Affinage

ELP3

Elongator complex protein 3 · UniProt Q9H9T3

Length
547 aa
Mass
62.3 kDa
Annotated
2026-04-28
48 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ELP3 is the catalytic subunit of the Elongator complex, functioning primarily as a tRNA-modifying enzyme that installs the 5-carboxymethyl (cm5U) modification at the wobble uridine (U34) of specific cytoplasmic tRNAs through an unprecedented radical SAM mechanism that uses acetyl-CoA as the acetyl donor (PMID:25151136, PMID:27455459). Its dual-domain architecture—a radical SAM domain harboring a [4Fe-4S] cluster and a KAT domain that binds acetyl-CoA—forms a composite active site in which acetate is hydrolyzed from acetyl-CoA and shuttled through a conserved molecular tunnel to the radical SAM center for radical-mediated addition to tRNA-U34 (PMID:16420352, PMID:30733442). Through this codon-dependent translational control, ELP3 regulates the synthesis of specific proteins (DEK, Sox9, Ric8b, Nprl2) that impact breast cancer metastasis, intestinal stem cell maintenance, macrophage polarization, and mTORC1/mTORC2 signaling, and its loss triggers a p53-dependent amino acid deprivation response via ATF4 overactivation (PMID:27811057, PMID:26527802, PMID:35920020, PMID:39085648, PMID:33507234). ELP3 also acetylates non-histone cytoplasmic substrates including Bruchpilot and connexin-43, functions as a genetic modifier of ALS through its tRNA modification activity, and stabilizes c-Myc independently of its acetyltransferase activity by competing with the E3 ligase FBXW7β (PMID:22153374, PMID:28507509, PMID:18996918, PMID:29415125, PMID:37771073).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 High

    Establishing that Elp3 is not merely a HAT but is the Elongator subunit directly responsible for RNA interaction defined it as the catalytic core of the complex.

    Evidence Immunoprecipitation, two-hybrid mapping, and in vivo RNA-binding assays in yeast Elongator deletion mutants

    PMID:15138274

    Open questions at the time
    • Whether RNA binding reflects tRNA or mRNA substrates was not resolved
    • No structural basis for Elp3-RNA interaction
  2. 2005 Medium

    Demonstrating that human ELP3 complements yeast elp3Δ and requires an intact HAT B motif established cross-species conservation and confirmed the acetyltransferase domain is essential for function.

    Evidence Yeast complementation with HAT domain mutants and histone lysine-to-arginine substitutions

    PMID:15902492

    Open questions at the time
    • The relevant in vivo substrates (histone vs. non-histone) remained unclear
    • Single lab study
  3. 2006 High

    Discovery of a [4Fe-4S] cluster and SAM-binding activity in archaeal Elp3 revealed a second catalytic domain belonging to the radical SAM superfamily, fundamentally redefining ELP3 as a bifunctional enzyme.

    Evidence UV-visible/EPR spectroscopy, Fe assays, SAM-binding assay, and site-directed mutagenesis of cluster cysteines in archaeal Elp3

    PMID:16420352

    Open questions at the time
    • The substrate of the radical SAM activity was unknown
    • No structural data for the dual-domain architecture
  4. 2008 High

    Separation-of-function analysis showed the Fe4S4 cluster is required for Elongator complex integrity and accessory factor binding (Kti11/Kti12) but dispensable for HAT activity and RNAPII association, distinguishing the two catalytic functions.

    Evidence FeS cluster mutant analysis with tandem affinity purification and co-IP in yeast

    PMID:18986986

    Open questions at the time
    • The enzymatic product of the radical SAM domain remained unidentified
    • Whether FeS-dependent function relates to tRNA or chromatin was unresolved
  5. 2008 High

    Genetic association of ELP3 variants with ALS and demonstration that ELP3 loss causes motor axon defects in Drosophila and zebrafish established ELP3 as a neurodegeneration modifier gene.

