{"gene":"NUP42","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2006,"finding":"Gle1 (anchored to the NPC via Nup42) and inositol hexakisphosphate (InsP6) together stimulate the RNA-dependent ATPase activity of the DEAD-box protein Dbp5 during mRNA export; InsP6 alone had minimal effect and required both Dbp5 and Gle1 for maximal binding. Overexpression of DBP5 suppressed mRNA export and growth defects of an ipk1 nup42 double mutant, placing Nup42 in the same pathway.","method":"In vitro ATPase kinetic assays with recombinant proteins; genetic suppression analysis (DBP5 overexpression in ipk1 nup42 mutant); genetic epistasis in S. cerevisiae","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of ATPase stimulation with defined components, replicated genetically with epistasis analysis","pmids":["16783363"],"is_preprint":false},{"year":1999,"finding":"Human NLP1/NUPL2 (nucleoporin-like protein 1) interacts with the HIV-1 Rev nuclear export signal and with CRM1, both in yeast two-hybrid and mammalian cell assays. The protein contains FG repeats, high serine content, a putative zinc finger, and a coiled-coil domain, and is O-glycosylated.","method":"Yeast two-hybrid screening; wheat germ agglutinin chromatography for O-glycosylation; gene expression analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — yeast two-hybrid and biochemical fractionation, two orthogonal methods in a single lab, no reciprocal Co-IP","pmids":["10358091"],"is_preprint":false},{"year":1999,"finding":"Yeast Nup42 was identified as an Ulp1-interacting protein by two-hybrid screening, and Gle1 (another NPC component that interacts with Nup42) also co-immunoprecipitated with Ulp1, placing Nup42 at the NPC in association with the SUMO protease Ulp1.","method":"Yeast two-hybrid screening; co-immunoprecipitation","journal":"Journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — two-hybrid plus co-IP in a single study, single lab","pmids":["11056382"],"is_preprint":false},{"year":1999,"finding":"Yeast Nup42 (and Nup159) form a Nup/Crm1/RanGTP complex after reaction with a Rev/Crm1/RanGTP complex, concomitantly releasing Rev; RanBP1 can then displace the Nup, demonstrating that Nup42 is a reaction intermediate in Crm1-mediated nuclear export.","method":"In vitro binding assay with recombinant proteins; identification of putative reaction intermediates","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical reconstitution of sequential complex formation in vitro, single lab","pmids":["10347184"],"is_preprint":false},{"year":2004,"finding":"Genetic analysis in S. cerevisiae showed that nup42Δ ipk1Δ double mutants are synthetically lethal/sick, and complementation did not require the FG repeat domain of Nup42, indicating that IP6 produced by Ipk1 acts at a step after heterogeneous nuclear ribonucleoprotein targeting to the NPC and that Nup42 functions at the cytoplasmic face in the Gle1-IP6 mRNA export pathway.","method":"Synthetic lethality/fitness analysis; complementation with FG-domain deletion constructs; spatial restriction of Ipk1 using membrane anchors","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with multiple allele combinations and domain dissection, single lab","pmids":["15459192"],"is_preprint":false},{"year":2010,"finding":"In S. cerevisiae heat shock, Nup42 participates in thermotolerance: a nup42 nab2-T178A/S180A double mutant has decreased thermotolerance, linking Nup42 function to the MAP kinase Slt2-dependent mRNA retention pathway under stress.","method":"Genetic double-mutant analysis; thermotolerance assay","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — genetic epistasis in a clean genetic background, single lab, limited mechanistic follow-up specific to Nup42","pmids":["20823268"],"is_preprint":false},{"year":2012,"finding":"Human NLP1/NUPL2 localizes to the nuclear envelope and is mobile within the nucleus; it promotes formation of CRM1•RanGTP complexes (with or without NES cargo), which can be dissociated by RanBP1 and Nup214. The FG repeats of NLP1 are not required for CRM1 binding. Overexpression of NLP1 promotes CRM1-dependent export, and siRNA-mediated depletion reduces export rates.","method":"Fluorescence microscopy (localization); co-immunoprecipitation; siRNA knockdown with nuclear export assay; overexpression assay","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal biochemical assays, siRNA loss-of-function, overexpression gain-of-function, and direct localization with functional consequence, multiple orthogonal methods in a single study","pmids":["22250199"],"is_preprint":false},{"year":2014,"finding":"The FG repeat domains of both Nup42 and Nup159 at the cytoplasmic face of the NPC are required for efficient mRNP remodeling during export; deletion of both FG domains causes a cold-sensitive poly(A)+ mRNA export defect and synthetic lethality with dbp5 and gle1 mutants. FG domain swaps showed that only certain FG domains are functional at the cytoplasmic face, and fusing the Nup42 FG domain to Gle1 bypasses the need for endogenous Nup42 FG, demonstrating its role in positioning mRNPs for Gle1/Dbp5 remodeling.","method":"Genetic deletion and FG-domain swap analysis; poly(A)+ mRNA export assay; RNA cross-linking; synthetic lethality with dbp5/gle1 mutants","journal":"Genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple genetic perturbations, domain-swap rescue, RNA cross-linking, and epistasis all in one study supporting the same mechanistic conclusion","pmids":["24931410"],"is_preprint":false},{"year":2017,"finding":"The Nup42 carboxy-terminal domain (CTD) binds Gle1/hGle1B at an interface distinct from the Gle1-Dbp5/hDDX19B interaction site; a Nup42-CTD/Gle1-CTD/Dbp5 trimeric complex