{"gene":"VPS52","run_date":"2026-04-28T23:00:23","timeline":{"discoveries":[{"year":2003,"finding":"Vps52 is a core subunit of the tetrameric GARP (Golgi-Associated Retrograde Protein) complex (Vps51/52/53/54). The additional subunit Vps51p mediates the interaction between the Vps52/53/54 sub-complex and the late Golgi t-SNARE Tlg1p via binding to the conserved N-terminal domain of Tlg1p, providing a crucial link between tethering and fusion machinery. All four subunits are required for retrograde transport from both early and late endosomes back to the TGN.","method":"Genetic complementation, co-immunoprecipitation, two-hybrid interaction assays in yeast","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — reciprocal co-IP and epistasis in yeast ortholog system, replicated across multiple assays in a highly-cited foundational paper","pmids":["12686613"],"is_preprint":false},{"year":2005,"finding":"Human VPS52 (hVps52) is a subunit of the human GARP/VFT tethering complex and localizes to smooth membrane/Golgi fractions and perinuclear vesicular structures with endosomal character near the TGN. hVps52 specifically binds the small GTPase Rab6 (human homolog of yeast Ypt6p). In human cells, hVps52 mediates binding of the GARP complex to the orphan SNARE Syntaxin 10, revealing Syntaxin 10 as the human-specific GARP-associated SNARE for membrane docking and fusion at the Golgi.","method":"Subcellular fractionation, immunostaining with endosomal markers, co-immunoprecipitation","journal":"Experimental cell research","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (fractionation, co-IP, immunolocalization) in a well-cited paper establishing mammalian GARP function","pmids":["15878329"],"is_preprint":false},{"year":2008,"finding":"Depletion of VPS52 (along with VPS53 or VPS54) by RNAi impairs mannose 6-phosphate receptor (MPR)-dependent sorting of cathepsin D precursor to lysosomes, causing cathepsin D secretion into the medium, lysosomal swelling, and accumulation of recycling MPRs in light vesicles downstream of endosomes. GARP/VPS52 also blocks retrograde transport of TGN46 and the B subunit of Shiga toxin, establishing a general role for the GARP complex in retrograde cargo delivery to the TGN.","method":"RNAi knockdown in mammalian cells, cathepsin D trafficking assay, Shiga toxin transport assay, TGN46 localization","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 2 — clean RNAi KD with multiple defined cargo readouts, highly cited","pmids":["18367545"],"is_preprint":false},{"year":2009,"finding":"The mammalian GARP complex interacts specifically with SNAREs syntaxin 6, syntaxin 16, and Vamp4 (participants in endosome-to-TGN transport) via the N-terminal regions of VPS53 and VPS54 and the SNARE motifs of the SNAREs. GARP functions upstream of SNAREs, regulating their localization and assembly into SNARE complexes. In vitro data support a tethering role for GARP. These two functions — tethering and SNARE complex assembly — are consecutive, independent steps in retrograde transport.","method":"Co-immunoprecipitation, RNAi depletion, in vitro tethering assay, deletion mutagenesis of VPS53","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1-2 — in vitro tethering assay combined with co-IP and mutagenesis, highly cited","pmids":["19620288"],"is_preprint":false},{"year":2012,"finding":"The mouse t(w5) lethal mutation is caused by a loss-of-function mutation in Vps52. Vps52 acts in extraembryonic tissues to support growth and differentiation of the embryonic ectoderm via cell-cell interactions, and is also required for formation of embryonic structures at later developmental stages, revealing functions in multicellular development beyond its known role in endosomal retrograde trafficking.","method":"Positional cloning, genetic complementation, embryo phenotyping in Vps52 mutant mice","journal":"Cell reports","confidence":"High","confidence_rationale":"Tier 2 — positional cloning plus defined developmental phenotype with genetic complementation","pmids":["23142660"],"is_preprint":false},{"year":2017,"finding":"RNF41, an E3 ubiquitin ligase, interacts with VPS52 through their coiled-coil domains. RNF41 ubiquitinates VPS52 and relocates it away from VPS53 (a common subunit of GARP and EARP complexes) toward RNF41 bodies, indicating that RNF41-mediated ubiquitination regulates VPS52's association with the GARP and EARP complexes.","method":"Array MAPPIT protein-protein interaction screen, co-immunoprecipitation, coiled-coil domain interaction mapping, ubiquitination assay","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2-3 — MAPPIT screen plus co-IP and ubiquitination assay from a single lab","pmids":["28542518"],"is_preprint":false},{"year":2017,"finding":"Overexpression of VPS52 in gastric cancer cells activates the cathepsin D/Bax/cytochrome C/caspase 9/caspase 3 apoptotic pathway, reducing cell viability and inducing apoptosis in vitro, and reducing tumor volume in xenograft models in vivo. This identifies VPS52 as a tumor suppressor in gastric cancer that promotes apoptosis through cathepsin D activation.","method":"VPS52 overexpression in gastric cancer cell lines, cell viability assay, apoptosis assay, Western blot for apoptotic pathway components, xenograft mouse model","journal":"Journal of molecular medicine","confidence":"Medium","confidence_rationale":"Tier 2 — functional overexpression with pathway readouts in vitro and in vivo, single lab","pmids":["28791438"],"is_preprint":false},{"year":2020,"finding":"VPS52 