{"gene":"NUP107","run_date":"2026-06-10T05:19:52","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; it was localized to the NPC by immunoelectron microscopy.","method":"Molecular cloning, sequencing, immunoelectron microscopy, biochemical fractionation","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization by immunoelectron microscopy, molecular cloning and sequence analysis, replicated in subsequent studies","pmids":["8021268"],"is_preprint":false},{"year":1997,"finding":"Human Nup84 (NUP107) is tightly associated with CAN/Nup214 on the cytoplasmic face of the NPC; the NH2-terminal region of Nup84 contains the interaction site with CAN/Nup214, while the C-terminal putative coiled-coil domain is required for association with the cytoplasmic face of the NPC.","method":"Immunoprecipitation under nondenaturing conditions, mutagenesis, expression studies, cytoplasmic face localization determination","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, mutagenesis mapping of interaction domains, direct localization, foundational study replicated by subsequent work","pmids":["9166401"],"is_preprint":false},{"year":2003,"finding":"Depletion of Nup107 by siRNA caused co-depletion of Nup133 (but not Nup96 or Sec13) and prevented assembly of Nup358, Nup214, Nup153, and Tpr into the NPC, establishing Nup107 as a keystone nucleoporin required for assembly of a subset of nucleoporins into the NPC.","method":"siRNA knockdown in HeLa cells, Western blot, RT-PCR, immunofluorescence","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean siRNA KD with multiple downstream readouts, replicated and extended by multiple subsequent studies","pmids":["12552102"],"is_preprint":false},{"year":2004,"finding":"The Nup107-160 complex in vertebrates includes three additional WD-repeat nucleoporins (Nup37, Nup43, and Seh1/Sec13), and the entire complex is targeted to kinetochores from prophase to anaphase of mitosis.","method":"Biochemical co-purification, GFP-tagged nucleoporin imaging, specific antibody immunofluorescence, RNAi","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — biochemical complex identification combined with live-cell imaging and RNAi phenotyping; replicated in multiple subsequent studies","pmids":["15146057"],"is_preprint":false},{"year":2004,"finding":"The fission yeast Nup107-120 complex (ortholog of the vertebrate Nup107-160 complex) is required for mRNA export, nuclear pore distribution, and proper cell division; it functionally interacts with the small GTPase Ran/Spi1, as overexpression of a nonfunctional Ran allele is specifically toxic in nup120 and nup133b deletion mutants.","method":"Gene deletion, biochemical co-purification, nuclear envelope localization, genetic epistasis/synthetic lethality, mRNA export assay","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis with multiple orthogonal methods (deletion phenotypes, biochemical complex, genetic interaction with Ran)","pmids":["15226438"],"is_preprint":false},{"year":2005,"finding":"The yeast Nup84 subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation ('reverse recruitment'); Nup84 and associated subcomplex components can activate transcription themselves when fused to a heterologous DNA-binding domain, and Gcr1/Gcr2 bridge the NPC to the transcriptional machinery.","method":"In vivo transcriptional activation assay with heterologous DNA-binding domain fusions, genetic analysis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vivo functional assay with heterologous fusion constructs, single lab, mechanism not reconstituted in vitro","pmids":["15817685"],"is_preprint":false},{"year":2007,"finding":"The Nup107-160 complex interacts with CENP-F and its kinetochore recruitment mainly depends on the Ndc80 complex; depletion of the Nup107-160 complex from kinetochores causes mitotic delay, impaired chromosome congression, reduced kinetochore tension, and kinetochore-microtubule attachment defects; the Nup107-160 complex at kinetochores is required for recruitment of Crm1 and RanGAP1-RanBP2 to kinetochores.","method":"Co-immunoprecipitation, siRNA depletion, immunofluorescence, live-cell imaging, kinetochore tension measurement","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP plus multiple siRNA conditions, functional kinetochore readouts, downstream recruitment assays","pmids":["17363900"],"is_preprint":false},{"year":2007,"finding":"Nup107, Nup96, Nup133, and Nup160 subunits of the Nup107-160 complex are phosphorylated in a cell-cycle-dependent manner; phosphorylation sites cluster at the N-terminal disordered regions; the Nup107-160 subcomplex remains stable throughout the cell cycle, indicating phosphorylation regulates its association with the NPC rather than intra-complex interactions.","method":"In vivo 32P labeling, multi-stage mass spectrometry (MS/MS2/MS3), stable isotope labeling, cell-cycle synchronization","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Moderate — direct phosphorylation mapping by mass spectrometry with multiple stages of analysis; single lab but rigorous biochemical methods","pmids":["17360435"],"is_preprint":false},{"year":2008,"finding":"Crystal structure of the Nup107-Nup133 heterodimer reveals elongated structures interacting via a compact interface in tail-to-tail fashion; structure-guided mutagenesis shows Nup107 is the critical anchor for Nup133 to the NPC, positioning Nup133 at the NPC periphery.","method":"X-ray crystallography, structure-guided mutagenesis, NPC assembly assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure combined with mutagenesis validation; establishes molecular interaction architecture","pmids":["18570875"],"is_preprint":false},{"year":2009,"finding":"The Nup84-Nup145C-Sec13 heterotrimer forms the edge element of the NPC Y-complex lattice; the ACE1 heterotypic interaction between Nup84 and Nup145C is analogous to the homotypic ACE1 interaction of Sec31 in COPII lattice, supporting a lattice model for NPC scaffold architecture.","method":"X-ray crystallography of the 134-kDa heterotrimeric complex","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure of the heterotrimer at atomic resolution, directly establishes interaction interface","pmids":["19855394"],"is_preprint":false},{"year":2009,"finding":"Seh1, a component of the Nup107-160 complex, regulates centromeric localization of Aurora B and other chromosome passenger complex (CPC) proteins; Seh1 depletion causes impaired Aurora B localization, biorientation defects, and spindle midzone/midbody organization defects, while microtubule-kinetochore attachments remain intact.","method":"siRNA depletion, immunofluorescence, electron microscopy, live-cell imaging","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean siRNA KD with specific phenotypic readouts and EM validation; single lab","pmids":["19864462"],"is_preprint":false},{"year":2010,"finding":"Depletion of Nup107 by siRNA in senescent human diploid fibroblasts prevents effective nuclear translocation of phosphorylated ERK following EGF stimulation and decreases