ArticlePloS one2014
Selenium-based S-adenosylmethionine analog reveals the mammalian seven-beta-strand methyltransferase METTL10 to be an EF1A1 lysine methyltransferase.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 93 citations in OpenAlex.
- METTL18-catalyzed histidine methylation of YTHDF2 promotes mRNA stability.Science China. Life sciences · 2026Article
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- Assembling Ternary Dead-End Complex for Covalent Trapping of Protein Lysine Methyltransferases.Journal of the American Chemical Society · 2026Article
- METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The methyltransferase-like proteins as core regulators of nucleic acid modifications and post-translation modification of proteins in disease pathogenesis and therapeutic implications.Biomarker research · 2025Review
- Decoding the protein methylome: Identification, validation, and functional insights.Bioorganic & medicinal chemistry · 2025Review
- Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.Nucleic acids research · 2024Review
- Histidine N1-position-specific methyltransferase CARNMT1 targets C3H zinc finger proteins and modulates RNA metabolism.Genes & development · 2023Article
- METTL13 facilitates cell growth and metastasis in gastric cancer via an eEF1A/HN1L positive feedback circuit.Journal of cell communication and signaling · 2023Article
- METTLing in Stem Cell and Cancer Biology.Stem cell reviews and reports · 2023Review
- Article
- Defining the elusive oncogenic role of the methyltransferase TMT1B.Frontiers in oncology · 2023Review
- Article
- Protein methylation in mitochondria.The Journal of biological chemistry · 2022Review
- Nonhistone Lysine Methylation as a Protein Degradation Signal.Journal of chemistry · 2022Article
- SETD2 regulates the methylation of translation elongation factor eEF1A1 in clear cell renal cell carcinoma.Kidney cancer journal : official journal of the Kidney Cancer Association · 2022Article
- Evolution of Methyltransferase-Like (METTL) Proteins in Metazoa: A Complex Gene Family Involved in Epitranscriptomic Regulation and Other Epigenetic Processes.Molecular biology and evolution · 2021Article
- Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13.Life (Basel, Switzerland) · 2021Review
- On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits.International journal of molecular sciences · 2021Review
- Enzyme-mediated bioorthogonal technologies: catalysts, chemoselective reactions and recent methyltransferase applications.Current opinion in biotechnology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lysine methylation has been extensively studied in histones, where it has been shown to provide specific epigenetic marks for the regulation of gene expression; however, the molecular mechanism and physiological function of lysine methylation in proteins other than histones remains to be fully addressed. To better understand the substrate diversity of lysine methylation, S-adenosylmethionine (SAM) derivatives with alkyne-moieties have been synthesized. A selenium-based SAM analog, propargylic Se-adenosyl-l-selenomethionine (ProSeAM), has a wide spectrum of reactivity against various lysine methyltransferases (KMTs) with sufficient stability to support enzymatic reactions in vitro. By using ProSeAM as a chemical probe for lysine methylation, we identified substrates for two seven-beta-strand KMTs, METTL21A and METTL10, on a proteomic scale in mammalian cells. METTL21A has been characterized as a heat shock protein (HSP)-70 methyltransferase. Mammalian METTL10 remains functionally uncharacterized, although its ortholog in yeast, See1, has been shown to methylate the translation elongation factor eEF1A. By using ProSeAM-mediated alkylation followed by purification and quantitative MS analysis, we confirmed that METTL21A labels HSP70 family proteins. Furthermore, we demonstrated that METTL10 also methylates the eukaryotic elongation factor EF1A1 in mammalian cells. Subsequent biochemical characterization revealed that METTL10 specifically trimethylates EF1A1 at lysine 318 and that siRNA-mediated knockdown of METTL10 decreases EF1A1 methylation levels in vivo. Thus, our study emphasizes the utility of the synthetic cofactor ProSeAM as a chemical probe for the identification of non-histone substrates of KMTs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.