{"gene":"GOSR1","run_date":"2026-06-10T01:55:21","timeline":{"discoveries":[{"year":1996,"finding":"GS28 (GOSR1) was identified as a 28-kDa cis-Golgi integral membrane protein with a central coiled-coil domain and C-terminal membrane anchor, and was established as a core component of the Golgi SNARE complex participating in the docking and fusion stage of ER-to-Golgi transport, demonstrated by an in vitro ER-Golgi transport assay.","method":"cDNA cloning, in vitro ER-Golgi transport assay, biochemical co-immunoprecipitation","journal":"Science","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro transport assay with functional inhibition plus biochemical complex identification; foundational paper replicated by multiple subsequent studies","pmids":["8638159"],"is_preprint":false},{"year":1997,"finding":"GS28 and syntaxin 5 form a protein complex in Golgi extracts that is dissociated by the concerted, ATP-hydrolysis-dependent action of alpha-SNAP and NSF; after dissociation, GS28 (but not syntaxin 5) binds immobilized alpha-SNAP.","method":"Co-immunoprecipitation from Golgi extracts, ATP hydrolysis inhibition experiments, immobilized alpha-SNAP binding assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — direct biochemical reconstitution with ATP hydrolysis controls, multiple orthogonal methods in one study","pmids":["9325254"],"is_preprint":false},{"year":2001,"finding":"GS28 forms a SNARE complex with Ykt6, syntaxin 5, and Bet1 at the Golgi, as demonstrated by co-immunoprecipitation; this complex participates in a late stage of ER-to-Golgi transport.","method":"Co-immunoprecipitation, in vitro ER-Golgi transport assay with Ykt6 antibody inhibition, double immunofluorescence labeling","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — reciprocal Co-IP combined with functional in vitro transport inhibition; replicated in subsequent studies","pmids":["11323436"],"is_preprint":false},{"year":2002,"finding":"GS28 forms a distinct SNARE complex with syntaxin 5, GS15, and Ykt6 implicated in early intra-Golgi (medial) cisternae transport; GS15 co-immunoprecipitates with COPI coat components, placing this complex in COPI-dependent traffic.","method":"Co-immunoprecipitation, immuno-electron microscopy, siRNA knockdown of GS15, overexpression of dominant-negative GS15 mutants","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — multiple orthogonal methods (Co-IP, immuno-EM, siRNA, dominant-negative); independently consistent with prior complex characterizations","pmids":["12388752"],"is_preprint":false},{"year":2002,"finding":"NSF and alpha-SNAP mediate binding of GATE-16 to GS28 (a Golgi v-SNARE) in an ATPase-independent but ATP-requiring manner during Golgi reassembly; GATE-16 binding to GS28 prevents GS28 from interacting with its cognate t-SNARE syntaxin 5, thereby regulating SNARE function at the onset of Golgi reassembly.","method":"Cell-free Golgi cisternae assembly assay, NSF mutant analysis (G274E; comatose), biochemical binding assays","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — cell-free reconstitution with NSF mutants and biochemical binding validation; mechanistic dissection of two distinct NSF activities","pmids":["12070132"],"is_preprint":false},{"year":2004,"finding":"The syntaxin 5/GS28/Ykt6/GS15 SNARE complex functions in transport from the early/recycling endosome to the trans-Golgi network (EE/RE-TGN), as shown by specific inhibition of STxB retrograde transport by antibodies against each of these four SNAREs in an in vitro transport assay.","method":"In vitro STxB transport assay with SNARE-specific antibodies, siRNA knockdown of GS15 in HeLa cells, SNX3-overexpression morphological analysis","journal":"Molecular biology of the cell","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — in vitro reconstituted transport assay plus siRNA validation, multiple SNAREs tested systematically","pmids":["15215310"],"is_preprint":false},{"year":2009,"finding":"In C. elegans, GS28 and Ykt6 act cooperatively/redundantly in intra-Golgi transport; loss of GS28 combined with Ykt6 knockdown impairs embryonic development, seam cell proliferation/differentiation, and proper expression of Golgi-resident proteins.","method":"C. elegans deletion mutant generation, synthetic lethal RNAi screen, epistasis analysis","journal":"Genes to cells","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis with defined cellular phenotypes in a model organism; single lab but multiple readouts","pmids":["19624756"],"is_preprint":false},{"year":2011,"finding":"ORP7 negatively regulates GS28 protein stability through sequestration of GATE-16 via the N-terminal domain (aa 1–142 of ORP7 interacting with aa 30–117 of GATE-16); ORP7 knockdown increases GS28 levels, whereas ORP7 overexpression decreases GS28 levels via proteasomal degradation. The oxysterol 25-hydroxycholesterol potentiates GS28 destabilization in an ORP7-dependent manner.","method":"Yeast two-hybrid, bimolecular fluorescence complementation (BiFC), siRNA knockdown, overexpression with truncation mutants, proteasome inhibitor experiments","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — yeast two-hybrid confirmed by BiFC in living cells, domain mapping with truncation mutants, functional GS28 stability readout; single lab","pmids":["21669198"],"is_preprint":false},{"year":2012,"finding":"GS28 forms a complex with MDM2 and p53, prevents MDM2-mediated ubiquitination and proteasomal degradation of p53, and thereby enhances p53 stability and pro-apoptotic activity (Bax induction, Ser46 phosphorylation) specifically in response to cisplatin-induced DNA