Affinage

EEF1A2

Elongation factor 1-alpha 2 · UniProt Q05639

Length
463 aa
Mass
50.5 kDa
Annotated
2026-06-09
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EEF1A2 is a tissue-restricted isoform of the translation elongation factor eEF1A whose expression is reciprocal with eEF1A1 and is essential for postnatal survival of neurons and muscle, as established by the lethal motor neuron degeneration of the Eef1a2-null wasted mouse and its rescue by transgenic eEF1A2 (PMID:9539760, PMID:17640869, PMID:19094180). In its canonical role it delivers aminoacyl-tRNAs during elongation, an activity directly demonstrated through tRNA-binding and de novo synthesis assays of patient mutants and through complementation of yeast eEF1A deletion (PMID:37695913, PMID:32196822, PMID:28911200). Beyond bulk elongation, eEF1A2 binds the utrophin A 5'-UTR to drive cap-independent (IRES) translation specifically in skeletal muscle, a mechanism that can be pharmacologically exploited to improve the dystrophic phenotype of mdx mice (PMID:20053670, PMID:32332749). eEF1A2 has a second, isoform-specific cytoskeletal function as an actin-bundling protein; in dendritic spines, phosphorylation of isoform-specific sites toggles it between an elongation-competent state and an actin-regulating state, with mGluR signaling triggering its dissociation from its guanine-exchange factor (PMID:34257105), and disease mutations simultaneously increase tRNA binding while reducing actin bundling (PMID:37695913). eEF1A2 also functions as a potent oncogene: it transforms fibroblasts and confers anchorage-independent growth (PMID:12053177), and it activates PI3K/AKT signaling to promote migration, invasion and MMP-9-dependent metastasis, to stabilize MDM4 and inactivate p53, and to support JAK/STAT-dependent tumor cell survival (PMID:17130842, PMID:23739844, PMID:24285179, PMID:20505761). Mechanistically it directly binds and activates PI4KIIIβ to generate PI(4)P (PMID:17088255, PMID:21851817), interacts with HSP90β to amplify TGF-β/SMAD3 signaling (PMID:33473168), sequesters and inhibits the pro-apoptotic kinase PKR (PMID:30420615), and participates in HIF1A/VEGF angiogenic feedback (PMID:38012382). Its abundance and activity are heavily post-translationally controlled — by KAT8-installed K408 lactylation that boosts elongation (PMID:38359291), by METTL14 m6A and NSUN6 m5C marks on its mRNA (PMID:35013140, PMID:37614424), and by ubiquitin-dependent turnover regulated by SNX16 and A20 (PMID:31876369, PMID:37399716). eEF1A2 is the molecular target of the anticancer drug plitidepsin, which binds the domain 1/2 interface in the GTP conformation and releases PKR to trigger apoptosis (PMID:27713531, PMID:30420615). Heterozygous de novo EEF1A2 variants cause neurodevelopmental disease, acting through haploinsufficiency or toxic gain-of-function depending on the allele (PMID:32196822, PMID:37695913, PMID:28911200).

Mechanistic history

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

    Established that a tissue-specific elongation factor isoform is non-redundant and essential, reframing translation elongation machinery as developmentally specialized rather than uniform.

    Evidence Genetic deletion mapping and Northern blot of the lethal wasted mouse, showing reciprocal eEF1A1/eEF1A2 expression in heart and muscle

    PMID:9539760

    Open questions at the time
    • Did not define the molecular basis of why eEF1A1 cannot substitute
    • No structural or biochemical distinction between isoforms shown
  2. 2002 High

    Showed that an elongation factor can act as a bona fide oncogene, opening the question of how a translation factor drives transformation.

    Evidence Focus formation, anchorage-independent growth, and nude mouse xenografts of eEF1A2-expressing fibroblasts

    PMID:12053177

    Open questions at the time
    • Did not identify the signaling effectors mediating transformation
    • Did not separate translational from non-translational contributions
  3. 2006 High

    Identified the PI3K/AKT axis and direct PI4KIIIβ activation as the signaling mechanisms underlying eEF1A2 oncogenicity, distinguishing its moonlighting roles from elongation.

    Evidence siRNA/overexpression with phospho-Akt blots and inhibitors; in vitro lipid kinase assay with purified recombinant eEF1A2 and cellular PI4P measurement

    PMID:17088255 PMID:17130842

    Open questions at the time
    • Mechanism by which eEF1A2 activates PI3K not resolved
    • Did not show whether PI4KIIIβ activation and AKT activation are linked
  4. 2007 High

    Demonstrated isoform-specific protein partnerships, beginning the dissection of why eEF1A2 (not eEF1A1) confers survival advantages.

    Evidence Yeast two-hybrid and reciprocal co-IP of eEF1A2 with peroxiredoxin I; cell death and caspase assays; transgenic rescue confirming eEF1A2 loss alone causes wasted phenotype

    PMID:16888816 PMID:17640869

    Open questions at the time
    • Structural basis of isoform-specific Prdx-I binding not defined
    • Prdx-I interaction not linked to elongation activity
  5. 2010 High

    Revealed a non-canonical mRNA-selective translational role, showing eEF1A2 acts as an IRES trans-factor for utrophin A in muscle.

