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MGP000941

UniProt Annotations

Entry Information
Gene Nameeukaryotic translation initiation factor 4E binding protein 1
Protein Entry4EBP1_HUMAN
UniProt IDQ13541
SpeciesHuman
Comments
Comment typeDescription
FunctionRegulates eIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. {ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836}.
InteractionQ9UKV8:AGO2; NbExp=2; IntAct=EBI-74090, EBI-528269; P06730:EIF4E; NbExp=8; IntAct=EBI-74090, EBI-73440; P42345:MTOR; NbExp=2; IntAct=EBI-74090, EBI-359260; Q9JLN9:Mtor (xeno); NbExp=2; IntAct=EBI-74090, EBI-1571628; Q8N122:RPTOR; NbExp=5; IntAct=EBI-74090, EBI-1567928;
PtmPhosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser- 65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E. {ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17525332, ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:9465032}.
PtmUbiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr- 46, Ser-65 and Thr-70) or associated with eIF4E. {ECO:0000269|PubMed:22578813}.
SimilarityBelongs to the eIF4E-binding protein family. {ECO:0000305}.
SubunitHypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Interacts with RPTOR. {ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:17368478, ECO:0000269|PubMed:17631896, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:8521827}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/EIF4EBP1ID40432ch8p12.html";
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