{"gene":"EXOC8","run_date":"2026-06-09T23:54:43","timeline":{"discoveries":[{"year":1999,"finding":"Exo84p (EXOC8) is an essential component of the yeast exocyst complex required for secretory vesicle targeting and docking at the plasma membrane; depletion causes invertase secretion defects and vesicle accumulation. Exo84p co-immunoprecipitates with other exocyst components, co-sediments with the exocyst complex in velocity gradients, and its assembly into the complex requires Sec5p and Sec10p. Exo84p interacts with Sec5p and Sec10p by two-hybrid assay, and overexpression selectively suppresses a sec5 temperature-sensitive mutant. Exo84p localizes to the bud tip/mother-daughter connection (sites of polarized secretion) and is mislocalized in a sec5 mutant.","method":"Co-immunoprecipitation, velocity gradient sedimentation, two-hybrid assay, invertase secretion assay, electron microscopy, fluorescence microscopy, genetic suppression","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (co-IP, sedimentation, two-hybrid, secretion assay, EM, localization, genetic suppression) in a foundational study","pmids":["10438536"],"is_preprint":false},{"year":2005,"finding":"The Ral-binding domain of Exo84 adopts a pleckstrin homology domain fold and binds active RalA through an extended interface involving both switch regions. Key residues in Exo84 and RalA determine binding specificity. Exo84 and Sec5 competitively bind to active RalA, establishing a mechanism by which Ral GTPases can differentially regulate exocyst assembly.","method":"Crystal structure of RBD-Exo84/RalA complex at 2.0 Å, mutagenesis, biochemical binding assays","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure plus mutagenesis-validated binding specificity, multiple orthogonal methods","pmids":["15920473"],"is_preprint":false},{"year":2005,"finding":"The C-terminal domains of Exo84p form an 80 Å-long rod with an alpha-helical bundle fold that is structurally homologous to the N-terminal fold of Exo70p, revealing a common structural motif shared among exocyst subunits.","method":"X-ray crystallography (Exo84p C-terminal domains at 2.85 Å; Exo70p at 2.0 Å), structural comparison","journal":"Nature structural & molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structures of both domains with direct structural comparison and experimental validation of subunit interactions","pmids":["16249794"],"is_preprint":false},{"year":2005,"finding":"Exo84p is specifically involved in post-Golgi secretion and plays a critical role in exocyst complex assembly and polarized targeting. Pre-Golgi trafficking and polarized actin organization are required for Exo84p localization, but no single exocyst protein controls Exo84p polarization. Conversely, assembly of Sec10p, Sec15p, and Exo70p into the exocyst complex requires Exo84p.","method":"Temperature-sensitive yeast exo84 mutant analysis, electron microscopy, cargo traffic assays, fluorescence microscopy of exocyst localization, biochemical fractionation of exocyst composition","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (EM, cargo traffic, fluorescence microscopy, biochemical fractionation) in a systematic study","pmids":["15788396"],"is_preprint":false},{"year":2007,"finding":"Drosophila Exo84 (ortholog of EXOC8) is required for apical epithelial identity; loss-of-function causes failure of apical localization of the Crumbs transmembrane protein, mislocalization of adherens junction proteins, defects in apical cuticle secretion, and accumulation of apical and adherens junction proteins in an expanded recycling endosome compartment.","method":"Drosophila exo84 mutant analysis, immunofluorescence microscopy, genetic epistasis with dlg/lgl reduction","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotype and epistasis, single lab","pmids":["17698923"],"is_preprint":false},{"year":2001,"finding":"Yeast Exo84p physically associates with the U1 snRNP component Snp1p (two-hybrid and co-immunoprecipitation). A temperature-sensitive exo84 mutation causes increased pre-mRNA:mRNA ratios for RPL30 and actin transcripts, and causes a defect in splicing and prespliceosome formation in vitro, indicating a direct role for Exo84p in pre-mRNA splicing.","method":"Two-hybrid assay, co-immunoprecipitation, in vivo pre-mRNA accumulation assay, in vitro splicing assay","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP plus in vitro splicing assay, single lab, two orthogonal methods","pmids":["11425851"],"is_preprint":false},{"year":2013,"finding":"During mitosis in budding yeast, the cyclin-dependent kinase Cdk1 bound to mitotic cyclin Clb2 directly phosphorylates Exo84p. This phosphorylation disrupts exocyst complex assembly, inhibits exocytosis of select cargoes, and arrests cell surface expansion before the metaphase-anaphase transition.","method":"CDK kinase assay, immunoprecipitation, exocytosis assay, phosphorylation-site mutant analysis, fluorescence microscopy","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct kinase assay establishing phosphorylation, combined with mutant analysis and exocytosis readout, multiple orthogonal methods","pmids":["23836930"],"is_preprint":false},{"year":2014,"finding":"In Candida albicans, CaExo84 is phosphorylated by Cdk1 in a hyphal-specific cyclin Hgc1-dependent manner. Unlike in S. cerevisiae where phosphorylation disrupts exocyst assembly, CaExo84 phosphorylation does not alter its localization but reduces its affinity for phosphatidylserine, allowing it to recycle at the