Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation

Research output: Contribution to journalArticle


Hsp70 proteins constitute an evolutionarily conserved protein family of ATP-dependent molecular chaperones involved in a wide range of biological processes. Mammalian Hsp70 proteins are subject to various post-translational modifications, including methylation, but for most of these, a functional role has not been attributed. In this study, we identified the methyltransferase METTL21A as the enzyme responsible for trimethylation of a conserved lysine residue found in several human Hsp70 (HSPA) proteins. This enzyme, denoted by us as HSPA lysine (K) methyltransferase (HSPA-KMT), was found to catalyze trimethylation of various Hsp70 family members both in vitro and in vivo, and the reaction was stimulated by ATP. Furthermore, we show that HSPA-KMT exclusively methylates 70-kDa proteins in mammalian protein extracts, demonstrating that it is a highly specific enzyme. Finally, we show that trimethylation of HSPA8 (Hsc70) has functional consequences, as it alters the affinity of the chaperone for both the monomeric and fibrillar forms of the Parkinson disease-associated protein α-synuclein.


  • Magnus E Jakobsson
  • Anders Moen
  • Luc Bousset
  • Wolfgang Egge-Jacobsen
  • Stefan Kernstock
  • Ronald Melki
  • Pål Ø Falnes
External organisations
  • University of Oslo
  • The French National Centre for Scientific Research (CNRS)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology


  • Amino Acid Motifs, Amino Acid Sequence, Biomarkers/metabolism, Catalysis, Cloning, Molecular, Computational Biology, DNA Modification Methylases/chemistry, HEK293 Cells, HSP70 Heat-Shock Proteins/metabolism, Humans, Lysine/metabolism, Mass Spectrometry, Molecular Sequence Data, Open Reading Frames, Peptides/metabolism, Protein Binding, Protein Processing, Post-Translational, Recombinant Proteins/metabolism, alpha-Synuclein/metabolism
Original languageEnglish
Pages (from-to)27752-63
Number of pages12
JournalJournal of Biological Chemistry
Issue number39
Publication statusPublished - 2013 Sep 27
Publication categoryResearch
Externally publishedYes