{"gene":"NUP107","run_date":"2026-04-29T11:37:57","timeline":{"discoveries":[{"year":1994,"finding":"NUP107 was identified as a novel nuclear pore complex protein containing a leucine zipper in its carboxyl-terminal region and numerous kinase consensus sites, but lacking FG repeats, establishing it as a structural nucleoporin component.","method":"Molecular cloning, sequencing, and immunoelectron microscopy of isolated nuclear envelope proteins","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1/2 — original identification by biochemical isolation, cloning, and structural characterization; foundational paper","pmids":["8021268"],"is_preprint":false},{"year":2003,"finding":"NUP107 functions as a keystone nucleoporin required for the assembly of a subset of other nucleoporins into the NPC; depletion of Nup107 caused co-depletion of Nup133 protein and prevented assembly of Nup358, Nup214, Nup153, and Tpr into NPCs, while Nup96, Sec13, and p62 were unaffected.","method":"siRNA depletion of Nup107 in HeLa cells followed by immunofluorescence and western blotting of other nucleoporins","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 — clean siRNA knockdown with multiple molecular readouts, clear epistatic relationships established","pmids":["12552102"],"is_preprint":false},{"year":2004,"finding":"The entire Nup107-160 complex, including three newly identified members Nup37, Nup43, and Seh1, is recruited as a complete entity to kinetochores from prophase to anaphase during mitosis.","method":"GFP-tagged nucleoporins, RNAi depletion, specific antibodies, and live-cell fluorescence microscopy","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (GFP tagging, antibodies, RNAi), replicated across subunits","pmids":["15146057"],"is_preprint":false},{"year":2004,"finding":"The fission yeast Nup107-120 complex (ortholog of human Nup107-160) is required for mRNA export, nuclear pore distribution, and proper cell division; deletion mutants show cell division defects resembling Ran GTPase cycle mutants, and a functional/genetic link to the Ran/Spi1 pathway was established.","method":"Genetic deletion, biochemical fractionation, fluorescence microscopy, and genetic epistasis with Ran pathway mutants in S. pombe","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — multiple deletion mutants, biochemical confirmation of complex organization, genetic epistasis with Ran pathway","pmids":["15226438"],"is_preprint":false},{"year":2007,"finding":"The Nup107-160 complex is recruited to kinetochores mainly through the Ndc80 complex, interacts with CENP-F (which contributes only moderately to kinetochore targeting), and its presence at kinetochores is required for the recruitment of Crm1 and RanGAP1-RanBP2 to kinetochores. Depletion causes mitotic delay, impaired chromosome congression, reduced kinetochore tension, and kinetochore-microtubule attachment defects.","method":"siRNA depletion of multiple subunits, co-immunoprecipitation, immunofluorescence, live-cell imaging","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 — reciprocal Co-IP, multiple siRNA conditions, multiple functional readouts, molecular pathway placement","pmids":["17363900"],"is_preprint":false},{"year":2007,"finding":"Nup107, Nup96, Nup133, and Nup160 are phosphorylated in a cell-cycle-dependent manner, with phosphorylation sites clustered at N-terminal disordered regions and several events being specifically mitotic; phosphorylation does not disrupt intra-subcomplex interactions but likely regulates association of the Nup107-160 complex with the NPC and other proteins.","method":"In vivo 32P labeling, stable isotope labeling (SILAC), multi-stage mass spectrometry (MS/MS2/MS3), site-specific phosphorylation mapping","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 — comprehensive in vivo phosphorylation mapping with quantitative MS and site-specific cell-cycle analysis","pmids":["17360435"],"is_preprint":false},{"year":2008,"finding":"Crystal structure of human Nup107 C-terminal domain in complex with Nup133 C-terminal domain revealed that both proteins form elongated structures interacting via a compact interface in tail-to-tail fashion; structure-guided mutagenesis showed Nup107 is the critical anchor for Nup133 to the NPC, positioning Nup133 at the NPC periphery.","method":"X-ray crystallography of recombinant Nup107-Nup133 complex combined with structure-guided mutagenesis","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 — crystal structure plus mutagenesis validating functional interface","pmids":["18570875"],"is_preprint":false},{"year":2009,"finding":"Seh1, a component of the Nup107-160 complex, regulates chromosome alignment and segregation by controlling the centromeric localization of Aurora B and other chromosome passenger complex (CPC) proteins; microtubule-kinetochore attachments remain intact upon Seh1 depletion, but Aurora B mislocalization leads to biorientation defects and spindle midzone/midbody disorganization.","method":"Seh1 siRNA depletion, immunofluorescence, electron microscopy, live-cell imaging","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — clean KD with specific phenotypic readout, EM confirmation, multiple markers assessed","pmids":["19864462"],"is_preprint":false},{"year":2011,"finding":"SENP2 (SUMO-specific isopeptidase) is tethered to nuclear pore complexes partly through direct interaction with the Nup107-160 subcomplex via a dedicated targeting element in its N-terminus; disruption of this interaction enhances SENP2 substrate accessibility, implicating this tethering in SUMO pathway regulation.","method":"FRAP, Co-immunoprecipitation, deletion mutagenesis of SENP2 targeting elements","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2/3 — Co-IP plus FRAP plus mutagenesis, single lab study","pmids":["22031293"],"is_preprint":false},{"year":2012,"finding":"In C. elegans, NUP107/NPP-5 is essential for proper kinetochore localization of NUP133/NPP-15 but not NUP96/NPP-10C or ELYS/MEL-28; NPP-5 depletion reduces kinetochore NUF2/HIM-10 and Aurora B/AIR-2 kinase levels on mitotic chromatin; NPP-5 physically and genetically interacts with spindle assembly checkpoint protein MAD1/MDF-1 and is required for MAD1's nuclear envelope accumulation.","method":"Genetic disruption (C. elegans mutants), co-immunoprecipitation, immunofluorescence, genetic epistasis","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — first genetic NUP107 disruption in metazoan, Co-IP plus genetic interactions plus multiple immunofluorescence readouts","pmids":["22238360"],"is_preprint":false},{"year":2015,"finding":"Nup153 recruits the Nup107-160 complex to the inner nuclear membrane for NPC assembly specifically during interphase (not at mitotic exit); Nup153 binds directly to the inner nuclear membrane via an N-terminal amphipathic helix, and this binding facilitates Nup107-160 recruitment to assembly sites; transportin and Ran GTPase regulate this Nup153-membrane interaction.","method":"siRNA depletion, direct binding assays, mutagenesis of Nup153 amphipathic helix, cell fractionation, fluorescence microscopy","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1/2 — direct binding reconstitution, mutagenesis, and multiple functional readouts; replicated across conditions","pmids":["26051542"],"is_preprint":false},{"year":2015,"finding":"Biallelic NUP107 mutations disrupt binding of NUP107 to NUP133 and prevent NUP107 incorporation into NPCs in vitro; zebrafish nup107 morphants display hypoplastic glomerular structures and abnormal podocyte foot processes, establishing a role for NUP107 in podocyte function.","method":"In vitro binding assays with disease-associated