    Evidence Human genetic association, Drosophila mutagenesis screen, and zebrafish morpholino knockdown

    PMID:18996918

    Open questions at the time
    • Mechanism linking ELP3 to motor neuron vulnerability was unknown
    • Whether the ALS link involves tRNA modification or acetylation was unresolved
  6. 2011 High

    Identification of Bruchpilot as a direct acetylation substrate of ELP3 at presynaptic densities demonstrated that ELP3 acetylates non-histone cytoplasmic proteins with functional consequences for neurotransmitter release.

    Evidence Genetic loss/gain-of-function, acetylation assays, electron microscopy, and electrophysiology in Drosophila NMJ

    PMID:22153374

    Open questions at the time
    • Whether Bruchpilot acetylation occurs in mammalian synapses was untested
    • Structural basis for substrate recognition unknown
  7. 2014 High

    In vitro reconstitution proved that archaeal Elp3 alone catalyzes cm5U modification at tRNA wobble uridine using acetyl-CoA, resolving a decade-long question about the enzymatic function of the radical SAM domain.

    Evidence Purified archaeal Elp3 reconstitution with tRNA substrates and biochemical modification assay

    PMID:25151136

    Open questions at the time
    • How the KAT and rSAM domains cooperate mechanistically was structurally unresolved
    • Whether mammalian ELP3 can perform this reaction alone was unknown
  8. 2015 High

    Conditional knockout in mouse intestine showed Elp3 promotes Wnt-driven tumor initiation and stem cell maintenance by enabling Sox9 protein translation, providing the first in vivo evidence that ELP3 controls cancer-relevant mRNA translation.

    Evidence Conditional KO mouse models with Apc mutation, organoid assays, Sox9 translational analysis

    PMID:26527802

    Open questions at the time
    • Whether Sox9 translation depends specifically on U34-modified tRNAs was not shown at the codon level
    • Contribution of acetyltransferase vs. tRNA modification activity not separated
  9. 2016 High

    The crystal structure of bacterial Elp3 revealed the KAT and rSAM domains share a large interface forming a composite active site and tRNA-binding pocket, providing the first structural framework for the dual-domain mechanism.

    Evidence X-ray crystallography at 2.15 Å resolution with structure-guided yeast mutagenesis

    PMID:27455459

    Open questions at the time
    • No co-crystal with tRNA substrate
    • Inter-domain communication mechanism unresolved
  10. 2016 High

    Demonstrating that ELP3/CTU1 support breast cancer metastasis by enabling codon-biased translation of the oncoprotein DEK—rescued by a codon-usage mutant—established the codon-dependent translation mechanism as a driver of tumor invasion.

    Evidence Genetic ablation in PyMT mouse model, codon-usage mutant rescue, IRES-reporter and invasion assays

    PMID:27811057

    Open questions at the time
    • Genome-wide identification of codon-dependent mRNA targets was incomplete
    • Contribution of individual modified tRNA species not delineated
  11. 2018 High

    Direct measurement of mcm5s2U in motor neurons and survival extension in SOD1-G93A mice upon ELP3 overexpression mechanistically linked the tRNA modification activity to ALS pathogenesis.

    Evidence SOD1-G93A transgenic mice, tRNA modification mass spectrometry, mutant SOD1 solubility assay

    PMID:29415125

    Open questions at the time
    • Which specific codon-biased mRNAs mediate the neuroprotective effect was not identified
    • Whether ELP3 overexpression benefits non-SOD1 ALS models was untested
  12. 2019 High

    A co-crystal structure with an acetyl-CoA analog revealed how the KAT domain mediates non-canonical acetyltransferase chemistry and that tRNA binding stimulates acetyl-CoA hydrolysis, linking substrate recognition to catalytic activation.

    Evidence X-ray co-crystallography, site-directed mutagenesis, and in vitro tRNA-stimulated hydrolysis assay

    PMID:30733442

    Open questions at the time
    • How the acetyl moiety transfers from the KAT domain to the rSAM active site was not resolved
    • No structure with bound tRNA
  13. 2021 High

    Genetic epistasis in hematopoietic and T cell compartments showed that Elongator loss triggers a p53/ATF4-dependent amino acid deprivation response due to tRNA hypomodification, and combined loss of Elp3 and p53 cooperatively promotes leukemia—revealing how translational stress is sensed downstream of ELP3.

