Non-homologous functions of the AlkB homologs

J Mol Cell Biol. 2015 Dec;7(6):494-504. doi: 10.1093/jmcb/mjv029. Epub 2015 May 23.


The DNA repair enzyme AlkB was identified in E. coli more than three decades ago. Since then, nine mammalian homologs, all members of the superfamily of alpha-ketoglutarate and Fe(II)-dependent dioxygenases, have been identified (designated ALKBH1-8 and FTO). While E. coli AlkB serves as a DNA repair enzyme, only two mammalian homologs have been confirmed to repair DNA in vivo. The other mammalian homologs have remarkably diverse substrate specificities and biological functions. Substrates recognized by the different AlkB homologs comprise erroneous methyl- and etheno adducts in DNA, unique wobble uridine modifications in certain tRNAs, methylated adenines in mRNA, and methylated lysines on proteins. The phenotypes of organisms lacking or overexpressing individual AlkB homologs include obesity, severe sensitivity to inflammation, infertility, growth retardation, and multiple malformations. Here we review the present knowledge of the mammalian AlkB homologs and their implications for human disease and development.

Keywords: ALKBH; AlkB homologs; DNA repair; RNA repair; epigenetics; histone demethylation; tRNA modification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Computational Biology
  • DNA Methylation
  • DNA Repair / physiology
  • Dioxygenases / chemistry*
  • Dioxygenases / classification
  • Dioxygenases / metabolism
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / classification
  • Escherichia coli Proteins / metabolism
  • Humans
  • Ketoglutaric Acids / chemistry*
  • Mice
  • Mixed Function Oxygenases / chemistry*
  • Mixed Function Oxygenases / classification
  • Mixed Function Oxygenases / metabolism
  • Phylogeny
  • Protein Processing, Post-Translational
  • RNA Processing, Post-Transcriptional
  • RNA, Transfer / metabolism*
  • Sequence Homology, Amino Acid
  • Substrate Specificity


  • Escherichia coli Proteins
  • Ketoglutaric Acids
  • RNA, Transfer
  • Mixed Function Oxygenases
  • Dioxygenases
  • AlkB protein, E coli