plasma membrane and promote continuous hyphal extension throughout mitosis.","method":"CDK phosphorylation assay, localization microscopy, phosphatidylserine binding assay, phosphodeficient/phosphomimetic mutant analysis","journal":"Molecular biology of the cell","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct kinase assay and lipid binding assay with mutants, single lab","pmids":["24501427"],"is_preprint":false},{"year":2017,"finding":"TBK1 phosphorylates the exocyst subunit Exo84 (EXOC8) upon RalA activation by insulin. Phosphorylation of Exo84 by TBK1 reduces its affinity for RalA, enabling Exo84 release from the exocyst complex and facilitating GLUT4 vesicle fusion at the plasma membrane. Phosphorylation-mimicking or nonphosphorylatable Exo84 mutants both block insulin-stimulated GLUT4 translocation, indicating that dynamic cycling of Exo84 phosphorylation state is required.","method":"In vitro kinase assay, TBK1 knockdown/knockout in adipocytes, dominant-negative TBK1 overexpression, TBK1 inhibitor treatment, RalA binding assay, phosphomimetic/phosphodeficient mutant analysis, GLUT4 translocation assay, glucose uptake assay","journal":"Science signaling","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct kinase assay, multiple genetic and pharmacological perturbations, phosphomutant functional validation, multiple orthogonal readouts","pmids":["28325821"],"is_preprint":false},{"year":2019,"finding":"Cdk1 also phosphorylates Exo84 in late G1 phase (not only mitosis), disrupting exocyst complex assembly, inhibiting exocytic secretion, and arresting cell growth at the G1/S transition in budding yeast. Phosphodeficient and phosphomimetic exo84 mutants confirm this regulatory mechanism.","method":"CDK assay, immunoprecipitation, exocytic secretion assay, conditional cdc mutants, phosphodeficient/phosphomimetic mutant analysis, microscopy","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — direct CDK assay with mutant validation, single lab, multiple methods","pmids":["31171719"],"is_preprint":false},{"year":2012,"finding":"In C. elegans, exoc-8 (exo84 ortholog) loss-of-function causes behavioral defects and, in combination with rab-10 RNAi, causes a significant increase in endocytic vacuole size and upregulation of RAB-10 expression in intestinal epithelial cells, functionally linking EXOC8 to RAB-10-dependent endosomal trafficking.","method":"C. elegans mutant analysis, targeted RNAi screen for small GTPases, endocytic marker accumulation assay, fluorescence microscopy","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined trafficking phenotype and GTPase epistasis screen, single lab","pmids":["22389680"],"is_preprint":false},{"year":2012,"finding":"RalA binding to exocyst effectors Exo84 (EXOC8) and Sec5 is directly required for migration and invasion of prostate cancer cells; blocking RalA-Exocyst binding causes morphological changes and defects in single and coordinated cell migration.","method":"RalA-effector interaction blocking, cell migration assay, invasion assay, morphological analysis","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, indirect evidence blocking RalA-exocyst interaction without Exo84-specific mutants; does not isolate Exo84 from Sec5","pmids":["22761837"],"is_preprint":false},{"year":2025,"finding":"Active Merlin (NF2 tumor suppressor) competitively inhibits RalB binding to its exocyst effectors Sec5 and Exo84 (EXOC8) and regulates the kinetics of exocytosis in a RalB-dependent manner, as established by direct binding assays and proximity biotinylation.","method":"Proximity biotinylation (BioID), direct binding assays, competitive binding assay with RalB/Sec5/Exo84, exocytosis kinetics assay","journal":"bioRxiv","confidence":"Low","confidence_rationale":"Tier 3 / Weak — preprint, single lab, direct binding assay but Exo84-specific mechanistic detail is limited in the abstract","pmids":[],"is_preprint":true}],"current_model":"EXOC8 (Exo84) is an essential subunit of the octameric exocyst complex that tethers secretory vesicles to the plasma membrane for exocytosis; its C-terminal domain adopts an alpha-helical rod fold structurally homologous to Exo70, it is required for assembly of Sec10p/Sec15p/Exo70p into the complex, it binds active RalA/RalB GTPases through a PH-domain fold in competition with Sec5, and its activity is regulated by Cdk1-mediated phosphorylation during both late G1 and mitosis (disrupting exocyst assembly to arrest growth), as well as by TBK1-mediated phosphorylation downstream of insulin-stimulated RalA activation (controlling GLUT4 vesicle tethering and fusion at the plasma membrane in mammalian adipocytes)."},"narrative":{"mechanistic_narrative":"EXOC8 (Exo84) is an essential subunit of the octameric exocyst complex that tethers and docks post-Golgi secretory vesicles at sites of polarized secretion on the plasma membrane [PMID:10438536, PMID:15788396]. It is a structural organizing hub of the complex: its C-terminal domains form an ~80 Å alpha-helical rod fold structurally homologous to Exo70, and Exo84 incorporation is required for assembly of Sec10, Sec15, and Exo70 into the holocomplex, while its own assembly depends on Sec5 and Sec10 [PMID:16249794, PMID:15788396, PMID:10438536]. Through a pleckstrin-homology domain fold, Exo84 binds active RalA/RalB GTPases across both switch regions in competition with Sec5, providing a switch by which Ral signaling differentially controls exocyst assembly and vesicle tethering [PMID:15920473, PMID:28325821]. Exocyst