mutants, zebrafish morpholino knockdown, electron microscopy of podocyte morphology","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 1/2 — in vitro reconstitution of mutant interactions plus in vivo vertebrate model with structural phenotype","pmids":["26411495"],"is_preprint":false},{"year":2015,"finding":"A fraction of the Nup107-160 complex (Y-complex) localizes dynamically within intranuclear GLFG bodies, colocalizing with Nup98; this intranuclear localization requires the C-terminal domain of Nup98, and FRAP studies show the Y-complex shuttles into and out of GLFG bodies more dynamically than at nuclear pores.","method":"GFP tagging, fluorescence microscopy, FRAP, Nup98 C-terminal domain deletion analysis","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2/3 — FRAP plus domain mapping, single lab but multiple methods","pmids":["25904327"],"is_preprint":false},{"year":2015,"finding":"Apaf-1 associates with NUP107 and this association is required for Apaf-1 nuclear import upon DNA damage; the CED-4 domain of Apaf-1 directly binds the central domain of NUP107 in an ATR-regulated, phosphorylation-dependent manner; expression of the Apaf-1-interacting domain of NUP107 interfered with Apaf-1 nuclear translocation and reduced Chk-1 activation and cell cycle arrest.","method":"Co-immunoprecipitation, domain mapping, dominant-negative overexpression, cell cycle assays","journal":"Cell cycle","confidence":"Medium","confidence_rationale":"Tier 2/3 — Co-IP with domain mapping plus functional rescue/interference, single lab","pmids":["25695197"],"is_preprint":false},{"year":2010,"finding":"Nup107 depletion by siRNA in young human diploid fibroblasts prevents nuclear translocation of phosphorylated ERK following EGF stimulation and decreases c-Fos expression, placing Nup107 as required for nuclear import of activated ERK in growth factor signaling.","method":"siRNA knockdown, subcellular fractionation/immunofluorescence of phospho-ERK, western blotting for c-Fos","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2/3 — clean KD with specific signaling readout, single lab single method type","pmids":["20833136"],"is_preprint":false},{"year":2025,"finding":"In C9-ALS motor neurons derived from patient iPSCs, G3BP1 (a core stress granule component) shows enhanced interaction with NUP107, and NUP107 colocalizes with and aggregates into stress granules; knockdown of the C. elegans NUP107 ortholog npp-5 alleviates ALS-associated phenotypes including reduced lifespan and impaired motility.","method":"Co-immunoprecipitation from iPSC-derived motor neurons, immunofluorescence colocalization, C. elegans genetic knockdown with behavioral phenotype assays","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2/3 — Co-IP from disease-relevant cells plus ortholog genetic rescue, single study","pmids":["40891053"],"is_preprint":false},{"year":2025,"finding":"In Xenopus, Nup107 is required for nuclear retention and processing of pri-miR427 transcripts; depletion of Nup107 leads to premature nuclear export of pri-miR427, reduced mature miR427 production, stabilization of maternal transcripts, and failure of maternal-to-zygotic transition with germ layer patterning defects.","method":"Morpholino depletion in Xenopus, RNA-sequencing time course, functional epistasis with miR427 targets including REST","journal":"Development","confidence":"Medium","confidence_rationale":"Tier 2 — loss-of-function with molecular pathway placement and RNA-seq, ortholog in established model system","pmids":["39791357"],"is_preprint":false},{"year":2012,"finding":"Loss of zygotic nup107 in zebrafish results in tissue-specific defects (loss of pharyngeal skeletons, intestine degeneration, absence of swim bladder, smaller eyes) with extensive apoptosis; affected tissues show disturbed FG-repeat nucleoporins, reduced nuclear pore number, and impaired mRNA nuclear export.","method":"Tol2 transposon insertional mutagenesis in zebrafish, immunofluorescence, in situ hybridization, mRNA export assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 — vertebrate genetic model with molecular readouts of NPC function and mRNA export","pmids":["22965233"],"is_preprint":false}],"current_model":"NUP107 is a keystone structural scaffold component of the conserved Nup107-160 (Y-complex) nuclear pore subcomplex that anchors NUP133 at the NPC periphery (via a direct tail-to-tail interaction defined by crystal structure), is required for the assembly of multiple other nucleoporins (Nup133, Nup358, Nup214, Nup153, Tpr) into the NPC, is recruited to kinetochores during mitosis via the Ndc80 complex to promote CPC (Aurora B) localization, chromosome congression, and spindle checkpoint signaling (including MAD1 interaction), is targeted to interphase NPC assembly sites through Nup153-mediated recruitment to the inner nuclear membrane, undergoes cell-cycle-regulated mitotic phosphorylation at N-terminal disordered regions that controls its association with the NPC, mediates nuclear import of specific cargoes including phospho-ERK and Apaf-1 (the latter in an ATR-phosphorylation-dependent manner), and in disease contexts is mislocalized into stress granules by C9orf72 ALS mutations or causes nephrotic syndrome when mutated in ways that disrupt its interaction with NUP133."},"narrative":{"teleology":[{"year":1994,"claim":"Establishing NUP107 as a structural (non-FG-repeat) nucleoporin with kinase consensus sites answered the question of whether this protein belongs to the scaffold or transport-interface class of NPC components.","evidence":"Molecular cloning, sequencing, and immuno-EM of isolated nuclear envelope fractions","pmids":["8021268"],"confidence":"High","gaps":["No functional data on what NUP107 does within the NPC","Kinase sites identified but not mapped to specific kinases or cell-cycle phases"]},{"year":2003,"claim":"Demonstrating that NUP107 depletion causes co-loss of NUP133 and prevents assembly of NUP358, NUP214, NUP153, and Tpr into NPCs established NUP107 as a keystone nucleoporin with hierarchical assembly functions.","evidence":"siRNA depletion in HeLa cells with immunofluorescence and western blotting of multiple nucleoporins","pmids":["12552102"],"confidence":"High","gaps":["Mechanism by which NUP107 loss prevents downstream nucleoporin assembly was unclear","Whether NUP107 acts as a direct binding platform or indirectly through complex integrity was not resolved"]},{"year":2004,"claim":"Discovery that the entire Nup107-160 complex relocates to kinetochores during mitosis, combined with fission yeast genetic data linking the orthologous complex to mRNA export and the Ran pathway, expanded NUP107's role beyond interphase NPC function to mitotic regulation and RNA export.","evidence":"GFP tagging, RNAi, and live-cell imaging in human cells; genetic deletion and epistasis with Ran pathway in S. pombe","pmids":["15146057","15226438"],"confidence":"High","gaps":["Mechanism of kinetochore recruitment unknown","Which mitotic functions depend on Y-complex versus individual subunits was unresolved"]},{"year":2007,"claim":"Identification of the Ndc80 complex as the primary kinetochore receptor for the Nup107-160 complex, together with comprehensive mitotic phosphorylation mapping of NUP107, resolved how the Y-complex reaches kinetochores and how its NPC association is cell-cycle-regulated.","evidence":"Reciprocal Co-IP, multiple siRNA conditions, live-cell imaging for kinetochore recruitment; SILAC-based quantitative phosphoproteomics with cell-cycle staging","pmids":["17363900","17360435"],"confidence":"High","gaps":["Functional consequences of individual phosphorylation sites untested","Whether