forms in the presence of IP6. Deletion of NUP42 abrogates the Gle1-Dbp5 interaction. In vitro, Nup42-CTD and IP6 stimulate Gle1/hGle1B activation of Dbp5 and DDX19B in similar, non-additive manners. This mechanism is fully conserved between yeast and human cells.","method":"Structure-function analysis with domain deletions/point mutants; co-immunoprecipitation; in vitro ATPase reconstitution; mRNA export assays in S. cerevisiae and human cells","journal":"Traffic (Copenhagen, Denmark)","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro reconstitution of ATPase activation, multiple domain mutants, confirmed in both yeast and human cells with orthogonal methods","pmids":["28869701"],"is_preprint":false},{"year":2018,"finding":"Crystal structures of Gle1•Nup42 from three organisms reveal a conserved binding mode; crystal structures of human Gle1•Nup42•DDX19 capture the structural rearrangement in DDX19 from an auto-inhibited to an RNA-binding competent state. Biochemical reconstitution showed that human DDX19 activation does not require IP6 (unlike fungal homologs), and that Gle1 thermostability affects DDX19 activation. Disease-linked mutations reduce Gle1 thermostability.","method":"X-ray crystallography (Gle1•Nup42 and Gle1•Nup42•DDX19); in vitro ATPase reconstitution; thermal stability assays; mutation analysis","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — multiple crystal structures with biochemical reconstitution and mutagenesis validating the structural findings","pmids":["29899397"],"is_preprint":false},{"year":2019,"finding":"In fission yeast, the Nup42 ortholog Amo1 (NUPL2) is required at the nuclear periphery for propagation of heterochromatin. Amo1 associates with the Rix1-containing RNA processing complex (RIXC) and the histone chaperone complex FACT. RIXC connects heterochromatin protein Swi6HP1 to Amo1 at the nuclear rim; Amo1 in turn enables Swi6 association with FACT, which precludes histone turnover, thereby promoting gene silencing and epigenetic stability.","method":"Genetic screen; co-immunoprecipitation/co-purification; ChIP; epistasis analysis; deletion mutants with silencing and histone turnover readouts","journal":"Cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (Co-IP, ChIP, genetic epistasis, histone turnover assays) in a single high-quality study demonstrating a defined mechanism","pmids":["31883795"],"is_preprint":false},{"year":2022,"finding":"Mislocalization of Nup42 (along with Nup159) to petal-like structures occurs when yeast Brl1 AαH (amphipathic α-helix) function is compromised, linking Brl1-mediated INM/ONM fusion during NPC assembly to proper cytoplasmic-face localization of Nup42.","method":"Fluorescence microscopy of Nup localization in brl1 mutants; AlphaFold structural prediction followed by mutagenesis","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization readout in a defined mutant background, single lab; Nup42 mislocalization is a secondary finding in a Brl1 study","pmids":["35293775"],"is_preprint":false},{"year":2024,"finding":"During coronavirus (IBV) infection, NUP42 (along with other FG-Nups) undergoes cytosolic dispersion from the nuclear envelope and exhibits a size mobility shift. The IBV nucleocapsid N protein, by recruiting p-PKCα to RACK1, drives phosphorylation and cytoplasmic redistribution of NUP62 and dispersal of FG-Nups including NUP42, thereby disrupting nucleocytoplasmic trafficking and suppressing innate immune gene expression.","method":"Immunofluorescence microscopy; SDS-PAGE mobility shift; interactome/co-immunoprecipitation; siRNA knockdown; viral infection model","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — NUP42 dispersion and mobility shift are observed directly, but the mechanistic details of the modification causing NUP42 shift are not fully resolved for NUP42 specifically; single lab","pmids":["39602452"],"is_preprint":false},{"year":2026,"finding":"Nup42 suppresses heat-induced mRNA condensation: loss of Nup42 triggers nuclear condensation of chaperone mRNAs that are exported but remain translationally incompetent, impairing chaperone production and causing thermosensitivity. A genome-wide CRISPRi screen identified Nup42 as the strongest suppressor of heat-induced mRNA condensation, and co-transcriptional mRNP packaging was found to be a critical determinant of condensation in Nup42-deficient cells.","method":"Genome-wide CRISPRi screen (FRep-Seq); mRNA fractionation; translation assays; thermosensitivity assays","journal":"bioRxiv","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genome-wide functional screen plus orthogonal biochemical and phenotypic validation in a single preprint study; not yet peer-reviewed","pmids":["41727045"],"is_preprint":true}],"current_model":"NUP42/NUPL2 is a cytoplasmic-face nucleoporin whose carboxy-terminal domain anchors Gle1 at the nuclear pore complex, enabling Gle1 and IP6 to activate the DEAD-box ATPase Dbp5/DDX19B for mRNP remodeling and directional mRNA export; its FG repeats additionally position mRNPs for this remodeling step, and in the nucleus it serves as an accessory factor for CRM1-dependent protein export, while its ortholog in fission yeast (Amo1) links the nuclear periphery to heterochromatin maintenance by bridging the RIXC complex and the FACT histone chaperone to suppress histone turnover."