{"gene":"VSIG2","run_date":"2026-04-28T23:00:23","timeline":{"discoveries":[{"year":1998,"finding":"VSIG2 (human CTH) was identified as a member of a novel immunoglobulin superfamily (IgSF) subset defined by the Xenopus cortical thymocyte marker CTX. The protein contains one variable-type and one C2-type IgSF domain (each encoded by two half-domain exons), a transmembrane segment free of charged residues, and a ~70 amino acid cytoplasmic tail. The variable domain is not produced by somatic rearrangement but by constitutive splicing of two half-domain exons. The C2 domain carries an extra pair of cysteines. Human CTH (VSIG2) and mouse CTM share these structural and genetic features with CTX/ChT1 but, unlike the Xenopus/chicken orthologs, are not lymphocyte-specific, placing VSIG2 in a conserved vertebrate IgSF subfamily that also includes the A33 antigen and CAR.","method":"cDNA cloning, gene structure analysis (exon mapping), sequence homology, domain architecture determination","journal":"European journal of immunology","confidence":"Medium","confidence_rationale":"Tier 2 — structural characterization by cloning and gene analysis in a single foundational study; domain architecture confirmed by sequencing and comparative genomics","pmids":["9862345"],"is_preprint":false},{"year":2003,"finding":"VSIG2 was identified as a novel secreted or transmembrane protein through the Secreted Protein Discovery Initiative (SPDI), using a biological signal sequence trap in yeast and computational signal sequence prediction algorithms applied to human cDNA libraries, establishing it as a cell-surface protein with a signal peptide.","method":"Signal sequence trap (yeast biological assay), signal sequence prediction algorithms, full-length cDNA cloning","journal":"Genome research","confidence":"Low","confidence_rationale":"Tier 3 — identification by large-scale screen with computational support; no functional follow-up in same study","pmids":["12975309"],"is_preprint":false},{"year":2015,"finding":"VSIG2 was detected as part of the human protein interactome by high-throughput affinity-purification mass spectrometry (AP-MS) in HEK293T cells (BioPlex network), placing it within a network of co-associated proteins and enabling inference of its protein community membership.","method":"Affinity purification–mass spectrometry (AP-MS) at proteome scale","journal":"Cell","confidence":"Low","confidence_rationale":"Tier 3 — high-throughput AP-MS; specific VSIG2 interactions not individually validated","pmids":["26186194"],"is_preprint":false},{"year":2017,"finding":"BioPlex 2.0 further mapped VSIG2 protein–protein interactions by AP-MS in HEK293T cells at expanded proteome scale, providing additional co-association data and community-level functional context for VSIG2.","method":"Affinity purification–mass spectrometry (AP-MS), Markov clustering for community detection","journal":"Nature","confidence":"Low","confidence_rationale":"Tier 3 — large-scale AP-MS without individual validation of VSIG2 interactions","pmids":["28514442"],"is_preprint":false},{"year":2021,"finding":"BioPlex 3.0 confirmed and expanded VSIG2 protein interactions by performing AP-MS in both HEK293T and HCT116 cell lines, allowing cross-cell-line validation of VSIG2 co-associations and revealing cell-type-specific interaction rewiring.","method":"Affinity purification–mass spectrometry (AP-MS) in two cell lines, cross-cell-line comparison","journal":"Cell","confidence":"Low","confidence_rationale":"Tier 3 — proteome-scale AP-MS; VSIG2-specific interactions not individually validated but replicated across two cell lines","pmids":["33961781"],"is_preprint":false},{"year":2023,"finding":"In pancreatic ductal adenocarcinoma (PDAC), VSIG2 acts as a scaffold protein that simultaneously binds LAMTOR2 and mTOR, stabilizing their interaction and enhancing LAMTOR2-mediated phosphorylation/activation of mTOR and downstream signaling molecules. Overexpression of VSIG2 promotes PDAC cell proliferation, invasion, and migration, while VSIG2 knockdown reverses these effects. VSIG2 co-localizes with LAMTOR2 and mTOR as shown by immunofluorescence, and the VSIG2–LAMTOR2–mTOR ternary interaction was identified by mass spectrometry and confirmed by co-immunoprecipitation.","method":"Mass spectrometry (interactome), co-immunoprecipitation, immunofluorescence co-localization, western blotting (phosphorylation), CCK-8/colony formation/Transwell/scratch assays (loss- and gain-of-function), subcutaneous xenograft model","journal":"Cell communication and signaling : CCS","confidence":"Medium","confidence_rationale":"Tier 2 — reciprocal Co-IP plus MS identification of binding partners, orthogonal localization, and in vivo validation; single lab","pmids":["37626304"],"is_preprint":false},{"year":2025,"finding":"VSIG2 functions as an immunosuppressive ligand on the surface of activated antigen-presenting cells. It specifically binds to Nectin-2 (but not PD-1 or CTLA-4) and this interaction strongly inhibits T cell activation and proliferation. The VSIG2–Nectin-2 axis activates the STAT1/IRF1/GBP2 signaling pathway in T cells. Recombinant human VSIG2-Ig protein alleviated experimental autoimmune encephalomyelitis symptoms in vivo, and anti-VSIG2 antibodies inhibited pancreatic cancer growth.","method":"Binding assays (specificity screen against known immune receptors), T cell activation/proliferation assays, in vivo EAE model (VSIG2-Ig treatment), in vivo tumor growth assay (anti-VSIG2 antibody), pathway analysis (STAT1/IRF1/GBP2)","journal":"Journal of neuroinflammation","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding specificity established, functional loss/gain-of-function in vitro and in vivo, pathway identification; single lab but multiple orthogonal methods","pmids":["41350674"],"is_preprint":false},{"year":2025,"finding":"In gastric cancer (GC), VSIG2 suppresses tumor progression by directly interacting with ANXA2 (Annexin A2) at the cell membrane. Highly expressed VSIG2 competes with the E3 ubiquitin ligase FBXW10 for binding to ANXA2, and this competition relies on FBXW10-mediated K63 polyubiquitination of ANXA2 to promote ANXA2 membrane localization, which in turn inactivates NF-κB signaling and suppresses GC proliferation and metastasis. Co-immunoprecipitation, immunofluorescence, and ubiquitination assays confirmed the VSIG2–ANXA2 direct interaction and the FBXW10/K63-ubiquitin-dependent membrane targeting mechanism.","method":"Co-immunoprecipitation, immunofluorescence co-localization, ubiquitination assay (K63 linkage specificity), CCK-8/EdU/Transwell/wound healing assays, nude mouse subcutaneous tumor and liver metastasis models","journal":"Acta biochimica et biophysica Sinica","confidence":"Medium","confidence_rationale":"Tier 2 — direct binding by Co-IP confirmed, ubiquitination linkage specified, in vivo validation; single lab with multiple orthogonal methods","pmids":["41185558"],"is_preprint":false}],"current_model":"VSIG2 is an IgSF cell-surface protein that functions both as a tumor-cell-intrinsic scaffold (binding LAMTOR2 and mTOR to enhance mTOR activation in PDAC, and competing with FBXW10 for ANXA2 to suppress NF-κB via K63 ubiquitination-dependent membrane localization of ANXA2 in gastric cancer) and as an immunosuppressive ligand on antigen-presenting cells (binding Nectin-2 to inhibit T cell activation through the STAT1/IRF1/GBP2 pathway)."},"narrative":{"teleology":[{"year":1998,"claim":"Cloning of human CTH (VSIG2) established it as a new IgSF member with a distinctive V+C2 domain architecture encoded by half-domain exons, placing it in a conserved vertebrate subfamily alongside A33 and CAR and raising questions about its function outside lymphocytes.","evidence":"cDNA cloning, exon mapping, and comparative sequence analysis across species","pmids":["9862345"],"confidence":"Medium","gaps":["No functional role assigned; expression pattern outside lymphocytes not characterized","No binding partner or ligand identified","No loss-of-function data"]},{"year":2003,"claim":"A large-scale secreted protein discovery screen confirmed VSIG2 as a signal-peptide-bearing cell-surface protein, consistent with receptor or ligand function but without functional characterization.","evidence":"Signal sequence trap in yeast and computational prediction from human cDNA libraries","pmids":["12975309"],"confidence":"Low","gaps":["No functional follow-up; identification was part of a high-throughput screen without individual validation","Subcellular localization not directly imaged","No interacting partners tested"]},{"year":2023,"claim":"The first mechanistic role for VSIG2 was defined in PDAC, where it was shown to scaffold a LAMTOR2–mTOR ternary complex, enhancing mTOR phosphorylation and driving tumor cell proliferation and invasion — revealing VSIG2 as a signaling scaffold rather than solely a cell-surface receptor.","evidence":"Mass spectrometry interactome, reciprocal co-immunoprecipitation, immunofluorescence co-localization, gain/loss-of-function assays, and xenograft models in PDAC cells","pmids":["37626304"],"confidence":"Medium","gaps":["Single-lab study; the VSIG2–LAMTOR2–mTOR interaction has not been reconstituted with purified components","Which domain of VSIG2 mediates LAMTOR2 versus mTOR binding is unknown","Contribution of the extracellular Ig domains versus the cytoplasmic tail to scaffold function not dissected"]},{"year":2025,"claim":"Two studies expanded VSIG2's functional repertoire in opposite directions: as an immunosuppressive ligand binding Nectin-2 to inhibit T cells via STAT1/IRF1/GBP2, and as a tumor suppressor in gastric cancer that competes with FBXW10 for ANXA2, promoting K63-ubiquitination-dependent ANXA2 membrane localization to inactivate NF-κB.","evidence":"Binding specificity assays excluding PD-1/CTLA-4, T cell proliferation assays, EAE and tumor models (immunosuppression study); Co-IP, ubiquitination assays with K63 linkage specificity, xenograft and metastasis models (gastric cancer study)","pmids":["41350674","41185558"],"confidence":"Medium","gaps":["Both studies are from single laboratories and await independent replication","How VSIG2 simultaneously acts as an extracellular Nectin-2 ligand and an intracellular ANXA2/LAMTOR2 scaffold in the same cell is unresolved","Structural basis of the VSIG2–Nectin-2 interaction is undetermined","Context-dependent tumor-promoting (PDAC) versus tumor-suppressive (GC) roles are not reconciled mechanistically"]},{"year":null,"claim":"Key open questions include which domain(s) mediate each interaction, how tissue context determines the oncogenic versus tumor-suppressive output, and whether the immune-checkpoint and intracellular scaffold functions operate simultaneously or are mutually exclusive on the same cell.