Affinage

SETD3

Actin-histidine N-methyltransferase · UniProt Q86TU7

Length
594 aa
Mass
67.3 kDa
Annotated
2026-04-28
49 papers in source corpus 23 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SETD3 is a SET-domain methyltransferase whose principal physiological activity is N3-methylation of β-actin histidine 73, a modification that reduces nucleotide exchange on actin monomers and promotes F-actin polymerization, with critical consequences for smooth muscle contractility, mitochondrial F-actin dynamics and oxidative phosphorylation, and cytoskeletal integrity (PMID:30626964, PMID:30526847, PMID:38896010). The catalytic mechanism involves a ~105° rotation of the His73 imidazole ring to shift its proton from N3 to N1, enabling deprotonated N3 to accept the methyl group from SAM—a mechanism distinct from lysine methyltransferases (PMID:31388018, PMID:31911441). Beyond actin, SETD3 methylates MCM7 at H459 to facilitate CDT1-mediated MCM helicase loading and replication origin firing (PMID:39455502), dimethylates CHD1 at K209 to stabilize the chromodomein remodeler and activate NF-κB target genes (PMID:41045985), scaffolds BRD2 and hnRNPK on chromatin to regulate transcription and pre-mRNA splicing (PMID:40944926, PMID:39391005), and interacts with enteroviral 2A protease to support viral RNA replication independently of its methyltransferase activity (PMID:31527793). SETD3 protein levels are cell-cycle regulated through a GSK3β–FBXW7β phosphodegron, USP27-mediated deubiquitination, and a NUDT16/CHFR axis that couples ADP-ribosylation to proteasomal turnover (PMID:28442573, PMID:35018513, PMID:38272222).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2011 Medium

    Before SETD3's true substrate was known, its SET domain was shown to have histone methyltransferase activity in vitro, and knockdown in C2C12 myoblasts blocked muscle gene activation with MyoD, establishing SETD3 as a chromatin-associated transcriptional regulator of myogenesis.

    Evidence In vitro HMT assay on H3K4/K36, shRNA knockdown, ChIP, and reporter assays in C2C12 cells

    PMID:21832073

    Open questions at the time
    • Later work cast doubt on histones as physiological substrates; the in vitro histone methylation has not been reproduced with rigorous controls
    • Mechanism by which SETD3 activates myogenin transcription is unclear—direct histone methylation vs. scaffolding
  2. 2015 Medium

    An interaction between SETD3 and the replication clamp PCNA was identified, providing an early hint of a role at replication forks, though no functional consequence was established.

    Evidence BiFC screen, Co-IP from human cell extracts, and recombinant protein pulldown

    PMID:26030842

    Open questions at the time
    • No functional consequence of the SETD3–PCNA interaction was shown
    • Whether SETD3 acts on chromatin at replication forks was not tested
  3. 2016 Medium

    A proteomic interactome study identified FoxM1 as both an interaction partner and in vitro methylation substrate of SETD3, and ChIP showed co-occupancy at the VEGF promoter that is lost under hypoxia, implicating SETD3 in transcriptional regulation beyond histones.

    Evidence Co-IP/MS, in vitro methyltransferase assay on FoxM1, ChIP at VEGF promoter under normoxia and hypoxia

    PMID:27845446

    Open questions at the time
    • FoxM1 methylation site and functional impact were not mapped
    • Causal link between SETD3-FoxM1 dissociation and VEGF de-repression not established
  4. 2017 High

    Discovery that SETD3 stability is cell-cycle regulated via a GSK3β-phosphorylated CPD1 phosphodegron recognized by FBXW7β established the first post-translational regulatory axis controlling SETD3 protein levels, peaking in S phase.

    Evidence Reciprocal Co-IP, phosphodegron mutagenesis, GSK3β inhibition, FBXW7β depletion, and xenograft mouse model

    PMID:28442573

    Open questions at the time
    • Why SETD3 levels must peak in S phase was unclear at the time
    • Other E3 ligases that target SETD3 were not investigated
  5. 2018 High

    Two independent studies converged to identify β-actin His73 as the sole physiological substrate of SETD3, resolving the long-standing question of the actin histidine methyltransferase identity; crystal structures defined the extensive peptide-clamping mechanism, and proteomics confirmed no other detectable substrates.

