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Showing EEF1A1 — EEF1A is a alias.

EEF1A1

Elongation factor 1-alpha 1 · UniProt P68104

Length
462 aa
Mass
50.1 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

eEF1A1 is a multifunctional GTPase whose canonical role is the GTP-dependent delivery of aminoacyl-tRNA to the elongating ribosome, a function defined biochemically through its nucleotide-specificity NKMD motif required for GTP hydrolysis and translational fidelity (PMID:9786872) and structurally through crystal structures of the eEF1A–eEF1Bα complex showing that the exchange factor inserts between the switch regions to destroy the Mg²⁺-binding site and competes with the CCA-aminoacyl end of tRNA, channeling translation substrates (PMID:11106763, PMID:11373622). Cyclic-peptide inhibitors (didemnin B, ternatin-4, SR-A3) trap eEF1A·GTP·aa-tRNA ternary complexes in an intermediate state of aa-tRNA selection, defining the drug-binding site and the dynamics of factor release (PMID:36264623, PMID:36123449). eEF1A activity is gated by a network of regulators and modifications: TCTP and ZPR1 act as nucleotide-dissociation inhibitors that favor the GDP-bound form (PMID:14623968, PMID:17704259), TGF-β receptor TβR-I phosphorylates Ser300 to reduce aa-tRNA binding and suppress translation (PMID:20832312), and a suite of lysine methyltransferases—eEF1A-KMT4 (K36), METTL13 (N-terminus and K55), METTL21B (K165), and METTL10 (K318)—trimethylate the factor to tune codon-specific elongation rates, with METTL13-mediated K55 dimethylation increasing intrinsic GTPase activity and supporting Ras-driven oncogenic growth (PMID:28520920, PMID:30143613, PMID:30612740, PMID:28108655, PMID:25144183). Beyond elongation, eEF1A1 carries diverse moonlighting functions: it bundles F-actin through Ca²⁺/calmodulin-regulated dimerization (PMID:16877446, PMID:18275242, PMID:18221514), orchestrates the heat shock response by recruiting HSF1 to the HSP70 promoter and stabilizing HSP70 mRNA (PMID:25233275), exports SNAG-domain transcription factors and TD-NEM/polyalanine-containing proteins from the nucleus via the Exportin5–aa-tRNA pathway (PMID:18799616, PMID:24209753, PMID:28246169), retains AID in the cytoplasm in a tRNA-free state to limit class switch recombination (PMID:22042842, PMID:25824822), inhibits the Gcn2 stress kinase (PMID:21849502), and in its GDP-bound form activates sphingosine kinase 1 (PMID:20838377). eEF1A is co-opted by pathogens, supporting viral RNA replication and HIV-1 reverse transcription (PMID:15033564, PMID:17626087, PMID:26624286) and serving as the host target of antiviral plitidepsin against SARS-CoV-2 (PMID:33495306). Its own biogenesis requires the dedicated ribosome-associated chaperone Chp1, recruited via NAC, which protects nascent eEF1A from proteolysis (PMID:38360885).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    Established that a defined nucleotide-specificity motif governs eEF1A's GTPase chemistry and translational fidelity, anchoring its catalytic identity.

    Evidence Site-directed mutagenesis of yeast eEF1A NKMD motif with in vitro poly(U) translation and GTP hydrolysis assays

    PMID:9786872

    Open questions at the time
    • Does not resolve the full conformational cycle on the ribosome
    • Yeast ortholog; human residue effects inferred
  2. 2001 High

    Resolved the atomic mechanism of guanine-nucleotide exchange, showing eEF1Bα drives GDP release by displacing the catalytic Mg²⁺ and competing with aa-tRNA binding.

    Evidence Crystal structures of eEF1A–eEF1Bα at 1.67Å and of GDP/GDPNP intermediates plus lethal K205A mutagenesis

    PMID:11106763 PMID:11373622

    Open questions at the time
    • Static structures do not capture exchange kinetics in cells
    • Does not address regulation of exchange by upstream signals
  3. 2007 High

    Identified ZPR1 (and earlier TCTP) as nucleotide-state-selective regulators that displace the exchange factor and bias eEF1A toward the GDP-bound form, revealing layered control of activation.

    Evidence Crystallography, co-IP, nucleotide-exchange displacement assays and yeast complementation; TCTP via Y2H/Co-IP/exchange assay

    PMID:14623968 PMID:17704259

    Open questions at the time
    • Physiological conditions selecting between these regulators unresolved
    • Connection to specific signaling inputs not mapped
  4. 2010 High

    Showed that signaling kinases directly modulate eEF1A translational output, with TβR-I phosphorylation of Ser300 suppressing translation and PASKIN phosphorylation of Thr432 promoting it.