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No crystal or cryo-EM structure available for VSIG2 or its complexes","No genetic mouse model to assess physiological non-redundant function","Relationship between mTOR-scaffolding function and Nectin-2-binding function has not been tested"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[5,7]},{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[6]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,1,6,7]}],"pathway":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[6]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[5,6,7]},{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[6]}],"complexes":[],"partners":["LAMTOR2","MTOR","ANXA2","FBXW10","NECTIN2"],"other_free_text":[]},"mechanistic_narrative":"VSIG2 is a type I transmembrane immunoglobulin superfamily (IgSF) member containing one variable-type and one C2-type Ig domain, a transmembrane segment, and a cytoplasmic tail, belonging to a conserved vertebrate IgSF subfamily that includes the A33 antigen and CAR [PMID:9862345]. In pancreatic ductal adenocarcinoma, VSIG2 functions as an intracellular scaffold that simultaneously binds LAMTOR2 and mTOR, stabilizing their interaction to enhance mTOR phosphorylation and promote tumor cell proliferation and invasion [PMID:37626304]. In gastric cancer, VSIG2 suppresses tumor progression by competing with the E3 ligase FBXW10 for binding to ANXA2, thereby promoting FBXW10-mediated K63 polyubiquitination-dependent membrane localization of ANXA2 and consequent inactivation of NF-κB signaling [PMID:41185558]. On the surface of antigen-presenting cells, VSIG2 serves as an immunosuppressive ligand that binds Nectin-2 to inhibit T cell activation through the STAT1/IRF1/GBP2 pathway, and blockade of this axis with anti-VSIG2 antibodies inhibits pancreatic cancer growth in vivo [PMID:41350674]."},"prefetch_data":{"uniprot":{"accession":"Q96IQ7","full_name":"V-set and immunoglobulin domain-containing protein 2","aliases":["Cortical thymocyte-like protein","CT-like protein"],"length_aa":327,"mass_kda":34.3,"function":"","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q96IQ7/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/VSIG2","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/VSIG2","total_profiled":1310},"omim":[{"mim_id":"611693","title":"COXSACKIEVIRUS- AND ADENOVIRUS RECEPTOR-LIKE MEMBRANE PROTEIN; CLMP","url":"https://www.omim.org/entry/611693"},{"mim_id":"606011","title":"V-SET AND IMMUNOGLOBULIN DOMAINS-CONTAINING PROTEIN 2; VSIG2","url":"https://www.omim.org/entry/606011"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nucleoplasm","reliability":"Approved"}],"tissue_specificity":"Tissue enriched","tissue_distribution":"Detected in many","driving_tissues":[{"tissue":"stomach 1","ntpm":584.2}],"url":"https://www.proteinatlas.org/search/VSIG2"},"hgnc":{"alias_symbol":["CTXL","CTH"],"prev_symbol":[]},"alphafold":{"accession":"Q96IQ7","domains":[{"cath_id":"2.60.40.10","chopping":"26-143","consensus_level":"high","plddt":91.4475,"start":26,"end":143},{"cath_id":"2.60.40.10","chopping":"150-233","consensus_level":"high","plddt":90.0786,"start":150,"end":233}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96IQ7","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q96IQ7-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q96IQ7-F1-predicted_aligned_error_v6.png","plddt_mean":80.19},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=VSIG2","jax_strain_url":"https://www.jax.org/strain/search?query=VSIG2"},"sequence":{"accession":"Q96IQ7","fasta_url":"https://rest.uniprot.org/uniprotkb/Q96IQ7.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q96IQ7/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q96IQ7"}},"corpus_meta":[{"pmid":"30646578","id":"PMC_30646578","title":"Epigenetic 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therapy","url":"https://pubmed.ncbi.nlm.nih.gov/20659327","citation_count":91,"is_preprint":false,"source_track":"gene2pubmed"}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":28746,"output_tokens":1211,"usd":0.052201},"stage2":{"model":"claude-opus-4-6","input_tokens":4416,"output_tokens":1541,"usd":0.090908},"total_usd":0.393098,"stage1_batch_id":"msgbatch_01BparvgRZ9S2LMidvaoo86K","stage2_batch_id":"msgbatch_01NkBfv9SVZWthhS7j6mU6G3","note":"batch pricing = 50% of standard","round2_stage1":{"model":"claude-sonnet-4-6","input_tokens":34214,"output_tokens":2866,"usd":0.072816},"round2_rules_fired":"R2","round2_stage2":{"model":"claude-opus-4-6","input_tokens":5888,"output_tokens":3547,"usd":0.177173}},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"VSIG2 acts as a scaffold protein that simultaneously binds LAMTOR2 and mTOR, stabilizing their interaction and enhancing LAMTOR2-mediated phosphorylation/activation of mTOR and downstream signaling molecules, thereby promoting PDAC cell proliferation, invasion, and migration.\",\n      \"method\": \"Mass spectrometry, co-immunoprecipitation, immunofluorescence, loss-of-function/overexpression with proliferation/invasion/migration assays, western blotting for phospho-mTOR and downstream targets, subcutaneous xenograft model\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, MS-identified interaction, functional KD/OE with defined phenotype and pathway placement, replicated in vivo\",\n      \"pmids\": [\"37626304\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VSIG2 functions as an immunosuppressive ligand on the surface of activated antigen-presenting cells; it specifically binds Nectin-2 (not PD-1 or CTLA-4), inhibits T cell activation and proliferation, and regulates the STAT1/IRF1/GBP2 signaling pathway in T cells.