is a novel Arf6-binding protein identified by yeast two-hybrid screening. VPS52 interacts specifically with GTP-bound Arf6 (active form) among the Arf family. In hippocampal neurons, VPS52 localizes to the trans-Golgi network and vesicular endomembranes in cell bodies and dendritic shafts. Knockdown of Vps52 increases total axon and dendrite length; this phenotype is rescued by full-length Vps52 but only partially by a mutant lacking Arf6-binding ability, indicating that the Arf6 interaction specifically regulates dendritic (but not axonal) outgrowth.","method":"Yeast two-hybrid screening, immunohistochemistry, shRNA knockdown, rescue with mutant constructs in hippocampal neurons","journal":"Brain research","confidence":"Medium","confidence_rationale":"Tier 2 — yeast two-hybrid plus domain-specific rescue experiments establishing functional requirement of Arf6 interaction for dendritic regulation","pmids":["32473257"],"is_preprint":false},{"year":2021,"finding":"VPS52 functions as a Rab6 effector responsible for Rab6-dependent secretory cargo trafficking. Knockout of VPS52 in human cells results in attenuated secretion and lysosomal accumulation of secretory cargos, phenocopying Rab6 knockout. The previously uncharacterized C-terminal region of VPS52 is functionally important for restoring secretory cargo trafficking and for lysosomal protein sorting.","method":"CRISPR knockout cell lines, secretory cargo trafficking assays, lysosomal protein sorting assay, C-terminal deletion rescue experiments","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — clean KO with defined cargo phenotype plus domain deletion rescue, single lab","pmids":["34023780"],"is_preprint":false}],"current_model":"VPS52 is a core subunit of the tetrameric GARP (Golgi-Associated Retrograde Protein) and EARP complexes that mediates retrograde vesicle tethering and SNARE complex assembly at the TGN; it binds Rab6 and (via Vps51) connects to TGN-resident SNAREs to orchestrate endosome-to-TGN retrograde transport of cargos including mannose 6-phosphate receptors, cathepsin D, and secretory proteins, while in neurons it additionally interacts with GTP-Arf6 to negatively regulate neurite outgrowth, and its ubiquitination by RNF41 regulates its association with GARP/EARP."},"narrative":{"teleology":[{"year":2003,"claim":"Identification of Vps52 as a subunit of the tetrameric GARP/VFT complex established the molecular composition of the tethering machinery for endosome-to-TGN retrograde transport and revealed that the fourth subunit Vps51 bridges the complex to the t-SNARE Tlg1p.","evidence":"Genetic complementation, co-immunoprecipitation, and yeast two-hybrid assays in S. cerevisiae","pmids":["12686613"],"confidence":"High","gaps":["Mammalian GARP composition and cognate SNAREs not yet defined","Direct tethering activity of the GARP complex not demonstrated in vitro"]},{"year":2005,"claim":"Demonstration that human VPS52 binds Rab6 and associates with Syntaxin 10 extended the GARP tethering model to mammals, identifying the GTPase receptor and the species-specific SNARE partner at the TGN.","evidence":"Subcellular fractionation, immunofluorescence, and co-immunoprecipitation in human cells","pmids":["15878329"],"confidence":"High","gaps":["Structural basis of VPS52–Rab6 interaction unknown","Whether VPS52 or another GARP subunit directly contacts Syntaxin 10 not resolved"]},{"year":2008,"claim":"Functional depletion studies proved GARP/VPS52 is required for retrograde trafficking of multiple cargos—mannose 6-phosphate receptors, TGN46, and Shiga toxin—establishing the complex as a general retrograde tethering factor rather than pathway-specific.","evidence":"RNAi knockdown with cathepsin D secretion, Shiga toxin transport, and TGN46 localization assays in mammalian cells","pmids":["18367545"],"confidence":"High","gaps":["Relative contribution of individual GARP subunits to cargo selectivity not dissected","Whether GARP also participates in anterograde pathways not addressed"]},{"year":2009,"claim":"Reconstitution of GARP tethering activity in vitro and mapping of SNARE interactions to VPS53/VPS54 N-termini demonstrated that GARP performs two separable functions—vesicle tethering and SNARE complex assembly—as consecutive steps in retrograde transport.","evidence":"In vitro tethering assay, co-immunoprecipitation, and deletion mutagenesis","pmids":["19620288"],"confidence":"High","gaps":["Direct structural model of GARP–SNARE interaction lacking","Specific role of VPS52 within the tethering versus SNARE-assembly steps not separated"]},{"year":2012,"claim":"Positional cloning of the mouse t(w5) lethal as a Vps52 loss-of-function allele revealed that GARP-mediated trafficking is essential for embryonic development, particularly extraembryonic tissue differentiation and ectodermal patterning.","evidence":"Positional cloning, genetic complementation, and embryo phenotyping in mutant mice","pmids":["23142660"],"confidence":"High","gaps":["Which specific trafficking cargos underlie the developmental defect is unknown","Whether GARP complex integrity is completely lost or partially retained in the mutant not determined"]},{"year":2017,"claim":"Discovery that RNF41 ubiquitinates VPS52 via coiled-coil domain interaction and displaces it from VPS53 provided the first post-translational regulatory mechanism controlling GARP/EARP complex assembly.","evidence":"MAPPIT interaction screen, co-immunoprecipitation, coiled-coil domain mapping, and ubiquitination