Gene Symbol: EIF4EBP2
Description: eukaryotic translation initiation factor 4E binding protein 2
Alias: 4EBP2, PHASII, eukaryotic translation initiation factor 4E-binding protein 2, 4E-BP2, eIF4E-binding protein 2, phosphorylated, heat and acid stable regulated by insulin protein II
Species: human
Products:     EIF4EBP2

Top Publications

  1. Bidinosti M, Ran I, Sanchez Carbente M, Martineau Y, Gingras A, Gkogkas C, et al. Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission. Mol Cell. 2010;37:797-808 pubmed publisher
    ..4E-BP2 deamidation may represent a compensatory mechanism for the developmental reduction of PI3K-Akt-mTOR signaling. ..
  2. Mader S, Lee H, Pause A, Sonenberg N. The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4 gamma and the translational repressors 4E-binding proteins. Mol Cell Biol. 1995;15:4990-7 pubmed
    ..These results shed light on the mechanisms of eIF-4F assembly and on the translational regulation by insulin and growth factors. ..
  3. Martín Flores N, Fernández Santiago R, Antonelli F, Cerquera C, Moreno V, Marti M, et al. MTOR Pathway-Based Discovery of Genetic Susceptibility to L-DOPA-Induced Dyskinesia in Parkinson's Disease Patients. Mol Neurobiol. 2019;56:2092-2100 pubmed publisher
    ..As for the time to LID onset, we found significant associations with SNP rs1043098 in the EIF4EBP2 gene and also with an epistatic interaction involving EIF4EBP2 rs1043098, RICTOR rs2043112, and PRKCA rs4790904...
  4. Blandino Rosano M, Barbaresso R, Jimenez Palomares M, Bozadjieva N, Werneck de Castro J, Hatanaka M, et al. Loss of mTORC1 signalling impairs β-cell homeostasis and insulin processing. Nat Commun. 2017;8:16014 pubmed publisher
    ..of mTORC1 in controlling insulin processing by regulating cap-dependent translation of carboxypeptidase E in a 4EBP2/eIF4E-dependent manner...
  5. Aguilar Valles A, Matta Camacho E, Khoutorsky A, Gkogkas C, Nader K, Lacaille J, et al. Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2. J Neurosci. 2015;35:11125-32 pubmed publisher
    ..Deletion of the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 gene (Eif4ebp2), encoding the suppressor of mRNA translation initiation 4E-BP2, leads to an imbalance in excitatory-to-..
  6. Giannakou A, Sicko R, Zhang W, Romitti P, Browne M, Caggana M, et al. Copy number variants in Ebstein anomaly. PLoS ONE. 2017;12:e0188168 pubmed publisher
    ..we identified four CNVs overlapping or in close proximity to the transcription factors HES3, TRIM71, CUX1 and EIF4EBP2. This study supports the relationship of genetic factors to EA and demonstrates that defects in cardiomyocytes ..
  7. Ding M, van der Kwast T, Vellanki R, Foltz W, McKee T, Sonenberg N, et al. The mTOR Targets 4E-BP1/2 Restrain Tumor Growth and Promote Hypoxia Tolerance in PTEN-driven Prostate Cancer. Mol Cancer Res. 2018;16:682-695 pubmed publisher
    ..targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2)...
  8. Lawrence J, Fadden P, Haystead T, Lin T. PHAS proteins as mediators of the actions of insulin, growth factors and cAMP on protein synthesis and cell proliferation. Adv Enzyme Regul. 1997;37:239-67 pubmed
    ..Pharmacological and genetic evidence indicates that the mTOR/p70S6K pathway is involved in the control of PHAS-I and -II. Thus, PHAS proteins may be mediators of the effects of this pathway on protein synthesis and cell proliferation. ..
  9. Abiko F, Tomoo K, Mizuno A, Morino S, Imataka H, Ishida T. Binding preference of eIF4E for 4E-binding protein isoform and function of eIF4E N-terminal flexible region for interaction, studied by SPR analysis. Biochem Biophys Res Commun. 2007;355:667-72 pubmed

More Information


  1. Tudor J, Davis E, Peixoto L, Wimmer M, van Tilborg E, Park A, et al. Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis. Sci Signal. 2016;9:ra41 pubmed publisher
    ..synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2)...
