{"gene":"DNMBP","run_date":"2026-06-09T23:54:42","timeline":{"discoveries":[{"year":2003,"finding":"Tuba (DNMBP) is a scaffold protein containing four N-terminal SH3 domains that bind dynamin, a central DH domain that functions as a Cdc42-specific GEF (not activating Rac or Rho), a BAR domain (which replaces the typical PH domain following DH domains), and a C-terminal SH3 domain that directly binds N-WASP and Ena/VASP proteins, linking dynamin to actin regulatory proteins.","method":"Co-immunoprecipitation, pulldown assays, in vitro GEF activity assay, forced mitochondrial targeting of C-terminal SH3 domain to assess F-actin recruitment","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (binding assays, GEF activity, forced targeting), single foundational paper with rigorous domain-level dissection","pmids":["14506234"],"is_preprint":false},{"year":2005,"finding":"The four N-terminal SH3 domains of Tuba bind dynamin with exceptionally high avidity; the DH domain is a Cdc42-specific GEF unique in being followed by a BAR domain rather than a PH domain; the C-terminal SH3 domain directly binds N-WASP and Ena/VASP and recruits a larger actin regulatory complex.","method":"Biochemical pulldown, co-immunoprecipitation, GEF activity assays, domain characterization","journal":"Methods in enzymology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — replication and elaboration of foundational domain-function findings with multiple biochemical methods across two papers","pmids":["16413298"],"is_preprint":false},{"year":2006,"finding":"Tuba is concentrated at the apical-most region of cell junctions in simple epithelia via interaction with ZO-1. RNAi-mediated depletion of Tuba alters the geometrical configuration of cell junctions (curved/slack appearance), modifies junctional F-actin and E-cadherin assembly, and retards junction formation. Suppression of Cdc42 or N-WASP mimics Tuba depletion; overexpression of dominant-active Cdc42 or N-WASP rescues Tuba-depleted cells, establishing a Tuba→Cdc42→N-WASP pathway for junction shaping.","method":"RNAi knockdown, immunofluorescence, calcium-switch junction formation assay, dominant-active rescue, co-immunoprecipitation with ZO-1","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal genetic epistasis (KD + rescue), localization linked to functional consequence, replicated across multiple experimental approaches in one rigorous study","pmids":["17015620"],"is_preprint":false},{"year":2006,"finding":"Tuba overexpression stimulates dorsal ruffles and actin-driven motility of intracellular puncta requiring the C-terminal SH3, DH/GEF, and BAR domains. Tuba is recruited to PIP5Kα-generated lipid vesicles and promotes N-WASP-dependent actin comet formation. RNAi knockdown of Tuba attenuates PIP5Kα-generated comet formation and invasive behavior of B16 melanoma cells.","method":"Overexpression, RNAi knockdown, fluorescence microscopy, domain deletion analysis, invasiveness assays","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — multiple readouts in one lab, domain-level dissection, but localization-to-function link is partially indirect","pmids":["16757518"],"is_preprint":false},{"year":2010,"finding":"Tuba, as a Cdc42-specific GEF, is required for Cdc42 enrichment at the apical cortex of epithelial cysts. Loss of Tuba causes a multilumen phenotype by disrupting spindle orientation; this is rescued by human Tuba or constitutively active Cdc42 but not by a GEF-dead Tuba mutant, placing Tuba upstream of Cdc42→aPKC→spindle orientation in epithelial ductal morphogenesis.","method":"RNAi screen (70 GEFs), RNAi knockdown, rescue with Tuba WT vs. GEF-dead mutant, active Cdc42 rescue, immunofluorescence, aPKC activity assay","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — GEF-dead mutant rescue experiment establishes catalytic requirement; multiple orthogonal approaches; genetic epistasis with Cdc42 and aPKC","pmids":["20479467"],"is_preprint":false},{"year":2011,"finding":"Tuba and N-WASP function cooperatively at the pre-apical patch (PAP) to position the central lumen during epithelial cyst morphogenesis; each depends on the other for localization to the PAP, and the cooperative function requires the polyproline region of N-WASP.","method":"RNAi knockdown, immunofluorescence localization, multilumen phenotype assay in Caco-2 cysts","journal":"Cell adhesion & migration","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — mutual dependency of localization shown by KD, functional rescue not fully demonstrated, single lab","pmids":["21677511"],"is_preprint":false},{"year":2013,"finding":"The Listeria virulence factor InlC binds the sixth SH3 domain (SH3-6) of human Tuba, competitively disrupting its physiological interaction with N-WASP and Mena; the InlC/Tuba SH3-6 interaction is centered on Phe146 of InlC stacking on Asn1569 of Tuba, and replacing Phe146 with Ala largely abrogates affinity and in vivo mimics deletion of inlC.","method":"Crystal structure of Tuba SH3-6 complexes with InlC, N-WASP, and Mena; site-directed mutagenesis (F146A); in vivo spreading assays","journal":"Structure (London, England : 1993)","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with functional mutagenesis validation and in vivo confirmation in a single rigorous study","pmids":["24332715"],"is_preprint":false},{"year":2014,"finding":"DDR1 (Discoidin Domain Receptor 1) signals through Tuba and Cdc42 to promote linear invadosome formation