damage.","method":"Co-immunoprecipitation, shRNA knockdown, overexpression, ubiquitination assay, p53-null cell rescue with ectopic p53","journal":"The Biochemical journal","confidence":"Medium","confidence_rationale":"Tier 2–3 / Moderate — Co-IP of GS28-MDM2-p53 complex, ubiquitination assay, and p53-null rescue; single lab with multiple complementary readouts","pmids":["22397410"],"is_preprint":false},{"year":2013,"finding":"GS28 (together with GS27) is enriched in COPI-coated Golgi vesicles and is extracted from Golgi cisternae into these vesicles during intra-Golgi transport; re-addition of GS28/GS27-containing Golgi vesicles restores in vitro intra-Golgi transport, indicating that segregation of GS28 into vesicles regulates intra-Golgi transport by controlling inter-cisternal connectivity.","method":"Subcellular fractionation, in vitro intra-Golgi transport assay, EM morphometry, εCOP degradation (auxin-inducible degron), immunofluorescence","journal":"Traffic","confidence":"Medium","confidence_rationale":"Tier 1–2 / Moderate — in vitro reconstitution of intra-Golgi transport with vesicle re-addition, corroborated by EM; single lab","pmids":["23387339"],"is_preprint":false},{"year":2014,"finding":"In Drosophila photoreceptors, Gos28 (ortholog of human GOSR1) mediates intra-Golgi transport of rhodopsin downstream of alpha-mannosidase II in the medial-Golgi; key residues in the SNARE motif are required for function whereas the transmembrane domain is dispensable for vesicle fusion, consistent with a t-SNARE role. Human GOS28 (GOSR1) rescues both rhodopsin trafficking defects and retinal degeneration in Drosophila gos28 mutants, demonstrating functional conservation.","method":"Drosophila gos28 loss-of-function mutants, site-directed mutagenesis of SNARE motif, transgenic rescue with human GOSR1, immunofluorescence co-localization with Golgi markers","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1–2 / Strong — genetic loss-of-function with defined trafficking phenotype, SNARE motif mutagenesis, and cross-species rescue with human protein; multiple orthogonal methods","pmids":["25261468"],"is_preprint":false},{"year":2011,"finding":"GS28 knockdown in neuronal SK-N-SH cells under glutathione-depleted conditions exacerbates H2O2-induced necroptotic cell death via sequential activation of RIP1/p38 MAPK/ROS signaling, suggesting GS28 has a protective role against necroptosis mediated by p38 MAPK inhibition.","method":"siRNA knockdown, p38 chemical inhibitor, necrostatin-1 pretreatment, flow cytometry, immunoblot for p38 activation","journal":"The Korean journal of physiology & pharmacology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — siRNA knockdown with pharmacological inhibitors; single lab, indirect pathway placement, no direct binding or biochemical reconstitution","pmids":["21860593"],"is_preprint":false}],"current_model":"GOSR1 (GS28) is a Golgi-localized Qb-SNARE that functions as a core component of multiple SNARE complexes—including syntaxin 5/GS28/Ykt6/Bet1 for late ER-to-Golgi transport, syntaxin 5/GS28/Ykt6/GS15 for intra-Golgi and endosome-to-TGN retrograde transport—where GS28–syntaxin 5 complex assembly/disassembly is driven by ATP-hydrolysis-dependent NSF/alpha-SNAP activity, while GATE-16 binding (facilitated by ATPase-independent NSF activity) protects GS28 from premature t-SNARE engagement during Golgi reassembly; additionally, COPI vesicles extract GS28 from cisternae to regulate inter-cisternal connectivity, ORP7 controls GS28 stability via GATE-16 sequestration and proteasomal degradation, and GS28 interacts with MDM2–p53 to inhibit p53 ubiquitination and enhance DNA-damage-induced apoptosis."},"narrative":{"mechanistic_narrative":"GOSR1 (GS28) is a cis-Golgi integral membrane Qb-SNARE that functions as a core component of the SNARE machinery driving vesicular transport through the secretory pathway [PMID:8638159]. It assembles into compositionally distinct SNARE complexes with syntaxin 5 as the central partner: a syntaxin 5/GS28/Ykt6/Bet1 complex acting in a late stage of ER-to-Golgi transport [PMID:11323436], and a syntaxin 5/GS28/Ykt6/GS15 complex operating in intra-Golgi (medial cisternae) transport and in retrograde transport from early/recycling endosomes to the trans-Golgi network [PMID:12388752, PMID:15215310]. The conserved SNARE motif is essential for fusion activity, and its t-SNARE function is so well preserved that human GOSR1 rescues rhodopsin trafficking and retinal degeneration in Drosophila gos28 mutants [PMID:25261468]. GS28–syntaxin 5 complexes are dynamically cycled by the ATP-hydrolysis-dependent action of NSF and alpha-SNAP, which dissociate assembled complexes [PMID:9325254], while a distinct ATPase-independent NSF activity promotes binding of GATE-16 to GS28 to shield it from premature engagement with syntaxin 5 during Golgi reassembly [PMID:12070132]. GS28 levels and trafficking are further regulated by extraction into COPI-coated vesicles to control inter-cisternal connectivity [PMID:23387339] and by ORP7, which destabilizes GS28 through GATE-16 sequestration and proteasomal degradation [PMID:21669198]. Beyond membrane traffic, GS28 also associates with MDM2 and p53 to inhibit p53 ubiquitination and enhance DNA-damage-induced apoptosis [PMID:22397410].","teleology":[{"year":1996,"claim":"Established the existence and identity of GS28 as a dedicated Golgi SNARE, answering whether a distinct integral membrane protein mediates the docking/fusion step of ER-to-Golgi transport.","evidence":"cDNA cloning and in vitro ER-Golgi transport assay with biochemical co-immunoprecipitation of a Golgi SNARE