EIF3J

UniProt ID: O75822
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

EIF3J (eukaryotic translation initiation factor 3 subunit J) is a cytoplasmic accessory subunit of the 13-subunit eIF-3 complex, the largest eukaryotic translation initiation factor. eIF-3 associates with the 40S ribosomal subunit and orchestrates several steps of cap-dependent translation initiation, promoting recruitment of eIF-1, eIF-1A, the eIF-2-GTP-Met-tRNAi ternary complex and eIF-5 to form the 43S pre-initiation complex, stimulating mRNA recruitment and scanning to the AUG start codon, and contributing to disassembly/recycling of post-termination ribosomal complexes while preventing premature 40S-60S subunit joining. EIF3J is a loosely associated, sub-stoichiometric ("labile") subunit that docks onto the complex through EIF3B; it positions near the 40S mRNA entry channel/decoding region and is required for stable binding of eIF-3 (and its subcomplexes) to the 40S subunit, thereby modulating mRNA loading and 40S availability. It is a non-catalytic accessory factor (its initiation-factor activity is contributed in the context of the assembled complex) and is phosphorylated in a serum-stimulation-dependent manner.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005852 eukaryotic translation initiation factor 3 complex
IBA
GO_REF:0000033
ACCEPT
Summary: EIF3J is a (labile) subunit of the eIF-3 complex, well supported across eukaryotes and by direct human evidence. This is the core cellular-component annotation.
Reason: EIF3J is documented as a component of the 13-subunit eIF-3 complex, binding via EIF3B; the IBA is corroborated by IDA/IPI evidence.
Supporting Evidence:
file:human/EIF3J/EIF3J-uniprot.txt
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex
GO:0001732 formation of cytoplasmic translation initiation complex
IEA
GO_REF:0000104
ACCEPT
Summary: As part of eIF-3, EIF3J participates in assembly of the 43S/48S translation initiation complexes on the 40S subunit. A genuine core process annotation.
Reason: eIF-3 facilitates recruitment of initiation factors and ternary complex to form the 43S PIC; EIF3J contributes to this assembly.
Supporting Evidence:
file:human/EIF3J/EIF3J-uniprot.txt
facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to
GO:0002183 cytoplasmic translational initiation
IEA
GO_REF:0000104
ACCEPT
Summary: EIF3J participates in cytoplasmic translation initiation as an eIF-3 subunit. This is the core biological process.
Reason: eIF-3 is required for several steps in initiation of protein synthesis; this is EIF3J's central biological role.
Supporting Evidence:
file:human/EIF3J/EIF3J-uniprot.txt
required for several steps in the initiation of protein synthesis
GO:0003743 translation initiation factor activity
IEA
GO_REF:0000120
ACCEPT
Summary: EIF3J contributes translation initiation factor activity as an accessory subunit of eIF-3. The activity is exerted in the context of the assembled complex rather than by EIF3J alone.
Reason: The core molecular function of EIF3J is translation initiation factor activity via the eIF-3 complex; note the curated experimental annotations use the contributes_to qualifier, reflecting its accessory role.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0003743 translation initiation factor activity molecular_function ECO:0000501 IEA
GO:0005737 cytoplasm
IEA
GO_REF:0000120
ACCEPT
Summary: EIF3J is cytoplasmic, consistent with its role in cytoplasmic translation initiation.
Reason: Cytoplasm is the documented subcellular location and the site of translation initiation.
Supporting Evidence:
file:human/EIF3J/EIF3J-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005852 eukaryotic translation initiation factor 3 complex
IEA
GO_REF:0000120
ACCEPT
Summary: Electronic transfer of eIF-3 complex membership, redundant with the IBA/IDA/IPI evidence.
Reason: Correct core cellular component, corroborated by stronger evidence.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000501 IEA
GO:0016282 eukaryotic 43S preinitiation complex
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: Via eIF-3, EIF3J is part of the transient 43S pre-initiation complex on the 40S subunit. A genuine but transient assembly intermediate.
Reason: The 43S PIC is a transient initiation intermediate that contains eIF-3; a real but non-core localization relative to the stable eIF-3 complex membership.
Supporting Evidence:
file:human/EIF3J/EIF3J-uniprot.txt
to form the 43S pre-initiation complex (43S PIC)
GO:0033290 eukaryotic 48S preinitiation complex
IEA
GO_REF:0000104
KEEP AS NON CORE
Summary: Via eIF-3, EIF3J is part of the transient 48S pre-initiation complex (after mRNA recruitment and start-codon scanning). A transient assembly intermediate.
Reason: The 48S PIC is a transient initiation intermediate; real but non-core relative to stable eIF-3 complex membership.
Supporting Evidence:
file:human/EIF3J/EIF3J-uniprot.txt
stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for
GO:0005515 protein binding
IPI
PMID:14688252
The j-subunit of human translation initiation factor eIF3 is...
KEEP AS NON CORE
Summary: Interaction with EIF3B (P55884), the subunit through which EIF3J docks onto eIF-3; this study shows EIF3J is required for stable binding of eIF-3 to 40S subunits. Deep-research synthesis further localizes EIF3J binding to the 40S near the mRNA entry channel and A-site, where it binds anti-cooperatively with mRNA and acts as a gatekeeper for mRNA accommodation. Bare protein binding is uninformative, but the interaction is biologically central.
Reason: Records the functionally important EIF3J-EIF3B interaction, but the term is uninformative; the informative function (eIF-3 membership and 40S/mRNA-entry-channel binding) is captured by complex/initiation annotations and core_functions.
Supporting Evidence:
PMID:14688252
j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro
file:human/EIF3J/EIF3J-deep-research-falcon.md
Binds the 40S small subunit near the mRNA entry channel and A-site; competes anti-cooperatively with accommodated mRNA
GO:0005515 protein binding
IPI
PMID:16932749
p97/DAP5 is a ribosome-associated factor that facilitates pr...
KEEP AS NON CORE
Summary: Interaction reported in a study of the ribosome-associated factor p97/DAP5. Bare protein binding is uninformative.
Reason: Records a real interaction but uninformative term; not core to EIF3J's function.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16932749 UniProtKB:Q04637
GO:0005515 protein binding
IPI
PMID:18628297
Human DDX3 functions in translation and interacts with the t...
KEEP AS NON CORE
Summary: Interaction with EIF4G1 (Q04637) in a study of DDX3 in translation and eIF3. Bare protein binding is uninformative.
Reason: Records a real translation-related interaction but uninformative term; not core.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18628297 UniProtKB:P55884
GO:0005515 protein binding
IPI
PMID:22113938
A bead-based approach for large-scale identification of in v...
KEEP AS NON CORE
Summary: Interaction with the casein kinase 2 catalytic subunit CSNK2A1 (P68400) from a kinase-substrate screen; consistent with EIF3J being phosphorylated. Bare protein binding is uninformative.
Reason: Records a kinase-substrate interaction (EIF3J is phosphorylated) but uninformative term; not a core function.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:22113938 UniProtKB:P68400
GO:0005515 protein binding
IPI
PMID:25852190
Integrative analysis of kinase networks in TRAIL-induced apo...
KEEP AS NON CORE
Summary: Interaction with CSNK2A1 (P68400) from a kinase-network apoptosis study. Bare protein binding is uninformative.
Reason: Records a kinase interaction but uninformative term; not core.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25852190 UniProtKB:P68400
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: HuRI binary interactome capturing an EIF3J-ABCE1 (P61221) interaction. ABCE1 is the ribosome-recycling ATPase; deep-research synthesis indicates EIF3J specifically (not merely the eIF-3 holo-complex) functionally couples to ABCE1/RLI1 and enhances post-termination ribosome recycling, so this interaction is biologically meaningful even though the bare term is uninformative.
Reason: Records a recycling-relevant interaction (ABCE1) with EIF3J-subunit-specific functional support in the recycling literature, but the term itself is uninformative; the recycling role is captured at the complex level.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:P61221
file:human/EIF3J/EIF3J-deep-research-falcon.md
physically/ functionally associates with ABCE1/RLI1, the ATPase required for post-termination ribosome recycling
GO:0005515 protein binding
IPI
PMID:32707033
Kinase Interaction Network Expands Functional and Disease Ro...
KEEP AS NON CORE
Summary: Interaction with CSNK2A1 (P68400) from a kinase-interaction-network study. Bare protein binding is uninformative.
Reason: Records a kinase interaction but uninformative term; not core.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32707033 UniProtKB:P68400
GO:0005515 protein binding
IPI
PMID:32911434
A functionally defined high-density NRF2 interactome reveals...
KEEP AS NON CORE
Summary: Interaction with NFE2L2/NRF2 (Q16236) from an NRF2-interactome screen. Bare protein binding is uninformative and likely peripheral.
Reason: Records a real interaction but uninformative term and peripheral to translation initiation; not core.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32911434 UniProtKB:Q16236
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
KEEP AS NON CORE
Summary: BioPlex affinity-purification capturing an EIF3J-CSNK2A1 (P68400) interaction. Bare protein binding is uninformative.
Reason: Records a kinase interaction but uninformative term; not core.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:P68400
GO:0005515 protein binding
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
KEEP AS NON CORE
Summary: OpenCell endogenous-tagging interactome capturing EIF3J interactions with EIF3B (P55884) and ABCE1 (P61221), consistent with eIF-3 docking and recycling roles. Bare protein binding is uninformative.
Reason: Records biologically consistent interactions (EIF3B, ABCE1) but uninformative term; captured by complex/initiation annotations.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:P55884
GO:0042802 identical protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
KEEP AS NON CORE
Summary: EIF3J self-interaction reported in the HuRI binary interactome (consistent with the EIF3J-EIF3J IntAct entry). A real homotypic interaction but not a core function.
Reason: Records a self-interaction; not part of the core translation-initiation function.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0042802 identical protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:O75822
GO:0001732 formation of cytoplasmic translation initiation complex
NAS
PMID:16920360
eIF3: a versatile scaffold for translation initiation comple...
ACCEPT
Summary: Author statement (eIF3 review) that eIF-3 serves as a scaffold for assembly of translation initiation complexes; EIF3J participates as a subunit.
Reason: Consistent with eIF-3's documented role in initiation-complex assembly; core process for EIF3J as a subunit.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0001732 formation of cytoplasmic translation initiation complex biological_process ECO:0005547 NAS PMID:16920360
GO:0005852 eukaryotic translation initiation factor 3 complex
IPI
PMID:17322308
Structural characterization of the human eukaryotic initiati...
ACCEPT
Summary: Direct (ComplexPortal/MS) evidence placing EIF3J in the eIF-3 complex. Core cellular component.
Reason: Mass-spectrometry characterization of human eIF-3 confirms EIF3J as a component.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000353 IPI PMID:17322308
GO:0005829 cytosol
TAS
Reactome:R-HSA-156808
ACCEPT
Summary: Reactome curated cytosolic localization for translation-initiation reactions.
Reason: Correct cytosolic localization, consistent with the cytoplasmic site of action.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-156808
GO:0005829 cytosol
TAS
Reactome:R-HSA-156823
ACCEPT
Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
Reason: Correct cytosolic localization.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-156823
GO:0005829 cytosol
TAS
Reactome:R-HSA-157849
ACCEPT
Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
Reason: Correct cytosolic localization.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-157849
GO:0005829 cytosol
TAS
Reactome:R-HSA-72619
ACCEPT
Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
Reason: Correct cytosolic localization.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72619
GO:0005829 cytosol
TAS
Reactome:R-HSA-72621
ACCEPT
Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
Reason: Correct cytosolic localization.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72621
GO:0005829 cytosol
TAS
Reactome:R-HSA-72676
ACCEPT
Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
Reason: Correct cytosolic localization.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72676
GO:0005829 cytosol
TAS
Reactome:R-HSA-72691
ACCEPT
Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
Reason: Correct cytosolic localization.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72691
GO:0005829 cytosol
TAS
Reactome:R-HSA-72697
ACCEPT
Summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
Reason: Correct cytosolic localization.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72697
GO:0003743 translation initiation factor activity
IC
PMID:17322308
Structural characterization of the human eukaryotic initiati...
ACCEPT
Summary: Curator-inferred (from eIF-3 complex membership) that EIF3J contributes to translation initiation factor activity. The contributes_to qualifier correctly reflects its accessory role within the complex.
Reason: This is the core molecular function annotation for EIF3J, appropriately qualified as contributes_to for a non-catalytic accessory subunit.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0003743 translation initiation factor activity molecular_function ECO:0000305 IC PMID:17322308
GO:0003743 translation initiation factor activity
IC
PMID:18599441
Mass spectrometry reveals modularity and a complete subunit ...
ACCEPT
Summary: Curator-inferred translation initiation factor activity from eIF-3 complex membership (subunit interaction map study). Redundant with the other IC annotation.
Reason: Core molecular function, appropriately qualified contributes_to.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0003743 translation initiation factor activity molecular_function ECO:0000305 IC PMID:18599441
GO:0005852 eukaryotic translation initiation factor 3 complex
IDA
PMID:17322308
Structural characterization of the human eukaryotic initiati...
ACCEPT
Summary: Direct MS-based evidence for EIF3J as an eIF-3 component. Core cellular component.
Reason: Directly demonstrated eIF-3 complex membership.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000314 IDA PMID:17322308
GO:0005852 eukaryotic translation initiation factor 3 complex
IDA
PMID:18599441
Mass spectrometry reveals modularity and a complete subunit ...
ACCEPT
Summary: Direct MS-based evidence for EIF3J as an eIF-3 component (subunit interaction map). Core cellular component.
Reason: Directly demonstrated eIF-3 complex membership.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000314 IDA PMID:18599441
GO:0006413 translational initiation
IC
PMID:17322308
Structural characterization of the human eukaryotic initiati...
ACCEPT
Summary: Curator-inferred involvement in translational initiation from eIF-3 membership. Core biological process.
Reason: EIF3J participates in translation initiation as an eIF-3 subunit.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0006413 translational initiation biological_process ECO:0000305 IC PMID:17322308
GO:0006413 translational initiation
IC
PMID:18599441
Mass spectrometry reveals modularity and a complete subunit ...
ACCEPT
Summary: Curator-inferred involvement in translational initiation from eIF-3 membership. Redundant with the other IC annotation.
Reason: Core biological process for EIF3J as an eIF-3 subunit.
Supporting Evidence:
file:human/EIF3J/EIF3J-goa.tsv
GO:0006413 translational initiation biological_process ECO:0000305 IC PMID:18599441