and matrix degradation on collagen I fibrils; DDR1 kinase activity and Src are not required, but Cdc42 activation by DDR1 is Tuba-dependent, as both Tuba and Cdc42 localize to linear invadosomes and are required for their formation.","method":"SiRNA knockdown, immunofluorescence colocalization, Cdc42 activity assay (pulldown), matrix degradation assay, collagen gel invasion assay","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal knockdown and activity assays, pathway placement by epistasis, colocalization with functional readout","pmids":["25422375"],"is_preprint":false},{"year":2016,"finding":"Tuba (Dynamin Binding Protein) is required for ciliogenesis and nephrogenesis: Tuba knockdown in MDCK cells abolishes primary cilia, impairs apical polarization, and inhibits HGF-induced tubulogenesis. In zebrafish, tuba morphants exhibit ciliary mutant phenotypes in multiple ciliated organs; co-injection of sub-threshold tuba and cdc42 morpholinos causes genetic synergy and disorganized pronephric duct cilia, placing Tuba in the same Cdc42/ciliogenesis pathway.","method":"RNAi knockdown in MDCK cells, zebrafish morpholino knockdown, genetic epistasis (tuba + cdc42 double morpholino), immunofluorescence, electroretinography","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — genetic epistasis in two model systems (cell culture + zebrafish), multiple phenotypic readouts, synergy experiment with Cdc42 morpholino","pmids":["26895965"],"is_preprint":false},{"year":2018,"finding":"Bi-allelic loss-of-function variants in DNMBP cause infantile cataracts in humans. RNAi knockdown of the Drosophila ortholog still life (sif) in lens-secreting cells disrupts lens-secreting cell development, delocalizes E-cadherin, alters septate junction distribution in cone cells, and reduces electroretinography amplitudes. In human epithelial cells, DNMBP regulates tight junction shape and E-cadherin assembly pattern.","method":"Exome sequencing (human genetics), Drosophila RNAi knockdown, immunofluorescence (E-cadherin/septate junction localization), electroretinography, human cell knockdown","journal":"American journal of human genetics","confidence":"High","confidence_rationale":"Tier 2 / Strong — cross-species genetic validation (human LOF variants + Drosophila ortholog KD), multiple functional readouts, mechanistic link to E-cadherin and junction regulation","pmids":["30290152"],"is_preprint":false},{"year":2018,"finding":"A Tuba/Cdc42/Par6A trimeric complex is required to ensure singularity of the apical domain during enterocyte polarization. Tuba, Cdc42, and Par6A co-immunoprecipitate and partially colocalize at the apical membrane; Par6A is required to restrict Cdc42 signaling at the apical domain; rescue experiments using Par6A mutants show that the ability to form this trimeric complex correlates with restoration of apical domain singularity.","method":"Co-immunoprecipitation, CRISPR knockout of Par6A, rescue with Par6A mutants, live imaging of active Cdc42 (FRAP), immunofluorescence colocalization","journal":"PloS one","confidence":"High","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP, KO rescue with structure-function mutants, live imaging, single lab with multiple orthogonal methods","pmids":["30408122"],"is_preprint":false},{"year":2021,"finding":"Tuba activates Cdc42 downstream of Rab8a during neuronal polarization. Rab8a activity generates a proximal-to-distal axonal gradient of Tuba in cultured neurons; gain-of-function of Rab8a or Tuba produces supernumerary axons, while loss-of-function abrogates axon specification, phenocopying Cdc42 loss. In vivo, dominant-negative Rab8a or Tuba knockdown impairs cortical neuronal migration in mice.","method":"Gain-of-function and loss-of-function (RNAi/dominant negative) in cultured rat hippocampal neurons, in utero electroporation for cortical migration in mice, immunofluorescence of Tuba gradient","journal":"The Journal of neuroscience","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple gain/loss of function experiments, in vitro and in vivo validation, genetic epistasis establishing Rab8a→Tuba→Cdc42 pathway","pmids":["33478991"],"is_preprint":false},{"year":2025,"finding":"The ubiquitin ligase Nedd4-2 (NEDD4L) binds DNMBP/Tuba preferentially under hyperosmotic stress and ubiquitinates it, targeting DNMBP to P-body condensates. DNMBP itself promotes P-body formation under hyperosmolarity. Both Nedd4-2 and DNMBP are required for Cdc42 activation following hyperosmotic treatment; DNMBP knockout suppresses Cdc42 and its downstream effector p38-MAPK.","method":"BioID proximity labeling screen (miniTurbo-Nedd4-2), co-immunoprecipitation, ubiquitination assay, P-body localization by immunofluorescence, DNMBP knockout, Cdc42 and p38-MAPK activity assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID screen plus functional validation (KO, activity assays, localization), single lab, novel finding not yet independently replicated","pmids":["40975170"],"is_preprint":false}],"current_model":"DNMBP/Tuba is a multidomain scaffold and Cdc42-specific GEF that links dynamin (via four N-terminal SH3 domains) to actin regulatory proteins (N-WASP, Ena/VASP) through its C-terminal SH3 domain, while its central DH domain (flanked by a BAR domain rather than a PH domain) activates Cdc42 to control cell junction geometry, apical domain singularity, epithelial cyst lumen formation via Cdc42→aPKC→spindle orientation, ciliogenesis and nephrogenesis, linear invadosome formation downstream of DDR1, and neuronal polarity downstream of Rab8a; under hyperosmotic stress, the ubiquitin ligase Nedd4-2 ubiquitinates DNMBP and targets it to P-bodies to facilitate Cdc42 and p38-MAPK activation, and loss-of-function variants in DNMBP cause infantile cataracts in humans."