},"narrative":{"mechanistic_narrative":"NUP42 (NUPL2) is a cytoplasmic-face FG-nucleoporin that functions as a key positioning and scaffolding factor in directional mRNA export at the nuclear pore complex [PMID:24931410, PMID:28869701]. Its carboxy-terminal domain anchors Gle1, binding at an interface distinct from the Gle1-Dbp5/DDX19B site, to assemble a Nup42-CTD/Gle1/Dbp5 complex that, together with IP6, stimulates the RNA-dependent ATPase activity of the DEAD-box protein Dbp5/DDX19B for mRNP remodeling; loss of NUP42 abolishes the Gle1-Dbp5 interaction, and this activation mechanism is conserved from yeast to human [PMID:16783363, PMID:28869701]. Crystal structures of Gle1•Nup42•DDX19 capture the rearrangement of DDX19 from an auto-inhibited to an RNA-binding-competent state, with human DDX19 activation being IP6-independent [PMID:29899397]. In parallel, the FG repeats of Nup42 (with those of Nup159) position mRNPs for Gle1/Dbp5 remodeling, since fusing the Nup42 FG domain to Gle1 bypasses the requirement for endogenous Nup42 FG [PMID:24931410]. NUP42 also serves as an accessory factor for CRM1-dependent protein export: human NUPL2 binds CRM1 and the HIV-1 Rev NES, promotes formation of CRM1•RanGTP complexes independently of its FG repeats, and acts as a reaction intermediate that is displaced by RanBP1 and Nup214 [PMID:10358091, PMID:10347184, PMID:22250199]. Beyond export, NUP42 contributes to stress responses, suppressing heat-induced nuclear condensation of chaperone mRNAs to sustain chaperone production and thermotolerance [PMID:41727045], and its fission yeast ortholog Amo1 bridges the RIXC complex and the FACT histone chaperone at the nuclear periphery to suppress histone turnover and maintain heterochromatin [PMID:31883795].","teleology":[{"year":1999,"claim":"Established the first molecular partners of human NUPL2, placing it on the CRM1-dependent protein export pathway through interaction with the HIV-1 Rev NES and CRM1.","evidence":"Yeast two-hybrid and WGA chromatography for O-glycosylation in human cells","pmids":["10358091"],"confidence":"Medium","gaps":["No reciprocal Co-IP or in-cell functional consequence demonstrated","Role of the zinc finger and coiled-coil domains undefined"]},{"year":1999,"claim":"Reconstituted the sequential biochemistry showing Nup42 acts as a Crm1/RanGTP reaction intermediate that releases export cargo and is in turn displaced by RanBP1, defining its mechanistic position in nuclear export.","evidence":"In vitro binding assays with recombinant Rev/Crm1/RanGTP and Nup proteins","pmids":["10347184"],"confidence":"Medium","gaps":["In vitro reconstitution only, no cellular validation","Relative contribution of Nup42 versus Nup159 unresolved"]},{"year":1999,"claim":"Linked yeast Nup42 to the SUMO protease Ulp1 at the NPC, hinting at a connection between Nup42-anchored complexes and SUMO regulation.","evidence":"Yeast two-hybrid screening and co-immunoprecipitation in S. cerevisiae","pmids":["11056382"],"confidence":"Medium","gaps":["Functional significance of the Ulp1 association not established","No follow-up connecting SUMO processing to Nup42 export function"]},{"year":2004,"claim":"Genetically placed Nup42 at the cytoplasmic face in the Gle1-IP6 mRNA export pathway and showed its FG repeats are dispensable for this genetic function, separating positioning from anchoring roles.","evidence":"Synthetic lethality and FG-domain complementation analysis in S. cerevisiae","pmids":["15459192"],"confidence":"Medium","gaps":["Did not define the biochemical step Nup42 contributes to","Direct Gle1 anchoring role not yet structurally resolved"]},{"year":2006,"claim":"Demonstrated that Gle1, anchored via Nup42, together with IP6 stimulates Dbp5 ATPase activity, establishing the biochemical output of the Nup42/Gle1 module in mRNA export.","evidence":"In vitro ATPase kinetics with recombinant proteins and DBP5 genetic suppression of ipk1 nup42 mutants in S. cerevisiae","pmids":["16783363"],"confidence":"High","gaps":["Direct Nup42-Gle1 interaction interface not yet defined","Did not establish how Nup42 contributes structurally to activation"]},{"year":2010,"claim":"Connected Nup42 to stress-responsive mRNA retention, showing its function intersects the Slt2 MAP kinase pathway controlling thermotolerance.","evidence":"Genetic double-mutant (nup42 nab2) thermotolerance assay in S. cerevisiae","pmids":["20823268"],"confidence":"Medium","gaps":["Mechanism of Nup42 in mRNA retention not resolved","Direct molecular link to Slt2 signaling not shown"]},{"year":2012,"claim":"Provided cellular gain- and loss-of-function evidence that human NUPL2 promotes CRM1-dependent export and forms RanBP1/Nup214-dissociable CRM1•RanGTP complexes independently of its FG repeats.","evidence":"Fluorescence localization, reciprocal Co-IP, siRNA knockdown, and overexpression export assays in mammalian cells","pmids":["22250199"],"confidence":"High","gaps":["How NUPL2 stabilizes CRM1•RanGTP mechanistically unresolved","Relationship between protein-export and mRNA-export functions not integrated"]},{"year":2014,"claim":"Resolved the role of the Nup42 FG domain, showing it positions mRNPs for Gle1/Dbp5 remodeling at the cytoplasmic face, separable from Gle1 anchoring.","evidence":"Genetic FG-domain deletion/swap, RNA cross-linking, and synthetic lethality with dbp5/gle1 in S. cerevisiae","pmids":["24931410"],"confidence":"High","gaps":["Structural basis of FG-mRNP positioning not defined","FG-domain specificity determinants only partially mapped"]},{"year":2017,"claim":"Defined the Nup42 CTD as the Gle1 anchor and showed a Nup42-CTD/Gle1/Dbp5 trimeric complex with IP6 activates the ATPase, with the mechanism conserved between yeast and human.","evidence":"Domain deletion/point mutants, Co-IP, in vitro ATPase reconstitution, and mRNA export assays in yeast and human cells","pmids":["28869701"],"confidence":"High","gaps":["Atomic structure of the trimeric complex not yet provided in this study","How CTD binding alters Gle1 activity not structurally explained"]},{"year":2018,"claim":"Provided