AlkB is a dioxygenase that repairs alkylation damage to DNA and RNA []. AlkB homologues (ABHs) are found in all multicellular organisms, as well as in many bacteria and fungi, and some viruses []. Nine mammalian AlkB homologues exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes [].This entry represents AlkB homologue 2 (ALKBH2, ABH2), which has a strong preference for double-stranded DNA []. Together with alkyl-N-adenine-DNA glycosylase, comprises the cellular defence against 1,N(6)-ethenoadenine lesions []. ABH2 also has an important role in maintaining ribosomal DNA gene integrity and transcription []. This entry also includes uncharacterised bacterial homologues.
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 [, ].AlkB homologue 6 (ALKBH6) is a probable dioxygenase that requires molecular oxygen, alpha-ketoglutarate and iron. Its function is not known.
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 [].
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 [, ].ALKBH4 has been demonstrated to be an active Fe(II)/2OG-dependent decarboxylase in vitro[]. ALKBH4 mediates demethylation of actin and thereby regulates the actin-myosin II interaction. Depletion of ALKBH4 leads to defects in cytokinesis and cell motility [].This entry also includes Nmad-1, one of the five members of the ALKB family found in C. elegans, which is a 6mA DNA demethylase and may be involved in epigenetic inheritance [].
