ArticleThe Journal of biological chemistry2013
Identification and characterization of a novel human methyltransferase modulating Hsp70 protein function through lysine methylation.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Who cites it
74 citing papers in PubMed, 105 citations in OpenAlex.
- Methylation-driven SOX18 nuclear translocation by IGF2BP1-stabilized METTL21A promotes lymphatic metastasis in gastric cancer.Oncogene · 2026Article
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- Molecular insight into transcriptome profiling of aerobic exercise induced changes in aged skeletal muscle.npj aging · 2026Article
- Aggregation-prone alpha-synuclein proteoforms and dysregulated molecular signatures in the vermiform appendix of synucleinopathy patients.bioRxiv : the preprint server for biology · 2025Article
- METTL21A promotes hepatocellular carcinoma progression via methylating and stabilizing BAG3.NPJ precision oncology · 2025Article
- Decoding the protein methylome: Identification, validation, and functional insights.Bioorganic & medicinal chemistry · 2025Review
- Targeting chaperone modifications: Innovative approaches to cancer treatment.The Journal of biological chemistry · 2024Review
- Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.Nucleic acids research · 2024Review
- Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions.Biomolecules · 2024Review
- The interaction of GRP78 and Zika virus E and NS1 proteins occurs in a chaperone-client manner.Scientific reports · 2024Article
- Phosphorylated Adapter RNA Export Protein Is Methylated at Lys 381 by an Methyltransferase-like 21C (METTL21C).International journal of molecular sciences · 2023Article
- HSPA6 and its role in cancers and other diseases.Molecular biology reports · 2022Review
- Computationally-Aided Modeling of Hsp70-Client Interactions: Past, Present, and Future.The journal of physical chemistry. B · 2022Article
- Functional Analysis of Conserved Hypothetical Proteins from the Antarctic Bacterium,Microorganisms · 2022Article
- Protein methylation in mitochondria.The Journal of biological chemistry · 2022Review
- Regulation by Different Types of Chaperones of Amyloid Transformation of Proteins Involved in the Development of Neurodegenerative Diseases.International journal of molecular sciences · 2022Review
- Nonhistone Lysine Methylation as a Protein Degradation Signal.Journal of chemistry · 2022Article
- Structure, Activity and Function of the Dual Protein Lysine and Protein N-Terminal Methyltransferase METTL13.Life (Basel, Switzerland) · 2021Review
- Stoichiometric Analysis of Shifting in Subcellular Compartmentalization of HSP70 within Ischemic Penumbra.Molecules (Basel, Switzerland) · 2021Article
- Large-scale identification of protein histidine methylation in human cells.NAR genomics and bioinformatics · 2021Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hsp70 proteins constitute an evolutionarily conserved protein family of ATP-dependent molecular chaperones involved in a wide range of biological processes. Mammalian Hsp70 proteins are subject to various post-translational modifications, including methylation, but for most of these, a functional role has not been attributed. In this study, we identified the methyltransferase METTL21A as the enzyme responsible for trimethylation of a conserved lysine residue found in several human Hsp70 (HSPA) proteins. This enzyme, denoted by us as HSPA lysine (K) methyltransferase (HSPA-KMT), was found to catalyze trimethylation of various Hsp70 family members both in vitro and in vivo, and the reaction was stimulated by ATP. Furthermore, we show that HSPA-KMT exclusively methylates 70-kDa proteins in mammalian protein extracts, demonstrating that it is a highly specific enzyme. Finally, we show that trimethylation of HSPA8 (Hsc70) has functional consequences, as it alters the affinity of the chaperone for both the monomeric and fibrillar forms of the Parkinson disease-associated protein α-synuclein.
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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.