Affinage

EEF1A1

Elongation factor 1-alpha 1 · UniProt P68104

Length
462 aa
Mass
50.1 kDa
Annotated
2026-04-28
100 papers in source corpus 41 papers cited in narrative 41 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EEF1A1 encodes a GTPase translation elongation factor that delivers aminoacyl-tRNA to the ribosomal A-site in a GTP-dependent cycle, regulated by the guanine nucleotide exchange factor eEF1Bα (which catalyzes GDP/GTP exchange by destroying the Mg²⁺ binding site) and inhibited by the guanine nucleotide dissociation inhibitor TCTP (PMID:11106763, PMID:11373622, PMID:14623968). Beyond its canonical role in translation—where its activity is fine-tuned by lysine methylation at multiple sites (K36, K55, K165, K318) that alter GTPase activity and codon-specific elongation rates (PMID:30612740, PMID:28108655, PMID:28520920, PMID:25144183)—eEF1A1 functions as a multifunctional hub: it bundles actin filaments (regulated by Ca²⁺/calmodulin and eEF1Bα) (PMID:19095653, PMID:18221514), mediates nuclear export of TD-NEM-bearing proteins from the cytoplasmic face of the nuclear envelope (PMID:18799616), serves as the major export cargo of Exportin-5 via aminoacylated tRNA (PMID:12426392), and couples the heat shock response by recruiting HSF1 to the HSP70 promoter and stabilizing HSP70 mRNA (PMID:25233275). eEF1A1 also inhibits Gcn2-mediated eIF2α phosphorylation as part of amino acid sensing (PMID:21849502), activates sphingosine kinase 1 in a GDP-bound-state-specific manner (PMID:20838377), retains AID in the cytoplasm of B cells (PMID:22042842), and is the essential host target of the antiviral drug plitidepsin (PMID:33495306).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1998 High

    Mutagenesis of the NKMD nucleotide-specificity motif established that GTP binding affinity and hydrolysis rate are critical determinants of eEF1A translational fidelity, quantifying for the first time how the GTPase cycle controls decoding accuracy.

    Evidence Site-directed mutagenesis of yeast eEF1A with in vitro poly(U) translation and misincorporation assays

    PMID:9786872

    Open questions at the time
    • No structural context for how NKMD mutations alter the active site
    • Mammalian relevance not directly tested
  2. 2001 High

    Crystal structures of the eEF1A–eEF1Bα complex and nucleotide-exchange intermediates revealed that Mg²⁺ removal is the central catalytic event in GDP/GTP exchange and that eEF1Bα and aminoacyl-tRNA compete for the same eEF1A surface, establishing the structural basis for the elongation factor activation cycle.

    Evidence X-ray crystallography (1.67–3.0 Å) of yeast eEF1A–eEF1Bα complexes with lethal mutant validation

    PMID:11106763 PMID:11373622

    Open questions at the time
    • No mammalian eEF1A–eEF1Bα structure at the time
    • Ribosome-bound conformational changes not captured
  3. 2002 High

    Discovery that eEF1A forms a stable ternary complex with GDP and uncharged tRNA (Kd ~20 nM), then recruits PheRS, provided evidence for tRNA channeling during elongation—suggesting aminoacyl-tRNA is handed between synthetase and elongation factor without free diffusion.

    Evidence Gel retardation, SPR (BIAcore), and fluorescence binding with purified mammalian components

    PMID:12354112

    Open questions at the time
    • Channeling not demonstrated in vivo
    • Generality across all tRNA species unclear
  4. 2002 High

    Identification of eEF1A as the predominant export substrate of Exportin-5, exported via aminoacylated tRNA, established a tRNA-dependent mechanism for actively excluding translation factors from the nucleus.

    Evidence Biochemical fractionation, RanBP21 binding assays, and cellular localization in mammalian cells

    PMID:12426392

    Open questions at the time
    • Whether eEF1A nuclear exclusion is complete or dynamic not resolved
    • Functional consequences of nuclear eEF1A pools not tested
  5. 2003 High

    TCTP was identified as a guanine nucleotide dissociation inhibitor (GDI) for eEF1A, stabilizing the GDP-bound form and opposing eEF1Bβ-mediated exchange, adding a negative regulatory layer to the eEF1A GTPase cycle.

    Evidence Yeast two-hybrid, in vitro/in vivo binding, GTPase nucleotide exchange assay

    PMID:14623968

    Open questions at the time
    • Physiological contexts triggering TCTP-mediated inhibition not defined
    • Interplay between TCTP and eEF1Bα on the ribosome unknown
  6. 2007 High

    Crystal structure of ZPR1 revealed it preferentially binds GDP-bound eEF1A and displaces eEF1Bα from nucleotide-free complexes, establishing ZPR1 as an additional negative regulator of the eEF1A activation cycle with growth-regulatory consequences.

    Evidence X-ray crystallography, nucleotide exchange kinetics, competitive displacement, structure-guided mutagenesis with growth assays

    PMID:17704259

    Open questions at the time
    • Downstream signaling consequences of ZPR1-mediated eEF1A sequestration not defined
    • In vivo relevance beyond yeast not tested
  7. 2008 High

    Multiple studies established eEF1A's non-translational roles: eEF1Bα was shown to coordinate eEF1A's dual functions in actin bundling and translation via a shared binding surface, and eEF1A was demonstrated to mediate nuclear export of TD-NEM-containing proteins (VHL, PABP1) from the cytoplasmic face of the nuclear envelope.

    Evidence In vitro actin bundling + mutagenesis in yeast; siRNA/antibody depletion + nuclear export assays in mammalian cells

    PMID:18799616 PMID:19095653

    Open questions at the time
    • How eEF1A on the cytoplasmic side of the NPC communicates with nuclear cargo not resolved
    • Structural basis for actin-binding surface on eEF1A not determined
  8. 2009 High

    The Legionella effector SidI was found to target eEF1A and eEF1Bγ, inhibiting host translation and activating the HSF1 stress response through eEF1A, revealing pathogen exploitation of the eEF1A hub and linking it to stress signaling.