\",\n      \"method\": \"Binding assays, functional T cell proliferation/activation assays, VSIG2-Ig fusion protein treatment in experimental autoimmune encephalomyelitis model, anti-VSIG2 antibody treatment in pancreatic cancer model, pathway analysis\",\n      \"journal\": \"Journal of neuroinflammation\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — direct binding identification, functional in vivo models with defined mechanistic pathway, multiple orthogonal approaches\",\n      \"pmids\": [\"41350674\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VSIG2 directly interacts with ANXA2 at the cell membrane in gastric cancer cells. Highly expressed VSIG2 competes with FBXW10 for ANXA2 binding, promoting FBXW10-mediated K63 polyubiquitination of ANXA2 that induces membrane localization of ANXA2 and inactivates NF-κB, thereby suppressing gastric cancer progression.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence, ubiquitination assays, CCK-8/EdU/Transwell/wound healing assays in vitro, nude mouse subcutaneous tumor and liver metastasis models in vivo\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP, ubiquitination assay, multiple orthogonal functional readouts in vitro and in vivo\",\n      \"pmids\": [\"41185558\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Knockdown of lncRNA-VSIG2-1:1 (a long noncoding RNA derived from the VSIG2 locus) promotes proliferation, migration, and tube formation of human pulmonary microvascular endothelial cells by activating the VEGF/PI3K/AKT signaling pathway; FISH assay determined its subcellular localization.\",\n      \"method\": \"lncRNA array, qRT-PCR, FISH for subcellular localization, adenoviral vector-mediated silencing/overexpression, CCK-8, migration, tubule formation assays, RNA-seq, western blotting for VEGF/p-PI3K/p-AKT\",\n      \"journal\": \"Respiratory research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 — single lab, lncRNA distinct from VSIG2 protein, KD with pathway placement but limited mechanistic depth\",\n      \"pmids\": [\"39568008\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VSIG2 is an immunoglobulin superfamily protein that functions both as a scaffold to recruit LAMTOR2 and mTOR and enhance mTOR phosphorylation in cancer cells, and as an immunosuppressive ligand on antigen-presenting cells that binds Nectin-2 to inhibit T cell activation via the STAT1/IRF1/GBP2 pathway; in gastric cancer, VSIG2 competes with FBXW10 for ANXA2 binding to promote K63-polyubiquitination-driven membrane localization of ANXA2 and NF-κB inactivation.\"\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\nI'll classify each paper first, then extract discoveries only from KEEP papers.\n\n**Classification:**\n\n- Papers [1]-[12] from retrieved corpus (CTH/cystathionine γ-lyase, capillary transit-time heterogeneity, cartilage thickness, chemotherapy abbreviation): EXCLUDE — alias collisions, none about VSIG2 protein\n- Paper [11] VSIG2 promotes malignant progression of PDAC (PMID:37626304): KEEP\n- Paper [23] lncRNA VSIG2-1:1 (PMID:39568008): EXCLUDE — alt-locus product (lncRNA)\n- Paper [28] VSIG2 hinders gastric cancer progression (PMID:41185558): KEEP\n- Paper [31] VSIG2 as immunosuppressive ligand with Nectin-2 (PMID:41350674): KEEP\n- Papers [37],[43] proteomics/social isolation mentioning VSIG2 as expression correlate: EXCLUDE — no mechanistic findings\n- Remaining retrieved papers: EXCLUDE (CTH enzyme, cartilage thickness, chemotherapy, etc.)\n\n**Gene2pubmed curated papers:**\n- PMID:25056061 (schizophrenia GWAS): EXCLUDE — no mechanism\n- PMID:12477932, 14702039, 15489334 (cDNA sequencing): EXCLUDE — no mechanism\n- PMID:26186194, 28514442, 33961781 (BioPlex interactomes): KEEP — VSIG2 interactions identified by AP-MS\n- PMID:12975309 (SPDI): KEEP — identifies VSIG2 as transmembrane/secreted protein\n- PMID:17192395 (megakaryocyte expression): EXCLUDE — expression only\n- PMID:9862345 (CTX/CTH Xenopus — defines CTH/VSIG2 family): KEEP — foundational structural characterization\n- PMID:15340161 (signal peptide prediction): EXCLUDE — computational tool\n- PMID:20659327 (SLE GWAS): EXCLUDE — GWAS association only\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"VSIG2 (human CTH) was identified as a member of a novel immunoglobulin superfamily (IgSF) subset defined by the Xenopus cortical thymocyte marker CTX. The protein contains one variable-type and one C2-type IgSF domain (each encoded by two half-domain exons), a transmembrane segment free of charged residues, and a ~70 amino acid cytoplasmic tail. The variable domain is not produced by somatic rearrangement but by constitutive splicing of two half-domain exons. The C2 domain carries an extra pair of cysteines. Human CTH (VSIG2) and mouse CTM share these structural and genetic features with CTX/ChT1 but, unlike the Xenopus/chicken orthologs, are not lymphocyte-specific, placing VSIG2 in a conserved vertebrate IgSF subfamily that also includes the A33 antigen and CAR.\",\n      \"method\": \"cDNA cloning, gene structure analysis (exon mapping), sequence homology, domain architecture determination\",\n      \"journal\": \"European journal of immunology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — structural characterization by cloning and gene analysis in a single foundational study; domain architecture confirmed by sequencing and comparative genomics\",\n      \"pmids\": [\"9862345\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"VSIG2 was identified as a novel secreted or transmembrane protein through the Secreted Protein Discovery Initiative (SPDI), using a biological signal sequence trap in yeast and computational signal sequence prediction algorithms applied to human cDNA libraries, establishing it as a cell-surface protein with a signal peptide.