{"gene":"NUP133","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2001,"finding":"Nup133 (and Nup160) are novel vertebrate nucleoporins that form a complex with Nup107, Nup96, and Sec13 (the Nup160 complex) at the basket side of the nuclear pore; specific Nup133 fragments block poly[A]+ RNA export but not protein import or export, establishing a direct role in mRNA export.","method":"Pulldown from Xenopus egg extracts, immunofluorescence, co-immunoprecipitation, in vivo transport assays with dominant-negative fragments","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal pulldowns, complex reconstitution from egg extracts, functional transport assays with specific fragments; replicated across multiple orthogonal methods in one rigorous study","pmids":["11684705"],"is_preprint":false},{"year":1995,"finding":"Yeast Nup133 (RAT3/NUP133) is required for mRNA export and proper nuclear pore complex distribution; loss-of-function causes temperature-dependent nuclear accumulation of poly(A)+ RNA and constitutive clustering of NPCs.","method":"Temperature-sensitive mutation isolation, fluorescent in situ hybridization for poly(A)+ RNA, indirect immunofluorescence, electron microscopy, gene disruption","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic loss-of-function with defined cellular phenotypes (mRNA export block, NPC clustering), replicated independently by two groups (PMID 7626806 and 7862658)","pmids":["7626806","7862658"],"is_preprint":false},{"year":1995,"finding":"Disruption of yeast NUP133 leads to clustering of nuclear pore complexes, consistent with a role in maintaining NPC distribution within the nuclear envelope.","method":"Gene disruption, cell fractionation, co-enrichment with NPC fraction","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic disruption with defined cellular phenotype, independently replicated by Li et al. (PMID 7626806)","pmids":["7862658"],"is_preprint":false},{"year":2004,"finding":"Human Nup133 contains two structural domains: a C-terminal domain mediating interaction with Nup107 (and thus NPC integration), and an N-terminal seven-bladed beta-propeller domain whose surface properties suggest it mediates multiple protein interactions.","method":"Crystal structure of N-terminal beta-propeller domain, domain deletion/interaction mapping","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure of N-terminal domain plus functional domain-mapping experiments, single lab but multiple orthogonal methods","pmids":["15557116"],"is_preprint":false},{"year":2008,"finding":"Crystal structure of the human Nup107–Nup133 C-terminal domain complex reveals a tight tail-to-tail interface; structure-guided mutagenesis shows Nup107 is the critical anchor for Nup133 within the NPC scaffold, positioning Nup133 at the NPC periphery.","method":"Crystal structure determination, structure-guided mutagenesis, binding assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal structure combined with functional mutagenesis validating the interface, single lab with two orthogonal methods","pmids":["18570875"],"is_preprint":false},{"year":2009,"finding":"Crystal structures of yNup170 and hNup107–hNup133 show conserved domain architecture, indicating Nup157/170 and Nup133 share a common ancestral helical element (distinct from ACE1) that constitutes a major alpha-helical building block of the NPC scaffold.","method":"Crystal structure determination and structural comparison","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — crystal structures from single lab, structural/evolutionary inference without functional mutagenesis validation","pmids":["19674973"],"is_preprint":false},{"year":2011,"finding":"The N-terminal domain of Nup133 is required for anchoring the dynein/dynactin complex to the nuclear envelope in prophase via an interaction network involving CENP-F and NudE/NudEL; this tethers centrosomes to the nuclear envelope at the G2/M transition and contributes to bipolar spindle assembly.","method":"Dominant-negative N-terminal domain constructs, co-immunoprecipitation, live-cell imaging, siRNA knockdown","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IPs defining the interaction network, dominant-negative and rescue experiments, live imaging of centrosome dynamics; multiple orthogonal methods in single lab","pmids":["21383080"],"is_preprint":false},{"year":2011,"finding":"Crystal structure of the C-terminal domain of yeast Nup133 (ScNup133 residues 944–1157) shows an all-alpha-helical fold distinct from the two-block arrangement seen in the human Nup133 C-terminal domain bound to Nup107, indicating structural divergence between homologs.","method":"X-ray crystallography at 1.9 Å resolution","journal":"Proteins","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — high-resolution crystal structure from single lab, structural observation without functional mutagenesis follow-up","pmids":["21365675"],"is_preprint":false},{"year":2014,"finding":"Integrative structural modeling of full-length yeast Nup133 reveals an amphipathic lipid packing sensor (ALPS) motif in the N-terminal beta-propeller region; mutational studies and chemical cross-linking validate the model and suggest the ALPS motif mediates membrane anchoring of the NPC in the nuclear envelope.","method":"Integrative modeling using crystal structures, SAXS, negative-stain EM, mutational studies, chemical cross-linking/mass spectrometry","journal":"Molecular & cellular proteomics","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — multiple orthogonal structural methods plus mutational validation in single study, but functional membrane-anchoring activity not directly