    Evidence RNA-affinity chromatography/MS, UV-crosslinking, IRES reporter assays and transgenic mice; parallel shRNA work linking knockdown to JAK/STAT and PI3K/AKT defects

    PMID:20053670 PMID:20505761

    Open questions at the time
    • Sequence/structural determinants of 5'-UTR recognition not mapped
    • Whether IRES binding uses the tRNA or actin surface unknown
  6. 2013 Medium

    Connected eEF1A2 to tumor-suppressor control and downstream proteolytic/metastatic programs, positioning it within established cancer pathways.

    Evidence Yeast two-hybrid and domain mapping of p16(INK4a) interaction with translation reporter assays; siRNA/overexpression with MMP-9 zymography and Akt inhibition in pancreatic cancer

    PMID:23444377 PMID:23739844

    Open questions at the time
    • p16-eEF1A2 interaction not confirmed by mammalian co-IP
    • Direct vs indirect control of MMP-9 not established
  7. 2016 High

    Identified eEF1A2 as the direct molecular target of plitidepsin, providing both a pharmacological tool and a defined binding site on the protein.

    Evidence Binding affinity (KD 80 nM), [14C]-drug pull-down, resistance selection with ectopic rescue, live-cell FLIM-FRET, and molecular modeling of the domain 1/2 interface in GTP conformation

    PMID:27713531

    Open questions at the time
    • Co-crystal structure not solved
    • Whether drug binding blocks elongation or moonlighting functions not separated
  8. 2018 Medium

    Explained the apoptotic consequence of plitidepsin by showing eEF1A2 sequesters and inhibits the pro-apoptotic kinase PKR.

    Evidence Reciprocal co-IP, HPLC-MS, proximity ligation assay, and plitidepsin displacement experiments linking PKR release to MAPK/NF-κB-driven apoptosis

    PMID:30420615

    Open questions at the time
    • Stoichiometry and structural basis of PKR sequestration not defined
    • Single lab; functional consequence shown chemically rather than genetically
  9. 2021 High

    Resolved how a single protein partitions between elongation and actin functions, showing phosphorylation toggles eEF1A2 between the two activities in dendritic spines.

    Evidence Phosphomutant/phosphomimetic constructs with translation, actin-dynamics, spine-density, and GEF-interaction readouts under mGluR signaling

    PMID:34257105

    Open questions at the time
    • The kinase responsible for spine phosphorylation not identified
    • Identity of the GEF in this context not molecularly defined
  10. 2023 High

    Mechanistically connected patient mutations to disease by showing dual disruption of tRNA availability and actin bundling, distinguishing haploinsufficient from gain-of-function alleles.

    Evidence Heterologous expression in HEK293 and cortical neurons with puromycin synthesis, elongation rate, tRNA-binding and actin-bundling assays; prior yeast complementation and zebrafish rescue defining variant effects

    PMID:28911200 PMID:32196822 PMID:37695913

    Open questions at the time
    • How increased tRNA binding mechanistically slows elongation not fully explained
    • In vivo neuronal phenotypes of specific gain-of-function alleles not modeled
  11. 2024 Medium

    Established post-translational and post-transcriptional regulatory layers controlling eEF1A2 abundance and elongation activity in cancer.

    Evidence KAT8-mediated K408 lactylation with translation/tumor assays; METTL14 m6A and NSUN6 m5C mRNA modifications; SNX16 and A20 ubiquitination control; SIMALR lncRNA enhancing GTPase activity

    PMID:31876369 PMID:35013140 PMID:37399716 PMID:37614424 PMID:38359291 PMID:39154122

    Open questions at the time
    • Interplay between these regulatory marks not integrated
    • Several mechanisms shown in single labs without independent replication