c-Fos expression, implicating Nup107 in nuclear trafficking of signal molecules.","method":"siRNA knockdown, immunofluorescence for phospho-ERK, Western blot for c-Fos","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — siRNA KD with specific signaling readouts; single lab, limited mechanistic depth","pmids":["20833136"],"is_preprint":false},{"year":2011,"finding":"SENP2 interacts with the Nup107-160 nucleoporin subcomplex through a distinct N-terminal targeting element; disruption of this interaction (along with karyopherin-mediated tethering) enhances SENP2 substrate accessibility, suggesting NPC-tethering regulates SUMO pathway activity.","method":"FRAP, Co-IP/pulldown, deletion/mutant constructs, NPC localization assays in human cells","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FRAP plus pulldown plus mutant analysis; single lab","pmids":["22031293"],"is_preprint":false},{"year":2011,"finding":"The yeast Nup84 complex is required for efficient transcription elongation, as demonstrated by a G-less-based run-on assay and RNA polymerase II chromatin immunoprecipitation.","method":"G-less-based run-on (GLRO) assay, RNA polymerase II ChIP, mutant analysis","journal":"The EMBO journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal in vivo assays (GLRO + ChIP); single lab, yeast system","pmids":["21478823"],"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; NUP107 physically and genetically interacts with spindle assembly checkpoint protein MAD1/MDF-1, and is required for MAD1's nuclear envelope accumulation.","method":"Genetic disruption (null mutant), immunofluorescence, Co-immunoprecipitation, genetic epistasis, nuclear protein import assay","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — first metazoan genetic NUP107 null with multiple orthogonal analyses including physical and genetic interaction with MAD1","pmids":["22238360"],"is_preprint":false},{"year":2013,"finding":"Reconstituted octameric Nup84 complex from Chaetomium thermophilum (carrying Nup37 and Elys) forms a dimer with side-to-side arrangement; crosslinking mass spectrometry mapped key protein interfaces within the Y-complex; Elys binds cooperatively requiring both Nup37 and Nup120.","method":"Protein reconstitution, electron microscopy, crosslinking mass spectrometry","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 / Moderate — reconstitution plus EM plus crosslinking MS mapping of interfaces; single lab but multiple orthogonal methods","pmids":["23954503"],"is_preprint":false},{"year":2015,"finding":"Nup153 recruits the Nup107-160 complex to assembly sites at the inner nuclear membrane for interphasic (but not mitotic exit) NPC assembly; Nup153 binds directly to the inner nuclear membrane via an N-terminal amphipathic helix, and transportin and Ran regulate this membrane interaction.","method":"siRNA depletion, immunofluorescence, in vitro membrane binding assay, mutational analysis","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct membrane binding assay, NPC assembly pathway dissection, multiple orthogonal methods; demonstrates mechanistic distinction between interphasic and mitotic assembly","pmids":["26051542"],"is_preprint":false},{"year":2015,"finding":"Three of four NUP107 disease mutations detected in patients with steroid-resistant nephrotic syndrome impair NUP107 binding to NUP133 and NUP107 incorporation into NPCs in vitro, establishing that loss of NUP107–NUP133 interaction is a molecular mechanism underlying the disease.","method":"In vitro binding assay, NPC incorporation assay with mutant proteins, zebrafish morpholino knockdown","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro binding and incorporation assays for mutants plus zebrafish KD model; single lab","pmids":["26411495"],"is_preprint":false},{"year":2015,"finding":"A fraction of Nup107 (as part of the Y-complex) localizes within intranuclear GLFG bodies along with Nup98 and Elys; this intranuclear pool of the Y-complex is dynamically mobile (shown by FRAP), unlike the stable NPC-associated pool; Y-complex recruitment into GLFG bodies requires the C-terminal domain of Nup98.","method":"Immunofluorescence, co-localization, FRAP, GFP-tagging, siRNA depletion","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FRAP plus co-localization plus domain mapping; single lab","pmids":["25904327"],"is_preprint":false},{"year":2015,"finding":"Nup107 directly binds Apaf-1 via the CED-4 domain of Apaf-1 and the central domain of Nup107 in an ATR-regulated, phosphorylation-dependent manner; this interaction is required for Apaf-1 nuclear import upon DNA damage, which in turn is required for Chk-1 activation and intra-S phase checkpoint.","method":"Co-immunoprecipitation, direct binding assay, dominant-negative interference, siRNA, cell cycle checkpoint assay","journal":"Cell cycle (Georgetown, Tex.)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus direct binding domain mapping plus dominant-negative validation; single lab","pmids":["25695197"],"is_preprint":false},{"year":2019,"finding":"In fission yeast, the Nup107-160 complex components show asymmetrical localization: spNup132 and spNup107 localize only to the nuclear side, while spNup131, spNup120, spNup85, spNup96, spNup37, spEly5, and spSeh1 localize only to the cytoplasmic side; fusion of spNup96 with spNup107 caused cytoplasmic mislocalization of spNup107 and led to cell cycle defects similar to spNup132 deletion.","method":"Immunoelectron microscopy, fluorescence microscopy, domain-fusion experiments, cell cycle analysis","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — two orthogonal localization methods (immunoEM + fluorescence) plus functional fusion experiments demonstrating causal relationship","pmids":["31170156"],"is_preprint":false},{"year":2019,"finding":"The yeast Nup84 complex is required for efficient nucleotide excision repair (NER) of UV-induced lesions, repair of replication-born DSBs by sister chromatid recombination (SCR), and prevention of chromosomal rearrangements; nup84Δ cells show exacerbated UV sensitivity in S phase and delayed replication fork progression.","method":"UV sensitivity assays, NER assays, sister chromatid recombination assays, replication fork progression analysis","journal":"Nucleic acids research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple DNA repair pathway assays in deletion mutants; single lab, no reconstitution","pmids":["30715474"],"is_preprint":false},{"year":2020,"finding":"Crystal structures of the full-length yeast Nup84-Nup133CTD complex and the Nup133NTD (bound to nanobodies) reveal high flexibility of this dimeric unit; the Nup133 NTD contains a structurally conserved amphipathic lipid packing sensor (ALPS) motif confirmed by liposome interaction studies.","method":"X-ray crystallography (nanobody-bound structures), liposome interaction assay","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structures plus biochemical liposome interaction validation of ALPS motif","pmids":["33247142"],"is_preprint":false},{"year":2025,"finding":"In