},"narrative":{"mechanistic_narrative":"DNMBP (Tuba) is a multidomain scaffold and Cdc42-specific guanine nucleotide exchange factor that couples the membrane-fission machinery to actin regulators and Cdc42 signaling to control epithelial junction geometry, apical polarity, and tissue morphogenesis [PMID:14506234, PMID:17015620]. Its four N-terminal SH3 domains bind dynamin with high avidity, a central DH domain selectively activates Cdc42 (not Rac or Rho), an adjacent BAR domain replaces the canonical PH module, and a C-terminal SH3 domain directly engages the actin nucleation-promoting factors N-WASP and Ena/VASP [PMID:14506234, PMID:16413298]. At apical cell junctions, DNMBP is recruited through ZO-1 and shapes junctional F-actin and E-cadherin assembly via a Tuba→Cdc42→N-WASP cascade [PMID:17015620]. This GEF activity is catalytically required for apical Cdc42 enrichment, which drives aPKC-dependent spindle orientation and single-lumen formation in epithelial cysts, with N-WASP cooperating at the pre-apical patch and a Tuba/Cdc42/Par6A complex restricting Cdc42 to ensure apical domain singularity [PMID:20479467, PMID:21677511, PMID:30408122]. The same Tuba→Cdc42 module is deployed for ciliogenesis and nephrogenesis, for DDR1-driven linear invadosome formation and matrix degradation on collagen, and for Rab8a-dependent axon specification and cortical neuronal migration [PMID:25422375, PMID:26895965, PMID:33478991]. Under hyperosmotic stress, Nedd4-2 (NEDD4L) ubiquitinates DNMBP and targets it to P-body condensates to enable Cdc42 and downstream p38-MAPK activation [PMID:40975170]. Bi-allelic loss-of-function variants in DNMBP cause infantile cataracts in humans, consistent with its role in epithelial junction and E-cadherin regulation [PMID:30290152].","teleology":[{"year":2003,"claim":"Established the domain architecture and biochemical logic of DNMBP, defining it as a scaffold that physically bridges dynamin to actin regulators while functioning as a Cdc42-specific GEF.","evidence":"Co-IP, pulldowns, in vitro GEF assays, and forced mitochondrial targeting of the C-terminal SH3 domain","pmids":["14506234"],"confidence":"High","gaps":["Cellular context in which dynamin–actin coupling occurs not defined","No structural detail of the DH-BAR module"]},{"year":2005,"claim":"Confirmed and elaborated the high-avidity dynamin binding by the four SH3 domains and the unusual DH-BAR arrangement, consolidating the Cdc42-specific GEF identity.","evidence":"Biochemical pulldown, co-IP, and GEF activity assays with domain characterization","pmids":["16413298"],"confidence":"High","gaps":["Functional consequence of the BAR domain in lieu of PH not resolved"]},{"year":2006,"claim":"Placed DNMBP at apical cell junctions and demonstrated a Tuba→Cdc42→N-WASP pathway shaping junction geometry, F-actin, and E-cadherin, connecting the scaffold to epithelial morphogenesis.","evidence":"RNAi knockdown, calcium-switch junction assays, dominant-active rescue, and ZO-1 co-IP; plus overexpression/knockdown studies of PIP5Kα-driven actin comets and melanoma invasiveness","pmids":["17015620","16757518"],"confidence":"High","gaps":["Mechanism of ZO-1-mediated apical targeting not fully defined","Comet/invasion link is partially indirect"]},{"year":2010,"claim":"Demonstrated that DNMBP GEF catalytic activity is required for apical Cdc42 enrichment and correct spindle orientation, establishing Tuba upstream of Cdc42→aPKC in single-lumen morphogenesis.","evidence":"GEF screen, RNAi, rescue with WT vs GEF-dead Tuba and active Cdc42, aPKC activity assay in epithelial cysts","pmids":["20479467"],"confidence":"High","gaps":["How apical Cdc42 spatially couples to spindle machinery not detailed"]},{"year":2011,"claim":"Showed DNMBP and N-WASP are mutually dependent for pre-apical patch localization, refining the cooperative basis of lumen positioning.","evidence":"RNAi knockdown and multilumen phenotype assays in Caco-2 cysts","pmids":["21677511"],"confidence":"Medium","gaps":["Functional rescue not fully demonstrated","Single lab"]},{"year":2013,"claim":"Resolved at atomic resolution how the SH3-6 domain engages N-WASP and Mena and how the Listeria factor InlC competitively hijacks this interface, defining a structural basis for DNMBP's partner binding.","evidence":"Crystal structures of Tuba SH3-6 with InlC, N-WASP and Mena plus F146A mutagenesis and in vivo spreading assays","pmids":["24332715"],"confidence":"High","gaps":["Physiological regulation of SH3-6 occupancy not addressed"]},{"year":2014,"claim":"Identified DNMBP as the GEF coupling DDR1 receptor signaling to Cdc42 for linear invadosome formation and collagen degradation, independent of DDR1 kinase activity and Src.","evidence":"siRNA knockdown, Cdc42 activity pulldown, colocalization, and matrix degradation/invasion assays","pmids":["25422375"],"confidence":"High","gaps":["Mechanism by which DDR1 recruits Tuba unknown"]},{"year":2016,"claim":"Extended DNMBP function to ciliogenesis and nephrogenesis, showing genetic synergy with Cdc42 across cell and zebrafish models.","evidence":"RNAi in MDCK cells, zebrafish morpholino