    Evidence Yeast lethality screen, co-IP, dominant-negative SidI mutants, HSF1 activation assay

    PMID:19386084

    Open questions at the time
    • Enzymatic modification of eEF1A by SidI not biochemically characterized
    • Direct mechanism linking eEF1A perturbation to HSF1 activation unclear
  9. 2010 High

    Three independent studies expanded eEF1A's signaling roles: TβR-I phosphorylation of Ser300 inhibits aminoacyl-tRNA binding and translation; GDP-bound eEF1A specifically activates sphingosine kinase 1; and Ca²⁺/calmodulin selectively inhibits eEF1A1 (not eEF1A2) tRNA-binding and actin-bundling activities.

    Evidence In vitro kinase assay + translation assay; SK1 activity with defined nucleotide forms + TCTP overexpression; ELISA binding + in vitro functional assays

    PMID:18221514 PMID:20832312 PMID:20838377

    Open questions at the time
    • Physiological contexts triggering Ser300 phosphorylation in vivo not mapped
    • Structural basis for GDP-specific SK1 activation unknown
    • Ca²⁺/CaM regulation not validated in vivo
  10. 2011 High

    eEF1A was identified as an inhibitor of Gcn2-mediated eIF2α phosphorylation (released upon amino acid starvation) and as a cytoplasmic retention factor for AID in B cells, broadening its role as a sensor/sequestration hub beyond translation.

    Evidence Purified-protein kinase assays, co-IP, GST pulldowns (Gcn2); endogenous tagging, co-IP, domain mapping (AID)

    PMID:21849502 PMID:22042842

    Open questions at the time
    • Whether eEF1A–Gcn2 and eEF1A–AID interactions are mutually exclusive not tested
    • Mechanism by which uncharged tRNA displaces eEF1A from Gcn2 not structurally resolved
  11. 2012 High

    A conserved PUF–Ago–eEF1A complex was shown to inhibit eEF1A GTPase activity and attenuate translation elongation, establishing a mechanism by which miRNA/PUF factors repress expression post-initiation via direct elongation factor inhibition.

    Evidence Co-IP in C. elegans and mammals, in vitro GTPase assay, in vitro translation, ribosome profiling

    PMID:22231398

    Open questions at the time
    • Target mRNA specificity of PUF–Ago–eEF1A repression not defined
    • Structural basis for PUF–Ago inhibition of eEF1A GTPase activity unknown
  12. 2014 High

    eEF1A1 was shown to couple the heat shock transcriptional and translational responses by recruiting HSF1 to the HSP70 promoter, then stabilizing HSP70 mRNA and facilitating its transport to ribosomes—a non-canonical function essential for thermotolerance.

    Evidence ChIP, RNA immunoprecipitation, live-cell imaging, siRNA knockdown, thermotolerance assay in mammalian cells

    PMID:25233275

    Open questions at the time
    • How eEF1A1 transitions from chromatin to mRNA not mechanistically defined
    • Whether this function requires GTPase activity unknown
  13. 2017 High

    Four dedicated methyltransferases were identified that modify distinct lysine residues on eEF1A (K36 by eEF1A-KMT4, K55 by METTL13, K165 by METTL21B, K318 by METTL10), each altering translation dynamics as shown by ribosome profiling, establishing eEF1A as one of the most heavily methylated non-histone proteins and linking these marks to codon-specific elongation rates.

    Evidence In vitro methyltransferase assays, X-ray crystallography (METTL13), ribosome profiling in KO cells, MS site-mapping

    PMID:25144183 PMID:28108655 PMID:28520920 PMID:30143613 PMID:30612740

    Open questions at the time
    • Crosstalk between methylation marks not studied
    • Whether methylation is reversible (demethylases) not established
    • Relative contribution of each site to overall elongation rate unknown
  14. 2021 High

    Plitidepsin's anti-SARS-CoV-2 activity was demonstrated to depend on eEF1A inhibition using a drug-resistant eEF1A mutant, confirming eEF1A as a druggable host factor required for viral replication.

    Evidence Drug-resistant mutant generation, in vitro antiviral assay, in vivo mouse models of SARS-CoV-2

    PMID:33495306

    Open questions at the time
    • Precise step of viral life cycle requiring eEF1A not defined
    • Whether translational inhibition or a non-canonical eEF1A function mediates antiviral effect not distinguished
  15. 2022 High

    Cryo-EM and single-molecule FRET revealed that didemnin B and ternatin-4 trap eEF1A at an intermediate state of aa-tRNA selection, preventing eEF1A release and accommodation, providing an atomic-level mechanism for translational inhibition by this drug class.

    Evidence Cryo-EM, single-molecule FRET, in vitro translation

    PMID:36264623

    Open questions at the time
    • Whether trapped intermediate is identical in mammalian vs. bacterial ribosomes not tested
    • Structural basis for plitidepsin action specifically not resolved in this study

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include how the multiple non-canonical functions of eEF1A1 (actin bundling, nuclear export, stress signaling, AID retention, SK1 activation, Gcn2 regulation) are coordinated in space and time, whether dedicated eEF1A1 pools exist for translation vs. moonlighting functions, and whether the extensive lysine methylation code is read by specific effectors or merely tunes GTPase kinetics.
  • No integrative model linking multiple eEF1A1 functions in a single cell type
  • Subcellular pool-specific proteomics not performed
  • No methylation reader proteins identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 6 GO:0045182 translation regulator activity 6 GO:0003723 RNA binding 4 GO:0008092 cytoskeletal protein binding 3 GO:0098772 molecular function regulator activity 2 GO:0044183 protein folding chaperone 1
Localization
GO:0005840 ribosome 4 GO:0005829 cytosol 3 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 2
Pathway
R-HSA-392499 Metabolism of proteins 10 R-HSA-8953854 Metabolism of RNA 3 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2 R-HSA-8953897 Cellular responses to stimuli 2 R-HSA-168256 Immune System 1 R-HSA-74160 Gene expression (Transcription) 1
Partners
AICDADLC1EEF1B2GCN2HSF1SPHK1TPT1ZPR1
Complex memberships
PUF–Ago–eEF1AeEF1A–AID (~11S complex)eEF1A–eEF1Bα (eEF1 complex)