C9orf72-ALS motor neurons, G3BP1 (a core stress granule component) exhibits enhanced interaction with Nup107, and Nup107 colocalizes with and aggregates in stress granules; knockdown of the C. elegans Nup107 ortholog (npp-5) alleviates ALS-associated phenotypes including reduced lifespan and impaired motility.","method":"Co-immunoprecipitation in iPSC-derived motor neurons, immunofluorescence co-localization, C. elegans npp-5 RNAi knockdown with lifespan/motility assays","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP plus co-localization plus in vivo rescue in C. elegans; single lab, multiple orthogonal methods","pmids":["40891053"],"is_preprint":false},{"year":2025,"finding":"In Xenopus, Nup107 is required to prevent premature nuclear export of pri-miR427 before processing; depletion of Nup107 leads to reduced mature miR427 production, stabilization of maternal transcripts including REST, and disruption of the maternal-to-zygotic transition with expansion of ectoderm at the expense of endoderm and mesoderm.","method":"Morpholino depletion in Xenopus embryos, RNA-sequencing time course, nuclear/cytoplasmic fractionation, miRNA quantification, in situ hybridization","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — morpholino depletion with RNA-seq plus fractionation plus mechanistic link to miRNA processing; single lab","pmids":["39791357"],"is_preprint":false},{"year":2026,"finding":"In Drosophila, Nup107 is required for nuclear translocation and transcriptional activation by the ecdysone receptor (EcR) and for transcription of Halloween genes (ecdysone biosynthesis genes); Nup107 functions epistatically downstream of the Torso receptor tyrosine kinase/Ras/MAPK pathway to activate EcR signaling during metamorphosis.","method":"RNAi knockdown, genetic epistasis (overexpression of torso/ras in Nup107-depleted background), EcR nuclear localization assay, gene expression analysis","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with genetic epistasis rescue experiment; single lab, Drosophila model","pmids":["41805630"],"is_preprint":false}],"current_model":"NUP107 is a core scaffold nucleoporin that forms the heptameric Nup107-160/Y-complex (including Nup160, Nup133, Nup96, Sec13, Seh1, Nup37, Nup43, and ELYS), which serves as a structural building block of the nuclear pore complex (NPC) where Nup107 acts as the critical anchor for Nup133; the complex is required for NPC assembly (especially interphasic assembly, recruited by Nup153), undergoes mitotic phosphorylation at N-terminal disordered regions, localizes to kinetochores in mitosis where it recruits the Ndc80 complex, promotes proper Aurora B/CPC localization, and recruits Crm1/RanGAP1-RanBP2; in the nucleus it also regulates transcription elongation, DNA damage repair (NER and SCR), and selective nuclear import/export events including Apaf-1 import and pri-miRNA retention, while disease-causing mutations disrupt the Nup107-Nup133 interface and NPC incorporation."},"narrative":{"mechanistic_narrative":"NUP107 is a core scaffold nucleoporin that, with Nup160, Nup133, Nup96, Sec13, Seh1, Nup37, Nup43, and ELYS, forms the heptameric Nup107-160/Y-complex serving as a structural building block of the nuclear pore complex (NPC) [PMID:15146057, PMID:23954503]. First identified as a non-FG NPC protein bearing a C-terminal leucine zipper and numerous kinase consensus sites [PMID:8021268], NUP107 functions as a keystone subunit: its depletion co-depletes Nup133 and blocks assembly of Nup358, Nup214, Nup153, and Tpr into the NPC [PMID:12552102]. Structurally, NUP107 and Nup133 form an elongated tail-to-tail heterodimer in which NUP107 acts as the critical anchor positioning Nup133 at the NPC periphery [PMID:18570875, PMID:33247142], while the Nup84–Nup145C–Sec13 heterotrimer constitutes the edge element of a COPII-like Y-complex lattice [PMID:19855394, PMID:23954503]. Interphasic NPC assembly is initiated by Nup153, which recruits the Nup107-160 complex to inner nuclear membrane assembly sites [PMID:26051542], and the complex's association with the NPC is modulated by cell-cycle-dependent phosphorylation clustered in N-terminal disordered regions [PMID:17360435]. During mitosis the entire complex is targeted to kinetochores, where its recruitment depends on the Ndc80 complex and is required for chromosome congression, kinetochore-microtubule attachment, and kinetochore tension, and where it recruits Crm1 and RanGAP1-RanBP2 and supports proper Aurora B/CPC localization [PMID:17363900, PMID:19864462]. Beyond NPC structure, the complex participates in transcription elongation [PMID:21478823], nucleotide excision repair and sister-chromatid recombination [PMID:30715474], and selective nucleocytoplasmic transport events including ATR-regulated Apaf-1 nuclear import for the intra-S checkpoint [PMID:25695197] and retention of pri-miRNA prior to processing during the maternal-to-zygotic transition [PMID:39791357]. NUP107 mutations cause steroid-resistant nephrotic syndrome by disrupting the NUP107–NUP133 interface and NPC incorporation [PMID:26411495].","teleology":[{"year":1994,"claim":"Establishing NUP107 as a bona fide nucleoporin defined the molecular entity and hinted at regulatory and structural features before any complex was known.","evidence":"Molecular cloning, sequencing, and immunoelectron microscopy localization to the NPC","pmids":["8021268"],"confidence":"High","gaps":["No interaction partners or complex membership defined","Functional role of the leucine zipper and kinase sites untested"]},{"year":1997,"claim":"Mapping NUP107 association with CAN/Nup214 on the cytoplasmic face localized the protein and assigned interaction-determining domains, the first step toward complex architecture.","evidence":"Reciprocal Co-IP under non-denaturing conditions plus mutagenesis mapping in human cells","pmids":["9166401"],"confidence":"High","gaps":["Full Y-complex composition not yet known","Stoichiometry and direct vs indirect contacts unresolved"]},{"year":2003,"claim":"Defining NUP107 as a keystone nucleoporin showed that its loss collapses assembly of a specific subset of nucleoporins, establishing a hierarchy in NPC construction.","evidence":"siRNA depletion in HeLa cells with Western blot, RT-PCR, and immunofluorescence readouts of downstream nucleoporins","pmids":["12552102"],"confidence":"High","gaps":["Mechanism of selective recruitment of downstream nups not defined","Order of assembly steps not resolved"]},{"year":2004,"claim":"Cataloguing the full vertebrate Nup107-160 complex and its mitotic kinetochore targeting expanded its role beyond interphase NPC structure into mitosis.","evidence":"Biochemical co-purification, GFP imaging, antibody immunofluorescence and RNAi in vertebrate cells; gene deletion, complex purification, and Ran genetic interaction in fission yeast","pmids":["15146057","15226438"],"confidence":"High","gaps":["Kinetochore function of the complex not yet mechanistically dissected","How the complex links to mRNA export and Ran not