SETD3 protein is the actin-specific histidine N-methyltransferase
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 β-actin as an essential example. The evolutionary conserved methylation of β-actin H73 is catalyzed...
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| Hauptverfasser: | , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
Dec 11, 2018
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| In: |
eLife
Year: 2018, Jahrgang: 7 |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.37921 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.7554/eLife.37921
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| Verfasserangaben: | Sebastian Kwiatkowski, Agnieszka K Seliga, Didier Vertommen, Marianna Terreri, Takao Ishikawa, Iwona Grabowska, Marcel Tiebe, Aurelio A Teleman, Adam K Jagielski, Maria Veiga-da-Cunha, Jakub Drozak |
| Zusammenfassung: | 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 β-actin as an essential example. The evolutionary conserved methylation of β-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 β-actin at H73. Knocking-out SETD3 in both human HAP1 cells and in Drosophila melanogaster resulted in the absence of methylation at β-actin H73 in vivo, whereas β-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. |
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| Beschreibung: | N im Texst ist schräg gestellt Gesehen am 04.11.2019 |
| Beschreibung: | Online Resource |
| ISSN: | 2050-084X |
| DOI: | 10.7554/eLife.37921 |