ArticlePLoS genetics2013
A newly uncovered group of distantly related lysine methyltransferases preferentially interact with molecular chaperones to regulate their activity.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
108 citing papers in PubMed, 155 citations in OpenAlex.
- Isothiocyanates are detected in human synovial fluid following broccoli consumption and can affect the tissues of the knee joint.Scientific reports · 2017Trial
- Decoding Protein-Methylating METTLs in Humans: Structural, Functional, and Disease Insights over the Past Decade.International journal of molecular sciences · 2026Review
- An Atlas of Short Linear Motif-Mediated Human Protein-Protein Interactions.bioRxiv : the preprint server for biology · 2026Article
- Neuron type-specific translatomes in dorsal hippocampus during early memory consolidation.Nature communications · 2026Article
- ASPL couples the assembly of stress granules with their VCP-mediated disassembly.Science advances · 2025Article
- Therapeutic Targeting of Protein Lysine and Arginine Methyltransferases: Principles and Strategies for Inhibitor Design.International journal of molecular sciences · 2025Review
- Neuron type-specific mRNA translation programs provide a gateway for memory consolidation.bioRxiv : the preprint server for biology · 2025Article
- METTL21A promotes hepatocellular carcinoma progression via methylating and stabilizing BAG3.NPJ precision oncology · 2025Article
- Closing in on human methylation-the versatile family of seven-β-strand (METTL) methyltransferases.Nucleic acids research · 2024Review
- The interaction of GRP78 and Zika virus E and NS1 proteins occurs in a chaperone-client manner.Scientific reports · 2024Article
- Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy.Journal of translational medicine · 2024Review
- Identification of a novelFrontiers in pediatrics · 2024Article
- METTL18 functions as a Phenotypic Regulator in Src-Dependent Oncogenic Responses of HER2-Negative Breast Cancer.International journal of biological sciences · 2024Article
- Therapeutic targeting potential of the protein lysine and arginine methyltransferases to reverse cancer chemoresistance.Frontiers in molecular biosciences · 2024Review
- Phosphorylated Adapter RNA Export Protein Is Methylated at Lys 381 by an Methyltransferase-like 21C (METTL21C).International journal of molecular sciences · 2023Article
- A cryptic microdeletion del(12)(p11.21p11.23) within an unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Scientific reports · 2023Article
- Structural basis for recognition and methylation of p97 by METTL21D, a valosin-containing protein lysine methyltransferase.iScience · 2023Article
- Roles and regulatory mechanisms of KIN17 in cancers (Review).Oncology letters · 2023Review
- A microdeletion del(12)(p11.21p11.23) with a cryptic unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Research square · 2023Article
- Structural remodeling of AAA+ ATPase p97 by adaptor protein ASPL facilitates posttranslational methylation by METTL21D.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
48 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Methylation is a post-translational modification that can affect numerous features of proteins, notably cellular localization, turnover, activity, and molecular interactions. Recent genome-wide analyses have considerably extended the list of human genes encoding putative methyltransferases. Studies on protein methyltransferases have revealed that the regulatory function of methylation is not limited to epigenetics, with many non-histone substrates now being discovered. We present here our findings on a novel family of distantly related putative methyltransferases. Affinity purification coupled to mass spectrometry shows a marked preference for these proteins to associate with various chaperones. Based on the spectral data, we were able to identify methylation sites in substrates, notably trimethylation of K135 of KIN/Kin17, K561 of HSPA8/Hsc70 as well as corresponding lysine residues in other Hsp70 isoforms, and K315 of VCP/p97. All modification sites were subsequently confirmed in vitro. In the case of VCP, methylation by METTL21D was stimulated by the addition of the UBX cofactor ASPSCR1, which we show directly interacts with the methyltransferase. This stimulatory effect was lost when we used VCP mutants (R155H, R159G, and R191Q) known to cause Inclusion Body Myopathy with Paget's disease of bone and Fronto-temporal Dementia (IBMPFD) and/or familial Amyotrophic Lateral Sclerosis (ALS). Lysine 315 falls in proximity to the Walker B motif of VCP's first ATPase/D1 domain. Our results indicate that methylation of this site negatively impacts its ATPase activity. Overall, this report uncovers a new role for protein methylation as a regulatory pathway for molecular chaperones and defines a novel regulatory mechanism for the chaperone VCP, whose deregulation is causative of degenerative neuromuscular diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.