EIF3E (also known as INT6 or eIF3-p48) encodes eukaryotic translation initiation factor 3 subunit E, a 48 kDa PCI domain-containing non-core subunit of the eIF3 complex. EIF3E forms part of module C of eIF3 together with EIF3C, EIF3D, EIF3K and EIF3L. It functions as a structural component of eIF3 that bridges cap-recognition machinery to the 43S/48S pre-initiation complex, supporting mRNA-selective translation initiation. EIF3E partners with EIF3D to form a functional d-e module that promotes selective translation of membrane-associated and mitochondrial protein mRNAs. Additionally, EIF3E plays a specialized role in nonsense-mediated mRNA decay (NMD), participating in the pioneer round of translation through interactions with the nuclear cap-binding protein CBP80 and the NMD factor UPF2. The protein localizes to both cytoplasm and nucleus, with nuclear localization in PML bodies that varies with cell cycle phase. EIF3E contributes to start codon fidelity and controls translation of specific mRNA cohorts including MAPK pathway components and TOP mRNAs encoding ribosomal proteins.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005852 eukaryotic translation initiation factor 3 complex | IBA GO_REF:0000033 | ACCEPT | Summary: EIF3E is a well-established component of the eIF3 complex. Multiple structural and biochemical studies confirm its membership in eIF3, where it forms part of module C together with EIF3C, EIF3D, EIF3K and EIF3L. Mass spectrometry and structural studies have characterized the eIF3 complex extensively. Reason: Core annotation. EIF3E membership in the eIF3 complex is definitively established through multiple lines of evidence including mass spectrometry characterization, cryo-EM structures, and biochemical reconstitution. The IBA annotation is fully supported by experimental data from multiple laboratories. Supporting Evidence: PMID:17322308 Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry PMID:18599441 Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3 PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 file:human/EIF3E/EIF3E-deep-research-perplexity.md See deep research file for comprehensive analysis |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: EIF3E exhibits dual localization in cytoplasm and nucleus. The protein contains nuclear localization and export signals enabling shuttling between compartments. Nuclear EIF3E accumulates in PML bodies and participates in pioneer round translation and NMD in the nuclear compartment. Reason: Nuclear localization of EIF3E has been demonstrated by immunofluorescence microscopy and cell fractionation studies. The nuclear pool is functionally important for pioneer round translation and NMD. The annotation is supported by phylogenetic analysis and experimental data. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA decay |
| GO:0006413 translational initiation | IBA GO_REF:0000033 | ACCEPT | Summary: EIF3E is a component of eIF3 which is essential for translation initiation. The eIF3 complex associates with the 40S ribosomal subunit and facilitates recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex. EIF3 also stimulates mRNA recruitment and scanning for AUG recognition. Reason: Translational initiation is the core function of the eIF3 complex. EIF3E as a component contributes to this function. Multiple reconstitution and functional studies confirm this role. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression |
| GO:0001732 formation of cytoplasmic translation initiation complex | IEA GO_REF:0000104 | ACCEPT | Summary: EIF3E participates in formation of translation initiation complexes as part of eIF3. The eIF3 complex bridges cap-binding machinery to the 43S/48S pre-initiation complex. Reason: This annotation correctly reflects EIF3E's role as a component of eIF3 in forming translation initiation complexes. The IEA annotation based on UniRule is consistent with experimental evidence. Supporting Evidence: PMID:16920360 eIF3: a versatile scaffold for translation initiation complexes |
| GO:0002183 cytoplasmic translational initiation | IEA GO_REF:0000104 | ACCEPT | Summary: EIF3E functions in cytoplasmic translation initiation as part of the eIF3 complex. However, EIF3E also participates in nuclear pioneer round translation. Reason: Cytoplasmic translational initiation is a core function of eIF3. While EIF3E also has nuclear roles, its participation in cytoplasmic translation initiation is well established. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 |