assay","pmids":["28542518"],"confidence":"Medium","gaps":["Ubiquitination site(s) on VPS52 not mapped","Functional consequence for endosome-to-TGN transport not tested","Not independently confirmed by a second group"]},{"year":2020,"claim":"Identification of VPS52 as an Arf6-GTP effector in neurons, where the Arf6-binding region selectively regulates dendritic but not axonal outgrowth, expanded VPS52 function beyond canonical GARP tethering to neuronal morphogenesis.","evidence":"Yeast two-hybrid screen, shRNA knockdown, and domain-mutant rescue in hippocampal neurons","pmids":["32473257"],"confidence":"Medium","gaps":["Whether Arf6–VPS52 interaction operates through the GARP complex or independently is unresolved","Downstream effectors mediating dendritic outgrowth regulation not identified"]},{"year":2021,"claim":"CRISPR knockout of VPS52 phenocopied Rab6 loss for secretory cargo export and lysosomal sorting, establishing VPS52/GARP as a Rab6 effector in the anterograde secretory pathway and assigning a functional role to the previously uncharacterized VPS52 C-terminal domain.","evidence":"CRISPR knockout, secretory and lysosomal sorting assays, C-terminal deletion rescue in human cells","pmids":["34023780"],"confidence":"Medium","gaps":["Structural basis of the C-terminal domain's contribution unknown","Whether VPS52 KO secretory defect is solely GARP-dependent or also involves EARP not tested"]},{"year":null,"claim":"No high-resolution structure of VPS52 within the GARP complex exists, and the mechanistic basis by which VPS52 simultaneously coordinates Rab6, Arf6, and SNARE interactions across different cellular contexts remains unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No atomic-resolution structure of VPS52 or GARP complex available","How RNF41-mediated ubiquitination modulates GARP versus EARP partitioning in vivo is untested","Physiological relevance of VPS52 tumor-suppressive activity in gastric cancer requires genetic validation"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,3]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[1,7]},{"term_id":"GO:0005768","term_label":"endosome","supporting_discovery_ids":[1,2]},{"term_id":"GO:0031410","term_label":"cytoplasmic vesicle","supporting_discovery_ids":[1,7]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,1,2,3,8]},{"term_id":"R-HSA-9612973","term_label":"Autophagy","supporting_discovery_ids":[2,8]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[5]}],"complexes":["GARP complex (VPS51/VPS52/VPS53/VPS54)","EARP complex"],"partners":["VPS51","VPS53","VPS54","RAB6A","STX10","STX6","STX16","ARF6"],"other_free_text":[]},"mechanistic_narrative":"VPS52 is a core subunit of the GARP (Golgi-Associated Retrograde Protein) tethering complex that orchestrates retrograde vesicle transport from endosomes to the trans-Golgi network and supports anterograde secretory trafficking. Within the tetrameric GARP complex (VPS51/52/53/54), VPS52 directly binds the small GTPase Rab6 and, through VPS51, connects to TGN-resident SNAREs (Tlg1p in yeast; Syntaxin 10, Syntaxin 6, Syntaxin 16, and VAMP4 in mammals), coupling vesicle tethering to SNARE complex assembly for membrane fusion [PMID:12686613, PMID:15878329, PMID:19620288]. Loss of VPS52 impairs retrograde delivery of mannose 6-phosphate receptors and cathepsin D to lysosomes, blocks Shiga toxin and TGN46 recycling, and attenuates Rab6-dependent secretory cargo export [PMID:18367545, PMID:34023780]. In mice, Vps52 loss-of-function (the t(w5) lethal allele) causes embryonic lethality with defective extraembryonic tissue differentiation, and in neurons VPS52 interacts with GTP-Arf6 to negatively regulate dendritic outgrowth [PMID:23142660, PMID:32473257]."},"prefetch_data":{"uniprot":{"accession":"Q8N1B4","full_name":"Vacuolar protein sorting-associated protein 52 homolog","aliases":["SAC2 suppressor of actin mutations 2-like protein"],"length_aa":723,"mass_kda":82.2,"function":"Acts as a component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (PubMed:15878329, PubMed:18367545). Acts as a component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (PubMed:25799061)","subcellular_location":"Golgi apparatus, trans-Golgi network membrane; Endosome membrane; Recycling endosome","url":"https://www.uniprot.org/uniprotkb/Q8N1B4/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/VPS52","classification":"Not Classified","n_dependent_lines":425,"n_total_lines":1208,"dependency_fraction":0.3518211920529801},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/VPS52","total_profiled":1310},"omim":[{"mim_id":"616465","title":"VPS50, EARP/GARPII COMPLEX SUBUNIT; VPS50","url":"https://www.omim.org/entry/616465"},{"mim_id":"615850","title":"VPS53 SUBUNIT OF GARP COMPLEX; VPS53","url":"https://www.omim.org/entry/615850"},{"mim_id":"615738","title":"VPS51 SUBUNIT OF GARP COMPLEX; VPS51","url":"https://www.omim.org/entry/615738"},{"mim_id":"614633","title":"VPS54 SUBUNIT OF GARP COMPLEX; VPS54","url":"https://www.omim.org/entry/614633"},{"mim_id":"603443","title":"VPS52 SUBUNIT OF GARP COMPLEX; VPS52","url":"https://www.omim.org/entry/603443"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in many","driving_tissues":[],"url":"https://www.proteinatlas.org/search/VPS52"},"hgnc":{"alias_symbol":["ARE1"],"prev_symbol":["SACM2L"]},"alphafold":{"accession":"Q8N1B4","domains":[{"cath_id":"-","chopping":"178-276","consensus_level":"high","plddt":92.0921,"start":178,"end":276},{"cath_id":"-","chopping":"307-326_339-478","consensus_level":"high","plddt":93.721,"start":307,"end":478},{"cath_id":"-","chopping":"607-718","consensus_level":"high","plddt":90.3438,"start":607,"end":718}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N1B4","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N1B4-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q8N1B4-F1-predicted_aligned_error_v6.png","plddt_mean":85.