Open questions

Synthesis pass · forward-looking unresolved questions
  • How eEF1A2's elongation, IRES-trans-factor, actin-bundling, and signaling activities are coordinated within a single tissue context, and which surface determines each isoform-specific partnership, remains unresolved.
  • No high-resolution structure of mammalian eEF1A2 with partners
  • Mechanism switching between elongation and moonlighting functions in vivo unclear
  • Whether oncogenic signaling depends on elongation activity not definitively separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 3 GO:0008092 cytoskeletal protein binding 3 GO:0045182 translation regulator activity 3 GO:0003924 GTPase activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3
Partners
CDKN2AEIF2AK2HSP90AB1KAT8PI4KBPRDX1SNX16TNFAIP3
Complex memberships
eEF1B complex (eEF1A2-associated)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 The lethal wasted (wst) mouse phenotype is caused by a 15.8 kb deletion that abolishes expression of Eef1a2, a tissue-specific translation elongation factor. eEF1A2 expression is reciprocal with eEF1A1 in heart and muscle postnatally, establishing that tissue-specific isoforms of the translation elongation apparatus are essential for postnatal survival. Genetic deletion mapping, Northern blot expression analysis, in vivo mouse genetics Proceedings of the National Academy of Sciences of the United States of America High 9539760
2007 Transgenic rescue experiments established that loss of eEF1A2 function alone is responsible for all abnormalities in wasted mice, including motor neuron degeneration. eEF1A2 is expressed at high levels in specific cell types including pancreatic islet cells and enteroendocrine cells. Expression of eEF1A1 and eEF1A2 is mutually exclusive in individual cell types, and the motor neuron degeneration phenotype relates precisely to the relative expression of the two isoforms. Transgenic rescue, anti-peptide antibody immunohistochemistry, cell-type-specific expression analysis The Journal of biological chemistry High 17640869
2002 EEF1A2 has oncogenic properties: it enhances focus formation, allows anchorage-independent growth, decreases doubling time of rodent fibroblasts, and makes NIH3T3 fibroblasts tumorigenic in nude mice, establishing EEF1A2 as a functional oncogene. Focus formation assay, anchorage-independent growth assay, xenograft tumor model Nature genetics High 12053177
2006 eEF1A2 expression is sufficient to activate Akt in a PI3K-dependent manner, stimulate filopodia formation dependent on PI3K, ROCK, and Akt kinases, and promote cell migration and invasion in breast cancer cells. siRNA-mediated reduction of eEF1A2 reduces Akt activity. siRNA knockdown, Western blot for phospho-Akt, filopodia imaging, migration/invasion assays with kinase inhibitors Oncogene High 17130842
2006 eEF1A2 directly binds to and activates phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ). Purified recombinant eEF1A2 increases PI4KIIIβ lipid kinase activity in vitro, and eEF1A2 expression in cells increases cellular PI4-kinase activity and intracellular phosphatidylinositol 4-phosphate abundance. siRNA knockdown of eEF1A2 concomitantly reduces PI4-kinase activity. In vitro lipid kinase assay with purified recombinant proteins, siRNA knockdown, cellular PI4P measurement The Journal of biological chemistry High 17088255
2007 Mouse eEF1A2 interacts with peroxiredoxin I (Prdx-I) but not with its isoform eEF1A1. The eEF1A2–Prdx-I complex confers resistance to peroxide-induced cell death, reducing activation of caspases 3 and 8 and increasing Akt expression. This interaction is isoform-specific. Yeast two-hybrid screening, co-immunoprecipitation from cells and mouse tissues, double transfectant cell death assays, caspase activation assays Journal of cellular biochemistry Medium 16888816
2014 EEF1A2 acts as an upstream inducer of PI3K to support MDM4 stabilization in hepatocellular carcinoma. The EEF1A2/PI3K/AKT/mTOR axis promotes protumorigenic stabilization of MDM4 via post-transcriptional mechanism, inactivating p53. EEF1A2, phosphorylated AKT, and MDM4 expression are strongly correlated (each rho >0.8) in human HCC. Silencing and overexpression experiments in HCC cell lines, PI3K/AKT/mTOR pathway inhibition, Western blot, in vivo AKT mouse model, human HCC tissue correlation analysis Hepatology (Baltimore, Md.) Medium 24285179
2010 eEF1A2 binds the 5'-UTR of utrophin A mRNA and promotes IRES-dependent (cap-independent) translation specifically in skeletal muscle. RNA-affinity chromatography identified eEF1A2 as a trans-factor binding the utrophin A 5'-UTR; UV-crosslinking confirmed specificity. Cells lacking eEF1A2 had reduced IRES activity, while eEF1A2 overexpression increased it. RNA-affinity chromatography combined with mass spectrometry, UV-crosslinking, IRES reporter assays in cultured cells, transgenic mice Human molecular genetics High 20053670
2016 eEF1A2 is the primary anticancer target of plitidepsin. The drug interacts with eEF1A2 with a KD of 80 nM. Tumor cell lines selected for ≥100-fold plitidepsin resistance show reduced eEF1A2 protein levels; ectopic eEF1A2 expression in resistant cells restores plitidepsin sensitivity. FLIM-phasor FRET experiments demonstrate drug-protein complex formation in living cells. Molecular modelling identifies a binding site at the interface of domains 1 and 2 of eEF1A2 in the GTP conformation. Binding affinity measurements, [14C]-plitidepsin cell lysate pull-down, resistance selection, ectopic expression rescue, FLIM-phasor FRET in living cells, molecular modelling Scientific reports High 27713531
2013 Tumor suppressor p16(INK4a) directly interacts with eEF1A2 (identified by yeast two-hybrid), binding all domains except D2 (250–327 aa). Ectopic p16(INK4a) expression decreases eEF1A2 expression and suppresses protein synthesis as measured by luciferase reporter activity. Microinjection of p16(INK4a) mRNA into Xenopus embryos suppressed luciferase mRNA translation, and combined p16(INK4a) plus morpholino-eEF1A2 further reduced translational activity. Yeast two-hybrid, domain mapping, luciferase reporter translation assay, Xenopus embryo microinjection with morpholino knockdown Journal of cell science Medium 23444377