knockdown, tuba+cdc42 double-morphant synergy, immunofluorescence","pmids":["26895965"],"confidence":"High","gaps":["Molecular link between Tuba and the ciliary apparatus not defined"]},{"year":2018,"claim":"Connected DNMBP to human disease and refined a polarity mechanism: LOF variants cause infantile cataracts, and a Tuba/Cdc42/Par6A trimeric complex restricts Cdc42 to ensure apical domain singularity.","evidence":"Exome sequencing with Drosophila sif RNAi and E-cadherin/junction readouts; Co-IP, Par6A CRISPR KO and mutant rescue with live Cdc42 FRAP imaging","pmids":["30290152","30408122"],"confidence":"High","gaps":["How LOF variants disrupt GEF/scaffold function at molecular level not shown","Mechanism of Par6A-mediated Cdc42 spatial restriction incomplete"]},{"year":2021,"claim":"Positioned DNMBP downstream of Rab8a in neuronal polarization, identifying a Rab8a→Tuba→Cdc42 axis that specifies axons and drives cortical migration.","evidence":"Gain/loss of function in rat hippocampal neurons, in utero electroporation in mice, immunofluorescence of the Tuba axonal gradient","pmids":["33478991"],"confidence":"High","gaps":["How Rab8a generates the proximal-to-distal Tuba gradient not resolved"]},{"year":2025,"claim":"Revealed stress-responsive regulation of DNMBP: Nedd4-2 ubiquitinates it and targets it to P-bodies to enable hyperosmotic Cdc42 and p38-MAPK activation.","evidence":"BioID proximity screen, Co-IP, ubiquitination assay, P-body imaging, DNMBP KO and Cdc42/p38 activity assays","pmids":["40975170"],"confidence":"Medium","gaps":["Not independently replicated","Functional consequence of P-body sequestration of DNMBP unclear","Role of ubiquitination in GEF activity not defined"]},{"year":null,"claim":"How DNMBP's distinct partner interactions (dynamin, N-WASP, ZO-1, Par6A, Rab8a, DDR1, Nedd4-2) are differentially deployed across epithelial, ciliary, neuronal, and stress contexts remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No integrated structural model of the full-length protein","Determinants of context-specific scaffolding not defined","Regulation of GEF output by upstream signals incompletely mapped"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1,4,7]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,10]},{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[0,3]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[2,10]},{"term_id":"GO:0005856","term_label":"cytoskeleton","supporting_discovery_ids":[0,3]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[8]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,7,11,12]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[4,8,11]},{"term_id":"R-HSA-1500931","term_label":"Cell-Cell communication","supporting_discovery_ids":[2,9]}],"complexes":["Tuba/Cdc42/Par6A trimeric complex"],"partners":["DNM1","WASL","ENAH","TJP1","CDC42","PARD6A","DDR1","NEDD4L"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q6XZF7","full_name":"Dynamin-binding protein","aliases":["Scaffold protein Tuba"],"length_aa":1577,"mass_kda":177.3,"function":"Plays a critical role as a guanine nucleotide exchange factor (GEF) for CDC42 in several intracellular processes associated with the actin and microtubule cytoskeleton. Regulates the structure of apical junctions through F-actin organization in epithelial cells (PubMed:17015620, PubMed:19767742). Participates in the normal lumenogenesis of epithelial cell cysts by regulating spindle orientation (PubMed:20479467). Plays a role in ciliogenesis (By similarity). May play a role in membrane trafficking between the cell surface and the Golgi (By similarity)","subcellular_location":"Cytoplasm; Golgi apparatus, Golgi stack; Cytoplasm, cytoskeleton; Synapse; Cell junction","url":"https://www.uniprot.org/uniprotkb/Q6XZF7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/DNMBP","classification":"Not Classified","n_dependent_lines":2,"n_total_lines":1208,"dependency_fraction":0.0016556291390728477},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"BIN3","stoichiometry":10.0},{"gene":"CAPZB","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/DNMBP","total_profiled":1310},"omim":[{"mim_id":"618415","title":"CATARACT 48; CTRCT48","url":"https://www.omim.org/entry/618415"},{"mim_id":"611282","title":"DYNAMIN-BINDING PROTEIN; DNMBP","url":"https://www.omim.org/entry/611282"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoli","reliability":"Approved"},{"location":"Golgi apparatus","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"},{"location":"Nucleoplasm","reliability":"Additional"},{"location":"Nuclear bodies","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/DNMBP"},"hgnc":{"alias_symbol":["KIAA1010","Tuba","ARHGEF36"],"prev_symbol":[]},"alphafold":{"accession":"Q6XZF7","domains":[{"cath_id":"2.30.30.40","chopping":"144-208","consensus_level":"medium","plddt":83.9528,"start":144,"end":208},{"cath_id":"2.30.30.40","chopping":"248-301","consensus_level":"medium","plddt":87.3269,"start":248,"end":301},{"cath_id":"1.20.1270.60","chopping":"996-1224","consensus_level":"high","plddt":85.4759,"start":996,"end":1224},{"cath_id":"2.30.30.40","chopping":"1518-1575","consensus_level":"medium","plddt":88.8181,"start":1518,"end":1575}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6XZF7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6XZF7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6XZF7-F1-predicted_aligned_error_v6.png","plddt_mean":63.94},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=DNMBP","jax_strain_url":"https://www.jax.org/strain/search?query=DNMBP"},"sequence":{"accession":"Q6XZF7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6XZF7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6XZF7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6XZF7"}},"corpus_meta":[{"pmid":"17015620","id":"PMC_17015620","title":"Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells.","date":"2006","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/17015620","citation_count":185,"is_preprint":false},{"pmid":"14506234","id":"PMC_14506234","title":"Tuba, a novel protein containing bin/amphiphysin/Rvs and Dbl homology domains, links dynamin to regulation of the actin cytoskeleton.