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    EIF4EBP1 eukaryotic translation initiation factor 4E binding protein 1 [ Homo sapiens ]

    Gene ID: 1978, updated on 15-Jan-2012
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    Summary

    Official Symbol
    EIF4EBP1provided by HGNC
    Official Full Name
    eukaryotic translation initiation factor 4E binding protein 1provided by HGNC
    Primary source
    HGNC:3288
    See related
    Ensembl:ENSG00000187840; HPRD:03746; MIM:602223; Vega:OTTHUMG00000164012
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    BP-1; 4EBP1; 4E-BP1; PHAS-I
    Summary
    This gene encodes one member of a family of translation repressor proteins. The protein directly interacts with eukaryotic translation initiation factor 4E (eIF4E), which is a limiting component of the multisubunit complex that recruits 40S ribosomal subunits to the 5' end of mRNAs. Interaction of this protein with eIF4E inhibits complex assembly and represses translation. This protein is phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from eIF4E and activation of mRNA translation. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    8p12
    Sequence :
    Chromosome: 8; NC_000008.10 (37888020..37917883)
    See EIF4EBP1 in Epigenomics, MapViewer

    Chromosome 8 - NC_000008.10Genomic Context describing neighboring genes Neighboring gene glutamic-oxaloacetic transaminase 1-like 1 Neighboring gene adrenergic, beta-3-, receptor Neighboring gene ash2 (absent, small, or homeotic)-like (Drosophila) Neighboring gene steroidogenic acute regulatory protein

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Identification and function of the second eIF4E-binding region in N-terminal domain of eIF4G: comparison with eIF4E-binding protein. Umenaga Y, et al. Biochem Biophys Res Commun, 2011 Oct 28. PMID 21964297.
    2. A directed protein interaction network for investigating intracellular signal transduction. Vinayagam A, et al. Sci Signal, 2011 Sep 6. PMID 21900206.
    3. Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator. Shuda M, et al. J Clin Invest, 2011 Sep. PMID 21841310.
    4. Eukaryotic translation initiation factor 4E binding protein 1 (4EBP-1) function is suppressed by Src and protein phosphatase 2A (PP2A) on extracellular matrix. Nho RS, et al. J Biol Chem, 2011 Sep 16. PMID 21784851.
    5. The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model. Pons B, et al. Int J Oncol, 2011 Nov. PMID 21750861.