\",\n      \"method\": \"Signal sequence trap (yeast biological assay), signal sequence prediction algorithms, full-length cDNA cloning\",\n      \"journal\": \"Genome research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — identification by large-scale screen with computational support; no functional follow-up in same study\",\n      \"pmids\": [\"12975309\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"VSIG2 was detected as part of the human protein interactome by high-throughput affinity-purification mass spectrometry (AP-MS) in HEK293T cells (BioPlex network), placing it within a network of co-associated proteins and enabling inference of its protein community membership.\",\n      \"method\": \"Affinity purification–mass spectrometry (AP-MS) at proteome scale\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — high-throughput AP-MS; specific VSIG2 interactions not individually validated\",\n      \"pmids\": [\"26186194\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"BioPlex 2.0 further mapped VSIG2 protein–protein interactions by AP-MS in HEK293T cells at expanded proteome scale, providing additional co-association data and community-level functional context for VSIG2.\",\n      \"method\": \"Affinity purification–mass spectrometry (AP-MS), Markov clustering for community detection\",\n      \"journal\": \"Nature\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — large-scale AP-MS without individual validation of VSIG2 interactions\",\n      \"pmids\": [\"28514442\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"BioPlex 3.0 confirmed and expanded VSIG2 protein interactions by performing AP-MS in both HEK293T and HCT116 cell lines, allowing cross-cell-line validation of VSIG2 co-associations and revealing cell-type-specific interaction rewiring.\",\n      \"method\": \"Affinity purification–mass spectrometry (AP-MS) in two cell lines, cross-cell-line comparison\",\n      \"journal\": \"Cell\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — proteome-scale AP-MS; VSIG2-specific interactions not individually validated but replicated across two cell lines\",\n      \"pmids\": [\"33961781\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In pancreatic ductal adenocarcinoma (PDAC), VSIG2 acts as a scaffold protein that simultaneously binds LAMTOR2 and mTOR, stabilizing their interaction and enhancing LAMTOR2-mediated phosphorylation/activation of mTOR and downstream signaling molecules. Overexpression of VSIG2 promotes PDAC cell proliferation, invasion, and migration, while VSIG2 knockdown reverses these effects. VSIG2 co-localizes with LAMTOR2 and mTOR as shown by immunofluorescence, and the VSIG2–LAMTOR2–mTOR ternary interaction was identified by mass spectrometry and confirmed by co-immunoprecipitation.\",\n      \"method\": \"Mass spectrometry (interactome), co-immunoprecipitation, immunofluorescence co-localization, western blotting (phosphorylation), CCK-8/colony formation/Transwell/scratch assays (loss- and gain-of-function), subcutaneous xenograft model\",\n      \"journal\": \"Cell communication and signaling : CCS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — reciprocal Co-IP plus MS identification of binding partners, orthogonal localization, and in vivo validation; single lab\",\n      \"pmids\": [\"37626304\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"VSIG2 functions as an immunosuppressive ligand on the surface of activated antigen-presenting cells. It specifically binds to Nectin-2 (but not PD-1 or CTLA-4) and this interaction strongly inhibits T cell activation and proliferation. The VSIG2–Nectin-2 axis activates the STAT1/IRF1/GBP2 signaling pathway in T cells. Recombinant human VSIG2-Ig protein alleviated experimental autoimmune encephalomyelitis symptoms in vivo, and anti-VSIG2 antibodies inhibited pancreatic cancer growth.\",\n      \"method\": \"Binding assays (specificity screen against known immune receptors), T cell activation/proliferation assays, in vivo EAE model (VSIG2-Ig treatment), in vivo tumor growth assay (anti-VSIG2 antibody), pathway analysis (STAT1/IRF1/GBP2)\",\n      \"journal\": \"Journal of neuroinflammation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding specificity established, functional loss/gain-of-function in vitro and in vivo, pathway identification; single lab but multiple orthogonal methods\",\n      \"pmids\": [\"41350674\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"In gastric cancer (GC), VSIG2 suppresses tumor progression by directly interacting with ANXA2 (Annexin A2) at the cell membrane. Highly expressed VSIG2 competes with the E3 ubiquitin ligase FBXW10 for binding to ANXA2, and this competition relies on FBXW10-mediated K63 polyubiquitination of ANXA2 to promote ANXA2 membrane localization, which in turn inactivates NF-κB signaling and suppresses GC proliferation and metastasis. Co-immunoprecipitation, immunofluorescence, and ubiquitination assays confirmed the VSIG2–ANXA2 direct interaction and the FBXW10/K63-ubiquitin-dependent membrane targeting mechanism.