Core Functions

Accessory (labile) subunit of the eIF-3 complex that contributes translation initiation factor activity, helping eIF-3 assemble the 43S/48S pre-initiation complexes on the 40S ribosomal subunit and recruit/scan mRNA during cap-dependent translation initiation.

Supporting Evidence:
  • file:human/EIF3J/EIF3J-uniprot.txt
    required for several steps in the initiation of protein synthesis
  • PMID:14688252
    j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro

Structural component of the eIF-3 complex; EIF3J docks onto eIF-3 through EIF3B and is required for stable association of eIF-3 with the 40S ribosomal subunit, positioning near the mRNA entry channel and modulating mRNA loading and 40S availability (including in ribosome recycling).

Supporting Evidence:
  • file:human/EIF3J/EIF3J-uniprot.txt
    EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B
  • file:human/EIF3J/EIF3J-deep-research-falcon.md
    Binds the 40S small subunit near the mRNA entry channel and A-site; competes anti-cooperatively with accommodated mRNA

References

Annotation inferences using phylogenetic trees.
Automatic annotation of UniProtKB entries based on UniRule rules.
Combined Automated Annotation using Multiple IEA Methods.
The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro.
  • EIF3J (the j-subunit) is required for stable binding of eIF-3 and its subcomplexes to 40S ribosomal subunits.
eIF3: a versatile scaffold for translation initiation complexes.
  • eIF-3 acts as a scaffold for assembly of translation initiation complexes.
p97/DAP5 is a ribosome-associated factor that facilitates protein synthesis and cell proliferation by modulating the synthesis of cell cycle proteins.
Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry.
  • Mass-spectrometry characterization of human eIF-3 confirms EIF3J as a subunit of the complex.
Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3.
  • Subunit interaction map of eIF-3 places EIF3J as a labile subunit binding via EIF3B.
Human DDX3 functions in translation and interacts with the translation initiation factor eIF3.
A bead-based approach for large-scale identification of in vitro kinase substrates.
Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
A reference map of the human binary protein interactome.
Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
A functionally defined high-density NRF2 interactome reveals new conditional regulators of ARE transactivation.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
eIF3 targets cell-proliferation messenger RNAs for translational activation or repression.
  • eIF-3 selectively targets a subset of cell-proliferation mRNAs for translational activation or repression via stem-loop binding.
eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation.
  • eIF-3 (via eIF3d) mediates specialized cap-dependent translation initiation.
Reactome:R-HSA-156808
Reactome translation-initiation reaction (cytosolic).
Reactome:R-HSA-156823
Reactome translation-initiation reaction (cytosolic).
Reactome:R-HSA-157849
Reactome translation-initiation reaction (cytosolic).
Reactome:R-HSA-72619
Reactome translation-initiation reaction (cytosolic).
Reactome:R-HSA-72621
Reactome translation-initiation reaction (cytosolic).
Reactome:R-HSA-72676
Reactome translation-initiation reaction (cytosolic).
Reactome:R-HSA-72691
Reactome translation-initiation reaction (cytosolic).
Reactome:R-HSA-72697
Reactome translation-initiation reaction (cytosolic).
file:human/EIF3J/EIF3J-deep-research-falcon.md
Falcon deep research report for EIF3J
  • eIF3j binds the human 40S near the mRNA entry channel and A-site (anti-cooperatively with mRNA) as a gatekeeper for mRNA accommodation, and is displaced upon mRNA recruitment; it also functionally couples to ABCE1/RLI1 to enhance post-termination ribosome recycling.
file:human/EIF3J/EIF3J-uniprot.txt
UniProt entry O75822 (EIF3J_HUMAN), Eukaryotic translation initiation factor 3 subunit J.
  • EIF3J is a labile/loosely-associated subunit of the eIF-3 complex that binds via EIF3B; eIF-3 associates with the 40S subunit, drives 43S/48S pre-initiation complex formation, mRNA recruitment and scanning, and post-termination ribosome recycling; cytoplasmic; phosphorylated upon serum stimulation.