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Crystal structure of yeast eEF1A in complex with the catalytic C-terminus of eEF1Bα (1.67 Å) revealed that eEF1Bα destroys the Mg²⁺ binding site in eEF1A to facilitate GDP/GTP exchange, and that the same domain of eEF1A that interacts with eEF1Bα also binds the CCA-aminoacyl end of tRNA, establishing a competition mechanism between the exchange factor and aminoacyl-tRNA. X-ray crystallography (1.67 Å resolution) Molecular cell High 11106763
2001 Crystal structures of intermediate nucleotide-exchange states (eEF1A–eEF1Bα–GDP–Mg²⁺, –GDP, and –GDPNP) showed that Mg²⁺ removal is the central catalytic event in nucleotide exchange; mutation of eEF1Bα Lys205, which inserts into the Mg²⁺ binding site, is lethal. X-ray crystallography (2.05–3.0 Å) combined with in vivo lethality assay Nature structural biology High 11373622
2002 eEF1A is the predominant export substrate of Exportin-5 (Exp5/RanBP21) and is exported from the nucleus via aminoacylated tRNAs; this cargo–exportin interaction is indirect, mediated through the tRNA. Exp5 and other exportins actively exclude eEF1A and other translation factors from the nucleus, suppressing nuclear translation. Identification of nuclear export substrate by biochemical fractionation, RanBP21 binding assays, cellular localization The EMBO journal High 12426392
2003 TCTP (translationally controlled tumor protein) acts as a guanine nucleotide dissociation inhibitor (GDI) for eEF1A: it preferentially stabilizes the GDP-bound form and impairs the GDP-to-GTP exchange promoted by eEF1Bβ. TCTP interacts with both eEF1Bβ and eEF1A in vitro and in vivo. Yeast two-hybrid, in vitro and in vivo binding assays, MS confirmation, GTPase nucleotide exchange assay Proceedings of the National Academy of Sciences of the United States of America High 14623968
2002 Mammalian eEF1A forms a stable noncanonical ternary complex with GDP and uncharged tRNA (Kd ~20 nM), which then interacts with phenylalanyl-tRNA synthetase (PheRS) to form a quaternary complex (Kd ~9 nM), supporting tRNA channeling during the elongation cycle. Gel retardation, surface plasmon resonance (BIAcore), fluorescence binding assay European journal of biochemistry High 12354112
2009 The Legionella pneumophila effector SidI specifically interacts with eEF1A and eEF1Bgamma, inhibiting host protein synthesis. SidI mutants that retain target binding but lose toxicity suggest SidI enzymatically modifies eEF1A/eEF1Bgamma. This interaction also leads to eEF1A-mediated activation of HSF1 stress response. Yeast lethality screen, co-immunoprecipitation, dominant-negative SidI mutants, HSF1 activation assay Cellular microbiology High 19386084
2012 A conserved PUF–Ago–eEF1A complex attenuates translation elongation. FBF-1 (PUF)–CSR-1 (Ago) heterodimer inhibits eEF1A GTPase activity in vitro, and mammalian PUM2–Ago–eEF1A inhibits translation after initiation, causing ribosome accumulation within the ORF near the exit tunnel. Co-immunoprecipitation in C. elegans and mammals, recombinant protein in vitro GTPase assay, in vitro translation assay, ribosome profiling Nature structural & molecular biology High 22231398
2014 eEF1A1 (but not eEF1A2) participates in the heat shock response by recruiting HSF1 to the HSP70 promoter to activate transcription, then associates with elongating RNA Pol II and the HSP70 mRNA 3'UTR to stabilize the mRNA and facilitate its transport to active ribosomes. eEF1A1-depleted cells show severely impaired HSR and thermotolerance. ChIP, RNA immunoprecipitation, live-cell imaging, siRNA knockdown, thermotolerance assay eLife High 25233275
2019 METTL13 dimethylates eEF1A at lysine 55 (eEF1AK55me2), increasing eEF1A's intrinsic GTPase activity in vitro and protein production in cells. This modification is upregulated in Ras-driven cancers and METTL13 deletion dramatically reduces neoplastic growth in mouse models and PDX tumors. In vitro methyltransferase assay, GTPase assay, ribosome profiling, mouse tumor models, PDX, CRISPR knockout Cell High 30612740
2018 Human METTL13 contains two distinct methyltransferase domains: one methylates the eEF1A N-terminus and one methylates Lys55. Structural analysis provides mechanistic insight into N-terminal recognition. Loss of METTL13 alters translation dynamics and codon-specific translation rates as shown by ribosome profiling. In vitro methyltransferase assay, X-ray crystallography, ribosome profiling, site-directed mutagenesis Nature communications High 30143613
2014 METTL10 (a seven-β-strand methyltransferase) specifically trimethylates human EF1A1 at lysine 318 in mammalian cells; siRNA knockdown of METTL10 decreases EF1A1 K318 methylation levels in vivo. ProSeAM chemical probe labeling, quantitative MS proteomics, siRNA knockdown, in vitro methyltransferase assay PloS one High 25144183
2017 METTL21B specifically methylates Lys-165 of human eEF1A in an aminoacyl-tRNA- and GTP-dependent manner. This methylation is dynamic, tissue-variable, and inducible by ER stress. Genetic ablation of METTL21B in mammalian cells substantially alters mRNA translation as measured by ribosome profiling. In vitro methyltransferase assay, ribosome profiling, cell-based KO, MS site-mapping Nucleic acids research High 28108655
2017 A novel 7BS methyltransferase (eEF1A-KMT4) methylates K36 of eEF1A in vitro and in vivo; knockout of EEF1AKMT4 affects translation dynamics and alters codon-specific translation speed as shown by ribosome profiling. In vitro enzymology, KO cell lines, ribosome profiling, MS site-mapping Nucleic acids research High 28520920
2010 TβR-I (type I TGF-β receptor) phosphorylates eEF1A1 at Ser300 in vitro and in vivo. Ser300 is important for aminoacyl-tRNA binding; phosphorylation or mutation at Ser300 inhibits protein synthesis in vitro and in vivo and correlates with inhibition of cell proliferation. In vitro kinase assay, site-directed mutagenesis, in vitro/in vivo translation assay, cell proliferation assay Current biology : CB High 20832312