| GO:0003743 translation initiation factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: EIF3E contributes to translation initiation factor activity as a component of the eIF3 complex. The eIF3 complex is essential for multiple steps in translation initiation. Reason: Translation initiation factor activity is the core molecular function of eIF3. EIF3E contributes to this activity as a subunit of the complex. The annotation uses appropriate qualifier "contributes_to" in primary annotations. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression |
| GO:0005634 nucleus | IEA GO_REF:0000104 | ACCEPT | Summary: Nuclear localization of EIF3E is supported by multiple experimental studies showing shuttling between cytoplasm and nucleus, with accumulation in PML bodies. Reason: Duplicate of IBA annotation for nucleus. Both are valid as nuclear localization is experimentally confirmed. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: EIF3E localizes predominantly to the cytoplasm where it functions in translation initiation as part of the eIF3 complex at ribosomes and polysomes. Reason: Cytoplasmic localization is well established for EIF3E where it carries out its primary function in translation initiation. Endogenous tagging confirms predominantly cytoplasmic localization. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate annotation for eIF3 complex membership. EIF3E is a well-characterized component of the 13-subunit human eIF3 complex. Reason: Redundant with IBA annotation but correct. EIF3E membership in eIF3 is definitively established. Supporting Evidence: PMID:18599441 Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3 |
| GO:0006412 translation | IEA GO_REF:0000043 | ACCEPT | Summary: EIF3E is involved in translation through its role in translation initiation. The annotation to the general term "translation" is correct but less informative than specific initiation annotations. Reason: This general annotation is correct but less specific than the translational initiation annotations. It captures the broader biological process involvement correctly. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 |
| GO:0006413 translational initiation | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate annotation for translational initiation. This is a core function of EIF3E as part of the eIF3 complex. Reason: Redundant with IBA annotation but correct. Translational initiation is a core function. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 |
| GO:0016282 eukaryotic 43S preinitiation complex | IEA GO_REF:0000104 | ACCEPT | Summary: EIF3E as part of eIF3 is a component of the 43S preinitiation complex. The eIF3 complex facilitates assembly of the 43S PIC containing the 40S ribosomal subunit, eIF1, eIF1A, and eIF2-GTP-Met-tRNAi ternary complex. Reason: EIF3 is a core component of the 43S preinitiation complex. This annotation correctly reflects EIF3E's participation in this complex as an eIF3 subunit. Supporting Evidence: PMID:16920360 eIF3: a versatile scaffold for translation initiation complexes |
| GO:0016605 PML body | IEA GO_REF:0000044 | ACCEPT | Summary: EIF3E localizes to PML nuclear bodies. Immunofluorescence microscopy demonstrates co-localization of EIF3E with PML bodies in the nucleus. Reason: PML body localization of EIF3E is experimentally confirmed by immunofluorescence microscopy. The nuclear pool of EIF3E accumulates in PML bodies. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies |
| GO:0032991 protein-containing complex | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: EIF3E is part of protein-containing complexes including the eIF3 complex. However, this is too general an annotation when more specific complex annotations exist. Reason: While technically correct, this annotation is too general when more specific annotations (eIF3 complex, 43S/48S preinitiation complexes) exist. The specific complex annotations provide more informative functional context. |
| GO:0033290 eukaryotic 48S preinitiation complex | IEA GO_REF:0000104 | ACCEPT | Summary: EIF3E as part of eIF3 is a component of the 48S preinitiation complex, formed when the 43S PIC binds mRNA and scans to find the start codon. Reason: EIF3 is a component of the 48S preinitiation complex. This annotation correctly reflects EIF3E's participation in this complex as an eIF3 subunit. Supporting Evidence: PMID:16920360 eIF3: a versatile scaffold for translation initiation complexes |