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence co-localization, ubiquitination assay (K63 linkage specificity), CCK-8/EdU/Transwell/wound healing assays, nude mouse subcutaneous tumor and liver metastasis models\",\n      \"journal\": \"Acta biochimica et biophysica Sinica\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — direct binding by Co-IP confirmed, ubiquitination linkage specified, in vivo validation; single lab with multiple orthogonal methods\",\n      \"pmids\": [\"41185558\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"VSIG2 is an IgSF cell-surface protein that functions both as a tumor-cell-intrinsic scaffold (binding LAMTOR2 and mTOR to enhance mTOR activation in PDAC, and competing with FBXW10 for ANXA2 to suppress NF-κB via K63 ubiquitination-dependent membrane localization of ANXA2 in gastric cancer) and as an immunosuppressive ligand on antigen-presenting cells (binding Nectin-2 to inhibit T cell activation through the STAT1/IRF1/GBP2 pathway).\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"VSIG2 is an immunoglobulin superfamily member that functions as both a signaling scaffold in cancer cells and an immunosuppressive ligand on antigen-presenting cells. In pancreatic ductal adenocarcinoma, VSIG2 simultaneously binds LAMTOR2 and mTOR, stabilizing their interaction and enhancing mTOR phosphorylation to promote cell proliferation and invasion [PMID:37626304]. On activated antigen-presenting cells, VSIG2 engages Nectin-2 to inhibit T cell activation and proliferation through the STAT1/IRF1/GBP2 signaling axis, and anti-VSIG2 antibody treatment reverses immunosuppression in a pancreatic cancer model [PMID:41350674]. In gastric cancer, VSIG2 interacts with ANXA2 at the cell membrane, competing with FBXW10 for ANXA2 binding and thereby enabling FBXW10-mediated K63-polyubiquitination of ANXA2, which drives ANXA2 membrane localization and NF-κB inactivation to suppress tumor progression [PMID:41185558].\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"VSIG2's first defined molecular function was established: it acts as a scaffold bridging LAMTOR2 and mTOR to enhance mTOR signaling, answering how VSIG2 promotes PDAC cell proliferation and invasion.\",\n      \"evidence\": \"Mass spectrometry identification of LAMTOR2/mTOR interactions, reciprocal Co-IP, phospho-mTOR western blots, loss/gain-of-function assays, and xenograft models in PDAC cells\",\n      \"pmids\": [\"37626304\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Structural basis of simultaneous LAMTOR2 and mTOR binding is unknown\",\n        \"Whether the scaffold function operates in non-PDAC contexts is untested\",\n        \"No crystal or cryo-EM structure of the VSIG2–LAMTOR2–mTOR complex\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"VSIG2 was identified as an immunosuppressive ligand that binds Nectin-2 on T cells to suppress activation via STAT1/IRF1/GBP2 signaling, resolving a distinct extracellular function separate from its intracellular scaffold role.\",\n      \"evidence\": \"Binding assays demonstrating Nectin-2 specificity, VSIG2-Ig fusion protein in an EAE model, anti-VSIG2 antibody treatment in a pancreatic cancer model, T cell proliferation and pathway analysis\",\n      \"pmids\": [\"41350674\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether VSIG2–Nectin-2 interaction co-operates with or is independent of the LAMTOR2–mTOR scaffold function is unknown\",\n        \"Binding affinity and structural interface for VSIG2–Nectin-2 are not defined\",\n        \"The relative contribution of VSIG2 versus other Nectin-2 ligands (e.g., TIGIT) to T cell suppression is not delineated\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"A tumor-suppressive axis was uncovered in gastric cancer: VSIG2 competes with FBXW10 for ANXA2 binding, enabling FBXW10-mediated K63-polyubiquitination and membrane retention of ANXA2 that inactivates NF-κB, revealing context-dependent pro- versus anti-tumorigenic roles.\",\n      \"evidence\": \"Reciprocal Co-IP, ubiquitination assays, functional proliferation/migration/invasion assays, subcutaneous tumor and liver metastasis models in nude mice\",\n      \"pmids\": [\"41185558\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The binding interface between VSIG2 and ANXA2 and the competitive mechanism with FBXW10 lack structural detail\",\n        \"Whether the ANXA2/NF-κB axis operates in tissues beyond gastric cancer is untested\",\n        \"How VSIG2 expression is regulated to determine its pro- or anti-tumorigenic context is unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the dual functions of VSIG2 — intracellular scaffold (mTOR), extracellular immunosuppressive ligand (Nectin-2), and ANXA2-dependent tumor suppressor — are coordinated across cell types and tumor microenvironments remains an open question.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No unified model integrating the scaffold, immune checkpoint, and NF-κB suppression functions\",\n        \"Tissue-specific transcriptional and post-translational regulation of VSIG2 is largely uncharacterized\",\n        \"No structural data exist for any VSIG2 complex\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0048018\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0162582\", \"supporting_discovery_ids\": [0, 1, 2]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"LAMTOR2\",\n      \"MTOR\",\n      \"NECTIN2\",\n      \"ANXA2\",\n      \"FBXW10\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\n--- ROUND 2 (R2/R3, augmented corpus) ---\n\n```json\n{\n  \"mechanistic_narrative\": \"VSIG2 is a type I transmembrane immunoglobulin superfamily (IgSF) member containing one variable-type and one C2-type Ig domain, a transmembrane segment, and a cytoplasmic tail, belonging to a conserved vertebrate