Suggested Questions for Experts

Q: Does human EIF3J have a distinct, separable role in 40S ribosome recycling/availability (post-termination) versus initiation, as suggested by yeast Hcr1?

Q: How does the sub-stoichiometric/labile association of EIF3J with eIF-3 regulate switching between mRNA-entry-channel occupancy and mRNA loading?

Q: What is the functional consequence of serum-stimulated phosphorylation of EIF3J for its association with eIF-3 and selective mRNA translation?

Suggested Experiments

Experiment: Selective EIF3J depletion/rescue with ribosome profiling and 40S/80S subunit-availability assays to dissect its contribution to initiation versus post-termination recycling.

Experiment: Cryo-EM of 40S-eIF-3 complexes with and without EIF3J to define its occupancy of the mRNA entry channel and effect on mRNA accommodation.

Experiment: Phosphomutant (phospho-null/phospho-mimetic) EIF3J variants to test how serum-stimulated phosphorylation modulates eIF-3 binding and translational output.

Deep Research

Falcon

(EIF3J-deep-research-falcon.md)
Comprehensive Research Report: Functional Annotation of Human EIF3J (eIF3j, UniProt O75822) Falcon Edison Scientific Literature 32 citations 1 artifacts 2026-06-20T07:03:40.981421

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Comprehensive Research Report: Functional Annotation of Human EIF3J (eIF3j, UniProt O75822)

1. Introduction and Verification

Extensive review of recent and foundational literature confirms the correct targeting of the human gene EIF3J. EIF3J encodes the eukaryotic translation initiation factor 3 subunit J (eIF3j), as annotated in UniProt O75822, and matches the provided protein/domain description. All reviewed sources describe its role within the human eIF3 system; ambiguous alternative gene/protein symbols were not detected in retrieved authoritative literature (wagner2016humaneif3band pages 1-2, valasek2017embracedbyeif3 pages 1-2).

2. Key Concepts and Definitions

eIF3j is a non-enzymatic, ribosome-associated translation factor classified as a peripheral, substoichiometric member of the eIF3 multiprotein complex. Unlike core eIF3 subunitsโ€”which form the PCI/MPN octamer or "yeast-like core"โ€”eIF3j associates transiently with the eIF3 complex and the small (40S) ribosomal subunit (wagner2016humaneif3band pages 1-2). It is best described as an eIF3-associated factor rather than a bona fide core subunit (valasek2017embracedbyeif3 pages 1-2, valasek2017embracedbyeif3 pages 3-4, sokabe2017ahelicaseindependentactivity pages 1-1).

Domain Structure: Human eIF3j comprises an N-terminal region mediating interaction with the RRM domain of eIF3b (the core scaffolding subunit), and a C-terminal region required for specific regulatory activity (notably, inhibition of circular RNA translation) (valasek2017embracedbyeif3 pages 3-4, song2022eif3jinhibitstranslation pages 1-2).

Primary Function: eIF3j regulates translation initiation, ribosome recycling, and selected non-canonical translation processes, without direct enzymatic activity or substrate specificity.

3. Molecular Function and Mechanism

  • Initiation Complex Remodeling: eIF3j binds the human 40S ribosomal subunit near the mRNA entry channel and A-site, with anti-cooperative binding relative to mRNA. It acts as a โ€œgatekeeperโ€ for mRNA accommodation in the 43S pre-initiation complex (PIC), and its displacement signals successful mRNA entry (sokabe2017ahelicaseindependentactivity pages 1-1).
  • Dependence on eIF4A/ATP: Recruitment of mRNA together with eIF4F, eIF4A, and eIF4B leads to eIF3j dissociation from the 43S PIC. This is an ATP-dependent, but helicase-independent, step (sokabe2017ahelicaseindependentactivity pages 1-1).
  • Interaction Partners: eIF3j interacts directly with eIF3b RRM domain (confirmed by NMR), and physically/ functionally associates with ABCE1/RLI1, the ATPase required for post-termination ribosome recycling (valasek2017embracedbyeif3 pages 3-4, young2022rebirthofthe pages 3-4, young2022rebirthofthe pages 4-6).
  • Ribosome Recycling: eIF3j enhances the efficiency of ABCE1/RLI1-driven 80S ribosome splitting and subsequent recycling of the small subunit, facilitating readiness for subsequent rounds of translation (young2022rebirthofthe pages 4-6, young2022rebirthofthe pages 3-4).
  • Circular RNA Translation: Recent evidence identifies eIF3j as a potent inhibitor of translation from a subset of circular RNAs, acting via its C-terminal region to promote dissociation of eIF3 from the ribosomeโ€“circRNA complex (song2022eif3jinhibitstranslation pages 1-2, song2022eif3jinhibitstranslation pages 4-5, hwang2024molecularmechanismsof pages 1-2). This function appears selective for some transcripts, demonstrating transcript-specific regulatory potential beyond canonical mRNA translation.

4. Subcellular Localization

EIF3J is predominantly cytoplasmic, consistent with its roles in mRNA translation (initiation and recycling) on cytoplasmic ribosomes. There is no significant evidence for nuclear or mitochondrial localization in humans (duan2023eif3mrnaselectivity pages 1-2, sokabe2017ahelicaseindependentactivity pages 1-1).

5. Pathways and Biological Processes

  • Translational Control: eIF3j is implicated in canonical cap-dependent translation initiation, post-termination ribosome recycling, and select non-canonical translation processes.
  • Termination and Readthrough: Functional studies in yeast (and to some extent supported by broader eIF3 evidence in humans) suggest eIF3j modulates stop codon recognition, with loss of eIF3j increasing stop codon readthrough (valasek2017embracedbyeif3 pages 10-11, valasek2017embracedbyeif3 pages 11-12).
  • Transcript Selectivity: Inhibition of circRNA translation and possible involvement in select mRNA regulatory events point to context-dependent, transcript-specific effects (song2022eif3jinhibitstranslation pages 1-2).
  • Immune Response Crosstalk: Depletion of eIF3 subunits (including those interacting with eIF3j) can activate NF-ฮบB and interferon gamma signaling, but eIF3j's direct signaling role appears secondary to its translation regulatory activities (she2023translationalfidelityscreens pages 1-2).

6. Structure-Function Relationships

  • Domain Insights: The best-resolved structural information for eIF3j is the NMR structure of its N-terminal region (residues 35-69) in complex with the eIF3b RRM (valasek2017embracedbyeif3 pages 3-4), and the known requirement for the C-terminus in regulatory activities on circRNA translation (song2022eif3jinhibitstranslation pages 1-2).
  • Superfamily Membership: Belongs to the eIF3 subunit J family (IPR013906, IPR023194); conserved across eukaryotes.
  • Cryo-EM Context: Recent high-resolution maps of the human translational initiation complex help frame eIF3jโ€™s proximity to the mRNA entry channel and other factors gating mRNA entry, though eIF3j itself is not always resolved (querido2024thestructureof pages 1-2).

7. Current Applications and Relevance (2022โ€“2024 Developments)

  • Transcriptome-Wide Selectivity: Emerging roles in selective regulation of circRNAs in metazoans (Song et al., 2022) (song2022eif3jinhibitstranslation pages 1-2).
  • Tissue-specific Expression: Recent transcriptomic studies note that EIF3J expression level varies across human tissues (e.g., lower in ovary, higher in brain/liver/testis), possibly reflecting tissue-specific translational needs (young2022rebirthofthe pages 1-3).
  • Viral Targeting: eIF3jโ€™s ribosome-binding site is targeted by viruses such as SARS-CoV-2 (via Nsp1), emphasizing its interface as a potential drug target or vulnerability during infection (yuan2020nonstructuralprotein1 pages 1-7).