reconstituted","pmids":["25139911"],"is_preprint":false},{"year":2018,"finding":"Nup133 loss-of-function specifically perturbs nuclear basket assembly in mouse embryonic stem cells: it is required for stable incorporation of Tpr into approximately half of NPCs and for proper Nup153 dynamics, with the central domain of Nup133 mediating this function.","method":"CRISPR/null mutation in mESCs, single-pore detection by fluorescence microscopy, FRAP of Nup153, domain mapping with rescue constructs","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with quantitative single-pore readout, FRAP, and domain-specific rescue; multiple orthogonal methods in single lab","pmids":["29791854"],"is_preprint":false},{"year":2018,"finding":"A homozygous splicing mutation in NUP133 (c.3335-11T>A) impairs NUP133–NUP107 protein interaction as shown by immunoprecipitation; nup133 morphant zebrafish exhibit microcephaly, reduced neuronal cells, underdeveloped glomeruli, and podocyte foot process fusion, all rescued by wild-type but not mutant human NUP133 mRNA.","method":"Immunoprecipitation assay, zebrafish nup133 morpholino knockdown with mRNA rescue","journal":"Annals of neurology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP demonstrating impaired interaction, in vivo morphant rescue experiment with wild-type vs. mutant mRNA; two orthogonal methods, single lab","pmids":["30427554"],"is_preprint":false},{"year":2020,"finding":"The Nup133 N-terminal domain contains a structurally conserved ALPS motif that directly interacts with liposomes, confirming a membrane-anchoring function for this motif within the Y complex.","method":"Cryo-EM/nanobody-bound crystal structures, liposome interaction studies","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Moderate — crystal/cryo structure plus direct liposome binding assay validating the ALPS motif function; two orthogonal methods in single study","pmids":["33247142"],"is_preprint":false},{"year":2020,"finding":"In oligodendrocyte progenitor cells, Nup133 protein level decline following hyperoxia correlates with decreased Nrf1 mRNA, and Nrf1 is identified as a direct downstream transcriptional target of Nup133, contributing to sex-differential oxidative stress responses.","method":"Hyperoxia treatment of primary OPCs, western blotting, mRNA quantification, cell culture knockdown/overexpression","journal":"Molecular and cellular pediatrics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, correlation-based with limited mechanistic follow-up; Nrf1 described as 'direct downstream target' but mechanistic details not fully resolved in abstract","pmids":["32844334"],"is_preprint":false},{"year":2022,"finding":"CRISPR/Cas9-mediated loss of NUP133 in human podocytes disrupts nuclear pore assembly, alters the podocyte-specific transcriptome, and impairs cellular protrusion generation; SRNS-associated NUP133 mutations primarily impair Y-complex protein interactions and reduce NUP133 protein levels, causing partial loss-of-function.","method":"CRISPR/Cas9 genome editing in human podocytes, transcriptome analysis, NPC assembly assays, cytoskeleton/protrusion assays, protein interaction analysis","journal":"Cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined cellular phenotypes across multiple readouts; single lab with multiple orthogonal methods","pmids":["35455939"],"is_preprint":false}],"current_model":"NUP133 is a scaffold nucleoporin that integrates into the NPC via a tight interaction with NUP107 (mediated by its C-terminal alpha-helical domain), positions itself at the NPC periphery within the Y-complex/Nup107-160 complex, mediates mRNA export and proper NPC distribution, anchors the NPC to the nuclear envelope membrane through an N-terminal ALPS motif, promotes nuclear basket assembly (Tpr/Nup153 incorporation) through its central domain, and in prophase recruits dynein/dynactin to the nuclear envelope via CENP-F and NudE/NudEL to tether centrosomes and facilitate bipolar spindle assembly."},"narrative":{"mechanistic_narrative":"NUP133 is a scaffold nucleoporin of the conserved Y-complex (Nup107-160 complex) that builds the structural core of the nuclear pore complex (NPC) and supports nucleocytoplasmic transport [PMID:11684705, PMID:7626806, PMID:7862658]. It integrates into the NPC scaffold through a tight tail-to-tail interface between its C-terminal alpha-helical domain and Nup107, which serves as the critical anchor positioning NUP133 at the NPC periphery [PMID:15557116, PMID:18570875]. Its N-terminal seven-bladed beta-propeller domain harbors an amphipathic lipid packing sensor (ALPS) motif that binds membranes directly, anchoring the NPC to the curved nuclear envelope membrane [PMID:15557116, PMID:25139911, PMID:33247142]. Beyond scaffolding, NUP133 is required for mRNA export and for proper NPC distribution within the nuclear envelope, since loss of function causes nuclear accumulation of poly(A)+ RNA and clustering of pores [PMID:11684705, PMID:7626806, PMID:7862658]. Its central domain promotes nuclear basket assembly by enabling stable incorporation of Tpr and proper Nup153 dynamics [PMID:29791854], while its N-terminal domain performs a mitotic role, recruiting the dynein/dynactin complex to the nuclear envelope in prophase via a CENP-F and NudE/NudEL network to tether centrosomes and support bipolar spindle assembly [PMID:21383080]. Loss-of-function and partial-loss-of-function mutations in NUP133, which impair NUP133-NUP107/Y-complex interactions, cause a Mendelian disease spectrum including steroid-resistant nephrotic syndrome and neurodevelopmental phenotypes, recapitulated by disrupted NPC assembly and altered cell-type-specific function in podocytes and in