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14506234","citation_count":140,"is_preprint":false},{"pmid":"20479467","id":"PMC_20479467","title":"Tuba, a Cdc42 GEF, is required for polarized spindle orientation during epithelial cyst formation.","date":"2010","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/20479467","citation_count":110,"is_preprint":false},{"pmid":"25422375","id":"PMC_25422375","title":"Discoidin domain receptor 1 controls linear invadosome formation via a Cdc42-Tuba pathway.","date":"2014","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/25422375","citation_count":93,"is_preprint":false},{"pmid":"26286255","id":"PMC_26286255","title":"Early salpingectomy (TUbectomy) with delayed oophorectomy to improve quality of life as alternative for risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers (TUBA study): a prospective non-randomised multicentre study.","date":"2015","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/26286255","citation_count":90,"is_preprint":false},{"pmid":"16757518","id":"PMC_16757518","title":"Tuba stimulates intracellular N-WASP-dependent actin assembly.","date":"2006","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/16757518","citation_count":62,"is_preprint":false},{"pmid":"37045546","id":"PMC_37045546","title":"TUBectomy with delayed oophorectomy as an alternative to risk-reducing salpingo-oophorectomy in high-risk women to assess the safety of prevention: the TUBA-WISP II study protocol.","date":"2023","source":"International journal of gynecological cancer : official journal of the International Gynecological Cancer Society","url":"https://pubmed.ncbi.nlm.nih.gov/37045546","citation_count":45,"is_preprint":false},{"pmid":"30290152","id":"PMC_30290152","title":"Bi-allelic Loss-of-Function Variants in DNMBP Cause Infantile Cataracts.","date":"2018","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/30290152","citation_count":32,"is_preprint":false},{"pmid":"33985412","id":"PMC_33985412","title":"Deletion of Ulk1 inhibits neointima formation by enhancing KAT2A/GCN5-mediated acetylation of TUBA/α-tubulin in vivo.","date":"2021","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/33985412","citation_count":30,"is_preprint":false},{"pmid":"31878840","id":"PMC_31878840","title":"Autophagic degradation of KAT2A/GCN5 promotes directional migration of vascular smooth muscle cells by reducing 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RNAi-mediated depletion of Tuba alters the geometrical configuration of cell junctions (curved/slack appearance), modifies junctional F-actin and E-cadherin assembly, and retards junction formation. Suppression of Cdc42 or N-WASP mimics Tuba depletion; overexpression of dominant-active Cdc42 or N-WASP rescues Tuba-depleted cells, establishing a Tuba→Cdc42→N-WASP pathway for junction shaping.\",\n      \"method\": \"RNAi knockdown, immunofluorescence, calcium-switch junction formation assay, dominant-active rescue, co-immunoprecipitation with ZO-1\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal genetic epistasis (KD + rescue), localization linked to functional consequence, replicated across multiple experimental approaches in one rigorous study\",\n      \"pmids\": [\"17015620\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Tuba overexpression stimulates dorsal ruffles and actin-driven motility of intracellular puncta requiring the C-terminal SH3, DH/GEF, and BAR domains. Tuba is recruited to PIP5Kα-generated lipid vesicles and promotes N-WASP-dependent actin comet formation. RNAi knockdown of Tuba attenuates PIP5Kα-generated comet formation and invasive behavior of B16 melanoma cells.\",\n      \"method\": \"Overexpression, RNAi knockdown, fluorescence microscopy, domain deletion analysis, invasiveness assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — multiple readouts in one lab, domain-level dissection, but localization-to-function link is partially indirect\",\n      \"pmids\": [\"16757518\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Tuba, as a Cdc42-specific GEF, is required for Cdc42 enrichment at the apical cortex of epithelial cysts. Loss of Tuba causes a multilumen phenotype by disrupting spindle orientation; this is rescued by human Tuba or constitutively active Cdc42 but not by a GEF-dead Tuba mutant, placing Tuba upstream of Cdc42→aPKC→spindle orientation in epithelial ductal morphogenesis.