resolved"]},{"year":2005,"claim":"Linking the yeast Nup84 subcomplex to transcriptional activation introduced a gene-regulatory function for the scaffold beyond transport.","evidence":"In vivo transcriptional activation assay with heterologous DNA-binding-domain fusions and genetic analysis","pmids":["15817685"],"confidence":"Medium","gaps":["Mechanism not reconstituted in vitro","Relevance to metazoan NUP107 transcription untested"]},{"year":2007,"claim":"Showing kinetochore-localized Nup107-160 is recruited via Ndc80 and is required for congression, tension, and downstream Crm1/RanGAP1-RanBP2 recruitment defined its active mitotic role.","evidence":"Co-IP, siRNA depletion, immunofluorescence, live-cell imaging and kinetochore tension measurement; separately, in vivo 32P labeling and multi-stage MS mapped cell-cycle phosphorylation","pmids":["17363900","17360435"],"confidence":"High","gaps":["Kinases responsible for the mapped phosphosites not identified","How phosphorylation controls NPC association mechanistically not shown"]},{"year":2008,"claim":"The Nup107-Nup133 crystal structure with structure-guided mutagenesis established NUP107 as the molecular anchor positioning Nup133 at the NPC.","evidence":"X-ray crystallography of the heterodimer plus structure-guided mutagenesis and NPC assembly assays","pmids":["18570875"],"confidence":"High","gaps":["Higher-order lattice context not resolved here","Dynamics of the interface in vivo not addressed"]},{"year":2009,"claim":"Structural and functional work defined the Y-complex edge element and assigned Seh1 a role in CPC/Aurora B localization, deepening both architectural and mitotic understanding.","evidence":"X-ray crystallography of the Nup84-Nup145C-Sec13 heterotrimer; siRNA depletion, immunofluorescence, EM and live imaging for Seh1","pmids":["19855394","19864462"],"confidence":"High","gaps":["Seh1 CPC role studied in a single lab","How edge element assembles into the full ring not shown"]},{"year":2012,"claim":"Reconstitution and a metazoan NUP107 null connected Y-complex architecture to kinetochore Nup133 recruitment and to spindle checkpoint MAD1, unifying structural and functional data across species.","evidence":"Protein reconstitution, EM and crosslinking MS (C. thermophilum, 2013); genetic null, immunofluorescence, Co-IP and epistasis in C. elegans (2012)","pmids":["22238360","23954503"],"confidence":"High","gaps":["Direct vs indirect MAD1 interaction not fully resolved","Generality of kinetochore Nup133 dependence across cell types untested"]},{"year":2015,"claim":"Multiple 2015 studies resolved how the complex is recruited for interphasic assembly, defined a mobile intranuclear pool, linked NUP107 to Apaf-1-dependent DNA-damage checkpoint signaling, and established a disease mechanism.","evidence":"Nup153 recruitment and membrane-binding assays; FRAP of GLFG-body Y-complex pool; Apaf-1 binding/domain mapping and checkpoint assays; in vitro binding/incorporation assays of nephrotic syndrome mutants with zebrafish knockdown","pmids":["26051542","25904327","25695197","26411495"],"confidence":"Medium","gaps":["Function of the mobile intranuclear Y-complex pool unclear","Apaf-1 import and disease findings each from single labs without independent replication"]},{"year":2019,"claim":"Asymmetric localization data and DNA repair assays refined where NUP107 sits within the NPC and broadened its genome-maintenance roles.","evidence":"ImmunoEM, fluorescence microscopy and domain-fusion in fission yeast; UV sensitivity, NER, sister-chromatid recombination and fork progression assays in budding yeast","pmids":["31170156","30715474"],"confidence":"High","gaps":["Whether asymmetric positioning holds in metazoa not tested","Direct role of NUP107 protein in NER vs indirect via NPC tethering not separated"]},{"year":2020,"claim":"Full-length Nup84-Nup133 structures revealed conformational flexibility and confirmed an ALPS lipid-sensing motif, connecting the scaffold to membrane curvature recognition.","evidence":"Nanobody-bound X-ray crystallography plus liposome interaction assays","pmids":["33247142"],"confidence":"High","gaps":["Functional consequence of flexibility in assembled NPCs not shown","ALPS motif role in vivo not directly tested"]},{"year":2025,"claim":"Developmental and disease studies extended NUP107 function to pri-miRNA retention during the maternal-to-zygotic transition, EcR signaling in metamorphosis, and stress-granule association in C9orf72-ALS.","evidence":"Morpholino depletion with RNA-seq and fractionation in Xenopus; RNAi and genetic epistasis in Drosophila; Co-IP and co-localization in iPSC motor neurons with C. elegans rescue","pmids":["39791357","41805630","40891053"],"confidence":"Medium","gaps":["Mechanism of selective pri-miRNA retention unresolved","Each developmental/disease link from a single lab","Whether ALS phenotypes reflect direct NUP107 aggregation or transport failure unclear"]},{"year":null,"claim":"How NUP107 phosphorylation, conformational flexibility, and membrane-sensing are coordinated to control NPC assembly versus its many off-pore functions remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["Kinases and signals coupling phosphorylation to NPC association unidentified","Mechanistic basis for selective transport (Apaf-1, pri-miRNA, EcR) not unified","Tissue-specificity of nephrotic-syndrome disease phenotype unexplained"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2,8,9]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[2,8,16]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[22]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[16,14]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[18,24]},{"term_id":"GO:0005694","term_label":"chromosome","supporting_discovery_ids":[3,6]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[2,16,19]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[3,6,10]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[5,13,25]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[21]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[4,24]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[2,16]}],"complexes":["Nup107-160 / Y-complex","nuclear pore complex (NPC)","kinetochore"],"partners":["NUP133","NUP96","SEC13","SEH1","NUP37","ELYS","NUP153","NUP214"],"other_free_text":[]}},"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 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it was localized to the NPC by immunoelectron microscopy.\",\n      \"method\": \"Molecular cloning, sequencing, immunoelectron microscopy, biochemical fractionation\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization by immunoelectron microscopy, molecular cloning and sequence analysis, replicated in subsequent studies\",\n      \"pmids\": [\"8021268\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"Human Nup84 (NUP107) is tightly associated with CAN/Nup214 on the cytoplasmic face of the NPC; the NH2-terminal region of Nup84 contains the interaction site with CAN/Nup214, while the C-terminal putative coiled-coil domain is required for association with the cytoplasmic face of the NPC.