function through Exo84 is gated by phosphorylation: Cdk1/Clb2 directly phosphorylates Exo84 in both late G1 and mitosis to disrupt complex assembly, inhibit exocytosis, and arrest cell-surface expansion [PMID:23836930, PMID:31171719], and in mammalian adipocytes TBK1 phosphorylates Exo84 downstream of insulin-stimulated RalA activation, lowering its RalA affinity to release it from the complex and drive GLUT4 vesicle fusion [PMID:28325821]. Beyond canonical secretion, EXOC8 contributes to apical epithelial polarity and recycling-endosome trafficking in metazoan models [PMID:17698923, PMID:22389680].","teleology":[{"year":1999,"claim":"Established EXOC8/Exo84 as a bona fide, essential exocyst subunit needed for vesicle targeting and docking, answering whether it physically belongs to the secretion machinery.","evidence":"Co-IP, velocity gradient co-sedimentation, two-hybrid, invertase secretion assay, EM and localization in yeast","pmids":["10438536"],"confidence":"High","gaps":["Did not define Exo84's molecular role in tethering beyond complex membership","No structural basis for subunit interactions"]},{"year":2005,"claim":"Defined the structural and assembly logic of Exo84, showing a conserved alpha-helical rod fold shared with Exo70 and a reciprocal assembly dependency that makes Exo84 a core organizer of the complex.","evidence":"X-ray crystallography of Exo84 and Exo70 C-terminal domains plus ts-mutant exocyst composition analysis in yeast","pmids":["16249794","15788396"],"confidence":"High","gaps":["Full octameric architecture not resolved","Mechanism by which Exo84 nucleates Sec10/Sec15/Exo70 incorporation not detailed"]},{"year":2005,"claim":"Revealed how Ral GTPases regulate the exocyst, showing Exo84 binds active RalA through a PH fold in direct competition with Sec5.","evidence":"Crystal structure of RBD-Exo84/RalA at 2.0 Å with mutagenesis and binding assays","pmids":["15920473"],"confidence":"High","gaps":["Functional consequence of Exo84-vs-Sec5 competition for vesicle tethering not established in this study","RalB binding not addressed"]},{"year":2001,"claim":"Proposed a non-canonical nuclear role linking Exo84 to U1 snRNP and pre-mRNA splicing, raising the question of moonlighting functions.","evidence":"Two-hybrid, co-IP with Snp1p, in vivo pre-mRNA accumulation and in vitro splicing assays in yeast","pmids":["11425851"],"confidence":"Medium","gaps":["Splicing defect could be indirect/secondary to ts-allele effects","Not connected to the exocyst's membrane function","No mammalian confirmation"]},{"year":2007,"claim":"Extended EXOC8 function to metazoan epithelial polarity, showing it is required for apical localization of polarity determinants and apical secretion.","evidence":"Drosophila exo84 mutant analysis, immunofluorescence, genetic epistasis with dlg/lgl","pmids":["17698923"],"confidence":"Medium","gaps":["Direct molecular partners in the apical pathway not defined","Single-organism, single-lab finding"]},{"year":2012,"claim":"Linked EXOC8 to RAB-10-dependent endosomal trafficking, broadening its role beyond plasma-membrane secretion to recycling-endosome dynamics.","evidence":"C. elegans exoc-8 loss-of-function with rab-10 RNAi, endocytic marker accumulation and small-GTPase epistasis screen","pmids":["22389680"],"confidence":"Medium","gaps":["Direct EXOC8-RAB-10 interaction not shown","Mechanism of endosome size control unresolved"]},{"year":2013,"claim":"Identified cell-cycle control of the exocyst via direct Cdk1/Clb2 phosphorylation of Exo84 in mitosis that disrupts assembly and halts surface expansion.","evidence":"CDK kinase assay, exocytosis readout and phospho-site mutants in budding yeast","pmids":["23836930"],"confidence":"High","gaps":["Phospho-acceptor residues' structural effect on assembly not detailed","Conservation in mammals untested"]},{"year":2014,"claim":"Showed phosphoregulation of Exo84 is rewired across species, with Candida Cdk1 phosphorylation reducing phosphatidylserine affinity to sustain hyphal growth rather than disrupting assembly.","evidence":"CDK assay, lipid-binding assay, phosphomutant localization in C. albicans","pmids":["24501427"],"confidence":"Medium","gaps":["Lipid-binding domain mapped indirectly","Single-lab, single-organism"]},{"year":2017,"claim":"Established a mammalian signaling axis in which TBK1 phosphorylates EXOC8 downstream of insulin/RalA to release it from the exocyst and enable GLUT4 vesicle fusion, requiring dynamic phosphocycling.","evidence":"In vitro kinase assay, TBK1 knockdown/KO/inhibition in adipocytes, RalA binding assay, phosphomutants, GLUT4 translocation and glucose uptake assays","pmids":["28325821"],"confidence":"High","gaps":["Phosphatase that reverses the modification not identified","Structural basis of reduced RalA affinity not resolved"]},{"year":2019,"claim":"Demonstrated Cdk1 phosphorylation of Exo84 also acts at the G1/S transition, generalizing exocyst phosphoregulation across multiple cell-cycle stages.","evidence":"CDK assay, exocytic secretion assay, conditional cdc mutants and phosphomutants in yeast","pmids":["31171719"],"confidence":"Medium","gaps":["Overlap/distinction with mitotic phospho-sites not fully resolved","Mammalian relevance untested"]},{"year":2025,"claim":"Proposed that Merlin/NF2 competitively inhibits RalB binding to Sec5 and Exo84 to tune exocytosis kinetics, implicating EXOC8 in tumor-suppressor-controlled secretion.","evidence":"BioID proximity biotinylation, competitive binding assays and exocytosis