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FLASH GENE
Symbol EIF4E contributors: mct - updated : 20-10-2017
HGNC name eukaryotic translation initiation factor 4E
HGNC id 3287
Location 4q23      Physical location : 99.799.606 - 99.851.786
Synonym name
  • mRNA cap-binding protein
  • eIF-4F 25 kDa subunit
  • Synonym symbol(s) EIF4EL1, EIF4E1, CBP, EIF4F, MGC111573, AUTS19, CBP1, eIF-4E
    DNA
    TYPE functioning gene
    STRUCTURE 52.18 kb     8 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   HRE
    text structure
  • EIF4E promoter harbors multiple potential hypoxia response elements, and HIF1A utilized hypoxia response elements in the proximal promoter region to activate EIF4E expression
  • MAPPING cloned Y linked N status confirmed
    Physical map
    MGC46496 4q22.3-q23 hypothetical protein MGC46496 RAP1GDS1 4q21 RAP1, GTP-GDP dissociation stimulator 1 TM4SF9 4q22.3 transmembrane 4 superfamily member 9 LOC132556 4q23 similar to Transcription factor BTF3 homolog 3 EIF4E 4q21-q25 eukaryotic translation initiation factor 4E METAP1 4q22.3 methionyl aminopeptidase 1 ADH5 4q21-q23 alcohol dehydrogenase 5 (class III), chi polypeptide ADH4 4q21-q24 alcohol dehydrogenase 4 (class II), pi polypeptide LOC359806 4q24 PCNA pseudogene p1PCNA ADH6 4q21-q25 alcohol dehydrogenase 6 (class V) ADH1A 4q21-q23 alcohol dehydrogenase 1A (class I), alpha polypeptide ADH1B 4q21-q23 alcohol dehydrogenase IB (class I), beta polypeptide ADH1C 4q21-q23 alcohol dehydrogenase 1C (class I), gamma polypeptide ADH7 4q23-q24 alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide DKFZP434G072 4q23 hypothetical protein DKFZp434G072 MGC27034 4q23 hypothetical protein MGC27034 MTP 4q24 microsomal triglyceride transfer protein (large polypeptide, 88kDa) LOC285556 4q23 hypothetical protein LOC285556 DAPP1 4q25-q27 dual adaptor of phosphotyrosine and 3-phosphoinositides MAP2K1IP1 4q24-q26 mitogen-activated protein kinase kinase 1 interacting protein 1 FLJ14281 4q23 hypothetical protein FLJ14281 H2AFZ 4q24 H2A histone family, member Z LOC256880 4q23 hypothetical LOC256880 LOC115265 EMCN 4q23 endomucin
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 4749 - 217 - 1992 1384058
    8 - 4842 - 248 - 1992 1384058
    7 - 3406 - 237 - 1992 1384058
    - - 11815 - 245 - 1992 1384058
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivepharynx   highly
    Reproductivemale systemtestis  highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  predominantly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    Homologene
    FAMILY
  • eukaryotic initiation factor 4E family
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    intracellular,nuclear envelope
    text
  • localizes to the nucleus
  • is also localized predominantly in the perinuclear area
  • basic FUNCTION
  • messenger RNA CAP binding protein
  • translation initiation factor that binds to the cap structure and is part of a complex (eIF-4F) that promotes mRNA binding to ribosomes
  • also involved in a nuclear function
  • translational regulator acting downstream of AKT1 and FRAP1 in oncogenesis and drug resistance
  • EIF4EBP1, EIF4EBP2 regulate the Stress granules (SGs) localization of EIF4E
  • central node in a RNA regulon that modulates the expression of genes involved in proliferation and survival
  • controls gene expression through its effects on mRNA export and cap-dependent translation, both of which contribute to its oncogenic potential
  • plays a key role in learning and memory through its control of translation within the synapse
  • can rescue both cell cycle progression and Ras-induced transformation in RND3-expressing cells, indicating that the inhibition of eIF4E function is critical to mediate the anti-proliferative effects of RND3
  • PARK2 and EIF4E act in a common pathway, likely modulating cap-dependent translation initiation events
  • key role for the MKNK1, MKNK2/EIF4E pathway in the regulatory effects of IFNG on normal hematopoiesis
  • co-ordinative roles for DDX3X, EIF4E and PABPC1 in integrating environmental stress with translational regulation
  • serves as a master switch that controls eukaryotic translation
  • activity of EIF4E is under homeostatic control via the regulation of the levels of its repressor protein EIF4EBP1 through ubiquitination
  • important role of EIF4EBP2 and EIF4E in postsynaptic translational control of neuronal mRNAs
  • translational control by EIF4E regulates the synthesis of neuroligins, maintaining the excitation-to-inhibition balance, and its dysregulation engenders ASD-like phenotypes
  • EIF4E3 repressed the expression of a pool of target mRNAs common with EIF4E
  • represses target expression and oncogenic transformation, in direct contrast to EIF4E, which stimulates these processes
  • EIF4E, EIF4E2, and EIF4E3, are essential for translation initiation
  • the formation of the ANGEL1/EIF4E complex is independent of the MTOR signaling pathway and its downstream target EIF4EBP1
  • unphosphorylated HSPB1 associates with EIF4E in osteoblasts and suppresses the translation initiation process
  • EIF4E plays a pivotal role in the control of cap-dependent translation initiation, modulates the fate of specific mRNAs, occurs in processing bodies (PBs) and is required for formation of stress granules (SGs)