    Evidence Conditional KO mouse models with Elp3/p53 double KO, ATF4 overexpression/knockdown epistasis, Chop KO rescue

    PMID:33483347 PMID:33507234

    Open questions at the time
    • Whether ATF4 overactivation is GCN2-dependent was not fully dissected
    • Applicability to solid tumors unknown
  14. 2022 High

    Ribosome profiling in macrophages revealed that Elp3 enables codon-biased translation of Ric8b (an mTORC2 activator) and mitochondrial ribosome subunits, connecting tRNA modification to mTORC2 signaling and M2 macrophage polarization.

    Evidence Conditional myeloid KO, ribosome profiling, mTORC2 activity assays, codon-usage analysis

    PMID:35920020

    Open questions at the time
    • Whether ELP3 regulates mTORC2 in non-immune cell types was untested
    • Structural basis for tRNA-codon selectivity unresolved
  15. 2022 Medium

    Discovery of a mitochondrial splice variant (mt-ELP3) that localizes to the mitochondrial matrix and modifies mt-tRNAs expanded ELP3 function beyond cytoplasmic tRNA modification to organellar translation control.

    Evidence Subcellular fractionation, tRNA modification assay, angiogenin protection assay, mitochondrial translation measurement

    PMID:36045139

    Open questions at the time
    • The specific mt-tRNA modifications catalyzed were not fully characterized
    • Single lab; independent confirmation needed
    • Physiological consequence of mt-ELP3 loss in vivo unknown
  16. 2024 High

    Identifying Nprl2 (Gator1 subunit) as a codon-dependent translational target of Elp3 in intestinal epithelium linked ELP3-mediated tRNA modification to mTORC1 regulation, ATF4 stabilization, and tuft cell differentiation for type 2 immunity.

    Evidence Conditional epithelial KO, ribosome profiling, mTORC1 activity assay, in vivo helminth infection model

    PMID:39085648

    Open questions at the time
    • Whether Nprl2 translation is the sole mediator of mTORC1 hyperactivation was not excluded
    • Contribution of ELP3 acetyltransferase activity vs. tRNA modification not separated in this context
  17. 2024 Medium

    Demonstrating that ELP3 stabilizes c-Myc independently of its acetyltransferase activity by competing with FBXW7β for c-Myc binding uncovered a non-enzymatic scaffolding function.

    Evidence Co-IP, ubiquitination competition assay, ELP3 knockdown/reconstitution with c-Myc rescue, xenograft growth assay

    PMID:37771073

    Open questions at the time
    • Whether c-Myc stabilization occurs within or outside the Elongator complex was not determined
    • Single lab; independent validation needed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the full structural basis of how the molecular tunnel transports acetate between domains, how ELP3 selects specific tRNA substrates, the relative physiological contributions of its tRNA modification versus protein acetylation activities in different tissues, and the in vivo function of the mitochondrial ELP3 isoform.
  • No co-crystal structure of ELP3 bound to its tRNA substrate
  • Systematic separation of tRNA modification vs. acetyltransferase functions in mammalian models lacking
  • In vivo role of mt-ELP3 not tested by loss-of-function

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0140096 catalytic activity, acting on a protein 4 GO:0140098 catalytic activity, acting on RNA 3 GO:0003723 RNA binding 1
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 3
Pathway
R-HSA-1643685 Disease 6 R-HSA-8953854 Metabolism of RNA 6 R-HSA-392499 Metabolism of proteins 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
ALKELP1ELP2FBXW7KTI11KTI12OGTSNAI1
Complex memberships
Elongator complex