    Evidence In vitro kinase assays, phosphosite mutagenesis, in vitro translation and proliferation readouts

    PMID:17595531 PMID:20832312

    Open questions at the time
    • Crosstalk between phosphosites not characterized
    • Phosphatases reversing these marks unknown
  5. 2017 High

    Defined a dedicated lysine-methyltransferase network (eEF1A-KMT4/K36, METTL21B/K165, METTL10/K318) that post-translationally tunes codon-specific elongation rates.

    Evidence In vitro methylation assays, enzyme knockouts with ribosome profiling, chemical-probe MS

    PMID:25144183 PMID:28108655 PMID:28520920

    Open questions at the time
    • How individual marks integrate to set codon usage is unresolved
    • Demethylation/turnover of these marks not addressed
  6. 2019 High

    Demonstrated that METTL13 methylation of the N-terminus and K55 boosts intrinsic GTPase activity and translational output, linking eEF1A modification to Ras-driven oncogenesis.

    Evidence In vitro GTPase assays with methylated eEF1A, crystallography, METTL13 KO mouse and PDX models

    PMID:30143613 PMID:30612740

    Open questions at the time
    • Selectivity of dependence across tumor genotypes not fully defined
    • Mechanism linking GTPase rate to growth not dissected at single-codon level
  7. 2006 Medium

    Established eEF1A's actin-bundling moonlighting activity as a Ca²⁺/calmodulin-regulated, dimer-dependent process distinct from translation.

    Evidence Gel filtration, cosedimentation, EM and Ca²⁺/calmodulin treatment in Tetrahymena; domain mapping; ELISA calmodulin binding

    PMID:16877446 PMID:18221514 PMID:18275242

    Open questions at the time
    • Largely ortholog-based; human in vivo relevance partly inferred
    • Coordination with translational pool in cells not quantified
  8. 2014 High

    Revealed eEF1A1 as a master coordinator of the heat shock response acting at both transcription (HSF1 recruitment) and mRNA stability levels, an isoform-specific nuclear-associated function.

    Evidence siRNA knockdown, ChIP, RIP, live-cell imaging and thermotolerance assays

    PMID:25233275

    Open questions at the time
    • Mechanism of HSF1 recruitment by a cytoplasmic factor not structurally defined
    • Single-lab study
  9. 2015 High

    Defined eEF1A as a cytoplasmic retention factor and nuclear-export adaptor controlling localization of regulatory proteins, requiring a tRNA-free form for AID retention and the Exportin5–aa-tRNA route for transcription-factor export.

    Evidence Endogenous tagging, co-IP, domain mapping, chemical inhibition with CSR/translocation readouts; export assays for SNAG and TD-NEM/polyalanine proteins

    PMID:18799616 PMID:22042842 PMID:24209753 PMID:25824822 PMID:28246169

    Open questions at the time
    • How the same factor distinguishes retention versus export substrates is unresolved
    • Structural basis of substrate recognition not determined
  10. 2021 High

    Validated eEF1A as the host target of antiviral cyclic peptides and clarified the inhibitory mechanism as trapping of the ternary complex during aa-tRNA selection.

    Evidence Drug-resistant mutant selection, cryo-EM and single-molecule FRET, in vivo SARS-CoV-2 and lymphoma models; HIV-1 RT binding via biolayer interferometry

    PMID:26624286 PMID:33495306 PMID:36123449 PMID:36264623

    Open questions at the time
    • Therapeutic window between antiviral/antitumor effect and translation toxicity not defined
    • Selectivity over eEF1A2 not fully addressed
  11. 2024 High

    Identified Chp1 as a dedicated ribosome-associated chaperone required for eEF1A biogenesis, showing nascent eEF1A needs specialized co-translational protection from degradation.

    Evidence Ribosome association, proteomics, aggregation and Hsf1 reporter assays, pathogenic variant expression

    PMID:38360885

    Open questions at the time
    • Structural basis of Chp1–nascent eEF1A recognition unknown
    • Human disease relevance shown for eEF1A2 variants, not eEF1A1

