Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol EIF4EBP1 contributors: mct/npt - updated : 20-10-2017
HGNC name eukaryotic translation initiation factor 4E binding protein 1
HGNC id 3288
Location 8p11.23      Physical location : 37.888.019 - 37.917.882
Synonym name
  • phosphorylated heat- and acid-stable protein regulated by insulin 1
  • eIF4E-binding protein 1
  • Synonym symbol(s) 4EBP1, PHAS-1, BP-1, MGC4316, 4E-BP1, PHAS-I
    DNA
    TYPE functioning gene
    STRUCTURE 29.86 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 877 - 118 - 1995 7651417
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Epithelialsecretoryglandularendocrine 
    Epithelialsecretoryglandularexocrine 
    Muscularstriatumskeletal  
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a C terminal region for phosphorylation and regulation of function, and conserved motif within the flexible C-terminus of the translational regulator EIF4EBP1 is required for tight binding to the mRNA cap-binding protein EIF4E
  • secondary structure an alpha helical structure involved in the control of translation initiation
    conjugated PhosphoP , Other
    HOMOLOGY
    interspecies homolog to murine Eif4ebp1 (91.5pc)
    homolog to rattus Eif4ebp1 (93.2pc)
    intraspecies paralog to EIF4EBP2
    paralog to EIF4EBP3
    Homologene
    FAMILY
  • eIF4E-binding protein family
  • CATEGORY regulatory , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • translational repressor, negatively regulating translation by EIF4E, by preventing its assembly into the EIF4F complex
  • acting as a tumor suppressor
  • mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathway
  • EIF4EBP1, EIF4EBP2 regulate the Stress granules (SGs) localization of EIF4E
  • is essential for TGFbeta-mediated inhibition of cell proliferation (Azar 2009)
  • activated EIF4EBP1 represses tumorigenesis and IGF-I-mediated activation of the eIF4F complex in mesothelioma (Jacobson 2009)
  • modifier of cytoplasmic EIF4E relocalization during the heat shock response (Sukarieh 2009)
  • EIF4EBP1, beyond its role in translation regulation, can function as a regulator of mitosis via interacting with PLK1, and possibly plays a role in genomic stability maintaining
  • EIF4EBP1 is neither a major nor robust physiological substrate of LRRK2 in mammalian cells or brain
  • requirement of the EIF4EBP1 and EIF4EBP2 for the synergistic down-regulation of protein synthesis by hypertonic conditions and MTOR inhibition
  • has pro-tumorigenic functions as it promotes tumor adaptation to metabolic and genotoxic stress by selectively enhancing or preventing the translation of specific transcripts
  • FGF signaling differentially impacts protein synthesis through either stimulation or repression, in a cell-type-dependent manner, with EIF4EBP1 being a key player
  • CELLULAR PROCESS cell life, cell death/apoptosis
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    involved in insulin mediated control pathway
    a component
  • assembling with eIF4A, PABPC1, eIF4E, eIF4BP2, eIF4BP3, MNK1 and eIF4G to form the eukaryotic translation initiation complex eIF4F
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding in its non-phosphorylated form to EIF4E
  • interacting with RPTOR
  • represses translation initiation by binding to eukaryotic initiation factor 4E (EIF4E)
  • EIF4E2 interaction with EIF4EBP1 is necessary for this observed impaired signaling to EIF4EBP1 and RPS6KB1
  • EIF4EBP1 inhibits cap-dependent translation by binding to the EIF4E translation initiation factor
  • activity of EIF4E is under homeostatic control via the regulation of the levels of its repressor protein EIF4EBP1 through ubiquitination
  • PPM1G binds to EIF4EBP1 in cells (PPM1G is a novel regulator of cap-dependent protein translation by negatively controlling the phosphorylation of EIF4EBP1)
  • MTOR controls mitochondrial activity and biogenesis by selectively promoting translation of nucleus-encoded mitochondria-related mRNAs via inhibition of the eukaryotic translation initiation factor EIF4EBP1, EIF4EBP2
  • RPTOR in MTOR complex 1 is believed to recruit EIF4EBP1, facilitating phosphorylation of EIF4EBP1 by the kinase MTOR
  • GSPT2 biomarker for hepatocellular carcinoma, influencing cell cycle and phosphoralation status of EIF4EBP1
  • MTOR activation inhibits eukaryotic translation initiation factor 4E-binding protein (EIF4EBP1) and activates ribosomal protein S6 kinase 1 (RPS6KB1), both of which stimulate translation
  • regulation of EIF4EBP1 in skeletal muscle may serve as an important conduit through which MTOR controls metabolism
  • translational control by EIF4EBP1 downstream of MTOR effects the expression of neuroligin 1 and excitatory synaptic transmission in the spinal cord, and thereby contributes to enhanced mechanical nociception
  • EIF4EBP1 has tumor suppressor activity by inhibiting EIF4E and, thus, blocking mRNA translation and proliferation
  • ability of EIF4E to recognize the cap is prevented by its binding to EIF4E binding protein (EIF4EBP1), which thereby inhibits cap-dependent translation by sequestering EIF4E
  • cell & other
    REGULATION
    induced by SMAD4 through binding to a conserved element in the EIF4EBP1 promoter (Azar 2009)
    Other phosphorylation events govern the proapoptotic potency of EIF4EBP1
    phosphorylated in response to various signals including UV irradiation and insulin signaling, resulting in its dissociation from EIF4E and activation of mRNA translation
    phosphorylated by mTORC1
    phosphorylation inhibited by RhoE (Villalonga 2009)
    phosphorylation of EIF4EBP1 causes its release from EIF4E to allow cap-dependent translation to proceed
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    hyperphosphorylated in some cancers
    tumoral        
    phosphorylated EIF4EBP1 expression in endometrial cancer correlates with aggressive tumors and prognosis (Castellvi 2009)
    tumoral     --over  
    upregulation in eutopic endometrium may be associated with the pathogenesis of endometriosis (Laudanski 2009)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • expression of mTOR and EIF4EBP1 characterize high-grade, high-stage endometrial adenocarcinomas and might be predictive markers of a response to rapamycin (Darb-Esfahani 2009)
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    for cancer therapy, potentially (small-molecule inhibitors that pharmacologically mimic function)
    cancerskin 
    phosphorylated EIF4EBP1 is associated with poor survival in melanoma and effective inhibition of the pathways responsible for EIF4EBP1 phosphorylation should be considered to improve the treatment outcome of metastatic melanoma patients
    ANIMAL & CELL MODELS
  • elevated Eif4ebp1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of Eif4ebp1 within its PEST motif