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 The archaeal Elp3 subunit contains a Fe4S4 cluster (confirmed by UV-visible spectroscopy and EPR) and binds S-adenosylmethionine (SAM); site-directed mutagenesis identified the cysteines responsible for cluster formation, and SAM binding alters the EPR spectrum of the FeS cluster, indicating Elp3 has a second catalytic function beyond its HAT domain as a member of the Radical SAM superfamily. UV-visible and EPR spectroscopy, colorimetric and atomic absorption Fe assays, site-directed mutagenesis, SAM-binding assay Molecular microbiology High 16420352
2004 Within the six-subunit yeast holo-Elongator complex, Elp3 is required for RNA binding; Elp2 is dispensable for complex integrity and HAT activity, but Elp3 is essential for Elongator-nascent RNA interaction in vivo. Immunoprecipitation, two-hybrid interaction mapping, in vitro binary interaction studies, in vivo RNA-binding assays The Journal of biological chemistry High 15138274
2005 Human ELP3 functionally complements yeast elp3Δ cells; the HAT domain (specifically the B motif) is essential for ELP3 function, and acetylation of histone H3-K14 and H4-K8 are required for full ELP3-dependent transcription elongation. Yeast complementation, in vivo HAT domain deletion/mutation, histone lysine-to-arginine mutations Molecular genetics and genomics Medium 15902492
2008 The Elp3 Fe4S4 cluster is required for Elongator complex integrity and for association with accessory factors Kti11 and Kti12, but is not required for HAT activity, RNA binding, or association of Elongator with RNA polymerase II chromatin; FeS cluster mutations do not support a role for Elongator in histone demethylation. Genetic and biochemical analysis of FeS cluster mutants, tandem affinity purification, co-immunoprecipitation The Journal of biological chemistry High 18986986
2008 ELP3 variants are associated with ALS; loss-of-function ELP3 mutations (R475K, R456K) in Drosophila impair neuronal communication and survival, and ELP3 knockdown in zebrafish causes dose-dependent motor axonal abnormalities. Mutagenesis screen in Drosophila, antisense morpholino knockdown in zebrafish, human genetic association Human molecular genetics High 18996918
2008 Elp3 and Gcn5 are both required for histone H3 acetylation at the hsp70 genes SSA3 and SSA4 in yeast; Elp3 exerts its effects mainly through RNA polymerase II elongation, while Gcn5 affects RNAPII recruitment. ChIP assay, genetic deletion, transcription analysis The Biochemical journal Medium 17910533
2009 ELP3 localizes to mitochondria and to actin-rich domains at the edges of HeLa cells, suggesting cytoplasmic roles beyond histone acetylation. Immunofluorescence with two different ELP3 antibodies Neuroscience letters Medium 19429107
2010 ELP3 loss in the Drosophila nervous system leads to hyperactivity, sleep loss, expansion of synaptic bouton number, increased axonal length and branching at the larval NMJ, and misregulation of neuromotility genes; ELP3 regulates synaptic bouton expansion during neurogenesis. Targeted RNAi knockdown in Drosophila nervous system, behavioral assays, morphological analysis of NMJ Journal of neurochemistry Medium 20626565
2011 In Drosophila neurons, ELP3 is necessary and sufficient to acetylate the ELKS family member Bruchpilot at the presynaptic density; loss of ELP3 causes morphological defects in presynaptic densities resulting in increased vesicle tethering and enhanced neurotransmitter release. Genetic loss-of-function and overexpression, acetylation assays, electron microscopy of presynaptic densities, electrophysiology Neuron High 22153374
2013 In Toxoplasma gondii, Elp3 localizes to the outer mitochondrial membrane via a unique C-terminal transmembrane domain (tail-anchored), orienting its catalytic domains toward the cytosol; this localization is essential for parasite viability and is independent of the Elongator complex (which is absent in Apicomplexa). A form of Elp3 also localizes to mitochondria in mammalian cells. Selective permeabilization, subcellular fractionation, transmembrane domain mutagenesis, genetic essentiality assay The Journal of biological chemistry High 23878194