phosphorylation directly controls NPC dissociation or kinetochore binding was not distinguished"]},{"year":2008,"claim":"Crystal structure of the NUP107–NUP133 C-terminal domain complex, showing a tail-to-tail architecture, answered how NUP107 anchors NUP133 at the NPC periphery and provided a structural basis for disease mutations.","evidence":"X-ray crystallography of recombinant human NUP107–NUP133 complex with structure-guided mutagenesis","pmids":["18570875"],"confidence":"High","gaps":["Full-length Y-complex architecture not resolved","Whether the NUP107–NUP133 interface is regulated post-translationally was not addressed"]},{"year":2009,"claim":"Showing that the Y-complex subunit Seh1 controls Aurora B/CPC localization at centromeres connected the kinetochore-localized Y-complex to the error correction machinery for chromosome biorientation.","evidence":"Seh1 siRNA depletion with immunofluorescence, EM, and live-cell imaging","pmids":["19864462"],"confidence":"High","gaps":["Whether NUP107 itself is the CPC-recruiting subunit or acts indirectly through Seh1 was unclear","Mechanism of CPC recruitment by Y-complex components not defined"]},{"year":2010,"claim":"Demonstrating that NUP107 is required for nuclear translocation of phospho-ERK after EGF stimulation established a specific cargo-selective transport function for NUP107 in growth factor signaling.","evidence":"siRNA knockdown in human diploid fibroblasts with subcellular fractionation and western blotting","pmids":["20833136"],"confidence":"Medium","gaps":["Whether NUP107 directly binds phospho-ERK or acts indirectly through NPC structural integrity not determined","Single cell type and single lab study"]},{"year":2012,"claim":"Genetic studies in C. elegans and zebrafish established that NUP107 physically interacts with MAD1 for spindle checkpoint signaling, controls Aurora B levels at kinetochores, and is required in vivo for tissue-specific NPC integrity, mRNA export, and cell survival.","evidence":"C. elegans mutant analysis with Co-IP and genetic epistasis; zebrafish insertional mutagenesis with immunofluorescence and mRNA export assays","pmids":["22238360","22965233"],"confidence":"High","gaps":["Whether tissue-specific phenotypes in zebrafish reflect differential NUP107 dependence versus differential sensitivity to NPC loss","Direct versus indirect nature of MAD1 interaction with NUP107 at molecular level"]},{"year":2015,"claim":"Four parallel advances resolved how NUP107 reaches interphase NPCs (via Nup153-mediated inner nuclear membrane recruitment), how its mutation causes human disease (biallelic mutations disrupting NUP133 binding cause nephrotic syndrome with podocyte defects), and defined a novel cargo-specific transport function (ATR-phosphorylation-dependent Apaf-1 nuclear import through direct NUP107 binding).","evidence":"Direct binding assays and mutagenesis of Nup153; in vitro binding of NUP107 disease mutants and zebrafish morpholino knockdown with podocyte EM; Co-IP and domain mapping for Apaf-1–NUP107 interaction","pmids":["26051542","26411495","25695197"],"confidence":"High","gaps":["Whether Nup153-mediated recruitment is the sole interphase pathway for Y-complex insertion","Molecular mechanism linking NUP107 loss specifically to podocyte failure versus general NPC dysfunction","Apaf-1 import mechanism based on single-lab Co-IP and dominant-negative approach"]},{"year":2025,"claim":"Recent work revealed NUP107 mislocalization into stress granules in C9-ALS motor neurons and a developmental role in nuclear retention and processing of pri-miRNAs required for the maternal-to-zygotic transition.","evidence":"Co-IP from iPSC-derived motor neurons with C. elegans genetic rescue; morpholino depletion in Xenopus with RNA-seq time course and epistasis","pmids":["40891053","39791357"],"confidence":"Medium","gaps":["Whether NUP107 stress-granule sequestration is causal for ALS pathology or a secondary consequence","Whether pri-miRNA retention function is a general NPC property or specific to NUP107/Y-complex","Neither finding independently replicated"]},{"year":null,"claim":"Open questions include the precise structural mechanism by which the Y-complex recruits CPC/Aurora B to kinetochores, how individual NUP107 phosphorylation events regulate its partitioning between NPCs and kinetochores, and whether NUP107's cargo-selective transport roles (phospho-ERK, Apaf-1, pri-miRNA retention) reflect direct NUP107-cargo contacts or indirect effects of Y-complex-dependent NPC architecture.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstituted system for Y-complex–CPC interaction","Phosphosite mutant analysis in mammalian cells lacking","Structural basis for cargo selectivity through NUP107 unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,1,6,11]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[0,1,6,10]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[2,4,7,9]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[12,13]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[2,4,5,7,9]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[1,10,14]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[3,16,17]}],"complexes":["Nup107-160 complex (Y-complex)","Nuclear pore complex"],"partners":["NUP133","NUP96","NUP153","NDC80","MAD1","SEH1L","G3BP1","APAF1"],"other_free_text":[]},"mechanistic_narrative":"NUP107 is a structural scaffold nucleoporin of the conserved Nup107-160 (Y-complex) that is essential for nuclear pore complex assembly, selective nucleocytoplasmic transport, and mitotic chromosome segregation. Its C-terminal domain forms a direct tail-to-tail interaction with NUP133 that anchors NUP133 at the NPC periphery, and depletion of NUP107 prevents incorporation of NUP133, NUP358, NUP214, NUP153, and Tpr into nuclear pores while also impairing mRNA export and nuclear import of specific cargoes including phospho-ERK and Apaf-1 [PMID:18570875, PMID:12552102, PMID:20833136, PMID:25695197]. During mitosis, the Nup107-160 complex is recruited to kinetochores via the Ndc80 complex, where it promotes Aurora B/CPC localization, chromosome congression, spindle checkpoint signaling through interaction with MAD1, and recruitment of CRM1 and RanGAP1-RanBP2 [PMID:17363900, PMID:22238360, PMID:19864462]. Biallelic NUP107 mutations that disrupt the NUP107–NUP133 interaction cause steroid-resistant nephrotic syndrome with podocyte foot process effacement [PMID:26411495]."},"prefetch_data":{"uniprot":{"accession":"P57740","full_name":"Nuclear pore complex protein Nup107","aliases":["107 kDa nucleoporin","Nucleoporin Nup107"],"length_aa":925,"mass_kda":106.4,"function":"Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance (PubMed:12552102, PubMed:15229283, PubMed:30179222). Required for the assembly of peripheral proteins into the NPC (PubMed:12552102, PubMed:15229283). May anchor NUP62 to the NPC (PubMed:15229283). Involved in nephrogenesis (PubMed:30179222)","subcellular_location":"Nucleus membrane; Nucleus, nuclear pore complex; Chromosome, centromere, kinetochore","url":"https://www.uniprot.org/uniprotkb/P57740/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP107","classification":"Common Essential","n_dependent_lines":1133,"n_total_lines":1208,"dependency_fraction":0.9379139072847682},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000111581","cell_line_id":"CID001715","localizations":[{"compartment":"nuclear_membrane","grade":3}],"interactors":[{"gene":"NUP85","stoichiometry":10.0},{"gene":"NUP133","stoichiometry":10.0},{"gene":"NUP98","stoichiometry":10.0},{"gene":"CLIP1","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"MAPRE1","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2},{"gene":"RAN","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2},{"gene":"SEC13","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID001715","total_profiled":1310},"omim":[{"mim_id":"618349","title":"GALLOWAY-MOWAT