zebrafish [PMID:30427554, PMID:35455939].","teleology":[{"year":1995,"claim":"Established the first functional role for Nup133 by showing it is needed for both mRNA export and proper spatial organization of NPCs within the nuclear envelope.","evidence":"Temperature-sensitive yeast mutants and gene disruption with poly(A)+ RNA FISH, immunofluorescence, and EM","pmids":["7626806","7862658"],"confidence":"High","gaps":["Did not define the protein partners or domains mediating these functions","Mechanistic link between scaffold integration and mRNA export left open"]},{"year":2001,"claim":"Placed vertebrate Nup133 within a defined nucleoporin subcomplex and showed it directly contributes to mRNA export, generalizing the yeast role to metazoans.","evidence":"Pulldown/co-IP from Xenopus egg extracts plus dominant-negative fragment transport assays","pmids":["11684705"],"confidence":"High","gaps":["Did not resolve which Nup133 domain contacts which complex member","No structural basis for complex assembly"]},{"year":2004,"claim":"Resolved the bipartite domain organization of human Nup133, separating an NPC-integration function (C-terminal) from a protein-interaction beta-propeller (N-terminal).","evidence":"Crystal structure of the N-terminal beta-propeller and domain interaction mapping","pmids":["15557116"],"confidence":"High","gaps":["Functional partners of the beta-propeller surface not identified","No structure of the C-terminal Nup107-binding region"]},{"year":2008,"claim":"Defined the molecular basis of NPC scaffold integration by solving the Nup107-Nup133 C-terminal interface and showing Nup107 is the critical anchor.","evidence":"Crystal structure of the Nup107-Nup133 C-terminal complex with structure-guided mutagenesis and binding assays","pmids":["18570875"],"confidence":"High","gaps":["Did not address membrane attachment of the assembled scaffold","In-cell consequences of interface mutants not fully mapped"]},{"year":2009,"claim":"Positioned Nup133 within the evolutionary architecture of the NPC, identifying a shared ancestral alpha-helical building block with Nup157/170.","evidence":"Comparative crystal structure analysis of yNup170 and hNup107-Nup133","pmids":["19674973"],"confidence":"Medium","gaps":["Evolutionary inference without functional mutagenesis","Does not establish a distinct cellular function"]},{"year":2011,"claim":"Revealed a mitosis-specific moonlighting function: the N-terminal domain anchors dynein/dynactin to the nuclear envelope to tether centrosomes and promote bipolar spindle assembly.","evidence":"Dominant-negative constructs, reciprocal co-IPs defining the CENP-F/NudE-NudEL network, siRNA, and live-cell imaging","pmids":["21383080"],"confidence":"High","gaps":["Direct binding partner of the Nup133 N-terminus within the network not pinpointed","How interphase scaffold role and mitotic role are coordinated unknown"]},{"year":2014,"claim":"Provided a full-length structural model of yeast Nup133 and identified an ALPS motif in the N-terminal region as a candidate membrane-anchoring element for the NPC.","evidence":"Integrative modeling (crystal structures, SAXS, negative-stain EM) with mutational studies and cross-linking MS","pmids":["25139911"],"confidence":"Medium","gaps":["Membrane-anchoring activity not directly reconstituted in this study","Conservation to human ALPS not yet shown"]},{"year":2018,"claim":"Demonstrated a discrete scaffold-independent role in nuclear basket assembly mediated by the central domain, linking Nup133 to Tpr incorporation and Nup153 dynamics.","evidence":"CRISPR-null mESCs with single-pore fluorescence detection, Nup153 FRAP, and domain-specific rescue constructs","pmids":["29791854"],"confidence":"High","gaps":["Why only ~half of NPCs require Nup133 for Tpr incorporation is unexplained","Molecular mechanism connecting central domain to basket recruitment unknown"]},{"year":2018,"claim":"Connected NUP133 to human disease, showing a splicing mutation impairs the NUP133-NUP107 interaction and causes neurodevelopmental and renal phenotypes correctable by wild-type but not mutant protein.","evidence":"Immunoprecipitation of mutant interaction plus zebrafish morphant rescue with WT vs mutant human mRNA","pmids":["30427554"],"confidence":"Medium","gaps":["Cell-type-specific mechanism linking NPC defect to phenotypes not resolved","Morpholino-based knockdown rather than stable genetic model"]},{"year":2020,"claim":"Confirmed direct membrane binding by the conserved N-terminal ALPS motif, establishing it as a genuine membrane-anchoring element of the Y complex.","evidence":"Cryo-EM/nanobody-bound crystal structures with liposome interaction assays","pmids":["33247142"],"confidence":"High","gaps":["In-cell contribution of ALPS-mediated anchoring to NPC stability not quantified","Regulation of membrane engagement during pore assembly unclear"]},{"year":2020,"claim":"Proposed a transcriptional/stress-response link in which Nup133 levels influence Nrf1 expression in oligodendrocyte progenitors under hyperoxia.","evidence":"Hyperoxia treatment of primary OPCs with western blot, mRNA quantification, and knockdown/overexpression","pmids":["32844334"],"confidence":"Low","gaps":["Correlation-based with limited mechanistic follow-up; direct regulation of Nrf1 not biochemically established","Sex-differential effect mechanism unresolved"]},{"year":2022,"claim":"Linked NUP133 loss-of-function to podocyte dysfunction, tying impaired NPC assembly and Y-complex interactions to altered transcriptome and defective cell protrusions in SRNS.","evidence":"CRISPR/Cas9 knockout in human podocytes with transcriptomics, NPC assembly assays, protrusion/cytoskeleton