title: Elongation factor methyltransferase 3--a novel eukaryotic lysine methyltransferase.
abstract: Here we describe the discovery of Saccharomycescerevisiae protein YJR129Cp as a new eukaryotic seven-beta-strand lysine methyltransferase. An immunoblotting screen of 21 putative methyltransferases showed a loss in the methylation of elongation factor 2 (EF2) on knockout of YJR129C. Mass spectrometric analysis of EF2 tryptic peptides localised this loss of methylation to lysine 509, in peptide LVEGLKR. In vitro methylation, using recombinant methyltransferases and purified EF2, validated YJR129Cp as responsible for methylation of lysine 509 and Efm2p as responsible for methylation at lysine 613. Contextualised on previously described protein structures, both sites of methylation were found at the interaction interface between EF2 and the 40S ribosomal subunit. In line with the recently discovered Efm1 and Efm2 we propose that YJR129C be named elongation factor methyltransferase 3 (Efm3). The human homolog of Efm3 is likely to be the putative methyltransferase FAM86A, according to sequence homology and multiple lines of literature evidence.
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia.
authors.forename: Lelin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Hamey
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia.
authors.forename: Gene
authors.initials: G
authors.lastname: Hart-Smith
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Erce
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia. Electronic address: m.wilkins@unsw.edu.au.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Wilkins
mesh_terms: D000595:Amino Acid Sequence; D055786:Gene Knockout Techniques; D005800:Genes, Fungal; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020652:Peptide Elongation Factor 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054682:Ribosome Subunits, Small, Eukaryotic / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein; D013379:Substrate Specificity
chemical_list: D020652:Peptide Elongation Factor 2; D010446:Peptide Fragments; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D008780:Methyltransferases; C523514:YJR129C protein, S cerevisiae; D008239:Lysine
keywords: Elongation factor 2; Lysine methyltransferase; Methylation; Saccharomyces cerevisiae