2018 eEF1A2 binds to double-stranded RNA-activated protein kinase (PKR), inhibiting its pro-apoptotic kinase activity likely through sequestration. Targeting eEF1A2 with plitidepsin releases PKR from the complex, facilitating PKR activation, triggering MAPK signaling and NF-κB-dependent extrinsic apoptosis, leading to tumor cell death. Co-immunoprecipitation, HPLC-mass spectrometry, proximity ligation assay, plitidepsin displacement experiments, cell death assays British journal of cancer Medium 30420615
2021 Phosphorylation of isoform-specific sites in eEF1A2 coordinates translation and actin dynamics in dendritic spines. A nonphosphorylatable eEF1A2 mutant stimulates mRNA translation but reduces actin dynamics and spine density. A phosphomimetic mutant exhibits decreased F-actin association and is inactive as a translation elongation factor. Metabotropic glutamate receptor signaling triggers transient phosphorylation-dependent dissociation of eEF1A2 from its guanine exchange factor in dendritic spines. Phosphomutant/phosphomimetic expression, translation assays, actin dynamics imaging, dendritic spine density quantification, mGluR signaling experiments with co-localization Science signaling High 34257105
2023 Three patient-associated EEF1A2 mutations (G70S, E122K, D252H) decrease de novo protein synthesis and elongation rates in HEK293 cells. In mouse cortical neurons these mutations decrease protein synthesis and alter neuronal morphology independently of endogenous eEF1A2 levels, indicating toxic gain-of-function. Mutant eEF1A2 proteins display increased tRNA binding and decreased actin-bundling activity, suggesting dual disruption of tRNA availability and actin cytoskeleton. Heterologous expression in HEK293 cells and mouse cortical neurons, puromycin incorporation (de novo synthesis assay), elongation rate measurement, tRNA binding assay, actin-bundling assay Proceedings of the National Academy of Sciences of the United States of America High 37695913
2009 Three-dimensional homology models of eEF1A1 and eEF1A2 based on yeast eEF1A crystal structure reveal that nearly all variant surface-exposed residues lie in two proximal but distinct sub-clusters on one face of the protein. No buried residue differences are predicted to affect protein fold or domain-domain interactions. Predicted variant-specific phosphorylation sites may explain functional differences between the two isoforms. Comparative 3D homology modelling validated against yeast crystal structure, surface electrostatic and lipophilic property analysis, sequence-based phosphorylation prediction PloS one Medium 19636410
2013 eEF1A2 promotes cell migration, invasion, and peritoneal metastasis in pancreatic cancer through upregulation of MMP-9 expression and activity. This effect is dependent on eEF1A2-induced Akt activation; inhibition of MMP-9 activity or Akt reduces the promoting effect of eEF1A2 on cell migration and invasion. siRNA knockdown, ectopic overexpression, migration/invasion assays, MMP-9 activity assay (gelatin zymography), Akt inhibition, in vivo peritoneal metastasis mouse model Clinical & experimental metastasis Medium 23739844
2010 shRNA-mediated knockdown of Eef1a2 in mouse plasmacytomas causes growth inhibition from delayed G1-S progression and apoptosis under serum-starved conditions. Transcriptional profiling and Western blot reveal impaired JAK/STAT and PI3K/AKT signaling as downstream consequences of Eef1a2 knockdown. shRNA knockdown, flow cytometry cell cycle analysis, apoptosis assay, transcriptional profiling, Western blot for JAK/STAT and PI3K/AKT pathway components PloS one Medium 20505761
2021 EEF1A2 interacts with HSP90AB1 (Hsp90β) to increase TGF-β receptor I and II expression, enhancing SMAD3 phosphorylation and nuclear localization, thereby promoting epithelial-mesenchymal transition and metastasis of lung adenocarcinoma cells. LC-MS/MS proteomics identification of binding partners, co-immunoprecipitation, immunofluorescence co-localization, in vitro and in vivo metastasis assays, Western blot for TGF-β signaling components British journal of cancer Medium 33473168
2020 Heterozygous de novo EEF1A2 variants are functionally validated as protein-damaging using heterologous expression and complementation analysis in yeast. Pathogenic variants disrupt both the protein synthesis and integrated stress response functions of eEF1A2, and appear to act via haploinsufficiency. Heterologous expression, yeast complementation assay, functional translation assays Human mutation Medium 32196822
2017 In zebrafish, eef1a2 deficiency (morpholino knockdown) causes skeletal muscle weakness, cardiac failure, and small heads. Human wild-type EEF1A2 mRNA rescues the morphant phenotype, but the pathogenic p.P333L mutant RNA does not, confirming that the mutation impairs eEF1A2 function. In yeast, previously identified de novo mutations fail to complement eEF1A ortholog deletion (growth defect), while p.P333L causes a milder growth defect without dominant-negative effect. Zebrafish morpholino knockdown, mRNA rescue experiment, yeast complementation assay Human molecular genetics High 28911200
2017 eEF1A1 (but not eEF1A2) binds calmodulin, which interferes with eEF1A1's tRNA-binding and actin-bundling activities in vitro. Both isoforms exhibit actin-bundling activity but form morphologically distinct bundle types. eEF1A2 cannot be controlled by Ca2+-mediated regulatory systems through calmodulin. In vitro binding assays, actin-bundling assay, tRNA-binding assay, calmodulin pull-down Biological chemistry Medium 27483363
2014 The eEF1B complex subunits (eEF1Bα, eEF1Bδ, eEF1Bγ) co-localize with both eEF1A1 and eEF1A2 in sufficiently close proximity to suggest complex formation. Ablation of any eEF1B subunit in human cell lines has a small but significant impact on cell viability and cycling. Co-localization immunofluorescence/proximity assay, siRNA knockdown of eEF1B subunits, cell viability and cell cycle assays PloS one Low 25436608