complex","pmids":["8638159"],"confidence":"High","gaps":["Did not resolve the full subunit composition of the functional fusion complex","No structural model of the SNARE bundle"]},{"year":1997,"claim":"Showed how GS28-containing complexes are recycled, defining the enzymatic logic of complex disassembly.","evidence":"Co-IP from Golgi extracts with ATP-hydrolysis inhibition and immobilized alpha-SNAP binding assays","pmids":["9325254"],"confidence":"High","gaps":["Did not establish the kinetics or in vivo regulation of disassembly","Did not identify which assembled complex is the physiological NSF substrate"]},{"year":2001,"claim":"Defined a specific four-SNARE complex (syntaxin 5/GS28/Ykt6/Bet1) for late ER-to-Golgi transport, identifying GS28's cognate partners at this step.","evidence":"Reciprocal co-immunoprecipitation plus in vitro transport assay with Ykt6 antibody inhibition","pmids":["11323436"],"confidence":"High","gaps":["Did not distinguish which SNARE provides t- versus v-SNARE roles structurally","Stoichiometry of the complex not determined"]},{"year":2002,"claim":"Identified a distinct GS28 complex (with GS15) for intra-Golgi transport and linked it to COPI traffic, showing GS28 operates in compositionally separate complexes at different transport steps.","evidence":"Co-IP, immuno-EM, siRNA knockdown and dominant-negative GS15 mutants","pmids":["12388752"],"confidence":"High","gaps":["Mechanism of complex switching between Bet1- and GS15-containing forms unknown","Did not define how COPI selects this complex"]},{"year":2002,"claim":"Revealed a regulatory checkpoint protecting GS28 from premature t-SNARE pairing, distinguishing two separable NSF activities during Golgi reassembly.","evidence":"Cell-free Golgi cisternae assembly assay with NSF comatose mutant and biochemical GATE-16 binding assays","pmids":["12070132"],"confidence":"High","gaps":["How GATE-16 release is timed to permit fusion not resolved","Structural basis of GATE-16/GS28 interaction unknown"]},{"year":2004,"claim":"Extended the GS15-containing complex to a new transport route, showing the same four-SNARE assembly drives endosome-to-TGN retrograde transport.","evidence":"In vitro STxB retrograde transport assay with SNARE-specific antibodies plus siRNA knockdown in HeLa cells","pmids":["15215310"],"confidence":"High","gaps":["Did not identify the upstream tethering factors directing this complex to the retrograde route","Regulation distinguishing anterograde versus retrograde use of the same complex unclear"]},{"year":2009,"claim":"Tested the physiological requirement for GS28 in a whole organism, revealing functional redundancy with Ykt6 in intra-Golgi transport and development.","evidence":"C. elegans deletion mutants, synthetic-lethal RNAi screen and epistasis analysis","pmids":["19624756"],"confidence":"Medium","gaps":["Molecular basis of GS28/Ykt6 redundancy not biochemically defined","Mammalian relevance of the redundancy not tested"]},{"year":2011,"claim":"Identified a post-translational control of GS28 abundance, linking oxysterol/ORP7 signaling to GATE-16 sequestration and proteasomal turnover of GS28.","evidence":"Yeast two-hybrid, BiFC, truncation mapping, siRNA/overexpression and proteasome inhibitor experiments","pmids":["21669198"],"confidence":"Medium","gaps":["E3 ligase mediating GS28 degradation not identified","Single lab; physiological context of oxysterol regulation untested"]},{"year":2011,"claim":"Proposed a non-trafficking protective role for GS28 against oxidative necroptotic death via p38 MAPK suppression.","evidence":"siRNA knockdown with p38 inhibitor and necrostatin-1 in glutathione-depleted SK-N-SH cells","pmids":["21860593"],"confidence":"Low","gaps":["No direct binding or biochemical link between GS28 and the RIP1/p38/ROS axis","Indirect pathway placement; single lab, not independently confirmed"]},{"year":2012,"claim":"Uncovered a moonlighting role for GS28 in the DNA-damage response, showing it stabilizes p53 by blocking MDM2-mediated ubiquitination.","evidence":"Co-IP, shRNA knockdown, ubiquitination assay and p53-null rescue after cisplatin treatment","pmids":["22397410"],"confidence":"Medium","gaps":["Whether the GS28-MDM2-p53 interaction is direct or Golgi-localized unclear","Single lab; structural basis of the trimeric complex unknown"]},{"year":2013,"claim":"Linked GS28 sorting into COPI vesicles to Golgi architecture, showing its extraction from cisternae regulates inter-cisternal connectivity during intra-Golgi transport.","evidence":"Subcellular fractionation, in vitro intra-Golgi transport with vesicle re-addition, EM morphometry and auxin-inducible degron depletion of εCOP","pmids":["23387339"],"confidence":"Medium","gaps":["Sorting signal that directs GS28 into COPI vesicles not defined","Single lab reconstitution"]},{"year":2014,"claim":"Demonstrated in vivo conservation of GS28 t-SNARE function and the dispensability of its transmembrane domain for fusion via cross-species rescue.","evidence":"Drosophila gos28 loss-of-function mutants, SNARE-motif mutagenesis and transgenic rescue with human GOSR1","pmids":["25261468"],"confidence":"High","gaps":["Did not test human GOSR1 in mammalian loss-of-function context","Did not resolve how transmembrane-anchorless GS28 supports fusion mechanistically"]},{"year":null,"claim":"How GS28's membrane-trafficking roles mechanistically intersect with its apoptotic and stress-protective functions, and whether the latter are direct, remains unresolved.","evidence":"No timeline study reconciles the SNARE function with the p53/p38 roles or provides structural information on GS28 