    Evidence Crystal structures, in vitro methyltransferase reconstitution, quantitative proteomics, SETD3 KO mice, CRISPR KO in HAP1 cells and Drosophila

    PMID:30526847 PMID:30626964

    Open questions at the time
    • Whether additional non-actin substrates exist at low stoichiometry was not excluded by proteomics sensitivity
    • The signaling context controlling SETD3 access to actin monomers was not explored
  6. 2018 High

    SETD3 knockout female mice exhibited primary dystocia from failed uterine contractions, directly linking actin His73 methylation to smooth muscle contractility in vivo and demonstrating a critical physiological role.

    Evidence SETD3 KO mouse breeding, primary human uterine smooth muscle cell contraction assay

    PMID:30626964

    Open questions at the time
    • Whether dystocia reflects reduced F-actin content, altered actomyosin dynamics, or both was not dissected
    • Non-uterine smooth muscle phenotypes were not systematically examined
  7. 2019 High

    Detailed structural and enzymological studies resolved the unique catalytic mechanism: His73 imidazole rotates ~105° within the SETD3 active site to shift the proton from N3 to N1, enabling nucleophilic attack by the deprotonated N3 on SAM, distinguishing histidine methylation from lysine methylation.

    Evidence X-ray crystallography of pre-reactive and post-reactive complexes, active-site mutagenesis, enzyme kinetics

    PMID:30785395 PMID:31388018

    Open questions at the time
    • Whether this mechanism generalizes to other histidine methyltransferases was unknown
    • Transition-state analogues for SETD3 have not been developed
  8. 2019 High

    A genome-scale CRISPR screen identified SETD3 as essential for enteroviral RNA replication; the interaction with viral 2A protease was mapped by AP-MS and shown to be methyltransferase-independent, revealing a non-enzymatic host-factor role.

    Evidence Genome-scale CRISPR screen, quantitative AP-MS, 2A protease mutagenesis, multiple in vivo mouse infection models

    PMID:31527793

    Open questions at the time
    • The molecular mechanism by which SETD3 binding to 2A facilitates RNA replication remains unknown
    • Whether therapeutic disruption of SETD3–2A interaction is feasible was not addressed
  9. 2019 Medium

    SETD3 was shown to interact with p53 in response to DNA damage and to be required for p53 recruitment to target promoters, adding a nuclear scaffolding function relevant to apoptosis in addition to its cytoplasmic methyltransferase role.

    Evidence Co-IP, ChIP, catalytic-dead mutant, apoptosis assay in colon cancer cells after doxorubicin

    PMID:30683849

    Open questions at the time
    • Whether SETD3 methylates p53 or acts purely as a scaffold was not resolved
    • Independence from actin methylation in the p53 pathway was not tested
  10. 2020 High

    Active-site engineering showed that only two substitutions (N255F/W273A) switch SETD3 from histidine to lysine specificity, defining the minimal determinants of His vs. Lys selectivity and confirming that the target nitrogen occupies the same position relative to SAM.

    Evidence Active-site mutagenesis, X-ray crystallography, enzyme kinetics on His- and Lys-containing peptides

    PMID:31911441 PMID:32503840

    Open questions at the time
    • Whether the engineered lysine-methyltransferase variant functions in vivo was not tested
    • Implications for evolution of SET-domain substrate specificity were not explored
  11. 2022 Medium

    USP27 was identified as a deubiquitinase that stabilizes SETD3, adding a second layer of post-translational control beyond FBXW7β-mediated degradation and linking SETD3 stability to hepatocellular carcinoma proliferation.

    Evidence Co-IP, in vivo ubiquitination assay, USP27 knockdown/inhibition, tumor growth assay

    PMID:35018513

    Open questions at the time
    • Whether USP27 counteracts specifically FBXW7β-mediated ubiquitination was not tested
    • USP27 regulation of SETD3 in non-cancer contexts is unknown
  12. 2024 Medium

    Multiple 2024 studies expanded SETD3 biology in three directions: (i) outer mitochondrial membrane localization and mechanosensitive regulation of mitochondrial F-actin, morphology, and OXPHOS; (ii) methylation of MCM7-H459 required for MCM loading and replication origin firing, regulated by CDK2 phosphorylation of SETD3-S21; and (iii) a NUDT16 dePARylation/CHFR ubiquitination axis that controls SETD3 turnover and BRCA2 recruitment to stalled forks.

