{"gene":"TRAPPC13","run_date":"2026-06-10T10:51:55","timeline":{"discoveries":[{"year":2017,"finding":"Human TRAPPC13 is a subunit of a mammalian TRAPPIII complex that is critically involved in the survival response to Golgi-disrupting agents. Loss of TRAPPC13 partially preserves the secretory pathway and viability in response to brefeldin A, in a manner dependent on ARF1 and the large GEF GBF1, with concomitant reduced caspase activation and ER stress marker induction. TRAPPC13 depletion reduces Rab1a and Rab1b activity, impairs autophagic flux, and increases susceptibility to Shigella flexneri infection.","method":"siRNA knockdown, cell viability assays, caspase activation measurement, ER stress marker induction, Rab1a/Rab1b GTPase activity assays, autophagy flux assays, bacterial infectivity assay","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KD with multiple defined cellular phenotype readouts (Rab activity, autophagy flux, caspase activation), single lab, multiple orthogonal methods","pmids":["28536105"],"is_preprint":false},{"year":2021,"finding":"TRAPPC13 is a TRAPPIII-specific subunit in the mammalian TRAPPIII complex (alongside TRAPPC8, TRAPPC11, TRAPPC12). The TRAPPIII complex exhibits GEF activity specifically toward Rab1 and Rab43, with no detectable activity against 18 other Rabs tested. TRAPPIII complex-specific subunits confer differences in protein dynamics at the Rab binding site compared to TRAPPII, and GEF activity is enhanced on lipid membranes.","method":"Biochemical GEF assays (fluorescence-based nucleotide exchange), hydrogen-deuterium exchange mass spectrometry (HDX-MS), electron microscopy, reconstituted complexes on lipid membranes","journal":"Journal of molecular biology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of TRAPPIII complex, GEF assays with panel of 20 Rabs, HDX-MS structural dynamics, membrane reconstitution, multiple orthogonal methods in single rigorous study","pmids":["34229011"],"is_preprint":false},{"year":2016,"finding":"TRAPPC13 localizes highly enriched at the base of primary cilia (ciliary base/centrosomal region) in human hTERT-RPE1 cells, as determined by expression of epitope-tagged full-length and truncated constructs combined with quantitative immunofluorescence microscopy.","method":"Epitope-tagged overexpression, quantitative immunofluorescence microscopy, western blotting in hTERT-RPE1 cells","journal":"Methods in molecular biology (Clifton, N.J.)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, overexpression-based localization only, no functional consequence established for the ciliary localization","pmids":["27514913"],"is_preprint":false},{"year":2019,"finding":"Aspergillus nidulans TRAPPIII contains homologues of metazoan TRAPPC11, TRAPPC12, and TRAPPC13 subunits, which are absent in S. cerevisiae. These subunits are recruited to the TRAPPIII complex by Tca17/TRAPPC2L, which binds to the 'Trs33 side' of the core complex. Genetic analysis using constitutively-active (GEF-independent) RAB1* alleles established that TRAPPIII's essential role is activation of RAB1.","method":"Size-fractionation chromatography, single-step purification coupled to mass spectrometry, negative-stain electron microscopy, constitutively-active RAB mutant genetic epistasis in A. nidulans null mutants","journal":"PLoS genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal biochemical and genetic methods in a fungal ortholog system, compositional and epistasis evidence, single study","pmids":["31869332"],"is_preprint":false},{"year":2025,"finding":"In Fusarium graminearum, TRAPPC13 is a TRAPPIII-specific subunit that collaborates with FgTrs85 (core subunit), TRAPPC11, and TRAPPC12. TRAPPC13 interacts with FgTrs85 to promote autophagosome biogenesis by recruiting FgAtg9 to the phagophore assembly site. Overexpression of constitutively active FgRab1-GTP suppresses phenotypic defects of TRAPPIII mutants, supporting TRAPPIII's function as a GEF for Rab1.","method":"Genetic deletion/functional analysis, localization studies, protein interaction assays, constitutively-active Rab1-GTP epistasis rescue experiments in F. graminearum","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with