kinetics (preprint)","pmids":[],"confidence":"Low","gaps":["Preprint, single lab","Exo84-specific mechanistic detail limited","Functional consequence in tumor context not established"]},{"year":null,"claim":"How the multiple kinase inputs (Cdk1, TBK1) and Ral/Merlin binding states are integrated on EXOC8 to time exocyst assembly and disassembly in mammalian cells remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No phosphatase identified for any Exo84 phospho-site","No structure of the full mammalian exocyst showing Exo84 in context","Integration of cell-cycle and signaling phospho-inputs unknown"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,2,3]},{"term_id":"GO:0008289","term_label":"lipid binding","supporting_discovery_ids":[7]},{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[2]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,8]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[4,10]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,3,8]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1,8]},{"term_id":"R-HSA-1640170","term_label":"Cell Cycle","supporting_discovery_ids":[6,9]}],"complexes":["exocyst"],"partners":["SEC5","SEC10","RALA","RALB","TBK1","CDK1","SNP1","NF2"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q8IYI6","full_name":"Exocyst complex component 8","aliases":["Exocyst complex 84 kDa subunit"],"length_aa":725,"mass_kda":81.8,"function":"Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane","subcellular_location":"Cytoplasm; Cytoplasm, perinuclear region; Cell projection, growth cone; Cell projection","url":"https://www.uniprot.org/uniprotkb/Q8IYI6/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/EXOC8","classification":"Not Classified","n_dependent_lines":467,"n_total_lines":1208,"dependency_fraction":0.38658940397350994},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/EXOC8","total_profiled":1310},"omim":[{"mim_id":"619076","title":"NEURODEVELOPMENTAL DISORDER WITH MICROCEPHALY, SEIZURES, AND BRAIN ATROPHY; NEDMISB","url":"https://www.omim.org/entry/619076"},{"mim_id":"619072","title":"NEURODEVELOPMENTAL DISORDER WITH SEIZURES AND BRAIN ATROPHY; NEDSEBA","url":"https://www.omim.org/entry/619072"},{"mim_id":"617368","title":"SH3 DOMAIN-BINDING PROTEIN 1; SH3BP1","url":"https://www.omim.org/entry/617368"},{"mim_id":"615283","title":"EXOCYST COMPLEX COMPONENT 8; EXOC8","url":"https://www.omim.org/entry/615283"},{"mim_id":"613439","title":"CONSORTIN; CNST","url":"https://www.omim.org/entry/613439"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/EXOC8"},"hgnc":{"alias_symbol":["SEC84","EXO84","Exo84p"],"prev_symbol":[]},"alphafold":{"accession":"Q8IYI6","domains":[{"cath_id":"-","chopping":"23-77","consensus_level":"medium","plddt":78.2682,"start":23,"end":77},{"cath_id":"2.30.29.30","chopping":"168-294","consensus_level":"high","plddt":80.0513,"start":168,"end":294},{"cath_id":"-","chopping":"347-528","consensus_level":"high","plddt":82.2987,"start":347,"end":528},{"cath_id":"1.10.357","chopping":"546-714","consensus_level":"high","plddt":85.3208,"start":546,"end":714}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IYI6","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IYI6-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8IYI6-F1-predicted_aligned_error_v6.png","plddt_mean":73.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=EXOC8","jax_strain_url":"https://www.jax.org/strain/search?query=EXOC8"},"sequence":{"accession":"Q8IYI6","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8IYI6.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8IYI6/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8IYI6"}},"corpus_meta":[{"pmid":"10438536","id":"PMC_10438536","title":"Exo84p is an exocyst protein essential for secretion.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10438536","citation_count":160,"is_preprint":false},{"pmid":"15920473","id":"PMC_15920473","title":"Exo84 and Sec5 are competitive regulatory Sec6/8 effectors to the RalA GTPase.","date":"2005","source":"The EMBO journal","url":"https://pubmed.ncbi.nlm.nih.gov/15920473","citation_count":123,"is_preprint":false},{"pmid":"16249794","id":"PMC_16249794","title":"The structures of exocyst subunit Exo70p and the Exo84p C-terminal domains reveal a common motif.","date":"2005","source":"Nature structural & molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/16249794","citation_count":119,"is_preprint":false},{"pmid":"17698923","id":"PMC_17698923","title":"The Drosophila homolog of the Exo84 exocyst subunit promotes apical epithelial identity.","date":"2007","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/17698923","citation_count":100,"is_preprint":false},{"pmid":"15788396","id":"PMC_15788396","title":"The critical role of Exo84p in the organization and polarized localization of the exocyst complex.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15788396","citation_count":37,"is_preprint":false},{"pmid":"28325821","id":"PMC_28325821","title":"Phosphorylation of the exocyst protein Exo84 by TBK1 promotes insulin-stimulated GLUT4 trafficking.","date":"2017","source":"Science signaling","url":"https://pubmed.ncbi.nlm.nih.gov/28325821","citation_count":32,"is_preprint":false},{"pmid":"23836930","id":"PMC_23836930","title":"Mitotic phosphorylation of Exo84 disrupts exocyst assembly and arrests cell growth.","date":"2013","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/23836930","citation_count":29,"is_preprint":false},{"pmid":"24501427","id":"PMC_24501427","title":"In Candida albicans, phosphorylation of Exo84 by Cdk1-Hgc1 is necessary for efficient hyphal extension.","date":"2014","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/24501427","citation_count":27,"is_preprint":false},{"pmid":"11425851","id":"PMC_11425851","title":"New roles for the Snp1 and Exo84 proteins in yeast pre-mRNA splicing.