    Evidence Live imaging and fractionation, SETD3 loss-of-function with mitochondrial assays; NS-seq, MCM loading and CDK2 phosphorylation assays; Co-IP, PARylation and ubiquitination assays, BRCA2 recruitment assays

    PMID:38272222 PMID:38896010 PMID:39455502

    Open questions at the time
    • MCM7-H459 methylation by SETD3 has not been independently replicated
    • Whether mitochondrial outer-membrane SETD3 is distinct from cytosolic or nuclear pools is unresolved
    • The relationship between NUDT16-dependent SETD3 stabilization and the FBXW7β/USP27 pathways is unknown
  13. 2024 Medium

    Nuclear SETD3 was found to interact with hnRNPK to regulate genome-wide pre-mRNA exon skipping, specifically controlling FNIP1 splicing to promote TFEB nuclear translocation and lysosomal/mitochondrial biogenesis, and separately to regulate Wnt/β-catenin signaling during mESC endoderm differentiation.

    Evidence TurboID proximity labeling, RNA-seq, FNIP1/TFEB pathway assays; shRNA screen, PLA, Wnt reporter, KO mESCs

    PMID:38334393 PMID:39391005

    Open questions at the time
    • Whether SETD3's splicing role requires its catalytic activity or is purely scaffolding is unknown
    • Direct methylation of hnRNPK or β-catenin by SETD3 was not tested
  14. 2025 Medium

    Recent work identified BRD2 as a nuclear SETD3 partner required for BRD2 chromatin recruitment in mESCs, CHD1-K209 dimethylation as a novel lysine methylation substrate stabilizing CHD1 and activating NF-κB genes, and showed that the BWCFF-associated actin G74S mutation impairs SETD3-mediated His73 methylation in patient fibroblasts.

    Evidence Nuclear interactome MS, PLA, domain deletion, ChIP, RNA-seq in mESCs; in vitro methyltransferase assay, MS on CHD1-K209; molecular docking, enzymatic turnover, patient fibroblast MS

    PMID:40490999 PMID:40944926 PMID:41045985

    Open questions at the time
    • CHD1 lysine dimethylation by SETD3 has not been independently replicated and seems at odds with SETD3's established histidine specificity
    • The BWCFF link is through the actin substrate mutation, not a SETD3 mutation; whether SETD3 contributes independently to BWCFF pathogenesis is unclear
    • α-Centractin (ACTR1A) methylation was identified only in vitro and lacks in vivo validation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: (1) whether MCM7 and CHD1 are bona fide in vivo substrates comparable in stoichiometry to actin-His73; (2) how cytoplasmic, mitochondrial, and nuclear SETD3 pools are coordinated; (3) the structural basis for SETD3's scaffolding roles with 2A protease, BRD2, and hnRNPK; and (4) whether SETD3 can be therapeutically targeted to block enteroviral infection without disrupting actin methylation.
  • No quantitative in vivo stoichiometry for non-actin substrates
  • No structural model of SETD3 in complex with viral 2A, BRD2, or hnRNPK
  • Mechanism of SETD3 partitioning among subcellular compartments is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 8 GO:0140096 catalytic activity, acting on a protein 5 GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-392499 Metabolism of proteins 5 GO:0005856 cytoskeleton 3 R-HSA-1640170 Cell Cycle 2 R-HSA-162582 Signal Transduction 1 R-HSA-1643685 Disease 1 R-HSA-5357801 Programmed Cell Death 1 R-HSA-69306 DNA Replication 1
Partners
ACTBBRD2FBXW7HNRNPKMCM7NUDT16TP53USP27X