constitutively-active Rab1, interaction evidence, multiple phenotypic readouts; fungal ortholog system, single lab","pmids":["41134853"],"is_preprint":false}],"current_model":"TRAPPC13 is a subunit specific to the TRAPPIII complex (alongside TRAPPC8, TRAPPC11, TRAPPC12), which functions as a guanine nucleotide exchange factor (GEF) activating Rab1 (and Rab43) to regulate ER-to-Golgi trafficking, autophagic flux, and the cellular response to Golgi stress; TRAPPC13 loss reduces Rab1 activity, impairs autophagy, and modulates cell survival under Golgi-disrupting conditions in a GBF1/ARF1-dependent manner, and the protein also localizes to the base of primary cilia."},"narrative":{"mechanistic_narrative":"TRAPPC13 is a TRAPPIII-specific subunit of the mammalian TRAPP complex that, together with TRAPPC8, TRAPPC11, and TRAPPC12, contributes to a guanine nucleotide exchange factor (GEF) activity directed specifically at Rab1 and Rab43, with no detectable activity against 18 other Rabs and enhanced exchange on lipid membranes [PMID:34229011]. Through this Rab1-activating function, TRAPPC13 supports ER-to-Golgi trafficking, autophagic flux, and the cellular survival response to Golgi-disrupting stress: its depletion lowers Rab1a/Rab1b activity, impairs autophagy, and increases susceptibility to Shigella flexneri infection, while paradoxically preserving the secretory pathway and viability after brefeldin A treatment in a GBF1/ARF1-dependent manner with reduced caspase activation and ER stress [PMID:28536105]. The TRAPPIII-specific role in Rab1 activation is conserved in fungi, where constitutively active Rab1-GTP rescues TRAPPIII-mutant defects, and where TRAPPC13 cooperates with the core subunit Trs85 to drive autophagosome biogenesis by recruiting Atg9 to the phagophore assembly site [PMID:31869332, PMID:41134853]. Beyond these functions, the structural basis of how TRAPPC13 specifically tunes Rab-site dynamics and its reported enrichment at the base of primary cilia have not been mechanistically resolved in the available corpus.","teleology":[{"year":2016,"claim":"Established a candidate subcellular address for TRAPPC13, placing it at the ciliary base/centrosomal region and raising the question of a ciliary role distinct from bulk Golgi trafficking.","evidence":"epitope-tagged overexpression and quantitative immunofluorescence in hTERT-RPE1 cells","pmids":["27514913"],"confidence":"Low","gaps":["Overexpression-based localization only, not validated at endogenous levels","No functional consequence established for the ciliary localization","Relationship between ciliary-base pool and TRAPPIII trafficking function unknown"]},{"year":2017,"claim":"Defined TRAPPC13 as a TRAPPIII subunit with a measurable cellular function, linking it to Rab1 activation, autophagic flux, and a survival response to Golgi stress.","evidence":"siRNA knockdown with Rab1a/Rab1b activity assays, autophagy flux, caspase/ER-stress readouts, and Shigella infectivity in human cells","pmids":["28536105"],"confidence":"Medium","gaps":["Did not establish direct GEF activity biochemically","Mechanism by which TRAPPC13 loss preserves viability via GBF1/ARF1 not resolved","Single lab, knockdown-based"]},{"year":2019,"claim":"Used fungal genetics to show that the essential role of TRAPPIII (containing the TRAPPC11/12/13 module) is activation of Rab1, and that these metazoan-type subunits are recruited via Tca17/TRAPPC2L.","evidence":"size-fractionation, MS, negative-stain EM, and constitutively-active RAB1* epistasis in Aspergillus nidulans null mutants","pmids":["31869332"],"confidence":"Medium","gaps":["Specific contribution of TRAPPC13 versus other subunits to GEF activity not isolated","Conducted in fungal ortholog system","Subunit recruitment hierarchy in mammalian complex not directly tested"]},{"year":2021,"claim":"Provided direct biochemical proof that the reconstituted TRAPPIII complex is a Rab1/Rab43-specific GEF and that complex-specific subunits alter dynamics at the Rab binding site.","evidence":"in vitro GEF assays against a panel of 20 Rabs, HDX-MS, EM, and membrane-reconstituted complexes","pmids":["34229011"],"confidence":"High","gaps":["The