readouts, and interaction analysis","pmids":["35455939"],"confidence":"Medium","gaps":["Direct mechanistic chain from NPC defect to protrusion failure not fully resolved","Single cell-type model"]},{"year":null,"claim":"How NUP133's distinct domain functions (scaffold integration, membrane anchoring, basket assembly, mitotic dynein recruitment, and putative transcriptional effects) are coordinated and how partial loss-of-function selectively impairs specialized cell types remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model linking domain-specific activities to tissue-specific disease","Mechanism of selective NPC clustering versus mRNA export defect unresolved","Direct transcriptional regulation activity not biochemically established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,3,4]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[8,11]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[6,9]}],"localization":[{"term_id":"GO:0005635","term_label":"nuclear envelope","supporting_discovery_ids":[6,8,11]}],"pathway":[{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-8953854","term_label":"Metabolism of RNA","supporting_discovery_ids":[0,1]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[6]},{"term_id":"R-HSA-1852241","term_label":"Organelle biogenesis and maintenance","supporting_discovery_ids":[9,13]},{"term_id":"R-HSA-1643685","term_label":"Disease","supporting_discovery_ids":[10,13]}],"complexes":["Nup107-160 complex (Y-complex)","Nup160 complex"],"partners":["NUP107","NUP96","NUP160","SEC13","CENP-F","NDE1/NDEL1","TPR","NUP153"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8WUM0","full_name":"Nuclear pore complex protein Nup133","aliases":["133 kDa nucleoporin","Nucleoporin Nup133"],"length_aa":1156,"mass_kda":129.0,"function":"Involved in poly(A)+ RNA transport. Involved in nephrogenesis (PubMed:30179222)","subcellular_location":"Nucleus, nuclear pore complex; Chromosome, centromere, kinetochore","url":"https://www.uniprot.org/uniprotkb/Q8WUM0/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":true,"resolved_as":"","url":"https://depmap.org/portal/gene/NUP133","classification":"Common Essential","n_dependent_lines":1207,"n_total_lines":1208,"dependency_fraction":0.9991721854304636},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"NUP107","stoichiometry":10.0},{"gene":"NUP98","stoichiometry":10.0},{"gene":"CLIP1","stoichiometry":0.2},{"gene":"CLTA","stoichiometry":0.2},{"gene":"CLTB","stoichiometry":0.2},{"gene":"HIST2H2BE","stoichiometry":0.2},{"gene":"NUMA1","stoichiometry":0.2},{"gene":"RAB11A","stoichiometry":0.2},{"gene":"RAN","stoichiometry":0.2},{"gene":"RANBP1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/NUP133","total_profiled":1310},"omim":[{"mim_id":"621033","title":"NUP210-LIKE PROTEIN; NUP210L","url":"https://www.omim.org/entry/621033"},{"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":"618177","title":"NEPHROTIC SYNDROME, TYPE 18; NPHS18","url":"https://www.omim.org/entry/618177"},{"mim_id":"616730","title":"NEPHROTIC SYNDROME, TYPE 11; NPHS11","url":"https://www.omim.org/entry/616730"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Nuclear membrane","reliability":"Supported"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NUP133"},"hgnc":{"alias_symbol":["FLJ10814"],"prev_symbol":[]},"alphafold":{"accession":"Q8WUM0","domains":[{"cath_id":"2.130.10.10","chopping":"71-252","consensus_level":"medium","plddt":83.6966,"start":71,"end":252},{"cath_id":"2.130.10.10","chopping":"280-444","consensus_level":"medium","plddt":90.0396,"start":280,"end":444},{"cath_id":"-","chopping":"634-854","consensus_level":"medium","plddt":84.4848,"start":634,"end":854},{"cath_id":"1.20.58.1380","chopping":"944-1027","consensus_level":"medium","plddt":88.654,"start":944,"end":1027},{"cath_id":"1.25.40.700","chopping":"1028-1155","consensus_level":"high","plddt":76.6481,"start":1028,"end":1155},{"cath_id":"1.20.272","chopping":"514-551_558-625","consensus_level":"medium","plddt":73.7049,"start":514,"end":625}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WUM0","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WUM0-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8WUM0-F1-predicted_aligned_error_v6.png","plddt_mean":78.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NUP133","jax_strain_url":"https://www.jax.org/strain/search?query=NUP133"},"sequence":{"accession":"Q8WUM0","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8WUM0.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8WUM0/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8WUM0"}},"corpus_meta":[{"pmid":"11684705","id":"PMC_11684705","title":"Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export.","date":"2001","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11684705","citation_count":154,"is_preprint":false},{"pmid":"21383080","id":"PMC_21383080","title":"A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase.","date":"2011","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/21383080","citation_count":154,"is_preprint":false},{"pmid":"15557116","id":"PMC_15557116","title":"Structural and functional analysis of Nup133 domains reveals modular building blocks of the nuclear pore complex.","date":"2004","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/15557116","citation_count":95,"is_preprint":false},{"pmid":"7626806","id":"PMC_7626806","title":"Mutation or deletion of the Saccharomyces cerevisiae RAT3/NUP133 gene causes temperature-dependent nuclear accumulation of poly(A)+ RNA and constitutive clustering of nuclear pore complexes.","date":"1995","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/7626806","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":"7862658","id":"PMC_7862658","title":"Disruption of the nucleoporin gene NUP133 results in clustering of nuclear pore complexes.","date":"1995","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/7862658","citation_count":81,"is_preprint":false},{"pmid":"19674973","id":"PMC_19674973","title":"Architectural nucleoporins Nup157/170 and Nup133 are structurally related and descend from a second ancestral element.