| GO:0071540 eukaryotic translation initiation factor 3 complex, eIF3e | IEA GO_REF:0000104 | ACCEPT | Summary: This annotation indicates EIF3E is specifically the eIF3e subunit of the eIF3 complex. This is a highly specific cellular component annotation. Reason: EIF3E encodes the eIF3e subunit. This specific annotation correctly identifies its position within the eIF3 complex. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: This annotation is transferred from mouse ortholog. Postsynaptic density localization is not a well-characterized feature of EIF3E function. Reason: While eIF3 components may be present at synapses for local protein synthesis, this is not a core localization or function of EIF3E. The annotation is based on ortholog transfer rather than direct experimental evidence for human EIF3E. |
| GO:0005515 protein binding | IPI PMID:10504338 Interaction between the Ret finger protein and the Int-6 gen... | KEEP AS NON CORE | Summary: This publication demonstrates interaction between EIF3E (Int-6) and TRIM27 (Ret finger protein), as well as EIF3C. These interactions were identified by yeast two-hybrid and confirmed by co-immunoprecipitation. Reason: While the protein-protein interaction is valid, "protein binding" is too vague. The interaction with TRIM27 and eIF3C subunits is biologically meaningful but the general term is uninformative. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | KEEP AS NON CORE | Summary: Large-scale protein-protein interaction mapping study. The specific interaction partners are not detailed in this annotation. Reason: High-throughput interaction data. The general "protein binding" annotation is uninformative but the data may be useful for network analyses. Supporting Evidence: PMID:16189514 Towards a proteome-scale map of the human protein-protein interaction network. |
| GO:0005515 protein binding | IPI PMID:17324924 Mammalian tumor suppressor Int6 specifically targets hypoxia... | KEEP AS NON CORE | Summary: This study demonstrates EIF3E interaction with EPAS1 (HIF-2alpha) and its role in targeting EPAS1 for proteasomal degradation. Reason: The interaction with EPAS1 is interesting but represents a specialized function in hypoxia response regulation, not a core function of EIF3E in translation. Supporting Evidence: PMID:17324924 2007 Feb 26. Mammalian tumor suppressor Int6 specifically targets hypoxia inducible factor 2 alpha for degradation by hypoxia- and pVHL-independent regulation. |
| GO:0005515 protein binding | IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by... | KEEP AS NON CORE | Summary: Large-scale mass spectrometry-based protein-protein interaction mapping. Identified interaction with EIF3A. Reason: High-throughput data. EIF3E interaction with other eIF3 subunits is expected as part of complex assembly. Supporting Evidence: PMID:17353931 Large-scale mapping of human protein-protein interactions by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:18599441 Mass spectrometry reveals modularity and a complete subunit ... | ACCEPT | Summary: Comprehensive mass spectrometry study revealing the complete eIF3 subunit interaction map. Demonstrates EIF3E interactions with EIF3B, EIF3C, EIF3D, EIF3K, EIF3L, and EIF3A. Reason: This key study maps the complete eIF3 subunit interactions. EIF3E interactions with other eIF3 subunits are essential for complex assembly and function. While "protein binding" is general, these are functionally important interactions. Supporting Evidence: PMID:18599441 Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3 |
| GO:0005515 protein binding | IPI PMID:18628297 Human DDX3 functions in translation and interacts with the t... | KEEP AS NON CORE | Summary: Study showing DDX3 (DEAD-box RNA helicase) interaction with eIF3 including EIF3B. Reason: DDX3 interaction with eIF3 is interesting for understanding translation regulation but is not a core function of EIF3E specifically. Supporting Evidence: PMID:18628297 Jul 15. Human DDX3 functions in translation and interacts with the translation initiation factor eIF3. |
| GO:0005515 protein binding | IPI PMID:19748344 Subunit architecture of multiprotein assemblies determined u... | ACCEPT | Summary: Gas-phase mass spectrometry study of multiprotein assemblies. Confirms EIF3E interactions with EIF3K and EIF3L subunits. Reason: Confirms eIF3 subunit interactions. EIF3E, EIF3K, and EIF3L are part of the same module within eIF3. Supporting Evidence: PMID:19748344 Subunit architecture of multiprotein assemblies determined using restraints from gas-phase measurements |
