ArticleNature communications2021
The methyltransferase METTL9 mediates pervasive 1-methylhistidine modification in mammalian proteomes.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 2 of them syntheses that pooled it.
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Who cites it
70 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.
- Metabolomics and Cardiovascular Risk in Patients with Heart Failure: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2024Pooled it
- Targeting Mitochondrial Oxidative Phosphorylation Eradicates Acute Myeloid Leukemic Stem Cells.Frontiers in oncology · 2022Pooled it
- METTL18-catalyzed histidine methylation of YTHDF2 promotes mRNA stability.Science China. Life sciences · 2026Article
- Modulation of Thermodynamic Profiles: Regulation of Imidazole Affinity by Porphyrin Distortion in Aqueous Solution.ACS omega · 2026Article
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- Orphan Enzymes in the Mammalian L-Fucose Degradation Pathway.Biomolecules · 2026Review
- Histidine Ethylation by Histidine Methyltransferases SETD3 and METTL9.Chembiochem : a European journal of chemical biology · 2026Article
- Myocardial metabolic remodeling in human end-stage ischemic and non-ischemic cardiomyopathy.Journal of molecular and cellular cardiology · 2026Article
- Substrate selectivity of human histidine methyltransferase METTL9.Protein science : a publication of the Protein Society · 2026Article
- Uncovering a role for METTL13 in malignant transformation of human hematopoietic stem cells and in the progression of pediatric leukemia.Cell death & disease · 2026Article
- METTL18 ensures pancreatic function by maintaining proper translation and proteostasis.Molecular metabolism · 2026Article
- Update of the Methyltransferase Gene Family: Classification, Evolution and Biological Functions.Human genomics · 2026Review
- The Protein Histidine Methyltransferase METTL9-From Mechanism to Biological Function.Life (Basel, Switzerland) · 2026Review
- Femoral arteriovenous concentration differences reveal metabolomic shifts in peripheral artery disease (PAD): A case-control study.Vascular medicine (London, England) · 2025Article
- Review
- 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
- Serum Metabolomics Reveals Potential Differences in Gut Microbiota-Associated Metabolites in Twins Discordant for Type 1 Diabetes.Diabetes · 2025Article
- Uncovering a role for METTL13 in malignant transformation of human hematopoietic stem cells and in the progression of pediatric leukemia.Research square · 2025Article
- METTL13 Promotes Pre-Leukemic Transformation and the Development of Pediatric Leukemia.bioRxiv : the preprint server for biology · 2025Article
- Urinary 3-methylhistidine as a potential biomarker for sepsis-associated acute kidney injury: multidimensional metabolomics analysis in mice and human.Annals of intensive care · 2025Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 11 institutions in 8 countries.
Funding
Abstract
Post-translational methylation plays a crucial role in regulating and optimizing protein function. Protein histidine methylation, occurring as the two isomers 1- and 3-methylhistidine (1MH and 3MH), was first reported five decades ago, but remains largely unexplored. Here we report that METTL9 is a broad-specificity methyltransferase that mediates the formation of the majority of 1MH present in mouse and human proteomes. METTL9-catalyzed methylation requires a His-x-His (HxH) motif, where "x" is preferably a small amino acid, allowing METTL9 to methylate a number of HxH-containing proteins, including the immunomodulatory protein S100A9 and the NDUFB3 subunit of mitochondrial respiratory Complex I. Notably, METTL9-mediated methylation enhances respiration via Complex I, and the presence of 1MH in an HxH-containing peptide reduced its zinc binding affinity. Our results establish METTL9-mediated 1MH as a pervasive protein modification, thus setting the stage for further functional studies on protein histidine methylation.
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Registered trials
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.