IgSF subfamily that includes the A33 antigen and CAR [PMID:9862345]. In pancreatic ductal adenocarcinoma, VSIG2 functions as an intracellular scaffold that simultaneously binds LAMTOR2 and mTOR, stabilizing their interaction to enhance mTOR phosphorylation and promote tumor cell proliferation and invasion [PMID:37626304]. In gastric cancer, VSIG2 suppresses tumor progression by competing with the E3 ligase FBXW10 for binding to ANXA2, thereby promoting FBXW10-mediated K63 polyubiquitination-dependent membrane localization of ANXA2 and consequent inactivation of NF-κB signaling [PMID:41185558]. On the surface of antigen-presenting cells, VSIG2 serves as an immunosuppressive ligand that binds Nectin-2 to inhibit T cell activation through the STAT1/IRF1/GBP2 pathway, and blockade of this axis with anti-VSIG2 antibodies inhibits pancreatic cancer growth in vivo [PMID:41350674].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Cloning of human CTH (VSIG2) established it as a new IgSF member with a distinctive V+C2 domain architecture encoded by half-domain exons, placing it in a conserved vertebrate subfamily alongside A33 and CAR and raising questions about its function outside lymphocytes.\",\n      \"evidence\": \"cDNA cloning, exon mapping, and comparative sequence analysis across species\",\n      \"pmids\": [\"9862345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional role assigned; expression pattern outside lymphocytes not characterized\",\n        \"No binding partner or ligand identified\",\n        \"No loss-of-function data\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"A large-scale secreted protein discovery screen confirmed VSIG2 as a signal-peptide-bearing cell-surface protein, consistent with receptor or ligand function but without functional characterization.\",\n      \"evidence\": \"Signal sequence trap in yeast and computational prediction from human cDNA libraries\",\n      \"pmids\": [\"12975309\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional follow-up; identification was part of a high-throughput screen without individual validation\",\n        \"Subcellular localization not directly imaged\",\n        \"No interacting partners tested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The first mechanistic role for VSIG2 was defined in PDAC, where it was shown to scaffold a LAMTOR2–mTOR ternary complex, enhancing mTOR phosphorylation and driving tumor cell proliferation and invasion — revealing VSIG2 as a signaling scaffold rather than solely a cell-surface receptor.\",\n      \"evidence\": \"Mass spectrometry interactome, reciprocal co-immunoprecipitation, immunofluorescence co-localization, gain/loss-of-function assays, and xenograft models in PDAC cells\",\n      \"pmids\": [\"37626304\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; the VSIG2–LAMTOR2–mTOR interaction has not been reconstituted with purified components\",\n        \"Which domain of VSIG2 mediates LAMTOR2 versus mTOR binding is unknown\",\n        \"Contribution of the extracellular Ig domains versus the cytoplasmic tail to scaffold function not dissected\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Two studies expanded VSIG2's functional repertoire in opposite directions: as an immunosuppressive ligand binding Nectin-2 to inhibit T cells via STAT1/IRF1/GBP2, and as a tumor suppressor in gastric cancer that competes with FBXW10 for ANXA2, promoting K63-ubiquitination-dependent ANXA2 membrane localization to inactivate NF-κB.\",\n      \"evidence\": \"Binding specificity assays excluding PD-1/CTLA-4, T cell proliferation assays, EAE and tumor models (immunosuppression study); Co-IP, ubiquitination assays with K63 linkage specificity, xenograft and metastasis models (gastric cancer study)\",\n      \"pmids\": [\"41350674\", \"41185558\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Both studies are from single laboratories and await independent replication\",\n        \"How VSIG2 simultaneously acts as an extracellular Nectin-2 ligand and an intracellular ANXA2/LAMTOR2 scaffold in the same cell is unresolved\",\n        \"Structural basis of the VSIG2–Nectin-2 interaction is undetermined\",\n        \"Context-dependent tumor-promoting (PDAC) versus tumor-suppressive (GC) roles are not reconciled mechanistically\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include which domain(s) mediate each interaction, how tissue context determines the oncogenic versus tumor-suppressive output, and whether the immune-checkpoint and intracellular scaffold functions operate simultaneously or are mutually exclusive on the same cell.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No crystal or cryo-EM structure available for VSIG2 or its complexes\",\n        \"No genetic mouse model to assess physiological non-redundant function\",\n        \"Relationship between mTOR-scaffolding function and Nectin-2-binding function has not been tested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 6, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [6]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 6, 7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"LAMTOR2\",\n      \"MTOR\",\n      \"ANXA2\",\n      \"FBXW10\",\n      \"NECTIN2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I made an error in the pathway section — I accidentally included a GO cellular component term. Let me fix that:\n\n```json\n{\n  \"mechanistic_narrative\": \"VSIG2 is a type I transmembrane immunoglobulin superfamily (IgSF) member