| GO:0005515 protein binding | IPI PMID:20890303 Int6 regulates both proteasomal degradation and translation ... | ACCEPT | Summary: Study showing Int6/EIF3E regulates both proteasomal degradation and translation initiation in mammary epithelium. Confirms interaction with EIF3D. Reason: EIF3E-EIF3D interaction is functionally important as they form the d-e module within eIF3 that promotes selective translation of membrane/mitochondrial proteins. Supporting Evidence: PMID:20890303 Int6 regulates both proteasomal degradation and translation initiation and is critical for proper formation of acini by human mammary epithelium |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | KEEP AS NON CORE | Summary: Human liver protein interaction network study. Identifies EIF3E interaction with NPM1. Reason: High-throughput interactome data. NPM1 interaction is not well characterized functionally for EIF3E. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver. |
| GO:0005515 protein binding | IPI PMID:22190034 Global landscape of HIV-human protein complexes | KEEP AS NON CORE | Summary: HIV-human protein interaction study. Identifies interaction with viral proteins. Reason: Viral protein interactions may be relevant for viral translation but are not core functions of EIF3E. Supporting Evidence: PMID:22190034 Global landscape of HIV-human protein complexes. |
| GO:0005515 protein binding | IPI PMID:23623729 Architecture of human translation initiation factor 3 | ACCEPT | Summary: Architecture of human translation initiation factor 3 determined by cross-linking mass spectrometry. Confirms interactions between EIF3E and EIF3D, EIF3C, EIF3K, EIF3L. Reason: Key structural study confirming EIF3E interactions within the eIF3 complex. The cross-linking data provides spatial information about subunit organization. Supporting Evidence: PMID:23623729 Architecture of human translation initiation factor 3 |
| GO:0005515 protein binding | IPI PMID:24705354 The palmitoyl acyltransferase HIP14 shares a high proportion... | KEEP AS NON CORE | Summary: Study of HIP14 (ZDHHC17) interactors relevant to Huntington's disease. EIF3E identified as an interactor. Reason: The interaction with HIP14 is not well characterized for EIF3E function. May be relevant for understanding palmitoylation of translation factors. Supporting Evidence: PMID:24705354 Apr 4. The palmitoyl acyltransferase HIP14 shares a high proportion of interactors with huntingtin: implications for a role in the pathogenesis of Huntington's disease. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network | KEEP AS NON CORE | Summary: Proteome-scale human interactome network. High-throughput interaction data. Reason: High-throughput interactome data. General protein binding annotation is uninformative. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | KEEP AS NON CORE | Summary: Human interactome organized by stoichiometries and abundances. Confirms EIF3E-NPM1 interaction. Reason: High-throughput interactome data. NPM1 interaction is not a core function. Supporting Evidence: PMID:26496610 Oct 22. A human interactome in three quantitative dimensions organized by stoichiometries and abundances. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | ACCEPT | Summary: Architecture of human interactome study. Confirms interactions with multiple eIF3 subunits. Reason: Confirms eIF3 subunit interactions essential for complex assembly. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks |
| GO:0005515 protein binding | IPI PMID:30833792 A protein-interaction network of interferon-stimulated genes... | KEEP AS NON CORE | Summary: Protein interaction network of interferon-stimulated genes. EIF3E interacts with CD74 and DDX60. Reason: Interactions relevant to interferon response but not core EIF3E function. Supporting Evidence: PMID:30833792 Mar 4. A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | KEEP AS NON CORE | Summary: Study of genetic variant effects on protein interactions. Reason: High-throughput variant effect data. General protein binding is uninformative. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome | KEEP AS NON CORE | Summary: Reference binary protein interactome map. Multiple interaction partners identified. Reason: High-throughput interactome data. General protein binding is uninformative. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Interactome mapping of neurodegenerative disease proteins. Multiple interactions identified including with CRYAA, PRKCA, YWHAG. Reason: Potentially relevant to EIF3E role in neurodegeneration but not core translation function. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | ACCEPT | Summary: Cell-specific interactome remodeling study. Confirms eIF3 subunit interactions. Reason: Confirms core eIF3 complex interactions. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | ACCEPT | Summary: OpenCell endogenous tagging study. Confirms EIF3E interactions with EIF3B, EIF3A, EIF3K. Reason: Endogenous protein localization and interaction study. Confirms core eIF3 subunit interactions and cytoplasmic localization. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization |
| GO:0005515 protein binding | IPI PMID:39251607 Systematic identification of post-transcriptional regulatory... | KEEP AS NON CORE | Summary: Post-transcriptional regulatory module study. EIF3E interaction with NPM1. Reason: High-throughput data. NPM1 interaction is not a core EIF3E function. Supporting Evidence: PMID:39251607 Systematic identification of post-transcriptional regulatory modules. |
| GO:0001732 formation of cytoplasmic translation initiation complex | NAS PMID:16920360 eIF3: a versatile scaffold for translation initiation comple... | ACCEPT | Summary: Review article describing eIF3 as a versatile scaffold for translation initiation complexes. EIF3E participates in formation of these complexes as an eIF3 subunit. Reason: Core function. eIF3 is essential for translation initiation complex formation and EIF3E is an integral component. Supporting Evidence: PMID:16920360 eIF3: a versatile scaffold for translation initiation complexes |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IPI PMID:17322308 Structural characterization of the human eukaryotic initiati... | ACCEPT | Summary: Mass spectrometry characterization of the human eIF3 complex identifying all 13 subunits including EIF3E. Reason: Definitive experimental evidence for EIF3E as a component of the eIF3 complex. Supporting Evidence: PMID:17322308 Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Immunofluorescence data showing cytosolic localization. EIF3E is predominantly cytoplasmic where it functions in translation initiation. Reason: Core localization. Cytosolic localization is well established for EIF3E as part of the translation machinery. Supporting Evidence: PMID:35271311 OpenCell: Endogenous tagging for the cartography of human cellular organization |
| GO:0005515 protein binding | IPI PMID:21745818 Mechanisms of translational regulation by a human eIF5-mimic... | ACCEPT | Summary: Study of BZW2/5MP1, an eIF5-mimic protein that interacts with eIF3 including EIF3E. Reason: BZW2 interaction with eIF3 is functionally relevant for translational regulation. Supporting Evidence: PMID:21745818 Mechanisms of translational regulation by a human eIF5-mimic protein |
| GO:0006446 regulation of translational initiation | ISS GO_REF:0000024 | ACCEPT | Summary: EIF3E regulates translational initiation as part of the eIF3 complex. The complex can both activate and repress translation of specific mRNAs. Reason: Core function. eIF3 regulates translation initiation both positively and negatively for different mRNA targets. Supporting Evidence: PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | KEEP AS NON CORE | Summary: E-cadherin interactome study. EIF3E identified as an interactor of E-cadherin complex. Reason: Cadherin binding is not a core function of EIF3E. This may reflect association with membrane-localized translation machinery near adhesion junctions. Supporting Evidence: PMID:25468996 E-cadherin interactome complexity and robustness resolved by quantitative proteomics. |
| GO:0045727 positive regulation of translation | IPI PMID:24092755 Human eukaryotic initiation factor 4G (eIF4G) protein binds ... | ACCEPT | Summary: Study showing eIF4G binds to eIF3c, eIF3d, and eIF3e to promote mRNA recruitment to the ribosome, thereby positively regulating translation. Reason: Core function. EIF3E participates in positive regulation of translation through interaction with eIF4G which bridges the cap-binding complex to the ribosome. Supporting Evidence: PMID:24092755 Human eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome |
| GO:0003743 translation initiation factor activity | IDA PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translati... | ACCEPT | Summary: Direct demonstration that eIF3 targets cell-proliferation mRNAs for translational activation or repression. EIF3E contributes to this activity. Reason: Core molecular function. This study provides direct evidence for eIF3 translation initiation factor activity and mRNA-selective regulation. Supporting Evidence: PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IDA PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translati... | ACCEPT | Summary: Study directly demonstrating eIF3 complex function in mRNA-selective translation. Reason: Core annotation. Direct experimental evidence for EIF3E as a component of functional eIF3 complex. Supporting Evidence: PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells | KEEP AS NON CORE | Summary: NK cell membrane proteome study identifying EIF3E. This may reflect association with membrane-localized polysomes. Reason: Membrane association is not a core feature of EIF3E. May reflect localized translation at endoplasmic reticulum or plasma membrane. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | ACCEPT | Summary: mRNA-bound proteome study identifying EIF3E. As a translation factor, EIF3E is expected to associate with mRNA. Reason: RNA binding is a core function of eIF3. The complex directly binds to specific mRNA structures to regulate translation. Supporting Evidence: PMID:22681889 The mRNA-bound proteome and its global occupancy profile on protein-coding transcripts PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: B-cell exosome proteome study. EIF3E identified in exosomes. Reason: Exosomal localization is not a core function. Many cytoplasmic proteins are found in exosomes. Supporting Evidence: PMID:20458337 2010 May 11. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-156808 | ACCEPT | Summary: Reactome annotation for translation initiation complex formation. EIF3E is cytosolic where it functions in translation. Reason: Cytosolic localization is core for translation function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-156823 | ACCEPT | Summary: Reactome annotation. Redundant cytosol annotation. Reason: Core localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-157849 | ACCEPT | Summary: Reactome annotation. Redundant cytosol annotation. Reason: Core localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72619 | ACCEPT | Summary: Reactome annotation for eIF2:GTP hydrolysis and eIF release. Reason: Core localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72621 | ACCEPT | Summary: Reactome annotation for ribosomal scanning. Reason: Core localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72676 | ACCEPT | Summary: Reactome annotation for eIF3 and eIF1A binding to 40S subunit. Reason: Core localization and function. Supporting Evidence: Reactome:R-HSA-72676 eIF3 and eIF1A bind to the 40S subunit |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72691 | ACCEPT | Summary: Reactome annotation for 43S pre-initiation complex formation. Reason: Core localization and function. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-72697 | ACCEPT | Summary: Reactome annotation for start codon recognition. Reason: Core localization and function. |
| GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay | IMP PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA deca... | ACCEPT | Summary: Key study demonstrating that EIF3E/INT6 is required for nonsense-mediated mRNA decay. EIF3E knockdown specifically inhibits NMD without affecting general translation, establishing it as a specialized NMD factor. Reason: Core specialized function. EIF3E is uniquely required for NMD through its role in pioneer round translation and interaction with UPF2 and CBP80. Supporting Evidence: PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA decay |
| GO:0000785 chromatin | NAS PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA deca... | UNDECIDED | Summary: This annotation suggests chromatin localization based on the NMD study. However, the primary evidence in this paper relates to NMD function rather than direct chromatin association. Reason: The evidence for chromatin localization is not clear from the cited reference. The paper primarily addresses NMD function and nuclear localization but not direct chromatin association. Supporting Evidence: PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA decay. |
| GO:0003743 translation initiation factor activity | IC PMID:17322308 Structural characterization of the human eukaryotic initiati... | ACCEPT | Summary: Inferred from EIF3E membership in the eIF3 complex demonstrated by mass spectrometry. Reason: Core molecular function. Translation initiation factor activity is correctly inferred from complex membership. Supporting Evidence: PMID:17322308 Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry |
| GO:0003743 translation initiation factor activity | IDA PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 | ACCEPT | Summary: Biochemical reconstitution study demonstrating that a six-subunit complex including EIF3E has translation initiation activity. Reason: Core molecular function. Direct experimental evidence from reconstituted complex. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 |
| GO:0003743 translation initiation factor activity | IC PMID:18599441 Mass spectrometry reveals modularity and a complete subunit ... | ACCEPT | Summary: Inferred from EIF3E as a component of the complete eIF3 complex mapped by mass spectrometry. Reason: Core molecular function. Supporting Evidence: PMID:18599441 Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3 |
| GO:0005515 protein binding | IPI PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA deca... | ACCEPT | Summary: NMD study demonstrating EIF3E interaction with UPF2, EIF4G1, NCBP1 (CBP80), and other eIF3 subunits. Reason: Important interactions for NMD function. EIF3E-UPF2 and EIF3E-CBP80 interactions are essential for pioneer round translation and NMD. Supporting Evidence: PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA decay |
| GO:0005634 nucleus | IDA PMID:10504338 Interaction between the Ret finger protein and the Int-6 gen... | ACCEPT | Summary: Immunofluorescence demonstrating nuclear localization of EIF3E, including co-localization with PML bodies. Reason: Direct experimental evidence for nuclear localization. The nuclear pool of EIF3E is functionally important for pioneer round translation and NMD. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies |
| GO:0005852 eukaryotic translation initiation factor 3 complex | NAS PMID:10504338 Interaction between the Ret finger protein and the Int-6 gen... | ACCEPT | Summary: Study identifying EIF3E interactions including with EIF3C, supporting eIF3 complex membership. Reason: Core annotation. eIF3 complex membership is well established. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IDA PMID:17322308 Structural characterization of the human eukaryotic initiati... | ACCEPT | Summary: Mass spectrometry identification of EIF3E as a component of the purified eIF3 complex. Reason: Definitive experimental evidence for eIF3 complex membership. Supporting Evidence: PMID:17322308 Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IDA PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 | ACCEPT | Summary: Reconstitution study showing EIF3E is part of the functional eIF3 complex. Reason: Core annotation. Direct biochemical evidence. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IDA PMID:18599441 Mass spectrometry reveals modularity and a complete subunit ... | ACCEPT | Summary: Complete subunit interaction map of eIF3 by mass spectrometry confirming EIF3E as a subunit. Reason: Core annotation. Comprehensive structural characterization. Supporting Evidence: PMID:18599441 Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3 |
| GO:0006413 translational initiation | IC PMID:17322308 Structural characterization of the human eukaryotic initiati... | ACCEPT | Summary: Inferred from eIF3 complex membership. Reason: Core biological process. Supporting Evidence: PMID:17322308 Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry |
| GO:0006413 translational initiation | IDA PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 | ACCEPT | Summary: Direct demonstration of translational initiation activity for reconstituted eIF3 containing EIF3E. Reason: Core biological process. Direct biochemical evidence. Supporting Evidence: PMID:17581632 Reconstitution reveals the functional core of mammalian eIF3 |
| GO:0006413 translational initiation | IC PMID:18599441 Mass spectrometry reveals modularity and a complete subunit ... | ACCEPT | Summary: Inferred from eIF3 complex membership. Reason: Core biological process. Supporting Evidence: PMID:18599441 Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3 |
| GO:0006446 regulation of translational initiation | NAS PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA deca... | ACCEPT | Summary: EIF3E regulates translational initiation, particularly in the context of NMD and pioneer round translation. Reason: Core function. EIF3E regulates translation initiation both positively (general translation) and negatively (NMD substrates). Supporting Evidence: PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA decay |