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11425851","citation_count":25,"is_preprint":false},{"pmid":"32103185","id":"PMC_32103185","title":"Regulation of human cerebral cortical development by EXOC7 and EXOC8, components of the exocyst complex, and roles in neural progenitor cell proliferation and survival.","date":"2020","source":"Genetics in medicine : official journal of the American College of Medical Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32103185","citation_count":24,"is_preprint":false},{"pmid":"22761837","id":"PMC_22761837","title":"Sec5 and Exo84 mediate distinct aspects of RalA-dependent cell polarization.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22761837","citation_count":15,"is_preprint":false},{"pmid":"22389680","id":"PMC_22389680","title":"Exocyst subunits Exo70 and Exo84 cooperate with small GTPases to regulate behavior and endocytic trafficking in C. elegans.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/22389680","citation_count":14,"is_preprint":false},{"pmid":"35460391","id":"PMC_35460391","title":"A novel nonsense variant in EXOC8 underlies a neurodevelopmental disorder.","date":"2022","source":"Neurogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/35460391","citation_count":6,"is_preprint":false},{"pmid":"31171719","id":"PMC_31171719","title":"Cyclin-dependent kinase-mediated phosphorylation of the exocyst subunit Exo84 in late G1 phase suppresses exocytic secretion and cell growth in yeast.","date":"2019","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31171719","citation_count":6,"is_preprint":false},{"pmid":"40189122","id":"PMC_40189122","title":"EXOC8 of Epinephelus coioides involved in SGIV infection via innate immunity and apoptosis.","date":"2025","source":"Developmental and comparative immunology","url":"https://pubmed.ncbi.nlm.nih.gov/40189122","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2025.06.13.659557","title":"Active Merlin Binds RalB to Regulate Exocytosis","date":"2025-06-19","source":"bioRxiv","url":"https://doi.org/10.1101/2025.06.13.659557","citation_count":0,"is_preprint":true},{"pmid":null,"id":"bio_10.1101_2024.11.07.24316796","title":"Exploring the Molecular Pathways of Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease Using Proteomic Analysis","date":"2024-11-08","source":"bioRxiv","url":"https://doi.org/10.1101/2024.11.07.24316796","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9566,"output_tokens":3488,"usd":0.040509,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11017,"output_tokens":3546,"usd":0.071868,"stage2_stop_reason":"end_turn"},"total_usd":0.112377,"stage1_batch_id":"msgbatch_01AsR7g8dGTEiEw9U83bJeWn","stage2_batch_id":"msgbatch_01YV5ZyxtFNUZEjxRcpd9jzb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1999,\n      \"finding\": \"Exo84p (EXOC8) is an essential component of the yeast exocyst complex required for secretory vesicle targeting and docking at the plasma membrane; depletion causes invertase secretion defects and vesicle accumulation. Exo84p co-immunoprecipitates with other exocyst components, co-sediments with the exocyst complex in velocity gradients, and its assembly into the complex requires Sec5p and Sec10p. Exo84p interacts with Sec5p and Sec10p by two-hybrid assay, and overexpression selectively suppresses a sec5 temperature-sensitive mutant. Exo84p localizes to the bud tip/mother-daughter connection (sites of polarized secretion) and is mislocalized in a sec5 mutant.\",\n      \"method\": \"Co-immunoprecipitation, velocity gradient sedimentation, two-hybrid assay, invertase secretion assay, electron microscopy, fluorescence microscopy, genetic suppression\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (co-IP, sedimentation, two-hybrid, secretion assay, EM, localization, genetic suppression) in a foundational study\",\n      \"pmids\": [\"10438536\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The Ral-binding domain of Exo84 adopts a pleckstrin homology domain fold and binds active RalA through an extended interface involving both switch regions. Key residues in Exo84 and RalA determine binding specificity. Exo84 and Sec5 competitively bind to active RalA, establishing a mechanism by which Ral GTPases can differentially regulate exocyst assembly.\",\n      \"method\": \"Crystal structure of RBD-Exo84/RalA complex at 2.0 Å, mutagenesis, biochemical binding assays\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure plus mutagenesis-validated binding specificity, multiple orthogonal methods\",\n      \"pmids\": [\"15920473\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"The C-terminal domains of Exo84p form an 80 Å-long rod with an alpha-helical bundle fold that is structurally homologous to the N-terminal fold of Exo70p, revealing a common structural motif shared among exocyst subunits.