SYNDROME 8; GAMOS8","url":"https://www.omim.org/entry/618349"},{"mim_id":"618348","title":"GALLOWAY-MOWAT SYNDROME 7; GAMOS7","url":"https://www.omim.org/entry/618348"},{"mim_id":"618078","title":"OVARIAN DYSGENESIS 6; ODG6","url":"https://www.omim.org/entry/618078"},{"mim_id":"616730","title":"NEPHROTIC SYNDROME, TYPE 11; NPHS11","url":"https://www.omim.org/entry/616730"},{"mim_id":"610853","title":"AT-HOOK-CONTAINING TRANSCRIPTION FACTOR 1; AHCTF1","url":"https://www.omim.org/entry/610853"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Nucleoplasm","reliability":"Uncertain"},{"location":"Nuclear membrane","reliability":"Additional"},{"location":"Centrosome","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP107"},"hgnc":{"alias_symbol":["NUP84"],"prev_symbol":[]},"alphafold":{"accession":"P57740","domains":[{"cath_id":"-","chopping":"132-239","consensus_level":"medium","plddt":82.2312,"start":132,"end":239},{"cath_id":"1.10.3450.20","chopping":"264-500","consensus_level":"high","plddt":87.3503,"start":264,"end":500},{"cath_id":"-","chopping":"632-716_730-735","consensus_level":"medium","plddt":81.5619,"start":632,"end":735},{"cath_id":"1.20.190.50","chopping":"758-915","consensus_level":"high","plddt":90.348,"start":758,"end":915}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P57740","model_url":"https://alphafold.ebi.ac.uk/files/AF-P57740-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P57740-F1-predicted_aligned_error_v6.png","plddt_mean":79.25},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP107","jax_strain_url":"https://www.jax.org/strain/search?query=NUP107"},"sequence":{"accession":"P57740","fasta_url":"https://rest.uniprot.org/uniprotkb/P57740.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P57740/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P57740"}},"corpus_meta":[{"pmid":"15146057","id":"PMC_15146057","title":"The entire Nup107-160 complex, including three new members, is targeted as one entity to kinetochores in mitosis.","date":"2004","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/15146057","citation_count":223,"is_preprint":false},{"pmid":"17363900","id":"PMC_17363900","title":"The human Nup107-160 nuclear pore subcomplex contributes to proper kinetochore functions.","date":"2007","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/17363900","citation_count":171,"is_preprint":false},{"pmid":"12552102","id":"PMC_12552102","title":"Depletion of a single nucleoporin, Nup107, prevents the assembly of a subset of nucleoporins into the nuclear pore complex.","date":"2003","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/12552102","citation_count":129,"is_preprint":false},{"pmid":"26051542","id":"PMC_26051542","title":"Nup153 Recruits the Nup107-160 Complex to the Inner Nuclear Membrane for Interphasic Nuclear Pore Complex Assembly.","date":"2015","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/26051542","citation_count":115,"is_preprint":false},{"pmid":"15817685","id":"PMC_15817685","title":"Reverse recruitment: the Nup84 nuclear pore subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation.","date":"2005","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/15817685","citation_count":114,"is_preprint":false},{"pmid":"26411495","id":"PMC_26411495","title":"Biallelic Mutations in Nuclear Pore Complex Subunit NUP107 Cause Early-Childhood-Onset Steroid-Resistant Nephrotic Syndrome.","date":"2015","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/26411495","citation_count":99,"is_preprint":false},{"pmid":"9166401","id":"PMC_9166401","title":"Nup84, a novel nucleoporin that is associated with CAN/Nup214 on the cytoplasmic face of the nuclear pore complex.","date":"1997","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9166401","citation_count":88,"is_preprint":false},{"pmid":"18570875","id":"PMC_18570875","title":"Structural and functional studies of Nup107/Nup133 interaction and its implications for the architecture of the nuclear pore complex.","date":"2008","source":"Molecular cell","url":"https://pubmed.ncbi.nlm.nih.gov/18570875","citation_count":84,"is_preprint":false},{"pmid":"17360435","id":"PMC_17360435","title":"Cell-cycle-dependent phosphorylation of the nuclear pore Nup107-160 subcomplex.","date":"2007","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/17360435","citation_count":83,"is_preprint":false},{"pmid":"28280135","id":"PMC_28280135","title":"Homozygous mutation in NUP107 leads to microcephaly with steroid-resistant nephrotic condition similar to Galloway-Mowat syndrome.","date":"2017","source":"Journal of medical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28280135","citation_count":71,"is_preprint":false},{"pmid":"22288649","id":"PMC_22288649","title":"Putative members of the Arabidopsis Nup107-160 nuclear pore sub-complex contribute to pathogen defense.","date":"2012","source":"The Plant journal : for cell and molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/22288649","citation_count":70,"is_preprint":false},{"pmid":"15226438","id":"PMC_15226438","title":"The fission yeast Nup107-120 complex functionally interacts with the small GTPase Ran/Spi1 and is required for mRNA export, nuclear pore distribution, and proper cell division.","date":"2004","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/15226438","citation_count":70,"is_preprint":false},{"pmid":"19864462","id":"PMC_19864462","title":"The Nup107-160 nucleoporin complex promotes mitotic events via control of the localization state of the chromosome passenger complex.","date":"2009","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/19864462","citation_count":69,"is_preprint":false},{"pmid":"19855394","id":"PMC_19855394","title":"Molecular architecture of the Nup84-Nup145C-Sec13 edge element in the nuclear pore complex lattice.","date":"2009","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/19855394","citation_count":65,"is_preprint":false},{"pmid":"22031293","id":"PMC_22031293","title":"The SUMO-specific isopeptidase SENP2 associates dynamically with nuclear pore complexes through interactions with karyopherins and the Nup107-160 nucleoporin subcomplex.","date":"2011","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/22031293","citation_count":51,"is_preprint":false},{"pmid":"21478823","id":"PMC_21478823","title":"A novel assay identifies transcript elongation roles for the Nup84 complex and RNA processing factors.","date":"2011","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/21478823","citation_count":49,"is_preprint":false},{"pmid":"22238360","id":"PMC_22238360","title":"Dissection of the NUP107 nuclear pore subcomplex reveals a novel interaction with spindle assembly checkpoint protein MAD1 in Caenorhabditis elegans.","date":"2012","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/22238360","citation_count":45,"is_preprint":false},{"pmid":"23954503","id":"PMC_23954503","title":"Protein interfaces of the conserved Nup84 complex from Chaetomium thermophilum shown by crosslinking mass spectrometry and electron microscopy.","date":"2013","source":"Structure (London, England : 1993)","url":"https://pubmed.ncbi.nlm.nih.gov/23954503","citation_count":42,"is_preprint":false},{"pmid":"25904327","id":"PMC_25904327","title":"Intranuclear dynamics of the Nup107-160 complex.","date":"2015","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/25904327","citation_count":36,"is_preprint":false},{"pmid":"8021268","id":"PMC_8021268","title":"Nup107 