  • EIF4E acts in the nuclear export and translation of a subset of mRNAs, and these functions contribute to its oncogenic potential
  • CELLULAR PROCESS cell life, proliferation/growth
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS
    text
  • rate limiting factor protein biosynthesis
  • control of cell growth
  • PATHWAY
    metabolism
    signaling
    a component
  • assembling with eIF4E kinase (MNK1), eIF4A, eIF4B, eIF4F, eIF4G, PABPC1 to form the eukaryotic translation initiation complex
  • CYFIP1-EIF4E complex is detected in synaptoneurosomes
  • complexing with importin A and B and eIF4ENIF1, mediating the nuclear import of eIF4E
  • central component in the initiation and regulation of translation in eukaryotic cells
  • EIF4E2 functions are likely to be distinct from those of EIF4E, both in the cytoplasm and nucleus, and EIF4E2 shuttles through nuclei in a CRM1-dependent manner, but in an EIF4ENIF1-independent manner, also unlike EIF4E
  • EIF4E/EIF4ENIF1 complex is present in granules with the processing body proteins LSM1 and DDX6, and disruption of this complex causes premature and enhanced neurogenesis and neural precursor depletion
  • INTERACTION
    DNA
    RNA binding
    small molecule
    protein
  • interaction between FMR1/CYFIP1 and EIF4E is increased and possibly stabilized by the presence of target mRNAs
  • interaction with LRPPRC (promotes mRNA export by recruiting eIF4E away from its potent inhibitor, PML)
  • interacting with HDAC2 (By stimulating EIF4E sumoylation, HDAC2 induces the formation of the active eukaryotic initiation factor 4F (EIF4F) complex and induces the protein synthesis of a subset of eIF4E-responsive genes that are essential for cell proliferation and preventing apoptosis)
  • MKNK1/MKNK2-EIF4G1 interaction is important for EIF4E phosphorylation
  • EIF4EBP1 inhibits cap-dependent translation by binding to the EIF4E translation initiation factor
  • serves as a master switch that controls mRNA translation through the promotive binding to EIF4G1 and the regulative binding with the endogenous inhibitor EIF4EBP1
  • XPO1 and EIF4E seem to play an important role in the nucleocytoplasmic export of human NOS2 mRNA
  • EIF4EBP2 specifically binds to EIF4E and is critical in the control of protein synthesis
  • EIF4E localization is independent of ANGEL1
  • previously unrecognized role for BANK1 in CpG-induced responses by splenic B cells on MAPK14 signaling and control of translation initiation of IL6 via MKNK1/MKNK2 and EIF4E
  • is a novel pancreatic acinar cell-specific stress response kinase that regulates digestive enzyme abundance and EIF4E phosphorylation
  • interaction of EIF4E with the initiation factor EIF4G1 recruits the 40S ribosomal particle to the 5prime end of mRNAs, facilitates scanning to the AUG start codon, and is crucial for eukaryotic translation of nearly all genes
  • ANGEL1, is a partner of EIF4E
  • MKNK1, MKNK2, can modulate oncogenic translation by regulating EIF4E-EIF4E3 levels and activity in diffuse large B-cell lymphoma (DLBCL)
  • MKNK1, MKNK2 increased the binding of EIF4E to the cytoplasmic FMR1-interacting protein 1 (CYFIP1), which binds the fragile-X mental retardation protein, FMR1, a translational repressor
  • BDNF induces the release of CYFIP1 from EIF4E, and this depends on MNKNK1
  • EIF4ENIF1 must interact with EIF4E to engender mRNA decay
  • EIF4EBP1 has tumor suppressor activity by inhibiting EIF4E and, thus, blocking mRNA translation and proliferation
  • phosphorylation of EIF4EBP1 causes its release from EIF4E to allow cap-dependent translation to proceed
  • 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
  • EIF4G1 plays a central role in translation initiation through its interactions with the cap-binding protein EIF4E
  • cell & other
    REGULATION
    activated by HIF1A (HIF1A utilized hypoxia response elements in the proximal promoter region to activate EIF4E expression)
    Other phosphorylation of EIF4E confers resistance to various cell stressors and a direct interaction or regulation of EIF4ENIF1 by EIF4E is required
    deregulation of EIF4E activities is a key component in cancer initiation and progression
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification    
    in head and neck squamous cell carcinomas
    tumoral     --over  
    leads to increased tumours and metastases
    tumoral     --other  
    aberrant expression promotes tumorigenesis and has been implicated in cancer development and progression
    Susceptibility to autism
    Variant & Polymorphism insertion/deletion in autism, single nucleotide insertion at position -25 in the basal element of the EIF4E promoter, enhancing binding of a nuclear factor and EIF4E promoter activity
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    therapies targeting eIF4E in the clinic, including the use of a physical mimic of the m7G cap ribavirin in refractory acute myeloid leukaemias (AMLs) in a phase I/II clinical trial
    psychiatryautism 
    pharmacological manipulation of EIF4E may provide therapeutic benefit for those with autism caused by disturbance of the converging pathways controlling EIF4E activity
    cancer  
    EIF4E phosphorylation pathway is a potential therapeutic target for cancer and chemical compounds that prevent the phosphorylation of EIF4E could act as anticancer drugs
    ANIMAL & CELL MODELS