{"gene":"LGALS9B","run_date":"2026-06-10T02:59:49","timeline":{"discoveries":[{"year":2024,"finding":"LGALS9B competes with the E3 ubiquitin ligase HERC5 for binding to EEF1D (eukaryotic translation elongation factor 1 delta), thereby preventing HERC5-mediated proteasomal degradation of EEF1D and stabilizing EEF1D protein levels.","method":"Co-immunoprecipitation/binding competition assay, knockdown/overexpression with protein stability readout (in vitro and in vivo)","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal binding assay and functional KD/OE with defined molecular phenotype, but single lab and limited orthogonal validation described in abstract","pmids":["39639171"],"is_preprint":false},{"year":2024,"finding":"LGALS9B-mediated stabilization of EEF1D leads to activation of the PI3K/AKT signaling pathway, promoting gastric cancer cell proliferation, migration, and invasion.","method":"Knockdown and overexpression experiments in vitro and in vivo with pathway activity readout (PI3K/AKT signaling) and phenotypic assays (proliferation, migration, invasion)","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean KD/OE with defined cellular and signaling phenotype, single lab, no independent replication reported","pmids":["39639171"],"is_preprint":false}],"current_model":"LGALS9B stabilizes the EEF1D protein by competing with the E3 ligase HERC5 for EEF1D binding, thereby preventing its degradation; the resulting EEF1D enrichment activates the PI3K/AKT signaling pathway to promote gastric cancer cell proliferation, migration, and invasion."},"narrative":{"mechanistic_narrative":"LGALS9B functions as a post-translational stabilizer of the eukaryotic translation elongation factor EEF1D in gastric cancer cells, where it competes with the E3 ubiquitin ligase HERC5 for binding to EEF1D and thereby blocks HERC5-mediated proteasomal degradation of EEF1D [PMID:39639171]. The resulting accumulation of EEF1D drives activation of the PI3K/AKT signaling pathway, promoting cancer cell proliferation, migration, and invasion [PMID:39639171]. Beyond this competitive-binding axis and its downstream signaling output, no further mechanistic detail for LGALS9B has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"Established how LGALS9B controls EEF1D abundance: rather than acting catalytically, it physically competes with the E3 ligase HERC5 for EEF1D, answering whether the protein's effect is stabilizing and direct.","evidence":"Co-immunoprecipitation/binding competition assay with knockdown/overexpression and protein stability readouts, in vitro and in vivo","pmids":["39639171"],"confidence":"Medium","gaps":["Single lab with limited orthogonal validation described","Binding interface and stoichiometry of LGALS9B-EEF1D-HERC5 competition not defined","Whether this mechanism operates outside gastric cancer cells is untested"]},{"year":2024,"claim":"Connected the molecular stabilization event to a downstream phenotype, showing EEF1D enrichment activates PI3K/AKT signaling to drive malignant cell behaviors.","evidence":"Knockdown and overexpression with PI3K/AKT pathway activity readout and proliferation/migration/invasion assays, in vitro and in vivo","pmids":["39639171"],"confidence":"Medium","gaps":["No independent replication reported","Mechanistic link between EEF1D level and PI3K/AKT activation not resolved at molecular level","Contribution of LGALS9B independent of the EEF1D axis unknown"]},{"year":null,"claim":"Whether LGALS9B has functions beyond EEF1D stabilization and any enzymatic or carbohydrate-binding activity remains uncharacterized in the available corpus.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of the LGALS9B-EEF1D interaction","No characterization of LGALS9B localization or expression regulation","No data on additional binding partners or substrates"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[0]}],"localization":[],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[1]}],"complexes":[],"partners":["EEF1D","HERC5"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q3B8N2","full_name":"Galectin-9B","aliases":["Galectin-9-like protein A"],"length_aa":356,"mass_kda":39.7,"function":"Binds galactosides","subcellular_location":"","url":"https://www.uniprot.org/uniprotkb/Q3B8N2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/LGALS9B","classification":"Not Classified","n_dependent_lines":209,"n_total_lines":1047,"dependency_fraction":0.19961795606494748},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/LGALS9B","total_profiled":1310},"omim":[],"hpa":{"profiled":true,"resolved_as":"","reliability":"Uncertain","locations":[{"location":"Cytosol","reliability":"Uncertain"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in some","driving_tissues":[{"tissue":"esophagus","ntpm":14.6},{"tissue":"intestine","ntpm":10.4},{"tissue":"stomach 