2008 eEF1A plays a role in nuclear protein export in mammalian cells: it interacts specifically with the TD-NEM (transcription-dependent nuclear export motif) of VHL and PABP1, and siRNA knockdown or antibody-mediated depletion of eEF1A prevents nuclear export of TD-NEM-containing proteins. eEF1A acts from the cytoplasmic side of the nuclear envelope without entering the nucleus. siRNA knockdown, antibody-mediated depletion, nuclear retention assay, in vitro nuclear export assay, co-IP, point mutations Molecular biology of the cell High 18799616
2021 The antiviral drug plitidepsin exerts its anti-SARS-CoV-2 activity through inhibition of eEF1A; a drug-resistant eEF1A mutant was used to confirm that eEF1A is the essential host target mediating antiviral efficacy. Drug-resistant mutant generation, in vitro antiviral assay, in vivo mouse models of SARS-CoV-2 Science (New York, N.Y.) High 33495306
2007 Crystal structure of the ZPR1 domain tandem shows that ZPR1 binds preferentially to GDP-bound eEF1A but does not directly affect nucleotide exchange kinetics. However, ZPR1 efficiently displaces eEF1Bα from nucleotide-free eEF1A complexes, suggesting a role as a negative regulator of eEF1A activation. Structure-based mutations abolishing eEF1A binding impair cell growth and proliferation. X-ray crystallography, nucleotide exchange kinetics assay, competitive displacement assay, structure-guided mutagenesis, cell growth/proliferation assay Proceedings of the National Academy of Sciences of the United States of America High 17704259
2008 eEF1Bα can disrupt eEF1A-induced actin organization. Mutational analysis shows that eEF1Bα Phe163, which contacts the domain of eEF1A involved in binding actin, aa-tRNA, and eEF1Bα, is critical for nucleotide exchange activity and cell morphology. This reveals that eEF1Bα coordinates eEF1A's dual roles in actin bundling and protein synthesis. In vitro actin bundling assay, eEF1Bα site-directed mutagenesis, growth and morphology phenotyping in yeast, nucleotide exchange assay The Journal of biological chemistry High 19095653
2011 eEF1A binds the Gcn2 kinase C-terminal domain (CTD) and inhibits Gcn2-mediated phosphorylation of eIF2α (but not Gcn2 autophosphorylation). This interaction is diminished in amino-acid-starved cells and by uncharged tRNA in vitro, implicating eEF1A as an inhibitor of the Gcn2 amino acid sensing pathway. Affinity purification (His-eEF1A), co-IP, GST pulldown with purified proteins, in vitro kinase assay The Journal of biological chemistry High 21849502
2011 Cytosolic AID in B cells is held in an ~11S complex in good stoichiometry with eEF1A; this interaction depends on the C-terminal domain of eEF1A and is destroyed by AID mutations that affect cytosolic retention. Thus eEF1A functions as a cytosolic retention factor for AID. Endogenous tagging (avoiding overexpression), co-IP, domain mapping, AID cytosolic retention mutations Proceedings of the National Academy of Sciences of the United States of America High 22042842
2010 eEF1A directly activates sphingosine kinase 1 (SK1); this activation is dependent on the guanine nucleotide state: eEF1A·GDP, but not eEF1A·GTP, activates SK1 in vitro. Elevating eEF1A·GDP levels via the GDI TCTP increases SK1 activity in cells. A truncated eEF1A1 variant (PTI-1) lacking the G-protein domain constitutively activates SK1 and this is required for PTI-1-induced neoplastic transformation. In vitro SK1 activity assay with defined nucleotide-bound forms, TCTP overexpression in cells, SK1 inhibitors/dominant-negative SK1 rescue experiment Oncogene High 20838377
2012 eEF1A associates with defective ribosomal products (DRiPs) to generate a signal for aggresome formation. Knockdown of eEF1A suppresses aggresome formation independently of translation inhibition, as shown by the Legionella toxin SidI which strongly inhibits translation but has marginal effect on aggresome formation. siRNA knockdown, SidI toxin pharmacological dissection, aggresome detection assay Journal of cell science Medium 22357952
2009 The SAM domain of tumor suppressor DLC1 interacts with EF1A1 (but not EF1A2). Mutations in a hydrophobic patch (F38, L39, F40) abolish the interaction. DLC1 SAM facilitates EF1A1 distribution to membrane periphery/ruffles upon growth factor stimulation and modulates cell migration in a GAP-independent manner. Protein precipitation/MS, co-IP, SAM domain NMR structure, mutagenesis, cell migration assay, subcellular localization Journal of cell science High 19158340
2004 eEF1A·GTP binding to the valylated 3'-tRNA-like structure of TYMV viral RNA strongly represses minus-strand synthesis by the viral RdRp; this repression is dependent on aminoacylation of the viral RNA and correlates with eEF1A·GTP binding affinity, suggesting eEF1A coordinates translation vs. replication of the viral genome. In vitro RdRp transcription assay with purified components, titration of eEF1A·GTP concentration Virology High 15033564
2010 eEF1A1 specifically interacts with Ca²⁺/calmodulin (CaM), whereas eEF1A2 does not. Ca²⁺/CaM interaction interferes with eEF1A1's tRNA-binding and actin-bundling activities in vitro, providing a Ca²⁺-dependent regulatory mechanism specific to the eEF1A1 isoform. ELISA-based binding test, in vitro tRNA-binding and actin-bundling assays, molecular dynamics simulation BMC structural biology Medium 18221514
1998 Site-directed mutagenesis of the nucleotide specificity sequence NKMD (residues 153–156) of yeast eEF1A demonstrated that this sequence is critical for GTP binding affinity, GTP hydrolysis rate, and translational fidelity; all viable mutants showed 1–2 orders of magnitude increase in GTP Km. Site-directed mutagenesis, in vitro poly(U)-directed polyphenylalanine synthesis, GTP hydrolysis assay, misincorporation assay The Journal of biological chemistry High 9786872
2004 eEF1A exhibits chaperone-like activity: it promotes full renaturation of phenylalanyl-tRNA synthetase (PheRS) and seryl-tRNA synthetase (SerRS) from denatured states and protects them against dilution-induced denaturation. Both GDP- and GTP-bound forms show similar renaturation activity. In vitro renaturation assay with purified eEF1A and aminoacyl-tRNA synthetases, comparison with BSA control The international journal of biochemistry & cell biology Medium 15109577