\",\n      \"method\": \"X-ray crystallography (Exo84p C-terminal domains at 2.85 Å; Exo70p at 2.0 Å), structural comparison\",\n      \"journal\": \"Nature structural & molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structures of both domains with direct structural comparison and experimental validation of subunit interactions\",\n      \"pmids\": [\"16249794\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Exo84p is specifically involved in post-Golgi secretion and plays a critical role in exocyst complex assembly and polarized targeting. Pre-Golgi trafficking and polarized actin organization are required for Exo84p localization, but no single exocyst protein controls Exo84p polarization. Conversely, assembly of Sec10p, Sec15p, and Exo70p into the exocyst complex requires Exo84p.\",\n      \"method\": \"Temperature-sensitive yeast exo84 mutant analysis, electron microscopy, cargo traffic assays, fluorescence microscopy of exocyst localization, biochemical fractionation of exocyst composition\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (EM, cargo traffic, fluorescence microscopy, biochemical fractionation) in a systematic study\",\n      \"pmids\": [\"15788396\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"Drosophila Exo84 (ortholog of EXOC8) is required for apical epithelial identity; loss-of-function causes failure of apical localization of the Crumbs transmembrane protein, mislocalization of adherens junction proteins, defects in apical cuticle secretion, and accumulation of apical and adherens junction proteins in an expanded recycling endosome compartment.\",\n      \"method\": \"Drosophila exo84 mutant analysis, immunofluorescence microscopy, genetic epistasis with dlg/lgl reduction\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function with defined cellular phenotype and epistasis, single lab\",\n      \"pmids\": [\"17698923\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Yeast Exo84p physically associates with the U1 snRNP component Snp1p (two-hybrid and co-immunoprecipitation). A temperature-sensitive exo84 mutation causes increased pre-mRNA:mRNA ratios for RPL30 and actin transcripts, and causes a defect in splicing and prespliceosome formation in vitro, indicating a direct role for Exo84p in pre-mRNA splicing.\",\n      \"method\": \"Two-hybrid assay, co-immunoprecipitation, in vivo pre-mRNA accumulation assay, in vitro splicing assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP plus in vitro splicing assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"11425851\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"During mitosis in budding yeast, the cyclin-dependent kinase Cdk1 bound to mitotic cyclin Clb2 directly phosphorylates Exo84p. This phosphorylation disrupts exocyst complex assembly, inhibits exocytosis of select cargoes, and arrests cell surface expansion before the metaphase-anaphase transition.\",\n      \"method\": \"CDK kinase assay, immunoprecipitation, exocytosis assay, phosphorylation-site mutant analysis, fluorescence microscopy\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct kinase assay establishing phosphorylation, combined with mutant analysis and exocytosis readout, multiple orthogonal methods\",\n      \"pmids\": [\"23836930\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In Candida albicans, CaExo84 is phosphorylated by Cdk1 in a hyphal-specific cyclin Hgc1-dependent manner. Unlike in S. cerevisiae where phosphorylation disrupts exocyst assembly, CaExo84 phosphorylation does not alter its localization but reduces its affinity for phosphatidylserine, allowing it to recycle at the plasma membrane and promote continuous hyphal extension throughout mitosis.\",\n      \"method\": \"CDK phosphorylation assay, localization microscopy, phosphatidylserine binding assay, phosphodeficient/phosphomimetic mutant analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct kinase assay and lipid binding assay with mutants, single lab\",\n      \"pmids\": [\"24501427\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TBK1 phosphorylates the exocyst subunit Exo84 (EXOC8) upon RalA activation by insulin. Phosphorylation of Exo84 by TBK1 reduces its affinity for RalA, enabling Exo84 release from the exocyst complex and facilitating GLUT4 vesicle fusion at the plasma membrane. Phosphorylation-mimicking or nonphosphorylatable Exo84 mutants both block insulin-stimulated GLUT4 translocation, indicating that dynamic cycling of Exo84 phosphorylation state is required.\",\n      \"method\": \"In vitro kinase assay, TBK1 knockdown/knockout in adipocytes, dominant-negative TBK1 overexpression, TBK1 inhibitor treatment, RalA binding assay, phosphomimetic/phosphodeficient mutant analysis, GLUT4 translocation assay, glucose uptake assay\",\n      \"journal\": \"Science signaling\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct kinase assay, multiple genetic and pharmacological perturbations, phosphomutant functional validation, multiple orthogonal readouts\",\n      \"pmids\": [\"28325821\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Cdk1 also phosphorylates Exo84 in late G1 phase (not only mitosis), disrupting exocyst complex assembly, inhibiting exocytic secretion, and arresting cell growth at the G1/S transition in budding yeast. Phosphodeficient and phosphomimetic exo84 mutants confirm this regulatory mechanism.\",\n      \"method\": \"CDK assay, immunoprecipitation, exocytic secretion assay, conditional cdc mutants, phosphodeficient/phosphomimetic mutant analysis, microscopy\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — direct CDK assay with mutant validation, single lab, multiple methods\",\n      \"pmids\": [\"31171719\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"In C. elegans, exoc-8 (exo84 ortholog) loss-of-function causes behavioral defects and, in combination with rab-10 RNAi, causes a significant increase in endocytic vacuole size and upregulation of RAB-10 expression in intestinal epithelial cells, functionally linking EXOC8 to RAB-10-dependent endosomal trafficking.