\",\n      \"method\": \"Immunoprecipitation under nondenaturing conditions, mutagenesis, expression studies, cytoplasmic face localization determination\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, mutagenesis mapping of interaction domains, direct localization, foundational study replicated by subsequent work\",\n      \"pmids\": [\"9166401\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"Depletion of Nup107 by siRNA caused co-depletion of Nup133 (but not Nup96 or Sec13) and prevented assembly of Nup358, Nup214, Nup153, and Tpr into the NPC, establishing Nup107 as a keystone nucleoporin required for assembly of a subset of nucleoporins into the NPC.\",\n      \"method\": \"siRNA knockdown in HeLa cells, Western blot, RT-PCR, immunofluorescence\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean siRNA KD with multiple downstream readouts, replicated and extended by multiple subsequent studies\",\n      \"pmids\": [\"12552102\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The Nup107-160 complex in vertebrates includes three additional WD-repeat nucleoporins (Nup37, Nup43, and Seh1/Sec13), and the entire complex is targeted to kinetochores from prophase to anaphase of mitosis.\",\n      \"method\": \"Biochemical co-purification, GFP-tagged nucleoporin imaging, specific antibody immunofluorescence, RNAi\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — biochemical complex identification combined with live-cell imaging and RNAi phenotyping; replicated in multiple subsequent studies\",\n      \"pmids\": [\"15146057\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The fission yeast Nup107-120 complex (ortholog of the vertebrate Nup107-160 complex) is required for mRNA export, nuclear pore distribution, and proper cell division; it functionally interacts with the small GTPase Ran/Spi1, as overexpression of a nonfunctional Ran allele is specifically toxic in nup120 and nup133b deletion mutants.\",\n      \"method\": \"Gene deletion, biochemical co-purification, nuclear envelope localization, genetic epistasis/synthetic lethality, mRNA export assay\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis with multiple orthogonal methods (deletion phenotypes, biochemical complex, genetic interaction with Ran)\",\n      \"pmids\": [\"15226438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The yeast Nup84 subcomplex mediates Rap1/Gcr1/Gcr2 transcriptional activation ('reverse recruitment'); Nup84 and associated subcomplex components can activate transcription themselves when fused to a heterologous DNA-binding domain, and Gcr1/Gcr2 bridge the NPC to the transcriptional machinery.\",\n      \"method\": \"In vivo transcriptional activation assay with heterologous DNA-binding domain fusions, genetic analysis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vivo functional assay with heterologous fusion constructs, single lab, mechanism not reconstituted in vitro\",\n      \"pmids\": [\"15817685\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The Nup107-160 complex interacts with CENP-F and its kinetochore recruitment mainly depends on the Ndc80 complex; depletion of the Nup107-160 complex from kinetochores causes mitotic delay, impaired chromosome congression, reduced kinetochore tension, and kinetochore-microtubule attachment defects; the Nup107-160 complex at kinetochores is required for recruitment of Crm1 and RanGAP1-RanBP2 to kinetochores.\",\n      \"method\": \"Co-immunoprecipitation, siRNA depletion, immunofluorescence, live-cell imaging, kinetochore tension measurement\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP plus multiple siRNA conditions, functional kinetochore readouts, downstream recruitment assays\",\n      \"pmids\": [\"17363900\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Nup107, Nup96, Nup133, and Nup160 subunits of the Nup107-160 complex are phosphorylated in a cell-cycle-dependent manner; phosphorylation sites cluster at the N-terminal disordered regions; the Nup107-160 subcomplex remains stable throughout the cell cycle, indicating phosphorylation regulates its association with the NPC rather than intra-complex interactions.\",\n      \"method\": \"In vivo 32P labeling, multi-stage mass spectrometry (MS/MS2/MS3), stable isotope labeling, cell-cycle synchronization\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — direct phosphorylation mapping by mass spectrometry with multiple stages of analysis; single lab but rigorous biochemical methods\",\n      \"pmids\": [\"17360435\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Crystal structure of the Nup107-Nup133 heterodimer reveals elongated structures interacting via a compact interface in tail-to-tail fashion; structure-guided mutagenesis shows Nup107 is the critical anchor for Nup133 to the NPC, positioning Nup133 at the NPC periphery.\",\n      \"method\": \"X-ray crystallography, structure-guided mutagenesis, NPC assembly assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure combined with mutagenesis validation; establishes molecular interaction architecture\",\n      \"pmids\": [\"18570875\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The Nup84-Nup145C-Sec13 heterotrimer forms the edge element of the NPC Y-complex lattice; the ACE1 heterotypic interaction between Nup84 and Nup145C is analogous to the homotypic ACE1 interaction of Sec31 in COPII lattice, supporting a lattice model for NPC scaffold architecture.\",\n      \"method\": \"X-ray crystallography of the 134-kDa heterotrimeric complex\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure of the heterotrimer at atomic resolution, directly establishes interaction interface\",\n      \"pmids\": [\"19855394\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Seh1, a component of the Nup107-160 complex, regulates centromeric localization of Aurora B and other chromosome passenger complex (CPC) proteins; Seh1 depletion causes impaired Aurora B localization, biorientation defects, and spindle midzone/midbody organization defects, while microtubule-kinetochore attachments remain intact.\",\n      \"method\": \"siRNA depletion, immunofluorescence, electron microscopy, live-cell imaging\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean siRNA KD with specific phenotypic readouts and EM validation; single lab\",\n      \"pmids\": [\"19864462\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Depletion of Nup107 by siRNA in senescent human diploid fibroblasts prevents effective nuclear translocation of phosphorylated ERK following EGF stimulation and decreases c-Fos expression, implicating Nup107 in nuclear trafficking of signal molecules.\",\n      \"method\": \"siRNA knockdown, immunofluorescence for phospho-ERK, Western blot for c-Fos\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — siRNA KD with specific signaling readouts; single lab, limited mechanistic depth\",\n      \"pmids\": [\"20833136\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"SENP2 interacts with the Nup107-160 nucleoporin subcomplex through a distinct N-terminal targeting element; disruption of this interaction (along with karyopherin-mediated tethering) enhances SENP2 substrate accessibility, suggesting NPC-tethering regulates SUMO pathway activity.