atomic-resolution mechanism, capturing the Gle1•Nup42•DDX19 rearrangement of DDX19 to an RNA-competent state and showing human DDX19 activation is IP6-independent and tied to Gle1 thermostability.","evidence":"Multiple X-ray crystal structures with ATPase reconstitution, thermal stability assays, and disease-mutation analysis","pmids":["29899397"],"confidence":"High","gaps":["In vivo dynamics of the remodeling cycle at the NPC not captured","How disease-linked Gle1 destabilization perturbs export in cells not directly shown"]},{"year":2019,"claim":"Revealed a distinct chromatin function for the fission yeast ortholog Amo1, bridging the RIXC complex and FACT at the nuclear periphery to suppress histone turnover and maintain heterochromatin.","evidence":"Genetic screen, Co-IP/co-purification, ChIP, epistasis, and histone-turnover readouts in S. pombe","pmids":["31883795"],"confidence":"High","gaps":["Whether human NUPL2 has an analogous chromatin-silencing role unknown","Connection between heterochromatin function and export function unestablished"]},{"year":2022,"claim":"Linked proper cytoplasmic-face localization of Nup42 to Brl1-mediated nuclear membrane fusion during NPC assembly.","evidence":"Fluorescence microscopy of Nup42 localization in brl1 mutants with AlphaFold-guided mutagenesis in S. cerevisiae","pmids":["35293775"],"confidence":"Medium","gaps":["Nup42 mislocalization is a secondary observation in a Brl1 study","Direct assembly determinants for Nup42 not mapped"]},{"year":2024,"claim":"Showed NUP42 is a target of viral subversion, undergoing dispersion and a mobility shift during coronavirus infection that contributes to disruption of nucleocytoplasmic trafficking.","evidence":"Immunofluorescence, SDS-PAGE mobility shift, interactome, and siRNA in an IBV infection model","pmids":["39602452"],"confidence":"Medium","gaps":["The specific modification driving the NUP42 mobility shift is not resolved","Direct contribution of NUP42 dispersal to immune suppression not isolated from other FG-Nups"]},{"year":2026,"claim":"Identified Nup42 as the strongest suppressor of heat-induced mRNA condensation, connecting its export function to maintenance of translatable chaperone mRNAs and thermotolerance.","evidence":"Genome-wide CRISPRi screen (FRep-Seq), mRNA fractionation, translation, and thermosensitivity assays (preprint)","pmids":["41727045"],"confidence":"Medium","gaps":["Not yet peer-reviewed","How co-transcriptional mRNP packaging is mechanistically coupled to Nup42 unresolved","Direct molecular determinant of condensation suppression unknown"]},{"year":null,"claim":"How NUP42's roles in mRNA export, CRM1-dependent protein export, stress-induced mRNA condensation, and peripheral chromatin maintenance are coordinated within a single protein at the pore remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified structural/functional model linking the export and chromatin functions","Whether the human protein recapitulates the ortholog's chromatin role untested","In vivo dynamics of the Gle1/Dbp5 remodeling cycle at the pore not captured"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,8]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[6,8]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[7]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[6]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[6]}],"pathway":[{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,7,8]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[3,6]},{"term_id":"R-HSA-4839726","term_label":"Chromatin organization","supporting_discovery_ids":[10]}],"complexes":["nuclear pore complex (cytoplasmic face)","Nup42-CTD/Gle1/Dbp5 (DDX19) complex"],"partners":["GLE1","DBP5","DDX19B","CRM1","NUP159","NUP214","ULP1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O15504","full_name":"Nucleoporin NUP42","aliases":["NLP-1","NUP42 homolog","Nucleoporin hCG1","Nucleoporin-42","Nucleoporin-like protein 2"],"length_aa":423,"mass_kda":44.9,"function":"Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm (Microbial infection) In case of infection by HIV-1, it may participate in the docking of viral Vpr at the nuclear envelope","subcellular_location":"Nucleus, nuclear pore complex; Nucleus membrane","url":"https://www.uniprot.org/uniprotkb/O15504/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP42","classification":"Not Classified","n_dependent_lines":49,"n_total_lines":1208,"dependency_fraction":0.04056291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"NCL","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2},{"gene":"RAN","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2},{"gene":"SNRPA","stoichiometry":0.2},{"gene":"SNRPF","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NUP42","total_profiled":1310},"omim":[{"mim_id":"619998","title":"NUCLEOPORIN 42; NUP42","url":"https://www.omim.org/entry/619998"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear membrane","reliability":"Supported"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP42"},"hgnc":{"alias_symbol":["NLP_1","CG1","hCG1","H_RG271G13.9"],"prev_symbol":["NUPL2"]},"alphafold":{"accession":"O15504","domains":[{"cath_id":"-","chopping":"110-208","consensus_level":"high","plddt":79.3231,"start":110,"end":208},{"cath_id":"-","chopping":"391-421","consensus_level":"high","plddt":81.8639,"start":391,"end":421}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O15504","model_url":"https://alphafold.ebi.ac.uk/files/AF-O15504-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O15504-F1-predicted_aligned_error_v6.png","plddt_mean":55.34},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP42","jax_strain_url":"https://www.jax.org/strain/search?query=NUP42"},"sequence":{"accession":"O15504","fasta_url":"https://rest.uniprot.org/uniprotkb/O15504.