  2. Sukarieh R, Sonenberg N, Pelletier J. The eIF4E-binding proteins are modifiers of cytoplasmic eIF4E relocalization during the heat shock response. Am J Physiol Cell Physiol. 2009;296:C1207-17 pubmed publisher
    ..Herein, we demonstrate that localization of eIF4E to SGs is dependent on the presence of a family of repressor proteins, eIF4E-binding proteins (4E-BPs). Our results demonstrate that 4E-BPs regulate the SG localization of eIF4E. ..
  3. Joshi B, Cameron A, Jagus R. Characterization of mammalian eIF4E-family members. Eur J Biochem. 2004;271:2189-203 pubmed
    ..It is hypothesized that each eIF4E-family member fills a specialized niche in the recruitment of mRNAs by the ribosome through differences in their abilities to bind cap and/or to interact with eIF4G and the 4E-BPs. ..
  4. Tee A, Proud C. Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motif. Mol Cell Biol. 2002;22:1674-83 pubmed
    ..This suggests that the N-terminal sequence of 4E-BP1 is required for optimal regulation of 4E-BPs by insulin. ..
  5. Grolleau A, Wietzerbin J, Beretta L. Defect in the regulation of 4E-BP1 and 2, two repressors of translation initiation, in the retinoid acid resistant cell lines, NB4-R1 and NB4-R2. Leukemia. 2000;14:1909-14 pubmed
    ..This indicates that 4E-BP1 down-regulation is associated with granulocytic maturation, whereas post-transcriptional regulation of 4E-BP2 expression is associated with the early action of RA. ..
  6. Wang L, Rhodes C, Lawrence J. Activation of mammalian target of rapamycin (mTOR) by insulin is associated with stimulation of 4EBP1 binding to dimeric mTOR complex 1. J Biol Chem. 2006;281:24293-303 pubmed
  7. Bah A, Vernon R, Siddiqui Z, Krzeminski M, Muhandiram R, Zhao C, et al. Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch. Nature. 2015;519:106-9 pubmed publisher
  8. Fukuyo A, In Y, Ishida T, Tomoo K. Structural scaffold for eIF4E binding selectivity of 4E-BP isoforms: crystal structure of eIF4E binding region of 4E-BP2 and its comparison with that of 4E-BP1. J Pept Sci. 2011;17:650-7 pubmed publisher
  9. Bidinosti M, Martineau Y, Frank F, Sonenberg N. Repair of isoaspartate formation modulates the interaction of deamidated 4E-BP2 with mTORC1 in brain. J Biol Chem. 2010;285:19402-8 pubmed publisher
    ..Further, we show that 4E-BP2 containing isoaspartates lacks the augmented association with raptor that is a feature of deamidated 4E-BP2. ..
  10. Shenberger J, Adams M, Zimmer S. Oxidant-induced hypertrophy of A549 cells is accompanied by alterations in eukaryotic translation initiation factor 4E and 4E-binding protein-1. Am J Respir Cell Mol Biol. 2002;27:250-6 pubmed
    ..These findings suggest that oxidant-mediated alterations in protein synthesis and cell morphology occur in concert with changes in factors known to regulate translation kinetics. ..
  11. Tsukiyama Kohara K, Vidal S, Gingras A, Glover T, Hanash S, Heng H, et al. Tissue distribution, genomic structure, and chromosome mapping of mouse and human eukaryotic initiation factor 4E-binding proteins 1 and 2. Genomics. 1996;38:353-63 pubmed
    ..Mouse 4E-BP1 and 4E-BP2 map to chromosomes 8 (A4-B1) and 10 (B4-B5), respectively, and human 4E-BP1 and 4E-BP2 localize to chromosomes 8p12 and 10q21-q22, respectively. ..
  12. Burnett P, Barrow R, Cohen N, Snyder S, Sabatini D. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci U S A. 1998;95:1432-7 pubmed
    ..This raises the possibility that, in vivo, an unidentified kinase analogous to p70(S6k) is activated by RAFT1 phosphorylation and acts at the rapamycin-sensitive phosphorylation sites of 4E-BP1. ..
  13. Grolleau A, Sonenberg N, Wietzerbin J, Beretta L. Differential regulation of 4E-BP1 and 4E-BP2, two repressors of translation initiation, during human myeloid cell differentiation. J Immunol. 1999;162:3491-7 pubmed
    ..Taken together, these data provide evidence for differential regulation of the translational machinery during human myeloid differentiation, specific to the monocytic/macrophage pathway or to the granulocytic pathway. ..