\",\n      \"method\": \"FRAP, Co-IP/pulldown, deletion/mutant constructs, NPC localization assays in human cells\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FRAP plus pulldown plus mutant analysis; single lab\",\n      \"pmids\": [\"22031293\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The yeast Nup84 complex is required for efficient transcription elongation, as demonstrated by a G-less-based run-on assay and RNA polymerase II chromatin immunoprecipitation.\",\n      \"method\": \"G-less-based run-on (GLRO) assay, RNA polymerase II ChIP, mutant analysis\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal in vivo assays (GLRO + ChIP); single lab, yeast system\",\n      \"pmids\": [\"21478823\"],\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; NUP107 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 (null mutant), immunofluorescence, Co-immunoprecipitation, genetic epistasis, nuclear protein import assay\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — first metazoan genetic NUP107 null with multiple orthogonal analyses including physical and genetic interaction with MAD1\",\n      \"pmids\": [\"22238360\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Reconstituted octameric Nup84 complex from Chaetomium thermophilum (carrying Nup37 and Elys) forms a dimer with side-to-side arrangement; crosslinking mass spectrometry mapped key protein interfaces within the Y-complex; Elys binds cooperatively requiring both Nup37 and Nup120.\",\n      \"method\": \"Protein reconstitution, electron microscopy, crosslinking mass spectrometry\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — reconstitution plus EM plus crosslinking MS mapping of interfaces; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"23954503\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Nup153 recruits the Nup107-160 complex to assembly sites at the inner nuclear membrane for interphasic (but not mitotic exit) NPC assembly; Nup153 binds directly to the inner nuclear membrane via an N-terminal amphipathic helix, and transportin and Ran regulate this membrane interaction.\",\n      \"method\": \"siRNA depletion, immunofluorescence, in vitro membrane binding assay, mutational analysis\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct membrane binding assay, NPC assembly pathway dissection, multiple orthogonal methods; demonstrates mechanistic distinction between interphasic and mitotic assembly\",\n      \"pmids\": [\"26051542\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Three of four NUP107 disease mutations detected in patients with steroid-resistant nephrotic syndrome impair NUP107 binding to NUP133 and NUP107 incorporation into NPCs in vitro, establishing that loss of NUP107–NUP133 interaction is a molecular mechanism underlying the disease.\",\n      \"method\": \"In vitro binding assay, NPC incorporation assay with mutant proteins, zebrafish morpholino knockdown\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro binding and incorporation assays for mutants plus zebrafish KD model; single lab\",\n      \"pmids\": [\"26411495\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"A fraction of Nup107 (as part of the Y-complex) localizes within intranuclear GLFG bodies along with Nup98 and Elys; this intranuclear pool of the Y-complex is dynamically mobile (shown by FRAP), unlike the stable NPC-associated pool; Y-complex recruitment into GLFG bodies requires the C-terminal domain of Nup98.\",\n      \"method\": \"Immunofluorescence, co-localization, FRAP, GFP-tagging, siRNA depletion\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FRAP plus co-localization plus domain mapping; single lab\",\n      \"pmids\": [\"25904327\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Nup107 directly binds Apaf-1 via the CED-4 domain of Apaf-1 and the central domain of Nup107 in an ATR-regulated, phosphorylation-dependent manner; this interaction is required for Apaf-1 nuclear import upon DNA damage, which in turn is required for Chk-1 activation and intra-S phase checkpoint.\",\n      \"method\": \"Co-immunoprecipitation, direct binding assay, dominant-negative interference, siRNA, cell cycle checkpoint assay\",\n      \"journal\": \"Cell cycle (Georgetown, Tex.)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus direct binding domain mapping plus dominant-negative validation; single lab\",\n      \"pmids\": [\"25695197\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In fission yeast, the Nup107-160 complex components show asymmetrical localization: spNup132 and spNup107 localize only to the nuclear side, while spNup131, spNup120, spNup85, spNup96, spNup37, spEly5, and spSeh1 localize only to the cytoplasmic side; fusion of spNup96 with spNup107 caused cytoplasmic mislocalization of spNup107 and led to cell cycle defects similar to spNup132 deletion.\",\n      \"method\": \"Immunoelectron microscopy, fluorescence microscopy, domain-fusion experiments, cell cycle analysis\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two orthogonal localization methods (immunoEM + fluorescence) plus functional fusion experiments demonstrating causal relationship\",\n      \"pmids\": [\"31170156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The yeast Nup84 complex is required for efficient nucleotide excision repair (NER) of UV-induced lesions, repair of replication-born DSBs by sister chromatid recombination (SCR), and prevention of chromosomal rearrangements; nup84Δ cells show exacerbated UV sensitivity in S phase and delayed replication fork progression.\",\n      \"method\": \"UV sensitivity assays, NER assays, sister chromatid recombination assays, replication fork progression analysis\",\n      \"journal\": \"Nucleic acids research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple DNA repair pathway assays in deletion mutants; single lab, no reconstitution\",\n      \"pmids\": [\"30715474\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Crystal structures of the full-length yeast Nup84-Nup133CTD complex and the Nup133NTD (bound to nanobodies) reveal high flexibility of this dimeric unit; the Nup133 NTD contains a structurally conserved amphipathic lipid packing sensor (ALPS) motif confirmed by liposome interaction studies.