Calmodulin methyltransferase is an evolutionarily conserved enzyme that trimethylates Lys-115 in calmodulin

• Published in: Nature communications 2010-07, Vol.1 (4), p.1-6, Article 43
• Main Authors: Houtz, Robert L, Magnani, Roberta, Dirk, Lynnette M.A, Trievel, Raymond C
• Format: Article
• Language: English
• Subjects: 631/45/612/1238; 631/80/458/1648; 631/80/86/1999; Amino Acid Sequence; Animals; Anura; Calcium; Calcium signalling; Calcium-binding protein; Calmodulin; Calmodulin - metabolism; Calmodulin-lysine N-methyltransferase; Chromatography, Liquid; Chromatography, Thin Layer; Conserved sequence; Electrophoresis, Polyacrylamide Gel; Enzymes; Escherichia; Evolution; frogs; Humanities and Social Sciences; Humans; Insect Proteins - chemistry; Insect Proteins - genetics; Insect Proteins - metabolism; insects; Lysine; Lysine - metabolism; Mass spectrometry; Mass spectroscopy; Methylation; Methyltransferase; Methyltransferases - chemistry; Methyltransferases - genetics; Methyltransferases - metabolism; Molecular Sequence Data; multidisciplinary; Plant Proteins - chemistry; Plant Proteins - genetics; Plant Proteins - metabolism; Post-translation; Protein Processing, Post-Translational; Protein Structure, Secondary; Proteins; Rats; Residues; Science; Science (multidisciplinary); Sequence Homology, Amino Acid; Tandem Mass Spectrometry
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms1044

Calmodulin (CaM) is a key mediator of calcium-dependent signalling and is subject to regulatory post-translational modifications, including trimethylation of Lys-115. In this paper, we identify a class I, non-SET domain protein methyltransferase, calmodulin-lysine N -methyltransferase (EC 2.1.1.60). A polypeptide chosen from a fraction enriched in calmodulin methyltransferase activity was trypsinized and analysed by tandem mass spectrometry. The amino-acid sequence obtained identified conserved, homologous proteins of unknown function across a wide range of species, thus implicating a broad role for lysine methylation in calcium-dependent signalling. Encoded by c2orf34, the human homologue is a component of two related multigene deletion syndromes in humans. Human, rat, frog, insect and plant homologues were cloned and Escherichia coli -recombinant proteins catalysed the formation of a trimethyllysyl residue at position 115 in CaM, as verified by product analyses and mass spectrometry. Calmodulin is a key mediator of calcium-dependent signalling and is subject to post-translational modifications. Here, evolutionarily conserved methyltransferases are identified which trimethylate Lys-115 of calmodulin, implying a broad role in calcium-dependent signalling.