EIF4EBP2 Gene

Name	eukaryotic translation initiation factor 4E binding protein 2
Description	This gene encodes a member of the eukaryotic translation initiation factor 4E binding protein family. The gene products of this family bind eIF4E and inhibit translation initiation. However, insulin and other growth factors can release this inhibition via a phosphorylation-dependent disruption of their binding to eIF4E. Regulation of protein production through these gene products have been implicated in cell proliferation, cell differentiation and viral infection. [provided by RefSeq, Oct 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The eukaryotic translation initiation factor 4E‐binding protein 2 (4E‐BP2, encoded by EIF4EBP2) is a key regulatory molecule that restrains cap‐dependent translation by binding to eIF4E and thereby limiting the formation of the eIF4F complex. In neurons, where 4E‐BP2 is preferentially enriched, its regulation is essential for synaptic plasticity and proper cognitive function. Studies have shown that multisite phosphorylation of 4E‐BP2 triggers conformational changes that reduce its affinity for eIF4E, thus permitting translation of mRNAs required for long‐term potentiation and memory formation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, genetic ablation of 4E‐BP2 in mice leads to increased translation of specific synaptic proteins—such as neuroligins—resulting in an elevated excitatory/inhibitory synaptic balance and the emergence of autism spectrum disorder–like phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond the nervous system, 4E‐BP2 functions as a metabolic brake in multiple tissues. Loss of 4E‐BP2 (often tested in combination with 4E‐BP1) has been linked to enhanced adipogenesis and increased sensitivity to diet‐induced obesity, highlighting its role in restraining protein synthesis that supports metabolic processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Similarly, in innate immunity, the combined deficiency of 4E‐BPs lowers the threshold for type‐I interferon production by releasing translational repression of key regulatory mRNAs such as Irf7."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the realm of synaptic regulation, 4E‐BP2 deletion converts early LTP into a more prolonged, late LTP form and impairs multiple aspects of learning and memory, demonstrating that tight control over cap‐dependent translation by 4E‐BP2 is required for normal brain function"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In cancer biology, the balance between eIF4E and its binding proteins (including 4E‐BP2) is a critical determinant of tumor cell sensitivity to mTOR inhibitors. Perturbations that reduce 4E‐BP2 levels or alter its phosphorylation status blunt its repressive action, allowing for the enhanced translation of oncogenic mRNAs. Indeed, experimental modulation of the eIF4E/4E‐BP stoichiometry has been shown to influence tumor growth, with genetic studies suggesting that EIF4EBP2 variants contribute to cancer risk."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, in the brain a unique posttranslational modification of 4E‐BP2—namely asparagine deamidation—has been identified, which increases its binding to mTOR pathway components and further fine‐tunes its control over translation during development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings underscore the importance of 4E‐BP2 as a versatile translational repressor that integrates signals from mTOR and other pathways to govern protein synthesis in diverse biological contexts, including synaptic plasticity, immune responses, metabolic regulation, and oncogenesis.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alaji Bah, Robert M Vernon, Zeba Siddiqui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Folding of an intrinsically disordered protein by phosphorylation as a regulatory switch."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature13999"}], "href": "https://doi.org/10.1038/nature13999"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25533957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25533957"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christos G Gkogkas, Arkady Khoutorsky, Israeli Ran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autism-related deficits via dysregulated eIF4E-dependent translational control."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature11628"}], "href": "https://doi.org/10.1038/nature11628"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23172145"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23172145"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Olivier Le Bacquer, Emmanuel Petroulakis, Sabina Paglialunga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated sensitivity to diet-induced obesity and insulin resistance in mice lacking 4E-BP1 and 4E-BP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI29528"}], "href": "https://doi.org/10.1172/JCI29528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17273556"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17273556"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rodney Colina, Mauro Costa-Mattioli, Ryan J O Dowling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Translational control of the innate immune response through IRF-7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature06730"}], "href": "https://doi.org/10.1038/nature06730"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18272964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18272964"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jessica L Banko, Francis Poulin, Lingfei Hou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The translation repressor 4E-BP2 is critical for eIF4F complex formation, synaptic plasticity, and memory in the hippocampus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.2423-05.2005"}], "href": "https://doi.org/10.1523/JNEUROSCI.2423-05.2005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16237163"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16237163"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jessica L Banko, Lingfei Hou, Francis Poulin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of eukaryotic initiation factor 4E by converging signaling pathways during metabotropic glutamate receptor-dependent long-term depression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.5196-05.2006"}], "href": "https://doi.org/10.1523/JNEUROSCI.5196-05.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16495443"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16495443"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jessica L Banko, Maayan Merhav, Elad Stern, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Behavioral alterations in mice lacking the translation repressor 4E-BP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Learn Mem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.nlm.2006.08.012"}], "href": "https://doi.org/10.1016/j.nlm.2006.08.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17029989"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17029989"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tommy Alain, Masahiro Morita, Bruno D Fonseca, et al. "}, {"type": "b", "children": [{"type": "t", "text": "eIF4E/4E-BP ratio predicts the efficacy of mTOR targeted therapies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-2395"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-2395"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23100465"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23100465"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "L J Coleman, M B Peter, T J Teall, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.bjc.6605044"}], "href": "https://doi.org/10.1038/sj.bjc.6605044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19367274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19367274"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Martha L Slattery, Abbie Lundgreen, Jennifer S Herrick, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Associations between genetic variation in RUNX1, RUNX2, RUNX3, MAPK1 and eIF4E and riskof colon and rectal cancer: additional support for a TGF-β-signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Carcinogenesis (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/carcin/bgq245"}], "href": "https://doi.org/10.1093/carcin/bgq245"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21088106"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21088106"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Michael Bidinosti, Israeli Ran, Maria R Sanchez-Carbente, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2010.02.022"}], "href": "https://doi.org/10.1016/j.molcel.2010.02.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20347422"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20347422"}]}]}]}
Synonyms	4EBP2, PHASII
Proteins	4EBP2_HUMAN
NCBI Gene ID	1979
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EIF4EBP2 has 7,039 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 123 datasets.

Click the + buttons to view associations for EIF4EBP2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EIF4EBP2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of EIF4EBP2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of EIF4EBP2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of EIF4EBP2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of EIF4EBP2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of EIF4EBP2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of EIF4EBP2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of EIF4EBP2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of EIF4EBP2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of EIF4EBP2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of EIF4EBP2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF4EBP2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of EIF4EBP2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EIF4EBP2 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EIF4EBP2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EIF4EBP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of EIF4EBP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EIF4EBP2 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of EIF4EBP2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EIF4EBP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing EIF4EBP2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing EIF4EBP2 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EIF4EBP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with EIF4EBP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of EIF4EBP2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EIF4EBP2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EIF4EBP2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EIF4EBP2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of EIF4EBP2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EIF4EBP2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with EIF4EBP2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with EIF4EBP2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with EIF4EBP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EIF4EBP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at EIF4EBP2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of EIF4EBP2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EIF4EBP2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing EIF4EBP2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with EIF4EBP2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with EIF4EBP2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of EIF4EBP2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.