Open questions

Synthesis pass · forward-looking unresolved questions
  • How eEF1A's many moonlighting roles (actin, nuclear export, stress signaling, viral support) are partitioned from the translational pool within a single cell, and how nucleotide state, modification, and partner availability jointly select among them, remains unresolved.
  • No integrated model linking PTM state to functional partitioning
  • Quantitative flux between translational and non-translational pools unmeasured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 4 GO:0003924 GTPase activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0045182 translation regulator activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005829 cytosol 3 GO:0005840 ribosome 3 GO:0005856 cytoskeleton 2
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1643685 Disease 3 R-HSA-9609507 Protein localization 3 R-HSA-8953854 Metabolism of RNA 2 R-HSA-8953897 Cellular responses to stimuli 2
Partners
AICDAEEF1B2EIF2AK4METTL13SNAI1TPT1VHLZPR1
Complex memberships
PUM2–Ago–eEF1A complexeEF1A·GTP·aa-tRNA ternary complexeEF1A–eEF1Bα (eEF1B complex)

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Crystal structure of the eEF1A–eEF1Bα complex determined at 1.67 Å resolution revealed that eEF1Bα inserts one end between the switch 1 and 2 regions of eEF1A to destroy the Mg²⁺ binding site, and the other end contacts domain 2 of eEF1A in the region that binds the CCA-aminoacyl end of tRNA, suggesting competition between eEF1Bα and aa-tRNA as a central element in channeling translation substrates. X-ray crystallography (1.67 Å), structural analysis Molecular cell High 11106763
2001 Crystal structures of eEF1A–eEF1Bα–GDP–Mg²⁺, –GDP, and –GDPNP intermediates defined the nucleotide exchange mechanism; a lethal K205A mutation in eEF1Bα that inserts into the Mg²⁺ binding site of eEF1A confirmed the essential role of Mg²⁺ displacement in nucleotide exchange. X-ray crystallography (2.05–3.0 Å), site-directed mutagenesis, in vivo viability assay Nature structural biology High 11373622
1998 Site-directed mutagenesis of yeast eEF1A at the nucleotide specificity sequence NKMD (residues 153–156) produced viable mutants with increased Km for GTP and reduced GTP hydrolysis rates; N153D was lethal, establishing that this sequence is critical for GTPase function and translational fidelity. Site-directed mutagenesis, in vitro poly(U)-directed translation assay, GTP hydrolysis assay The Journal of biological chemistry High 9786872
2002 Exportin 5 (Exp5/RanBP21) mediates nuclear export of eEF1A indirectly via aminoacylated tRNAs; eEF1A binds Exp5 only through aa-tRNA, not directly. Fractionation showed that eEF1A and all other elongation factors are strictly excluded from nuclei, arguing that nuclear translation is actively suppressed. Nuclear fractionation, transport reconstitution assays, subcellular 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 of eEF1A and impairs the GDP→GTP exchange promoted by eEF1Bβ, as shown by in vitro and in vivo binding assays. Yeast two-hybrid, co-immunoprecipitation, MS, in vitro nucleotide exchange assay Proceedings of the National Academy of Sciences of the United States of America High 14623968
2004 eEF1A·GTP binding to the valylated 3′ tRNA-like structure of TYMV genomic RNA strongly represses minus-strand RNA synthesis by the viral RdRp in vitro; repression was aa-tRNA-dependent and required eEF1A·GTP but not the GDP form, suggesting a regulatory switch between translation and replication roles. In vitro RdRp transcription assay, eEF1A·GTP binding competition Virology High 15033564
2007 eEF1A binds the 3′ stem-loop of West Nile virus genomic RNA and colocalizes with viral replication complexes; mutations that decreased in vitro eEF1A binding to the 3′ SL reduced viral minus-strand RNA synthesis without affecting polyprotein translation, establishing that eEF1A facilitates flavivirus minus-strand synthesis. RNase footprinting, nitrocellulose filter binding, infectious clone mutagenesis, minus-strand RNA quantification, co-immunoprecipitation, immunofluorescence colocalization Journal of virology High 17626087
2008 eEF1A plays a central role in nuclear export of proteins in mammalian cells via a transcription-dependent nuclear export motif (TD-NEM); eEF1A interacts specifically with TD-NEM of VHL and PABP1, and siRNA knockdown or antibody depletion of eEF1A prevents nuclear export of TD-NEM-containing proteins. eEF1A acts from the cytoplasmic face of the nuclear envelope without itself entering the nucleus. siRNA knockdown, antibody-mediated depletion, in vivo and in vitro nuclear export assay, point mutagenesis of TD-NEM, actinomycin D treatment Molecular biology of the cell High 18799616