complexes","pmids":[],"confidence":"Low","gaps":["No structural model of any GS28-containing complex","Direct versus indirect basis of the MDM2-p53 and p38 connections unestablished","No human disease link characterized in the corpus"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0005198","term_label":"structural molecule activity","supporting_discovery_ids":[0,2,3,10]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,4]}],"localization":[{"term_id":"GO:0005794","term_label":"Golgi apparatus","supporting_discovery_ids":[0,3,9]},{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]}],"pathway":[{"term_id":"R-HSA-5653656","term_label":"Vesicle-mediated transport","supporting_discovery_ids":[0,2,3,5]},{"term_id":"R-HSA-9609507","term_label":"Protein localization","supporting_discovery_ids":[5]},{"term_id":"R-HSA-5357801","term_label":"Programmed Cell Death","supporting_discovery_ids":[8]}],"complexes":["syntaxin 5/GS28/Ykt6/Bet1 SNARE complex","syntaxin 5/GS28/Ykt6/GS15 SNARE complex","GS28-MDM2-p53 complex"],"partners":["STX5","YKT6","BET1","GS15","GABARAPL2","OSBPL7","MDM2","TP53"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O95249","full_name":"Golgi SNAP receptor complex member 1","aliases":["28 kDa Golgi SNARE protein","28 kDa cis-Golgi SNARE p28","GOS-28"],"length_aa":250,"mass_kda":28.6,"function":"Involved in transport from the ER to the Golgi apparatus as well as in intra-Golgi transport. It belongs to a super-family of proteins called t-SNAREs or soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor. May play a protective role against hydrogen peroxide induced cytotoxicity under glutathione depleted conditions in neuronal cells by regulating the intracellular ROS levels via inhibition of p38 MAPK (MAPK11, MAPK12, MAPK13 and MAPK14). Participates in docking and fusion stage of ER to cis-Golgi transport. Plays an important physiological role in VLDL-transport vesicle-Golgi fusion and thus in VLDL delivery to the hepatic cis-Golgi","subcellular_location":"Golgi apparatus membrane","url":"https://www.uniprot.org/uniprotkb/O95249/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/GOSR1","classification":"Not Classified","n_dependent_lines":38,"n_total_lines":1208,"dependency_fraction":0.03145695364238411},"opencell":{"profiled":true,"resolved_as":"","ensg_id":"ENSG00000108587","cell_line_id":"CID000753","localizations":[{"compartment":"vesicles","grade":3}],"interactors":[{"gene":"BET1L","stoichiometry":10.0},{"gene":"BNIP1","stoichiometry":10.0},{"gene":"SCFD1","stoichiometry":10.0},{"gene":"NSF","stoichiometry":10.0},{"gene":"GOSR2","stoichiometry":10.0},{"gene":"ZW10","stoichiometry":4.0},{"gene":"SLC35E1","stoichiometry":4.0},{"gene":"VAMP3;VAMP2","stoichiometry":0.2},{"gene":"NAPA","stoichiometry":0.2},{"gene":"USE1","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/target/CID000753","total_profiled":1310},"omim":[{"mim_id":"615417","title":"BET1-LIKE PROTEIN; BET1L","url":"https://www.omim.org/entry/615417"},{"mim_id":"607029","title":"VESICLE-ASSOCIATED MEMBRANE PROTEIN 5; VAMP5","url":"https://www.omim.org/entry/607029"},{"mim_id":"604027","title":"GOLGI SNAP RECEPTOR COMPLEX MEMBER 2; GOSR2","url":"https://www.omim.org/entry/604027"},{"mim_id":"604026","title":"GOLGI SNAP RECEPTOR COMPLEX MEMBER 1; GOSR1","url":"https://www.omim.org/entry/604026"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/GOSR1"},"hgnc":{"alias_symbol":["GOS28","P28","GS28","GOS-28","GOLIM2"],"prev_symbol":[]},"alphafold":{"accession":"O95249","domains":[{"cath_id":"1.20.58,1.20.58","chopping":"2-42_61-153","consensus_level":"high","plddt":87.1021,"start":2,"end":153}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O95249","model_url":"https://alphafold.ebi.ac.uk/files/AF-O95249-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O95249-F1-predicted_aligned_error_v6.png","plddt_mean":84.31},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=GOSR1","jax_strain_url":"https://www.jax.org/strain/search?query=GOSR1"},"sequence":{"accession":"O95249","fasta_url":"https://rest.uniprot.org/uniprotkb/O95249.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O95249/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O95249"}},"corpus_meta":[{"pmid":"15215310","id":"PMC_15215310","title":"Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex in transport from the early/recycling endosome to the trans-Golgi network.","date":"2004","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/15215310","citation_count":135,"is_preprint":false},{"pmid":"8638159","id":"PMC_8638159","title":"GS28, a 28-kilodalton Golgi SNARE that participates in ER-Golgi transport.","date":"1996","source":"Science (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/8638159","citation_count":125,"is_preprint":false},{"pmid":"11323436","id":"PMC_11323436","title":"Ykt6 forms a SNARE complex with syntaxin 5, GS28, and Bet1 and participates in a late stage in endoplasmic reticulum-Golgi transport.