\",\n      \"method\": \"RNAi screen (70 GEFs), RNAi knockdown, rescue with Tuba WT vs. GEF-dead mutant, active Cdc42 rescue, immunofluorescence, aPKC activity assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — GEF-dead mutant rescue experiment establishes catalytic requirement; multiple orthogonal approaches; genetic epistasis with Cdc42 and aPKC\",\n      \"pmids\": [\"20479467\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Tuba and N-WASP function cooperatively at the pre-apical patch (PAP) to position the central lumen during epithelial cyst morphogenesis; each depends on the other for localization to the PAP, and the cooperative function requires the polyproline region of N-WASP.\",\n      \"method\": \"RNAi knockdown, immunofluorescence localization, multilumen phenotype assay in Caco-2 cysts\",\n      \"journal\": \"Cell adhesion & migration\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — mutual dependency of localization shown by KD, functional rescue not fully demonstrated, single lab\",\n      \"pmids\": [\"21677511\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"The Listeria virulence factor InlC binds the sixth SH3 domain (SH3-6) of human Tuba, competitively disrupting its physiological interaction with N-WASP and Mena; the InlC/Tuba SH3-6 interaction is centered on Phe146 of InlC stacking on Asn1569 of Tuba, and replacing Phe146 with Ala largely abrogates affinity and in vivo mimics deletion of inlC.\",\n      \"method\": \"Crystal structure of Tuba SH3-6 complexes with InlC, N-WASP, and Mena; site-directed mutagenesis (F146A); in vivo spreading assays\",\n      \"journal\": \"Structure (London, England : 1993)\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with functional mutagenesis validation and in vivo confirmation in a single rigorous study\",\n      \"pmids\": [\"24332715\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"DDR1 (Discoidin Domain Receptor 1) signals through Tuba and Cdc42 to promote linear invadosome formation and matrix degradation on collagen I fibrils; DDR1 kinase activity and Src are not required, but Cdc42 activation by DDR1 is Tuba-dependent, as both Tuba and Cdc42 localize to linear invadosomes and are required for their formation.\",\n      \"method\": \"SiRNA knockdown, immunofluorescence colocalization, Cdc42 activity assay (pulldown), matrix degradation assay, collagen gel invasion assay\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal knockdown and activity assays, pathway placement by epistasis, colocalization with functional readout\",\n      \"pmids\": [\"25422375\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Tuba (Dynamin Binding Protein) is required for ciliogenesis and nephrogenesis: Tuba knockdown in MDCK cells abolishes primary cilia, impairs apical polarization, and inhibits HGF-induced tubulogenesis. In zebrafish, tuba morphants exhibit ciliary mutant phenotypes in multiple ciliated organs; co-injection of sub-threshold tuba and cdc42 morpholinos causes genetic synergy and disorganized pronephric duct cilia, placing Tuba in the same Cdc42/ciliogenesis pathway.\",\n      \"method\": \"RNAi knockdown in MDCK cells, zebrafish morpholino knockdown, genetic epistasis (tuba + cdc42 double morpholino), immunofluorescence, electroretinography\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — genetic epistasis in two model systems (cell culture + zebrafish), multiple phenotypic readouts, synergy experiment with Cdc42 morpholino\",\n      \"pmids\": [\"26895965\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Bi-allelic loss-of-function variants in DNMBP cause infantile cataracts in humans. RNAi knockdown of the Drosophila ortholog still life (sif) in lens-secreting cells disrupts lens-secreting cell development, delocalizes E-cadherin, alters septate junction distribution in cone cells, and reduces electroretinography amplitudes. In human epithelial cells, DNMBP regulates tight junction shape and E-cadherin assembly pattern.\",\n      \"method\": \"Exome sequencing (human genetics), Drosophila RNAi knockdown, immunofluorescence (E-cadherin/septate junction localization), electroretinography, human cell knockdown\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — cross-species genetic validation (human LOF variants + Drosophila ortholog KD), multiple functional readouts, mechanistic link to E-cadherin and junction regulation\",\n      \"pmids\": [\"30290152\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"A Tuba/Cdc42/Par6A trimeric complex is required to ensure singularity of the apical domain during enterocyte polarization. Tuba, Cdc42, and Par6A co-immunoprecipitate and partially colocalize at the apical membrane; Par6A is required to restrict Cdc42 signaling at the apical domain; rescue experiments using Par6A mutants show that the ability to form this trimeric complex correlates with restoration of apical domain singularity.\",\n      \"method\": \"Co-immunoprecipitation, CRISPR knockout of Par6A, rescue with Par6A mutants, live imaging of active Cdc42 (FRAP), immunofluorescence colocalization\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP, KO rescue with structure-function mutants, live imaging, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"30408122\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Tuba activates Cdc42 downstream of Rab8a during neuronal polarization. Rab8a activity generates a proximal-to-distal axonal gradient of Tuba in cultured neurons; gain-of-function of Rab8a or Tuba produces supernumerary axons, while loss-of-function abrogates axon specification, phenocopying Cdc42 loss. In vivo, dominant-negative Rab8a or Tuba knockdown impairs cortical neuronal migration in mice.