2022 Single-molecule fluorescence imaging and cryo-EM showed that didemnin B and ternatin-4 both bind the same site on eEF1A and trap eEF1A in an intermediate state of aa-tRNA selection, preventing eEF1A release and aa-tRNA accommodation. The two drugs show distinct effects on the dynamics of aa-tRNA selection despite sharing the binding site. Single-molecule FRET imaging, cryo-EM, in vitro translation assay eLife High 36264623
2010 Narciclasine directly binds to recombinant human eEF1A in a nanomolar range (but not to actin or eEF2), and 5 nM narciclasine impairs eEF1A-related actin bundling activity; eEF1A targeting leads to actin cytoskeleton disorganization with cytokinesis impairment and protein synthesis inhibition. Direct binding assay with recombinant human eEF1A, yeast-purified eEF1A, actin bundling assay, molecular docking FASEB journal Medium 20643906
2008 BPOZ-2 (a CUL3 E3 ubiquitin ligase adaptor) directly binds eEF1A1 through its ankyrin repeats and both BTB/POZ domains (interacting with domains I and III of eEF1A1), promotes eEF1A1 ubiquitylation and degradation, inhibits GTP binding to eEF1A1, and prevents translation in vitro. Yeast two-hybrid, pull-down, co-IP, in vitro translation assay, ubiquitylation assay, GTP binding assay Genes to cells Medium 18459963
2016 FAT10 stabilizes eEF1A1 by competing with ubiquitin for binding to the same lysines on eEF1A1; FAT10 overexpression decreases ubiquitin-eEF1A1 complex and increases FAT10-eEF1A1 complex, thereby preventing proteasomal degradation of eEF1A1. Co-IP, ubiquitination assay, domain mapping, proliferation assay Cancer research Medium 27312528
2010 PKCβI phosphorylates eEF1A2 at Ser53 in the nucleus of insulin-stimulated C2C12 myoblasts; only PKCβI (not other PKC isoforms) co-immunoprecipitates with eEF1A in the nucleus, and the PKCβI–eEF1A2 association is dependent on the phosphorylation status of eEF1A2. Nuclear proteomics, LC-MS/MS, co-IP, site-directed mutagenesis of Ser53 Molecular & cellular proteomics : MCP Medium 20923971
2009 EF1A1 binds the osteopontin (OPN) 5'-UTR and regulates OPN mRNA stability. EF1A1 binding to the 5'-UTR is actin-dependent: in Hep3B cells EF1A1 is bound to actin and also bound to OPN mRNA; pharmacological manipulation increasing the G:F actin ratio releases EF1A1 from actin and increases OPN mRNA stability. RNA-protein binding assay, mRNA stability measurement, actin manipulation, EF1A1 deletion constructs Experimental cell research Medium 19026636
2022 tRF-Val (a 3'-tRNA-derived fragment) directly binds EEF1A1, mediates its transport into the nucleus, and promotes its interaction with MDM2, thus inhibiting the p53 pathway to promote gastric cancer progression. RNA pull-down, co-IP, subcellular fractionation, siRNA knockdown, in vivo tumor model Cell death & disease Medium 35585048
2017 eEF1A1 promotes HCC cell proliferation through the STAT1–cyclin D1 pathway: eEF1A1 overexpression or knockdown alters G1 phase progression by regulating STAT1 activity, which in turn controls cyclin D1 transcription by binding its promoter. siRNA knockdown, overexpression, cell cycle analysis, ChIP (STAT1 on cyclin D1 promoter), in vitro and in vivo proliferation assay Biochemical and biophysical research communications Medium 29079187
2017 eEF1A1 interacts with SMAD4 and represses SMAD4 transactivation. The small peptide sPEP1 (encoded by HNF4A-AS1) facilitates physical interaction between eEF1A1 and SMAD4, leading to transcriptional upregulation of stem cell genes and promotion of NB stem cell self-renewal. Co-IP, rescue experiments with interaction-defective mutants, in vivo tumor model Oncogene Medium 35318442
2017 Expanded polyalanine (poly(A)) tracts function as nuclear export signals and interact with eEF1A1; knockdown of eEF1A1 partially corrects the cytoplasmic mislocalization of expanded poly(A) proteins and restores their nuclear function, identifying eEF1A1 as a mediator of poly(A) disease protein mislocalization. GST pulldown + MS, siRNA knockdown, subcellular localization assay, rescue experiment The Journal of biological chemistry Medium 28246169
2008 eEF1A1 binds the novel muscle protein IGFN1 (which is substantially upregulated during muscle denervation) in vitro; the interaction was identified by yeast two-hybrid in human skeletal muscle cDNA library and confirmed biochemically, suggesting a mechanism for down-regulation of protein synthesis via eEF1A1 during denervation. Yeast two-hybrid, in vitro binding confirmation, expression analysis in denervated muscle Journal of cellular biochemistry Low 18756455
2012 MLIF (monocyte locomotion inhibitory factor) binds directly to eEF1A1 (identified by biotin-conjugated MLIF pull-down + MS). eEF1A1 is required for MLIF-enhanced eNOS mRNA stabilization and eNOS expression; knockdown of eEF1A1 attenuates MLIF-mediated inhibition of inflammatory adhesion molecules. Biotin pulldown + MS, siRNA knockdown, mRNA stability assay, adhesion molecule expression Stroke Medium 22829547
2018 eEF1A interacts with HIV-1 reverse transcriptase (RT) through surface-exposed acidic residues in the RT thumb domain alpha-J helix (D250, E297, E298, E300). Mutation E300R significantly impairs eEF1A–RT interaction, delays reverse transcription and viral core uncoating, and strongly inhibits HIV-1 replication in CD4+ T cells without affecting RT catalytic activity or heterodimerization. Co-IP/binding assay with RT mutants, in vitro RT activity assay, uncoating assay, HIV-1 replication assay in CD4+ T cells mBio High 29588400
2001 Peptide elongation factor eEF1A-1 (but not eEF1A-2) promotes cell death in differentiated myotubes: adenoviral introduction of eEF1A-1 accelerates serum deprivation-induced apoptosis (caspase-3 activation), whereas antisense eEF1A-1 protects myotubes. This establishes an isoform-specific pro-death function for eEF1A-1 in skeletal muscle. Adenoviral gene transfer, antisense expression, caspase-3 activation assay, cell death measurement The Journal of biological chemistry Medium 11724805

