Based on homology with E. coli AlkB, nine mammalian AlkB homologues have been identified. Like E. coli AlkB, ALKBH2 and ALKBH3 have been shown to possess DNA repair activity. However, findings suggest a wide functional diversity for other mammalian AlkB proteins, with substrates ranging from DNA and RNA to protein [, ].ALKBH5 is an dioxygenase that has been shown to specifically demethylate m(6)A in single-stranded RNA [, , ]. Reversible m(6)A modification is one of the most abundant RNA modifications, and is probably involved in broad and fundamental functions in mammalian cells []. ALKBH5 may have a role in the regulation of cellular responses to hypoxia [].