2014 Archaeal Elp3 alone can catalyze the wobble uridine C5 modification (cm5U) on tRNA via a radical mechanism using acetyl-CoA, demonstrating that Elp3 is the catalytic enzyme for tRNA U34 modification and performs unprecedented chemistry on acetyl-CoA. In vitro reconstitution of tRNA modification activity with purified archaeal Elp3, biochemical assay Nature chemical biology High 25151136
2014 KAT9/ELP3 is identified as a potential acetyltransferase of G6PD on lysine 403; acetylation of G6PD by ELP3 inhibits its dimerization and abolishes its activity. Co-immunoprecipitation, in vitro acetyltransferase assay, acetylation mimetic mutant rescue experiments The EMBO journal Medium 24769394
2016 Crystal structure of D. mccartyi Elp3 (DmcElp3) at 2.15 Å reveals that the KAT and radical SAM domains share a large interface, form a composite active site and tRNA-binding pocket, with an Fe-S cluster at the dimerization interface; structure-guided mutagenesis in yeast Elp3 confirmed functional relevance of this arrangement for tRNA modification. X-ray crystallography, structure-guided mutagenesis in yeast Nature structural & molecular biology High 27455459
2016 ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, support breast cancer metastasis by enabling translation of the oncoprotein DEK, which in turn promotes IRES-dependent translation of LEF1; a DEK codon-usage mutant that bypasses U34 tRNA modification rescues LEF1 expression in ELP3/CTU1-depleted cells. Genetic ablation (PyMT mouse model), codon-usage mutant rescue, IRES-reporter assays, invasion/metastasis assays The Journal of experimental medicine High 27811057
2015 Elp3 is required for Wnt-driven intestinal tumor initiation and radiation-induced regeneration by promoting Sox9 protein translation; Elp3 deficiency reduces Lgr5+/Dclk1+/Sox9+ cancer stem cells and Elp3-specific ablation in Lgr5+ cells delays tumor appearance in Apc-mutated intestines. Conditional knockout mouse models, ex vivo organoids, genetic epistasis (Elp3/Sox9 depletion), protein translation analysis The Journal of experimental medicine High 26527802
2016 In Xenopus, Elp3 binds Snail1 through its zinc-finger domain and inhibits Snail1 ubiquitination by β-Trcp without disrupting the Snail1/Trcp interaction, thereby stabilizing Snail1 and activating N-cadherin in neural crest cells to regulate their migration. Co-immunoprecipitation, morpholino knockdown in Xenopus, ubiquitination assay, domain mapping Scientific reports Medium 27189455
2017 Loss of Elp3 reduces acetylation of connexin-43 (Cx43) in cortical progenitors, impairs its membrane distribution in apical progenitors of the cerebral cortex, and delays projection neuron migration; HDAC6 is identified as a deacetylase of Cx43. Conditional knockout (Elp3cKO), neuroblastoma cell line Elp1 depletion, acetylation assays, immunofluorescence Frontiers in cellular neuroscience Medium 28507509
2018 ELP3 modifies tRNA wobble uridines (mcm5s2U) in motor neurons; ELP3 overexpression in SOD1G93A mice extends survival and attenuates denervation; ELP3 depletion in vitro reduces mcm5s2U and increases insoluble mutant SOD1, which is reversed by exogenous ELP3, establishing ELP3-mediated tRNA modification as a modifier of ALS. Transgenic mouse model (SOD1G93A), zebrafish morpholino knockdown, in vitro tRNA modification mass spectrometry, mutant SOD1 solubility assay Human molecular genetics High 29415125
2019 Co-crystal structure of bacterial Elp3 (DmcElp3) bound to an acetyl-CoA analog reveals how the KAT domain mediates non-canonical acetyltransferase activity; key active site residues were identified by mutagenesis, the N-terminus is required for tRNA substrate recognition, and specific tRNA species induce acetyl-CoA hydrolysis. X-ray co-crystallography, site-directed mutagenesis, in vitro acetyltransferase/hydrolysis assay with tRNA substrates Nature communications High 30733442
2019 ELP3 acetyltransferase is phosphorylated on Tyr202 by the oncogenic anaplastic lymphoma kinase (ALK); this phosphorylation is present in NPM-ALK-expressing tumor cells and Y202 phosphorylation-deficient ELP3 reduces cell growth and impairs gene expression. Mass spectrometry phospho-mapping, co-immunoprecipitation, ALK kinase assay, Y202 mutagenesis, cell growth and gene expression assays The Biochemical journal Medium 31341009