\",\n      \"method\": \"X-ray crystallography (nanobody-bound structures), liposome interaction assay\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structures plus biochemical liposome interaction validation of ALPS motif\",\n      \"pmids\": [\"33247142\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In C9orf72-ALS motor neurons, G3BP1 (a core stress granule component) exhibits enhanced interaction with Nup107, and Nup107 colocalizes with and aggregates in 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 in iPSC-derived motor neurons, immunofluorescence co-localization, C. elegans npp-5 RNAi knockdown with lifespan/motility assays\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP plus co-localization plus in vivo rescue in C. elegans; single lab, multiple orthogonal methods\",\n      \"pmids\": [\"40891053\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In Xenopus, Nup107 is required to prevent premature nuclear export of pri-miR427 before processing; depletion of Nup107 leads to reduced mature miR427 production, stabilization of maternal transcripts including REST, and disruption of the maternal-to-zygotic transition with expansion of ectoderm at the expense of endoderm and mesoderm.\",\n      \"method\": \"Morpholino depletion in Xenopus embryos, RNA-sequencing time course, nuclear/cytoplasmic fractionation, miRNA quantification, in situ hybridization\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — morpholino depletion with RNA-seq plus fractionation plus mechanistic link to miRNA processing; single lab\",\n      \"pmids\": [\"39791357\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"In Drosophila, Nup107 is required for nuclear translocation and transcriptional activation by the ecdysone receptor (EcR) and for transcription of Halloween genes (ecdysone biosynthesis genes); Nup107 functions epistatically downstream of the Torso receptor tyrosine kinase/Ras/MAPK pathway to activate EcR signaling during metamorphosis.\",\n      \"method\": \"RNAi knockdown, genetic epistasis (overexpression of torso/ras in Nup107-depleted background), EcR nuclear localization assay, gene expression analysis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with genetic epistasis rescue experiment; single lab, Drosophila model\",\n      \"pmids\": [\"41805630\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP107 is a core scaffold nucleoporin that forms the heptameric Nup107-160/Y-complex (including Nup160, Nup133, Nup96, Sec13, Seh1, Nup37, Nup43, and ELYS), which serves as a structural building block of the nuclear pore complex (NPC) where Nup107 acts as the critical anchor for Nup133; the complex is required for NPC assembly (especially interphasic assembly, recruited by Nup153), undergoes mitotic phosphorylation at N-terminal disordered regions, localizes to kinetochores in mitosis where it recruits the Ndc80 complex, promotes proper Aurora B/CPC localization, and recruits Crm1/RanGAP1-RanBP2; in the nucleus it also regulates transcription elongation, DNA damage repair (NER and SCR), and selective nuclear import/export events including Apaf-1 import and pri-miRNA retention, while disease-causing mutations disrupt the Nup107-Nup133 interface and NPC incorporation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP107 is a core scaffold nucleoporin that, with Nup160, Nup133, Nup96, Sec13, Seh1, Nup37, Nup43, and ELYS, forms the heptameric Nup107-160/Y-complex serving as a structural building block of the nuclear pore complex (NPC) [#3, #15]. First identified as a non-FG NPC protein bearing a C-terminal leucine zipper and numerous kinase consensus sites [#0], NUP107 functions as a keystone subunit: its depletion co-depletes Nup133 and blocks assembly of Nup358, Nup214, Nup153, and Tpr into the NPC [#2]. Structurally, NUP107 and Nup133 form an elongated tail-to-tail heterodimer in which NUP107 acts as the critical anchor positioning Nup133 at the NPC periphery [#8, #22], while the Nup84–Nup145C–Sec13 heterotrimer constitutes the edge element of a COPII-like Y-complex lattice [#9, #15]. Interphasic NPC assembly is initiated by Nup153, which recruits the Nup107-160 complex to inner nuclear membrane assembly sites [#16], and the complex's association with the NPC is modulated by cell-cycle-dependent phosphorylation clustered in N-terminal disordered regions [#7]. During mitosis the entire complex is targeted to kinetochores, where its recruitment depends on the Ndc80 complex and is required for chromosome congression, kinetochore-microtubule attachment, and kinetochore tension, and where it recruits Crm1 and RanGAP1-RanBP2 and supports proper Aurora B/CPC localization [#6, #10]. Beyond NPC structure, the complex participates in transcription elongation [#13], nucleotide excision repair and sister-chromatid recombination [#21], and selective nucleocytoplasmic transport events including ATR-regulated Apaf-1 nuclear import for the intra-S checkpoint [#19] and retention of pri-miRNA prior to processing during the maternal-to-zygotic transition [#24]. NUP107 mutations cause steroid-resistant nephrotic syndrome by disrupting the NUP107–NUP133 interface and NPC incorporation [#17].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Establishing NUP107 as a bona fide nucleoporin defined the molecular entity and hinted at regulatory and structural features before any complex was known.\",\n      \"evidence\": \"Molecular cloning, sequencing, and immunoelectron microscopy localization to the NPC\",\n      \"pmids\": [\"8021268\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"No interaction partners or complex membership defined\", \"Functional role of the leucine zipper and kinase sites untested\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Mapping NUP107 association with CAN/Nup214 on the cytoplasmic face localized the protein and assigned interaction-determining domains, the first step toward complex architecture.\",\n      \"evidence\": \"Reciprocal Co-IP under non-denaturing conditions plus mutagenesis mapping in human cells\",\n      \"pmids\": [\"9166401\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full Y-complex composition not yet known\", \"Stoichiometry and direct vs indirect contacts unresolved\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Defining NUP107 as a keystone nucleoporin showed that its loss collapses assembly of a specific subset of nucleoporins, establishing a hierarchy in NPC construction.\",\n      \"evidence\": \"siRNA depletion in HeLa cells with Western blot, RT-PCR, and immunofluorescence readouts of downstream nucleoporins\",\n      \"pmids\": [\"12552102\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of selective recruitment of downstream nups not defined\", \"Order of assembly steps not resolved\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Cataloguing the full vertebrate Nup107-160 complex and its mitotic kinetochore targeting expanded its role beyond interphase NPC structure into mitosis.\",\n      \"evidence\": \"Biochemical co-purification, GFP imaging, antibody immunofluorescence and RNAi in vertebrate cells; gene deletion, complex purification, and Ran genetic interaction in fission yeast\",\n      \"pmids\": [\"15146057\", \"15226438\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinetochore function of the complex not yet mechanistically dissected\", \"How the complex links to mRNA export and Ran not resolved\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Linking the yeast Nup84 subcomplex to transcriptional activation introduced a gene-regulatory function for the scaffold beyond transport.