    See all (138) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. We propose that high p-4E-BP1 and p-eIF4E levels are central factors in cell signaling and reflect the oncogenic potential of cell signaling pathways in breast cancer.
      Title: The effect of p-4E-BP1 and p-eIF4E on cell proliferation in a breast cancer model.
    2. This clearly indicates the importance of the second binding region for the difference in function between eIF4G and 4E-BP for eIF4E
      Title: Identification and function of the second eIF4E-binding region in N-terminal domain of eIF4G: comparison with eIF4E-binding protein.
    3. Data show that the eIF4E binding preference for 4E-BP2 over 4E-BP1 is based on stacking of Arg63 side chain on Trp73 indole ring of eIF4E and construction of hydrophobic space around the Trp73 indole ring by the Leu59-Leu60 sequence of 4E-BP2.
      Title: 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.
    4. when lung fibroblasts are attached to collagen matrix, the beta1 integrin/Src/PP2A-mediated 4EBP-1 regulatory pathway is activated
      Title: Eukaryotic translation initiation factor 4E binding protein 1 (4EBP-1) function is suppressed by Src and protein phosphatase 2A (PP2A) on extracellular matrix.
    5. Data show that 4E-BP1 inhibition by Merkel cell polyomavirus small T antigen is required for Merkel cell polyomavirus neoplastic cell transformation.
      Title: Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator.
    6. Data suggest that knockdown of raptor relieves autophagy and the eIF4E effector pathway from rapamycin resistance.
      Title: Relieving autophagy and 4EBP1 from rapamycin resistance.
    7. potential prognostic factor for survival in patients with lung adenocarcinoma
      Title: Prognostic significance of expression of eukaryotic initiation factor 4E and 4E binding protein 1 in patients with pathological stage I invasive lung adenocarcinoma.
    8. The immunohistochemical expression pattern of 4E-BP1 exhibits regional and cellular specificity in reactive lymphoid tissues.
      Title: Expression and phosphorylation of eukaryotic translation initiation factor 4E binding protein 1 in B-cell lymphomas and reactive lymphoid tissues.
    9. Data show that 4E-BP1 gene transcription increases in a cell density-dependent manner, and that 4E-BP1 protein accumulation is involved in cell cycle arrest at contact inhibition likely through downregulation of cyclin D1 expression.
      Title: Control of contact-inhibition by 4E-BP1 upregulation.
    10. assessment of phosphorylated-4E-BP1 expression could identify a subpopulation of earlier stage esophageal squamous cell carcinoma patients with poor prognosis.
      Title: High expression of phosphorylated 4E-binding protein 1 is an adverse prognostic factor in esophageal squamous cell carcinoma.
    Submit: New GeneRIF Correction See all (70)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_004086.1 NP_001959.1 EIF4E    BIND  PubMed EIF4E interacts with EIF4EBP1 (4EBP1). 
    NP_004086.1     BIND  PubMed mTOR-Rheb complex phosphorylates EIF4EBP1 (4E-BP1). 
    NP_004086.1     BIND  PubMed mTORC2 complex phosphorylates 4E-bp1. This interaction was modeled on a demonstrated interaction between human mTOR2 and 4E-bp1 from an unspecified species. 
    NP_004086.1     BIND  PubMed mTORC1 complex phosphorylates 4E-bp1. This interaction was modeled on a demonstrated interaction between human mTORC1 and 4E-bp1 from an unspecified species. 
    Q13541 P31749 AKT1    HPRD  PubMed  
    Q13541 Q13315 ATM    HPRD  PubMed  
    Q13541 O43683 BUB1    HPRD  PubMed  
    Q13541 DERPC CHTF8    HPRD  PubMed  
    Q13541 P68400 CSNK2A1    HPRD  PubMed  
    Q13541 P19784 CSNK2A2    HPRD  PubMed  
    Q13541 P06730 EIF4E    HPRD  PubMed  
    Q13541 O60573 EIF4E2    HPRD  PubMed  
    Q13541 P28482 MAPK1    HPRD  PubMed  
    Q13541 Q16539 MAPK14    HPRD  PubMed  
    Q13541 Q8IW41 MAPKAPK5    HPRD  PubMed  
    Q13541 P42345 MTOR    HPRD  PubMed  
    Q13541 P53602 MVD    HPRD  PubMed  
    Q13541 Protein phosphatase 2A, catalytic subunit, alpha isoform PPP2CA    HPRD  PubMed  
    Q13541 Ras homolog enriched in brain like 1 RHEBL1    HPRD  PubMed  
    Q13541 P51449 RORC    HPRD  PubMed  
    Q13541 O75582 RPS6KA5    HPRD  PubMed  
    Q13541 P23443 RPS6KB1    HPRD  PubMed  
    Q13541 Raptor RPTOR    HPRD  PubMed  
    BioGRID:108293 BioGRID:106962 ATM    BioGRID  PubMed Protein-peptide 
    BioGRID:108293 BioGRID:120262 CHTF8    BioGRID  PubMed Two-hybrid 
    BioGRID:108293 BioGRID:108292 EIF4E    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Co-purification; Reconstituted Complex; Two-hybrid 
    BioGRID:108293 BioGRID:109187 GSK3B    BioGRID  PubMed Two-hybrid 
    BioGRID:108293 BioGRID:110221 LRPAP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:108293 BioGRID:32836 MEC1    BioGRID  PubMed Biochemical Activity 
    BioGRID:108293 BioGRID:108757 MTOR    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:108293 BioGRID:248568 Mtor    BioGRID  PubMed Reconstituted Complex 
    BioGRID:108293 BioGRID:111512 PPP2R2A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:108293 BioGRID:121582 RPTOR    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:108293 BioGRID:115691 UBAC1    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • AMPK signaling, organism-specific biosystem (from WikiPathways)
      AMPK signaling, organism-specific biosystemAMPK signaling pathway, a fuel sensor and regulator, promotes ATP-producing and inhibits ATP-consuming pathways in various tissues. AMPK is a heterotrimer composed of alpha-catalytic and beta and gam...
    • Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S, organism-specific biosystem (from REACTOME)
      Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S, organism-specific biosystemThe cap-binding complex is constituted by the initiation factors eIF4A, eIF4G and eIF4E. First, eIF4E must be released from the inactive eIF4E:4E-BP complex. Then eIF4A interacts with eIF4G, and eIF...
    • Acute myeloid leukemia, organism-specific biosystem (from KEGG)
      Acute myeloid leukemia, organism-specific biosystemAcute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation...
    • Acute myeloid leukemia, conserved biosystem (from KEGG)
      Acute myeloid leukemia, conserved biosystemAcute myeloid leukemia (AML) is a disease that is characterized by uncontrolled proliferation of clonal neoplastic cells and accumulation in the bone marrow of blasts with an impaired differentiation...
    • Alpha6-Beta4 Integrin Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Alpha6-Beta4 Integrin Signaling Pathway, organism-specific biosystem"Integrins are cell surface heterodimeric protein complex consisting of one alpha and one beta chain. Integrins act as cell adhesion molecules as well as participate in cellular signaling. The ligand...