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O15504/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O15504"}},"corpus_meta":[{"pmid":"16783363","id":"PMC_16783363","title":"Inositol 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cells","url":"https://pubmed.ncbi.nlm.nih.gov/42092527","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19349,"output_tokens":3881,"usd":0.058131,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11561,"output_tokens":4624,"usd":0.086703,"stage2_stop_reason":"end_turn"},"total_usd":0.144834,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2006,\n      \"finding\": \"Gle1 (anchored to the NPC via Nup42) and inositol hexakisphosphate (InsP6) together stimulate the RNA-dependent ATPase activity of the DEAD-box protein Dbp5 during mRNA export; InsP6 alone had minimal effect and required both Dbp5 and Gle1 for maximal binding. Overexpression of DBP5 suppressed mRNA export and growth defects of an ipk1 nup42 double mutant, placing Nup42 in the same pathway.\",\n      \"method\": \"In vitro ATPase kinetic assays with recombinant proteins; genetic suppression analysis (DBP5 overexpression in ipk1 nup42 mutant); genetic epistasis in S. cerevisiae\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of ATPase stimulation with defined components, replicated genetically with epistasis analysis\",\n      \"pmids\": [\"16783363\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Human NLP1/NUPL2 (nucleoporin-like protein 1) interacts with the HIV-1 Rev nuclear export signal and with CRM1, both in yeast two-hybrid and mammalian cell assays. The protein contains FG repeats, high serine content, a putative zinc finger, and a coiled-coil domain, and is O-glycosylated.\",\n      \"method\": \"Yeast two-hybrid screening; wheat germ agglutinin chromatography for O-glycosylation; gene expression analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — yeast two-hybrid and biochemical fractionation, two orthogonal methods in a single lab, no reciprocal Co-IP\",\n      \"pmids\": [\"10358091\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Yeast Nup42 was identified as an Ulp1-interacting protein by two-hybrid screening, and Gle1 (another NPC component that interacts with Nup42) also co-immunoprecipitated with Ulp1, placing Nup42 at the NPC in association with the SUMO protease Ulp1.\",\n      \"method\": \"Yeast two-hybrid screening; co-immunoprecipitation\",\n      \"journal\": \"Journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — two-hybrid plus co-IP in a single study, single lab\",\n      \"pmids\": [\"11056382\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"Yeast Nup42 (and Nup159) form a Nup/Crm1/RanGTP complex after reaction with a Rev/Crm1/RanGTP complex, concomitantly releasing Rev; RanBP1 can then displace the Nup, demonstrating that Nup42 is a reaction intermediate in Crm1-mediated nuclear export.\",\n      \"method\": \"In vitro binding assay with recombinant proteins; identification of putative reaction intermediates\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical reconstitution of sequential complex formation in vitro, single lab\",\n      \"pmids\": [\"10347184\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Genetic analysis in S. cerevisiae showed that nup42Δ ipk1Δ double mutants are synthetically lethal/sick, and complementation did not require the FG repeat domain of Nup42, indicating that IP6 produced by Ipk1 acts at a step after heterogeneous nuclear ribonucleoprotein targeting to the NPC and that Nup42 functions at the cytoplasmic face in the Gle1-IP6 mRNA export pathway.\",\n      \"method\": \"Synthetic lethality/fitness analysis; complementation with FG-domain deletion constructs; spatial restriction of Ipk1 using membrane anchors\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with multiple allele combinations and domain dissection, single lab\",\n      \"pmids\": [\"15459192\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"In S. cerevisiae heat shock, Nup42 participates in thermotolerance: a nup42 nab2-T178A/S180A double mutant has decreased thermotolerance, linking Nup42 function to the MAP kinase Slt2-dependent mRNA retention pathway under stress.\",\n      \"method\": \"Genetic double-mutant analysis; thermotolerance assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — genetic epistasis in a clean genetic background, single lab, limited mechanistic follow-up specific to Nup42\",\n      \"pmids\": [\"20823268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Human NLP1/NUPL2 localizes to the nuclear envelope and is mobile within the nucleus; it promotes formation of CRM1•RanGTP complexes (with or without NES cargo), which can be dissociated by RanBP1 and Nup214. The FG repeats of NLP1 are not required for CRM1 binding. Overexpression of NLP1 promotes CRM1-dependent export, and siRNA-mediated depletion reduces export rates.\",\n      \"method\": \"Fluorescence microscopy (localization); co-immunoprecipitation; siRNA knockdown with nuclear export assay; overexpression assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal biochemical assays, siRNA loss-of-function, overexpression gain-of-function, and direct localization with functional consequence, multiple orthogonal methods in a single study\",\n      \"pmids\": [\"22250199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"The FG repeat domains of both Nup42 and Nup159 at the cytoplasmic face of the NPC are required for efficient mRNP remodeling during export; deletion of both FG domains causes a cold-sensitive poly(A)+ mRNA export defect and synthetic lethality with dbp5 and gle1 mutants. FG domain swaps showed that only certain FG domains are functional at the cytoplasmic face, and fusing the Nup42 FG domain to Gle1 bypasses the need for endogenous Nup42 FG, demonstrating its role in positioning mRNPs for Gle1/Dbp5 remodeling.