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2021 Plitidepsin has potent preclinical efficacy against SARS-CoV-2 by targeting the host protein eEF1A. Science (New York, N.Y.) 253 33495306
2010 eEF1A: thinking outside the ribosome. The Journal of biological chemistry 214 20444696
2002 Exp5 exports eEF1A via tRNA from nuclei and synergizes with other transport pathways to confine translation to the cytoplasm. The EMBO journal 194 12426392
2015 The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections. Frontiers in oncology 173 25905039
2005 Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer research 170 15994932
2000 Structural basis for nucleotide exchange and competition with tRNA in the yeast elongation factor complex eEF1A:eEF1Balpha. Molecular cell 166 11106763
2003 Translationally controlled tumor protein acts as a guanine nucleotide dissociation inhibitor on the translation elongation factor eEF1A. Proceedings of the National Academy of Sciences of the United States of America 159 14623968
2019 METTL13 Methylation of eEF1A Increases Translational Output to Promote Tumorigenesis. Cell 150 30612740
2014 The translation elongation factor eEF1A1 couples transcription to translation during heat shock response. eLife 137 25233275
2009 Targeting eEF1A by a Legionella pneumophila effector leads to inhibition of protein synthesis and induction of host stress response. Cellular microbiology 118 19386084
2012 A conserved PUF-Ago-eEF1A complex attenuates translation elongation. Nature structural & molecular biology 113 22231398
2001 Peptide elongation factor eEF1A-2/S1 expression in cultured differentiated myotubes and its protective effect against caspase-3-mediated apoptosis. The Journal of biological chemistry 106 11724805
2001 Crystal structures of nucleotide exchange intermediates in the eEF1A-eEF1Balpha complex. Nature structural biology 103 11373622
2010 Targeting of eEF1A with Amaryllidaceae isocarbostyrils as a strategy to combat melanomas. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 99 20643906
2022 A novel 3'tRNA-derived fragment tRF-Val promotes proliferation and inhibits apoptosis by targeting EEF1A1 in gastric cancer. Cell death & disease 92 35585048
2007 Mouse translation elongation factor eEF1A-2 interacts with Prdx-I to protect cells against apoptotic death induced by oxidative stress. Journal of cellular biochemistry 84 16888816
2014 Selenium-based S-adenosylmethionine analog reveals the mammalian seven-beta-strand methyltransferase METTL10 to be an EF1A1 lysine methyltransferase. PloS one 81 25144183
2018 The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates. Nature communications 77 30143613
2017 SPL33, encoding an eEF1A-like protein, negatively regulates cell death and defense responses in rice. Journal of experimental botany 77 28199670
1996 Assignment of human elongation factor 1alpha genes: EEF1A maps to chromosome 6q14 and EEF1A2 to 20q13.3. Genomics 77 8812466
2017 The novel lysine specific methyltransferase METTL21B affects mRNA translation through inducible and dynamic methylation of Lys-165 in human eukaryotic elongation factor 1 alpha (eEF1A). Nucleic acids research 75 28108655
2008 eEF1A is a novel component of the mammalian nuclear protein export machinery. Molecular biology of the cell 74 18799616
2004 eEF1A binding to aminoacylated viral RNA represses minus strand synthesis by TYMV RNA-dependent RNA polymerase. Virology 69 15033564
2016 The Ubiquitin-like Protein FAT10 Stabilizes eEF1A1 Expression to Promote Tumor Proliferation in a Complex Manner. Cancer research 64 27312528
2009 Structural models of human eEF1A1 and eEF1A2 reveal two distinct surface clusters of sequence variation and potential differences in phosphorylation. PloS one 61 19636410
2011 Dissecting the expression of EEF1A1/2 genes in human prostate cancer cells: the potential of EEF1A2 as a hallmark for prostate transformation and progression. British journal of cancer 59 22095224
2009 The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration. Journal of cell science 51 19158340
1992 Actin crosslinking protein EF-1a of Dictyostelium discoideum has a unique bonding rule that allows square-packed bundles. Journal of structural biology 50 1296758
2007 A2 isoform of mammalian translation factor eEF1A displays increased tyrosine phosphorylation and ability to interact with different signalling molecules. The international journal of biochemistry & cell biology 48 17936057
2018 Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation. RNA biology 47 29447067
2017 Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation. Nucleic acids research 46 28520920
2008 Coordination of eukaryotic translation elongation factor 1A (eEF1A) function in actin organization and translation elongation by the guanine nucleotide exchange factor eEF1Balpha. The Journal of biological chemistry 46 19095653
2011 Evidence that eukaryotic translation elongation factor 1A (eEF1A) binds the Gcn2 protein C terminus and inhibits Gcn2 activity. The Journal of biological chemistry 44 21849502
2008 Novel cell death by downregulation of eEF1A1 expression in tetraploids. Cell death and differentiation 44 18820646