\",\n      \"method\": \"Gain-of-function and loss-of-function (RNAi/dominant negative) in cultured rat hippocampal neurons, in utero electroporation for cortical migration in mice, immunofluorescence of Tuba gradient\",\n      \"journal\": \"The Journal of neuroscience\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple gain/loss of function experiments, in vitro and in vivo validation, genetic epistasis establishing Rab8a→Tuba→Cdc42 pathway\",\n      \"pmids\": [\"33478991\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The ubiquitin ligase Nedd4-2 (NEDD4L) binds DNMBP/Tuba preferentially under hyperosmotic stress and ubiquitinates it, targeting DNMBP to P-body condensates. DNMBP itself promotes P-body formation under hyperosmolarity. Both Nedd4-2 and DNMBP are required for Cdc42 activation following hyperosmotic treatment; DNMBP knockout suppresses Cdc42 and its downstream effector p38-MAPK.\",\n      \"method\": \"BioID proximity labeling screen (miniTurbo-Nedd4-2), co-immunoprecipitation, ubiquitination assay, P-body localization by immunofluorescence, DNMBP knockout, Cdc42 and p38-MAPK activity assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID screen plus functional validation (KO, activity assays, localization), single lab, novel finding not yet independently replicated\",\n      \"pmids\": [\"40975170\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"DNMBP/Tuba is a multidomain scaffold and Cdc42-specific GEF that links dynamin (via four N-terminal SH3 domains) to actin regulatory proteins (N-WASP, Ena/VASP) through its C-terminal SH3 domain, while its central DH domain (flanked by a BAR domain rather than a PH domain) activates Cdc42 to control cell junction geometry, apical domain singularity, epithelial cyst lumen formation via Cdc42→aPKC→spindle orientation, ciliogenesis and nephrogenesis, linear invadosome formation downstream of DDR1, and neuronal polarity downstream of Rab8a; under hyperosmotic stress, the ubiquitin ligase Nedd4-2 ubiquitinates DNMBP and targets it to P-bodies to facilitate Cdc42 and p38-MAPK activation, and loss-of-function variants in DNMBP cause infantile cataracts in humans.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"DNMBP (Tuba) is a multidomain scaffold and Cdc42-specific guanine nucleotide exchange factor that couples the membrane-fission machinery to actin regulators and Cdc42 signaling to control epithelial junction geometry, apical polarity, and tissue morphogenesis [#0, #2]. Its four N-terminal SH3 domains bind dynamin with high avidity, a central DH domain selectively activates Cdc42 (not Rac or Rho), an adjacent BAR domain replaces the canonical PH module, and a C-terminal SH3 domain directly engages the actin nucleation-promoting factors N-WASP and Ena/VASP [#0, #1]. At apical cell junctions, DNMBP is recruited through ZO-1 and shapes junctional F-actin and E-cadherin assembly via a Tuba\\u2192Cdc42\\u2192N-WASP cascade [#2]. This GEF activity is catalytically required for apical Cdc42 enrichment, which drives aPKC-dependent spindle orientation and single-lumen formation in epithelial cysts, with N-WASP cooperating at the pre-apical patch and a Tuba/Cdc42/Par6A complex restricting Cdc42 to ensure apical domain singularity [#4, #5, #10]. The same Tuba\\u2192Cdc42 module is deployed for ciliogenesis and nephrogenesis, for DDR1-driven linear invadosome formation and matrix degradation on collagen, and for Rab8a-dependent axon specification and cortical neuronal migration [#7, #8, #11]. Under hyperosmotic stress, Nedd4-2 (NEDD4L) ubiquitinates DNMBP and targets it to P-body condensates to enable Cdc42 and downstream p38-MAPK activation [#12]. Bi-allelic loss-of-function variants in DNMBP cause infantile cataracts in humans, consistent with its role in epithelial junction and E-cadherin regulation [#9].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Established the domain architecture and biochemical logic of DNMBP, defining it as a scaffold that physically bridges dynamin to actin regulators while functioning as a Cdc42-specific GEF.\",\n      \"evidence\": \"Co-IP, pulldowns, in vitro GEF assays, and forced mitochondrial targeting of the C-terminal SH3 domain\",\n      \"pmids\": [\"14506234\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Cellular context in which dynamin\\u2013actin coupling occurs not defined\", \"No structural detail of the DH-BAR module\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Confirmed and elaborated the high-avidity dynamin binding by the four SH3 domains and the unusual DH-BAR arrangement, consolidating the Cdc42-specific GEF identity.\",\n      \"evidence\": \"Biochemical pulldown, co-IP, and GEF activity assays with domain characterization\",\n      \"pmids\": [\"16413298\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of the BAR domain in lieu of PH not resolved\"]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Placed DNMBP at apical cell junctions and demonstrated a Tuba\\u2192Cdc42\\u2192N-WASP pathway shaping junction geometry, F-actin, and E-cadherin, connecting the scaffold to epithelial morphogenesis.\",\n      \"evidence\": \"RNAi knockdown, calcium-switch junction assays, dominant-active rescue, and ZO-1 co-IP; plus overexpression/knockdown studies of PIP5K\\u03b1-driven actin comets and melanoma invasiveness\",\n      \"pmids\": [\"17015620\", \"16757518\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of ZO-1-mediated apical targeting not fully defined\", \"Comet/invasion link is partially indirect\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Demonstrated that DNMBP GEF catalytic activity is required for apical Cdc42 enrichment and correct spindle orientation, establishing Tuba upstream of Cdc42\\u2192aPKC in single-lumen morphogenesis.