\",\n      \"method\": \"C. elegans mutant analysis, targeted RNAi screen for small GTPases, endocytic marker accumulation assay, fluorescence microscopy\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined trafficking phenotype and GTPase epistasis screen, single lab\",\n      \"pmids\": [\"22389680\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"RalA binding to exocyst effectors Exo84 (EXOC8) and Sec5 is directly required for migration and invasion of prostate cancer cells; blocking RalA-Exocyst binding causes morphological changes and defects in single and coordinated cell migration.\",\n      \"method\": \"RalA-effector interaction blocking, cell migration assay, invasion assay, morphological analysis\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, indirect evidence blocking RalA-exocyst interaction without Exo84-specific mutants; does not isolate Exo84 from Sec5\",\n      \"pmids\": [\"22761837\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Active Merlin (NF2 tumor suppressor) competitively inhibits RalB binding to its exocyst effectors Sec5 and Exo84 (EXOC8) and regulates the kinetics of exocytosis in a RalB-dependent manner, as established by direct binding assays and proximity biotinylation.\",\n      \"method\": \"Proximity biotinylation (BioID), direct binding assays, competitive binding assay with RalB/Sec5/Exo84, exocytosis kinetics assay\",\n      \"journal\": \"bioRxiv\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — preprint, single lab, direct binding assay but Exo84-specific mechanistic detail is limited in the abstract\",\n      \"pmids\": [],\n      \"is_preprint\": true\n    }\n  ],\n  \"current_model\": \"EXOC8 (Exo84) is an essential subunit of the octameric exocyst complex that tethers secretory vesicles to the plasma membrane for exocytosis; its C-terminal domain adopts an alpha-helical rod fold structurally homologous to Exo70, it is required for assembly of Sec10p/Sec15p/Exo70p into the complex, it binds active RalA/RalB GTPases through a PH-domain fold in competition with Sec5, and its activity is regulated by Cdk1-mediated phosphorylation during both late G1 and mitosis (disrupting exocyst assembly to arrest growth), as well as by TBK1-mediated phosphorylation downstream of insulin-stimulated RalA activation (controlling GLUT4 vesicle tethering and fusion at the plasma membrane in mammalian adipocytes).\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"EXOC8 (Exo84) is an essential subunit of the octameric exocyst complex that tethers and docks post-Golgi secretory vesicles at sites of polarized secretion on the plasma membrane [#0, #3]. It is a structural organizing hub of the complex: its C-terminal domains form an ~80 Å alpha-helical rod fold structurally homologous to Exo70, and Exo84 incorporation is required for assembly of Sec10, Sec15, and Exo70 into the holocomplex, while its own assembly depends on Sec5 and Sec10 [#2, #3, #0]. Through a pleckstrin-homology domain fold, Exo84 binds active RalA/RalB GTPases across both switch regions in competition with Sec5, providing a switch by which Ral signaling differentially controls exocyst assembly and vesicle tethering [#1, #8]. Exocyst function through Exo84 is gated by phosphorylation: Cdk1/Clb2 directly phosphorylates Exo84 in both late G1 and mitosis to disrupt complex assembly, inhibit exocytosis, and arrest cell-surface expansion [#6, #9], and in mammalian adipocytes TBK1 phosphorylates Exo84 downstream of insulin-stimulated RalA activation, lowering its RalA affinity to release it from the complex and drive GLUT4 vesicle fusion [#8]. Beyond canonical secretion, EXOC8 contributes to apical epithelial polarity and recycling-endosome trafficking in metazoan models [#4, #10].\",\n  \"teleology\": [\n    {\n      \"year\": 1999,\n      \"claim\": \"Established EXOC8/Exo84 as a bona fide, essential exocyst subunit needed for vesicle targeting and docking, answering whether it physically belongs to the secretion machinery.\",\n      \"evidence\": \"Co-IP, velocity gradient co-sedimentation, two-hybrid, invertase secretion assay, EM and localization in yeast\",\n      \"pmids\": [\"10438536\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not define Exo84's molecular role in tethering beyond complex membership\", \"No structural basis for subunit interactions\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Defined the structural and assembly logic of Exo84, showing a conserved alpha-helical rod fold shared with Exo70 and a reciprocal assembly dependency that makes Exo84 a core organizer of the complex.\",\n      \"evidence\": \"X-ray crystallography of Exo84 and Exo70 C-terminal domains plus ts-mutant exocyst composition analysis in yeast\",\n      \"pmids\": [\"16249794\", \"15788396\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Full octameric architecture not resolved\", \"Mechanism by which Exo84 nucleates Sec10/Sec15/Exo70 incorporation not detailed\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Revealed how Ral GTPases regulate the exocyst, showing Exo84 binds active RalA through a PH fold in direct competition with Sec5.