\",\n      \"method\": \"Genetic deletion and FG-domain swap analysis; poly(A)+ mRNA export assay; RNA cross-linking; synthetic lethality with dbp5/gle1 mutants\",\n      \"journal\": \"Genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple genetic perturbations, domain-swap rescue, RNA cross-linking, and epistasis all in one study supporting the same mechanistic conclusion\",\n      \"pmids\": [\"24931410\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The Nup42 carboxy-terminal domain (CTD) binds Gle1/hGle1B at an interface distinct from the Gle1-Dbp5/hDDX19B interaction site; a Nup42-CTD/Gle1-CTD/Dbp5 trimeric complex forms in the presence of IP6. Deletion of NUP42 abrogates the Gle1-Dbp5 interaction. In vitro, Nup42-CTD and IP6 stimulate Gle1/hGle1B activation of Dbp5 and DDX19B in similar, non-additive manners. This mechanism is fully conserved between yeast and human cells.\",\n      \"method\": \"Structure-function analysis with domain deletions/point mutants; co-immunoprecipitation; in vitro ATPase reconstitution; mRNA export assays in S. cerevisiae and human cells\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro reconstitution of ATPase activation, multiple domain mutants, confirmed in both yeast and human cells with orthogonal methods\",\n      \"pmids\": [\"28869701\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Crystal structures of Gle1•Nup42 from three organisms reveal a conserved binding mode; crystal structures of human Gle1•Nup42•DDX19 capture the structural rearrangement in DDX19 from an auto-inhibited to an RNA-binding competent state. Biochemical reconstitution showed that human DDX19 activation does not require IP6 (unlike fungal homologs), and that Gle1 thermostability affects DDX19 activation. Disease-linked mutations reduce Gle1 thermostability.\",\n      \"method\": \"X-ray crystallography (Gle1•Nup42 and Gle1•Nup42•DDX19); in vitro ATPase reconstitution; thermal stability assays; mutation analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — multiple crystal structures with biochemical reconstitution and mutagenesis validating the structural findings\",\n      \"pmids\": [\"29899397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In fission yeast, the Nup42 ortholog Amo1 (NUPL2) is required at the nuclear periphery for propagation of heterochromatin. Amo1 associates with the Rix1-containing RNA processing complex (RIXC) and the histone chaperone complex FACT. RIXC connects heterochromatin protein Swi6HP1 to Amo1 at the nuclear rim; Amo1 in turn enables Swi6 association with FACT, which precludes histone turnover, thereby promoting gene silencing and epigenetic stability.\",\n      \"method\": \"Genetic screen; co-immunoprecipitation/co-purification; ChIP; epistasis analysis; deletion mutants with silencing and histone turnover readouts\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (Co-IP, ChIP, genetic epistasis, histone turnover assays) in a single high-quality study demonstrating a defined mechanism\",\n      \"pmids\": [\"31883795\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Mislocalization of Nup42 (along with Nup159) to petal-like structures occurs when yeast Brl1 AαH (amphipathic α-helix) function is compromised, linking Brl1-mediated INM/ONM fusion during NPC assembly to proper cytoplasmic-face localization of Nup42.\",\n      \"method\": \"Fluorescence microscopy of Nup localization in brl1 mutants; AlphaFold structural prediction followed by mutagenesis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization readout in a defined mutant background, single lab; Nup42 mislocalization is a secondary finding in a Brl1 study\",\n      \"pmids\": [\"35293775\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"During coronavirus (IBV) infection, NUP42 (along with other FG-Nups) undergoes cytosolic dispersion from the nuclear envelope and exhibits a size mobility shift. The IBV nucleocapsid N protein, by recruiting p-PKCα to RACK1, drives phosphorylation and cytoplasmic redistribution of NUP62 and dispersal of FG-Nups including NUP42, thereby disrupting nucleocytoplasmic trafficking and suppressing innate immune gene expression.\",\n      \"method\": \"Immunofluorescence microscopy; SDS-PAGE mobility shift; interactome/co-immunoprecipitation; siRNA knockdown; viral infection model\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — NUP42 dispersion and mobility shift are observed directly, but the mechanistic details of the modification causing NUP42 shift are not fully resolved for NUP42 specifically; single lab\",\n      \"pmids\": [\"39602452\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"Nup42 suppresses heat-induced mRNA condensation: loss of Nup42 triggers nuclear condensation of chaperone mRNAs that are exported but remain translationally incompetent, impairing chaperone production and causing thermosensitivity. A genome-wide CRISPRi screen identified Nup42 as the strongest suppressor of heat-induced mRNA condensation, and co-transcriptional mRNP packaging was found to be a critical determinant of condensation in Nup42-deficient cells.