InterPro domain: IPR032857

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 [ 1 , 2 ].

ALKBH4 has been demonstrated to be an active Fe(II)/2OG-dependent decarboxylase in vitro [ 3 ]. ALKBH4 mediates demethylation of actin and thereby regulates the actin-myosin II interaction. Depletion of ALKBH4 leads to defects in cytokinesis and cell motility [ 4 ].

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 [ 5 ].

1. The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond. J. Biol. Chem. 290, 20734-42
2. Non-homologous functions of the AlkB homologs. J Mol Cell Biol
3. Spectroscopic and magnetic studies of wild-type and mutant forms of the Fe(II)- and 2-oxoglutarate-dependent decarboxylase ALKBH4. Biochem. J. 434, 391-8
4. ALKBH4-dependent demethylation of actin regulates actomyosin dynamics. Nat Commun 4, 1832
5. DNA Methylation on N6-Adenine in C. elegans. Cell 161, 868-78