8. Data Summary Table and Sources

The following table comprehensively summarizes specific findings, pathways, features, and structural insights, prioritized by publication year and experimental authority:

Aspect Key finding for human EIF3J/eIF3j Evidence/details Recent relevance (2022-2024) Source / year / URL
Gene/protein identity EIF3J encodes human eukaryotic translation initiation factor 3 subunit J (eIF3j), an eIF3-associated translation factor rather than a stable core eIF3 subunit Reviews and assembly studies distinguish mammalian eIF3 as a 12-subunit complex and describe eIF3j as loosely associated/substoichiometric, often treated as an eIF3-associated factor rather than a bona fide core subunit (wagner2016humaneif3band pages 1-2, valasek2017embracedbyeif3 pages 1-2) Still the prevailing model used in current eIF3 literature and structural studies Wagner et al., 2016, Nucleic Acids Research, https://doi.org/10.1093/nar/gkw972 ; Valรกลกek et al., 2017, Nucleic Acids Research, https://doi.org/10.1093/nar/gkx805
Primary molecular function Non-catalytic ribosome-associated translation factor that modulates mRNA recruitment, translation initiation complex dynamics, and ribosome recycling No enzymatic activity is described; instead, eIF3j acts through protein- and ribosome-binding interactions that alter 40S/mRNA/factor configurations (sokabe2017ahelicaseindependentactivity pages 1-1, young2022rebirthofthe pages 3-4) Current understanding emphasizes regulatory rather than catalytic function Sokabe & Fraser, 2017, PNAS, https://doi.org/10.1073/pnas.1620426114 ; Young & Guydosh, 2022, BioEssays, https://doi.org/10.1002/bies.202100269
Subunit association within eIF3 system eIF3j is substoichiometric and transiently associated with holo-eIF3 eIF3j binds the eIF3b RRM and is not required for the stable PCI/MPN octamer or yeast-like core assembly; this supports its classification as peripheral/associated (wagner2016humaneif3band pages 1-2, valasek2017embracedbyeif3 pages 3-4) Important for interpreting modern cryo-EM structures, which typically focus on core eIF3 architecture Wagner et al., 2016, https://doi.org/10.1093/nar/gkw972 ; Valรกลกek et al., 2017, https://doi.org/10.1093/nar/gkx805
Domain architecture Contains an eIF3j-specific domain and functionally important N- and C-terminal regions; the N-terminus mediates factor interactions and the C-terminus contributes to RNA-regulatory functions Structural review cites NMR information for the interaction of human eIF3j residues 35-69 with human eIF3b RRM; 2022 circRNA work found the C-terminus essential for inhibitory activity on circRNA translation (valasek2017embracedbyeif3 pages 3-4, song2022eif3jinhibitstranslation pages 1-2) The C-terminal regulatory role gained new attention in 2022 Valรกลกek et al., 2017, https://doi.org/10.1093/nar/gkx805 ; Song et al., 2022, Nucleic Acids Research, https://doi.org/10.1093/nar/gkac980
Direct interaction partner(s) Interacts with eIF3b and functionally couples to eIF3 and ABCE1/RLI1 Human eIF3j N-terminal peptide contacts eIF3b RRM; ribosome recycling literature and review evidence indicate physical/functional interplay with ABCE1 and eIF3 on post-termination ribosomes (valasek2017embracedbyeif3 pages 3-4, young2022rebirthofthe pages 3-4) These interactions underpin newer models of initiation-recycling continuity Valรกลกek et al., 2017, https://doi.org/10.1093/nar/gkx805 ; Young & Guydosh, 2022, https://doi.org/10.1002/bies.202100269
Ribosome binding site Binds the 40S small subunit near the mRNA entry channel and A-site; competes anti-cooperatively with accommodated mRNA Reconstituted human systems show high-affinity binding of eIF3j to the 43S PIC/40S and a marked reduction in affinity after mRNA recruitment; this is interpreted as reporting mRNA accommodation into the decoding site/entry channel (sokabe2017ahelicaseindependentactivity pages 1-1) Remains a key mechanistic framework for understanding eIF3j action in human initiation Sokabe & Fraser, 2017, https://doi.org/10.1073/pnas.1620426114
Role in cap-dependent initiation Regulates an early step of mRNA recruitment to the 43S PIC and is displaced as mRNA becomes fully accommodated Human reconstitution experiments indicate that eIF4F/eIF4A/eIF4B-dependent mRNA recruitment lowers eIF3j affinity for the 43S PIC; short RNAs that do not extend into the entry channel fail to displace eIF3j (sokabe2017ahelicaseindependentactivity pages 1-1) Supports the current view that eIF3j marks and/or gates mRNA entry into the 40S channel Sokabe & Fraser, 2017, https://doi.org/10.1073/pnas.1620426114
Dependence on eIF4A/ATP during initiation Full reduction in eIF3j affinity during mRNA recruitment requires ATP-dependent but unwinding-independent eIF4A activity This suggests eIF3j senses a regulated conformational transition of the human 43S PIC rather than only RNA helicase action (sokabe2017ahelicaseindependentactivity pages 1-1) Conceptually reinforced by 2024 human 48S structures showing factor-rich organization around entry and exit channels Sokabe & Fraser, 2017, https://doi.org/10.1073/pnas.1620426114 ; Querido et al., 2024, Nature Structural & Molecular Biology, https://doi.org/10.1038/s41594-023-01196-0
Role in ribosome recycling Promotes efficient post-termination recycling, especially by enhancing ABCE1/RLI1-mediated subunit splitting and/or subsequent 40S recycling transitions Reviews summarize yeast/human evidence that eIF3j improves ABCE1/RLI1 recycling efficiency, binds when one ABCE1 nucleotide-binding site is partially open, and may help control post-splitting 40S states (young2022rebirthofthe pages 3-4, young2022rebirthofthe pages 4-6) Ribosome recycling remains one of the most important non-initiation functions ascribed to eIF3j in recent synthesis articles Young & Guydosh, 2022, https://doi.org/10.1002/bies.202100269
Site of action in recycling Cytoplasmic post-termination 80S/40S ribosome complexes Reconstituted and structural/review evidence places eIF3j on ribosomal complexes after termination, participating with ABCE1 and canonical initiation/recycling factors on the small subunit (young2022rebirthofthe pages 3-4, young2022rebirthofthe pages 4-6) Helps explain functional continuity between recycling and re-initiation-capable 40S states Young & Guydosh, 2022, https://doi.org/10.1002/bies.202100269
Role in translation termination fidelity / readthrough eIF3j has been linked to stop-codon decoding outcomes via the broader eIF3 network; loss of eIF3j/HCR1 increased readthrough in yeast models Review of foundational work notes that eIF3 and eIF3j associate with terminating ribosomes and influence stop-codon readthrough/termination dynamics, though much mechanistic evidence comes from yeast systems (valasek2017embracedbyeif3 pages 10-11, valasek2017embracedbyeif3 pages 11-12) Useful as evolutionary/mechanistic context, but less directly established for human EIF3J than initiation/recycling roles Valรกลกek et al., 2017, https://doi.org/10.1093/nar/gkx805
Role in circular RNA translation eIF3j can act as a negative regulator of a subset of circRNA translation by promoting eIF3 dissociation from circRNA templates In a 2022 systematic screen, eIF3j was the strongest inhibitor among tested eIFs; binding of eIF3j to circSfl promoted dissociation of eIF3, and the eIF3j C-terminus plus a circRNA UTR regulon were required (song2022eif3jinhibitstranslation pages 1-2, song2022eif3jinhibitstranslation pages 4-5) One of the clearest newly described regulatory activities relevant to 2022-2024 literature Song et al., 2022, https://doi.org/10.1093/nar/gkac980 ; Hwang & Kim, 2024 review, https://doi.org/10.1038/s12276-024-01220-3
Subcellular localization Predominantly cytoplasmic site of action, consistent with roles in mRNA translation, ribosome binding, and ribosome recycling eIF3 subunits in mammalian cells show predominantly cytoplasmic localization, and eIF3j functions are consistently described on cytoplasmic 40S/43S/80S complexes rather than nuclear pathways (duan2023eif3mrnaselectivity pages 1-2, sokabe2017ahelicaseindependentactivity pages 1-1) No strong evidence in the retrieved set for a primary non-cytoplasmic human EIF3J role Duan et al., 2023, The EMBO Journal, https://doi.org/10.15252/embj.2022112362 ; Sokabe & Fraser, 2017, https://doi.org/10.1073/pnas.1620426114
Structural context in modern human initiation complexes Modern 48S cryo-EM maps emphasize eIF3 architecture at both mRNA entry and exit sides of the 40S, providing context for eIF3jโ€™s gatekeeping position even when eIF3j itself is not the focus of the map Human 48S structure shows eIF3 octamer/core plus peripheral subunits surrounding the mRNA path and a second eIF4A at the entry site, supporting a framework in which entry-channel factors such as eIF3j regulate mRNA accommodation (querido2024thestructureof pages 1-2) Important 2024 context for integrating older eIF3j biochemical data with current structural models Querido et al., 2024, https://doi.org/10.1038/s41594-023-01196-0
Viral/pathogen interface relevance eIF3j-binding surfaces on the 40S entry region are functionally important enough to be targeted or competed by pathogens/viral factors SARS-CoV-2 Nsp1 was proposed to compete with eIF3j for 40S binding and weaken eIF3 association; this supports the biological importance of eIF3jโ€™s 40S interface (yuan2020nonstructuralprotein1 pages 1-7) Highlights translational control interfaces relevant to infection biology Yuan et al., 2020, Molecular Cell, https://doi.org/10.1016/j.molcel.2020.10.034
Human tissue expression pattern EIF3J transcript abundance varies across human tissues rather than being uniformly invariant Transcriptomic survey identified relative tissue differences, including lower expression in ovary and higher expression in brain/liver/testis-related comparisons (young2022rebirthofthe pages 1-3) Provides recent systems-level context, although not direct functional proof Anisimova et al., 2023, International Journal of Molecular Sciences, https://doi.org/10.3390/ijms24098361
Current consensus summary Human EIF3J/eIF3j is best annotated as a peripheral, non-enzymatic 40S/eIF3-associated regulator that helps coordinate mRNA entry, initiation-complex remodeling, and ribosome recycling, with emerging transcript-selective inhibitory functions on circRNA translation This synthesis is supported by assembly studies, structural reviews, biochemical reconstitution, recycling reviews, and newer circRNA-focused work (wagner2016humaneif3band pages 1-2, valasek2017embracedbyeif3 pages 1-2, sokabe2017ahelicaseindependentactivity pages 1-1, young2022rebirthofthe pages 4-6, song2022eif3jinhibitstranslation pages 1-2) Most robust experimentally supported functions remain in cytoplasmic translation control rather than signaling or catalysis Wagner et al., 2016, https://doi.org/10.1093/nar/gkw972 ; Valรกลกek et al., 2017, https://doi.org/10.1093/nar/gkx805 ; Sokabe & Fraser, 2017, https://doi.org/10.1073/pnas.1620426114 ; Young & Guydosh, 2022, https://doi.org/10.1002/bies.202100269 ; Song et al., 2022, https://doi.org/10.1093/nar/gkac980