\",\n      \"method\": \"Genome-wide CRISPRi screen (FRep-Seq); mRNA fractionation; translation assays; thermosensitivity assays\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genome-wide functional screen plus orthogonal biochemical and phenotypic validation in a single preprint study; not yet peer-reviewed\",\n      \"pmids\": [\"41727045\"],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"NUP42/NUPL2 is a cytoplasmic-face nucleoporin whose carboxy-terminal domain anchors Gle1 at the nuclear pore complex, enabling Gle1 and IP6 to activate the DEAD-box ATPase Dbp5/DDX19B for mRNP remodeling and directional mRNA export; its FG repeats additionally position mRNPs for this remodeling step, and in the nucleus it serves as an accessory factor for CRM1-dependent protein export, while its ortholog in fission yeast (Amo1) links the nuclear periphery to heterochromatin maintenance by bridging the RIXC complex and the FACT histone chaperone to suppress histone turnover.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP42 (NUPL2) is a cytoplasmic-face FG-nucleoporin that functions as a key positioning and scaffolding factor in directional mRNA export at the nuclear pore complex [#7, #8]. Its carboxy-terminal domain anchors Gle1, binding at an interface distinct from the Gle1-Dbp5/DDX19B site, to assemble a Nup42-CTD/Gle1/Dbp5 complex that, together with IP6, stimulates the RNA-dependent ATPase activity of the DEAD-box protein Dbp5/DDX19B for mRNP remodeling; loss of NUP42 abolishes the Gle1-Dbp5 interaction, and this activation mechanism is conserved from yeast to human [#0, #8]. Crystal structures of Gle1\\u2022Nup42\\u2022DDX19 capture the rearrangement of DDX19 from an auto-inhibited to an RNA-binding-competent state, with human DDX19 activation being IP6-independent [#9]. In parallel, the FG repeats of Nup42 (with those of Nup159) position mRNPs for Gle1/Dbp5 remodeling, since fusing the Nup42 FG domain to Gle1 bypasses the requirement for endogenous Nup42 FG [#7]. NUP42 also serves as an accessory factor for CRM1-dependent protein export: human NUPL2 binds CRM1 and the HIV-1 Rev NES, promotes formation of CRM1\\u2022RanGTP complexes independently of its FG repeats, and acts as a reaction intermediate that is displaced by RanBP1 and Nup214 [#1, #3, #6]. Beyond export, NUP42 contributes to stress responses, suppressing heat-induced nuclear condensation of chaperone mRNAs to sustain chaperone production and thermotolerance [#13], and its fission yeast ortholog Amo1 bridges the RIXC complex and the FACT histone chaperone at the nuclear periphery to suppress histone turnover and maintain heterochromatin [#10].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established the first molecular partners of human NUPL2, placing it on the CRM1-dependent protein export pathway through interaction with the HIV-1 Rev NES and CRM1.\",\n      \"evidence\": \"Yeast two-hybrid and WGA chromatography for O-glycosylation in human cells\",\n      \"pmids\": [\"10358091\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No reciprocal Co-IP or in-cell functional consequence demonstrated\", \"Role of the zinc finger and coiled-coil domains undefined\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Reconstituted the sequential biochemistry showing Nup42 acts as a Crm1/RanGTP reaction intermediate that releases export cargo and is in turn displaced by RanBP1, defining its mechanistic position in nuclear export.\",\n      \"evidence\": \"In vitro binding assays with recombinant Rev/Crm1/RanGTP and Nup proteins\",\n      \"pmids\": [\"10347184\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"In vitro reconstitution only, no cellular validation\", \"Relative contribution of Nup42 versus Nup159 unresolved\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Linked yeast Nup42 to the SUMO protease Ulp1 at the NPC, hinting at a connection between Nup42-anchored complexes and SUMO regulation.\",\n      \"evidence\": \"Yeast two-hybrid screening and co-immunoprecipitation in S. cerevisiae\",\n      \"pmids\": [\"11056382\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional significance of the Ulp1 association not established\", \"No follow-up connecting SUMO processing to Nup42 export function\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Genetically placed Nup42 at the cytoplasmic face in the Gle1-IP6 mRNA export pathway and showed its FG repeats are dispensable for this genetic function, separating positioning from anchoring roles.\",\n      \"evidence\": \"Synthetic lethality and FG-domain complementation analysis in S. cerevisiae\",\n      \"pmids\": [\"15459192\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Did not define the biochemical step Nup42 contributes to\", \"Direct Gle1 anchoring role not yet structurally resolved\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrated that Gle1, anchored via Nup42, together with IP6 stimulates Dbp5 ATPase activity, establishing the biochemical output of the Nup42/Gle1 module in mRNA export.\",\n      \"evidence\": \"In vitro ATPase kinetics with recombinant proteins and DBP5 genetic suppression of ipk1 nup42 mutants in S. cerevisiae\",\n      \"pmids\": [\"16783363\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct Nup42-Gle1 interaction interface not yet defined\", \"Did not establish how Nup42 contributes structurally to activation\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Connected Nup42 to stress-responsive mRNA retention, showing its function intersects the Slt2 MAP kinase pathway controlling thermotolerance.\",\n      \"evidence\": \"Genetic double-mutant (nup42 nab2) thermotolerance assay in S. cerevisiae\",\n      \"pmids\": [\"20823268\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of Nup42 in mRNA retention not resolved\", \"Direct molecular link to Slt2 signaling not shown\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Provided cellular gain- and loss-of-function evidence that human NUPL2 promotes CRM1-dependent export and forms RanBP1/Nup214-dissociable CRM1\\u2022RanGTP complexes independently of its FG repeats.