individual catalytic contribution of TRAPPC13 within the complex was not isolated","No high-resolution structure of the TRAPPC13-containing complex with Rab","Physiological substrate selection between Rab1 and Rab43 in cells not addressed"]},{"year":2025,"claim":"Connected TRAPPIII Rab1 activation to a concrete autophagy step, showing TRAPPC13 cooperates with Trs85 to recruit Atg9 to the phagophore assembly site.","evidence":"genetic deletion, localization, interaction assays, and constitutively-active Rab1-GTP rescue in Fusarium graminearum","pmids":["41134853"],"confidence":"Medium","gaps":["Direct TRAPPC13-Atg9 interaction versus indirect recruitment not distinguished","Conducted in fungal ortholog system","Whether mammalian TRAPPC13 recruits ATG9 by the same mechanism untested"]},{"year":null,"claim":"How TRAPPC13 specifically shapes Rab-site dynamics within TRAPPIII and whether its ciliary-base localization reflects a distinct function remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structure of TRAPPC13 within the assembled mammalian TRAPPIII-Rab complex","Functional role of ciliary-base localization uncharacterized","Per-subunit dissection of GEF catalysis not performed"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[0,1,3,4]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0,1]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[2]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[0,4]}],"complexes":["TRAPPIII"],"partners":["TRAPPC8","TRAPPC11","TRAPPC12","TRAPPC2L","TRS85"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"A5PLN9","full_name":"Trafficking protein particle complex subunit 13","aliases":[],"length_aa":417,"mass_kda":46.5,"function":"","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/A5PLN9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TRAPPC13","classification":"Not Classified","n_dependent_lines":112,"n_total_lines":1208,"dependency_fraction":0.09271523178807947},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"TRAPPC1","stoichiometry":10.0},{"gene":"TRAPPC11","stoichiometry":10.0},{"gene":"TRAPPC2","stoichiometry":10.0},{"gene":"ARL3","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TRAPPC13","total_profiled":1310},"omim":[{"mim_id":"621423","title":"TRAFFICKING PROTEIN PARTICLE COMPLEX, SUBUNIT 13; TRAPPC13","url":"https://www.omim.org/entry/621423"},{"mim_id":"618030","title":"SHIELD COMPLEX, SUBUNIT 3; SHLD3","url":"https://www.omim.org/entry/618030"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"},{"location":"Plasma membrane","reliability":"Approved"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TRAPPC13"},"hgnc":{"alias_symbol":["FLJ13611","MGC48585"],"prev_symbol":["C5orf44"]},"alphafold":{"accession":"A5PLN9","domains":[{"cath_id":"2.60.40.10","chopping":"11-18_68-168","consensus_level":"high","plddt":91.4812,"start":11,"end":168},{"cath_id":"2.60.40.1230","chopping":"171-296","consensus_level":"high","plddt":84.866,"start":171,"end":296},{"cath_id":"2.60.40.10","chopping":"305-408","consensus_level":"high","plddt":92.9917,"start":305,"end":408}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/A5PLN9","model_url":"https://alphafold.ebi.ac.uk/files/AF-A5PLN9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-A5PLN9-F1-predicted_aligned_error_v6.png","plddt_mean":86.75},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TRAPPC13","jax_strain_url":"https://www.jax.org/strain/search?query=TRAPPC13"},"sequence":{"accession":"A5PLN9","fasta_url":"https://rest.uniprot.org/uniprotkb/A5PLN9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/A5PLN9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/A5PLN9"}},"corpus_meta":[{"pmid":"28536105","id":"PMC_28536105","title":"TRAPPC13 modulates autophagy and the response to Golgi stress.","date":"2017","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/28536105","citation_count":40,"is_preprint":false},{"pmid":"31374089","id":"PMC_31374089","title":"Subclinical endometritis in dairy cattle is associated with distinct mRNA expression patterns in blood and endometrium.","date":"2019","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/31374089","citation_count":24,"is_preprint":false},{"pmid":"31869332","id":"PMC_31869332","title":"Characterization