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 SETD3 is the physiological actin histidine methyltransferase that methylates β-actin at histidine 73 (His73). Structural studies reveal an extensive network of interactions that clamps the actin peptide onto the SETD3 surface to orient His73 correctly within the catalytic pocket and facilitate methyl transfer. His73 methylation reduces the nucleotide-exchange rate on actin monomers and modestly accelerates actin filament assembly. Quantitative proteomics confirmed actin His73 methylation as the only detectable physiological substrate of SETD3. Crystal structure, in vitro methyltransferase assay, quantitative proteomics (mass spectrometry), SETD3 knockout mice Nature High 30626964
2018 SETD3 catalyzes Nτ-methylation of β-actin His73 in vitro using recombinant rat and human SETD3. Knockout of SETD3 in human HAP1 cells and Drosophila results in complete loss of β-actin H73 methylation in vivo. SETD3-deficient HAP1 cells have less cellular F-actin and an increased glycolytic phenotype. In vitro methyltransferase assay, CRISPR knockout in human cells and Drosophila, mass spectrometry, F-actin quantification eLife High 30526847
2018 SETD3-deficient female mice exhibit primary maternal dystocia (failed uterine contractions during labor), and depletion of SETD3 impairs signal-induced contraction in primary human uterine smooth muscle cells, establishing a role for SETD3 and actin His73 methylation in smooth muscle contractility. SETD3 knockout mouse model, primary human uterine smooth muscle cell contraction assay Nature High 30626964
2019 SETD3 is required for enterovirus RNA replication step (not viral entry or translation), independent of its methyltransferase activity. SETD3 specifically interacts with the viral 2A protease of multiple enteroviral species via quantitative affinity purification-mass spectrometry; 2A mutants retaining protease activity but unable to bind SETD3 are severely compromised in RNA replication. Genome-scale CRISPR screen, quantitative AP-MS, 2A protease mutagenesis, multiple mouse models of enterovirus infection Nature microbiology High 31527793
2019 Crystal structures of SAH-bound SETD3 in complex with unmodified or His-methylated β-actin peptides reveal that recognition and methylation are highly sequence specific; both SETD3 and β-actin undergo pronounced conformational changes upon binding. The structures define the catalytic mechanism of SETD3-mediated histidine N3-methylation. X-ray crystallography, biochemical activity assays, enzyme kinetics eLife High 30785395
2019 SETD3 binds the N3-protonated form of actin His73 in a pre-reactive complex, and generates N1-protonated/N3-methylated histidine in the product complex. During the reaction, the imidazole ring of His73 rotates ~105°, shifting the proton from N3 to N1 to ensure the target N3 atom is deprotonated prior to methyl transfer, distinguishing SETD3 mechanistically from lysine methyltransferases. X-ray crystallography of pre-reactive and post-reactive complexes, mutagenesis, in vitro enzyme assays Nature communications High 31388018
2011 SETD3 functions as a histone H3K4 and H3K36 methyltransferase, is recruited to the myogenin gene promoter together with MyoD, activates transcription of muscle-related genes (myogenin, MCK, Myf6), and is required for skeletal muscle cell differentiation. In vitro histone methyltransferase assay, shRNA knockdown, reporter assays, chromatin immunoprecipitation (ChIP), overexpression in C2C12 cells The Journal of biological chemistry Medium 21832073
2017 SETD3 protein levels are cell cycle-regulated (peak in S phase, lowest in M phase). FBXW7β mediates SETD3 degradation by recognizing a CPD1 phosphodegron phosphorylated by GSK3β; mutations of the phosphorylated residues in CPD1 abolish FBXW7β–SETD3 interaction and prevent degradation. Co-immunoprecipitation, phosphorylation assays, CPD1 mutagenesis, GSK3β inhibition, FBXW7β depletion, xenograft mouse model The Journal of biological chemistry High 28442573
2016 SETD3 binds and methylates the transcription factor FoxM1. Under basal conditions, SETD3 and FoxM1 are co-enriched at the VEGF promoter; under hypoxia, both dissociate from the promoter, correlating with increased VEGF expression. SETD3 proteomic analysis identified 172 interacting proteins. Proteomics (co-immunoprecipitation/MS), in vitro methyltransferase assay on FoxM1, chromatin immunoprecipitation (ChIP) Scientific reports Medium 27845446
2019 SETD3 is a positive regulator of DNA-damage-induced apoptosis in colon cancer cells. SETD3 binds p53 in cells in response to doxorubicin, and the presence of SETD3 and its catalytic activity are required for p53 recruitment to target gene promoters. Co-immunoprecipitation, shRNA knockdown, catalytic mutant, apoptosis assay, chromatin immunoprecipitation Cell death & disease Medium 30683849
2020 SETD3 can methylate the sulfur atom of methionine substituted at the His73 position of actin, generating S-methylmethionine in an actin peptide context. The methionine substitution increases binding affinity for SETD3 76-fold but inhibits activity on histidine. Crystal structure at 1.9 Å shows the methionine thioether packed by Tyr312, Trp273, and Ile310 in the active site. X-ray crystallography (1.9 Å), in vitro methyltransferase assay, binding affinity measurement, mass spectrometry The Journal of biological chemistry High 32503840
2020 Active-site substitution N255F combined with W273A in SETD3 switches target specificity from histidine to lysine, generating a variant with 13-fold preference for lysine over histidine. X-ray crystallography shows that the N3 atom of histidine and the ε-amino nitrogen of lysine occupy the same active-site position relative to the SAM methyl group. Active-site mutagenesis, X-ray crystallography, in vitro enzyme kinetics The Journal of biological chemistry High 31911441