is a novel nuclear pore complex protein that contains a leucine zipper.","date":"1994","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/8021268","citation_count":35,"is_preprint":false},{"pmid":"33247142","id":"PMC_33247142","title":"Yeast Nup84-Nup133 complex structure details flexibility and reveals conservation of the membrane anchoring ALPS motif.","date":"2020","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/33247142","citation_count":33,"is_preprint":false},{"pmid":"27190346","id":"PMC_27190346","title":"NUP107 mutations in children with steroid-resistant nephrotic syndrome.","date":"2017","source":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","url":"https://pubmed.ncbi.nlm.nih.gov/27190346","citation_count":29,"is_preprint":false},{"pmid":"22713280","id":"PMC_22713280","title":"Dissecting the NUP107 complex: multiple components and even more functions.","date":"2012","source":"Nucleus (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/22713280","citation_count":26,"is_preprint":false},{"pmid":"31170156","id":"PMC_31170156","title":"Asymmetrical localization of Nup107-160 subcomplex components within the nuclear pore complex in fission yeast.","date":"2019","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31170156","citation_count":26,"is_preprint":false},{"pmid":"25695197","id":"PMC_25695197","title":"DNA damage-induced nuclear translocation of Apaf-1 is mediated by nucleoporin Nup107.","date":"2015","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/25695197","citation_count":25,"is_preprint":false},{"pmid":"22965233","id":"PMC_22965233","title":"Loss of zygotic NUP107 protein causes missing of pharyngeal skeleton and other tissue defects with impaired nuclear pore function in zebrafish embryos.","date":"2012","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/22965233","citation_count":23,"is_preprint":false},{"pmid":"30715474","id":"PMC_30715474","title":"The Nup84 complex coordinates the DNA damage response to warrant genome integrity.","date":"2019","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/30715474","citation_count":20,"is_preprint":false},{"pmid":"29363275","id":"PMC_29363275","title":"Functional study of a novel missense single-nucleotide variant of NUP107 in two daughters of Mexican origin with premature ovarian insufficiency.","date":"2018","source":"Molecular genetics & genomic medicine","url":"https://pubmed.ncbi.nlm.nih.gov/29363275","citation_count":20,"is_preprint":false},{"pmid":"20833136","id":"PMC_20833136","title":"Reduction of Nup107 attenuates the growth factor signaling in the senescent cells.","date":"2010","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/20833136","citation_count":16,"is_preprint":false},{"pmid":"24478780","id":"PMC_24478780","title":"Analysis of the Lotus japonicus nuclear pore NUP107-160 subcomplex reveals pronounced structural plasticity and functional redundancy.","date":"2014","source":"Frontiers in plant science","url":"https://pubmed.ncbi.nlm.nih.gov/24478780","citation_count":13,"is_preprint":false},{"pmid":"21326946","id":"PMC_21326946","title":"Characterization of the membrane-coating Nup84 complex: paradigm for the nuclear pore complex structure.","date":"2010","source":"Nucleus (Austin, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/21326946","citation_count":11,"is_preprint":false},{"pmid":"20490895","id":"PMC_20490895","title":"Depletion of a single nucleoporin, Nup107, induces apoptosis in eukaryotic cells.","date":"2010","source":"Molecular and cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20490895","citation_count":10,"is_preprint":false},{"pmid":"11180460","id":"PMC_11180460","title":"Disruption and functional analysis of six ORFs of chromosome IV: YDL103c (QRI1), YDL105w (QRI2), YDL112w (TRM3), YDL113c, YDL116w (NUP84) and YDL167c (NRP1).","date":"2001","source":"Yeast (Chichester, England)","url":"https://pubmed.ncbi.nlm.nih.gov/11180460","citation_count":9,"is_preprint":false},{"pmid":"38650033","id":"PMC_38650033","title":"Mutations in the NUP93, NUP107 and NUP160 genes cause steroid-resistant nephrotic syndrome in Chinese children.","date":"2024","source":"Italian journal of pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/38650033","citation_count":6,"is_preprint":false},{"pmid":"17768364","id":"PMC_17768364","title":"Purification, crystallization and preliminary X-ray analysis of a Nup107-Nup133 heterodimeric nucleoporin complex.","date":"2007","source":"Acta crystallographica. Section F, Structural biology and crystallization communications","url":"https://pubmed.ncbi.nlm.nih.gov/17768364","citation_count":6,"is_preprint":false},{"pmid":"32980454","id":"PMC_32980454","title":"Nup84 persists within the nuclear envelope of the rice blast fungus, Magnaporthe oryzae, during mitosis.","date":"2020","source":"Fungal genetics and biology : FG & B","url":"https://pubmed.ncbi.nlm.nih.gov/32980454","citation_count":3,"is_preprint":false},{"pmid":"40891053","id":"PMC_40891053","title":"C9orf72 ALS-causing mutations lead to mislocalization and aggregation of nucleoporin Nup107 into stress granules.","date":"2025","source":"FEBS letters","url":"https://pubmed.ncbi.nlm.nih.gov/40891053","citation_count":2,"is_preprint":false},{"pmid":"39791357","id":"PMC_39791357","title":"Nup107 contributes to the maternal-to-zygotic transition by preventing the premature nuclear export of pri-miR427.","date":"2025","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/39791357","citation_count":2,"is_preprint":false},{"pmid":"39473271","id":"PMC_39473271","title":"Recurrent Increased Nuchal Translucency Led to the Identification of Novel NUP107 Variants.","date":"2024","source":"American journal of medical genetics. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/39473271","citation_count":0,"is_preprint":false},{"pmid":"41805630","id":"PMC_41805630","title":"Nup107 is a crucial regulator of torso-mediated metamorphic transition in Drosophila melanogaster.","date":"2026","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/41805630","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.07.15.664992","title":"A tool to pulse-label yeast Nuclear Pore Complexes in imaging and biochemical experiments","date":"2025-07-16","source":"bioRxiv","url":"https://doi.org/10.1101/2025.07.15.664992","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.04.16.649118","title":"<i>C9orf72</i> ALS-causing mutations lead to nucleoporin Nup107 aggregation and subsequent pathological changes","date":"2025-04-17","source":"bioRxiv","url":"https://doi.org/10.1101/2025.04.16.649118","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2025.09.29.679220","title":"Nup43 positively regulates  <i>Drosophila</i>  fertility and Myosin VI-dependent actin cone assembly during spermiogenesis","date":"2025-09-30","source":"bioRxiv","url":"https://doi.org/10.1101/2025.09.29.679220","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.08.19.608657","title":"Nup107 is a crucial regulator of torso-mediated metamorphic transition in  <i>Drosophila melanogaster</i>","date":"2024-08-20","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.19.608657","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":19989,"output_tokens":4367,"usd":0.062736},"stage2":{"model":"claude-opus-4-6","input_tokens":7818,"output_tokens":2921,"usd":0.168173},"total_usd":0.230909,"stage1_batch_id":"msgbatch_012ZiiCUBfB62NCTQd4Bk1Jo","stage2_batch_id":"msgbatch_01Xuqq9aUHoQouS7UVGZNStZ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"NUP107 was identified as a novel nuclear pore complex protein containing a leucine zipper in its carboxyl-terminal region and numerous kinase consensus sites, but lacking FG repeats, establishing it as a structural nucleoporin component.