2020 Transient overexpression of eEF1A2 in mouse muscles increases IRES-mediated translation of utrophin A. FDA-approved drugs that increase eEF1A2 protein levels also upregulate utrophin A, and treatment of mdx mice with two top lead compounds improves the dystrophic phenotype, establishing eEF1A2-driven IRES translation of utrophin A as a therapeutically relevant mechanism. Transient overexpression in mouse muscle, IRES reporter assay, ELISA-based high-throughput drug screen, mdx mouse treatment with phenotypic assessment Nature communications High 32332749
2011 eEF1A2 expression phenocopies PI4KIIIβ in disrupting three-dimensional mammary acinar morphogenesis. Both eEF1A2 and PI4KIIIβ alter intracellular localization of PI(4)P and PI(4,5)P2 within acini, indicating that eEF1A2-mediated PI4P generation is relevant to mammary neoplasia. 3D acinar morphogenesis assay in MCF10A cells, PI(4)P and PI(4,5)P2 localization by immunofluorescence, ectopic expression of eEF1A2 and PI4KIIIβ Experimental cell research Medium 21851817
2024 KAT8 acts as a pan-lysine lactyltransferase (Kla writer) responsible for installing lactylation on eEF1A2 at K408. Lactylation of eEF1A2-K408 boosts translation elongation and enhances protein synthesis, contributing to colorectal carcinogenesis. Deletion of KAT8 inhibits CRC tumor growth, especially in a high-lactic tumor microenvironment. Global lactylation profiling in CRC, screening of eEF1A2-interacting proteins, KAT8 identification as lactyltransferase, site-specific lactylation at K408, in vitro and in vivo translation/tumor growth assays, KAT8 deletion experiments Proceedings of the National Academy of Sciences of the United States of America Medium 38359291
2022 METTL14-mediated m6A modification of EEF1A2 mRNA decreases EEF1A2 expression. Silencing METTL14 inhibits m6A modification of EEF1A2, increases EEF1A2 protein levels, and activates the Akt/mTOR pathway to promote spinal cord neuron survival. Overexpression of EEF1A2 promotes neuron viability and inhibits apoptosis via Akt/mTOR activation. m6A methylation assay, METTL14 silencing/overexpression, EEF1A2 overexpression, Western blot for Akt/mTOR pathway, apoptosis and viability assays in rat SCI model Cell death discovery Medium 35013140
2020 SNX16 interacts with eEF1A2 and inhibits its ubiquitination and proteasomal degradation, leading to eEF1A2 protein stabilization and downstream activation of c-Myc signaling in colorectal cancer. Co-immunoprecipitation of SNX16-eEF1A2 complex, ubiquitination assay, proteasome inhibitor experiments, c-Myc pathway analysis by Western blot Molecular oncology Medium 31876369
2023 A20 interacts with eEF1A2 through its ZnF4 domain to ubiquitinate and degrade eEF1A2. Nrf2 transcriptionally regulates A20 expression by binding its promoter. This Nrf2/A20/eEF1A2 axis modulates NF-κB pathway activity and regulates pyroptosis in cerebral ischemia-reperfusion injury. Co-immunoprecipitation, dual-luciferase reporter assay, chromatin immunoprecipitation, gene overexpression/silencing experiments, Western blot Biomedicine & pharmacotherapy Medium 37399716
2023 NSUN6 methylates EEF1A2 mRNA at m5C sites and increases mRNA stability in an m5C-dependent manner, thereby upregulating EEF1A2 expression and activating the Akt/mTOR signaling pathway in osteosarcoma. RNA immunoprecipitation (RIP), methylated RIP assay, NSUN6 knockdown/overexpression, mRNA stability assay, Western blot for Akt/mTOR pathway Experimental and therapeutic medicine Medium 37614424
2008 Loss of eEF1A2 expression in motor neurons of wasted mice triggers dying-back neuropathy with synaptic loss at the neuromuscular junction preceding axonal pathology, morphologically distinct from Wallerian degeneration. Loss of eEF1A2 also significantly delays Wallerian degeneration after nerve lesion, and correlates with reduced ZPR1 expression. In vivo neuromuscular junction morphology analysis, tibial nerve lesion model, immunohistochemistry for eEF1A2 and ZPR1, comparison of wasted vs. wild-type mice Journal of anatomy Medium 19094180
2024 SIMALR lncRNA binds eEF1A2 and enhances its endogenous GTPase activity. SIMALR further mediates activation of eEF1A2 phosphorylation to accelerate translation of ITGB4/ITGA6 mRNAs, promoting NPC malignant phenotype. RNA-binding assay (SIMALR-eEF1A2 interaction), GTPase activity assay, phosphorylation analysis, polysome profiling for target mRNA translation Oncogene Low 39154122
2023 EEF1A2 acts as an RNA-binding protein/transcriptional co-factor that cooperates with circ-CDYL to initiate COL14A1 transcription in hepatocellular carcinoma cancer stem cells, promoting ERK signaling and EMT-driven lung metastasis. Mechanistic studies identifying EEF1A2 as transcriptional co-factor with circ-CDYL; COL14A1 transcription assay; ERK signaling pathway analysis Cancer letters Low 37852428
2008 ZNF217-induced neoplastic properties in ovarian surface epithelial cells are mediated through eEF1A2: siRNA targeting eEF1A2 efficiently inhibits both anchorage independence and resistance to apoptosis conferred by ZNF217 overexpression, placing eEF1A2 downstream of ZNF217 in this oncogenic pathway. Lentiviral overexpression, siRNA knockdown, anchorage-independent growth assay, apoptosis resistance assay, array CGH, SNP analysis International journal of cancer Medium 18661515
2020 eEF1A2 knockdown in MPP+-treated dopaminergic cells decreases autophagy markers (LC3-II/LC3-I ratio, LC3 puncta, phospho-Beclin-1), reduces mitophagy, aggravates α-synuclein accumulation, and increases apoptosis, indicating eEF1A2 is required for autophagic flux and dopaminergic neuron survival under oxidative stress. eEF1A2 siRNA knockdown in differentiated SH-SY5Y cells with MPP+ treatment, LC3 immunofluorescence, mitochondrial membrane potential assay, caspase-3/7 activation assay Neuroscience research Medium 32275913
2023 EEF1A2 promotes HIF1A expression via ERK-Myc and mTOR signaling under normoxia, and hypoxia induces EEF1A2 expression; HIF1A binds the EEF1A2 promoter and induces its transcription, creating a positive feedback loop. EEF1A2 positively affects VEGF transcription and translation, increasing VEGF release to activate ERK and PI3K-AKT signaling in endothelial cells. Luciferase assay and EMSA confirming HIF1A binding to EEF1A2 promoter, RT-PCR, polysome profiling for VEGF translation, angiogenesis assays (CAM, tubulogenesis, aortic ring, Matrigel plug) British journal of cancer Medium 38012382