Table: This table summarizes the main experimentally supported functions and structural features of human EIF3J/eIF3j, emphasizing its 40S/eIF3-associated roles in translation initiation and ribosome recycling. It also highlights newer findings from 2022-2024, including selective inhibition of circRNA translation and modern structural context.

9. Expert Analysis and Perspectives

Leading-edge research now highlights eIF3j as a selective, modular regulator within cytoplasmic translation, best conceptualized as a non-catalytic RNAโ€“protein remodeling factor. Its physiological impacts are most apparent at the level of core protein synthesis, ribosome recycling efficiency, and context-dependent translation inhibition (such as for circular RNA translation). Emerging evidence supports a model where eIF3j integrates mRNA fate at the interface of ribosome structure, eIF3 complex status, and cellular stress/adaptation signals.

10. Authoritative Reviews and Recommendations (Selection)

11. Statistics, Gaps, and Future Directions

  • No evidence for catalytic activity, substrate specificity for metabolites, or direct signaling function was found.
  • All current evidence supports roles as an RNA/protein interaction hubโ€”direct mRNA or substrate specificity is not a feature of this factor.
  • Structure: While structural domains and key interactions have been defined (N-terminal with eIF3b, C-terminal regulatory effects), a full-length high-resolution structure for human eIF3j remains lacking.
  • Clinical/therapeutic application is speculative but ribosome interface targeting (e.g., during viral infection) may yield future avenues.

12. Conclusion

EIF3J (eIF3j) serves as a regulatory hub for cytoplasmic ribosomes, linking translation efficiency and selectivity at both initiation and recycling stages, with recently discovered control over circular RNA translation. Continued structural, genetic, and single-molecule studies will likely further clarify its roles in disease, adaptation, and metabolic stress responses.


References

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Artifacts

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๐Ÿ“š Additional Documentation

Notes

(EIF3J-notes.md)

EIF3J research notes

UniProt O75822 (EIF3J_HUMAN), eukaryotic translation initiation factor 3 subunit J. Cytoplasm.

Core role

EIF3J is a subunit of the 13-subunit eukaryotic translation initiation factor 3 (eIF-3) complex.
- UniProt FUNCTION: "Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis [PMID:25849773, PMID:27462815]. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC)."
- The eIF-3 complex "is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation." (UniProt) โ€” this is the ribosome-recycling / 40S-availability role.

EIF3J is a labile / loosely-associated subunit

  • UniProt SUBUNIT: "EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B." (sub-stoichiometric, loosely associated).
  • In cryo-EM/structural and biochemical work eIF3j occupies the 40S mRNA entry channel and the decoding region, modulating mRNA loading and is implicated in 40S availability / recycling.
  • IC annotations for "translation initiation factor activity" (GO:0003743) are inferred from being part of the eIF-3 complex (GO:0005852) [PMID:17322308, PMID:18599441]. EIF3J itself contributes_to this activity (contributes_to qualifier), consistent with it being a non-catalytic accessory subunit rather than the catalytic core.

Annotations

  • part_of GO:0005852 eukaryotic translation initiation factor 3 complex โ€” CORE (IBA, IDA, IPI all agree). ACCEPT.
  • GO:0003743 translation initiation factor activity (contributes_to, IC; also IEA) โ€” ACCEPT as core MF (with contributes_to qualifier retained โ€” it is an accessory subunit).
  • BP translational initiation / cytoplasmic translational initiation / formation of cytoplasmic translation initiation complex โ€” ACCEPT (core process).
  • 43S/48S preinitiation complex (GO:0016282, GO:0033290) โ€” ACCEPT as non-core CC (genuine but transient assembly intermediates; IEA UniRule).
  • cytoplasm / cytosol โ€” ACCEPT.
  • protein binding IPI (many: EIF3B P55884, EIF4G1 Q04637, CSNK2A1 P68400, ABCE1 P61221, NFE2L2 Q16236) โ€” uninformative term; KEEP_AS_NON_CORE. The biologically meaningful ones (EIF3B = how it joins eIF-3; ABCE1 = recycling factor) are captured by complex membership.
  • identical protein binding GO:0042802 (self, O75822) โ€” EIF3J self-interaction (IntAct), KEEP_AS_NON_CORE.

Notable interactions

  • EIF3B (P55884): the subunit through which EIF3J docks onto eIF-3 (PMID:14688252, 18628297, 35271311). Meaningful.
  • ABCE1 (P61221): the ribosome-recycling ATPase; consistent with EIF3J/eIF-3 role in post-termination recycling and 40S availability (PMID:32296183, 35271311).
  • CSNK2A1 (P68400): casein kinase 2 (phosphorylates EIF3J; phosphorylation enhanced on serum stimulation) โ€” regulatory.

Curation conclusions

  • CORE MF: translation initiation factor activity (GO:0003743), as an accessory eIF-3 subunit (contributes_to).
  • CORE CC: eukaryotic translation initiation factor 3 complex (GO:0005852).
  • CORE BP: cytoplasmic translational initiation (GO:0002183) / translational initiation (GO:0006413).
  • protein binding IPI = KEEP_AS_NON_CORE (uninformative).

Pn Notes

(EIF3J-pn-notes.md)

EIF3J PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: O75822
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07c
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: EIF3J (eukaryotic translation initiation factor 3 subunit J) is a cytoplasmic accessory subunit of the 13-subunit eIF-3 complex, the largest eukaryotic translation initiation factor. eIF-3 associates with the 40S ribosomal subunit and orchestrates several steps of cap-dependent translation initiation, promoting recruitment of eIF-1, eIF-1A, the eIF-2-GTP-Met-tRNAi ternary complex and eIF-5 to form the 43S pre-initiation complex, stimulating mRNA recruitment and scanning to the AUG start codon, and contributing to disassembly/recycling of post-termination ribosomal complexes while preventing premature 40S-60S subunit joining. EIF3J is a loosely associated, sub-stoichiometric ("labile") subunit that docks onto the complex through EIF3B; it positions near the 40S mRNA entry channel/decoding region and is required for stable binding of eIF-3 (and its subcomplexes) to the 40S subunit, thereby modulating mRNA loading and 40S availability. It is a non-catalytic accessory factor (its initiation-factor activity is contributed in the context of the assembled complex) and is phosphorylated in a serum-stimulation-dependent manner.
  • Existing/core annotation action counts: ACCEPT: 22; KEEP_AS_NON_CORE: 13

PN Consistency Summary

  • Consistency: Initiation row is fully consistent โ€” review accepts GO:0005852 (core CC) and GO:0006413 (core BP), both in GOA. The RQC row is weakly supported: EIF3J/eIF-3 contributes to post-termination ribosome disassembly/40S recycling and prevents premature 40S-60S joining (noted via the ABCE1 interaction PMID:32296183/35271311), but the review captures this only obliquely (ABCE1 protein-binding KEEP_AS_NON_CORE) and assigns NO QC/recycling process term. So GO:0006515 is not reflected in the review.
  • PN story / NEW pressure: RQC group projects GO:0006515 protein QC as new_to_goa. EIF3J's recycling role is real but is a recycling/40S-availability function, not protein quality control / misfolded-chain surveillance; GO:0006515 (protein QC for misfolded/incompletely synthesized proteins) mischaracterizes it and over-reaches. A ribosome-recycling/disassembly process term (e.g. GO:0032790 ribosome disassembly) would be more defensible than GO:0006515 if any RQC-row term is projected.
  • Evidence alignment: Dossier gives no reference titles. Review anchors PMID:14688252 (j-subunit/40S stable binding, VERIFIED), PMID:17322308/18599441 (eIF-3 MS). Initiation evidence overlaps cleanly; the RQC claim has no dedicated citation in either source.
  • Verdict: Initiation placement consistent and correct; RQC-group GO:0006515 projection over-reaches (EIF3J is a recycling accessory, not a protein-QC factor). Recommended edits: [MAP] drop GO:0006515 projection for EIF3J (or substitute GO:0032790 ribosome disassembly if a recycling term is wanted).

