{"gene":"NINL","run_date":"2026-06-10T05:19:52","timeline":{"discoveries":[{"year":2003,"finding":"NINL (Nlp/ninein-like protein) interacts with two components of the gamma-tubulin ring complex (gamma-TuRC) and stimulates microtubule nucleation. Plk1 phosphorylates Nlp and disrupts both its centrosome association and its gamma-tubulin interaction. Overexpression of an Nlp mutant lacking Plk1 phosphorylation sites severely disturbs mitotic spindle formation, indicating Nlp plays a role in microtubule organization during interphase and is displaced from the centrosome by Plk1 at mitotic onset.","method":"Co-immunoprecipitation, in vitro kinase assay, overexpression/mutagenesis, immunofluorescence microscopy","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro kinase assay plus mutagenesis plus Co-IP plus functional overexpression phenotype in a single focused study, replicated in subsequent work","pmids":["12852856"],"is_preprint":false},{"year":2005,"finding":"Nlp and ninein interact with the dynein-dynactin motor complex, and dynactin is required for the targeting of Nlp to the centrosome. Phosphorylation of Nlp by Plk1 negatively regulates its association with dynactin, thereby providing a mechanism by which Plk1 coordinates changes in microtubule organization with cell cycle progression.","method":"Co-immunoprecipitation, overexpression/dominant-negative dynactin, immunofluorescence, in vitro kinase assay","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — reciprocal Co-IP, kinase assay, and dominant-negative approach in a single study; functionally links dynactin interaction to centrosomal targeting","pmids":["16254247"],"is_preprint":false},{"year":2005,"finding":"NINL (Nlp) is also a substrate of Nek2 kinase in addition to Plk1. X-Nlp (Xenopus homolog) is a mother-centriole-specific protein. Overexpression of active Nek2 or Plk1 causes premature displacement of Nlp from interphase centrosomes. Nek2 phosphorylation of Nlp does not disrupt its gamma-tubulin interaction, but active Nek2 stimulates subsequent Plk1 phosphorylation of Nlp in vitro, suggesting that Nek2 primes Nlp for Plk1 phosphorylation at the G2/M transition.","method":"In vitro kinase assay, immunofluorescence, overexpression of kinase-active/inactive mutants, cell fractionation","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro kinase assays, dominant-negative epistasis, and localization experiments in a single rigorous study","pmids":["15684383"],"is_preprint":false},{"year":2009,"finding":"BRCA1 physically interacts and colocalizes with Nlp at the centrosome. Cells with BRCA1 mutations or BRCA1 silencing exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation, likely through BRCA1-mediated suppression of Plk1. siRNA-mediated depletion of Nlp results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy.","method":"Co-immunoprecipitation, colocalization by immunofluorescence, siRNA knockdown, BRCA1 mutation cell lines","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP and siRNA knockdown with defined cellular phenotype in a single lab, multiple methods","pmids":["19509300"],"is_preprint":false},{"year":2010,"finding":"Cdc2/cyclin B1 phosphorylates Nlp at Ser185 and Ser589. Ser185 phosphorylation is required for recognition of Nlp by Plk1, enabling Nlp departure from centrosomes at mitotic onset; Plk1 fails to dissociate an Nlp Ser185 mutant from the centrosome. Ser589 phosphorylation by Cdc2/cyclin B1 affects Nlp protein stability/degradation. Loss of these sites leads to multinucleated cells.","method":"In vitro kinase assay, site-directed mutagenesis, immunofluorescence, Western blot","journal":"Cancer biology & therapy","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro kinase assay with mutagenesis and functional rescue/failure, single lab","pmids":["20890132"],"is_preprint":false},{"year":2010,"finding":"Nlp localizes to the midbody during cytokinesis and is required for completion of cell division. Aurora B recruits Nlp to the midbody via direct physical interaction. Aurora B phosphorylates Nlp at Ser-185, Ser-448, and Ser-585; phosphorylation at Ser-448 and Ser-585 is required for Nlp association with Aurora B and midbody localization, while Ser-185 phosphorylation affects Nlp stability. Depletion of Nlp or disruption of phosphorylation sites causes aborted cytokinesis and chromosomal instability.","method":"Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, immunofluorescence, siRNA knockdown","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro kinase assay, mutagenesis, Co-IP, and siRNA knockdown with defined cytokinesis phenotype in a single study","pmids":["20864540"],"is_preprint":false},{"year":2010,"finding":"Overexpression of Nlp in NIH3T3 cells confers anchorage-independent growth and tumor formation in nude mice. Transgenic mice overexpressing Nlp develop spontaneous tumors and show centrosome amplification in MEFs, suggesting that Nlp overexpression mimics BRCA1 loss and contributes to genomic instability.","method":"Stable transfection/transformation assay, transgenic mouse model, immunohistochemistry, MEF centrosome analysis","journal":"The Journal of clinical investigation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — defined oncogenic phenotype in multiple model systems, single lab","pmids":["20093778"],"is_preprint":false},{"year":2015,"finding":"NINL physically interacts with the ciliopathy protein CC2D2A at the base of cilia. Knockdown of ninl in zebrafish leads