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2024 KAT8-catalyzed lactylation promotes eEF1A2-mediated protein synthesis and colorectal carcinogenesis. Proceedings of the National Academy of Sciences of the United States of America 222 38359291
2005 Chemoenzymatically synthesized multimeric Tn/STn MUC1 glycopeptides elicit cancer-specific anti-MUC1 antibody responses and override tolerance. Glycobiology 210 16207894
2002 Protein elongation factor EEF1A2 is a putative oncogene in ovarian cancer. Nature genetics 206 12053177
2016 Tumor-associated antigens: Tn antigen, sTn antigen, and T antigen. HLA 173 27679419
1996 Antibodies against mucin-associated sialyl-Tn epitopes correlate with survival of metastatic adenocarcinoma patients undergoing active specific immunotherapy with synthetic STn vaccine. Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy 164 8859725
1998 The lethal mutation of the mouse wasted (wst) is a deletion that abolishes expression of a tissue-specific isoform of translation elongation factor 1alpha, encoded by the Eef1a2 gene. Proceedings of the National Academy of Sciences of the United States of America 136 9539760
2006 eEF1A2 activates Akt and stimulates Akt-dependent actin remodeling, invasion and migration. Oncogene 120 17130842
2005 Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours. BMC cancer 115 16156888
1998 Mutation of invH, but not stn, reduces Salmonella-induced enteritis in cattle. Infection and immunity 110 9529064
2012 Structural and resting state functional connectivity of the subthalamic nucleus: identification of motor STN parts and the hyperdirect pathway. PloS one 108 22768059
1999 Evidence of a cellular immune response against sialyl-Tn in breast and ovarian cancer patients after high-dose chemotherapy, stem cell rescue, and immunization with Theratope STn-KLH cancer vaccine. Journal of immunotherapy (Hagerstown, Md. : 1997) 96 9924700
1995 Immunogenicity of synthetic TF-KLH (keyhole limpet hemocyanin) and sTn-KLH conjugates in colorectal carcinoma patients. Cancer immunology, immunotherapy : CII 95 7553688
2004 Vaccination with Theratope (STn-KLH) as treatment for breast cancer. Expert review of vaccines 92 15606349
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
2019 Cross-talk between Colon Cells and Macrophages Increases ST6GALNAC1 and MUC1-sTn Expression in Ulcerative Colitis and Colitis-Associated Colon Cancer. Cancer immunology research 83 31831633
2014 EEF1A2 inactivates p53 by way of PI3K/AKT/mTOR-dependent stabilization of MDM4 in hepatocellular carcinoma. Hepatology (Baltimore, Md.) 81 24285179
1996 Assignment of human elongation factor 1alpha genes: EEF1A maps to chromosome 6q14 and EEF1A2 to 20q13.3. Genomics 78 8812466
2016 Translation Elongation Factor eEF1A2 is a Novel Anticancer Target for the Marine Natural Product Plitidepsin. Scientific reports 74 27713531
2010 Effects of STN stimulation on the initiation and inhibition of saccade in Parkinson disease. Neurology 70 20194913
2014 De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability, autistic behaviors and epilepsy. Clinical genetics 68 24697219
2015 The androgen receptor controls expression of the cancer-associated sTn antigen and cell adhesion through induction of ST6GalNAc1 in prostate cancer. Oncotarget 67 26452038
2011 Enhancement of the immunogenicity of synthetic carbohydrate vaccines by chemical modifications of STn antigen. ACS chemical biology 67 21121644
2000 Clinical outcome of breast and ovarian cancer patients treated with high-dose chemotherapy, autologous stem cell rescue and THERATOPE STn-KLH cancer vaccine. Bone marrow transplantation 67 10871727
2007 Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21. Clinical cancer research : an official journal of the American Association for Cancer Research 66 17504999
2007 Translation elongation factor eEF1A2 is essential for post-weaning survival in mice. The Journal of biological chemistry 64 17640869
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
2015 miR-663 attenuates tumor growth and invasiveness by targeting eEF1A2 in pancreatic cancer. Molecular cancer 61 25744894
2010 Eef1a2 promotes cell growth, inhibits apoptosis and activates JAK/STAT and AKT signaling in mouse plasmacytomas. PloS one 61 20505761
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
2006 Expression of protein elongation factor eEF1A2 predicts favorable outcome in breast cancer. Breast cancer research and treatment 59 16897428
2013 The major thylakoid protein kinases STN7 and STN8 revisited: effects of altered STN8 levels and regulatory specificities of the STN kinases. Frontiers in plant science 57 24151498
2003 Rationale for the clinical development of STn-KLH (Theratope) and anti-MUC-1 vaccines in breast cancer. Clinical breast cancer 57 12620150
2013 eEF1A2 promotes cell migration, invasion and metastasis in pancreatic cancer by upregulating MMP-9 expression through Akt activation. Clinical & experimental metastasis 56 23739844
2016 Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability. Molecular genetics & genomic medicine 51 27441201