2021 Loss of Elp3 in hematopoietic progenitors activates a p53-dependent checkpoint through a misguided amino acid deprivation response accompanied by Atf4 overactivation and increased protein synthesis; deletion of p53 rescues hematopoiesis, while combined loss of p53 and Elongator cooperatively promotes leukemia/lymphoma. Conditional knockout mouse model, epistasis (Elp3/p53 double KO), translational analysis, Atf4 activation assays The Journal of experimental medicine High 33507234
2021 Loss of Elp3 in T cells delays entry into the first cell cycle and impairs T follicular helper (TFH) responses through progressive overactivation of Atf4; overexpression of Atf4 phenocopies Elp3 loss, and partial silencing of Atf4 or deletion of its effector Chop rescues TFH responses. Conditional T cell-specific knockout, Atf4 overexpression/knockdown, Chop KO epistasis, in vitro/in vivo immunization models Journal of immunology High 33483347
2022 A novel mitochondrial splice variant of ELP3 (mt-ELP3) localizes to the mitochondrial matrix and modifies mitochondrial tRNAs (mt-tRNAs); overexpression of mt-ELP3 protects mt-tRNAs from angiogenin-mediated cleavage, increases mitochondrial translation, and upregulates OXPHOS complex expression. Bioinformatics identification, subcellular fractionation, tRNA modification assay, mt-tRNA angiogenin protection assay, mitochondrial translation measurement Scientific reports Medium 36045139
2022 Elp3-dependent codon-biased translation promotes mTORC2 activation in macrophages by enabling translation of Ric8b (an mTORC2 activator) in a codon-dependent manner; Elp3 also promotes M2 macrophage polarization through translation of mitochondrial ribosome large subunit proteins (Mrpl3, Mrpl13, Mrpl47). Conditional myeloid KO, ribosome profiling, mTORC2 activity assays, codon-usage analysis, cytokine measurement The EMBO journal High 35920020
2024 ELP3 stabilizes c-Myc in an acetyltransferase-independent manner by competing with the E3 ligase FBXW7β for c-Myc binding, thereby inhibiting FBXW7β-mediated ubiquitination and proteasomal degradation of c-Myc; ELP3 knockdown reduces glycolysis and glutaminolysis and retards cell proliferation and xenograft growth. Co-immunoprecipitation, ubiquitination assay, ELP3 knockdown/reconstitution with c-Myc rescue, xenograft growth assay Journal of molecular cell biology Medium 37771073
2024 Loss of epithelial Elp3 in the intestine blocks codon-dependent translation of Nprl2 (a Gator1 subunit and mTORC1 inhibitor), causing enhanced mTORC1 activation and Atf4 stabilization in progenitor cells, which blocks tuft cell differentiation and impairs intestinal type 2 immunity against helminths. Conditional epithelial KO, ribosome profiling, mTORC1 activity assay, Atf4 overexpression epistasis, in vivo helminth infection model The EMBO journal High 39085648
2025 ELP3 is phosphorylated and regulated by O-GlcNAcylation at Ser408, catalyzed by OGT; OGT-mediated O-GlcNAcylation stabilizes ELP3 protein; loss of OGT reduces ELP3 stability and inhibits ferroptosis in trophoblasts. Immunoprecipitation, western blotting, OGT knockdown, ELP3 overexpression rescue Applied biochemistry and biotechnology Medium 41504842
2025 ELP3 interacts with JNK1 protein and promotes gastric cancer proliferation, migration, and invasion through histone acetylation-dependent activation of the JNK/MAPK pathway; inhibition of histone acetylation or JNK pathway suppresses ELP3 overexpression-driven cancer promotion. Co-immunoprecipitation, HAT activity assay, histone acetylation inhibitor (SAHA), JNK pathway inhibitor, cell proliferation/migration/invasion assays, xenograft Histology and histopathology Medium 41048082
2025 ELP3 acetylates axonal G3BP1 at K374 after axotomy; ELP3-dependent G3BP1 acetylation promotes stress granule disassembly, enhances axonal protein synthesis, and accelerates nerve regeneration and functional recovery; ELP3-depleted neurons show increased axonal G3BP1 granules and reduced axon growth. Mass spectrometry, ELP3 knockdown/KO in rodent neurons, acetylmimetic G3BP1 rescue, axon regeneration assay bioRxivpreprint Medium 41279176
2025 Elp3 harbors a conserved molecular tunnel that transports free acetate from the acetyl-CoA binding (KAT) domain to the radical SAM active site over 20 Å; acetate undergoes radical-mediated reaction and addition to tRNA U34, explaining how Elp3 bridges large inter-domain distances to catalyze tRNA carboxymethylation. Crystal structure determination, isotope incorporation experiments, enzymology, site-directed mutagenesis bioRxivpreprint High bio_10.1101_2025.05.07.652618