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11323436","citation_count":113,"is_preprint":false},{"pmid":"12388752","id":"PMC_12388752","title":"GS15 forms a SNARE complex with syntaxin 5, GS28, and Ykt6 and is implicated in traffic in the early cisternae of the Golgi apparatus.","date":"2002","source":"Molecular biology of the cell","url":"https://pubmed.ncbi.nlm.nih.gov/12388752","citation_count":104,"is_preprint":false},{"pmid":"12070132","id":"PMC_12070132","title":"Sequential SNARE disassembly and GATE-16-GOS-28 complex assembly mediated by distinct NSF activities drives Golgi membrane fusion.","date":"2002","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/12070132","citation_count":70,"is_preprint":false},{"pmid":"23387339","id":"PMC_23387339","title":"Segregation of the Qb-SNAREs GS27 and GS28 into Golgi vesicles regulates intra-Golgi transport.","date":"2013","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/23387339","citation_count":34,"is_preprint":false},{"pmid":"9325254","id":"PMC_9325254","title":"N-Ethylmaleimide-sensitive factor (NSF) and alpha-soluble NSF attachment proteins (SNAP) mediate dissociation of GS28-syntaxin 5 Golgi SNAP receptors (SNARE) complex.","date":"1997","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/9325254","citation_count":34,"is_preprint":false},{"pmid":"25261468","id":"PMC_25261468","title":"The Gos28 SNARE protein mediates intra-Golgi transport of rhodopsin and is required for photoreceptor survival.","date":"2014","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25261468","citation_count":18,"is_preprint":false},{"pmid":"21669198","id":"PMC_21669198","title":"OSBP-related protein 7 interacts with GATE-16 and negatively regulates GS28 protein stability.","date":"2011","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/21669198","citation_count":18,"is_preprint":false},{"pmid":"19624756","id":"PMC_19624756","title":"Functional analysis of GS28, an intra-Golgi SNARE, in Caenorhabditis elegans.","date":"2009","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/19624756","citation_count":16,"is_preprint":false},{"pmid":"22397410","id":"PMC_22397410","title":"Golgi-SNARE GS28 potentiates cisplatin-induced apoptosis by forming GS28-MDM2-p53 complexes and by preventing the ubiquitination and degradation of p53.","date":"2012","source":"The Biochemical journal","url":"https://pubmed.ncbi.nlm.nih.gov/22397410","citation_count":15,"is_preprint":false},{"pmid":"21860593","id":"PMC_21860593","title":"GS28 Protects Neuronal Cell Death Induced by Hydrogen Peroxide under Glutathione-Depleted Condition.","date":"2011","source":"The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/21860593","citation_count":13,"is_preprint":false},{"pmid":"10198168","id":"PMC_10198168","title":"cDNA characterization and chromosomal mapping of human golgi SNARE GS27 and GS28 to chromosome 17.","date":"1999","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/10198168","citation_count":6,"is_preprint":false},{"pmid":"31066958","id":"PMC_31066958","title":"Role of GS28 in sodium nitroprusside-induced cell death in cervical carcinoma cells.","date":"2019","source":"Journal of biochemical and molecular toxicology","url":"https://pubmed.ncbi.nlm.nih.gov/31066958","citation_count":5,"is_preprint":false},{"pmid":"36924089","id":"PMC_36924089","title":"Diverse Role of SNARE Protein GS28 in Vesicle Trafficking and Diseases.","date":"2023","source":"Current protein & peptide science","url":"https://pubmed.ncbi.nlm.nih.gov/36924089","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9274,"output_tokens":3252,"usd":0.038301,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":10680,"output_tokens":3923,"usd":0.075737,"stage2_stop_reason":"end_turn"},"total_usd":0.114038,"stage1_batch_id":"msgbatch_01DUPACZi7AAWwuZiUjseQF4","stage2_batch_id":"msgbatch_018yt7chE3f48PEFtDwtj6AE","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1996,\n      \"finding\": \"GS28 (GOSR1) was identified as a 28-kDa cis-Golgi integral membrane protein with a central coiled-coil domain and C-terminal membrane anchor, and was established as a core component of the Golgi SNARE complex participating in the docking and fusion stage of ER-to-Golgi transport, demonstrated by an in vitro ER-Golgi transport assay.\",\n      \"method\": \"cDNA cloning, in vitro ER-Golgi transport assay, biochemical co-immunoprecipitation\",\n      \"journal\": \"Science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro transport assay with functional inhibition plus biochemical complex identification; foundational paper replicated by multiple subsequent studies\",\n      \"pmids\": [\"8638159\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1997,\n      \"finding\": \"GS28 and syntaxin 5 form a protein complex in Golgi extracts that is dissociated by the concerted, ATP-hydrolysis-dependent action of alpha-SNAP and NSF; after dissociation, GS28 (but not syntaxin 5) binds immobilized alpha-SNAP.\",\n      \"method\": \"Co-immunoprecipitation from Golgi extracts, ATP hydrolysis inhibition experiments, immobilized alpha-SNAP binding assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — direct biochemical reconstitution with ATP hydrolysis controls, multiple orthogonal methods in one study\",\n      \"pmids\": [\"9325254\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"GS28 forms a SNARE complex with Ykt6, syntaxin 5, and Bet1 at the Golgi, as demonstrated by co-immunoprecipitation; this complex participates in a late stage of ER-to-Golgi transport.\",\n      \"method\": \"Co-immunoprecipitation, in vitro ER-Golgi transport assay with Ykt6 antibody inhibition, double immunofluorescence labeling\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — reciprocal Co-IP combined with functional in vitro transport inhibition; replicated in subsequent studies\",\n      \"pmids\": [\"11323436\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"GS28 forms a distinct SNARE complex with syntaxin 5, GS15, and Ykt6 implicated in early intra-Golgi (medial) cisternae transport; GS15 co-immunoprecipitates with COPI coat components, placing this complex in COPI-dependent traffic.