to photoreceptor outer segment loss, mislocalization of opsins, vesicle accumulation, and altered Rab8a localization, resembling cc2d2a-/- phenotypes. Partial ninl knockdown in cc2d2a-/- embryos enhances the retinal phenotype, indicating a genetic interaction. The NINL-associated interactome includes MICAL3, a Rab8-interacting protein involved in vesicle docking and fusion.","method":"Co-immunoprecipitation (pulldown), zebrafish morpholino knockdown, genetic interaction/epistasis, immunofluorescence localization, proteomics interactome","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal interaction evidence, zebrafish in vivo genetic epistasis, multiple phenotypic readouts in one study","pmids":["26485645"],"is_preprint":false},{"year":2015,"finding":"NINL interacts with DZANK1 and both proteins associate with complementary subunits of the cytoplasmic dynein 1 motor complex. Loss of Ninl, Dzank1, or both synergistically causes dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, mislocalization of Rhodopsin and Ush2a, and severely impaired retrograde melanosome transport in zebrafish, supporting a role for the NINL-DZANK1 module in assembly of the cytoplasmic dynein 1 complex.","method":"Yeast two-hybrid, co-immunoprecipitation, zebrafish morpholino/mutant phenotype analysis, immunofluorescence, retrograde transport assay","journal":"PLoS genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal interaction assays, zebrafish genetic in vivo phenotype, two independent labs (companion paper to PMID 26485645)","pmids":["26485514"],"is_preprint":false},{"year":2016,"finding":"Upon UVC irradiation, NINL (Nlp) translocates into the nucleus via its C-terminus (residues 1030–1382) and physically interacts with the NER factors XPA and ERCC1, enhancing their association. Nlp depletion impairs nucleotide excision repair (NER) activity and sensitizes cells to UV radiation.","method":"Co-immunoprecipitation, nuclear fractionation, NER activity assay, deletion mapping, immunofluorescence, siRNA knockdown","journal":"Cancer letters","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP, fractionation, functional NER assay and deletion mapping in a single lab","pmids":["26805762"],"is_preprint":false},{"year":2021,"finding":"NINL (Nlp) colocalizes with autophagosomes and physically interacts with LC3 (autophagosome marker), Rab7, and FYCO1. Nlp enhances the Rab7–FYCO1 interaction, thereby accelerating autophagic flux and autophagolysosome formation. NLP-deficient mice treated with DMBA show increased liver cancer incidence associated with hepatic autophagic defects.","method":"Co-immunoprecipitation, immunofluorescence colocalization, autophagy flux assay, mouse knockout/carcinogen model","journal":"Signal transduction and targeted therapy","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP with multiple partners and in vivo mouse knockout phenotype, single lab","pmids":["33859171"],"is_preprint":false},{"year":2022,"finding":"NINL has evolved under recurrent positive selection, particularly in its carboxy-terminal cargo-binding region. NINL knockout cells exhibit an impaired interferon response, resulting in increased permissiveness to viral replication. Proteases encoded by diverse picornaviruses and coronaviruses cleave and disrupt NINL function in a host- and virus-specific manner, identifying NINL as a component of the antiviral innate immune response and a target of viral antagonism.","method":"NINL knockout cells (interferon response assay, viral replication assay), viral protease cleavage assay, evolutionary analysis (signatures of positive selection)","journal":"eLife","confidence":"High","confidence_rationale":"Tier 2 / Strong — KO cell functional assays with defined interferon-response phenotype, plus direct protease cleavage assays across multiple virus families, multiple orthogonal methods in one study","pmids":["36222652"],"is_preprint":false},{"year":2024,"finding":"NINL (Nlp) acts as an adaptor/platform for ER-to-Golgi vesicle trafficking by directly binding SEC31A (a COPII coat component) and Rab1B, facilitating selection and continuity of specific cargoes (including β-Catenin and STING) through COPII- and COPI-coated vesicle transition. Nlp deficiency causes vesicle budding failure, ER protein accumulation, ER stress, Golgi fragmentation, and activation of the PERK-eIF2α UPR pathway. Nlp-deficient mice develop spontaneous B cell lymphoma, linked to defective secretory protein trafficking in lymphocytes.","method":"Co-immunoprecipitation (with SEC31A and Rab1B), knockdown/knockout cells, ER stress assay (PERK-eIF2α), immunofluorescence (Golgi fragmentation), mouse knockout model","journal":"International journal of biological sciences","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP with direct binding partners, functional KO phenotypes in cells and mice, single lab","pmids":["38904019"],"is_preprint":false}],"current_model":"NINL (ninein-like protein) is a centrosomal protein that promotes microtubule nucleation by interacting with the gamma-tubulin ring complex during interphase; at the G2/M transition it is sequentially phosphorylated by Nek2 and Plk1 (primed by Cdc2/cyclin B1), which disrupts its gamma-tubulin and dynactin interactions and displaces it from the centrosome; it is also phosphorylated by Aurora B at the midbody to complete cytokinesis; beyond the centrosome, NINL functions as a dynein activating adaptor (binding DZANK1 and dynein-dynactin subunits) essential for vesicle trafficking in photoreceptors and cilia biogenesis (interacting with CC2D2A, RAB8, and MICAL3), serves as a ER-to-Golgi cargo adaptor via SEC31A and Rab1B, enhances autophagosome transport by bridging Rab7 and FYCO1, participates in nucleotide excision repair by scaffolding XPA–ERCC1 in the nucleus after UV damage, and is a target of viral protease-mediated antagonism within the antiviral innate immune response."