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VPS52","jax_strain_url":"https://www.jax.org/strain/search?query=VPS52"},"sequence":{"accession":"Q8N1B4","fasta_url":"https://rest.uniprot.org/uniprotkb/Q8N1B4.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q8N1B4/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q8N1B4"}},"corpus_meta":[{"pmid":"12686613","id":"PMC_12686613","title":"Vps51p 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yeast. The complex interacts with a Rab GTPase and the t-SNARE Tlg1p at the late Golgi, and is required for retrograde transport from both early and late endosomes back to the TGN. Vps51p mediates the interaction between the Vps52/53/54 subcomplex and the t-SNARE Tlg1p via the conserved N-terminal domain of Tlg1p, linking tethering and fusion machinery.\",\n      \"method\": \"Genetic epistasis, co-immunoprecipitation, yeast mutant phenotyping, two-hybrid interaction assays\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP and genetic epistasis, foundational study with >150 citations replicated across labs\",\n      \"pmids\": [\"12686613\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Mouse Vps52 (ortholog of yeast VPS52) is required for retrograde trafficking of endosomes and plays a non-cell-autonomous role in embryonic development: it acts in extraembryonic tissues to support growth and differentiation of the embryonic ectoderm via cell-cell interactions, and is also required for later embryonic structure formation. Loss-of-function (t(w5) mutation) causes defects in embryonic ectoderm before gastrulation.\",\n      \"method\": \"Positional cloning of t(w5) mutation, loss-of-function mouse genetics, phenotypic analysis of embryonic ectoderm\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined developmental phenotype, single lab\",\n      \"pmids\": [\"23142660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"VPS52 induces apoptosis in gastric cancer cells via activation of the cathepsin D/Bax/cytochrome C/caspase 9/caspase 3 pathway. Overexpression of VPS52 reduced cell viability and increased apoptosis in vitro and reduced tumor growth in xenograft models in vivo.\",\n      \"method\": \"VPS52 overexpression in gastric cancer cell lines, xenograft mouse model, western blot for apoptotic pathway components\",\n      \"journal\": \"Journal of molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — defined cellular phenotype with pathway characterization, single lab\",\n      \"pmids\": [\"28791438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RNF41 (an E3 ubiquitin ligase) interacts with VPS52 via their coiled-coil domains, ubiquitinates VPS52, and relocates VPS52 away from VPS53 (a common subunit of GARP and EARP complexes) toward RNF41 bodies, thereby modulating VPS52's participation in retrograde transport complexes.\",\n      \"method\": \"Array MAPPIT protein-protein interaction screen, co-immunoprecipitation, ubiquitination assay, coiled-coil domain mapping\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP and biochemical ubiquitination assay, single lab with multiple methods\",\n      \"pmids\": [\"28542518\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Vps52 interacts specifically with GTP-bound Arf6 (among Arf family members) and negatively regulates neurite outgrowth in hippocampal neurons. Knockdown of Vps52 increased total axon and dendrite length; the Arf6-interaction-deficient Vps52 mutant failed to restore dendritic length but restored axon length, indicating Arf6 binding is specifically required for the dendritic regulation function. Vps52 localizes to trans-Golgi network and vesicular endomembranes in hippocampal neurons.\",\n      \"method\": \"Yeast two-hybrid screening, Co-IP, shRNA knockdown rescue with wild-type vs. Arf6-binding mutant Vps52, immunohistochemistry, subcellular fractionation\",\n      \"journal\": \"Brain research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — yeast two-hybrid confirmed by Co-IP, loss-of-function with domain-specific rescue mutant, single lab\",\n      \"pmids\": [\"32473257\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"VPS52, as a subunit of the GARP complex, acts as a Rab6 effector responsible for Rab6-dependent secretory cargo trafficking. Knockout of VPS52 resulted in attenuated secretion and lysosomal accumulation of secretory cargos—the same phenotype as Rab6 knockout. The C-terminal region of VPS52 was found to be functionally important for restoring secretory phenotypes and for lysosomal protein sorting.\",\n      \"method\": \"CRISPR/Cas9 knockout cell lines, secretion assay, lysosomal accumulation assay, rescue experiments with VPS52 C-terminal deletion mutants\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined trafficking phenotype, domain-deletion rescue, single lab\",\n      \"pmids\": [\"34023780\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VPS52 is a core subunit of the tetrameric GARP (and EARP) tethering complexes that mediates retrograde vesicular trafficking from endosomes to the trans-Golgi network by linking to t-SNAREs (via Vps51) and acting as a Rab6 and Arf6 effector; it is subject to ubiquitination by the E3 ligase RNF41 which displaces it from the GARP/EARP complex, and in neurons it negatively regulates neurite outgrowth through its Arf6-dependent and -independent functions.