ID:IF4E_HUMAN DESCRIPTION: RecName: Full=Eukaryotic translation initiation factor 4E; Short=eIF-4E; Short=eIF4E; AltName: Full=eIF-4F 25 kDa subunit; AltName: Full=mRNA cap-binding protein; FUNCTION: Its translation stimulation activity is repressed by binding to the complex CYFIP1-FMR1 (By similarity). Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures. Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit mediates the binding to the mRNA cap. SUBUNIT: eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4E is also known to interact with other partners. The interaction with EIF4ENIF1 mediates the import into the nucleus. Nonphosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP- kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Rapamycin can attenuate insulin stimulation, mediated by FKBPs. Interacts mutually exclusive with EIF4A1 or EIF4A2. Interacts with NGDN and PIWIL2. Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts directly with CYFIP1 (By similarity). Interacts with Lassa virus Z protein. Binds to MKNK2 in nucleus. Interacts with LIMD1, WTIP and AJUBA. INTERACTION: Q13541:EIF4EBP1; NbExp=4; IntAct=EBI-73440, EBI-74090; O60516:EIF4EBP3; NbExp=2; IntAct=EBI-73440, EBI-746950; Q9NRA8:EIF4ENIF1; NbExp=5; IntAct=EBI-73440, EBI-301024; Q04637:EIF4G1; NbExp=2; IntAct=EBI-73440, EBI-73711; Q04743:EMX2; NbExp=4; IntAct=EBI-73440, EBI-399831; Q8TEQ6:GEMIN5; NbExp=3; IntAct=EBI-73440, EBI-443630; Q9BUB5:MKNK1; NbExp=2; IntAct=EBI-73440, EBI-73837; SUBCELLULAR LOCATION: Cytoplasm, P-body. PTM: Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex. MASS SPECTROMETRY: Mass=24964.3; Method=Electrospray; Range=2-217; Source=PubMed:17036047; MASS SPECTROMETRY: Mass=24960; Method=Electrospray; Range=2-217; Source=PubMed:17631896; SIMILARITY: Belongs to the eukaryotic initiation factor 4E family. CAUTION: Was originally thought to be phosphorylated on Ser-53 (PubMed:3112145); this was later shown to be wrong (PubMed:7665584).
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P06730
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BioCarta from NCI Cancer Genome Anatomy Project h_eifPathway - Eukaryotic protein translation h_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase h_iresPathway - Internal Ribosome entry pathway h_igf1mtorpathway - Skeletal muscle hypertrophy is regulated via AKT/mTOR pathway h_mTORPathway - mTOR Signaling Pathway h_SARSpathway - SARS Coronavirus Protease
Reactome (by CSHL, EBI, and GO)
Protein P06730 (Reactome details) participates in the following event(s):
R-HSA-72631 Formation of the cap-binding eIF4F complex R-HSA-158447 Release of the Mature intronless derived mRNA, TAP, and Aly/Ref from the NPC R-HSA-158484 Release of the SLBP independent Histone mRNA from the NPC R-HSA-159050 Release of the Mature intronless transcript derived Histone mRNA:SLBP:eIF4E Complex R-HSA-72619 eIF2:GTP is hydrolyzed, eIFs are released R-HSA-72622 Release of eIF4E from the inactive eIF4E:4E-BP complex R-HSA-165708 Dissociation of phosphorylated 4EBP1 from eIF4E R-HSA-429955 CCR4-NOT complex deadenylates mRNA R-HSA-429992 PARN deadenylates mRNA R-HSA-165692 Phosphorylation of 4E-BP1 by activated mTORC1 R-HSA-72635 eIF4F binds to mRNP R-HSA-430021 PAN2-PAN3 complex partially deadenylates mRNA R-HSA-8941312 ZCCHC6, ZCCHC11 are mRNA uridyltransferases R-HSA-72621 Ribosomal scanning R-HSA-157849 Formation of translation initiation complexes containing mRNA that does not circularize R-HSA-72697 Start codon recognition R-HSA-156823 Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA R-HSA-156808 Formation of translation initiation complexes yielding circularized Ceruloplasmin mRNA in a 'closed-loop' conformation R-HSA-1678842 Competitive inhibition of translation initiation by ISGylated 4EHP R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S R-HSA-159231 Transport of Mature mRNA Derived from an Intronless Transcript R-HSA-159227 Transport of the SLBP independent Mature mRNA R-HSA-159230 Transport of the SLBP Dependant Mature mRNA R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit R-HSA-166208 mTORC1-mediated signalling R-HSA-429947 Deadenylation of mRNA R-HSA-72737 Cap-dependent Translation Initiation R-HSA-159234 Transport of Mature mRNAs Derived from Intronless Transcripts R-HSA-165159 mTOR signalling R-HSA-429914 Deadenylation-dependent mRNA decay R-HSA-72702 Ribosomal scanning and start codon recognition R-HSA-72649 Translation initiation complex formation R-HSA-156827 L13a-mediated translation R-HSA-1169408 ISG15 antiviral mechanism R-HSA-72613 Eukaryotic Translation Initiation R-HSA-72202 Transport of Mature Transcript to Cytoplasm R-HSA-162582 Signal Transduction R-HSA-8953854 Metabolism of RNA R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes R-HSA-72766 Translation R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA R-HSA-913531 Interferon Signaling R-HSA-392499 Metabolism of proteins R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168256 Immune System
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Common Gene Haplotype Alleles 