| GO:0016605 PML body | IDA PMID:10504338 Interaction between the Ret finger protein and the Int-6 gen... | ACCEPT | Summary: Immunofluorescence demonstrating EIF3E co-localization with PML bodies in the nucleus. Reason: Direct experimental evidence for PML body localization. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies |
| GO:0045947 negative regulation of translational initiation | NAS PMID:10504338 Interaction between the Ret finger protein and the Int-6 gen... | ACCEPT | Summary: EIF3E can negatively regulate translation, particularly through its role in NMD where it diverts mRNAs from translation to degradation. Reason: EIF3E participates in negative regulation of translation through NMD and through eIF3-mediated translational repression of specific mRNAs like BTG1. Supporting Evidence: PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA decay PMID:25849773 eIF3 targets cell-proliferation messenger RNAs for translational activation or repression PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies. |
| GO:0003743 translation initiation factor activity | IC PMID:9295280 The translation initiation factor eIF3-p48 subunit is encode... | ACCEPT | Summary: Original identification of EIF3E (INT-6) as the p48 subunit of eIF3, establishing its role as a translation initiation factor. Reason: Foundational study establishing EIF3E as a translation initiation factor. Supporting Evidence: PMID:9295280 The translation initiation factor eIF3-p48 subunit is encoded by int-6, a site of frequent integration by the mouse mammary tumor virus genome |
| GO:0005654 nucleoplasm | NAS PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA deca... | ACCEPT | Summary: Nuclear localization of EIF3E includes nucleoplasm, where it participates in pioneer round translation and NMD. Reason: EIF3E nuclear localization is well established and functionally important. Supporting Evidence: PMID:17468741 Human INT6/eIF3e is required for nonsense-mediated mRNA decay |
| GO:0005737 cytoplasm | IDA PMID:10504338 Interaction between the Ret finger protein and the Int-6 gen... | ACCEPT | Summary: Immunofluorescence showing cytoplasmic localization of EIF3E. Reason: Core localization. Cytoplasm is the primary site of translation initiation. Supporting Evidence: PMID:10504338 Interaction between the Ret finger protein and the Int-6 gene product and co-localisation into nuclear bodies |
| GO:0005852 eukaryotic translation initiation factor 3 complex | IDA PMID:9295280 The translation initiation factor eIF3-p48 subunit is encode... | ACCEPT | Summary: Original identification of EIF3E as the p48 subunit of the purified eIF3 complex. Reason: Foundational study establishing EIF3E as an eIF3 subunit. Supporting Evidence: PMID:9295280 The translation initiation factor eIF3-p48 subunit is encoded by int-6, a site of frequent integration by the mouse mammary tumor virus genome |
| GO:0006446 regulation of translational initiation | NAS PMID:9295280 The translation initiation factor eIF3-p48 subunit is encode... | ACCEPT | Summary: Original study describing EIF3E as a translation initiation factor involved in regulating initiation. Reason: Core function established in foundational study. Supporting Evidence: PMID:9295280 The translation initiation factor eIF3-p48 subunit is encoded by int-6, a site of frequent integration by the mouse mammary tumor virus genome |
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Download this section (compressed HTML)Q: What determines whether eIF3 binding to a specific mRNA results in translational activation versus repression, given that eIF3 can both activate (e.g., c-Jun) and repress (e.g., BTG1) translation of different mRNA targets through binding to 5' UTR stem-loop structures?
Q: What is the mechanism by which EIF3E is selectively required for NMD but not for general translation, given that EIF3E knockdown specifically inhibits NMD without affecting bulk translation?
Q: How does EIF3E nuclear-cytoplasmic shuttling relate to cell cycle regulation, given that nuclear EIF3E levels decrease during early S phase?
Experiment: Determine cryo-EM structures of EIF3E-containing eIF3 bound to specific target mRNAs to reveal how EIF3E contributes to mRNA-selective translation regulation.
Experiment: Perform proximity labeling (BioID/APEX) of nuclear versus cytoplasmic EIF3E pools to identify compartment-specific interaction partners and functions.
Experiment: Conduct ribosome profiling after acute EIF3E depletion to identify the specific mRNAs whose translation depends on EIF3E.
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