An Integrative Proteomic Approach Identifies Novel Cellular SMYD2 Substrates
datasetposted on 10.05.2016, 13:35 by Hazem Ahmed, Shili Duan, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Matthieu Schapira
Protein methylation is a post-translational modification with important roles in transcriptional regulation and other biological processes, but the enzyme–substrate relationship between the 68 known human protein methyltransferases and the thousands of reported methylation sites is poorly understood. Here, we propose a bioinformatic approach that integrates structural, biochemical, cellular, and proteomic data to identify novel cellular substrates of the lysine methyltransferase SMYD2. Of the 14 novel putative SMYD2 substrates identified by our approach, six were confirmed in cells by immunoprecipitation: MAPT, CCAR2, EEF2, NCOA3, STUB1, and UTP14A. Treatment with the selective SMYD2 inhibitor BAY-598 abrogated the methylation signal, indicating that methylation of these novel substrates was dependent on the catalytic activity of the enzyme. We believe that our integrative approach can be applied to other protein lysine methyltransferases, and help understand how lysine methylation participates in wider signaling processes.
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NCOAEEFproteomic datalysine methylationprotein methyltransferasesenzymeSMYD 2 substratesmethylation sitesmethylation signallysine methyltransferase SMYD 2.transcriptional regulationCCARSTUBUTP 14A TreatmentIntegrative Proteomic Approach Identifies Novel Cellular SMYD 2 Substrates Protein methylationbioinformatic approachprotein lysine methyltransferases14 novelnovel substratesMAPT