2015 SETD3 interacts with PCNA, validated by co-immunoprecipitation from human cell extracts and by interaction analyses using recombinant proteins, suggesting a potential role in DNA replication or repair. Bimolecular fluorescence complementation (BiFC) screen, co-immunoprecipitation, recombinant protein interaction assay Cell cycle Medium 26030842
2022 USP27 deubiquitinase stabilizes SETD3 by specifically interacting with it, negatively regulating its ubiquitination and enhancing its protein stability; inhibition of USP27 leads to downregulation of SETD3 protein level and blockade of hepatocellular carcinoma cell proliferation and tumorigenesis. Co-immunoprecipitation, ubiquitination assay, USP27 knockdown/inhibition, tumor growth assay Cellular and molecular life sciences Medium 35018513
2024 SETD3 is localized on the outer mitochondrial membrane and is a mechanosensitive enzyme that directly methylates actin at His73 to enhance F-actin polymerization around mitochondria. SETD3 loss leads to diminished F-actin around mitochondria, decreased mitochondrial branch length and movement, and impaired oxidative phosphorylation and mitochondrial complex I assembly. SETD3 levels are regulated by extracellular matrix stiffness. Live imaging/fractionation for localization, SETD3 loss-of-function, F-actin quantification, mitochondrial morphology/movement analysis, oxidative phosphorylation and complex I assays, ECM stiffness modulation Journal of cell science Medium 38896010
2024 SETD3 methylates MCM7 at histidine-459 (H459me), which is required for CDT1-mediated chromatin loading of the MCM helicase complex and replication origin firing. CDK2 phosphorylates SETD3 at Serine-21 during G1/S phase, which is required for DNA replication and cell cycle progression. Nascent-strand sequencing (NS-seq), biochemical binding assays, chromatin loading assay, CDK2 phosphorylation assay, H459 mutagenesis, SETD3 depletion Science China. Life sciences Medium 39455502
2024 NUDT16 dePARylase stabilizes SETD3 by reversing PARP1-mediated ADP-ribosylation of SETD3; in the absence of NUDT16, the E3 ligase CHFR recognizes PARylated SETD3 and targets it for proteasomal degradation. SETD3 associates with BRCA2 and promotes its recruitment to stalled replication forks and DNA damage sites. Co-immunoprecipitation, ubiquitination assay, PARylation assay, NUDT16/CHFR knockdown, DNA damage/replication stress assays, BRCA2 recruitment assay The Journal of biological chemistry Medium 38272222
2024 SETD3 interacts with hnRNPK and collaboratively regulates pre-mRNA exon skipping genome-wide. Specifically, SETD3 and hnRNPK are required for retention of exon 7 skipping in FNIP1, which promotes FNIP1-mediated nuclear translocation of TFEB and induction of lysosomal and mitochondrial biogenesis. In situ proximity labeling (TurboID) with mass spectrometry, genome-wide RNA-seq, biochemical interaction assays, functional FNIP1/TFEB pathway analysis Cell insight Medium 39391005
2024 SETD3 regulates endoderm differentiation of mouse ESCs through the canonical Wnt signaling pathway; in SETD3-deleted mESCs, Wnt transcriptional activity is reduced coincident with decreased nuclear β-catenin without changes in total β-catenin. A proximity ligation assay confirmed a physical interaction between SETD3 and β-catenin. shRNA screen, RNA-seq, proximity ligation assay (PLA), Wnt reporter assay, rescue experiments, SETD3 knockout mESCs FASEB journal Medium 38334393
2021 SETD3 downregulation mediates PTEN upregulation-induced ischemic neuronal death through suppression of actin polymerization and mitochondrial dysfunction (decreased ATP, reduced mitochondrial membrane potential, increased ROS). Suppressing PTEN protects against neuronal death partly through SETD3 and actin polymerization. OGD/R model, SETD3 knockdown, actin polymerization assay, mitochondrial function assays, PTEN inhibition Molecular neurobiology Medium 34218417
2025 SETD3 dimethylates CHD1 at lysine 209 (K209), enhancing CHD1 protein stability by reducing its ubiquitination. SETD3-mediated CHD1 K209 dimethylation increases H3K4me3 marks and promotes transcriptional activation of TNF-NFκB pathway genes. In vitro methyltransferase assay, mass spectrometry, ubiquitination assay, ChIP, transcriptomic analysis Cancer letters Medium 41045985
2025 α-centractin (ACTR1A), a key dynactin subunit, is an SETD3 interactor and in vitro methylation substrate identified by TurboID proximity labeling and radiochemical methylation assay, suggesting SETD3 may regulate dynein-mediated intracellular transport beyond actin. CRISPR KO in three human cell lines, fluorography, TurboID proximity labeling, mass spectrometry, radiochemical methyltransferase assay PeerJ Low 41142317
2025 SETD3 interacts with BRD2 (via SETD3 RSB domain and BRD2 BD2 domain) in the nucleus of mouse ESCs and is required for BRD2 recruitment to chromatin; absence of SETD3 causes altered chromatin environment and reduced BRD2 occupancy, leading to transcriptional changes. Mass spectrometry (nuclear SETD3 interactome), proximity ligation assay, domain deletion analysis, ChIP, RNA-seq The FEBS journal Medium 40944926
2025 The BWCFF-associated β-actin G74S mutation disrupts SETD3-mediated His73 methylation: molecular docking shows structural rearrangements of SETD3 to accommodate mutant actin, enzymatic assays confirm slower turnover of mutant actin peptides, and mass spectrometry confirms decreased His73 methylation in recombinant mutant β-actin and patient-derived fibroblasts. Molecular docking, enzymatic turnover assay, mass spectrometry of patient-derived fibroblasts FEBS letters Medium 40490999

