SETD3 protein is the actin-specific histidine N-methyltransferase
(2018) eLife — Vol. 7, p. e37921 [1-42] (2018)
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- Authors
Kwiatkowski, Sebastian 
Drozak, Jakub
- Abstract
- Protein histidine methylation is a rare post-translational modification of unknown biochemical importance. In vertebrates, only a few methylhistidine-containing proteins have been reported, including b-actin as an essential example. The evolutionary conserved methylation of b- actin H73 is catalyzed by an as yet unknown histidine N-methyltransferase. We report here that the protein SETD3 is the actin-specific histidine N-methyltransferase. In vitro, recombinant rat and human SETD3 methylated b-actin at H73. Knocking-out SETD3 in both human HAP1 cells and in Drosophila melanogaster resulted in the absence of methylation at b-actin H73 in vivo, whereas b- actin from wildtype cells or flies was > 90% methylated. As a consequence, we show that Setd3- deficient HAP1 cells have less cellular F-actin and an increased glycolytic phenotype. In conclusion, by identifying SETD3 as the actin-specific histidine N-methyltransferase, our work pioneers new research into the possible role of this modification in health and disease and questions the substrate specificity of SET-domain-containing enzymes.
- Affiliations
University of Warsaw Department of Metabolic Regulation
Citations
Kwiatkowski, S., Seliga, A. K., Vertommen, D., Terreri, M., Ishikawa, T., Grabowska, I., Tiebe, M., Teleman, A. A., Jagielski, A. K., Veiga da Cunha, M., & Drozak, J. (2018). SETD3 protein is the actin-specific histidine N-methyltransferase. eLife, 7, e37921 [1-42]. https://doi.org/10.7554/elife.37921 (Original work published 2018)