ArticlePloS one2016
The Human Mixed Lineage Leukemia 5 (MLL5), a Sequentially and Structurally Divergent SET Domain-Containing Protein with No Intrinsic Catalytic Activity.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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.
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Who cites it
24 citing papers in PubMed.
- KMT2E recruitment by H3 serotonylation regulates neurodevelopmental chromatin dynamics.bioRxiv : the preprint server for biology · 2026Article
- A SET domain-containing protein and HCF-1 maintain transgenerational epigenetic memory.Nature communications · 2026Article
- Defining Biological and Biochemical Functions of Noncanonical SET Domain Proteins.Journal of molecular biology · 2024Review
- The protein methylation network in yeast: A landmark in completeness for a eukaryotic post-translational modification.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- ASXL1/2 mutations and myeloid malignancies.Journal of hematology & oncology · 2022Review
- Neurobehavioral characteristics of mice withFrontiers in genetics · 2022Review
- Review
- Set4 regulates stress response genes and coordinates histone deacetylases within yeast subtelomeres.Life science alliance · 2021Article
- Trans-tail regulation-mediated suppression of cryptic transcription.Experimental & molecular medicine · 2021Review
- Ready, SET, Go: Post-translational regulation of the histone lysine methylation network in budding yeast.The Journal of biological chemistry · 2021Review
- MLL5, a histone modifying enzyme, regulates androgen receptor activity in prostate cancer cells by recruiting co-regulators, HCF1 and SET1.BMB reports · 2020Article
- SETD5-Coordinated Chromatin Reprogramming Regulates Adaptive Resistance to Targeted Pancreatic Cancer Therapy.Cancer cell · 2020Article
- The Autism-Related Protein SETD5 Controls Neural Cell Proliferation through Epigenetic Regulation of rDNA Expression.iScience · 2020Article
- MLL5α activates AR/NDRG1 signaling to suppress prostate cancer progression.American journal of cancer research · 2020Article
- Histone lysine methyltransferases in biology and disease.Nature structural & molecular biology · 2019Review
- Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy.American journal of human genetics · 2019Article
- SET domains and stress: uncovering new functions for yeast Set4.Current genetics · 2019Review
- Identification of common genetic risk variants for autism spectrum disorder.Nature genetics · 2019Article
- Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.Nature neuroscience · 2018Article
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
Mixed Lineage Leukemia 5 (MLL5) plays a key role in hematopoiesis, spermatogenesis and cell cycle progression. Chromatin binding is ensured by its plant homeodomain (PHD) through a direct interaction with the N-terminus of histone H3 (H3). In addition, MLL5 contains a Su(var)3-9, Enhancer of zeste, Trithorax (SET) domain, a protein module that usually displays histone lysine methyltransferase activity. We report here the crystal structure of the unliganded SET domain of human MLL5 at 2.1 Å resolution. Although it shows most of the canonical features of other SET domains, both the lack of key residues and the presence in the SET-I subdomain of an unusually large loop preclude the interaction of MLL5 SET with its cofactor and substrate. Accordingly, we show that MLL5 is devoid of any in vitro methyltransferase activity on full-length histones and histone H3 peptides. Hence, the three dimensional structure of MLL5 SET domain unveils the structural basis for its lack of methyltransferase activity and suggests a new regulatory mechanism.
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