Full Consistency Review

  • UniProt: O75822 ยท batch: proteostasis-batch-2026-06-07c ยท review status: COMPLETE
  • PN placement: 2 rows โ€” Translation|Cytosolic translation|Translation initiation|eIF3 complex and Translation|Cytosolic translation|Ribosome-associated QC|other RQC processes ; PN-node mapping: initiation type โ†’ GO:0005852 eIF3 complex (mapped); initiation group โ†’ GO:0006413 translational initiation (mapped); RQC group โ†’ GO:0006515 protein QC (mapped, new_to_goa); RQC type no_mapping.
  • Consistency: Initiation row is fully consistent โ€” review accepts GO:0005852 (core CC) and GO:0006413 (core BP), both in GOA. The RQC row is weakly supported: EIF3J/eIF-3 contributes to post-termination ribosome disassembly/40S recycling and prevents premature 40S-60S joining (noted via the ABCE1 interaction PMID:32296183/35271311), but the review captures this only obliquely (ABCE1 protein-binding KEEP_AS_NON_CORE) and assigns NO QC/recycling process term. So GO:0006515 is not reflected in the review.
  • PN story / NEW pressure: RQC group projects GO:0006515 protein QC as new_to_goa. EIF3J's recycling role is real but is a recycling/40S-availability function, not protein quality control / misfolded-chain surveillance; GO:0006515 (protein QC for misfolded/incompletely synthesized proteins) mischaracterizes it and over-reaches. A ribosome-recycling/disassembly process term (e.g. GO:0032790 ribosome disassembly) would be more defensible than GO:0006515 if any RQC-row term is projected.
  • Mapping strategy: Initiation mapping is correct and well-supported. The Ribosome-associated QC group โ†’ GO:0006515 is too broad/mischaracterizing for EIF3J (a recycling accessory, not a QC factor); recommend not projecting GO:0006515 here.
  • Evidence alignment: Dossier gives no reference titles. Review anchors PMID:14688252 (j-subunit/40S stable binding, VERIFIED), PMID:17322308/18599441 (eIF-3 MS). Initiation evidence overlaps cleanly; the RQC claim has no dedicated citation in either source.
  • Verdict: Initiation placement consistent and correct; RQC-group GO:0006515 projection over-reaches (EIF3J is a recycling accessory, not a protein-QC factor). Recommended edits: [MAP] drop GO:0006515 projection for EIF3J (or substitute GO:0032790 ribosome disassembly if a recycling term is wanted).

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07c
  • review_yaml: genes/human/EIF3J/EIF3J-ai-review.yaml
  • PN workbook rows: 2

PN row 1: Translation | Cytosolic translation | Translation initiation | eIF3 complex

  • UniProt: O75822
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Cytosolic translation|Translation initiation|eIF3 complex
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0005852 eukaryotic translation initiation factor 3 complex]
      rationale: This PN type denotes component membership in the eIF3 complex. Propagation to the matching GO cellular-component term is appropriate.
    • [group] Translation|Cytosolic translation|Translation initiation
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006413 translational initiation]
      rationale: This PN group denotes cytosolic translation initiation factors and complexes. Translational initiation is the shared process target.
    • [class] Translation|Cytosolic translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
      rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
    • [branch] Translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
      rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

PN row 2: Translation | Cytosolic translation | Ribosome-associated QC | other RQC processes

  • UniProt: O75822
  • In branches: TR
  • PN-node mapping records (path + ancestors):
    • [type] Translation|Cytosolic translation|Ribosome-associated QC|other RQC processes
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
    • [group] Translation|Cytosolic translation|Ribosome-associated QC
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0006515 protein quality control for misfolded or incompletely synthesized proteins]
      rationale: The PN ribosome-associated quality-control group covers surveillance and disposal of stalled or defective nascent-chain translation products. GO lacks a dedicated ribosome-associated QC term in the local cache, so the broader protein-quality-control process is the best supported target.
    • [class] Translation|Cytosolic translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0002181 cytoplasmic translation]
      rationale: The PN class Cytosolic translation is centered on the cytoplasmic translation apparatus and process, but it also houses supporting machinery such as ribosome biogenesis factors. The GO process term is a useful high-level label for the class, but propagating it to all members would over-annotate genes whose PN placement is through assembly or maturation context rather than core cytoplasmic translation.
    • [branch] Translation
      status=context_only scope=too_broad_to_propagate GO=[GO:0006412 translation]
      rationale: The PN Translation branch is organized around the translation apparatus and immediately associated cotranslational quality-control systems. GO translation is the closest high-level process label, but the PN branch also contains adjacent machinery such as ribosome biogenesis and nascent-chain handling. Keeping this relationship is useful for interpretation, but it is too broad to project safely onto every member.

Projected GO annotations (3)

  • GO:0006413 translational initiation | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Translation|Cytosolic translation|Translation initiation
  • GO:0005852 eukaryotic translation initiation factor 3 complex | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Translation|Cytosolic translation|Translation initiation|eIF3 complex
  • GO:0006515 protein quality control for misfolded or incompletely synthesized proteins | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Translation|Cytosolic translation|Ribosome-associated QC

