RGD Reference Report - SETD3 protein is the actin-specific histidine N-methyltransferase. - Rat Genome Database

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SETD3 protein is the actin-specific histidine N-methyltransferase.

Authors: Kwiatkowski, Sebastian  Seliga, Agnieszka K  Vertommen, Didier  Terreri, Marianna  Ishikawa, Takao  Grabowska, Iwona  Tiebe, Marcel  Teleman, Aurelio A  Jagielski, Adam K  Veiga-da-Cunha, Maria  Drozak, Jakub 
Citation: Kwiatkowski S, etal., Elife. 2018 Dec 11;7. pii: 37921. doi: 10.7554/eLife.37921.
RGD ID: 13838798
Pubmed: PMID:30526847   (View Abstract at PubMed)
PMCID: PMC6289574   (View Article at PubMed Central)
DOI: DOI:10.7554/eLife.37921   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Setd3Ratprotein-L-histidine N-tele-methyltransferase activity enablesIDA PMID:30526847UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Setd3  (SET domain containing 3, actin N3(tau)-histidine methyltransferase)


Additional Information