Ask about this productRelated genes to: SETD3 Blocking Peptide
- Gene:
- SETD3 NIH gene
- Name:
- SET domain containing 3, actin histidine methyltransferase
- Previous symbol:
- C14orf154
- Synonyms:
- FLJ23027
- Chromosome:
- 14q32.2
- Locus Type:
- gene with protein product
- Date approved:
- 2004-06-11
- Date modifiied:
- 2018-12-20
Related products to: SETD3 Blocking Peptide
Related articles to: SETD3 Blocking Peptide
- Endometriosis is a disease associated with pain symptoms and reduced fertility, characterized by the presence of endometrial tissue outside the uterus. is an actin-specific histidine N-methyltransferase that regulates actin stability and flexibility. Here, we investigate the effects of altered expression on cytoskeletal function and endometriotic cell motility. expression in endometriotic lesions was analyzed using EndometDB, and in uteri of the superfertile Dummerstorf mouse line FL1 by RT-qPCR. The functional impact of siRNA-mediated depletion on endometriotic 12Z cells and primary endometriotic stroma cells was studied in vitro. Cell motility, contractility, invasiveness, morphology and gene expression were analyzed by RT-qPCR, Western blotting, immunofluorescence, scratch wound, collagen contraction and Matrigel invasion assays. In patient tissue, expression was slightly increased in deep endometriotic lesions, whereas was downregulated 1.6-fold in the uteri of superfertile mice. depletion delayed cell motility, reduced invasiveness of 12Z cells, and reduced the capability to contract collagen gels. Cytoskeletal gene expression was moderately changed. Our data suggest that the histidine N-methyltransferase contributes to cytoskeletal remodeling that plays a key role in cell migration and invasion. A dysregulation of could therefore be related to the pathogenesis of endometriosis, particularly in deep endometriosis. - Source: PubMed
Publication date: 2026/07/07
Poloczek MelanieLudwig Carolin Lisa MichaelaSurmann HannaStrauß TheresaGabriel MichaelPoutanen MattiOto JuliaKiesel LudwigSchäfer Sebastian DHanker LarsWeitzel Joachim MGötte Martin - AdoMet-dependent histidine methyltransferases catalyze regioselective methylation of histidine residues in proteins. N-Methylation of His73 in β-actin is catalyzed by histidine methyltransferase SETD3, and represents a unique post-translational modification involved in the regulation of actin polymerization. Likewise, N-methylation of His375 in zinc transporter SLC39A5 is catalyzed by histidine methyltransferase METTL9, thereby modulating zinc-binding properties of SLC39A5. Here, we report biomolecular studies on the ability of human SETD3 and METTL9 to catalyze the histidine ethylation reaction beyond methylation. Combined synthetic, biocatalytic and computational analyses employing synthetic or in situ formed AdoMet analogs AdoEth and AdoSeEth reveal that AdoMet is the most efficient cosubstrate; however, SETD3 and METTL9 also have the capacity to catalyze ethylation of histidine in β-actin and SLC39A5 peptides, respectively. Computational analyses support the experimental observations and provide the structural origin for more efficient histidine methylation than ethylation reaction. This work provides an insight into the molecular requirements for histidine methyltransferase-catalyzed histidine methylation and most related ethylation reactions on the N- and N-positions in the imidazole ring, the knowledge important for functional assignment and design of chemical probes targeting histidine methyltransferases. - Source: PubMed
Hintzen Jordi C JYu ZhimeiAhmad SadafZhang XinZhao Yuan-YuanDeng HaoSchütz LeonieRam MarijaKaminska Julia ZDrozak JakubWeinhold ElmarGuo HongRentmeister AndreaQian PingMecinović Jasmin - ACTB is a cytoskeletal protein involved in intracellular trafficking. In recent years, it has become evident that, in addition to its established roles in these compartments, ACTB also participates in the regulation of transcription. However, the molecular mechanisms underlying this function remain poorly understood. The methyltransferase SETD3 has previously been shown to methylate ACTB at H73, thereby regulating ACTB polymerization and smooth muscle contraction. Here, we show that the genomic distribution of ACTB is SETD3-dependent and that this regulation modulates the transcription of genes involved in cell adhesion and mRNA translation in colorectal cancer cells. Proteomic analyses reveal that ACTB and SETD3 interact with multiple large protein complexes, including complexes associated with transcriptional regulation. Specifically, we demonstrate that SETD3-mediated ACTB methylation is required for the colocalization of SMARCA4, a subunit of the SWI/SNF BAF complex, at specific genomic loci. Genomic analyses further show that this colocalization enables the coordinated occupancy of SMARCA4 and H73-methylated ACTB at genes involved in cell adhesion and mRNA translation. Finally, phenotypic assays confirm these regulatory effects. Together, these findings uncover a new mechanistic layer of selective transcriptional regulation mediated by an ACTB-SETD3-SMARCA4 axis in colorectal cancer cells. - Source: PubMed
Publication date: 2026/04/07
Abaev-Schneiderman ElinaNguyen LinhShalev RazBiton Tzofit ElbazChopra AnandJagadeesan GiritharanSevilla-Sanchez DanielTickotsky Moskovitz NiliLevin LironFeldman MichalVan Rechem CapucineLevy Dan - Tfh cells play a crucial role in the pathogenesis of SLE. Our previous research confirmed that SETD3, which is upregulated in CD4 T cells of SLE patients, mediates the overexpression of CXCR5 by upregulating the CXCR5 promoter histones H3K4me3 and H3K36me3. However, the recent study demonstrates that SETD3, in contrast to other protein lysine methyltransferases, does not methylate histones; its sole verified substrate is H73 of actin. Consequently, the molecular mechanism by which SETD3 influences histone methylation requires further investigation. The most important transcription factor in the development and differentiation of Tfh cells is Bcl-6. Whether SETD3 can directly participate in the regulation of Tfh cell differentiation by regulating the expression of Bcl-6 remains to be further studied. - Source: PubMed
Publication date: 2025/11/21
Ding ShuXue ShengjieRao YuHu Ling-XueLiao Jie-Yue - Protein lysine methacrylation (Kmea) is a recently identified post-translational modification whose biofunction remains poorly understood. Until now, there has been no chemical labeling method for Kmea modification, which has severely hindered the discovery and functional studies of methacrylated proteins. Here, we developed a photocatalytic thia-Michael reaction system for the chemoselective labeling of protein methacrylation. By exploiting the dual effect of steric hindrance and the stability of the generated C-center radical, the reaction interference of the structural isomer crotonylation can be efficiently avoided. Based on this reaction, a multifunctional water-soluble benzenethiol-azide probe azDSH was designed and synthesized, and a workflow for the specific labeling, enrichment, and identification of Kmea proteins was developed. Proteomic identification of histone and nuclear protein extracts and whole-cell lysate revealed a number of novel Kmea proteins and modification sites besides histones, such as HMGB1, TdIF2, UHRF1, HNRPD, BRWD1, TAF1, TACC1, and SETD3, providing new targets for the study of epigenetic regulation. This study provides an effective method for the analysis of protein methacrylation modifications in biological systems. - Source: PubMed
Publication date: 2025/11/11
Gao MingWan QiongqiongZhou ShiboWu PengfeiNie WenjingChen Suming