    • Cap-dependent Translation Initiation, organism-specific biosystem (from REACTOME)
      Cap-dependent Translation Initiation, organism-specific biosystemTranslation initiation is a complex process in which the Met-tRNAi initiator, 40S, and 60S ribosomal subunits are assembled by eukaryotic initiation factors (eIFs) into an 80S ribosome at the start c...
    • ErbB signaling pathway, organism-specific biosystem (from WikiPathways)
      ErbB signaling pathway, organism-specific biosystemThe ErbB protein family or epidermal growth factor receptor (EGFR) family is a family of four structurally related receptor tyrosine kinases. Insufficient ErbB signaling in humans is associated with ...
    • ErbB signaling pathway, organism-specific biosystem (from KEGG)
      ErbB signaling pathway, organism-specific biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • ErbB signaling pathway, conserved biosystem (from KEGG)
      ErbB signaling pathway, conserved biosystemThe ErbB family of receptor tyrosine kinases (RTKs) couples binding of extracellular growth factor ligands to intracellular signaling pathways regulating diverse biologic responses, including prolife...
    • Eukaryotic Translation Initiation, organism-specific biosystem (from REACTOME)
      Eukaryotic Translation Initiation, organism-specific biosystemInitiation of translation in the majority of eukaryotic cellular mRNAs depends on the 5'-cap (m7GpppN) and involves ribosomal scanning of the 5' untranslated region (5'-UTR) for an initiating AUG sta...
    • Gene Expression, organism-specific biosystem (from REACTOME)
      Gene Expression, organism-specific biosystemGene Expression covers the process of transcription of mRNA genes, the processing of pre-mRNA, and its subsequent translation to result in a protein. The "expression" of non-protein-coding genes is ...
    • Hypertrophy Model, organism-specific biosystem (from WikiPathways)
      Hypertrophy Model, organism-specific biosystem
      Hypertrophy Model
    • IL-6 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-6 Signaling Pathway, organism-specific biosystemInterleukin-6 belongs to a family of cytokines which includes IL-11, ciliary neurotrophic factor (CNTF), cardiotropin-1, cardiotrophin-like cytokine, leukemia inhibitory factor (LIF) and Oncostatin M...
    • IRS-mediated signalling, organism-specific biosystem (from REACTOME)
      IRS-mediated signalling, organism-specific biosystemRelease of phospho-IRS from the insulin receptor triggers a cascade of signalling events via PI3K, SOS, RAF and the MAP kinases.
    • IRS-related events, organism-specific biosystem (from REACTOME)
      IRS-related events, organism-specific biosystemIRS is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving PI3K, SOS, RAF and the MAP kinases. The proteins mentioned unde...
    • Insulin Pathway, organism-specific biosystem (from Pathway Interaction Database)
      Insulin Pathway, organism-specific biosystem
      Insulin Pathway
    • Insulin Signaling, organism-specific biosystem (from WikiPathways)
      Insulin Signaling, organism-specific biosystem
      Insulin Signaling
    • Insulin receptor signalling cascade, organism-specific biosystem (from REACTOME)
      Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...
    • Insulin signaling pathway, organism-specific biosystem (from KEGG)
      Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Insulin signaling pathway, conserved biosystem (from KEGG)
      Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • PI3K Cascade, organism-specific biosystem (from REACTOME)
      PI3K Cascade, organism-specific biosystem
      PI3K Cascade
    • PKB-mediated events, organism-specific biosystem (from REACTOME)
      PKB-mediated events, organism-specific biosystemPKB and PDK1 are activated via membrane-bound PIP3. Activated PDK1 phosphorylates PKB, which in turn phosphorylates PDE3B. The latter hydrolyses cAMP to 5'AMP, depleting cAMP pools.
    • RNA transport, organism-specific biosystem (from KEGG)
      RNA transport, organism-specific biosystemRNA transport from the nucleus to the cytoplasm is fundamental for gene expression. The different RNA species that are produced in the nucleus are exported through the nuclear pore complexes (NPCs) ...
    • RNA transport, conserved biosystem (from KEGG)
      RNA transport, conserved biosystemRNA transport from the nucleus to the cytoplasm is fundamental for gene expression. The different RNA species that are produced in the nucleus are exported through the nuclear pore complexes (NPCs) ...
    • Release of eIF4E, organism-specific biosystem (from REACTOME)
      Release of eIF4E, organism-specific biosystemRaptor recruits mTOR to non-phosphorylated 4E-BP1 bound to eIF4E and positively modulates phosphorylation of 4E-BP1 by mTOR. 4E-BP1 is further phosphorylated on multiple sites by other unknown kinase...
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
      Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
    • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
      Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
    • Signaling mediated by p38-alpha and p38-beta, organism-specific biosystem (from Pathway Interaction Database)
      Signaling mediated by p38-alpha and p38-beta, organism-specific biosystem
      Signaling mediated by p38-alpha and p38-beta
    • Translation, organism-specific biosystem (from REACTOME)
      Translation, organism-specific biosystemProtein synthesis is accomplished through the process of translation of an mRNA sequence into a polypeptide chain. This process can be divided into three distinct stages: initiation, elongation and ...
    • Translation Factors, organism-specific biosystem (from WikiPathways)
      Translation Factors, organism-specific biosystemProtein synthesis is the ultimate step of gene expression and a key control point for regulation. In particular, it enables cells to rapidly manipulate protein production without new mRNA synthesis, ...
    • mTOR signaling pathway, organism-specific biosystem (from KEGG)
      mTOR signaling pathway, organism-specific biosystem
      mTOR signaling pathway
    • mTOR signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      mTOR signaling pathway, organism-specific biosystem
      mTOR signaling pathway
    • mTOR signaling pathway, conserved biosystem (from KEGG)
      mTOR signaling pathway, conserved biosystem
      mTOR signaling pathway
    • mTOR signalling, organism-specific biosystem (from REACTOME)
      mTOR signalling, organism-specific biosystem
      mTOR signalling
    • mTORC1-mediated signalling, organism-specific biosystem (from REACTOME)
      mTORC1-mediated signalling, organism-specific biosystem
      mTORC1-mediated signalling

