SETD3 protein is the actin-specific histidine N-methyltransferase.
Elife
; 72018 12 11.
Article
en En
| MEDLINE
| ID: mdl-30526847
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 ß-actin as an essential example. The evolutionary conserved methylation of ß-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 ß-actin at H73. Knocking-out SETD3 in both human HAP1 cells and in Drosophila melanogaster resulted in the absence of methylation at ß-actin H73 in vivo, whereas ß-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.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Procesamiento Proteico-Postraduccional
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N-Metiltransferasa de Histona-Lisina
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Actinas
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Músculo Esquelético
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Fibroblastos
Idioma:
En
Revista:
Elife
Año:
2018
Tipo del documento:
Article
País de afiliación:
Polonia