\",\n      \"method\": \"Molecular cloning, sequencing, and immunoelectron microscopy of isolated nuclear envelope proteins\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1/2 — original identification by biochemical isolation, cloning, and structural characterization; foundational paper\",\n      \"pmids\": [\"8021268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"NUP107 functions as a keystone nucleoporin required for the assembly of a subset of other nucleoporins into the NPC; depletion of Nup107 caused co-depletion of Nup133 protein and prevented assembly of Nup358, Nup214, Nup153, and Tpr into NPCs, while Nup96, Sec13, and p62 were unaffected.\",\n      \"method\": \"siRNA depletion of Nup107 in HeLa cells followed by immunofluorescence and western blotting of other nucleoporins\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean siRNA knockdown with multiple molecular readouts, clear epistatic relationships established\",\n      \"pmids\": [\"12552102\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The entire Nup107-160 complex, including three newly identified members Nup37, Nup43, and Seh1, is recruited as a complete entity to kinetochores from prophase to anaphase during mitosis.\",\n      \"method\": \"GFP-tagged nucleoporins, RNAi depletion, specific antibodies, and live-cell fluorescence microscopy\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (GFP tagging, antibodies, RNAi), replicated across subunits\",\n      \"pmids\": [\"15146057\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The fission yeast Nup107-120 complex (ortholog of human Nup107-160) is required for mRNA export, nuclear pore distribution, and proper cell division; deletion mutants show cell division defects resembling Ran GTPase cycle mutants, and a functional/genetic link to the Ran/Spi1 pathway was established.\",\n      \"method\": \"Genetic deletion, biochemical fractionation, fluorescence microscopy, and genetic epistasis with Ran pathway mutants in S. pombe\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple deletion mutants, biochemical confirmation of complex organization, genetic epistasis with Ran pathway\",\n      \"pmids\": [\"15226438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The Nup107-160 complex is recruited to kinetochores mainly through the Ndc80 complex, interacts with CENP-F (which contributes only moderately to kinetochore targeting), and its presence at kinetochores is required for the recruitment of Crm1 and RanGAP1-RanBP2 to kinetochores. Depletion causes mitotic delay, impaired chromosome congression, reduced kinetochore tension, and kinetochore-microtubule attachment defects.\",\n      \"method\": \"siRNA depletion of multiple subunits, co-immunoprecipitation, immunofluorescence, live-cell imaging\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, multiple siRNA conditions, multiple functional readouts, molecular pathway placement\",\n      \"pmids\": [\"17363900\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Nup107, Nup96, Nup133, and Nup160 are phosphorylated in a cell-cycle-dependent manner, with phosphorylation sites clustered at N-terminal disordered regions and several events being specifically mitotic; phosphorylation does not disrupt intra-subcomplex interactions but likely regulates association of the Nup107-160 complex with the NPC and other proteins.\",\n      \"method\": \"In vivo 32P labeling, stable isotope labeling (SILAC), multi-stage mass spectrometry (MS/MS2/MS3), site-specific phosphorylation mapping\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — comprehensive in vivo phosphorylation mapping with quantitative MS and site-specific cell-cycle analysis\",\n      \"pmids\": [\"17360435\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Crystal structure of human Nup107 C-terminal domain in complex with Nup133 C-terminal domain revealed that both proteins form elongated structures interacting via a compact interface in tail-to-tail fashion; structure-guided mutagenesis showed Nup107 is the critical anchor for Nup133 to the NPC, positioning Nup133 at the NPC periphery.\",\n      \"method\": \"X-ray crystallography of recombinant Nup107-Nup133 complex combined with structure-guided mutagenesis\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 — crystal structure plus mutagenesis validating functional interface\",\n      \"pmids\": [\"18570875\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Seh1, a component of the Nup107-160 complex, regulates chromosome alignment and segregation by controlling the centromeric localization of Aurora B and other chromosome passenger complex (CPC) proteins; microtubule-kinetochore attachments remain intact upon Seh1 depletion, but Aurora B mislocalization leads to biorientation defects and spindle midzone/midbody disorganization.\",\n      \"method\": \"Seh1 siRNA depletion, immunofluorescence, electron microscopy, live-cell imaging\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KD with specific phenotypic readout, EM confirmation, multiple markers assessed\",\n      \"pmids\": [\"19864462\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SENP2 (SUMO-specific isopeptidase) is tethered to nuclear pore complexes partly through direct interaction with the Nup107-160 subcomplex via a dedicated targeting element in its N-terminus; disruption of this interaction enhances SENP2 substrate accessibility, implicating this tethering in SUMO pathway regulation.\",\n      \"method\": \"FRAP, Co-immunoprecipitation, deletion mutagenesis of SENP2 targeting elements\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — Co-IP plus FRAP plus mutagenesis, single lab study\",\n      \"pmids\": [\"22031293\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"In C. elegans, NUP107/NPP-5 is essential for proper kinetochore localization of NUP133/NPP-15 but not NUP96/NPP-10C or ELYS/MEL-28; NPP-5 depletion reduces kinetochore NUF2/HIM-10 and Aurora B/AIR-2 kinase levels on mitotic chromatin; NPP-5 physically and genetically interacts with spindle assembly checkpoint protein MAD1/MDF-1 and is required for MAD1's nuclear envelope accumulation.\",\n      \"method\": \"Genetic disruption (C. elegans mutants), co-immunoprecipitation, immunofluorescence, genetic epistasis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — first genetic NUP107 disruption in metazoan, Co-IP plus genetic interactions plus multiple immunofluorescence readouts\",\n      \"pmids\": [\"22238360\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Nup153 recruits the Nup107-160 complex to the inner nuclear membrane for NPC assembly specifically during interphase (not at mitotic exit); Nup153 binds directly to the inner nuclear membrane via an N-terminal amphipathic helix, and this binding facilitates Nup107-160 recruitment to assembly sites; transportin and Ran GTPase regulate this Nup153-membrane interaction.\",\n      \"method\": \"siRNA depletion, direct binding assays, mutagenesis of Nup153 amphipathic helix, cell fractionation, fluorescence microscopy\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1/2 — direct binding reconstitution, mutagenesis, and multiple functional readouts; replicated across conditions\",\n      \"pmids\": [\"26051542\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Biallelic NUP107 mutations disrupt binding of NUP107 to NUP133 and prevent NUP107 incorporation into NPCs in vitro; zebrafish nup107 morphants display hypoplastic glomerular structures and abnormal podocyte foot processes, establishing a role for NUP107 in podocyte function.