2008 The SAM domain of RhoGAP DLC1 binds eEF1A1 (EF1A1); structural and mutagenesis analysis identified F38/L39 in the DLC1 SAM hydrophobic patch as an indispensable interaction motif. DLC1 SAM facilitates redistribution of eEF1A1 to the membrane periphery upon growth factor stimulation, and this interaction is required for full DLC1-mediated suppression of cell migration. Protein precipitation/MS, NMR solution structure of DLC1-SAM, site-directed mutagenesis, co-immunoprecipitation, cell migration assay Journal of cell science High 19158340
2008 BPOZ-2 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 suppresses translation in an in vitro reticulocyte assay. Yeast two-hybrid, pull-down, co-immunoprecipitation, in vitro ubiquitylation assay, GTP-binding assay, in vitro translation assay Genes to cells Medium 18459963
2009 The Legionella pneumophila Dot/Icm effector SidI specifically interacts with eEF1A and eEF1Bγ, inhibiting host protein synthesis; SidI mutants retaining target-binding but lacking toxicity were isolated, and L. pneumophila infection induces eEF1A-mediated HSF1 activation in a virulence-dependent manner. Yeast toxicity assay, co-immunoprecipitation, protein synthesis inhibition assay, SidI substitution mutagenesis, HSF1 activation measurement Cellular microbiology Medium 19386084
2009 EF1A1 binds the 5′-UTR of osteopontin (OPN) mRNA to regulate OPN mRNA stability; this interaction is actin-dependent: EF1A1 bound to F-actin in Hep3B cells is unavailable for mRNA binding, and pharmacologic increase of the G:F actin ratio releases EF1A1 to bind OPN mRNA and increase its half-life. mRNA half-life assay, RNA binding assay, actin co-sedimentation, pharmacologic G:F actin manipulation Experimental cell research Medium 19026636
2010 TGF-β type I receptor (TβR-I) phosphorylates eEF1A1 at Ser300 in vitro and in vivo; phosphorylation at Ser300 reduces aa-tRNA binding to eEF1A1 and inhibits protein synthesis and cell proliferation. Phosphomimetic Ser300 mutations phenocopy TGF-β-dependent inhibition of translation. In vitro kinase assay, site-directed mutagenesis, in vivo phosphorylation analysis, in vitro translation assay, cell proliferation assay Current biology High 20832312
2010 eEF1Bα disrupts eEF1A-induced actin organization, and eEF1Bα F163 in the domain shared with actin and aa-tRNA binding governs this activity. Combining the F163A lethal mutation with W130A intragenic suppressor or with the K205A mutation dramatically reduces eEF1Bα–eEF1A affinity and restores viability while increasing actin bundling, establishing that eEF1Bα coordinates the dual roles of eEF1A in actin organization and translation. Site-directed mutagenesis, actin bundling assay, nucleotide exchange activity assay, yeast growth phenotype, cell morphology analysis The Journal of biological chemistry Medium 19095653
2010 eEF1A·GDP (but not eEF1A·GTP) directly activates sphingosine kinase 1 (SK1) in vitro; enhancing cellular eEF1A·GDP levels via TCTP (a GDI) increases SK1 activity in cells. The truncated oncogenic isoform PTI-1, which lacks the G-protein domain, constitutively activates SK1, and SK1 inhibition blocks PTI-1-induced neoplastic transformation. In vitro SK1 activity assay with GTP/GDP-loaded eEF1A, cell-based SK1 activity assay, dominant-negative SK1 and chemical inhibitor rescue Oncogene Medium 20838377
2011 eEF1A binds the C-terminal domain (CTD) of Gcn2 kinase independently of ribosomes; this interaction is reduced during amino acid starvation and by uncharged tRNAs in vitro. Purified eEF1A inhibits Gcn2-mediated phosphorylation of eIF2α but not Gcn2 autophosphorylation, identifying eEF1A as a Gcn2 inhibitor that modulates the amino acid starvation response. Affinity purification (His-eEF1A), co-immunoprecipitation, GST pulldown with purified proteins, in vitro Gcn2 kinase assay The Journal of biological chemistry High 21849502
2011 Cytoplasmic AID in B cells exists in stoichiometric complex with eEF1A; the interaction depends on the C-terminal domain of eEF1A (not the GTP or tRNA binding regions) and on the AID region responsible for cytosolic retention, establishing eEF1A as a cytosolic retention factor for AID. Endogenous tagging of AID, co-immunoprecipitation, domain mapping, sucrose gradient sedimentation Proceedings of the National Academy of Sciences of the United States of America High 22042842