},"narrative":{"mechanistic_narrative":"NINL (ninein-like protein, Nlp) is a centrosomal organizer of microtubule arrays whose cell-cycle-regulated phosphorylation couples microtubule nucleation to mitotic progression [PMID:12852856, PMID:15684383]. During interphase it binds components of the gamma-tubulin ring complex to stimulate microtubule nucleation, and its centrosomal targeting depends on the dynein-dynactin motor [PMID:12852856, PMID:16254247]. At the G2/M transition a phosphorylation cascade displaces it from the centrosome: Cdc2/cyclin B1 phosphorylates Ser185 to prime recognition by Plk1, Nek2 further primes Plk1 phosphorylation, and Plk1 then disrupts both the gamma-tubulin and dynactin interactions to release NINL from the centrosome [PMID:16254247, PMID:15684383, PMID:20890132]. NINL is independently recruited to the midbody by Aurora B, which phosphorylates it to drive completion of cytokinesis; loss of NINL or its phosphosites produces aberrant spindles, aborted cytokinesis, aneuploidy, and chromosomal instability [PMID:19509300, PMID:20864540]. Beyond the centrosome NINL operates as a dynein-associated adaptor for membrane trafficking: it partners with DZANK1 to assemble cytoplasmic dynein 1 and with the ciliopathy protein CC2D2A, RAB8 and MICAL3 at the ciliary base, and its loss in zebrafish causes photoreceptor outer-segment defects, opsin/Ush2a mislocalization, vesicle accumulation and impaired retrograde transport [PMID:26485645, PMID:26485514]. It further acts as a vesicle-trafficking platform, bridging Rab7 and FYCO1 to accelerate autophagic flux and binding SEC31A and Rab1B to support COPII-mediated ER-to-Golgi cargo transport, with deficiency triggering ER stress and the PERK-eIF2alpha UPR [PMID:33859171, PMID:38904019]. NINL additionally translocates to the nucleus after UV damage to scaffold the XPA-ERCC1 nucleotide excision repair factors, and is a positively selected component of the antiviral interferon response that is cleaved by diverse picornaviral and coronaviral proteases [PMID:26805762, PMID:36222652].","teleology":[{"year":2003,"claim":"Established NINL's core molecular function by showing it binds the gamma-TuRC to nucleate microtubules and is regulated by Plk1, explaining how microtubule organization is reset at mitotic onset.","evidence":"Co-IP, in vitro kinase assay, and phospho-mutant overexpression in cultured cells","pmids":["12852856"],"confidence":"High","gaps":["Did not define upstream priming kinases","Structural basis of gamma-tubulin binding not resolved"]},{"year":2005,"claim":"Connected NINL's centrosomal targeting to the dynein-dynactin motor and showed Plk1 phosphorylation severs this link, providing a mechanism coupling motor-dependent localization to the cell cycle.","evidence":"Reciprocal Co-IP, dominant-negative dynactin, and in vitro kinase assay","pmids":["16254247"],"confidence":"High","gaps":["Which dynactin subunit mediates the interaction not pinpointed"]},{"year":2005,"claim":"Identified Nek2 as a second NINL kinase that primes Plk1 phosphorylation, ordering the G2/M phosphorylation cascade controlling centrosomal release.","evidence":"In vitro kinase assays with kinase-active/inactive mutants and localization in cells","pmids":["15684383"],"confidence":"High","gaps":["In vivo sequence of Nek2-then-Plk1 events not directly demonstrated"]},{"year":2009,"claim":"Linked NINL to genome stability by showing BRCA1 maintains its centrosomal localization and that NINL depletion causes spindle defects and aneuploidy.","evidence":"Co-IP, colocalization, siRNA knockdown in BRCA1-mutant cell lines","pmids":["19509300"],"confidence":"Medium","gaps":["BRCA1-Plk1-NINL regulatory chain inferred, not directly mapped","Single-lab finding"]},{"year":2010,"claim":"Mapped Cdc2/cyclin B1 phosphosites (Ser185, Ser589) defining how NINL is primed for Plk1 recognition and how its stability is controlled at mitosis.","evidence":"In vitro kinase assay, site-directed mutagenesis, immunofluorescence","pmids":["20890132"],"confidence":"Medium","gaps":["Degradation machinery acting on Ser589-phosphorylated NINL not identified"]},{"year":2010,"claim":"Extended NINL function into cytokinesis, showing Aurora B recruits and phosphorylates it at the midbody to complete cell division.","evidence":"Co-IP, in vitro kinase assay, mutagenesis, and siRNA knockdown with cytokinesis readout","pmids":["20864540"],"confidence":"High","gaps":["Midbody binding partners of NINL beyond Aurora B unresolved"]},{"year":2010,"claim":"Demonstrated that NINL dysregulation is oncogenic, with overexpression driving transformation, centrosome amplification, and spontaneous tumors in mice.","evidence":"Transformation assay, transgenic mouse model, MEF centrosome analysis","pmids":["20093778"],"confidence":"Medium","gaps":["Mechanistic link between overexpression and centrosome amplification not dissected","Single-lab finding"]},{"year":2015,"claim":"Revealed a ciliary/photoreceptor trafficking role by placing NINL with CC2D2A, RAB8 and MICAL3 at the cilium base and demonstrating a genetic