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19674973","citation_count":64,"is_preprint":false},{"pmid":"25139911","id":"PMC_25139911","title":"Integrative structure-function mapping of the nucleoporin Nup133 suggests a conserved mechanism for membrane anchoring of the nuclear pore complex.","date":"2014","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/25139911","citation_count":55,"is_preprint":false},{"pmid":"30427554","id":"PMC_30427554","title":"Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome.","date":"2018","source":"Annals of neurology","url":"https://pubmed.ncbi.nlm.nih.gov/30427554","citation_count":46,"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":"29791854","id":"PMC_29791854","title":"Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.","date":"2018","source":"Cell reports","url":"https://pubmed.ncbi.nlm.nih.gov/29791854","citation_count":24,"is_preprint":false},{"pmid":"21365675","id":"PMC_21365675","title":"Structure of the C-terminal domain of Saccharomyces cerevisiae Nup133, a component of the nuclear pore complex.","date":"2011","source":"Proteins","url":"https://pubmed.ncbi.nlm.nih.gov/21365675","citation_count":14,"is_preprint":false},{"pmid":"35455939","id":"PMC_35455939","title":"NUP133 Controls Nuclear Pore Assembly, Transcriptome Composition, and Cytoskeleton Regulation in Podocytes.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/35455939","citation_count":12,"is_preprint":false},{"pmid":"32844334","id":"PMC_32844334","title":"Nup133 and ERα mediate the differential effects of hyperoxia-induced damage in male and female OPCs.","date":"2020","source":"Molecular and cellular pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/32844334","citation_count":12,"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":"37041680","id":"PMC_37041680","title":"Steroid-resistant nephrotic syndrome caused by nuclear pore gene NUP133 variation.","date":"2023","source":"Clinical genetics","url":"https://pubmed.ncbi.nlm.nih.gov/37041680","citation_count":5,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8935,"output_tokens":3155,"usd":0.037065,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10720,"output_tokens":3959,"usd":0.076287,"stage2_stop_reason":"end_turn"},"total_usd":0.113352,"stage1_batch_id":"msgbatch_013a8chtv3AWyTqv4z4sEF4C","stage2_batch_id":"msgbatch_01AHsuW63vinsvuTgzmQ3n62","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2001,\n      \"finding\": \"Nup133 (and Nup160) are novel vertebrate nucleoporins that form a complex with Nup107, Nup96, and Sec13 (the Nup160 complex) at the basket side of the nuclear pore; specific Nup133 fragments block poly[A]+ RNA export but not protein import or export, establishing a direct role in mRNA export.\",\n      \"method\": \"Pulldown from Xenopus egg extracts, immunofluorescence, co-immunoprecipitation, in vivo transport assays with dominant-negative fragments\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal pulldowns, complex reconstitution from egg extracts, functional transport assays with specific fragments; replicated across multiple orthogonal methods in one rigorous study\",\n      \"pmids\": [\"11684705\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Yeast Nup133 (RAT3/NUP133) is required for mRNA export and proper nuclear pore complex distribution; loss-of-function causes temperature-dependent nuclear accumulation of poly(A)+ RNA and constitutive clustering of NPCs.\",\n      \"method\": \"Temperature-sensitive mutation isolation, fluorescent in situ hybridization for poly(A)+ RNA, indirect immunofluorescence, electron microscopy, gene disruption\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic loss-of-function with defined cellular phenotypes (mRNA export block, NPC clustering), replicated independently by two groups (PMID 7626806 and 7862658)\",\n      \"pmids\": [\"7626806\", \"7862658\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"Disruption of yeast NUP133 leads to clustering of nuclear pore complexes, consistent with a role in maintaining NPC distribution within the nuclear envelope.\",\n      \"method\": \"Gene disruption, cell fractionation, co-enrichment with NPC fraction\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic disruption with defined cellular phenotype, independently replicated by Li et al. (PMID 7626806)\",\n      \"pmids\": [\"7862658\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Human Nup133 contains two structural domains: a C-terminal domain mediating interaction with Nup107 (and thus NPC integration), and an N-terminal seven-bladed beta-propeller domain whose surface properties suggest it mediates multiple protein interactions.\",\n      \"method\": \"Crystal structure of N-terminal beta-propeller domain, domain deletion/interaction mapping\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure of N-terminal domain plus functional domain-mapping experiments, single lab but multiple orthogonal methods\",\n      \"pmids\": [\"15557116\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Crystal structure of the human Nup107–Nup133 C-terminal domain complex reveals a tight tail-to-tail interface; structure-guided mutagenesis shows Nup107 is the critical anchor for Nup133 within the NPC scaffold, positioning Nup133 at the NPC periphery.