FTO
GeneName
FTO
Summary
FTO, also known as fat mass and obesity associated protein or Grb10, is a 58 kDa protein that is predominantly expressed in the nucleus and cytoplasm of various tissues. It functions as a broad specificity oxidative DNA and RNA demethylase, playing a crucial role in the regulation of mRNA stability and the processing of small nuclear RNAs. FTO is involved in several biological processes, including adipose tissue development, lipid storage regulation, and the differentiation of brown fat cells, highlighting its importance in energy metabolism and thermoregulation.
Importance
FTO is relevant to: - Obesity research due to its association with fat mass regulation and energy balance - Metabolic disorders, as it influences lipid metabolism and adipocyte function - Cancer biology, given its role in mRNA regulation and potential implications in tumour growth - Epigenetics, through its demethylation activities that affect gene expression and cellular processes
Top Products
For researchers investigating FTO, we recommend two excellent primary antibodies that have garnered attention in the field. The first is the well-cited Anti-FTO antibody [5-2H10] (ab92821), a monoclonal antibody that has been validated in knockout models and is suitable for Western blotting (WB), immunocytochemistry (ICC), and flow cytometry (FC). With 69 citations, it demonstrates a strong reputation among researchers. Additionally, we offer the recombinant antibody, Anti-FTO antibody [EPR6895] (ab124892), which is also validated in knockout models. This product excels in Western blotting (WB) and immunohistochemistry (IHC), making it a versatile choice for various applications. With 66 citations, it further underscores its reliability and effectiveness in FTO research. Both antibodies provide robust options for those studying this important gene. The Anti-FTO antibody ELISA Kit (ab124892), supported by 66 citations, is an excellent option for researchers looking to accurately measure FTO levels in their samples.
Abcam Product Citation Summary
The data indicates that FTO is being extensively studied in various human and mouse models, particularly in the context of cancer, differentiation, and developmental biology. The use of Western blotting and immunocytochemistry highlights the importance of FTO in understanding cellular processes such as mRNA methylation and myogenic differentiation. The research spans multiple species, with a significant focus on human gastric cancer and mouse models for skeletal muscle development.
Abcam Product Citation Table
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.
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).
Involvement in disease
Growth retardation, developmental delay, and facial dysmorphism
GDFD
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Obesity
OBESITY
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.
None
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).
Sequence Similarities
Belongs to the fto family.
Tissue Specificity
Ubiquitously expressed, with relatively high expression in adrenal glands and brain; especially in hypothalamus and pituitary (PubMed:17434869, PubMed:17496892). Highly expressed in highly expressed in acute myeloid leukemias (AML) with t(11;11)(q23;23) with KMT2A/MLL1 rearrangements, t(15;17)(q21;q21)/PML-RARA, FLT3-ITD, and/or NPM1 mutations (PubMed:28017614).
Cellular localization
- Nucleus
- Nucleus speckle
- Cytoplasm
- 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).
Alternative names
KIAA1752, FTO, Alpha-ketoglutarate-dependent dioxygenase FTO, Fat mass and obesity-associated protein, U6 small nuclear RNA (2'-O-methyladenosine-N(6)-)-demethylase FTO, U6 small nuclear RNA N(6)-methyladenosine-demethylase FTO, mRNA (2'-O-methyladenosine-N(6)-)-demethylase FTO, mRNA N(6)-methyladenosine demethylase FTO, tRNA N1-methyl adenine demethylase FTO, m6A(m)-demethylase FTO