interaction with cc2d2a in vivo.","evidence":"Co-IP, zebrafish morpholino knockdown, genetic epistasis, interactome proteomics","pmids":["26485645"],"confidence":"High","gaps":["Direct vs indirect nature of NINL-MICAL3 interaction not separated"]},{"year":2015,"claim":"Defined the NINL-DZANK1 module as a dynein-1 assembly adaptor, showing synergistic photoreceptor and retrograde transport defects upon loss.","evidence":"Yeast two-hybrid, Co-IP, zebrafish mutant/morphant phenotypes, retrograde melanosome transport assay","pmids":["26485514"],"confidence":"High","gaps":["Stoichiometry of NINL-DZANK1-dynein assembly not resolved"]},{"year":2016,"claim":"Uncovered a nuclear, UV-inducible role in nucleotide excision repair, with NINL scaffolding XPA-ERCC1 to promote repair.","evidence":"Co-IP, nuclear fractionation, NER activity assay, deletion mapping, siRNA knockdown","pmids":["26805762"],"confidence":"Medium","gaps":["How the centrosomal protein relocalizes and is retained in the nucleus unclear","Single-lab finding"]},{"year":2021,"claim":"Identified NINL as an autophagy enhancer bridging Rab7 and FYCO1 to accelerate autophagic flux, with knockout promoting carcinogen-induced liver cancer.","evidence":"Co-IP, colocalization, autophagy flux assay, mouse knockout/carcinogen model","pmids":["33859171"],"confidence":"Medium","gaps":["Whether the Rab7-FYCO1 bridging requires dynein not addressed","Single-lab finding"]},{"year":2022,"claim":"Established NINL as an antiviral innate immune factor under positive selection that is directly cleaved by picornaviral and coronaviral proteases.","evidence":"Knockout cell interferon and viral replication assays, protease cleavage assays, evolutionary analysis","pmids":["36222652"],"confidence":"High","gaps":["Molecular step in the interferon pathway NINL acts on not defined"]},{"year":2024,"claim":"Defined NINL as an ER-to-Golgi cargo adaptor binding SEC31A and Rab1B, with deficiency causing ER stress, UPR activation, and B cell lymphoma in mice.","evidence":"Co-IP with SEC31A/Rab1B, knockdown/knockout cells, ER stress assays, mouse knockout","pmids":["38904019"],"confidence":"Medium","gaps":["Cargo selectivity mechanism not fully resolved","Single-lab finding"]},{"year":null,"claim":"How NINL's many roles—centrosomal microtubule nucleation, dynein-adaptor trafficking, autophagy, COPII transport, NER, and antiviral defense—are partitioned by isoform, localization, or context remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unifying model integrating centrosomal and trafficking/immune functions","Domain requirements for each function not comparatively mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[8,10,12]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[0,1,2]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[7,8]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[9]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[10,12]}],"pathway":[{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[0,5]},{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[8,12]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[10]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[9]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[11]}],"complexes":["cytoplasmic dynein 1 complex","gamma-tubulin ring complex (gamma-TuRC)"],"partners":["DZANK1","CC2D2A","MICAL3","SEC31A","RAB1B","RAB7","FYCO1","XPA"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9Y2I6","full_name":"Ninein-like protein","aliases":[],"length_aa":1382,"mass_kda":156.3,"function":"Involved in the microtubule organization in interphase cells. Overexpression induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery; it also interferes with mitotic spindle assembly. Involved in vesicle transport in photoreceptor cells (By similarity). May play a role in ovarian carcinogenesis","subcellular_location":"Cytoplasm, cytoskeleton, microtubule organizing center, centrosome; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q9Y2I6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/NINL","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/NINL","total_profiled":1310},"omim":[{"mim_id":"620905","title":"DOUBLE ZINC RIBBON AND ANKYRIN REPEAT DOMAINS 1; DZANK1","url":"https://www.omim.org/entry/620905"},{"mim_id":"611408","title":"LEBERILIN LCA5; LCA5","url":"https://www.omim.org/entry/611408"},{"mim_id":"609580","title":"NINEIN-LIKE PROTEIN; NINL","url":"https://www.omim.org/entry/609580"},{"mim_id":"608400","title":"USHERIN; USH2A","url":"https://www.omim.org/entry/608400"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Vesicles","reliability":"Approved"},{"location":"Primary cilium","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Microtubules","reliability":"Additional"},{"location":"Cytokinetic bridge","reliability":"Additional"},{"location":"Cytosol","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/NINL"},"hgnc":{"alias_symbol":["KIAA0980","NLP"],"prev_symbol":[]},"alphafold":{"accession":"Q9Y2I6","domains":[{"cath_id":"1.10.238.10","chopping":"2-76","consensus_level":"medium","plddt":80.3069,"start":2,"end":76},{"cath_id":"1.10.238.10","chopping":"210-264","consensus_level":"high","plddt":72.3296,"start":210,"end":264},{"cath_id":"-","chopping":"308-368","consensus_level":"medium","plddt":81.8493,"start":308,"end":368}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2I6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2I6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9Y2I6-F1-predicted_aligned_error_v6.png","plddt_mean":65.69},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=NINL","jax_strain_url":"https://www.jax.org/strain/search?query=NINL"},"sequence":{"accession":"Q9Y2I6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9Y2I6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9Y2I6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9Y2I6"}},"corpus_meta":[{"pmid":"28489820","id":"PMC_28489820","title":"Discovery 