containing one variable-type and one C2-type Ig domain, a transmembrane segment, and a cytoplasmic tail, belonging to a conserved vertebrate IgSF subfamily that includes the A33 antigen and CAR [PMID:9862345]. In pancreatic ductal adenocarcinoma, VSIG2 functions as an intracellular scaffold that simultaneously binds LAMTOR2 and mTOR, stabilizing their interaction to enhance mTOR phosphorylation and promote tumor cell proliferation and invasion [PMID:37626304]. In gastric cancer, VSIG2 suppresses tumor progression by competing with the E3 ligase FBXW10 for binding to ANXA2, thereby promoting FBXW10-mediated K63 polyubiquitination-dependent membrane localization of ANXA2 and consequent inactivation of NF-κB signaling [PMID:41185558]. On the surface of antigen-presenting cells, VSIG2 serves as an immunosuppressive ligand that binds Nectin-2 to inhibit T cell activation through the STAT1/IRF1/GBP2 pathway, and blockade of this axis with anti-VSIG2 antibodies inhibits pancreatic cancer growth in vivo [PMID:41350674].\",\n  \"teleology\": [\n    {\n      \"year\": 1998,\n      \"claim\": \"Cloning of human CTH (VSIG2) established it as a new IgSF member with a distinctive V+C2 domain architecture encoded by half-domain exons, placing it in a conserved vertebrate subfamily alongside A33 and CAR and raising questions about its function outside lymphocytes.\",\n      \"evidence\": \"cDNA cloning, exon mapping, and comparative sequence analysis across species\",\n      \"pmids\": [\"9862345\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional role assigned; expression pattern outside lymphocytes not characterized\",\n        \"No binding partner or ligand identified\",\n        \"No loss-of-function data\"\n      ]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"A large-scale secreted protein discovery screen confirmed VSIG2 as a signal-peptide-bearing cell-surface protein, consistent with receptor or ligand function but without functional characterization.\",\n      \"evidence\": \"Signal sequence trap in yeast and computational prediction from human cDNA libraries\",\n      \"pmids\": [\"12975309\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional follow-up; identification was part of a high-throughput screen without individual validation\",\n        \"Subcellular localization not directly imaged\",\n        \"No interacting partners tested\"\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The first mechanistic role for VSIG2 was defined in PDAC, where it was shown to scaffold a LAMTOR2–mTOR ternary complex, enhancing mTOR phosphorylation and driving tumor cell proliferation and invasion — revealing VSIG2 as a signaling scaffold rather than solely a cell-surface receptor.\",\n      \"evidence\": \"Mass spectrometry interactome, reciprocal co-immunoprecipitation, immunofluorescence co-localization, gain/loss-of-function assays, and xenograft models in PDAC cells\",\n      \"pmids\": [\"37626304\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single-lab study; the VSIG2–LAMTOR2–mTOR interaction has not been reconstituted with purified components\",\n        \"Which domain of VSIG2 mediates LAMTOR2 versus mTOR binding is unknown\",\n        \"Contribution of the extracellular Ig domains versus the cytoplasmic tail to scaffold function not dissected\"\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Two studies expanded VSIG2's functional repertoire in opposite directions: as an immunosuppressive ligand binding Nectin-2 to inhibit T cells via STAT1/IRF1/GBP2, and as a tumor suppressor in gastric cancer that competes with FBXW10 for ANXA2, promoting K63-ubiquitination-dependent ANXA2 membrane localization to inactivate NF-κB.\",\n      \"evidence\": \"Binding specificity assays excluding PD-1/CTLA-4, T cell proliferation assays, EAE and tumor models (immunosuppression study); Co-IP, ubiquitination assays with K63 linkage specificity, xenograft and metastasis models (gastric cancer study)\",\n      \"pmids\": [\"41350674\", \"41185558\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Both studies are from single laboratories and await independent replication\",\n        \"How VSIG2 simultaneously acts as an extracellular Nectin-2 ligand and an intracellular ANXA2/LAMTOR2 scaffold in the same cell is unresolved\",\n        \"Structural basis of the VSIG2–Nectin-2 interaction is undetermined\",\n        \"Context-dependent tumor-promoting (PDAC) versus tumor-suppressive (GC) roles are not reconciled mechanistically\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key open questions include which domain(s) mediate each interaction, how tissue context determines the oncogenic versus tumor-suppressive output, and whether the immune-checkpoint and intracellular scaffold functions operate simultaneously or are mutually exclusive on the same cell.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No crystal or cryo-EM structure available for VSIG2 or its complexes\",\n        \"No genetic mouse model to assess physiological non-redundant function\",\n        \"Relationship between mTOR-scaffolding function and Nectin-2-binding function has not been tested\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [5, 7]},\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 1, 6, 7]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [5, 6, 7]},\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"LAMTOR2\",\n      \"MTOR\",\n      \"ANXA2\",\n      \"FBXW10\",\n      \"NECTIN2\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}