2011 Cytoplasmic activation-induced cytidine deaminase (AID) exists in stoichiometric complex with translation elongation factor 1α (eEF1A). Proceedings of the National Academy of Sciences of the United States of America 43 22042842
2010 Phosphorylation of eEF1A1 at Ser300 by TβR-I results in inhibition of mRNA translation. Current biology : CB 43 20832312
2006 Tetrahymena eukaryotic translation elongation factor 1A (eEF1A) bundles filamentous actin through dimer formation. Journal of biochemistry 43 16877446
2008 The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein. International journal of cancer 42 18649364
2019 Genome-wide target interactome profiling reveals a novel EEF1A1 epigenetic pathway for oncogenic lncRNA MALAT1 in breast cancer. American journal of cancer research 41 31105998
2017 Overexpression of eEF1A1 regulates G1-phase progression to promote HCC proliferation through the STAT1-cyclin D1 pathway. Biochemical and biophysical research communications 41 29079187
2010 Guanine nucleotides regulate sphingosine kinase 1 activation by eukaryotic elongation factor 1A and provide a mechanism for eEF1A-associated oncogenesis. Oncogene 40 20838377
2009 The hepatitis delta virus RNA genome interacts with eEF1A1, p54(nrb), hnRNP-L, GAPDH and ASF/SF2. Virology 40 19464723
2007 Structural insights into the interaction of the evolutionarily conserved ZPR1 domain tandem with eukaryotic EF1A, receptors, and SMN complexes. Proceedings of the National Academy of Sciences of the United States of America 40 17704259
2003 Malaria parasites lacking eef1a have a normal S/M phase yet grow more slowly due to a longer G1 phase. Molecular microbiology 40 14651637
2002 Novel complexes of mammalian translation elongation factor eEF1A.GDP with uncharged tRNA and aminoacyl-tRNA synthetase. Implications for tRNA channeling. European journal of biochemistry 38 12354112
2016 Comparative mRNA Expression of eEF1A Isoforms and a PI3K/Akt/mTOR Pathway in a Cellular Model of Parkinson's Disease. Parkinson's disease 37 26981313
2021 CircRNA_0050463 promotes influenza A virus replication by sponging miR-33b-5p to regulate EEF1A1. Veterinary microbiology 36 33517193
2020 CagA orchestrates eEF1A1 and PKCδ to induce interleukin-6 expression in Helicobacter pylori-infected gastric epithelial cells. Gut pathogens 36 32636937
2015 Saccharomyces cerevisiae Eukaryotic Elongation Factor 1A (eEF1A) Is Methylated at Lys-390 by a METTL21-Like Methyltransferase. PloS one 36 26115316
2003 Identification of different isoforms of eEF1A in the nuclear fraction of human T-lymphoblastic cancer cell line specifically binding to aptameric cytotoxic GT oligomers. European journal of biochemistry 32 12869201
1998 Site-directed mutagenesis of yeast eEF1A. Viable mutants with altered nucleotide specificity. The Journal of biological chemistry 32 9786872
2012 Association of translation factor eEF1A with defective ribosomal products generates a signal for aggresome formation. Journal of cell science 31 22357952
2021 On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits. International journal of molecular sciences 30 34203525
2017 P21 activated kinase 4 binds translation elongation factor eEF1A1 to promote gastric cancer cell migration and invasion. Oncology reports 30 28393218
2016 EF1A1/HSC70 Cooperatively Suppress Brain Endothelial Cell Apoptosis via Regulating JNK Activity. CNS neuroscience & therapeutics 30 27324700
2004 Structural basis for the binding of didemnins to human elongation factor eEF1A and rationale for the potent antitumor activity of these marine natural products. Journal of medicinal chemistry 30 15317456
2014 EF1A interacting with nucleocapsid protein of transmissible gastroenteritis coronavirus and plays a role in virus replication. Veterinary microbiology 28 24974120
2021 High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector. PloS one 27 33529230
2006 Interaction of G-rich GT oligonucleotides with nuclear-associated eEF1A is correlated with their antiproliferative effect in haematopoietic human cancer cell lines. The FEBS journal 27 16689924
2010 eEF1A phosphorylation in the nucleus of insulin-stimulated C2C12 myoblasts: Ser⁵³ is a novel substrate for protein kinase C βI. Molecular & cellular proteomics : MCP 26 20923971
2008 Multiple molecular dynamics simulation of the isoforms of human translation elongation factor 1A reveals reversible fluctuations between "open" and "closed" conformations and suggests specific for eEF1A1 affinity for Ca2+-calmodulin. BMC structural biology 26 18221514
2008 Translation elongation factor eEF1A binds to a novel myosin binding protein-C-like protein. Journal of cellular biochemistry 26 18756455
2022 Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury. Cell death discovery 25 36123349
2012 From global phosphoproteomics to individual proteins: the case of translation elongation factor eEF1A. Expert review of proteomics 25 22292825
2023 Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1-EEF1A1 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 24 37075745
2022 Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes. eLife 24 36264623
2016 RPL13A and EEF1A1 Are Suitable Reference Genes for qPCR during Adipocyte Differentiation of Vascular Stromal Cells from Patients with Different BMI and HOMA-IR. PloS one 24 27304673
2008 EF1A1-actin interactions alter mRNA stability to determine differential osteopontin expression in HepG2 and Hep3B cells. Experimental cell research 24 19026636