Source papers

Stage 0 corpus · 49 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 SETD3 is an actin histidine methyltransferase that prevents primary dystocia. Nature 132 30626964
2018 SETD3 protein is the actin-specific histidine N-methyltransferase. eLife 96 30526847
2011 Histone methyltransferase SETD3 regulates muscle differentiation. The Journal of biological chemistry 78 21832073
2019 Enterovirus pathogenesis requires the host methyltransferase SETD3. Nature microbiology 61 31527793
2019 Structural insights into SETD3-mediated histidine methylation on β-actin. eLife 51 30785395
2017 Cell cycle-dependent degradation of the methyltransferase SETD3 attenuates cell proliferation and liver tumorigenesis. The Journal of biological chemistry 46 28442573
2011 Characterization of a novel histone H3K36 methyltransferase setd3 in zebrafish. Bioscience, biotechnology, and biochemistry 36 21307598
2019 SETD3 is a positive regulator of DNA-damage-induced apoptosis. Cell death & disease 35 30683849
2019 Structural basis for the target specificity of actin histidine methyltransferase SETD3. Nature communications 35 31388018
2016 Chromatin associated SETD3 negatively regulates VEGF expression. Scientific reports 34 27845446
2012 The role of a newly identified SET domain-containing protein, SETD3, in oncogenesis. Haematologica 32 23065515
2019 MiR-15b and miR-322 inhibit SETD3 expression to repress muscle cell differentiation. Cell death & disease 31 30796205
2018 SETD3 negatively regulates VEGF expression during hypoxic pulmonary hypertension in rats. Hypertension research : official journal of the Japanese Society of Hypertension 24 29950684
2021 SETD3 Downregulation Mediates PTEN Upregulation-Induced Ischemic Neuronal Death Through Suppression of Actin Polymerization and Mitochondrial Function. Molecular neurobiology 21 34218417
2015 A fluorescent bimolecular complementation screen reveals MAF1, RNF7 and SETD3 as PCNA-associated proteins in human cells. Cell cycle (Georgetown, Tex.) 21 26030842
2022 Stabilization of SETD3 by deubiquitinase USP27 enhances cell proliferation and hepatocellular carcinoma progression. Cellular and molecular life sciences : CMLS 20 35018513
2019 SETD3 is regulated by a couple of microRNAs and plays opposing roles in proliferation and metastasis of hepatocellular carcinoma. Clinical science (London, England : 1979) 19 31654063
2020 Characterization of a novel lncRNA (SETD3-OT) in turbot (Scophthalmus maximus L.). Fish & shellfish immunology 16 32278113
2020 An engineered variant of SETD3 methyltransferase alters target specificity from histidine to lysine methylation. The Journal of biological chemistry 15 31911441
2020 Characterization of SETD3 methyltransferase-mediated protein methionine methylation. The Journal of biological chemistry 15 32503840
2021 β-Actin Peptide-Based Inhibitors of Histidine Methyltransferase SETD3. ChemMedChem 14 34032009
2021 The Structure, Activity, and Function of the SETD3 Protein Histidine Methyltransferase. Life (Basel, Switzerland) 12 34685411
2019 SETD3 reduces KLC4 expression to improve the sensitization of cervical cancer cell to radiotherapy. Biochemical and biophysical research communications 12 31235251
2022 Histidine methyltransferase SETD3 methylates structurally diverse histidine mimics in actin. Protein science : a publication of the Protein Society 11 35481649
2020 Overexpression of CXCR5 in CD4+ T cells of SLE patients caused by excessive SETD3. Clinical immunology (Orlando, Fla.) 10 32240818