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2003,\n      \"finding\": \"Vps52 is a core subunit of the tetrameric GARP (Golgi-Associated Retrograde Protein) complex (Vps51/52/53/54). The additional subunit Vps51p mediates the interaction between the Vps52/53/54 sub-complex and the late Golgi t-SNARE Tlg1p via binding to the conserved N-terminal domain of Tlg1p, providing a crucial link between tethering and fusion machinery. All four subunits are required for retrograde transport from both early and late endosomes back to the TGN.\",\n      \"method\": \"Genetic complementation, co-immunoprecipitation, two-hybrid interaction assays in yeast\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal co-IP and epistasis in yeast ortholog system, replicated across multiple assays in a highly-cited foundational paper\",\n      \"pmids\": [\"12686613\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Human VPS52 (hVps52) is a subunit of the human GARP/VFT tethering complex and localizes to smooth membrane/Golgi fractions and perinuclear vesicular structures with endosomal character near the TGN. hVps52 specifically binds the small GTPase Rab6 (human homolog of yeast Ypt6p). In human cells, hVps52 mediates binding of the GARP complex to the orphan SNARE Syntaxin 10, revealing Syntaxin 10 as the human-specific GARP-associated SNARE for membrane docking and fusion at the Golgi.\",\n      \"method\": \"Subcellular fractionation, immunostaining with endosomal markers, co-immunoprecipitation\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (fractionation, co-IP, immunolocalization) in a well-cited paper establishing mammalian GARP function\",\n      \"pmids\": [\"15878329\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"Depletion of VPS52 (along with VPS53 or VPS54) by RNAi impairs mannose 6-phosphate receptor (MPR)-dependent sorting of cathepsin D precursor to lysosomes, causing cathepsin D secretion into the medium, lysosomal swelling, and accumulation of recycling MPRs in light vesicles downstream of endosomes. GARP/VPS52 also blocks retrograde transport of TGN46 and the B subunit of Shiga toxin, establishing a general role for the GARP complex in retrograde cargo delivery to the TGN.\",\n      \"method\": \"RNAi knockdown in mammalian cells, cathepsin D trafficking assay, Shiga toxin transport assay, TGN46 localization\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean RNAi KD with multiple defined cargo readouts, highly cited\",\n      \"pmids\": [\"18367545\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"The mammalian GARP complex interacts specifically with SNAREs syntaxin 6, syntaxin 16, and Vamp4 (participants in endosome-to-TGN transport) via the N-terminal regions of VPS53 and VPS54 and the SNARE motifs of the SNAREs. GARP functions upstream of SNAREs, regulating their localization and assembly into SNARE complexes. In vitro data support a tethering role for GARP. These two functions — tethering and SNARE complex assembly — are consecutive, independent steps in retrograde transport.\",\n      \"method\": \"Co-immunoprecipitation, RNAi depletion, in vitro tethering assay, deletion mutagenesis of VPS53\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — in vitro tethering assay combined with co-IP and mutagenesis, highly cited\",\n      \"pmids\": [\"19620288\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"The mouse t(w5) lethal mutation is caused by a loss-of-function mutation in Vps52. Vps52 acts in extraembryonic tissues to support growth and differentiation of the embryonic ectoderm via cell-cell interactions, and is also required for formation of embryonic structures at later developmental stages, revealing functions in multicellular development beyond its known role in endosomal retrograde trafficking.\",\n      \"method\": \"Positional cloning, genetic complementation, embryo phenotyping in Vps52 mutant mice\",\n      \"journal\": \"Cell reports\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — positional cloning plus defined developmental phenotype with genetic complementation\",\n      \"pmids\": [\"23142660\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"RNF41, an E3 ubiquitin ligase, interacts with VPS52 through their coiled-coil domains. RNF41 ubiquitinates VPS52 and relocates it away from VPS53 (a common subunit of GARP and EARP complexes) toward RNF41 bodies, indicating that RNF41-mediated ubiquitination regulates VPS52's association with the GARP and EARP complexes.\",\n      \"method\": \"Array MAPPIT protein-protein interaction screen, co-immunoprecipitation, coiled-coil domain interaction mapping, ubiquitination assay\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — MAPPIT screen plus co-IP and ubiquitination assay from a single lab\",\n      \"pmids\": [\"28542518\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Overexpression of VPS52 in gastric cancer cells activates the cathepsin D/Bax/cytochrome C/caspase 9/caspase 3 apoptotic pathway, reducing cell viability and inducing apoptosis in vitro, and reducing tumor volume in xenograft models in vivo. This identifies VPS52 as a tumor suppressor in gastric cancer that promotes apoptosis through cathepsin D activation.