    Clone Names

    • MGC4316

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    eukaryotic initiation factor 4E binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    G1/S transition of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    TOR signaling cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cellular protein metabolic process TAS
    Traceable Author Statement
    more info
    		  
    gene expression TAS
    Traceable Author Statement
    more info
    		  
    insulin receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    negative regulation of protein complex assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of translational initiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    translation TAS
    Traceable Author Statement
    more info
    		  
    translational initiation TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein complex IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    eukaryotic translation initiation factor 4E-binding protein 1
    Names
    eukaryotic translation initiation factor 4E-binding protein 1
    eIF4E-binding protein 1
    phosphorylated heat- and acid-stable protein regulated by insulin 1
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_004095.3 → NP_004086.1  eukaryotic translation initiation factor 4E-binding protein 1

      Status: REVIEWED

      Source sequence(s)
      AB044548, BC004459, BF964628
      Consensus CDS
      CCDS6100.1
      UniProtKB/Swiss-Prot
      Q13541
      Related
      ENSP00000340691, OTTHUMP00000225572, ENST00000338825, OTTHUMT00000376743
      Conserved Domains (1) summary
      pfam05456
      Location:5 – 118
      Blast Score: 337
      eIF_4EBP; Eukaryotic translation initiation factor 4E binding protein (EIF4EBP)

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000008.10 Reference GRCh37.p5 Primary Assembly

      Range
      37888020..37917883
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000140.1 Alternate HuRef

      Range
      36422762..36452631
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AP006545.1 (71476..101324) None
    genomic CH471080.2 EAW63341.1
      EAW63342.1
    mRNA AB044548.1 BAB18650.1
    mRNA AK312011.1 BAG34949.1
    mRNA BC004459.1 AAH04459.1
    mRNA BC058073.1 AAH58073.1
    mRNA BF964628.1 None
    mRNA BT007162.1 AAP35826.1
    mRNA CR456769.1 CAG33050.1
    mRNA L36055.1 AAA62269.1
    other-genetic DQ890570.2 ABM92187.1
    other-genetic DQ893731.2 ABM84657.1
    Protein Accession Links
    GenePept Link UniProtKB Link
    Q13541.3 GenPept UniProtKB/Swiss-Prot:Q13541
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

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