Source papers

Stage 0 corpus · 48 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Regulation of G6PD acetylation by SIRT2 and KAT9 modulates NADPH homeostasis and cell survival during oxidative stress. The EMBO journal 257 24769394
2008 Variants of the elongator protein 3 (ELP3) gene are associated with motor neuron degeneration. Human molecular genetics 227 18996918
2016 Elp3 links tRNA modification to IRES-dependent translation of LEF1 to sustain metastasis in breast cancer. The Journal of experimental medicine 145 27811057
2006 The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. Molecular microbiology 108 16420352
2014 Archaeal Elp3 catalyzes tRNA wobble uridine modification at C5 via a radical mechanism. Nature chemical biology 83 25151136
2011 ELP3 controls active zone morphology by acetylating the ELKS family member Bruchpilot. Neuron 83 22153374
2015 Elp3 drives Wnt-dependent tumor initiation and regeneration in the intestine. The Journal of experimental medicine 76 26527802
2012 Arabidopsis thaliana histone deacetylase 14 (HDA14) is an α-tubulin deacetylase that associates with PP2A and enriches in the microtubule fraction with the putative histone acetyltransferase ELP3. The Plant journal : for cell and molecular biology 70 22404109
2018 Elongator subunit 3 (ELP3) modifies ALS through tRNA modification. Human molecular genetics 66 29415125
2019 The Elongator subunit Elp3 is a non-canonical tRNA acetyltransferase. Nature communications 61 30733442
2016 Structural basis for tRNA modification by Elp3 from Dehalococcoides mccartyi. Nature structural & molecular biology 55 27455459
2011 Role of elongator subunit Elp3 in Drosophila melanogaster larval development and immunity. Genetics 48 21288872
2008 An iron-sulfur cluster domain in Elp3 important for the structural integrity of elongator. The Journal of biological chemistry 47 18986986
2008 Gcn5- and Elp3-induced histone H3 acetylation regulates hsp70 gene transcription in yeast. The Biochemical journal 37 17910533
2010 The histone acetyltransferase Elp3 plays in active role in the control of synaptic bouton expansion and sleep in Drosophila. Journal of neurochemistry 35 20626565
2022 Elp3-mediated codon-dependent translation promotes mTORC2 activation and regulates macrophage polarization. The EMBO journal 34 35920020
2014 ELP3 is involved in sexual and asexual development, virulence, and the oxidative stress response in Fusarium graminearum. Molecular plant-microbe interactions : MPMI 32 25083910
2004 Molecular architecture, structure-function relationship, and importance of the Elp3 subunit for the RNA binding of holo-elongator. The Journal of biological chemistry 31 15138274
2021 Loss of tRNA-modifying enzyme Elp3 activates a p53-dependent antitumor checkpoint in hematopoiesis. The Journal of experimental medicine 24 33507234
2013 Elongator protein 3 (Elp3) lysine acetyltransferase is a tail-anchored mitochondrial protein in Toxoplasma gondii. The Journal of biological chemistry 24 23878194
2005 The Elp3 subunit of human Elongator complex is functionally similar to its counterpart in yeast. Molecular genetics and genomics : MGG 23 15902492
2016 Indispensable role for mouse ELP3 in embryonic stem cell maintenance and early development. Biochemical and biophysical research communications 22 27476491
2014 Promoter hypermethylation may be an important mechanism of the transcriptional inactivation of ARRDC3, GATA5, and ELP3 in invasive ductal breast carcinoma. Molecular and cellular biochemistry 20 25148870
2023 Functional Characterization of the GNAT Family Histone Acetyltransferase Elp3 and GcnE in Aspergillus fumigatus. International journal of molecular sciences 15 36768506