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

๐Ÿ“„ View Raw YAML

id: O75822
gene_symbol: EIF3J
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: EIF3J (eukaryotic translation initiation factor 3 subunit J) is a cytoplasmic accessory subunit of the 13-subunit eIF-3 complex, the largest eukaryotic translation initiation factor. eIF-3 associates with the 40S ribosomal subunit and orchestrates several steps of cap-dependent translation initiation, promoting recruitment of eIF-1, eIF-1A, the eIF-2-GTP-Met-tRNAi ternary complex and eIF-5 to form the 43S pre-initiation complex, stimulating mRNA recruitment and scanning to the AUG start codon, and contributing to disassembly/recycling of post-termination ribosomal complexes while preventing premature 40S-60S subunit joining. EIF3J is a loosely associated, sub-stoichiometric ("labile") subunit that docks onto the complex through EIF3B; it positions near the 40S mRNA entry channel/decoding region and is required for stable binding of eIF-3 (and its subcomplexes) to the 40S subunit, thereby modulating mRNA loading and 40S availability. It is a non-catalytic accessory factor (its initiation-factor activity is contributed in the context of the assembled complex) and is phosphorylated in a serum-stimulation-dependent manner.
alternative_products:
- name: '1'
  id: O75822-1
- name: '2'
  id: O75822-2
  sequence_note: VSP_054593
- name: '3'
  id: O75822-3
  sequence_note: VSP_054776
existing_annotations:
- term:
    id: GO:0005852
    label: eukaryotic translation initiation factor 3 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: EIF3J is a (labile) subunit of the eIF-3 complex, well supported across eukaryotes and by direct human evidence. This is the core cellular-component annotation.
    action: ACCEPT
    reason: EIF3J is documented as a component of the 13-subunit eIF-3 complex, binding via EIF3B; the IBA is corroborated by IDA/IPI evidence.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
      supporting_text: Component of the eukaryotic translation initiation factor 3 (eIF-3) complex
- term:
    id: GO:0001732
    label: formation of cytoplasmic translation initiation complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  qualifier: involved_in
  review:
    summary: As part of eIF-3, EIF3J participates in assembly of the 43S/48S translation initiation complexes on the 40S subunit. A genuine core process annotation.
    action: ACCEPT
    reason: eIF-3 facilitates recruitment of initiation factors and ternary complex to form the 43S PIC; EIF3J contributes to this assembly.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
      supporting_text: facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to
- term:
    id: GO:0002183
    label: cytoplasmic translational initiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  qualifier: involved_in
  review:
    summary: EIF3J participates in cytoplasmic translation initiation as an eIF-3 subunit. This is the core biological process.
    action: ACCEPT
    reason: eIF-3 is required for several steps in initiation of protein synthesis; this is EIF3J's central biological role.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
      supporting_text: required for several steps in the initiation of protein synthesis
- term:
    id: GO:0003743
    label: translation initiation factor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: EIF3J contributes translation initiation factor activity as an accessory subunit of eIF-3. The activity is exerted in the context of the assembled complex rather than by EIF3J alone.
    action: ACCEPT
    reason: The core molecular function of EIF3J is translation initiation factor activity via the eIF-3 complex; note the curated experimental annotations use the contributes_to qualifier, reflecting its accessory role.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0003743 translation initiation factor activity molecular_function ECO:0000501 IEA
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: EIF3J is cytoplasmic, consistent with its role in cytoplasmic translation initiation.
    action: ACCEPT
    reason: Cytoplasm is the documented subcellular location and the site of translation initiation.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005852
    label: eukaryotic translation initiation factor 3 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: part_of
  review:
    summary: Electronic transfer of eIF-3 complex membership, redundant with the IBA/IDA/IPI evidence.
    action: ACCEPT
    reason: Correct core cellular component, corroborated by stronger evidence.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000501 IEA
- term:
    id: GO:0016282
    label: eukaryotic 43S preinitiation complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  qualifier: part_of
  review:
    summary: Via eIF-3, EIF3J is part of the transient 43S pre-initiation complex on the 40S subunit. A genuine but transient assembly intermediate.
    action: KEEP_AS_NON_CORE
    reason: The 43S PIC is a transient initiation intermediate that contains eIF-3; a real but non-core localization relative to the stable eIF-3 complex membership.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
      supporting_text: to form the 43S pre-initiation complex (43S PIC)
- term:
    id: GO:0033290
    label: eukaryotic 48S preinitiation complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000104
  qualifier: part_of
  review:
    summary: Via eIF-3, EIF3J is part of the transient 48S pre-initiation complex (after mRNA recruitment and start-codon scanning). A transient assembly intermediate.
    action: KEEP_AS_NON_CORE
    reason: The 48S PIC is a transient initiation intermediate; real but non-core relative to stable eIF-3 complex membership.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
      supporting_text: stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14688252
  qualifier: enables
  review:
    summary: Interaction with EIF3B (P55884), the subunit through which EIF3J docks onto eIF-3; this study shows EIF3J is required for stable binding of eIF-3 to 40S subunits. Deep-research synthesis further localizes EIF3J binding to the 40S near the mRNA entry channel and A-site, where it binds anti-cooperatively with mRNA and acts as a gatekeeper for mRNA accommodation. Bare protein binding is uninformative, but the interaction is biologically central.
    action: KEEP_AS_NON_CORE
    reason: Records the functionally important EIF3J-EIF3B interaction, but the term is uninformative; the informative function (eIF-3 membership and 40S/mRNA-entry-channel binding) is captured by complex/initiation annotations and core_functions.
    supported_by:
    - reference_id: PMID:14688252
      supporting_text: j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro
    - reference_id: file:human/EIF3J/EIF3J-deep-research-falcon.md
      supporting_text: Binds the 40S small subunit near the mRNA entry channel and A-site; competes anti-cooperatively with accommodated mRNA
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16932749
  qualifier: enables
  review:
    summary: Interaction reported in a study of the ribosome-associated factor p97/DAP5. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction but uninformative term; not core to EIF3J's function.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16932749 UniProtKB:Q04637
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18628297
  qualifier: enables
  review:
    summary: Interaction with EIF4G1 (Q04637) in a study of DDX3 in translation and eIF3. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a real translation-related interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:18628297 UniProtKB:P55884
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22113938
  qualifier: enables
  review:
    summary: Interaction with the casein kinase 2 catalytic subunit CSNK2A1 (P68400) from a kinase-substrate screen; consistent with EIF3J being phosphorylated. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a kinase-substrate interaction (EIF3J is phosphorylated) but uninformative term; not a core function.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:22113938 UniProtKB:P68400
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25852190
  qualifier: enables
  review:
    summary: Interaction with CSNK2A1 (P68400) from a kinase-network apoptosis study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a kinase interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25852190 UniProtKB:P68400
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: HuRI binary interactome capturing an EIF3J-ABCE1 (P61221) interaction. ABCE1 is the ribosome-recycling ATPase; deep-research synthesis indicates EIF3J specifically (not merely the eIF-3 holo-complex) functionally couples to ABCE1/RLI1 and enhances post-termination ribosome recycling, so this interaction is biologically meaningful even though the bare term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a recycling-relevant interaction (ABCE1) with EIF3J-subunit-specific functional support in the recycling literature, but the term itself is uninformative; the recycling role is captured at the complex level.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:P61221
    - reference_id: file:human/EIF3J/EIF3J-deep-research-falcon.md
      supporting_text: physically/ functionally associates with ABCE1/RLI1, the ATPase required for post-termination ribosome recycling
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32707033
  qualifier: enables
  review:
    summary: Interaction with CSNK2A1 (P68400) from a kinase-interaction-network study. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a kinase interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32707033 UniProtKB:P68400
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32911434
  qualifier: enables
  review:
    summary: Interaction with NFE2L2/NRF2 (Q16236) from an NRF2-interactome screen. Bare protein binding is uninformative and likely peripheral.
    action: KEEP_AS_NON_CORE
    reason: Records a real interaction but uninformative term and peripheral to translation initiation; not core.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32911434 UniProtKB:Q16236
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-purification capturing an EIF3J-CSNK2A1 (P68400) interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records a kinase interaction but uninformative term; not core.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:33961781 UniProtKB:P68400
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome capturing EIF3J interactions with EIF3B (P55884) and ABCE1 (P61221), consistent with eIF-3 docking and recycling roles. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records biologically consistent interactions (EIF3B, ABCE1) but uninformative term; captured by complex/initiation annotations.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:35271311 UniProtKB:P55884
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: EIF3J self-interaction reported in the HuRI binary interactome (consistent with the EIF3J-EIF3J IntAct entry). A real homotypic interaction but not a core function.
    action: KEEP_AS_NON_CORE
    reason: Records a self-interaction; not part of the core translation-initiation function.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0042802 identical protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:O75822
- term:
    id: GO:0001732
    label: formation of cytoplasmic translation initiation complex
  evidence_type: NAS
  original_reference_id: PMID:16920360
  qualifier: involved_in
  review:
    summary: Author statement (eIF3 review) that eIF-3 serves as a scaffold for assembly of translation initiation complexes; EIF3J participates as a subunit.
    action: ACCEPT
    reason: Consistent with eIF-3's documented role in initiation-complex assembly; core process for EIF3J as a subunit.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0001732 formation of cytoplasmic translation initiation complex biological_process ECO:0005547 NAS PMID:16920360
- term:
    id: GO:0005852
    label: eukaryotic translation initiation factor 3 complex
  evidence_type: IPI
  original_reference_id: PMID:17322308
  qualifier: part_of
  review:
    summary: Direct (ComplexPortal/MS) evidence placing EIF3J in the eIF-3 complex. Core cellular component.
    action: ACCEPT
    reason: Mass-spectrometry characterization of human eIF-3 confirms EIF3J as a component.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000353 IPI PMID:17322308
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-156808
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization for translation-initiation reactions.
    action: ACCEPT
    reason: Correct cytosolic localization, consistent with the cytoplasmic site of action.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-156808