  14. Mizuno A, In Y, Fujita Y, Abiko F, Miyagawa H, Kitamura K, et al. Importance of C-terminal flexible region of 4E-binding protein in binding with eukaryotic initiation factor 4E. FEBS Lett. 2008;582:3439-44 pubmed publisher
    ..regions in the interaction, the binding features of the sequentially N-, C-, or both-terminal-residue-deleted 4EBP2 mutants were investigated by surface plasmon resonance (SPR) analysis...
  15. Morita M, Gravel S, Chénard V, Sikström K, Zheng L, Alain T, et al. mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation. Cell Metab. 2013;18:698-711 pubmed publisher
  16. Lukhele S, Bah A, Lin H, Sonenberg N, Forman Kay J. Interaction of the eukaryotic initiation factor 4E with 4E-BP2 at a dynamic bipartite interface. Structure. 2013;21:2186-96 pubmed publisher
    ..The 4E-BP2 interface on eIF4E overlaps yet is more extensive than the eIF4G:eIF4E interface, suggesting that these key interactions may be differentially targeted for therapeutics. ..
  17. Dilling M, Germain G, Dudkin L, Jayaraman A, Zhang X, Harwood F, et al. 4E-binding proteins, the suppressors of eukaryotic initiation factor 4E, are down-regulated in cells with acquired or intrinsic resistance to rapamycin. J Biol Chem. 2002;277:13907-17 pubmed
    ..These results suggest that the 4E-BP:eIF4E ratio is an important determinant of rapamycin resistance and controls certain aspects of the malignant phenotype. ..
  18. Beretta L, Singer N, Hinderer R, Gingras A, Richardson B, Hanash S, et al. Differential regulation of translation and eIF4E phosphorylation during human thymocyte maturation. J Immunol. 1998;160:3269-73 pubmed
    ..These data provide evidence for differential regulation of the translational machinery during T cell development. ..
  19. Tomoo K, Matsushita Y, Fujisaki H, Abiko F, Shen X, Taniguchi T, et al. Structural basis for mRNA Cap-Binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods. Biochim Biophys Acta. 2005;1753:191-208 pubmed
    ..These results provide the structural basis for the mRNA cap-binding regulation of eIF4E by 4E-BP. ..
  20. Gingras A, Sonenberg N. Adenovirus infection inactivates the translational inhibitors 4E-BP1 and 4E-BP2. Virology. 1997;237:182-6 pubmed
    ..Findings similar to those described here were reported for 4E-BP1 by D. Feigenblum and R. J. Schneider (1996, Mol. Cell. Biol. 16, 5450-5457). ..
  21. Lin T, Lawrence J. Control of the translational regulators PHAS-I and PHAS-II by insulin and cAMP in 3T3-L1 adipocytes. J Biol Chem. 1996;271:30199-204 pubmed
    ..In summary, our results indicate that PHAS-I and -II are controlled by the mammalian target of rapamycin and p70(S6K) signaling pathway and that in 3T3-L1 adipocytes this pathway is inhibited by increased cAMP. ..
  22. Pause A, Belsham G, Gingras A, Donze O, Lin T, Lawrence J, et al. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function. Nature. 1994;371:762-7 pubmed
    ..The action of this new regulator of protein synthesis is therefore modulated by insulin, which acts to stimulate the overall rate of translation and promote cell growth. ..
  23. Zeng J, Jiang F, Wu Y. Mechanism of Phosphorylation-Induced Folding of 4E-BP2 Revealed by Molecular Dynamics Simulations. J Chem Theory Comput. 2017;13:320-328 pubmed publisher
    ..The region around phosphorylated T46 appears to fold before that around phosphorylated T37. These findings provide new insight into the intricate effects of protein phosphorylation. ..
  24. Mizutani R, Imamachi N, Yoshida H, Tochigi N, Oonishi T, Suzuki Y, et al. Oncofetal protein IGF2BP3 facilitates the activity of proto-oncogene protein eIF4E through the destabilization of EIF4E-BP2 mRNA. Oncogene. 2016;35:3495-502 pubmed publisher
    ..This is the first report demonstrating that IGF2BP3 is an RNA-destabilizing factor. Notably, here we provide the first evidence for the functional linkage between two previously well-known cancer biomarkers, IGF2BP3 and eIF4E. ..
  25. Ferguson G, Mothe Satney I, Lawrence J. Ser-64 and Ser-111 in PHAS-I are dispensable for insulin-stimulated dissociation from eIF4E. J Biol Chem. 2003;278:47459-65 pubmed
    ..eIF4E complex. The findings also indicate that PHAS-II, but not PHAS-III, contributes to the control of protein synthesis by insulin. ..