of Aspergillus nidulans TRAPPs uncovers unprecedented similarities between fungi and metazoans and reveals the modular assembly of TRAPPII.","date":"2019","source":"PLoS genetics","url":"https://pubmed.ncbi.nlm.nih.gov/31869332","citation_count":23,"is_preprint":false},{"pmid":"34229011","id":"PMC_34229011","title":"Biochemical Insight into Novel Rab-GEF Activity of the Mammalian TRAPPIII Complex.","date":"2021","source":"Journal of molecular biology","url":"https://pubmed.ncbi.nlm.nih.gov/34229011","citation_count":15,"is_preprint":false},{"pmid":"33630651","id":"PMC_33630651","title":"TRAPPC13 Is a Novel Target of Mesorhizobium amorphae Type III Secretion System Effector NopP.","date":"2021","source":"Molecular plant-microbe interactions : MPMI","url":"https://pubmed.ncbi.nlm.nih.gov/33630651","citation_count":8,"is_preprint":false},{"pmid":"27514913","id":"PMC_27514913","title":"Targeting of ASH Domain-Containing Proteins to the Centrosome.","date":"2016","source":"Methods in molecular biology (Clifton, N.J.)","url":"https://pubmed.ncbi.nlm.nih.gov/27514913","citation_count":7,"is_preprint":false},{"pmid":"41972297","id":"PMC_41972297","title":"Machine Learning Identifies TRAPPC13/COPS5 as Biomarkers and Vesicle Transport Subtypes in Parkinson's Disease.","date":"2026","source":"The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques","url":"https://pubmed.ncbi.nlm.nih.gov/41972297","citation_count":0,"is_preprint":false},{"pmid":"41134853","id":"PMC_41134853","title":"The TRAPPIII complex regulates development and virulence of Fusarium graminearum by coordinating autophagy and intracellular transport.","date":"2025","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/41134853","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6468,"output_tokens":1627,"usd":0.021905,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":8390,"output_tokens":2435,"usd":0.051412,"stage2_stop_reason":"end_turn"},"total_usd":0.073317,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"Human TRAPPC13 is a subunit of a mammalian TRAPPIII complex that is critically involved in the survival response to Golgi-disrupting agents. Loss of TRAPPC13 partially preserves the secretory pathway and viability in response to brefeldin A, in a manner dependent on ARF1 and the large GEF GBF1, with concomitant reduced caspase activation and ER stress marker induction. TRAPPC13 depletion reduces Rab1a and Rab1b activity, impairs autophagic flux, and increases susceptibility to Shigella flexneri infection.\",\n      \"method\": \"siRNA knockdown, cell viability assays, caspase activation measurement, ER stress marker induction, Rab1a/Rab1b GTPase activity assays, autophagy flux assays, bacterial infectivity assay\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KD with multiple defined cellular phenotype readouts (Rab activity, autophagy flux, caspase activation), single lab, multiple orthogonal methods\",\n      \"pmids\": [\"28536105\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"TRAPPC13 is a TRAPPIII-specific subunit in the mammalian TRAPPIII complex (alongside TRAPPC8, TRAPPC11, TRAPPC12). The TRAPPIII complex exhibits GEF activity specifically toward Rab1 and Rab43, with no detectable activity against 18 other Rabs tested. TRAPPIII complex-specific subunits confer differences in protein dynamics at the Rab binding site compared to TRAPPII, and GEF activity is enhanced on lipid membranes.\",\n      \"method\": \"Biochemical GEF assays (fluorescence-based nucleotide exchange), hydrogen-deuterium exchange mass spectrometry (HDX-MS), electron microscopy, reconstituted complexes on lipid membranes\",\n      \"journal\": \"Journal of molecular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of TRAPPIII complex, GEF assays with panel of 20 Rabs, HDX-MS structural dynamics, membrane reconstitution, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"34229011\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"TRAPPC13 localizes highly enriched at the base of primary cilia (ciliary base/centrosomal region) in human hTERT-RPE1 cells, as determined by expression of epitope-tagged full-length and truncated constructs combined with quantitative immunofluorescence microscopy.