\",\n      \"method\": \"VPS52 overexpression in gastric cancer cell lines, cell viability assay, apoptosis assay, Western blot for apoptotic pathway components, xenograft mouse model\",\n      \"journal\": \"Journal of molecular medicine\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional overexpression with pathway readouts in vitro and in vivo, single lab\",\n      \"pmids\": [\"28791438\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"VPS52 is a novel Arf6-binding protein identified by yeast two-hybrid screening. VPS52 interacts specifically with GTP-bound Arf6 (active form) among the Arf family. In hippocampal neurons, VPS52 localizes to the trans-Golgi network and vesicular endomembranes in cell bodies and dendritic shafts. Knockdown of Vps52 increases total axon and dendrite length; this phenotype is rescued by full-length Vps52 but only partially by a mutant lacking Arf6-binding ability, indicating that the Arf6 interaction specifically regulates dendritic (but not axonal) outgrowth.\",\n      \"method\": \"Yeast two-hybrid screening, immunohistochemistry, shRNA knockdown, rescue with mutant constructs in hippocampal neurons\",\n      \"journal\": \"Brain research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — yeast two-hybrid plus domain-specific rescue experiments establishing functional requirement of Arf6 interaction for dendritic regulation\",\n      \"pmids\": [\"32473257\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"VPS52 functions as a Rab6 effector responsible for Rab6-dependent secretory cargo trafficking. Knockout of VPS52 in human cells results in attenuated secretion and lysosomal accumulation of secretory cargos, phenocopying Rab6 knockout. The previously uncharacterized C-terminal region of VPS52 is functionally important for restoring secretory cargo trafficking and for lysosomal protein sorting.\",\n      \"method\": \"CRISPR knockout cell lines, secretory cargo trafficking assays, lysosomal protein sorting assay, C-terminal deletion rescue experiments\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — clean KO with defined cargo phenotype plus domain deletion rescue, single lab\",\n      \"pmids\": [\"34023780\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VPS52 is a core subunit of the tetrameric GARP (Golgi-Associated Retrograde Protein) and EARP complexes that mediates retrograde vesicle tethering and SNARE complex assembly at the TGN; it binds Rab6 and (via Vps51) connects to TGN-resident SNAREs to orchestrate endosome-to-TGN retrograde transport of cargos including mannose 6-phosphate receptors, cathepsin D, and secretory proteins, while in neurons it additionally interacts with GTP-Arf6 to negatively regulate neurite outgrowth, and its ubiquitination by RNF41 regulates its association with GARP/EARP.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"VPS52 is a core subunit of the tetrameric GARP tethering complex (Vps51/52/53/54) that mediates retrograde vesicular transport from endosomes to the trans-Golgi network by coupling Rab GTPase recognition to SNARE-dependent membrane fusion [PMID:12686613]. VPS52 functions as an effector for both Rab6, where its C-terminal region is required for secretory cargo trafficking and lysosomal protein sorting [PMID:34023780], and Arf6, where GTP-bound Arf6 binding specifically mediates VPS52's negative regulation of dendritic outgrowth in hippocampal neurons [PMID:32473257]. The E3 ubiquitin ligase RNF41 ubiquitinates VPS52 via coiled-coil domain interactions, displacing it from VPS53 and thereby modulating GARP/EARP complex assembly [PMID:28542518]. In mouse development, Vps52 loss of function disrupts embryonic ectoderm differentiation through a non-cell-autonomous mechanism requiring extraembryonic tissue function [PMID:23142660].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing the molecular identity of the GARP complex resolved how retrograde endosome-to-TGN tethering is organized: VPS52 forms a stable tetrameric complex with Vps51/53/54 that links Rab GTPase recognition to t-SNARE engagement at the late Golgi.\",\n      \"evidence\": \"Genetic epistasis, co-immunoprecipitation, two-hybrid assays, and mutant phenotyping in yeast\",\n      \"pmids\": [\"12686613\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mammalian GARP complex composition and regulation not yet addressed\",\n        \"Structural basis for VPS52 integration into the tetramer unknown\",\n        \"Whether VPS52 directly contacts the Rab GTPase or acts indirectly not resolved\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Demonstrating that Vps52 loss causes embryonic lethality before gastrulation established that GARP-dependent retrograde trafficking is essential for early mammalian development, acting non-cell-autonomously through extraembryonic tissues.\",\n      \"evidence\": \"Positional cloning of the mouse t(w5) mutation and phenotypic analysis of mutant embryos\",\n      \"pmids\": [\"23142660\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Specific cargos misrouted in the absence of Vps52 during embryogenesis not identified\",\n        \"Whether the developmental phenotype reflects GARP complex disruption versus a GARP-independent function of Vps52 not distinguished\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Two independent studies expanded VPS52 function beyond canonical trafficking: RNF41-mediated ubiquitination of VPS52 was shown to displace it from VPS53, providing a post-translational mechanism for GARP/EARP complex remodeling, while VPS52 overexpression in gastric cancer cells activated the cathepsin D–Bax–caspase apoptotic cascade.