\",\n      \"method\": \"Co-immunoprecipitation, immuno-electron microscopy, siRNA knockdown of GS15, overexpression of dominant-negative GS15 mutants\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — multiple orthogonal methods (Co-IP, immuno-EM, siRNA, dominant-negative); independently consistent with prior complex characterizations\",\n      \"pmids\": [\"12388752\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"NSF and alpha-SNAP mediate binding of GATE-16 to GS28 (a Golgi v-SNARE) in an ATPase-independent but ATP-requiring manner during Golgi reassembly; GATE-16 binding to GS28 prevents GS28 from interacting with its cognate t-SNARE syntaxin 5, thereby regulating SNARE function at the onset of Golgi reassembly.\",\n      \"method\": \"Cell-free Golgi cisternae assembly assay, NSF mutant analysis (G274E; comatose), biochemical binding assays\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — cell-free reconstitution with NSF mutants and biochemical binding validation; mechanistic dissection of two distinct NSF activities\",\n      \"pmids\": [\"12070132\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"The syntaxin 5/GS28/Ykt6/GS15 SNARE complex functions in transport from the early/recycling endosome to the trans-Golgi network (EE/RE-TGN), as shown by specific inhibition of STxB retrograde transport by antibodies against each of these four SNAREs in an in vitro transport assay.\",\n      \"method\": \"In vitro STxB transport assay with SNARE-specific antibodies, siRNA knockdown of GS15 in HeLa cells, SNX3-overexpression morphological analysis\",\n      \"journal\": \"Molecular biology of the cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — in vitro reconstituted transport assay plus siRNA validation, multiple SNAREs tested systematically\",\n      \"pmids\": [\"15215310\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"In C. elegans, GS28 and Ykt6 act cooperatively/redundantly in intra-Golgi transport; loss of GS28 combined with Ykt6 knockdown impairs embryonic development, seam cell proliferation/differentiation, and proper expression of Golgi-resident proteins.\",\n      \"method\": \"C. elegans deletion mutant generation, synthetic lethal RNAi screen, epistasis analysis\",\n      \"journal\": \"Genes to cells\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis with defined cellular phenotypes in a model organism; single lab but multiple readouts\",\n      \"pmids\": [\"19624756\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"ORP7 negatively regulates GS28 protein stability through sequestration of GATE-16 via the N-terminal domain (aa 1–142 of ORP7 interacting with aa 30–117 of GATE-16); ORP7 knockdown increases GS28 levels, whereas ORP7 overexpression decreases GS28 levels via proteasomal degradation. The oxysterol 25-hydroxycholesterol potentiates GS28 destabilization in an ORP7-dependent manner.\",\n      \"method\": \"Yeast two-hybrid, bimolecular fluorescence complementation (BiFC), siRNA knockdown, overexpression with truncation mutants, proteasome inhibitor experiments\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — yeast two-hybrid confirmed by BiFC in living cells, domain mapping with truncation mutants, functional GS28 stability readout; single lab\",\n      \"pmids\": [\"21669198\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"GS28 forms a complex with MDM2 and p53, prevents MDM2-mediated ubiquitination and proteasomal degradation of p53, and thereby enhances p53 stability and pro-apoptotic activity (Bax induction, Ser46 phosphorylation) specifically in response to cisplatin-induced DNA damage.\",\n      \"method\": \"Co-immunoprecipitation, shRNA knockdown, overexpression, ubiquitination assay, p53-null cell rescue with ectopic p53\",\n      \"journal\": \"The Biochemical journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2–3 / Moderate — Co-IP of GS28-MDM2-p53 complex, ubiquitination assay, and p53-null rescue; single lab with multiple complementary readouts\",\n      \"pmids\": [\"22397410\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"GS28 (together with GS27) is enriched in COPI-coated Golgi vesicles and is extracted from Golgi cisternae into these vesicles during intra-Golgi transport; re-addition of GS28/GS27-containing Golgi vesicles restores in vitro intra-Golgi transport, indicating that segregation of GS28 into vesicles regulates intra-Golgi transport by controlling inter-cisternal connectivity.\",\n      \"method\": \"Subcellular fractionation, in vitro intra-Golgi transport assay, EM morphometry, εCOP degradation (auxin-inducible degron), immunofluorescence\",\n      \"journal\": \"Traffic\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — in vitro reconstitution of intra-Golgi transport with vesicle re-addition, corroborated by EM; single lab\",\n      \"pmids\": [\"23387339\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"In Drosophila photoreceptors, Gos28 (ortholog of human GOSR1) mediates intra-Golgi transport of rhodopsin downstream of alpha-mannosidase II in the medial-Golgi; key residues in the SNARE motif are required for function whereas the transmembrane domain is dispensable for vesicle fusion, consistent with a t-SNARE role. Human GOS28 (GOSR1) rescues both rhodopsin trafficking defects and retinal degeneration in Drosophila gos28 mutants, demonstrating functional conservation.\",\n      \"method\": \"Drosophila gos28 loss-of-function mutants, site-directed mutagenesis of SNARE motif, transgenic rescue with human GOSR1, immunofluorescence co-localization with Golgi markers\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Strong — genetic loss-of-function with defined trafficking phenotype, SNARE motif mutagenesis, and cross-species rescue with human protein; multiple orthogonal methods\",\n      \"pmids\": [\"25261468\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"GS28 knockdown in neuronal SK-N-SH cells under glutathione-depleted conditions exacerbates H2O2-induced necroptotic cell death via sequential activation of RIP1/p38 MAPK/ROS signaling, suggesting GS28 has a protective role against necroptosis mediated by p38 MAPK inhibition.