\",\n      \"method\": \"Epitope-tagged overexpression, quantitative immunofluorescence microscopy, western blotting in hTERT-RPE1 cells\",\n      \"journal\": \"Methods in molecular biology (Clifton, N.J.)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, overexpression-based localization only, no functional consequence established for the ciliary localization\",\n      \"pmids\": [\"27514913\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Aspergillus nidulans TRAPPIII contains homologues of metazoan TRAPPC11, TRAPPC12, and TRAPPC13 subunits, which are absent in S. cerevisiae. These subunits are recruited to the TRAPPIII complex by Tca17/TRAPPC2L, which binds to the 'Trs33 side' of the core complex. Genetic analysis using constitutively-active (GEF-independent) RAB1* alleles established that TRAPPIII's essential role is activation of RAB1.\",\n      \"method\": \"Size-fractionation chromatography, single-step purification coupled to mass spectrometry, negative-stain electron microscopy, constitutively-active RAB mutant genetic epistasis in A. nidulans null mutants\",\n      \"journal\": \"PLoS genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal biochemical and genetic methods in a fungal ortholog system, compositional and epistasis evidence, single study\",\n      \"pmids\": [\"31869332\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In Fusarium graminearum, TRAPPC13 is a TRAPPIII-specific subunit that collaborates with FgTrs85 (core subunit), TRAPPC11, and TRAPPC12. TRAPPC13 interacts with FgTrs85 to promote autophagosome biogenesis by recruiting FgAtg9 to the phagophore assembly site. Overexpression of constitutively active FgRab1-GTP suppresses phenotypic defects of TRAPPIII mutants, supporting TRAPPIII's function as a GEF for Rab1.\",\n      \"method\": \"Genetic deletion/functional analysis, localization studies, protein interaction assays, constitutively-active Rab1-GTP epistasis rescue experiments in F. graminearum\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with constitutively-active Rab1, interaction evidence, multiple phenotypic readouts; fungal ortholog system, single lab\",\n      \"pmids\": [\"41134853\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TRAPPC13 is a subunit specific to the TRAPPIII complex (alongside TRAPPC8, TRAPPC11, TRAPPC12), which functions as a guanine nucleotide exchange factor (GEF) activating Rab1 (and Rab43) to regulate ER-to-Golgi trafficking, autophagic flux, and the cellular response to Golgi stress; TRAPPC13 loss reduces Rab1 activity, impairs autophagy, and modulates cell survival under Golgi-disrupting conditions in a GBF1/ARF1-dependent manner, and the protein also localizes to the base of primary cilia.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TRAPPC13 is a TRAPPIII-specific subunit of the mammalian TRAPP complex that, together with TRAPPC8, TRAPPC11, and TRAPPC12, contributes to a guanine nucleotide exchange factor (GEF) activity directed specifically at Rab1 and Rab43, with no detectable activity against 18 other Rabs and enhanced exchange on lipid membranes [#1]. Through this Rab1-activating function, TRAPPC13 supports ER-to-Golgi trafficking, autophagic flux, and the cellular survival response to Golgi-disrupting stress: its depletion lowers Rab1a/Rab1b activity, impairs autophagy, and increases susceptibility to Shigella flexneri infection, while paradoxically preserving the secretory pathway and viability after brefeldin A treatment in a GBF1/ARF1-dependent manner with reduced caspase activation and ER stress [#0]. The TRAPPIII-specific role in Rab1 activation is conserved in fungi, where constitutively active Rab1-GTP rescues TRAPPIII-mutant defects, and where TRAPPC13 cooperates with the core subunit Trs85 to drive autophagosome biogenesis by recruiting Atg9 to the phagophore assembly site [#3, #4]. Beyond these functions, the structural basis of how TRAPPC13 specifically tunes Rab-site dynamics and its reported enrichment at the base of primary cilia have not been mechanistically resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Established a candidate subcellular address for TRAPPC13, placing it at the ciliary base/centrosomal region and raising the question of a ciliary role distinct from bulk Golgi trafficking.