\",\n      \"evidence\": \"Co-IP, ubiquitination assays, and coiled-coil domain mapping for RNF41 interaction; overexpression and xenograft studies for apoptosis\",\n      \"pmids\": [\"28542518\", \"28791438\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Physiological signals triggering RNF41-dependent VPS52 ubiquitination unknown\",\n        \"Whether apoptosis induction by VPS52 overexpression reflects a physiological function or a consequence of trafficking disruption not resolved\",\n        \"Degradative versus non-degradative fate of ubiquitinated VPS52 not established\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identification of VPS52 as a GTP-Arf6 effector that negatively regulates neurite outgrowth revealed a neuronal-specific function, with Arf6 binding selectively required for dendritic but not axonal length control.\",\n      \"evidence\": \"Yeast two-hybrid and Co-IP for Arf6 interaction; shRNA knockdown with wild-type versus Arf6-binding-deficient rescue mutants in hippocampal neurons\",\n      \"pmids\": [\"32473257\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Downstream effectors linking VPS52–Arf6 to dendritic morphogenesis not identified\",\n        \"Whether Arf6 and Rab6 binding to VPS52 are mutually exclusive or concurrent not tested\",\n        \"Structural basis of the VPS52–Arf6 interaction not determined\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Defining VPS52 as the Rab6 effector subunit of GARP clarified how GARP integrates into the secretory pathway: VPS52 knockout phenocopied Rab6 knockout by causing lysosomal misrouting of secretory cargo, with the VPS52 C-terminal region being essential for this function.\",\n      \"evidence\": \"CRISPR/Cas9 VPS52 knockout cell lines, secretion and lysosomal accumulation assays, C-terminal deletion rescue\",\n      \"pmids\": [\"34023780\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the VPS52 C-terminus directly binds Rab6-GTP or acts through an intermediary not resolved\",\n        \"Structural model of full-length VPS52 or the GARP complex lacking\",\n        \"Contribution of individual GARP subunits to Rab6 versus Rab GTPase specificity not dissected\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"No high-resolution structural model of VPS52 within the GARP complex exists, and the mechanistic relationship between its dual roles as a Rab6 and Arf6 effector — and how RNF41-mediated ubiquitination modulates these functions in specific cellular contexts — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Atomic-resolution structure of VPS52 in the GARP complex not available\",\n        \"In vivo significance of RNF41-VPS52 regulation in trafficking not tested\",\n        \"Whether VPS52 has functions independent of the GARP/EARP complexes not systematically addressed\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 4, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 4]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [0, 4, 5]}\n    ],\n    \"complexes\": [\n      \"GARP (Vps51/52/53/54)\"\n    ],\n    \"partners\": [\n      \"VPS51\",\n      \"VPS53\",\n      \"VPS54\",\n      \"RNF41\",\n      \"ARF6\",\n      \"RAB6\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"VPS52 is a core subunit of the GARP (Golgi-Associated Retrograde Protein) tethering complex that orchestrates retrograde vesicle transport from endosomes to the trans-Golgi network and supports anterograde secretory trafficking. Within the tetrameric GARP complex (VPS51/52/53/54), VPS52 directly binds the small GTPase Rab6 and, through VPS51, connects to TGN-resident SNAREs (Tlg1p in yeast; Syntaxin 10, Syntaxin 6, Syntaxin 16, and VAMP4 in mammals), coupling vesicle tethering to SNARE complex assembly for membrane fusion [PMID:12686613, PMID:15878329, PMID:19620288]. Loss of VPS52 impairs retrograde delivery of mannose 6-phosphate receptors and cathepsin D to lysosomes, blocks Shiga toxin and TGN46 recycling, and attenuates Rab6-dependent secretory cargo export [PMID:18367545, PMID:34023780]. In mice, Vps52 loss-of-function (the t(w5) lethal allele) causes embryonic lethality with defective extraembryonic tissue differentiation, and in neurons VPS52 interacts with GTP-Arf6 to negatively regulate dendritic outgrowth [PMID:23142660, PMID:32473257].\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Identification of Vps52 as a subunit of the tetrameric GARP/VFT complex established the molecular composition of the tethering machinery for endosome-to-TGN retrograde transport and revealed that the fourth subunit Vps51 bridges the complex to the t-SNARE Tlg1p.\",\n      \"evidence\": \"Genetic complementation, co-immunoprecipitation, and yeast two-hybrid assays in S. cerevisiae\",\n      \"pmids\": [\"12686613\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Mammalian GARP composition and cognate SNAREs not yet defined\",\n        \"Direct tethering activity of the GARP complex not demonstrated in vitro\"\n      ]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Demonstration that human VPS52 binds Rab6 and associates with Syntaxin 10 extended the GARP tethering model to mammals, identifying the GTPase receptor and the species-specific SNARE partner at the TGN.