2006 Improving the antigenicity of sTn antigen by modification of its sialic acid residue for development of glycoconjugate cancer vaccines. Bioconjugate chemistry 51 17105234
2008 Synthetic and immunological studies of 5'-N-phenylacetyl sTn to develop carbohydrate-based cancer vaccines and to explore the impacts of linkage between carbohydrate antigens and carrier proteins. Bioconjugate chemistry 50 18816108
2021 EEF1A2 interacts with HSP90AB1 to promote lung adenocarcinoma metastasis via enhancing TGF-β/SMAD signalling. British journal of cancer 49 33473168
2001 Theratope vaccine (STn-KLH). Expert opinion on biological therapy 46 11728222
2014 Up-regulation of eEF1A2 promotes proliferation and inhibits apoptosis in prostate cancer. Biochemical and biophysical research communications 45 24853801
2009 eEF1A2 as a putative oncogene. Annals of the New York Academy of Sciences 45 19723040
1995 Salmonella enterotoxin (stn) gene is prevalent among strains of Salmonella enterica, but not among Salmonella bongori and other Enterobacteriaceae. FEMS immunology and medical microbiology 45 8580901
2003 The role of protein elongation factor eEF1A2 in ovarian cancer. Reproductive biology and endocrinology : RB&E 42 14588074
2009 Regulation and functional role of eEF1A2 in pancreatic carcinoma. Biochemical and biophysical research communications 38 19138673
2007 Real-time PCR method for Salmonella spp. targeting the stn gene. Journal of applied microbiology 38 17241358
2023 Hypoxia-induced circ-CDYL-EEF1A2 transcriptional complex drives lung metastasis of cancer stem cells from hepatocellular carcinoma. Cancer letters 34 37852428
2020 Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy. Human mutation 34 32196822
2020 Experimental investigation into the role of the subthalamic nucleus (STN) in motor control using optogenetics in mice. Brain research 34 33358727
1999 Serological studies on CEA, CA 19-9, STn and SLX in colorectal cancer. Hepato-gastroenterology 34 10370638
2006 Binding of elongation factor eEF1A2 to phosphatidylinositol 4-kinase beta stimulates lipid kinase activity and phosphatidylinositol 4-phosphate generation. The Journal of biological chemistry 33 17088255
2022 METTL14 promotes apoptosis of spinal cord neurons by inducing EEF1A2 m6A methylation in spinal cord injury. Cell death discovery 32 35013140
2020 Extended half-life target module for sustainable UniCAR T-cell treatment of STn-expressing cancers. Journal of experimental & clinical cancer research : CR 32 32370811
2018 Binding of eEF1A2 to the RNA-dependent protein kinase PKR modulates its activity and promotes tumour cell survival. British journal of cancer 32 30420615
2015 Two cases of early-onset myoclonic seizures with continuous parietal delta activity caused by EEF1A2 mutations. Brain & development 32 26682508
2013 Tumor suppressor p16(INK4a) inhibits cancer cell growth by downregulating eEF1A2 through a direct interaction. Journal of cell science 32 23444377
2003 The stn-1 syntrophin gene of C.elegans is functionally related to dystrophin and dystrobrevin. Journal of molecular biology 32 14499607
2021 On the Need to Tell Apart Fraternal Twins eEF1A1 and eEF1A2, and Their Respective Outfits. International journal of molecular sciences 31 34203525
2020 SNX16 activates c-Myc signaling by inhibiting ubiquitin-mediated proteasomal degradation of eEF1A2 in colorectal cancer development. Molecular oncology 31 31876369
2008 unc-44 Ankyrin and stn-2 gamma-syntrophin regulate sax-7 L1CAM function in maintaining neuronal positioning in Caenorhabditis elegans. Genetics 31 18791240
2007 Expression of eEF1A2 is associated with clear cell histology in ovarian carcinomas: overexpression of the gene is not dependent on modifications at the EEF1A2 locus. British journal of cancer 31 17437010
2017 Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death. Human molecular genetics 30 28911200
2010 The utrophin A 5'-UTR drives cap-independent translation exclusively in skeletal muscles of transgenic mice and interacts with eEF1A2. Human molecular genetics 30 20053670
2009 eEF1A2 and neuronal degeneration. Biochemical Society transactions 29 19909265
2019 Products of Chemoenzymatic Synthesis Representing MUC1 Tandem Repeat Unit with T-, ST- or STn-antigen Revealed Distinct Specificities of Anti-MUC1 Antibodies. Scientific reports 27 31719620
2008 Loss of translation elongation factor (eEF1A2) expression in vivo differentiates between Wallerian degeneration and dying-back neuronal pathology. Journal of anatomy 27 19094180
2012 Salmonella enterotoxin (Stn) regulates membrane composition and integrity. Disease models & mechanisms 26 22301710
2003 The role of cancer vaccines following autologous stem cell rescue in breast and ovarian cancer patients: experience with the STn-KLH vaccine (Theratope). Clinical breast cancer 25 12620152
1999 Sips, Sops, and SPIs but not stn influence Salmonella enteropathogenesis. Advances in experimental medicine and biology 25 10659368
2021 The elongation factor eEF1A2 controls translation and actin dynamics in dendritic spines. Science signaling 24 34257105