\",\n      \"evidence\": \"Crystal structure of RBD-Exo84/RalA at 2.0 Å with mutagenesis and binding assays\",\n      \"pmids\": [\"15920473\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Functional consequence of Exo84-vs-Sec5 competition for vesicle tethering not established in this study\", \"RalB binding not addressed\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Proposed a non-canonical nuclear role linking Exo84 to U1 snRNP and pre-mRNA splicing, raising the question of moonlighting functions.\",\n      \"evidence\": \"Two-hybrid, co-IP with Snp1p, in vivo pre-mRNA accumulation and in vitro splicing assays in yeast\",\n      \"pmids\": [\"11425851\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Splicing defect could be indirect/secondary to ts-allele effects\", \"Not connected to the exocyst's membrane function\", \"No mammalian confirmation\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Extended EXOC8 function to metazoan epithelial polarity, showing it is required for apical localization of polarity determinants and apical secretion.\",\n      \"evidence\": \"Drosophila exo84 mutant analysis, immunofluorescence, genetic epistasis with dlg/lgl\",\n      \"pmids\": [\"17698923\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct molecular partners in the apical pathway not defined\", \"Single-organism, single-lab finding\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Linked EXOC8 to RAB-10-dependent endosomal trafficking, broadening its role beyond plasma-membrane secretion to recycling-endosome dynamics.\",\n      \"evidence\": \"C. elegans exoc-8 loss-of-function with rab-10 RNAi, endocytic marker accumulation and small-GTPase epistasis screen\",\n      \"pmids\": [\"22389680\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct EXOC8-RAB-10 interaction not shown\", \"Mechanism of endosome size control unresolved\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Identified cell-cycle control of the exocyst via direct Cdk1/Clb2 phosphorylation of Exo84 in mitosis that disrupts assembly and halts surface expansion.\",\n      \"evidence\": \"CDK kinase assay, exocytosis readout and phospho-site mutants in budding yeast\",\n      \"pmids\": [\"23836930\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Phospho-acceptor residues' structural effect on assembly not detailed\", \"Conservation in mammals untested\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Showed phosphoregulation of Exo84 is rewired across species, with Candida Cdk1 phosphorylation reducing phosphatidylserine affinity to sustain hyphal growth rather than disrupting assembly.\",\n      \"evidence\": \"CDK assay, lipid-binding assay, phosphomutant localization in C. albicans\",\n      \"pmids\": [\"24501427\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Lipid-binding domain mapped indirectly\", \"Single-lab, single-organism\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Established a mammalian signaling axis in which TBK1 phosphorylates EXOC8 downstream of insulin/RalA to release it from the exocyst and enable GLUT4 vesicle fusion, requiring dynamic phosphocycling.\",\n      \"evidence\": \"In vitro kinase assay, TBK1 knockdown/KO/inhibition in adipocytes, RalA binding assay, phosphomutants, GLUT4 translocation and glucose uptake assays\",\n      \"pmids\": [\"28325821\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Phosphatase that reverses the modification not identified\", \"Structural basis of reduced RalA affinity not resolved\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Demonstrated Cdk1 phosphorylation of Exo84 also acts at the G1/S transition, generalizing exocyst phosphoregulation across multiple cell-cycle stages.\",\n      \"evidence\": \"CDK assay, exocytic secretion assay, conditional cdc mutants and phosphomutants in yeast\",\n      \"pmids\": [\"31171719\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Overlap/distinction with mitotic phospho-sites not fully resolved\", \"Mammalian relevance untested\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Proposed that Merlin/NF2 competitively inhibits RalB binding to Sec5 and Exo84 to tune exocytosis kinetics, implicating EXOC8 in tumor-suppressor-controlled secretion.\",\n      \"evidence\": \"BioID proximity biotinylation, competitive binding assays and exocytosis kinetics (preprint)\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Preprint, single lab\", \"Exo84-specific mechanistic detail limited\", \"Functional consequence in tumor context not established\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the multiple kinase inputs (Cdk1, TBK1) and Ral/Merlin binding states are integrated on EXOC8 to time exocyst assembly and disassembly in mammalian cells remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No phosphatase identified for any Exo84 phospho-site\", \"No structure of the full mammalian exocyst showing Exo84 in context\", \"Integration of cell-cycle and signaling phospho-inputs unknown\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 2, 3]},\n      {\"term_id\": \"GO:0008289\", \"supporting_discovery_ids\": [7]},\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 8]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [4, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 3, 8]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1, 8]},\n      {\"term_id\": \"R-HSA-1640170\", \"supporting_discovery_ids\": [6, 9]}\n    ],\n    \"complexes\": [\"exocyst\"],\n    \"partners\": [\"SEC5\", \"SEC10\", \"RALA\", \"RALB\", \"TBK1\", \"CDK1\", \"SNP1\", \"NF2\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":5,"faith_pct":100.0}}