2012 PUF proteins (FBF) and Argonaute (CSR-1/Ago) form a conserved complex with eEF1A in both C. elegans and mammals; FBF-1–CSR-1 heterodimer inhibits eEF1A GTPase activity in vitro; the mammalian PUM2–Ago–eEF1A complex inhibits translation of reporters after initiation, causing ribosome accumulation within the ORF at the site where the nascent peptide exits the ribosome. Co-immunoprecipitation, recombinant protein pulldown, in vitro GTPase assay, in vitro translation with polysome/ribosome profiling Nature structural & molecular biology High 22231398
2012 eEF1A associates with defective ribosomal products (DRiPs) at the ribosome to generate a signal that triggers aggresome formation upon proteasome inhibition; the Legionella toxin SidI, which inhibits translation but spares this eEF1A function, demonstrated that the aggresome-signaling role of eEF1A is separable from its translation elongation function. siRNA knockdown, aggresome formation assay, SidI toxin pharmacological dissection Journal of cell science Medium 22357952
2013 eEF1A binds to Snail transcription factors (via their SNAG domain) when Snail is bound to the E-cadherin promoter, and escorts Snail from the nucleus to the cytoplasm via the Exportin5–aa-tRNA complex; this export is regulated by phosphorylation of Snail, establishing a nuclear role for eEF1A in attenuating transcription factor activity. Co-immunoprecipitation, nuclear export assay, chromatin immunoprecipitation, phosphorylation analysis Cell reports Medium 24209753
2014 eEF1A1 isoform (but not eEF1A2) participates in the entire heat shock response: upon stress it recruits HSF1 to the HSP70 promoter to activate transcription, then associates with elongating RNA Pol II and the HSP70 mRNA 3′UTR to stabilize it and facilitate nuclear-to-ribosome transport. eEF1A1 depletion severely impairs HSR and thermotolerance. siRNA knockdown, ChIP, RNA immunoprecipitation, live-cell imaging, RT-qPCR, thermotolerance assay eLife High 25233275
2014 METTL10 trimethylates eEF1A1 at lysine 318 in mammalian cells; siRNA-mediated knockdown of METTL10 decreases eEF1A1 K318 methylation in vivo, as confirmed using a selenium-based SAM analog (ProSeAM) and quantitative MS. ProSeAM chemical probe, affinity purification, quantitative MS, siRNA knockdown, biochemical characterization PloS one High 25144183
2015 eEF1A is the cytoplasmic retention factor for AID; the mechanism is independent of protein synthesis but requires a tRNA-free form of eEF1A. eEF1A and HSP90 interactions with AID are inversely correlated and define two sequential complexes: HSP90 produces functional AID, which is then stored by eEF1A in the cytoplasm. Inhibiting eEF1A allows AID nuclear accumulation, increasing class switch recombination and chromosomal translocations. Chemical inhibition of eEF1A, co-immunoprecipitation, nuclear export assay, class switch recombination assay, chromosomal translocation assay The Journal of experimental medicine High 25824822
2015 Direct interaction between eEF1A and HIV-1 reverse transcriptase (RT) has KD ~3–4 nM; both RT thumb and connection domains are required. A single W252A mutation in the RT thumb impairs co-IP with eEF1A and reduces late reverse transcription and virus replication. Didemnin B binds eEF1A and inhibits HIV-1 reverse transcription by >2 logs; W252A RT confers resistance to didemnin B, confirming eEF1A–RT interaction as the antiviral target. Biolayer interferometry, co-immunoprecipitation, site-directed mutagenesis, reverse transcription quantification, virus replication assay, drug resistance analysis PLoS pathogens High 26624286
2016 FAT10 competes with ubiquitin for binding to the same lysines on eEF1A1, forming FAT10–eEF1A1 complexes instead of Ub–eEF1A1 complexes; FAT10 overexpression therefore decreases eEF1A1 ubiquitination and proteasomal degradation, stabilizing eEF1A1 and promoting cancer cell proliferation. Co-immunoprecipitation, ubiquitination assay, lysine mutagenesis, cell proliferation assay Cancer research Medium 27312528
2017 METTL21B specifically trimethylates eEF1A Lys-165 in an aminoacyl-tRNA- and GTP-dependent manner; this methylation is dynamic and inducible by ER stress. Genetic ablation of METTL21B in mammalian cells alters mRNA translation dynamics and changes codon-specific translation rates as measured by ribosome profiling. METTL21B also accumulates in centrosomes. In vitro methylation assay, in vivo methylation analysis, METTL21B knockout, ribosome profiling, immunofluorescence localization Nucleic acids research High 28108655