\",\n      \"evidence\": \"In vivo transcriptional activation assay with heterologous DNA-binding-domain fusions and genetic analysis\",\n      \"pmids\": [\"15817685\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism not reconstituted in vitro\", \"Relevance to metazoan NUP107 transcription untested\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Showing kinetochore-localized Nup107-160 is recruited via Ndc80 and is required for congression, tension, and downstream Crm1/RanGAP1-RanBP2 recruitment defined its active mitotic role.\",\n      \"evidence\": \"Co-IP, siRNA depletion, immunofluorescence, live-cell imaging and kinetochore tension measurement; separately, in vivo 32P labeling and multi-stage MS mapped cell-cycle phosphorylation\",\n      \"pmids\": [\"17363900\", \"17360435\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinases responsible for the mapped phosphosites not identified\", \"How phosphorylation controls NPC association mechanistically not shown\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"The Nup107-Nup133 crystal structure with structure-guided mutagenesis established NUP107 as the molecular anchor positioning Nup133 at the NPC.\",\n      \"evidence\": \"X-ray crystallography of the heterodimer plus structure-guided mutagenesis and NPC assembly assays\",\n      \"pmids\": [\"18570875\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Higher-order lattice context not resolved here\", \"Dynamics of the interface in vivo not addressed\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Structural and functional work defined the Y-complex edge element and assigned Seh1 a role in CPC/Aurora B localization, deepening both architectural and mitotic understanding.\",\n      \"evidence\": \"X-ray crystallography of the Nup84-Nup145C-Sec13 heterotrimer; siRNA depletion, immunofluorescence, EM and live imaging for Seh1\",\n      \"pmids\": [\"19855394\", \"19864462\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Seh1 CPC role studied in a single lab\", \"How edge element assembles into the full ring not shown\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Reconstitution and a metazoan NUP107 null connected Y-complex architecture to kinetochore Nup133 recruitment and to spindle checkpoint MAD1, unifying structural and functional data across species.\",\n      \"evidence\": \"Protein reconstitution, EM and crosslinking MS (C. thermophilum, 2013); genetic null, immunofluorescence, Co-IP and epistasis in C. elegans (2012)\",\n      \"pmids\": [\"22238360\", \"23954503\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs indirect MAD1 interaction not fully resolved\", \"Generality of kinetochore Nup133 dependence across cell types untested\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Multiple 2015 studies resolved how the complex is recruited for interphasic assembly, defined a mobile intranuclear pool, linked NUP107 to Apaf-1-dependent DNA-damage checkpoint signaling, and established a disease mechanism.\",\n      \"evidence\": \"Nup153 recruitment and membrane-binding assays; FRAP of GLFG-body Y-complex pool; Apaf-1 binding/domain mapping and checkpoint assays; in vitro binding/incorporation assays of nephrotic syndrome mutants with zebrafish knockdown\",\n      \"pmids\": [\"26051542\", \"25904327\", \"25695197\", \"26411495\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Function of the mobile intranuclear Y-complex pool unclear\", \"Apaf-1 import and disease findings each from single labs without independent replication\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Asymmetric localization data and DNA repair assays refined where NUP107 sits within the NPC and broadened its genome-maintenance roles.\",\n      \"evidence\": \"ImmunoEM, fluorescence microscopy and domain-fusion in fission yeast; UV sensitivity, NER, sister-chromatid recombination and fork progression assays in budding yeast\",\n      \"pmids\": [\"31170156\", \"30715474\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Whether asymmetric positioning holds in metazoa not tested\", \"Direct role of NUP107 protein in NER vs indirect via NPC tethering not separated\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Full-length Nup84-Nup133 structures revealed conformational flexibility and confirmed an ALPS lipid-sensing motif, connecting the scaffold to membrane curvature recognition.\",\n      \"evidence\": \"Nanobody-bound X-ray crystallography plus liposome interaction assays\",\n      \"pmids\": [\"33247142\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of flexibility in assembled NPCs not shown\", \"ALPS motif role in vivo not directly tested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Developmental and disease studies extended NUP107 function to pri-miRNA retention during the maternal-to-zygotic transition, EcR signaling in metamorphosis, and stress-granule association in C9orf72-ALS.\",\n      \"evidence\": \"Morpholino depletion with RNA-seq and fractionation in Xenopus; RNAi and genetic epistasis in Drosophila; Co-IP and co-localization in iPSC motor neurons with C. elegans rescue\",\n      \"pmids\": [\"39791357\", \"41805630\", \"40891053\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of selective pri-miRNA retention unresolved\", \"Each developmental/disease link from a single lab\", \"Whether ALS phenotypes reflect direct NUP107 aggregation or transport failure unclear\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NUP107 phosphorylation, conformational flexibility, and membrane-sensing are coordinated to control NPC assembly versus its many off-pore functions remains unresolved.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Kinases and signals coupling phosphorylation to NPC association unidentified\", \"Mechanistic basis for selective transport (Apaf-1, pri-miRNA, EcR) not unified\", \"Tissue-specificity of nephrotic-syndrome disease phenotype unexplained\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2, 8, 9]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [2, 8, 16]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [22]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [16, 14]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [18, 24]},\n      {\"term_id\": \"GO:0005694\", \"supporting_discovery_ids\": [3, 6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [2, 16, 19]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [3, 6, 10]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [5, 13, 25]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [21]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [4, 24]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [2, 16]}\n    ],\n    \"complexes\": [\n      \"Nup107-160 / Y-complex\",\n      \"nuclear pore complex (NPC)\",\n      \"kinetochore\"\n    ],\n    \"partners\": [\n      \"NUP133\",\n      \"NUP96\",\n      \"SEC13\",\n      \"SEH1\",\n      \"NUP37\",\n      \"ELYS\",\n      \"NUP153\",\n      \"NUP214\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}