\",\n      \"method\": \"Crystal structure determination, structure-guided mutagenesis, binding assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal structure combined with functional mutagenesis validating the interface, single lab with two orthogonal methods\",\n      \"pmids\": [\"18570875\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Crystal structures of yNup170 and hNup107–hNup133 show conserved domain architecture, indicating Nup157/170 and Nup133 share a common ancestral helical element (distinct from ACE1) that constitutes a major alpha-helical building block of the NPC scaffold.\",\n      \"method\": \"Crystal structure determination and structural comparison\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — crystal structures from single lab, structural/evolutionary inference without functional mutagenesis validation\",\n      \"pmids\": [\"19674973\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"The N-terminal domain of Nup133 is required for anchoring the dynein/dynactin complex to the nuclear envelope in prophase via an interaction network involving CENP-F and NudE/NudEL; this tethers centrosomes to the nuclear envelope at the G2/M transition and contributes to bipolar spindle assembly.\",\n      \"method\": \"Dominant-negative N-terminal domain constructs, co-immunoprecipitation, live-cell imaging, siRNA knockdown\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IPs defining the interaction network, dominant-negative and rescue experiments, live imaging of centrosome dynamics; multiple orthogonal methods in single lab\",\n      \"pmids\": [\"21383080\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Crystal structure of the C-terminal domain of yeast Nup133 (ScNup133 residues 944–1157) shows an all-alpha-helical fold distinct from the two-block arrangement seen in the human Nup133 C-terminal domain bound to Nup107, indicating structural divergence between homologs.\",\n      \"method\": \"X-ray crystallography at 1.9 Å resolution\",\n      \"journal\": \"Proteins\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — high-resolution crystal structure from single lab, structural observation without functional mutagenesis follow-up\",\n      \"pmids\": [\"21365675\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Integrative structural modeling of full-length yeast Nup133 reveals an amphipathic lipid packing sensor (ALPS) motif in the N-terminal beta-propeller region; mutational studies and chemical cross-linking validate the model and suggest the ALPS motif mediates membrane anchoring of the NPC in the nuclear envelope.\",\n      \"method\": \"Integrative modeling using crystal structures, SAXS, negative-stain EM, mutational studies, chemical cross-linking/mass spectrometry\",\n      \"journal\": \"Molecular & cellular proteomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple orthogonal structural methods plus mutational validation in single study, but functional membrane-anchoring activity not directly reconstituted\",\n      \"pmids\": [\"25139911\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Nup133 loss-of-function specifically perturbs nuclear basket assembly in mouse embryonic stem cells: it is required for stable incorporation of Tpr into approximately half of NPCs and for proper Nup153 dynamics, with the central domain of Nup133 mediating this function.\",\n      \"method\": \"CRISPR/null mutation in mESCs, single-pore detection by fluorescence microscopy, FRAP of Nup153, domain mapping with rescue constructs\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with quantitative single-pore readout, FRAP, and domain-specific rescue; multiple orthogonal methods in single lab\",\n      \"pmids\": [\"29791854\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"A homozygous splicing mutation in NUP133 (c.3335-11T>A) impairs NUP133–NUP107 protein interaction as shown by immunoprecipitation; nup133 morphant zebrafish exhibit microcephaly, reduced neuronal cells, underdeveloped glomeruli, and podocyte foot process fusion, all rescued by wild-type but not mutant human NUP133 mRNA.\",\n      \"method\": \"Immunoprecipitation assay, zebrafish nup133 morpholino knockdown with mRNA rescue\",\n      \"journal\": \"Annals of neurology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP demonstrating impaired interaction, in vivo morphant rescue experiment with wild-type vs. mutant mRNA; two orthogonal methods, single lab\",\n      \"pmids\": [\"30427554\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The Nup133 N-terminal domain contains a structurally conserved ALPS motif that directly interacts with liposomes, confirming a membrane-anchoring function for this motif within the Y complex.\",\n      \"method\": \"Cryo-EM/nanobody-bound crystal structures, liposome interaction studies\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — crystal/cryo structure plus direct liposome binding assay validating the ALPS motif function; two orthogonal methods in single study\",\n      \"pmids\": [\"33247142\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In oligodendrocyte progenitor cells, Nup133 protein level decline following hyperoxia correlates with decreased Nrf1 mRNA, and Nrf1 is identified as a direct downstream transcriptional target of Nup133, contributing to sex-differential oxidative stress responses.