\",\n      \"evidence\": \"GEF screen, RNAi, rescue with WT vs GEF-dead Tuba and active Cdc42, aPKC activity assay in epithelial cysts\",\n      \"pmids\": [\"20479467\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How apical Cdc42 spatially couples to spindle machinery not detailed\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed DNMBP and N-WASP are mutually dependent for pre-apical patch localization, refining the cooperative basis of lumen positioning.\",\n      \"evidence\": \"RNAi knockdown and multilumen phenotype assays in Caco-2 cysts\",\n      \"pmids\": [\"21677511\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional rescue not fully demonstrated\", \"Single lab\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Resolved at atomic resolution how the SH3-6 domain engages N-WASP and Mena and how the Listeria factor InlC competitively hijacks this interface, defining a structural basis for DNMBP's partner binding.\",\n      \"evidence\": \"Crystal structures of Tuba SH3-6 with InlC, N-WASP and Mena plus F146A mutagenesis and in vivo spreading assays\",\n      \"pmids\": [\"24332715\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological regulation of SH3-6 occupancy not addressed\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identified DNMBP as the GEF coupling DDR1 receptor signaling to Cdc42 for linear invadosome formation and collagen degradation, independent of DDR1 kinase activity and Src.\",\n      \"evidence\": \"siRNA knockdown, Cdc42 activity pulldown, colocalization, and matrix degradation/invasion assays\",\n      \"pmids\": [\"25422375\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which DDR1 recruits Tuba unknown\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Extended DNMBP function to ciliogenesis and nephrogenesis, showing genetic synergy with Cdc42 across cell and zebrafish models.\",\n      \"evidence\": \"RNAi in MDCK cells, zebrafish morpholino knockdown, tuba+cdc42 double-morphant synergy, immunofluorescence\",\n      \"pmids\": [\"26895965\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular link between Tuba and the ciliary apparatus not defined\"]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Connected DNMBP to human disease and refined a polarity mechanism: LOF variants cause infantile cataracts, and a Tuba/Cdc42/Par6A trimeric complex restricts Cdc42 to ensure apical domain singularity.\",\n      \"evidence\": \"Exome sequencing with Drosophila sif RNAi and E-cadherin/junction readouts; Co-IP, Par6A CRISPR KO and mutant rescue with live Cdc42 FRAP imaging\",\n      \"pmids\": [\"30290152\", \"30408122\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How LOF variants disrupt GEF/scaffold function at molecular level not shown\", \"Mechanism of Par6A-mediated Cdc42 spatial restriction incomplete\"]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Positioned DNMBP downstream of Rab8a in neuronal polarization, identifying a Rab8a\\u2192Tuba\\u2192Cdc42 axis that specifies axons and drives cortical migration.\",\n      \"evidence\": \"Gain/loss of function in rat hippocampal neurons, in utero electroporation in mice, immunofluorescence of the Tuba axonal gradient\",\n      \"pmids\": [\"33478991\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How Rab8a generates the proximal-to-distal Tuba gradient not resolved\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Revealed stress-responsive regulation of DNMBP: Nedd4-2 ubiquitinates it and targets it to P-bodies to enable hyperosmotic Cdc42 and p38-MAPK activation.\",\n      \"evidence\": \"BioID proximity screen, Co-IP, ubiquitination assay, P-body imaging, DNMBP KO and Cdc42/p38 activity assays\",\n      \"pmids\": [\"40975170\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Not independently replicated\", \"Functional consequence of P-body sequestration of DNMBP unclear\", \"Role of ubiquitination in GEF activity not defined\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How DNMBP's distinct partner interactions (dynamin, N-WASP, ZO-1, Par6A, Rab8a, DDR1, Nedd4-2) are differentially deployed across epithelial, ciliary, neuronal, and stress contexts remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No integrated structural model of the full-length protein\", \"Determinants of context-specific scaffolding not defined\", \"Regulation of GEF output by upstream signals incompletely mapped\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1, 4, 7]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 10]},\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [2, 10]},\n      {\"term_id\": \"GO:0005856\", \"supporting_discovery_ids\": [0, 3]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 7, 11, 12]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [4, 8, 11]},\n      {\"term_id\": \"R-HSA-1500931\", \"supporting_discovery_ids\": [2, 9]}\n    ],\n    \"complexes\": [\n      \"Tuba/Cdc42/Par6A trimeric complex\"\n    ],\n    \"partners\": [\n      \"DNM1\",\n      \"WASL\",\n      \"ENAH\",\n      \"TJP1\",\n      \"CDC42\",\n      \"PARD6A\",\n      \"DDR1\",\n      \"NEDD4L\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}