\",\n      \"evidence\": \"Fluorescence localization, reciprocal Co-IP, siRNA knockdown, and overexpression export assays in mammalian cells\",\n      \"pmids\": [\"22250199\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How NUPL2 stabilizes CRM1\\u2022RanGTP mechanistically unresolved\", \"Relationship between protein-export and mRNA-export functions not integrated\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Resolved the role of the Nup42 FG domain, showing it positions mRNPs for Gle1/Dbp5 remodeling at the cytoplasmic face, separable from Gle1 anchoring.\",\n      \"evidence\": \"Genetic FG-domain deletion/swap, RNA cross-linking, and synthetic lethality with dbp5/gle1 in S. cerevisiae\",\n      \"pmids\": [\"24931410\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis of FG-mRNP positioning not defined\", \"FG-domain specificity determinants only partially mapped\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined the Nup42 CTD as the Gle1 anchor and showed a Nup42-CTD/Gle1/Dbp5 trimeric complex with IP6 activates the ATPase, with the mechanism conserved between yeast and human.\",\n      \"evidence\": \"Domain deletion/point mutants, Co-IP, in vitro ATPase reconstitution, and mRNA export assays in yeast and human cells\",\n      \"pmids\": [\"28869701\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Atomic structure of the trimeric complex not yet provided in this study\", \"How CTD binding alters Gle1 activity not structurally explained\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Provided atomic-resolution mechanism, capturing the Gle1\\u2022Nup42\\u2022DDX19 rearrangement of DDX19 to an RNA-competent state and showing human DDX19 activation is IP6-independent and tied to Gle1 thermostability.\",\n      \"evidence\": \"Multiple X-ray crystal structures with ATPase reconstitution, thermal stability assays, and disease-mutation analysis\",\n      \"pmids\": [\"29899397\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo dynamics of the remodeling cycle at the NPC not captured\", \"How disease-linked Gle1 destabilization perturbs export in cells not directly shown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Revealed a distinct chromatin function for the fission yeast ortholog Amo1, bridging the RIXC complex and FACT at the nuclear periphery to suppress histone turnover and maintain heterochromatin.\",\n      \"evidence\": \"Genetic screen, Co-IP/co-purification, ChIP, epistasis, and histone-turnover readouts in S. pombe\",\n      \"pmids\": [\"31883795\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether human NUPL2 has an analogous chromatin-silencing role unknown\", \"Connection between heterochromatin function and export function unestablished\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked proper cytoplasmic-face localization of Nup42 to Brl1-mediated nuclear membrane fusion during NPC assembly.\",\n      \"evidence\": \"Fluorescence microscopy of Nup42 localization in brl1 mutants with AlphaFold-guided mutagenesis in S. cerevisiae\",\n      \"pmids\": [\"35293775\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Nup42 mislocalization is a secondary observation in a Brl1 study\", \"Direct assembly determinants for Nup42 not mapped\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Showed NUP42 is a target of viral subversion, undergoing dispersion and a mobility shift during coronavirus infection that contributes to disruption of nucleocytoplasmic trafficking.\",\n      \"evidence\": \"Immunofluorescence, SDS-PAGE mobility shift, interactome, and siRNA in an IBV infection model\",\n      \"pmids\": [\"39602452\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The specific modification driving the NUP42 mobility shift is not resolved\", \"Direct contribution of NUP42 dispersal to immune suppression not isolated from other FG-Nups\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified Nup42 as the strongest suppressor of heat-induced mRNA condensation, connecting its export function to maintenance of translatable chaperone mRNAs and thermotolerance.\",\n      \"evidence\": \"Genome-wide CRISPRi screen (FRep-Seq), mRNA fractionation, translation, and thermosensitivity assays (preprint)\",\n      \"pmids\": [\"41727045\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Not yet peer-reviewed\", \"How co-transcriptional mRNP packaging is mechanistically coupled to Nup42 unresolved\", \"Direct molecular determinant of condensation suppression unknown\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NUP42's roles in mRNA export, CRM1-dependent protein export, stress-induced mRNA condensation, and peripheral chromatin maintenance are coordinated within a single protein at the pore remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified structural/functional model linking the export and chromatin functions\", \"Whether the human protein recapitulates the ortholog's chromatin role untested\", \"In vivo dynamics of the Gle1/Dbp5 remodeling cycle at the pore not captured\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [6, 8]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [7]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 7, 8]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [3, 6]},\n      {\"term_id\": \"R-HSA-4839726\", \"supporting_discovery_ids\": [10]}\n    ],\n    \"complexes\": [\n      \"nuclear pore complex (cytoplasmic face)\",\n      \"Nup42-CTD/Gle1/Dbp5 (DDX19) complex\"\n    ],\n    \"partners\": [\n      \"GLE1\",\n      \"DBP5\",\n      \"DDX19B\",\n      \"CRM1\",\n      \"NUP159\",\n      \"NUP214\",\n      \"ULP1\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}