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reports","url":"https://pubmed.ncbi.nlm.nih.gov/40033048","citation_count":1,"is_preprint":false},{"pmid":"35760284","id":"PMC_35760284","title":"Nlp enhances biofilm formation by Yersinia pestis biovar microtus.","date":"2022","source":"Microbial pathogenesis","url":"https://pubmed.ncbi.nlm.nih.gov/35760284","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":47328,"output_tokens":3840,"usd":0.099792,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11539,"output_tokens":4048,"usd":0.079448,"stage2_stop_reason":"end_turn"},"total_usd":0.17924,"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\": 2003,\n      \"finding\": \"NINL (Nlp/ninein-like protein) interacts with two components of the gamma-tubulin ring complex (gamma-TuRC) and stimulates microtubule nucleation. Plk1 phosphorylates Nlp and disrupts both its centrosome association and its gamma-tubulin interaction. Overexpression of an Nlp mutant lacking Plk1 phosphorylation sites severely disturbs mitotic spindle formation, indicating Nlp plays a role in microtubule organization during interphase and is displaced from the centrosome by Plk1 at mitotic onset.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, overexpression/mutagenesis, immunofluorescence microscopy\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro kinase assay plus mutagenesis plus Co-IP plus functional overexpression phenotype in a single focused study, replicated in subsequent work\",\n      \"pmids\": [\"12852856\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Nlp and ninein interact with the dynein-dynactin motor complex, and dynactin is required for the targeting of Nlp to the centrosome. Phosphorylation of Nlp by Plk1 negatively regulates its association with dynactin, thereby providing a mechanism by which Plk1 coordinates changes in microtubule organization with cell cycle progression.\",\n      \"method\": \"Co-immunoprecipitation, overexpression/dominant-negative dynactin, immunofluorescence, in vitro kinase assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — reciprocal Co-IP, kinase assay, and dominant-negative approach in a single study; functionally links dynactin interaction to centrosomal targeting\",\n      \"pmids\": [\"16254247\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"NINL (Nlp) is also a substrate of Nek2 kinase in addition to Plk1. X-Nlp (Xenopus homolog) is a mother-centriole-specific protein. Overexpression of active Nek2 or Plk1 causes premature displacement of Nlp from interphase centrosomes. Nek2 phosphorylation of Nlp does not disrupt its gamma-tubulin interaction, but active Nek2 stimulates subsequent Plk1 phosphorylation of Nlp in vitro, suggesting that Nek2 primes Nlp for Plk1 phosphorylation at the G2/M transition.\",\n      \"method\": \"In vitro kinase assay, immunofluorescence, overexpression of kinase-active/inactive mutants, cell fractionation\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro kinase assays, dominant-negative epistasis, and localization experiments in a single rigorous study\",\n      \"pmids\": [\"15684383\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"BRCA1 physically interacts and colocalizes with Nlp at the centrosome. Cells with BRCA1 mutations or BRCA1 silencing exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation, likely through BRCA1-mediated suppression of Plk1. siRNA-mediated depletion of Nlp results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy.\",\n      \"method\": \"Co-immunoprecipitation, colocalization by immunofluorescence, siRNA knockdown, BRCA1 mutation cell lines\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP and siRNA knockdown with defined cellular phenotype in a single lab, multiple methods\",\n      \"pmids\": [\"19509300\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Cdc2/cyclin B1 phosphorylates Nlp at Ser185 and Ser589. Ser185 phosphorylation is required for recognition of Nlp by Plk1, enabling Nlp departure from centrosomes at mitotic onset; Plk1 fails to dissociate an Nlp Ser185 mutant from the centrosome. Ser589 phosphorylation by Cdc2/cyclin B1 affects Nlp protein stability/degradation. Loss of these sites leads to multinucleated cells.\",\n      \"method\": \"In vitro kinase assay, site-directed mutagenesis, immunofluorescence, Western blot\",\n      \"journal\": \"Cancer biology & therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro kinase assay with mutagenesis and functional rescue/failure, single lab\",\n      \"pmids\": [\"20890132\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Nlp localizes to the midbody during cytokinesis and is required for completion of cell division. Aurora B recruits Nlp to the midbody via direct physical interaction. Aurora B phosphorylates Nlp at Ser-185, Ser-448, and Ser-585; phosphorylation at Ser-448 and Ser-585 is required for Nlp association with Aurora B and midbody localization, while Ser-185 phosphorylation affects Nlp stability. Depletion of Nlp or disruption of phosphorylation sites causes aborted cytokinesis and chromosomal instability.