1","ntpm":29.1}],"url":"https://www.proteinatlas.org/search/LGALS9B"},"hgnc":{"alias_symbol":[],"prev_symbol":[]},"alphafold":{"accession":"Q3B8N2","domains":[{"cath_id":"2.60.120.200","chopping":"11-149","consensus_level":"high","plddt":96.5637,"start":11,"end":149},{"cath_id":"2.60.120.200","chopping":"229-356","consensus_level":"high","plddt":97.5088,"start":229,"end":356}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q3B8N2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q3B8N2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q3B8N2-F1-predicted_aligned_error_v6.png","plddt_mean":84.5},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=LGALS9B","jax_strain_url":"https://www.jax.org/strain/search?query=LGALS9B"},"sequence":{"accession":"Q3B8N2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q3B8N2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q3B8N2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q3B8N2"}},"corpus_meta":[{"pmid":"39639171","id":"PMC_39639171","title":"LGALS9B stabilizes EEF1D protein and activates the PI3K/AKT signaling pathway to promote gastric cancer occurrence and metastasis.","date":"2024","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/39639171","citation_count":2,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2652,"output_tokens":530,"usd":0.007953,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6828,"output_tokens":1139,"usd":0.031308,"stage2_stop_reason":"end_turn"},"total_usd":0.039261,"stage1_batch_id":"msgbatch_01BbTCMyrRPyhtEq6b1MdwCN","stage2_batch_id":"msgbatch_011dEed5bbxYvTAaQWKJevxu","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"LGALS9B competes with the E3 ubiquitin ligase HERC5 for binding to EEF1D (eukaryotic translation elongation factor 1 delta), thereby preventing HERC5-mediated proteasomal degradation of EEF1D and stabilizing EEF1D protein levels.\",\n      \"method\": \"Co-immunoprecipitation/binding competition assay, knockdown/overexpression with protein stability readout (in vitro and in vivo)\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal binding assay and functional KD/OE with defined molecular phenotype, but single lab and limited orthogonal validation described in abstract\",\n      \"pmids\": [\"39639171\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"LGALS9B-mediated stabilization of EEF1D leads to activation of the PI3K/AKT signaling pathway, promoting gastric cancer cell proliferation, migration, and invasion.\",\n      \"method\": \"Knockdown and overexpression experiments in vitro and in vivo with pathway activity readout (PI3K/AKT signaling) and phenotypic assays (proliferation, migration, invasion)\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean KD/OE with defined cellular and signaling phenotype, single lab, no independent replication reported\",\n      \"pmids\": [\"39639171\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"LGALS9B stabilizes the EEF1D protein by competing with the E3 ligase HERC5 for EEF1D binding, thereby preventing its degradation; the resulting EEF1D enrichment activates the PI3K/AKT signaling pathway to promote gastric cancer cell proliferation, migration, and invasion.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"LGALS9B functions as a post-translational stabilizer of the eukaryotic translation elongation factor EEF1D in gastric cancer cells, where it competes with the E3 ubiquitin ligase HERC5 for binding to EEF1D and thereby blocks HERC5-mediated proteasomal degradation of EEF1D [#0]. The resulting accumulation of EEF1D drives activation of the PI3K/AKT signaling pathway, promoting cancer cell proliferation, migration, and invasion [#1]. Beyond this competitive-binding axis and its downstream signaling output, no further mechanistic detail for LGALS9B has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"Established how LGALS9B controls EEF1D abundance: rather than acting catalytically, it physically competes with the E3 ligase HERC5 for EEF1D, answering whether the protein's effect is stabilizing and direct.\",\n      \"evidence\": \"Co-immunoprecipitation/binding competition assay with knockdown/overexpression and protein stability readouts, in vitro and in vivo\",\n      \"pmids\": [\"39639171\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab with limited orthogonal validation described\",\n        \"Binding interface and stoichiometry of LGALS9B-EEF1D-HERC5 competition not defined\",\n        \"Whether this mechanism operates outside gastric cancer cells is untested\"\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Connected the molecular stabilization event to a downstream phenotype, showing EEF1D enrichment activates PI3K/AKT signaling to drive malignant cell behaviors.\",\n      \"evidence\": \"Knockdown and overexpression with PI3K/AKT pathway activity readout and proliferation/migration/invasion assays, in vitro and in vivo\",\n      \"pmids\": [\"39639171\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No independent replication reported\",\n        \"Mechanistic link between EEF1D level and PI3K/AKT activation not resolved at molecular level\",\n        \"Contribution of LGALS9B independent of the EEF1D axis unknown\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether LGALS9B has functions beyond EEF1D stabilization and any enzymatic or carbohydrate-binding activity remains uncharacterized in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of the LGALS9B-EEF1D interaction\",\n        \"No characterization of LGALS9B localization or expression regulation\",\n        \"No data on additional binding partners or substrates\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"EEF1D\", \"HERC5\"],\n    \"other_free_text\": []\n  }\n}\n```","audit_flag":null,"evaluation":{"faith_supported":1,"faith_total":2,"faith_pct":50.0}}