identified. Certain variants of the FTO gene appear to be correlated with obesity in humans.

Human Fat mass and obesity associated (FTO) Protein General Information

 

• Protein names: Fat mass and obesity-associated protein
• Sequence length: 505 AA.
• Domain: 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.
• Sequence similarities: FTO belongs to the fto family.
• Cofactor: FTO binds 1 Fe2+ ion per subunit
• Enzyme regulation: FTO is activated by ascorbate. FTO is inhibited by N-oxalylglycine, fumarate and succinate
• Polymorphism: At least one intronic variation within the gene predisposes to childhood and adult obesity.
• Subunit structure: Monomer. FTO may also exist as homodimer
• Subcellular location: Nucleus
• Tissue specificity: Ubiquitously expressed, with relatively high expression in adrenal glands and brain; especially in hypothalamus and pituitary.
• Involvement in disease: Defects in FTO are the cause of growth retardation developmental delay coarse facies and early death (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.
• Biophysicochemical properties: pH dependence:
  Optimum pH is 5.5-6.
• Sequence caution: The sequence BAB21843.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

General information above from UniProt

Function for Fat mass and obesity associated (FTO) Protein

UniProtKB:

Fat mass and obesity associated (FTO) is dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation. FTO has highest activity towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine. FTO has low demethylase activity towards single-stranded DNA containing 1-methyladenine or 3-methylcytosine. FTO has no activity towards 1-methylguanine. FTO has no detectable activity towards double-stranded DNA. FTO requires molecular oxygen, alpha-ketoglutarate and iron. FTO contributes to the regulation of the global metabolic rate, energy expenditure and energy homeostasis. FTO contributes to the regulation of body size and body fat accumulation.

Genatlas:

• FTO is nucleic acid demethylase that may work on DNA or RNA
• FTO may have an important role for gender specific development of severe obesity and insulin resistance in children
• FTO could participate in the central control of energy homeostasis
• FTO is implicated in the regulation of lipolysis
• FTO is functionally involved in energy homeostasis by the control of energy expenditure
• FTO plays an essential role for normal development of the central nervous and cardiovascular systems
• effect of FTO on BMI may be mediated through impaired responsiveness to satiety
• FTO is directly involved in the regulation of energy intake and metabolism
• FTO and/or RPGRIP1L may participate in the leptin signaling pathway
• FTO and RPGRIP1L participate in the control of food intake by modulating leptin sensitivity in the arcuate hypothalamic
• FTO is proposed transcription co-factor, influencing expression of the gene encoding a satiety mediator, OXT

Homology for human Fat mass and obesity associated (FTO)

• homolog to to the DNA repair ALKBH1 protein

Phenotype Information for Fat mass and obesity associated (FTO)

• Gene/Locus: FTO
• Phenotype: Growth retardation, developmental delay, coarse facies, and early death

Phenotype Information for FTO from OMIM (Online Mendelian Inheritance in Man)