1997 Site-directed mutants of post-translationally modified sites of yeast eEF1A using a shuttle vector containing a chromogenic switch. Biochimica et biophysica acta 24 9061031
2013 Highly homologous eEF1A1 and eEF1A2 exhibit differential post-translational modification with significant enrichment around localised sites of sequence variation. Biology direct 23 24220286
2011 Neurite outgrowth mediated by translation elongation factor eEF1A1: a target for antiplatelet agent cilostazol. PloS one 23 21390260
2011 Actin bundling and polymerisation properties of eukaryotic elongation factor 1 alpha (eEF1A), histone H2A-H2B and lysozyme in vitro. Journal of structural biology 23 21964468
2009 Specific interaction between Sam68 and neuronal mRNAs: implication for the activity-dependent biosynthesis of elongation factor eEF1A. Journal of neuroscience research 23 18711726
2004 Immuno-characterization of the switch of peptide elongation factors eEF1A-1/EF-1alpha and eEF1A-2/S1 in the central nervous system during mouse development. Brain research. Developmental brain research 23 15013623
2022 HNF4A-AS1-encoded small peptide promotes self-renewal and aggressiveness of neuroblastoma stem cells via eEF1A1-repressed SMAD4 transactivation. Oncogene 22 35318442
2021 Nannocystin ax, an eEF1A inhibitor, induces G1 cell cycle arrest and caspase-independent apoptosis through cyclin D1 downregulation in colon cancer in vivo. Pharmacological research 22 34500061
2021 MLIF Modulates Microglia Polarization in Ischemic Stroke by Targeting eEF1A1. Frontiers in pharmacology 22 34557098
2017 Proteomic Identification of eEF1A1 as a Molecular Target of Curcumol for Suppressing Metastasis of MDA-MB-231 Cells. Journal of agricultural and food chemistry 21 28345336
2015 Critical role of eukaryotic elongation factor 1 alpha 1 (EEF1A1) in avian reovirus sigma-C-induced apoptosis and inhibition of viral growth. Archives of virology 21 25854689
2022 Nanoparticles (NPs)-mediated lncBCMA silencing to promote eEF1A1 ubiquitination and suppress breast cancer growth and metastasis. Acta pharmaceutica Sinica. B 20 37655325
2021 Long Non-Coding RNA CRYBG3 Promotes Lung Cancer Metastasis via Activating the eEF1A1/MDM2/MTBP Axis. International journal of molecular sciences 20 33809929
2020 Downregulation of eEF1A/EFT3-4 Enhances Dopaminergic Neurodegeneration After 6-OHDA Exposure in C. elegans Model. Frontiers in neuroscience 20 32425742
2012 A pentapeptide monocyte locomotion inhibitory factor protects brain ischemia injury by targeting the eEF1A1/endothelial nitric oxide synthase pathway. Stroke 20 22829547
2009 The role of translation elongation factor eEF1A in intracellular alkalinization-induced tumor cell growth. Laboratory investigation; a journal of technical methods and pathology 20 19506553
2022 METTL13 facilitates cell growth and metastasis in gastric cancer via an eEF1A/HN1L positive feedback circuit. Journal of cell communication and signaling 19 35925508
2017 Structural rationale for the cross-resistance of tumor cells bearing the A399V variant of elongation factor eEF1A1 to the structurally unrelated didemnin B, ternatin, nannocystin A and ansatrienin B. Journal of computer-aided molecular design 19 28900796
2010 Glutamate regulates eEF1A phosphorylation and ribosomal transit time in Bergmann glial cells. Neurochemistry international 19 20817065
2003 eEF1A isoforms change in abundance and actin-binding activity during maize endosperm development. Plant physiology 19 14526107
2019 Switch of the interactions between the ribosomal stalk and EF1A in the GTP- and GDP-bound conformations. Scientific reports 18 31611569
2002 Nerve growth factor specifically stimulates translation of eukaryotic elongation factor 1A-1 (eEF1A-1) mRNA by recruitment to polyribosomes in PC12 cells. The Journal of biological chemistry 18 11907030
2022 Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumour eEF1A antagonist SR-A3. Nature chemistry 17 36123449
2019 Fatty acylCoA synthetase FadD13 regulates proinflammatory cytokine secretion dependent on the NF-κB signalling pathway by binding to eEF1A1. Cellular microbiology 17 31364251
2017 Comparison of the ability of mammalian eEF1A1 and its oncogenic variant eEF1A2 to interact with actin and calmodulin. Biological chemistry 17 27483363
2008 BPOZ-2 directly binds to eEF1A1 to promote eEF1A1 ubiquitylation and degradation and prevent translation. Genes to cells : devoted to molecular & cellular mechanisms 17 18459963
2004 Chaperone-like activity of mammalian elongation factor eEF1A: renaturation of aminoacyl-tRNA synthetases. The international journal of biochemistry & cell biology 17 15109577
2022 DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p. Journal of oncology 16 35586205
2018 HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain. mBio 16 29588400
2017 Expanded polyalanine tracts function as nuclear export signals and promote protein mislocalization via eEF1A1 factor. The Journal of biological chemistry 16 28246169
2015 eEF1A Interacts with the NS5A Protein and Inhibits the Growth of Classical Swine Fever Virus. Viruses 16 26266418
2008 Roles of three domains of Tetrahymena eEF1A in bundling F-actin. Zoological science 16 18275242