\",\n      \"method\": \"In vitro binding assays with disease-associated mutants, zebrafish morpholino knockdown, electron microscopy of podocyte morphology\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1/2 — in vitro reconstitution of mutant interactions plus in vivo vertebrate model with structural phenotype\",\n      \"pmids\": [\"26411495\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"A fraction of the Nup107-160 complex (Y-complex) localizes dynamically within intranuclear GLFG bodies, colocalizing with Nup98; this intranuclear localization requires the C-terminal domain of Nup98, and FRAP studies show the Y-complex shuttles into and out of GLFG bodies more dynamically than at nuclear pores.\",\n      \"method\": \"GFP tagging, fluorescence microscopy, FRAP, Nup98 C-terminal domain deletion analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — FRAP plus domain mapping, single lab but multiple methods\",\n      \"pmids\": [\"25904327\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Apaf-1 associates with NUP107 and this association is required for Apaf-1 nuclear import upon DNA damage; the CED-4 domain of Apaf-1 directly binds the central domain of NUP107 in an ATR-regulated, phosphorylation-dependent manner; expression of the Apaf-1-interacting domain of NUP107 interfered with Apaf-1 nuclear translocation and reduced Chk-1 activation and cell cycle arrest.\",\n      \"method\": \"Co-immunoprecipitation, domain mapping, dominant-negative overexpression, cell cycle assays\",\n      \"journal\": \"Cell cycle\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — Co-IP with domain mapping plus functional rescue/interference, single lab\",\n      \"pmids\": [\"25695197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nup107 depletion by siRNA in young human diploid fibroblasts prevents nuclear translocation of phosphorylated ERK following EGF stimulation and decreases c-Fos expression, placing Nup107 as required for nuclear import of activated ERK in growth factor signaling.\",\n      \"method\": \"siRNA knockdown, subcellular fractionation/immunofluorescence of phospho-ERK, western blotting for c-Fos\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — clean KD with specific signaling readout, single lab single method type\",\n      \"pmids\": [\"20833136\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In C9-ALS motor neurons derived from patient iPSCs, G3BP1 (a core stress granule component) shows enhanced interaction with NUP107, and NUP107 colocalizes with and aggregates into stress granules; knockdown of the C. elegans NUP107 ortholog npp-5 alleviates ALS-associated phenotypes including reduced lifespan and impaired motility.\",\n      \"method\": \"Co-immunoprecipitation from iPSC-derived motor neurons, immunofluorescence colocalization, C. elegans genetic knockdown with behavioral phenotype assays\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2/3 — Co-IP from disease-relevant cells plus ortholog genetic rescue, single study\",\n      \"pmids\": [\"40891053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In Xenopus, Nup107 is required for nuclear retention and processing of pri-miR427 transcripts; depletion of Nup107 leads to premature nuclear export of pri-miR427, reduced mature miR427 production, stabilization of maternal transcripts, and failure of maternal-to-zygotic transition with germ layer patterning defects.\",\n      \"method\": \"Morpholino depletion in Xenopus, RNA-sequencing time course, functional epistasis with miR427 targets including REST\",\n      \"journal\": \"Development\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — loss-of-function with molecular pathway placement and RNA-seq, ortholog in established model system\",\n      \"pmids\": [\"39791357\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Loss of zygotic nup107 in zebrafish results in tissue-specific defects (loss of pharyngeal skeletons, intestine degeneration, absence of swim bladder, smaller eyes) with extensive apoptosis; affected tissues show disturbed FG-repeat nucleoporins, reduced nuclear pore number, and impaired mRNA nuclear export.\",\n      \"method\": \"Tol2 transposon insertional mutagenesis in zebrafish, immunofluorescence, in situ hybridization, mRNA export assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — vertebrate genetic model with molecular readouts of NPC function and mRNA export\",\n      \"pmids\": [\"22965233\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP107 is a keystone structural scaffold component of the conserved Nup107-160 (Y-complex) nuclear pore subcomplex that anchors NUP133 at the NPC periphery (via a direct tail-to-tail interaction defined by crystal structure), is required for the assembly of multiple other nucleoporins (Nup133, Nup358, Nup214, Nup153, Tpr) into the NPC, is recruited to kinetochores during mitosis via the Ndc80 complex to promote CPC (Aurora B) localization, chromosome congression, and spindle checkpoint signaling (including MAD1 interaction), is targeted to interphase NPC assembly sites through Nup153-mediated recruitment to the inner nuclear membrane, undergoes cell-cycle-regulated mitotic phosphorylation at N-terminal disordered regions that controls its association with the NPC, mediates nuclear import of specific cargoes including phospho-ERK and Apaf-1 (the latter in an ATR-phosphorylation-dependent manner), and in disease contexts is mislocalized into stress granules by C9orf72 ALS mutations or causes nephrotic syndrome when mutated in ways that disrupt its interaction with NUP133.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"NUP107 is a structural scaffold nucleoporin of the conserved Nup107-160 (Y-complex) that is essential for nuclear pore complex assembly, selective nucleocytoplasmic transport, and mitotic chromosome segregation. Its C-terminal domain forms a direct tail-to-tail interaction with NUP133 that anchors NUP133 at the NPC periphery, and depletion of NUP107 prevents incorporation of NUP133, NUP358, NUP214, NUP153, and Tpr into nuclear pores while also impairing mRNA export and nuclear import of specific cargoes including phospho-ERK and Apaf-1 [PMID:18570875, PMID:12552102, PMID:20833136, PMID:25695197]. During mitosis, the Nup107-160 complex is recruited to kinetochores via the Ndc80 complex, where it promotes Aurora B/CPC localization, chromosome congression, spindle checkpoint signaling through interaction with MAD1, and recruitment of CRM1 and RanGAP1-RanBP2 [PMID:17363900, PMID:22238360, PMID:19864462]. Biallelic NUP107 mutations that disrupt the NUP107–NUP133 interaction cause steroid-resistant nephrotic syndrome with podocyte foot process effacement [PMID:26411495].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing NUP107 as a structural (non-FG-repeat) nucleoporin with kinase consensus sites answered the question of whether this protein belongs to the scaffold or transport-interface class of NPC components.\",\n      \"evidence\": \"Molecular cloning, sequencing, and immuno-EM of isolated nuclear envelope fractions\",\n      \"pmids\": [\"8021268\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No functional data on what NUP107 does within the NPC\", \"Kinase sites identified but not mapped to specific kinases or cell-cycle phases\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Demonstrating that NUP107 depletion causes co-loss of NUP133 and prevents assembly of NUP358, NUP214, NUP153, and Tpr into NPCs established NUP107 as a keystone nucleoporin with hierarchical assembly functions.