\",\n      \"method\": \"siRNA knockdown, p38 chemical inhibitor, necrostatin-1 pretreatment, flow cytometry, immunoblot for p38 activation\",\n      \"journal\": \"The Korean journal of physiology & pharmacology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — siRNA knockdown with pharmacological inhibitors; single lab, indirect pathway placement, no direct binding or biochemical reconstitution\",\n      \"pmids\": [\"21860593\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"GOSR1 (GS28) is a Golgi-localized Qb-SNARE that functions as a core component of multiple SNARE complexes—including syntaxin 5/GS28/Ykt6/Bet1 for late ER-to-Golgi transport, syntaxin 5/GS28/Ykt6/GS15 for intra-Golgi and endosome-to-TGN retrograde transport—where GS28–syntaxin 5 complex assembly/disassembly is driven by ATP-hydrolysis-dependent NSF/alpha-SNAP activity, while GATE-16 binding (facilitated by ATPase-independent NSF activity) protects GS28 from premature t-SNARE engagement during Golgi reassembly; additionally, COPI vesicles extract GS28 from cisternae to regulate inter-cisternal connectivity, ORP7 controls GS28 stability via GATE-16 sequestration and proteasomal degradation, and GS28 interacts with MDM2–p53 to inhibit p53 ubiquitination and enhance DNA-damage-induced apoptosis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"GOSR1 (GS28) is a cis-Golgi integral membrane Qb-SNARE that functions as a core component of the SNARE machinery driving vesicular transport through the secretory pathway [#0]. It assembles into compositionally distinct SNARE complexes with syntaxin 5 as the central partner: a syntaxin 5/GS28/Ykt6/Bet1 complex acting in a late stage of ER-to-Golgi transport [#2], and a syntaxin 5/GS28/Ykt6/GS15 complex operating in intra-Golgi (medial cisternae) transport and in retrograde transport from early/recycling endosomes to the trans-Golgi network [#3, #5]. The conserved SNARE motif is essential for fusion activity, and its t-SNARE function is so well preserved that human GOSR1 rescues rhodopsin trafficking and retinal degeneration in Drosophila gos28 mutants [#10]. GS28\\u2013syntaxin 5 complexes are dynamically cycled by the ATP-hydrolysis-dependent action of NSF and alpha-SNAP, which dissociate assembled complexes [#1], while a distinct ATPase-independent NSF activity promotes binding of GATE-16 to GS28 to shield it from premature engagement with syntaxin 5 during Golgi reassembly [#4]. GS28 levels and trafficking are further regulated by extraction into COPI-coated vesicles to control inter-cisternal connectivity [#9] and by ORP7, which destabilizes GS28 through GATE-16 sequestration and proteasomal degradation [#7]. Beyond membrane traffic, GS28 also associates with MDM2 and p53 to inhibit p53 ubiquitination and enhance DNA-damage-induced apoptosis [#8].\",\n  \"teleology\": [\n    {\n      \"year\": 1996,\n      \"claim\": \"Established the existence and identity of GS28 as a dedicated Golgi SNARE, answering whether a distinct integral membrane protein mediates the docking/fusion step of ER-to-Golgi transport.\",\n      \"evidence\": \"cDNA cloning and in vitro ER-Golgi transport assay with biochemical co-immunoprecipitation of a Golgi SNARE complex\",\n      \"pmids\": [\"8638159\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the full subunit composition of the functional fusion complex\", \"No structural model of the SNARE bundle\"]\n    },\n    {\n      \"year\": 1997,\n      \"claim\": \"Showed how GS28-containing complexes are recycled, defining the enzymatic logic of complex disassembly.\",\n      \"evidence\": \"Co-IP from Golgi extracts with ATP-hydrolysis inhibition and immobilized alpha-SNAP binding assays\",\n      \"pmids\": [\"9325254\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not establish the kinetics or in vivo regulation of disassembly\", \"Did not identify which assembled complex is the physiological NSF substrate\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Defined a specific four-SNARE complex (syntaxin 5/GS28/Ykt6/Bet1) for late ER-to-Golgi transport, identifying GS28's cognate partners at this step.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation plus in vitro transport assay with Ykt6 antibody inhibition\",\n      \"pmids\": [\"11323436\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not distinguish which SNARE provides t- versus v-SNARE roles structurally\", \"Stoichiometry of the complex not determined\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Identified a distinct GS28 complex (with GS15) for intra-Golgi transport and linked it to COPI traffic, showing GS28 operates in compositionally separate complexes at different transport steps.\",\n      \"evidence\": \"Co-IP, immuno-EM, siRNA knockdown and dominant-negative GS15 mutants\",\n      \"pmids\": [\"12388752\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of complex switching between Bet1- and GS15-containing forms unknown\", \"Did not define how COPI selects this complex\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Revealed a regulatory checkpoint protecting GS28 from premature t-SNARE pairing, distinguishing two separable NSF activities during Golgi reassembly.