2017 A novel 7β-strand KMT (eEF1A-KMT4 / EEF1AKMT4) trimethylates eEF1A at Lys36 in vitro and in vivo; KO of this enzyme in mammalian cells alters translation dynamics and changes translation speed of distinct codons by ribosome profiling. In vitro methylation assay, KO cell lines, ribosome profiling, active site mutagenesis Nucleic acids research High 28520920
2017 Expanded polyalanine tracts function as nuclear export signals by interacting with eEF1A1; GST-pulldown and MS identified eEF1A1 as the binding partner. Knockdown of eEF1A1 partially corrects cytoplasmic mislocalization of expanded poly(A) proteins and restores their nuclear transcription factor function. GST pulldown/MS, siRNA knockdown, subcellular localization assay, transcriptional reporter assay The Journal of biological chemistry Medium 28246169
2018 Human METTL13 contains two distinct methyltransferase domains: one methylates the eEF1A N-terminus and the other dimethylates Lys55. Structural analysis provided mechanistic detail on N-terminal recognition. Loss of METTL13 function alters translation dynamics and codon-specific translation rates by ribosome profiling. In vitro methylation biochemistry, X-ray crystallography (structural analysis), ribosome profiling, domain mutagenesis Nature communications High 30143613
2019 METTL13 dimethylates eEF1A Lys55 (eEF1AK55me2) and this modification increases eEF1A's intrinsic GTPase activity in vitro and protein production in cells. METTL13 deletion and loss of eEF1AK55me2 dramatically reduce Ras-driven neoplastic growth in mouse models and patient-derived xenografts. In vitro GTPase assay with methylated vs unmethylated eEF1A, METTL13 KO mouse models, PDX models, metabolic labeling of protein synthesis Cell High 30612740
2021 Plitidepsin's antiviral activity against SARS-CoV-2 is mediated through inhibition of host eEF1A; a drug-resistant eEF1A mutant demonstrated this mechanistic link, and plitidepsin reduced viral replication by two orders of magnitude in mouse models. Drug-resistant mutant selection, in vitro antiviral assay, in vivo mouse infection models Science High 33495306
2022 Single-molecule fluorescence imaging and cryo-EM showed that didemnin B and ternatin-4 both bind to a common site on eEF1A·GTP·aa-tRNA ternary complex and trap eEF1A in an intermediate state of aa-tRNA selection, preventing eEF1A release and aa-tRNA accommodation on the ribosome; the two compounds produce distinct effects on ternary complex dynamics that explain differences in their inhibition efficacy. Single-molecule FRET imaging, cryogenic electron microscopy, in vitro translation assay eLife High 36264623
2022 SR-A3 (a ternatin-family cyclic peptide) binds eEF1A with enhanced residence time and rebinding kinetics compared to SS-A3 epimer; single-molecule fluorescence imaging of elongation reactions with purified eEF1A defined the stereospecific binding kinetics. Prolonged target engagement correlated with antitumor efficacy in a Myc-driven mouse lymphoma model. Single-molecule fluorescence imaging (in vitro reconstituted elongation), stereospecific synthesis, in vivo mouse lymphoma model Nature chemistry High 36123449
2006 Tetrahymena eEF1A forms homodimers that bundle F-actin; eEF1A dimers (but not monomers) bind and bundle F-actin at a ~1:1 stoichiometry. Ca²⁺/calmodulin converts eEF1A dimers to monomers, releasing them from actin bundles in a reversible manner, providing a Ca²⁺-dependent regulatory mechanism for actin organization. Gel filtration chromatography, cosedimentation assay, electron microscopy, Ca²⁺/calmodulin treatment Journal of biochemistry Medium 16877446
2008 Domain 3 of Tetrahymena eEF1A is the primary F-actin binding domain and influences dimer formation; all three domains bind calmodulin in a Ca²⁺-dependent manner with distinct Ca²⁺ concentration thresholds, with domain 3 serving a pivotal role in Ca²⁺/calmodulin-regulated actin bundling. GST-domain fusion protein binding assays, cosedimentation, calmodulin interaction assay with Ca²⁺ titration Zoological science Medium 18275242