\",\n      \"method\": \"Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis, immunofluorescence, siRNA knockdown\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro kinase assay, mutagenesis, Co-IP, and siRNA knockdown with defined cytokinesis phenotype in a single study\",\n      \"pmids\": [\"20864540\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Overexpression of Nlp in NIH3T3 cells confers anchorage-independent growth and tumor formation in nude mice. Transgenic mice overexpressing Nlp develop spontaneous tumors and show centrosome amplification in MEFs, suggesting that Nlp overexpression mimics BRCA1 loss and contributes to genomic instability.\",\n      \"method\": \"Stable transfection/transformation assay, transgenic mouse model, immunohistochemistry, MEF centrosome analysis\",\n      \"journal\": \"The Journal of clinical investigation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — defined oncogenic phenotype in multiple model systems, single lab\",\n      \"pmids\": [\"20093778\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"NINL physically interacts with the ciliopathy protein CC2D2A at the base of cilia. Knockdown of ninl in zebrafish leads to photoreceptor outer segment loss, mislocalization of opsins, vesicle accumulation, and altered Rab8a localization, resembling cc2d2a-/- phenotypes. Partial ninl knockdown in cc2d2a-/- embryos enhances the retinal phenotype, indicating a genetic interaction. The NINL-associated interactome includes MICAL3, a Rab8-interacting protein involved in vesicle docking and fusion.\",\n      \"method\": \"Co-immunoprecipitation (pulldown), zebrafish morpholino knockdown, genetic interaction/epistasis, immunofluorescence localization, proteomics interactome\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal interaction evidence, zebrafish in vivo genetic epistasis, multiple phenotypic readouts in one study\",\n      \"pmids\": [\"26485645\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"NINL interacts with DZANK1 and both proteins associate with complementary subunits of the cytoplasmic dynein 1 motor complex. Loss of Ninl, Dzank1, or both synergistically causes dysmorphic photoreceptor outer segments, accumulation of trans-Golgi-derived vesicles, mislocalization of Rhodopsin and Ush2a, and severely impaired retrograde melanosome transport in zebrafish, supporting a role for the NINL-DZANK1 module in assembly of the cytoplasmic dynein 1 complex.\",\n      \"method\": \"Yeast two-hybrid, co-immunoprecipitation, zebrafish morpholino/mutant phenotype analysis, immunofluorescence, retrograde transport assay\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal interaction assays, zebrafish genetic in vivo phenotype, two independent labs (companion paper to PMID 26485645)\",\n      \"pmids\": [\"26485514\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Upon UVC irradiation, NINL (Nlp) translocates into the nucleus via its C-terminus (residues 1030–1382) and physically interacts with the NER factors XPA and ERCC1, enhancing their association. Nlp depletion impairs nucleotide excision repair (NER) activity and sensitizes cells to UV radiation.\",\n      \"method\": \"Co-immunoprecipitation, nuclear fractionation, NER activity assay, deletion mapping, immunofluorescence, siRNA knockdown\",\n      \"journal\": \"Cancer letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP, fractionation, functional NER assay and deletion mapping in a single lab\",\n      \"pmids\": [\"26805762\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"NINL (Nlp) colocalizes with autophagosomes and physically interacts with LC3 (autophagosome marker), Rab7, and FYCO1. Nlp enhances the Rab7–FYCO1 interaction, thereby accelerating autophagic flux and autophagolysosome formation. NLP-deficient mice treated with DMBA show increased liver cancer incidence associated with hepatic autophagic defects.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence colocalization, autophagy flux assay, mouse knockout/carcinogen model\",\n      \"journal\": \"Signal transduction and targeted therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP with multiple partners and in vivo mouse knockout phenotype, single lab\",\n      \"pmids\": [\"33859171\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"NINL has evolved under recurrent positive selection, particularly in its carboxy-terminal cargo-binding region. NINL knockout cells exhibit an impaired interferon response, resulting in increased permissiveness to viral replication. Proteases encoded by diverse picornaviruses and coronaviruses cleave and disrupt NINL function in a host- and virus-specific manner, identifying NINL as a component of the antiviral innate immune response and a target of viral antagonism.\",\n      \"method\": \"NINL knockout cells (interferon response assay, viral replication assay), viral protease cleavage assay, evolutionary analysis (signatures of positive selection)\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — KO cell functional assays with defined interferon-response phenotype, plus direct protease cleavage assays across multiple virus families, multiple orthogonal methods in one study\",\n      \"pmids\": [\"36222652\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"NINL (Nlp) acts as an adaptor/platform for ER-to-Golgi vesicle trafficking by directly binding SEC31A (a COPII coat component) and Rab1B, facilitating selection and continuity of specific cargoes (including β-Catenin and STING) through COPII- and COPI-coated vesicle transition. Nlp deficiency causes vesicle budding failure, ER protein accumulation, ER stress, Golgi fragmentation, and activation of the PERK-eIF2α UPR pathway. Nlp-deficient mice develop spontaneous B cell lymphoma, linked to defective secretory protein trafficking in lymphocytes.