2020 Effects of eEF1A2 knockdown on autophagy in an MPP+-induced cellular model of Parkinson's disease. Neuroscience research 24 32275913
2017 Biallelic mutations in the gene encoding eEF1A2 cause seizures and sudden death in F0 mice. Scientific reports 24 28378778
2015 Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates. Organic & biomolecular chemistry 24 25679360
2014 Construction and validation of a Sambucus nigra biosensor for cancer-associated STn antigen. Biosensors & bioelectronics 24 24594592
2013 Highly homologous eEF1A1 and eEF1A2 exhibit differential post-translational modification with significant enrichment around localised sites of sequence variation. Biology direct 24 24220286
2006 Prevalence of virulence genes (ctxA, stn, OmpW and tcpA) among non-O1 Vibrio cholerae isolated from fresh water environment. International journal of hygiene and environmental health 24 16891156
2013 Emotion recognition in Parkinson's disease after subthalamic deep brain stimulation: differential effects of microlesion and STN stimulation. Cortex; a journal devoted to the study of the nervous system and behavior 23 24342106
2008 The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas. International journal of cancer 23 18661515
2003 Clinical development of the STn-KLH vaccine (Theratope). Clinical breast cancer 23 12620151
2021 Striatal Afferent BDNF Is Disrupted by Synucleinopathy and Partially Restored by STN DBS. The Journal of neuroscience : the official journal of the Society for Neuroscience 22 33472823
2020 Identification of therapeutics that target eEF1A2 and upregulate utrophin A translation in dystrophic muscles. Nature communications 22 32332749
2011 The lipid kinase PI4KIIIβ and the eEF1A2 oncogene co-operate to disrupt three-dimensional in vitro acinar morphogenesis. Experimental cell research 22 21851817
2024 Ac4C modification of lncRNA SIMALR promotes nasopharyngeal carcinoma progression through activating eEF1A2 to facilitate ITGB4/ITGA6 translation. Oncogene 21 39154122
2023 Biliverdin modulates the Nrf2/A20/eEF1A2 axis to alleviate cerebral ischemia-reperfusion injury by inhibiting pyroptosis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 37399716
2011 Synthetic and Immunological Studies of sTn Derivatives Carrying 5-N-(p-Substituted Phenylacetyl)Sialic Acid for the Development of Effective Cancer Vaccines. ACS medicinal chemistry letters 21 21691430
2020 EEF1A2 triggers stronger ERK mediated metastatic program in ER negative breast cancer cells than in ER positive cells. Life sciences 19 33035587
2016 Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines. Organic & biomolecular chemistry 19 27380866
2014 Characterisation of translation elongation factor eEF1B subunit expression in mammalian cells and tissues and co-localisation with eEF1A2. PloS one 19 25436608
2011 Prevalence of multiple drug resistance and screening of enterotoxin (stn) gene in Salmonella enterica serovars from water sources in Lagos, Nigeria. Public health 19 21277605
2000 The human elongation factor 1 A-2 gene (EEF1A2): complete sequence and characterization of gene structure and promoter activity. Genomics 19 10950927
1999 Prevalence of enterotoxin gene (stn) among different serovars of Salmonella. The Indian journal of medical research 19 10573653
2023 Loss of NSUN6 inhibits osteosarcoma progression by downregulating EEF1A2 expression and activation of Akt/mTOR signaling pathway via m5C methylation. Experimental and therapeutic medicine 17 37614424
2020 The Fastest Way to Stop: Inhibitory Control and IFG-STN Hyperdirect Connectivity. Neuron 17 32437650
2017 Comparison of the ability of mammalian eEF1A1 and its oncogenic variant eEF1A2 to interact with actin and calmodulin. Biological chemistry 17 27483363
2016 Implantation of autologous peripheral nerve grafts into the substantia nigra of subjects with idiopathic Parkinson's disease treated with bilateral STN DBS: a report of safety and feasibility. Journal of neurosurgery 17 27153166
2005 Synthesis of double C-glycoside analogue of sTn. The Journal of organic chemistry 17 16277348
2023 Molecular architecture and electron transfer pathway of the Stn family transhydrogenase. Nature communications 16 37673911
2012 Haploinsufficiency for translation elongation factor eEF1A2 in aged mouse muscle and neurons is compatible with normal function. PloS one 16 22848658
2023 EEF1A2 promotes HIF1A mediated breast cancer angiogenesis in normoxia and participates in a positive feedback loop with HIF1A in hypoxia. British journal of cancer 15 38012382
2020 Rhamnose modified bovine serum albumin as a carrier protein promotes the immune response against sTn antigen. Chemical communications (Cambridge, England) 15 33079080
2015 Efficient and Specific Detection of Salmonella in Food Samples Using a stn-Based Loop-Mediated Isothermal Amplification Method. BioMed research international 15 26543859
2023 Autism- and epilepsy-associated EEF1A2 mutations lead to translational dysfunction and altered actin bundling. Proceedings of the National Academy of Sciences of the United States of America 14 37695913

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