2007 ZPR1 binds preferentially to GDP-bound eEF1A; crystal structure of the ZPR1 domain tandem was determined and structure-based mutational analysis identified a conserved eEF1A-binding epitope required for normal cell growth, proliferation, and cell cycle progression. ZPR1 efficiently displaces eEF1Bα from nucleotide-free eEF1A complexes, suggesting it functions as a negative regulator of eEF1A activation. X-ray crystallography, co-immunoprecipitation, nucleotide exchange displacement assay, site-directed mutagenesis, yeast complementation Proceedings of the National Academy of Sciences of the United States of America High 17704259
2007 PASKIN kinase interacts with eEF1A1 through its PAS A and kinase domains (binding eEF1A1 C-terminus) and phosphorylates eEF1A1 primarily at Thr432; wild-type but not kinase-inactive PASKIN increases in vitro translation of a reporter cRNA, suggesting that PASKIN-dependent phosphorylation of eEF1A1 promotes translation. Yeast two-hybrid, mammalian two-hybrid, GST pulldown, in vitro kinase assay, MS, site-directed mutagenesis, in vitro translation assay Cellular physiology and biochemistry Medium 17595531
2010 eEF1A1 (but not eEF1A2) interacts with Ca²⁺/calmodulin; this interaction is predicted by molecular dynamics showing a less flexible calmodulin-binding region in eEF1A1, and confirmed experimentally by ELISA-based binding test. Calmodulin binding interferes with tRNA-binding and actin-bundling activities of eEF1A1 in vitro. Multiple molecular dynamics simulation, ELISA-based calmodulin binding assay, in vitro tRNA binding, in vitro actin bundling assay BMC structural biology Medium 18221514
2010 PKCβI co-immunoprecipitates with eEF1A in the nucleus of insulin-stimulated C2C12 myoblasts and phosphorylates eEF1A2 at Ser53 in vitro; the association between eEF1A2 and PKCβI is dependent on the phosphorylation status of eEF1A2, establishing PKCβI as a nuclear kinase for this elongation factor. Nuclear fractionation, co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, LC-MS/MS proteomics Molecular & cellular proteomics Medium 20923971
2002 Mammalian eEF1A·GDP forms a stable ternary complex with uncharged tRNA (Kd ~20 nM) and a quaternary complex with phenylalanyl-tRNA synthetase (Kd ~9 nM); direct eEF1A–PheRS interaction (Kd ~21 nM) is accelerated by tRNA, supporting a tRNA-channeling model in which the GDP-bound form of eEF1A participates in tRNA delivery to aminoacyl-tRNA synthetase. Gel retardation assay, surface plasmon resonance (BIAcore), fluorescence binding assay European journal of biochemistry Medium 12354112
2024 Chp1 is a dedicated ribosome-associated chaperone for eEF1A biogenesis: it is recruited to the ribosome via the nascent polypeptide-associated complex (NAC) during eEF1A synthesis. Absence of Chp1 causes instant proteolysis of nascent eEF1A, widespread protein aggregation, Hsf1 stress activation, and reduced cellular fitness. Chp1 also protects pathogenic eEF1A2 variants linked to epileptic-dyskinetic encephalopathy from degradation. Ribosome association assay, proteomics, protein aggregation assay, Hsf1 reporter assay, fitness assay, pathogenic variant expression Nature communications High 38360885
2019 Archaeal stalk protein aP1 C-terminal domain (CTD) binds eEF1A·GTP in a space between domains 1 and 3 of eEF1A (crystal structure at 3.0 Å); comparison with the aP1-CTD·eEF1A·GDP structure shows a marked change in binding mode upon GTP/GDP conformational switch, revealing how the stalk supports efficient elongation by engaging eEF1A in both nucleotide states. X-ray crystallography (3.0 Å), biochemical binding assay, in vitro translation assay Scientific reports Medium 31611569
2008 eEF1A associates with defective ribosomal products via its translation elongation activity and triggers aggresome formation; the novel eEF1A binding protein IGFN1 (found in yeast two-hybrid screen of human skeletal muscle library) interacts with eEF1A in vitro and is upregulated upon muscle denervation, suggesting it downregulates protein synthesis via eEF1A during denervation. Yeast two-hybrid, in vitro protein interaction confirmation Journal of cellular biochemistry Low 18756455
2012 eEF1A1 interacts with eEF1A1 is a cytoplasmic retention factor for AID; the mechanism requires a tRNA-free form of eEF1A confirmed by the functional consequence that inhibiting eEF1A releases AID to the nucleus increasing class switch recombination. (Note: primary mechanistic finding captured under PMID 22042842 and 25824822 above.) Chemical inhibition, nuclear accumulation assay The Journal of experimental medicine Low 25824822