\",\n      \"method\": \"Hyperoxia treatment of primary OPCs, western blotting, mRNA quantification, cell culture knockdown/overexpression\",\n      \"journal\": \"Molecular and cellular pediatrics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, correlation-based with limited mechanistic follow-up; Nrf1 described as 'direct downstream target' but mechanistic details not fully resolved in abstract\",\n      \"pmids\": [\"32844334\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CRISPR/Cas9-mediated loss of NUP133 in human podocytes disrupts nuclear pore assembly, alters the podocyte-specific transcriptome, and impairs cellular protrusion generation; SRNS-associated NUP133 mutations primarily impair Y-complex protein interactions and reduce NUP133 protein levels, causing partial loss-of-function.\",\n      \"method\": \"CRISPR/Cas9 genome editing in human podocytes, transcriptome analysis, NPC assembly assays, cytoskeleton/protrusion assays, protein interaction analysis\",\n      \"journal\": \"Cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined cellular phenotypes across multiple readouts; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"35455939\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NUP133 is a scaffold nucleoporin that integrates into the NPC via a tight interaction with NUP107 (mediated by its C-terminal alpha-helical domain), positions itself at the NPC periphery within the Y-complex/Nup107-160 complex, mediates mRNA export and proper NPC distribution, anchors the NPC to the nuclear envelope membrane through an N-terminal ALPS motif, promotes nuclear basket assembly (Tpr/Nup153 incorporation) through its central domain, and in prophase recruits dynein/dynactin to the nuclear envelope via CENP-F and NudE/NudEL to tether centrosomes and facilitate bipolar spindle assembly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NUP133 is a scaffold nucleoporin of the conserved Y-complex (Nup107-160 complex) that builds the structural core of the nuclear pore complex (NPC) and supports nucleocytoplasmic transport [#0, #1]. It integrates into the NPC scaffold through a tight tail-to-tail interface between its C-terminal alpha-helical domain and Nup107, which serves as the critical anchor positioning NUP133 at the NPC periphery [#3, #4]. Its N-terminal seven-bladed beta-propeller domain harbors an amphipathic lipid packing sensor (ALPS) motif that binds membranes directly, anchoring the NPC to the curved nuclear envelope membrane [#3, #8, #11]. Beyond scaffolding, NUP133 is required for mRNA export and for proper NPC distribution within the nuclear envelope, since loss of function causes nuclear accumulation of poly(A)+ RNA and clustering of pores [#0, #1, #2]. Its central domain promotes nuclear basket assembly by enabling stable incorporation of Tpr and proper Nup153 dynamics [#9], while its N-terminal domain performs a mitotic role, recruiting the dynein/dynactin complex to the nuclear envelope in prophase via a CENP-F and NudE/NudEL network to tether centrosomes and support bipolar spindle assembly [#6]. Loss-of-function and partial-loss-of-function mutations in NUP133, which impair NUP133-NUP107/Y-complex interactions, cause a Mendelian disease spectrum including steroid-resistant nephrotic syndrome and neurodevelopmental phenotypes, recapitulated by disrupted NPC assembly and altered cell-type-specific function in podocytes and in zebrafish [#10, #13].\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Established the first functional role for Nup133 by showing it is needed for both mRNA export and proper spatial organization of NPCs within the nuclear envelope.\",\n      \"evidence\": \"Temperature-sensitive yeast mutants and gene disruption with poly(A)+ RNA FISH, immunofluorescence, and EM\",\n      \"pmids\": [\"7626806\", \"7862658\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define the protein partners or domains mediating these functions\", \"Mechanistic link between scaffold integration and mRNA export left open\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Placed vertebrate Nup133 within a defined nucleoporin subcomplex and showed it directly contributes to mRNA export, generalizing the yeast role to metazoans.\",\n      \"evidence\": \"Pulldown/co-IP from Xenopus egg extracts plus dominant-negative fragment transport assays\",\n      \"pmids\": [\"11684705\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve which Nup133 domain contacts which complex member\", \"No structural basis for complex assembly\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Resolved the bipartite domain organization of human Nup133, separating an NPC-integration function (C-terminal) from a protein-interaction beta-propeller (N-terminal).\",\n      \"evidence\": \"Crystal structure of the N-terminal beta-propeller and domain interaction mapping\",\n      \"pmids\": [\"15557116\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional partners of the beta-propeller surface not identified\", \"No structure of the C-terminal Nup107-binding region\"]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Defined the molecular basis of NPC scaffold integration by solving the Nup107-Nup133 C-terminal interface and showing Nup107 is the critical anchor.\",\n      \"evidence\": \"Crystal structure of the Nup107-Nup133 C-terminal complex with structure-guided mutagenesis and binding assays\",\n      \"pmids\": [\"18570875\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not address membrane attachment of the assembled scaffold\", \"In-cell consequences of interface mutants not fully mapped\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Positioned Nup133 within the evolutionary architecture of the NPC, identifying a shared ancestral alpha-helical building block with Nup157/170.