2023 Amyloid pathology reduces ELP3 expression and tRNA modifications leading to impaired proteostasis. Biochimica et biophysica acta. Molecular basis of disease 13 37640114
2021 Loss of the Transfer RNA Wobble Uridine-Modifying Enzyme Elp3 Delays T Cell Cycle Entry and Impairs T Follicular Helper Cell Responses through Deregulation of Atf4. Journal of immunology (Baltimore, Md. : 1950) 13 33483347
2017 Loss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the Developing Cerebral Cortex. Frontiers in cellular neuroscience 11 28507509
2017 The Arabidopsis ELP3/ELO3 and ELP4/ELO1 genes enhance disease resistance in Fragaria vesca L. BMC plant biology 11 29191170
2012 Cloning and characterization of two genes coding for the histone acetyltransferases, Elp3 and Mof, in brown planthopper (BPH), Nilaparvata lugens (Stål). Gene 11 23142031
2009 ELP3 localises to mitochondria and actin-rich domains at edges of HeLa cells. Neuroscience letters 11 19429107
2022 The Elongator Subunit Elp3 Regulates Development, Stress Tolerance, Cell Cycle, and Virulence in the Entomopathogenic Fungus Beauveria bassiana. Journal of fungi (Basel, Switzerland) 9 36012822
2018 Elp3 and RlmN: A tale of two mitochondrial tail-anchored radical SAM enzymes in Toxoplasma gondii. PloS one 9 29293520
2018 The Arabidopsis Elongator Subunit ELP3 and ELP4 Confer Resistance to Bacterial Speck in Tomato. Frontiers in plant science 9 30087688
2017 Elp3 and Dph3 of Schizosaccharomyces pombe mediate cellular stress responses through tRNALysUUU modifications. Scientific reports 8 28775286
2016 Elongator Protein 3 (Elp3) stabilizes Snail1 and regulates neural crest migration in Xenopus. Scientific reports 8 27189455
2019 ELP3 Acetyltransferase is phosphorylated and regulated by the oncogenic anaplastic lymphoma kinase (ALK). The Biochemical journal 7 31341009
2011 Comparative studies of genome-wide maps of nucleosomes between deletion mutants of elp3 and hos2 genes of Saccharomyces cerevisiae. PloS one 7 21297980
2025 Elongator subunit Elp3 regulates reproduction in Tribolium castaneum by interacting with FOXO. Insect science 5 39744885
2024 ELP3 stabilizes c-Myc to promote tumorigenesis. Journal of molecular cell biology 5 37771073
2020 Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development. International journal of molecular sciences 4 32023806
2022 A novel splice variant of Elp3/Kat9 regulates mitochondrial tRNA modification and function. Scientific reports 3 36045139
2024 Loss of Elp3 blocks intestinal tuft cell differentiation via an mTORC1-Atf4 axis. The EMBO journal 2 39085648
2026 OGT Silencing Protects against Trophoblast Ferroptosis in Gestational Diabetes Mellitus Via ELP3 O-GlcNAcylation Suppression. Applied biochemistry and biotechnology 0 41504842
2025 Elp3 activates the JNK/MAPK pathway through histone acetylation to promote gastric cancer proliferation, migration, and invasion. Histology and histopathology 0 41048082
2025 Upregulation of ELP3 in acinar cells during acute pancreatitis is dispensable for homeostasis, inflammation, regeneration, and cancer initiation. Scientific reports 0 41198876
2025 Acetylation of Axonal G3BP1 through ELP3 Accelerates Axon Regeneration. bioRxiv : the preprint server for biology 0 41279176
2009 [Identification and application of yeast histone acetyltransferases Elp3 polyclonal antibody]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 19938466
2005 [The elp3 subunit of human elongator complex ignificantly complemented the growth defects of yeast elp3delta strain]. Shi yan sheng wu xue bao 0 16363116