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-156823
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-156823
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-157849
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-157849
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72619
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72619
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72621
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72621
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72676
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72676
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72691
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72691
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-72697
  qualifier: located_in
  review:
    summary: Reactome curated cytosolic localization, redundant with the other cytosol annotations.
    action: ACCEPT
    reason: Correct cytosolic localization.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005829 cytosol cellular_component ECO:0000304 TAS Reactome:R-HSA-72697
- term:
    id: GO:0003743
    label: translation initiation factor activity
  evidence_type: IC
  original_reference_id: PMID:17322308
  qualifier: contributes_to
  review:
    summary: Curator-inferred (from eIF-3 complex membership) that EIF3J contributes to translation initiation factor activity. The contributes_to qualifier correctly reflects its accessory role within the complex.
    action: ACCEPT
    reason: This is the core molecular function annotation for EIF3J, appropriately qualified as contributes_to for a non-catalytic accessory subunit.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0003743 translation initiation factor activity molecular_function ECO:0000305 IC PMID:17322308
- term:
    id: GO:0003743
    label: translation initiation factor activity
  evidence_type: IC
  original_reference_id: PMID:18599441
  qualifier: contributes_to
  review:
    summary: Curator-inferred translation initiation factor activity from eIF-3 complex membership (subunit interaction map study). Redundant with the other IC annotation.
    action: ACCEPT
    reason: Core molecular function, appropriately qualified contributes_to.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0003743 translation initiation factor activity molecular_function ECO:0000305 IC PMID:18599441
- term:
    id: GO:0005852
    label: eukaryotic translation initiation factor 3 complex
  evidence_type: IDA
  original_reference_id: PMID:17322308
  qualifier: part_of
  review:
    summary: Direct MS-based evidence for EIF3J as an eIF-3 component. Core cellular component.
    action: ACCEPT
    reason: Directly demonstrated eIF-3 complex membership.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000314 IDA PMID:17322308
- term:
    id: GO:0005852
    label: eukaryotic translation initiation factor 3 complex
  evidence_type: IDA
  original_reference_id: PMID:18599441
  qualifier: part_of
  review:
    summary: Direct MS-based evidence for EIF3J as an eIF-3 component (subunit interaction map). Core cellular component.
    action: ACCEPT
    reason: Directly demonstrated eIF-3 complex membership.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0005852 eukaryotic translation initiation factor 3 complex cellular_component ECO:0000314 IDA PMID:18599441
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IC
  original_reference_id: PMID:17322308
  qualifier: involved_in
  review:
    summary: Curator-inferred involvement in translational initiation from eIF-3 membership. Core biological process.
    action: ACCEPT
    reason: EIF3J participates in translation initiation as an eIF-3 subunit.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0006413 translational initiation biological_process ECO:0000305 IC PMID:17322308
- term:
    id: GO:0006413
    label: translational initiation
  evidence_type: IC
  original_reference_id: PMID:18599441
  qualifier: involved_in
  review:
    summary: Curator-inferred involvement in translational initiation from eIF-3 membership. Redundant with the other IC annotation.
    action: ACCEPT
    reason: Core biological process for EIF3J as an eIF-3 subunit.
    supported_by:
    - reference_id: file:human/EIF3J/EIF3J-goa.tsv
      supporting_text: GO:0006413 translational initiation biological_process ECO:0000305 IC PMID:18599441
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees.
  findings: []
- id: GO_REF:0000104
  title: Automatic annotation of UniProtKB entries based on UniRule rules.
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods.
  findings: []
- id: PMID:14688252
  title: The j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publications/PMID_14688252.md title matches YAML; directly establishes
      EIF3J's core function โ€” required for stable binding of eIF-3 (and subcomplexes) to 40S
      ribosomal subunits. This is the primary experimental support cited in core_functions."
  findings:
  - statement: EIF3J (the j-subunit) is required for stable binding of eIF-3 and its subcomplexes to 40S ribosomal subunits.
    reference_section_type: RESULTS
- id: PMID:16920360
  title: 'eIF3: a versatile scaffold for translation initiation complexes.'
  findings:
  - statement: eIF-3 acts as a scaffold for assembly of translation initiation complexes.
    reference_section_type: RESULTS
- id: PMID:16932749
  title: p97/DAP5 is a ribosome-associated factor that facilitates protein synthesis and cell proliferation by modulating the synthesis of cell cycle proteins.
  findings: []
- id: PMID:17322308
  title: Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry.
  findings:
  - statement: Mass-spectrometry characterization of human eIF-3 confirms EIF3J as a subunit of the complex.
    reference_section_type: RESULTS
- id: PMID:18599441
  title: Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3.
  findings:
  - statement: Subunit interaction map of eIF-3 places EIF3J as a labile subunit binding via EIF3B.
    reference_section_type: RESULTS
- id: PMID:18628297
  title: Human DDX3 functions in translation and interacts with the translation initiation factor eIF3.
  findings: []
- id: PMID:22113938
  title: A bead-based approach for large-scale identification of in vitro kinase substrates.
  findings: []
- id: PMID:25852190
  title: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: PMID:32707033
  title: Kinase Interaction Network Expands Functional and Disease Roles of Human Kinases.
  findings: []
- id: PMID:32911434
  title: A functionally defined high-density NRF2 interactome reveals new conditional regulators of ARE transactivation.
  findings: []
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
- id: PMID:25849773
  title: eIF3 targets cell-proliferation messenger RNAs for translational activation or repression.
  findings:
  - statement: eIF-3 selectively targets a subset of cell-proliferation mRNAs for translational activation or repression via stem-loop binding.
    reference_section_type: RESULTS
- id: PMID:27462815
  title: eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation.
  findings:
  - statement: eIF-3 (via eIF3d) mediates specialized cap-dependent translation initiation.
    reference_section_type: RESULTS
- id: Reactome:R-HSA-156808
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: Reactome:R-HSA-156823
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: Reactome:R-HSA-157849
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: Reactome:R-HSA-72619
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: Reactome:R-HSA-72621
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: Reactome:R-HSA-72676
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: Reactome:R-HSA-72691
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: Reactome:R-HSA-72697
  title: Reactome translation-initiation reaction (cytosolic).
  findings: []
- id: file:human/EIF3J/EIF3J-deep-research-falcon.md
  title: Falcon deep research report for EIF3J
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: "LLM-synthesized deep-research report (Edison/falcon); citations are author-year
      keys to reviews/primary papers, not independently re-verified here, hence UNVERIFIED.
      EIF3J-SUBUNIT-SPECIFIC claims that are well-anchored to primary literature and used below:
      (1) eIF3j binds the human 40S near the mRNA entry channel and A-site, anti-cooperatively with
      mRNA, acting as a gatekeeper for mRNA accommodation and being displaced upon mRNA recruitment
      in an ATP-dependent, helicase-independent manner (Sokabe & Fraser 2017, PNAS); (2) eIF3j
      functionally couples to ABCE1/RLI1 and enhances post-termination ribosome recycling (Young &
      Guydosh 2022, BioEssays); (3) eIF3j N-terminus contacts the eIF3b RRM (NMR) and its C-terminus
      mediates transcript-selective inhibition of a subset of circRNA translation (Song et al. 2022).
      DISTINGUISH from eIF3 HOLO-COMPLEX inference: the report repeatedly attributes whole-eIF3
      functions (43S/48S PIC formation, cap-dependent initiation, mRNA scanning, start-codon
      selectivity, NF-kB/IFN crosstalk) to the complex; these are NOT EIF3J-subunit-specific and were
      not used to strengthen subunit-level annotations. The eIF3j-specific, biochemically grounded
      roles are the mRNA-entry-channel/A-site gatekeeping and the ABCE1-coupled recycling role."
  findings:
  - statement: eIF3j binds the human 40S near the mRNA entry channel and A-site (anti-cooperatively with mRNA) as a gatekeeper for mRNA accommodation, and is displaced upon mRNA recruitment; it also functionally couples to ABCE1/RLI1 to enhance post-termination ribosome recycling.
    reference_section_type: RESULTS
- id: file:human/EIF3J/EIF3J-uniprot.txt
  title: UniProt entry O75822 (EIF3J_HUMAN), Eukaryotic translation initiation factor 3 subunit J.
  findings:
  - statement: EIF3J is a labile/loosely-associated subunit of the eIF-3 complex that binds via EIF3B; eIF-3 associates with the 40S subunit, drives 43S/48S pre-initiation complex formation, mRNA recruitment and scanning, and post-termination ribosome recycling; cytoplasmic; phosphorylated upon serum stimulation.
    reference_section_type: OTHER
core_functions:
- description: Accessory (labile) subunit of the eIF-3 complex that contributes translation initiation factor activity, helping eIF-3 assemble the 43S/48S pre-initiation complexes on the 40S ribosomal subunit and recruit/scan mRNA during cap-dependent translation initiation.
  molecular_function:
    id: GO:0003743
    label: translation initiation factor activity
  in_complex:
    id: GO:0005852
    label: eukaryotic translation initiation factor 3 complex
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
    supporting_text: required for several steps in the initiation of protein synthesis
  - reference_id: PMID:14688252
    supporting_text: j-subunit of human translation initiation factor eIF3 is required for the stable binding of eIF3 and its subcomplexes to 40 S ribosomal subunits in vitro
- description: Structural component of the eIF-3 complex; EIF3J docks onto eIF-3 through EIF3B and is required for stable association of eIF-3 with the 40S ribosomal subunit, positioning near the mRNA entry channel and modulating mRNA loading and 40S availability (including in ribosome recycling).
  molecular_function:
    id: GO:0003743
    label: translation initiation factor activity
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: file:human/EIF3J/EIF3J-uniprot.txt
    supporting_text: EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B
  - reference_id: file:human/EIF3J/EIF3J-deep-research-falcon.md
    supporting_text: Binds the 40S small subunit near the mRNA entry channel and A-site; competes anti-cooperatively with accommodated mRNA
  in_complex:
    id: GO:0005852
    label: eukaryotic translation initiation factor 3 complex
proposed_new_terms: []
suggested_questions:
- question: Does human EIF3J have a distinct, separable role in 40S ribosome recycling/availability (post-termination) versus initiation, as suggested by yeast Hcr1?
- question: How does the sub-stoichiometric/labile association of EIF3J with eIF-3 regulate switching between mRNA-entry-channel occupancy and mRNA loading?
- question: What is the functional consequence of serum-stimulated phosphorylation of EIF3J for its association with eIF-3 and selective mRNA translation?
suggested_experiments:
- description: Selective EIF3J depletion/rescue with ribosome profiling and 40S/80S subunit-availability assays to dissect its contribution to initiation versus post-termination recycling.
- description: Cryo-EM of 40S-eIF-3 complexes with and without EIF3J to define its occupancy of the mRNA entry channel and effect on mRNA accommodation.
- description: Phosphomutant (phospho-null/phospho-mimetic) EIF3J variants to test how serum-stimulated phosphorylation modulates eIF-3 binding and translational output.