\",\n      \"method\": \"Co-immunoprecipitation (with SEC31A and Rab1B), knockdown/knockout cells, ER stress assay (PERK-eIF2α), immunofluorescence (Golgi fragmentation), mouse knockout model\",\n      \"journal\": \"International journal of biological sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP with direct binding partners, functional KO phenotypes in cells and mice, single lab\",\n      \"pmids\": [\"38904019\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"NINL (ninein-like protein) is a centrosomal protein that promotes microtubule nucleation by interacting with the gamma-tubulin ring complex during interphase; at the G2/M transition it is sequentially phosphorylated by Nek2 and Plk1 (primed by Cdc2/cyclin B1), which disrupts its gamma-tubulin and dynactin interactions and displaces it from the centrosome; it is also phosphorylated by Aurora B at the midbody to complete cytokinesis; beyond the centrosome, NINL functions as a dynein activating adaptor (binding DZANK1 and dynein-dynactin subunits) essential for vesicle trafficking in photoreceptors and cilia biogenesis (interacting with CC2D2A, RAB8, and MICAL3), serves as a ER-to-Golgi cargo adaptor via SEC31A and Rab1B, enhances autophagosome transport by bridging Rab7 and FYCO1, participates in nucleotide excision repair by scaffolding XPA–ERCC1 in the nucleus after UV damage, and is a target of viral protease-mediated antagonism within the antiviral innate immune response.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"NINL (ninein-like protein, Nlp) is a centrosomal organizer of microtubule arrays whose cell-cycle-regulated phosphorylation couples microtubule nucleation to mitotic progression [#0, #2]. During interphase it binds components of the gamma-tubulin ring complex to stimulate microtubule nucleation, and its centrosomal targeting depends on the dynein-dynactin motor [#0, #1]. At the G2/M transition a phosphorylation cascade displaces it from the centrosome: Cdc2/cyclin B1 phosphorylates Ser185 to prime recognition by Plk1, Nek2 further primes Plk1 phosphorylation, and Plk1 then disrupts both the gamma-tubulin and dynactin interactions to release NINL from the centrosome [#1, #2, #4]. NINL is independently recruited to the midbody by Aurora B, which phosphorylates it to drive completion of cytokinesis; loss of NINL or its phosphosites produces aberrant spindles, aborted cytokinesis, aneuploidy, and chromosomal instability [#3, #5]. Beyond the centrosome NINL operates as a dynein-associated adaptor for membrane trafficking: it partners with DZANK1 to assemble cytoplasmic dynein 1 and with the ciliopathy protein CC2D2A, RAB8 and MICAL3 at the ciliary base, and its loss in zebrafish causes photoreceptor outer-segment defects, opsin/Ush2a mislocalization, vesicle accumulation and impaired retrograde transport [#7, #8]. It further acts as a vesicle-trafficking platform, bridging Rab7 and FYCO1 to accelerate autophagic flux and binding SEC31A and Rab1B to support COPII-mediated ER-to-Golgi cargo transport, with deficiency triggering ER stress and the PERK-eIF2alpha UPR [#10, #12]. NINL additionally translocates to the nucleus after UV damage to scaffold the XPA-ERCC1 nucleotide excision repair factors, and is a positively selected component of the antiviral interferon response that is cleaved by diverse picornaviral and coronaviral proteases [#9, #11].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established NINL's core molecular function by showing it binds the gamma-TuRC to nucleate microtubules and is regulated by Plk1, explaining how microtubule organization is reset at mitotic onset.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, and phospho-mutant overexpression in cultured cells\",\n      \"pmids\": [\"12852856\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define upstream priming kinases\", \"Structural basis of gamma-tubulin binding not resolved\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Connected NINL's centrosomal targeting to the dynein-dynactin motor and showed Plk1 phosphorylation severs this link, providing a mechanism coupling motor-dependent localization to the cell cycle.\",\n      \"evidence\": \"Reciprocal Co-IP, dominant-negative dynactin, and in vitro kinase assay\",\n      \"pmids\": [\"16254247\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Which dynactin subunit mediates the interaction not pinpointed\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Identified Nek2 as a second NINL kinase that primes Plk1 phosphorylation, ordering the G2/M phosphorylation cascade controlling centrosomal release.\",\n      \"evidence\": \"In vitro kinase assays with kinase-active/inactive mutants and localization in cells\",\n      \"pmids\": [\"15684383\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo sequence of Nek2-then-Plk1 events not directly demonstrated\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Linked NINL to genome stability by showing BRCA1 maintains its centrosomal localization and that NINL depletion causes spindle defects and aneuploidy.