\",\n      \"evidence\": \"Cell-free Golgi cisternae assembly assay with NSF comatose mutant and biochemical GATE-16 binding assays\",\n      \"pmids\": [\"12070132\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How GATE-16 release is timed to permit fusion not resolved\", \"Structural basis of GATE-16/GS28 interaction unknown\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Extended the GS15-containing complex to a new transport route, showing the same four-SNARE assembly drives endosome-to-TGN retrograde transport.\",\n      \"evidence\": \"In vitro STxB retrograde transport assay with SNARE-specific antibodies plus siRNA knockdown in HeLa cells\",\n      \"pmids\": [\"15215310\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not identify the upstream tethering factors directing this complex to the retrograde route\", \"Regulation distinguishing anterograde versus retrograde use of the same complex unclear\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Tested the physiological requirement for GS28 in a whole organism, revealing functional redundancy with Ykt6 in intra-Golgi transport and development.\",\n      \"evidence\": \"C. elegans deletion mutants, synthetic-lethal RNAi screen and epistasis analysis\",\n      \"pmids\": [\"19624756\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis of GS28/Ykt6 redundancy not biochemically defined\", \"Mammalian relevance of the redundancy not tested\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Identified a post-translational control of GS28 abundance, linking oxysterol/ORP7 signaling to GATE-16 sequestration and proteasomal turnover of GS28.\",\n      \"evidence\": \"Yeast two-hybrid, BiFC, truncation mapping, siRNA/overexpression and proteasome inhibitor experiments\",\n      \"pmids\": [\"21669198\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"E3 ligase mediating GS28 degradation not identified\", \"Single lab; physiological context of oxysterol regulation untested\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Proposed a non-trafficking protective role for GS28 against oxidative necroptotic death via p38 MAPK suppression.\",\n      \"evidence\": \"siRNA knockdown with p38 inhibitor and necrostatin-1 in glutathione-depleted SK-N-SH cells\",\n      \"pmids\": [\"21860593\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No direct binding or biochemical link between GS28 and the RIP1/p38/ROS axis\", \"Indirect pathway placement; single lab, not independently confirmed\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Uncovered a moonlighting role for GS28 in the DNA-damage response, showing it stabilizes p53 by blocking MDM2-mediated ubiquitination.\",\n      \"evidence\": \"Co-IP, shRNA knockdown, ubiquitination assay and p53-null rescue after cisplatin treatment\",\n      \"pmids\": [\"22397410\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether the GS28-MDM2-p53 interaction is direct or Golgi-localized unclear\", \"Single lab; structural basis of the trimeric complex unknown\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Linked GS28 sorting into COPI vesicles to Golgi architecture, showing its extraction from cisternae regulates inter-cisternal connectivity during intra-Golgi transport.\",\n      \"evidence\": \"Subcellular fractionation, in vitro intra-Golgi transport with vesicle re-addition, EM morphometry and auxin-inducible degron depletion of \\u03b5COP\",\n      \"pmids\": [\"23387339\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Sorting signal that directs GS28 into COPI vesicles not defined\", \"Single lab reconstitution\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Demonstrated in vivo conservation of GS28 t-SNARE function and the dispensability of its transmembrane domain for fusion via cross-species rescue.\",\n      \"evidence\": \"Drosophila gos28 loss-of-function mutants, SNARE-motif mutagenesis and transgenic rescue with human GOSR1\",\n      \"pmids\": [\"25261468\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not test human GOSR1 in mammalian loss-of-function context\", \"Did not resolve how transmembrane-anchorless GS28 supports fusion mechanistically\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How GS28's membrane-trafficking roles mechanistically intersect with its apoptotic and stress-protective functions, and whether the latter are direct, remains unresolved.\",\n      \"evidence\": \"No timeline study reconciles the SNARE function with the p53/p38 roles or provides structural information on GS28 complexes\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No structural model of any GS28-containing complex\", \"Direct versus indirect basis of the MDM2-p53 and p38 connections unestablished\", \"No human disease link characterized in the corpus\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005198\", \"supporting_discovery_ids\": [0, 2, 3, 10]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 4]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [0, 3, 9]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-5653656\", \"supporting_discovery_ids\": [0, 2, 3, 5]},\n      {\"term_id\": \"R-HSA-9609507\", \"supporting_discovery_ids\": [5]},\n      {\"term_id\": \"R-HSA-5357801\", \"supporting_discovery_ids\": [8]}\n    ],\n    \"complexes\": [\n      \"syntaxin 5/GS28/Ykt6/Bet1 SNARE complex\",\n      \"syntaxin 5/GS28/Ykt6/GS15 SNARE complex\",\n      \"GS28-MDM2-p53 complex\"\n    ],\n    \"partners\": [\n      \"STX5\",\n      \"YKT6\",\n      \"BET1\",\n      \"GS15\",\n      \"GABARAPL2\",\n      \"OSBPL7\",\n      \"MDM2\",\n      \"TP53\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":5,"faith_total":6,"faith_pct":83.33333333333333}}