Nine mammalian AlkB homologues exist, ALKBH1-8 and FTO [, ]. FTO, also known as Fat mass and obesity-associated protein, is an alpha-ketoglutarate-dependent dioxygenase involved in alkylated DNA and RNA repair []. FTO activity is highest towards single-stranded RNA containing 3-methyluracil, followed by single-stranded DNA containing 3-methylthymine []. It 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, as well as the regulation of body size and body fat accumulation [].
Alpha-ketoglutarate-dependent dioxygenase FTO, also known as Fat mass and obesity-associated protein, is a nucleus protein which belongs to the FTO family. This enzyme is a dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation []. FTO activity is highest 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. It 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. It contributes to the regulation of body size and body fat accumulation as well [].This domain is the catalytic AlkB-like domain from the FTO protein []. This domain catalyses a demethylase activity with a preference for 3-methylthymidine.
FTO contains two well-defined domains: an N- (residues 32-326) and a C- (residues 327-498) terminal domain. The N-terminal domain of this protein is a DNA demethylase []. This entry represents the C-terminal domain (CTD). This domain is α-helical with α7, α8 and α10 forming a three-helix bundle. One end of the helix bundle interacts with the N-terminal domain of FTO, and it has been suggested that the CTD plays a role in stabilising the NTD's conformation since the NTD only exhibits enzymatic activity when co-expressed with the CTD [].Alpha-ketoglutarate-dependent dioxygenase FTO, also known as Fat mass and obesity-associated protein, is a nucleus protein which belongs to the FTO family. This enzyme is a dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation []. FTO activity is highest 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. It 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. It contributes to the regulation of body size and body fat accumulation as well [].
Alpha-ketoglutarate-dependent dioxygenase FTO, also known as Fat mass and obesity-associated protein, is a nucleus protein which belongs to the FTO family. This enzyme is a dioxygenase that repairs alkylated DNA and RNA by oxidative demethylation []. FTO activity is highest 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. It 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. It contributes to the regulation of body size and body fat accumulation as well [].FTO contains two well-defined domains: an N- (residues 32-326) and a C- (residues 327-498) terminal domain. The N-terminal domain of this protein is a DNA demethylase []. This entry represents the C-terminal domain (CTD). This domain is α-helical with α7, α8 and α10 forming a three-helix bundle. One end of the helix bundle interacts with the N-terminal domain of FTO, and it has been suggested that the CTD plays a role in stabilising the NTD's conformation since the NTD only exhibits enzymatic activity when co-expressed with the CTD [].
Nine mammalian AlkB homologues exist, ALKBH1-8 and FTO [, ]. Differently to other AlkB homologues, AlkB homologue 7 (ALKBH7) does not exhibit any demethylase activity in DNA or RNA []and its substrate is still unknown []. ALKBH7 is located in the mitochondrial matrix. It is a key protein for programmed necrosis and fat metabolism [, , ]. After agent-induced DNA-damage, it triggers the collapse of mitochondrial membrane potential and large-scale loss of mitochondrial function that lead to energy depletion and cellular demise [].