\",\n      \"evidence\": \"Co-IP, colocalization, siRNA knockdown in BRCA1-mutant cell lines\",\n      \"pmids\": [\"19509300\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"BRCA1-Plk1-NINL regulatory chain inferred, not directly mapped\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Mapped Cdc2/cyclin B1 phosphosites (Ser185, Ser589) defining how NINL is primed for Plk1 recognition and how its stability is controlled at mitosis.\",\n      \"evidence\": \"In vitro kinase assay, site-directed mutagenesis, immunofluorescence\",\n      \"pmids\": [\"20890132\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Degradation machinery acting on Ser589-phosphorylated NINL not identified\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Extended NINL function into cytokinesis, showing Aurora B recruits and phosphorylates it at the midbody to complete cell division.\",\n      \"evidence\": \"Co-IP, in vitro kinase assay, mutagenesis, and siRNA knockdown with cytokinesis readout\",\n      \"pmids\": [\"20864540\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Midbody binding partners of NINL beyond Aurora B unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrated that NINL dysregulation is oncogenic, with overexpression driving transformation, centrosome amplification, and spontaneous tumors in mice.\",\n      \"evidence\": \"Transformation assay, transgenic mouse model, MEF centrosome analysis\",\n      \"pmids\": [\"20093778\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanistic link between overexpression and centrosome amplification not dissected\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Revealed a ciliary/photoreceptor trafficking role by placing NINL with CC2D2A, RAB8 and MICAL3 at the cilium base and demonstrating a genetic interaction with cc2d2a in vivo.\",\n      \"evidence\": \"Co-IP, zebrafish morpholino knockdown, genetic epistasis, interactome proteomics\",\n      \"pmids\": [\"26485645\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs indirect nature of NINL-MICAL3 interaction not separated\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Defined the NINL-DZANK1 module as a dynein-1 assembly adaptor, showing synergistic photoreceptor and retrograde transport defects upon loss.\",\n      \"evidence\": \"Yeast two-hybrid, Co-IP, zebrafish mutant/morphant phenotypes, retrograde melanosome transport assay\",\n      \"pmids\": [\"26485514\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Stoichiometry of NINL-DZANK1-dynein assembly not resolved\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Uncovered a nuclear, UV-inducible role in nucleotide excision repair, with NINL scaffolding XPA-ERCC1 to promote repair.\",\n      \"evidence\": \"Co-IP, nuclear fractionation, NER activity assay, deletion mapping, siRNA knockdown\",\n      \"pmids\": [\"26805762\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"How the centrosomal protein relocalizes and is retained in the nucleus unclear\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Identified NINL as an autophagy enhancer bridging Rab7 and FYCO1 to accelerate autophagic flux, with knockout promoting carcinogen-induced liver cancer.\",\n      \"evidence\": \"Co-IP, colocalization, autophagy flux assay, mouse knockout/carcinogen model\",\n      \"pmids\": [\"33859171\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the Rab7-FYCO1 bridging requires dynein not addressed\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Established NINL as an antiviral innate immune factor under positive selection that is directly cleaved by picornaviral and coronaviral proteases.\",\n      \"evidence\": \"Knockout cell interferon and viral replication assays, protease cleavage assays, evolutionary analysis\",\n      \"pmids\": [\"36222652\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular step in the interferon pathway NINL acts on not defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Defined NINL as an ER-to-Golgi cargo adaptor binding SEC31A and Rab1B, with deficiency causing ER stress, UPR activation, and B cell lymphoma in mice.\",\n      \"evidence\": \"Co-IP with SEC31A/Rab1B, knockdown/knockout cells, ER stress assays, mouse knockout\",\n      \"pmids\": [\"38904019\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Cargo selectivity mechanism not fully resolved\", \"Single-lab finding\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How NINL's many roles—centrosomal microtubule nucleation, dynein-adaptor trafficking, autophagy, COPII transport, NER, and antiviral defense—are partitioned by isoform, localization, or context remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unifying model integrating centrosomal and trafficking/immune functions\", \"Domain requirements for each function not comparatively mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [8, 10, 12]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [7, 8]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [10, 12]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [8, 12]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [10]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [9]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [11]}\n    ],\n    \"complexes\": [\"cytoplasmic dynein 1 complex\", \"gamma-tubulin ring complex (gamma-TuRC)\"],\n    \"partners\": [\"DZANK1\", \"CC2D2A\", \"MICAL3\", \"SEC31A\", \"RAB1B\", \"RAB7\", \"FYCO1\", \"XPA\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}