\",\n      \"evidence\": \"siRNA depletion in HeLa cells with immunofluorescence and western blotting of multiple nucleoporins\",\n      \"pmids\": [\"12552102\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which NUP107 loss prevents downstream nucleoporin assembly was unclear\", \"Whether NUP107 acts as a direct binding platform or indirectly through complex integrity was not resolved\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Discovery that the entire Nup107-160 complex relocates to kinetochores during mitosis, combined with fission yeast genetic data linking the orthologous complex to mRNA export and the Ran pathway, expanded NUP107's role beyond interphase NPC function to mitotic regulation and RNA export.\",\n      \"evidence\": \"GFP tagging, RNAi, and live-cell imaging in human cells; genetic deletion and epistasis with Ran pathway in S. pombe\",\n      \"pmids\": [\"15146057\", \"15226438\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of kinetochore recruitment unknown\", \"Which mitotic functions depend on Y-complex versus individual subunits was unresolved\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Identification of the Ndc80 complex as the primary kinetochore receptor for the Nup107-160 complex, together with comprehensive mitotic phosphorylation mapping of NUP107, resolved how the Y-complex reaches kinetochores and how its NPC association is cell-cycle-regulated.\",\n      \"evidence\": \"Reciprocal Co-IP, multiple siRNA conditions, live-cell imaging for kinetochore recruitment; SILAC-based quantitative phosphoproteomics with cell-cycle staging\",\n      \"pmids\": [\"17363900\", \"17360435\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequences of individual phosphorylation sites untested\", \"Whether phosphorylation directly controls NPC dissociation or kinetochore binding was not distinguished\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Crystal structure of the NUP107–NUP133 C-terminal domain complex, showing a tail-to-tail architecture, answered how NUP107 anchors NUP133 at the NPC periphery and provided a structural basis for disease mutations.\",\n      \"evidence\": \"X-ray crystallography of recombinant human NUP107–NUP133 complex with structure-guided mutagenesis\",\n      \"pmids\": [\"18570875\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full-length Y-complex architecture not resolved\", \"Whether the NUP107–NUP133 interface is regulated post-translationally was not addressed\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Showing that the Y-complex subunit Seh1 controls Aurora B/CPC localization at centromeres connected the kinetochore-localized Y-complex to the error correction machinery for chromosome biorientation.\",\n      \"evidence\": \"Seh1 siRNA depletion with immunofluorescence, EM, and live-cell imaging\",\n      \"pmids\": [\"19864462\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether NUP107 itself is the CPC-recruiting subunit or acts indirectly through Seh1 was unclear\", \"Mechanism of CPC recruitment by Y-complex components not defined\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrating that NUP107 is required for nuclear translocation of phospho-ERK after EGF stimulation established a specific cargo-selective transport function for NUP107 in growth factor signaling.\",\n      \"evidence\": \"siRNA knockdown in human diploid fibroblasts with subcellular fractionation and western blotting\",\n      \"pmids\": [\"20833136\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether NUP107 directly binds phospho-ERK or acts indirectly through NPC structural integrity not determined\", \"Single cell type and single lab study\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Genetic studies in C. elegans and zebrafish established that NUP107 physically interacts with MAD1 for spindle checkpoint signaling, controls Aurora B levels at kinetochores, and is required in vivo for tissue-specific NPC integrity, mRNA export, and cell survival.\",\n      \"evidence\": \"C. elegans mutant analysis with Co-IP and genetic epistasis; zebrafish insertional mutagenesis with immunofluorescence and mRNA export assays\",\n      \"pmids\": [\"22238360\", \"22965233\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether tissue-specific phenotypes in zebrafish reflect differential NUP107 dependence versus differential sensitivity to NPC loss\", \"Direct versus indirect nature of MAD1 interaction with NUP107 at molecular level\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Four parallel advances resolved how NUP107 reaches interphase NPCs (via Nup153-mediated inner nuclear membrane recruitment), how its mutation causes human disease (biallelic mutations disrupting NUP133 binding cause nephrotic syndrome with podocyte defects), and defined a novel cargo-specific transport function (ATR-phosphorylation-dependent Apaf-1 nuclear import through direct NUP107 binding).\",\n      \"evidence\": \"Direct binding assays and mutagenesis of Nup153; in vitro binding of NUP107 disease mutants and zebrafish morpholino knockdown with podocyte EM; Co-IP and domain mapping for Apaf-1–NUP107 interaction\",\n      \"pmids\": [\"26051542\", \"26411495\", \"25695197\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether Nup153-mediated recruitment is the sole interphase pathway for Y-complex insertion\", \"Molecular mechanism linking NUP107 loss specifically to podocyte failure versus general NPC dysfunction\", \"Apaf-1 import mechanism based on single-lab Co-IP and dominant-negative approach\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Recent work revealed NUP107 mislocalization into stress granules in C9-ALS motor neurons and a developmental role in nuclear retention and processing of pri-miRNAs required for the maternal-to-zygotic transition.\",\n      \"evidence\": \"Co-IP from iPSC-derived motor neurons with C. elegans genetic rescue; morpholino depletion in Xenopus with RNA-seq time course and epistasis\",\n      \"pmids\": [\"40891053\", \"39791357\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether NUP107 stress-granule sequestration is causal for ALS pathology or a secondary consequence\", \"Whether pri-miRNA retention function is a general NPC property or specific to NUP107/Y-complex\", \"Neither finding independently replicated\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Open questions include the precise structural mechanism by which the Y-complex recruits CPC/Aurora B to kinetochores, how individual NUP107 phosphorylation events regulate its partitioning between NPCs and kinetochores, and whether NUP107's cargo-selective transport roles (phospho-ERK, Apaf-1, pri-miRNA retention) reflect direct NUP107-cargo contacts or indirect effects of Y-complex-dependent NPC architecture.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reconstituted system for Y-complex–CPC interaction\", \"Phosphosite mutant analysis in mammalian cells lacking\", \"Structural basis for cargo selectivity through NUP107 unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 1, 6, 11]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [0, 1, 6, 10]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [2, 4, 7, 9]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [12, 13]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [2, 4, 5, 7, 9]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [1, 10, 14]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [3, 16, 17]}\n    ],\n    \"complexes\": [\n      \"Nup107-160 complex (Y-complex)\",\n      \"Nuclear pore complex\"\n    ],\n    \"partners\": [\n      \"NUP133\",\n      \"NUP96\",\n      \"NUP153\",\n      \"NDC80\",\n      \"MAD1\",\n      \"SEH1L\",\n      \"G3BP1\",\n      \"APAF1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}