\",\n      \"evidence\": \"Comparative crystal structure analysis of yNup170 and hNup107-Nup133\",\n      \"pmids\": [\"19674973\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Evolutionary inference without functional mutagenesis\", \"Does not establish a distinct cellular function\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Revealed a mitosis-specific moonlighting function: the N-terminal domain anchors dynein/dynactin to the nuclear envelope to tether centrosomes and promote bipolar spindle assembly.\",\n      \"evidence\": \"Dominant-negative constructs, reciprocal co-IPs defining the CENP-F/NudE-NudEL network, siRNA, and live-cell imaging\",\n      \"pmids\": [\"21383080\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct binding partner of the Nup133 N-terminus within the network not pinpointed\", \"How interphase scaffold role and mitotic role are coordinated unknown\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Provided a full-length structural model of yeast Nup133 and identified an ALPS motif in the N-terminal region as a candidate membrane-anchoring element for the NPC.\",\n      \"evidence\": \"Integrative modeling (crystal structures, SAXS, negative-stain EM) with mutational studies and cross-linking MS\",\n      \"pmids\": [\"25139911\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Membrane-anchoring activity not directly reconstituted in this study\", \"Conservation to human ALPS not yet shown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrated a discrete scaffold-independent role in nuclear basket assembly mediated by the central domain, linking Nup133 to Tpr incorporation and Nup153 dynamics.\",\n      \"evidence\": \"CRISPR-null mESCs with single-pore fluorescence detection, Nup153 FRAP, and domain-specific rescue constructs\",\n      \"pmids\": [\"29791854\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Why only ~half of NPCs require Nup133 for Tpr incorporation is unexplained\", \"Molecular mechanism connecting central domain to basket recruitment unknown\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected NUP133 to human disease, showing a splicing mutation impairs the NUP133-NUP107 interaction and causes neurodevelopmental and renal phenotypes correctable by wild-type but not mutant protein.\",\n      \"evidence\": \"Immunoprecipitation of mutant interaction plus zebrafish morphant rescue with WT vs mutant human mRNA\",\n      \"pmids\": [\"30427554\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cell-type-specific mechanism linking NPC defect to phenotypes not resolved\", \"Morpholino-based knockdown rather than stable genetic model\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Confirmed direct membrane binding by the conserved N-terminal ALPS motif, establishing it as a genuine membrane-anchoring element of the Y complex.\",\n      \"evidence\": \"Cryo-EM/nanobody-bound crystal structures with liposome interaction assays\",\n      \"pmids\": [\"33247142\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In-cell contribution of ALPS-mediated anchoring to NPC stability not quantified\", \"Regulation of membrane engagement during pore assembly unclear\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Proposed a transcriptional/stress-response link in which Nup133 levels influence Nrf1 expression in oligodendrocyte progenitors under hyperoxia.\",\n      \"evidence\": \"Hyperoxia treatment of primary OPCs with western blot, mRNA quantification, and knockdown/overexpression\",\n      \"pmids\": [\"32844334\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Correlation-based with limited mechanistic follow-up; direct regulation of Nrf1 not biochemically established\", \"Sex-differential effect mechanism unresolved\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked NUP133 loss-of-function to podocyte dysfunction, tying impaired NPC assembly and Y-complex interactions to altered transcriptome and defective cell protrusions in SRNS.\",\n      \"evidence\": \"CRISPR/Cas9 knockout in human podocytes with transcriptomics, NPC assembly assays, protrusion/cytoskeleton readouts, and interaction analysis\",\n      \"pmids\": [\"35455939\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct mechanistic chain from NPC defect to protrusion failure not fully resolved\", \"Single cell-type model\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NUP133's distinct domain functions (scaffold integration, membrane anchoring, basket assembly, mitotic dynein recruitment, and putative transcriptional effects) are coordinated and how partial loss-of-function selectively impairs specialized cell types remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model linking domain-specific activities to tissue-specific disease\", \"Mechanism of selective NPC clustering versus mRNA export defect unresolved\", \"Direct transcriptional regulation activity not biochemically established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 3, 4]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [8, 11]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [6, 9]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005643\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005635\", \"supporting_discovery_ids\": [6, 8, 11]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-8953854\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-1852241\", \"supporting_discovery_ids\": [9, 13]},\n      {\"term_id\": \"R-HSA-1643685\", \"supporting_discovery_ids\": [10, 13]}\n    ],\n    \"complexes\": [\"Nup107-160 complex (Y-complex)\", \"Nup160 complex\"],\n    \"partners\": [\"NUP107\", \"NUP96\", \"NUP160\", \"SEC13\", \"CENP-F\", \"NDE1/NDEL1\", \"TPR\", \"NUP153\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":6,"faith_total":6,"faith_pct":100.0}}