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.) 257 33495306
2010 eEF1A: thinking outside the ribosome. The Journal of biological chemistry 216 20444696
2002 Exp5 exports eEF1A via tRNA from nuclei and synergizes with other transport pathways to confine translation to the cytoplasm. The EMBO journal 195 12426392
2015 The eEF1A Proteins: At the Crossroads of Oncogenesis, Apoptosis, and Viral Infections. Frontiers in oncology 176 25905039
2005 Increased proteasome activity, ubiquitin-conjugating enzymes, and eEF1A translation factor detected in breast cancer tissue. Cancer research 171 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 152 30612740
2014 The translation elongation factor eEF1A1 couples transcription to translation during heat shock response. eLife 140 25233275
2007 Interaction between the cellular protein eEF1A and the 3'-terminal stem-loop of West Nile virus genomic RNA facilitates viral minus-strand RNA synthesis. Journal of virology 129 17626087
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 97 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 85 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
2017 SPL33, encoding an eEF1A-like protein, negatively regulates cell death and defense responses in rice. Journal of experimental botany 78 28199670
1996 Assignment of human elongation factor 1alpha genes: EEF1A maps to chromosome 6q14 and EEF1A2 to 20q13.3. Genomics 78 8812466
2018 The dual methyltransferase METTL13 targets N terminus and Lys55 of eEF1A and modulates codon-specific translation rates. Nature communications 77 30143613
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
2008 Gamendazole, an orally active indazole carboxylic acid male contraceptive agent, targets HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A), and stimulates Il1a transcription in rat Sertoli cells. Biology of reproduction 71 18218611
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 65 27312528
2009 Structural models of human eEF1A1 and eEF1A2 reveal two distinct surface clusters of sequence variation and potential differences in phosphorylation. PloS one 62 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
2018 Regulation of eukaryotic elongation factor 1 alpha (eEF1A) by dynamic lysine methylation. RNA biology 48 29447067
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
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 45 21849502
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 44 22042842
2010 Phosphorylation of eEF1A1 at Ser300 by TβR-I results in inhibition of mRNA translation. Current biology : CB 44 20832312
2008 Novel cell death by downregulation of eEF1A1 expression in tetraploids. Cell death and differentiation 44 18820646
2008 The human Y-encoded testis-specific protein interacts functionally with eukaryotic translation elongation factor eEF1A, a putative oncoprotein. International journal of cancer 43 18649364
2006 Tetrahymena eukaryotic translation elongation factor 1A (eEF1A) bundles filamentous actin through dimer formation. Journal of biochemistry 43 16877446
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
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 41 17704259
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
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
2021 On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits. International journal of molecular sciences 31 34203525
2015 Consecutive interactions with HSP90 and eEF1A underlie a functional maturation and storage pathway of AID in the cytoplasm. The Journal of experimental medicine 31 25824822
2012 Association of translation factor eEF1A with defective ribosomal products generates a signal for aggresome formation. Journal of cell science 31 22357952
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
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 28 33529230
2018 Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress. Scientific reports 28 30224719
2014 EF1A interacting with nucleocapsid protein of transmissible gastroenteritis coronavirus and plays a role in virus replication. Veterinary microbiology 28 24974120
2022 Overexpressing eukaryotic elongation factor 1 alpha (eEF1A) proteins to promote corticospinal axon repair after injury. Cell death discovery 27 36123349
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 27 18221514
2022 Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes. eLife 26 36264623
2013 eEF1A mediates the nuclear export of SNAG-containing proteins via the Exportin5-aminoacyl-tRNA complex. Cell reports 26 24209753
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 Translation elongation factor eEF1A binds to a novel myosin binding protein-C-like protein. Journal of cellular biochemistry 26 18756455
2023 Epigenetic Control of Translation Checkpoint and Tumor Progression via RUVBL1-EEF1A1 Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 25 37075745
2012 From global phosphoproteomics to individual proteins: the case of translation elongation factor eEF1A. Expert review of proteomics 25 22292825
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
2007 Male germ cell expression of the PAS domain kinase PASKIN and its novel target eukaryotic translation elongation factor eEF1A1. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 24 17595531
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 24 15013623
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
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
2022 Nanoparticles (NPs)-mediated lncBCMA silencing to promote eEF1A1 ubiquitination and suppress breast cancer growth and metastasis. Acta pharmaceutica Sinica. B 21 37655325
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
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
2010 Glutamate regulates eEF1A phosphorylation and ribosomal transit time in Bergmann glial cells. Neurochemistry international 19 20817065
2019 Switch of the interactions between the ribosomal stalk and EF1A in the GTP- and GDP-bound conformations. Scientific reports 18 31611569
2008 BPOZ-2 directly binds to eEF1A1 to promote eEF1A1 ubiquitylation and degradation and prevent translation. Genes to cells : devoted to molecular & cellular mechanisms 18 18459963
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
2023 TOPK promotes the growth of esophageal cancer in vitro and in vivo by enhancing YB1/eEF1A1 signal pathway. Cell death & disease 17 37328464
2022 DNAJA1 Stabilizes EF1A1 to Promote Cell Proliferation and Metastasis of Liver Cancer Mediated by miR-205-5p. Journal of oncology 17 35586205
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
2024 Chp1 is a dedicated chaperone at the ribosome that safeguards eEF1A biogenesis. Nature communications 16 38360885
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
2015 Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target. PLoS pathogens 16 26624286
2008 Roles of three domains of Tetrahymena eEF1A in bundling F-actin. Zoological science 16 18275242

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