\",\n      \"evidence\": \"Subcellular fractionation, immunofluorescence, and co-immunoprecipitation in human cells\",\n      \"pmids\": [\"15878329\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of VPS52–Rab6 interaction unknown\",\n        \"Whether VPS52 or another GARP subunit directly contacts Syntaxin 10 not resolved\"\n      ]\n    },\n    {\n      \"year\": 2008,\n      \"claim\": \"Functional depletion studies proved GARP/VPS52 is required for retrograde trafficking of multiple cargos—mannose 6-phosphate receptors, TGN46, and Shiga toxin—establishing the complex as a general retrograde tethering factor rather than pathway-specific.\",\n      \"evidence\": \"RNAi knockdown with cathepsin D secretion, Shiga toxin transport, and TGN46 localization assays in mammalian cells\",\n      \"pmids\": [\"18367545\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Relative contribution of individual GARP subunits to cargo selectivity not dissected\",\n        \"Whether GARP also participates in anterograde pathways not addressed\"\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Reconstitution of GARP tethering activity in vitro and mapping of SNARE interactions to VPS53/VPS54 N-termini demonstrated that GARP performs two separable functions—vesicle tethering and SNARE complex assembly—as consecutive steps in retrograde transport.\",\n      \"evidence\": \"In vitro tethering assay, co-immunoprecipitation, and deletion mutagenesis\",\n      \"pmids\": [\"19620288\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Direct structural model of GARP–SNARE interaction lacking\",\n        \"Specific role of VPS52 within the tethering versus SNARE-assembly steps not separated\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Positional cloning of the mouse t(w5) lethal as a Vps52 loss-of-function allele revealed that GARP-mediated trafficking is essential for embryonic development, particularly extraembryonic tissue differentiation and ectodermal patterning.\",\n      \"evidence\": \"Positional cloning, genetic complementation, and embryo phenotyping in mutant mice\",\n      \"pmids\": [\"23142660\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Which specific trafficking cargos underlie the developmental defect is unknown\",\n        \"Whether GARP complex integrity is completely lost or partially retained in the mutant not determined\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Discovery that RNF41 ubiquitinates VPS52 via coiled-coil domain interaction and displaces it from VPS53 provided the first post-translational regulatory mechanism controlling GARP/EARP complex assembly.\",\n      \"evidence\": \"MAPPIT interaction screen, co-immunoprecipitation, coiled-coil domain mapping, and ubiquitination assay\",\n      \"pmids\": [\"28542518\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Ubiquitination site(s) on VPS52 not mapped\",\n        \"Functional consequence for endosome-to-TGN transport not tested\",\n        \"Not independently confirmed by a second group\"\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identification of VPS52 as an Arf6-GTP effector in neurons, where the Arf6-binding region selectively regulates dendritic but not axonal outgrowth, expanded VPS52 function beyond canonical GARP tethering to neuronal morphogenesis.\",\n      \"evidence\": \"Yeast two-hybrid screen, shRNA knockdown, and domain-mutant rescue in hippocampal neurons\",\n      \"pmids\": [\"32473257\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether Arf6–VPS52 interaction operates through the GARP complex or independently is unresolved\",\n        \"Downstream effectors mediating dendritic outgrowth regulation not identified\"\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"CRISPR knockout of VPS52 phenocopied Rab6 loss for secretory cargo export and lysosomal sorting, establishing VPS52/GARP as a Rab6 effector in the anterograde secretory pathway and assigning a functional role to the previously uncharacterized VPS52 C-terminal domain.\",\n      \"evidence\": \"CRISPR knockout, secretory and lysosomal sorting assays, C-terminal deletion rescue in human cells\",\n      \"pmids\": [\"34023780\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Structural basis of the C-terminal domain's contribution unknown\",\n        \"Whether VPS52 KO secretory defect is solely GARP-dependent or also involves EARP not tested\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"No high-resolution structure of VPS52 within the GARP complex exists, and the mechanistic basis by which VPS52 simultaneously coordinates Rab6, Arf6, and SNARE interactions across different cellular contexts remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No atomic-resolution structure of VPS52 or GARP complex available\",\n        \"How RNF41-mediated ubiquitination modulates GARP versus EARP partitioning in vivo is untested\",\n        \"Physiological relevance of VPS52 tumor-suppressive activity in gastric cancer requires genetic validation\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1, 7]},\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1, 2]},\n      {\"term_id\": \"GO:0031410\", \"supporting_discovery_ids\": [1, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 1, 2, 3, 8]},\n      {\"term_id\": \"R-HSA-9612973\", \"supporting_discovery_ids\": [2, 8]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [5]}\n    ],\n    \"complexes\": [\n      \"GARP complex (VPS51/VPS52/VPS53/VPS54)\",\n      \"EARP complex\"\n    ],\n    \"partners\": [\n      \"VPS51\",\n      \"VPS53\",\n      \"VPS54\",\n      \"RAB6A\",\n      \"STX10\",\n      \"STX6\",\n      \"STX16\",\n      \"ARF6\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}