\",\n      \"evidence\": \"epitope-tagged overexpression and quantitative immunofluorescence in hTERT-RPE1 cells\",\n      \"pmids\": [\"27514913\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Overexpression-based localization only, not validated at endogenous levels\",\n        \"No functional consequence established for the ciliary localization\",\n        \"Relationship between ciliary-base pool and TRAPPIII trafficking function unknown\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Defined TRAPPC13 as a TRAPPIII subunit with a measurable cellular function, linking it to Rab1 activation, autophagic flux, and a survival response to Golgi stress.\",\n      \"evidence\": \"siRNA knockdown with Rab1a/Rab1b activity assays, autophagy flux, caspase/ER-stress readouts, and Shigella infectivity in human cells\",\n      \"pmids\": [\"28536105\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Did not establish direct GEF activity biochemically\",\n        \"Mechanism by which TRAPPC13 loss preserves viability via GBF1/ARF1 not resolved\",\n        \"Single lab, knockdown-based\"\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Used fungal genetics to show that the essential role of TRAPPIII (containing the TRAPPC11/12/13 module) is activation of Rab1, and that these metazoan-type subunits are recruited via Tca17/TRAPPC2L.\",\n      \"evidence\": \"size-fractionation, MS, negative-stain EM, and constitutively-active RAB1* epistasis in Aspergillus nidulans null mutants\",\n      \"pmids\": [\"31869332\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific contribution of TRAPPC13 versus other subunits to GEF activity not isolated\",\n        \"Conducted in fungal ortholog system\",\n        \"Subunit recruitment hierarchy in mammalian complex not directly tested\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Provided direct biochemical proof that the reconstituted TRAPPIII complex is a Rab1/Rab43-specific GEF and that complex-specific subunits alter dynamics at the Rab binding site.\",\n      \"evidence\": \"in vitro GEF assays against a panel of 20 Rabs, HDX-MS, EM, and membrane-reconstituted complexes\",\n      \"pmids\": [\"34229011\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The individual catalytic contribution of TRAPPC13 within the complex was not isolated\",\n        \"No high-resolution structure of the TRAPPC13-containing complex with Rab\",\n        \"Physiological substrate selection between Rab1 and Rab43 in cells not addressed\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Connected TRAPPIII Rab1 activation to a concrete autophagy step, showing TRAPPC13 cooperates with Trs85 to recruit Atg9 to the phagophore assembly site.\",\n      \"evidence\": \"genetic deletion, localization, interaction assays, and constitutively-active Rab1-GTP rescue in Fusarium graminearum\",\n      \"pmids\": [\"41134853\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct TRAPPC13-Atg9 interaction versus indirect recruitment not distinguished\",\n        \"Conducted in fungal ortholog system\",\n        \"Whether mammalian TRAPPC13 recruits ATG9 by the same mechanism untested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TRAPPC13 specifically shapes Rab-site dynamics within TRAPPIII and whether its ciliary-base localization reflects a distinct function remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structure of TRAPPC13 within the assembled mammalian TRAPPIII-Rab complex\",\n        \"Functional role of ciliary-base localization uncharacterized\",\n        \"Per-subunit dissection of GEF catalysis not performed\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [0, 1, 3, 4]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"complexes\": [\n      \"TRAPPIII\"\n    ],\n    \"partners\": [\n      \"TRAPPC8\",\n      \"TRAPPC11\",\n      \"TRAPPC12\",\n      \"TRAPPC2L\",\n      \"TRS85\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"faith_supported":3,"faith_total":3,"faith_pct":100.0}}