2021 Circ_SETD3 regulates gefitinib sensitivity and tumor progression by miR-873-5p-dependent regulation of APPBP2 in non-small cell lung cancer. Journal of chemotherapy (Florence, Italy) 9 34861803
2021 Up-regulation of SETD3 may contribute to post-stroke depression in rat through negatively regulating VEGF expression. Behavioural brain research 7 34499935
2023 The Role of Trp79 in β-Actin on Histidine Methyltransferase SETD3 Catalysis. Chembiochem : a European journal of chemical biology 6 37581408
2022 Structure-function conservation between the methyltransferases SETD3 and SETD6. Biochimie 6 35550916
2018 Phenotypic characterization of SETD3 knockout Drosophila. PloS one 6 30067821
2024 SETD3 regulates endoderm differentiation of mouse embryonic stem cells through canonical Wnt signaling pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 5 38334393
2024 SETD3 is a mechanosensitive enzyme that methylates actin on His73 to regulate mitochondrial dynamics and function. Journal of cell science 5 38896010
2022 Proteolytic Activities of Enterovirus 2A Do Not Depend on Its Interaction with SETD3. Viruses 5 35891342
2024 The dePARylase NUDT16 promotes radiation resistance of cancer cells by blocking SETD3 for degradation via reversing its ADP-ribosylation. The Journal of biological chemistry 4 38272222
2024 The methyltransferase SETD3 regulates mRNA alternative splicing through interacting with hnRNPK. Cell insight 3 39391005
2024 Examining prestructured β-actin peptides as substrates of histidine methyltransferase SETD3. Scientific reports 3 39488591
2022 SETD3 Methyltransferase Regulates PLK1 Expression to Promote In Situ Hepatic Carcinogenesis. Frontiers in oncology 3 35912180
2025 Disruption of SETD3-mediated histidine-73 methylation by the BWCFF-associated β-actin G74S mutation. FEBS letters 2 40490999
2024 SETD3 functions beyond histidine methylation. Life sciences 2 39299385
2024 SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM. Science China. Life sciences 2 39455502
2023 Zebrafish SETD3 mediated ubiquitination of phosphoprotein limits spring viremia of carp virus infection. Fish & shellfish immunology 2 37269914
2022 Computational Study of Methionine Methylation Process Catalyzed by SETD3. Interdisciplinary sciences, computational life sciences 2 35419695
2022 A novel SETD3-ALK fusion in lung adenocarcinoma and sustained clinical response to crizotinib. Lung cancer (Amsterdam, Netherlands) 2 36495785
2022 Structural and Energetic Origin of Different Product Specificities and Activities for SETD3 and Its Mutants on the Methylation of the β-Actin H73K Peptide: Insights from a QM/MM Study. Journal of chemical theory and computation 2 36520638
2025 SET domain containing 3 (SETD3) interacts with bromodomain-containing protein 2 (BRD2) and coordinates its chromatin association in mouse embryonic stem cells. The FEBS journal 0 40944926
2025 The Actin Histidine methyltransferase SETD3 is a CHD1 lysine di-methyltransferase. Cancer letters 0 41045985
2025 Alpha-centractin is a novel substrate of SETD3 methyltransferase in vitro. PeerJ 0 41142317
2025 Microglial hyperactivation and NLRP3 methylation mediated by SETD3 after anesthesia/surgery: Unraveling new mechanisms of perioperative neurocognitive disorders. Experimental neurology 0 41175962
2025 SETD3 regulates Bcl-6 expression and Tfh differentiation in SLE CD4+ T cells by manipulating histone methylation and acetylation. Clinical epigenetics 0 41272740