{"gene":"TG_214770","gene_symbol":"RAB1B","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2023,"finding":"Conditional knockdown of Rab1B in T. gondii caused a rapid defect in secretory trafficking to the rhoptry bulb, establishing a role for Rab1B at a trafficking intersection between the trans-Golgi network and endosome-like compartments for rhoptry protein sorting.","method":"CRISPR/Cas9 conditional knockdown (tetracycline-inducible TATi/Ty-Rab1B), confocal imaging localization to trans-Golgi network and endosome-like compartments, host GFP acquisition endocytic trafficking assay","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — CRISPR-based conditional knockdown with defined cellular phenotype (rhoptry sorting defect) and localization data, single lab with two orthogonal methods (imaging + functional assay)","pmids":["37548452"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"Rab1B regulates endocytic trafficking of host-derived material (GFP vesicles) in T. gondii; knockdown identified it as one of four prenylated proteins required for this process, and protein prenylation was shown to regulate the stability/activity of Rab1B.","method":"Alkyne-labeled click chemistry prenylated proteome characterization, CRISPR/Cas9 genome editing, host GFP acquisition endocytic trafficking assay, functional screening of 23 prenylated candidates","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional screening with CRISPR knockdown and endocytic assay, single lab, multiple orthogonal methods (click chemistry proteomics + genetic knockdown + imaging)","pmids":["37548452"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"Depletion of Rab1B caused strong disorganization of endo-membranes and differentially expressed genes associated with rhoptry, microneme, endoplasmic reticulum, and Golgi apparatus organelles, indicating Rab1B is involved in biogenesis of multiple secretory organelles. Multi-omics analyses also linked Rab1B to fatty acid biogenesis (myrisoleic acid, oleic acid) and TCA cycle metabolism, consistent with its role in endocytic nutrient scavenging.","method":"Tetracycline-inducible conditional knockdown, transmission electron microscopy, high-throughput transcriptomics (RNA-seq), non-targeted metabolomics, qRT-PCR validation, correlation analysis of DEMs and DEGs","journal":"Parasites & vectors","confidence":"Low","confidence_rationale":"Tier 3 / Weak — multi-omics correlative approach with conditional knockdown; mechanistic pathway placement is inferred from transcriptomic/metabolomic changes rather than direct biochemical reconstitution; single lab","pmids":["37941035"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgRab1B is a prenylated small GTPase that localizes to the trans-Golgi network and endosome-like compartments in Toxoplasma gondii, where it plays a dual role as a key vesicular regulator: its conditional depletion rapidly disrupts rhoptry bulb protein sorting (exocytic pathway) and impairs endocytic trafficking of host-derived material, with protein prenylation required for Rab1B stability and activity."},"narrative":{"mechanistic_narrative":"TgRab1B is a prenylated small GTPase that functions as a vesicular trafficking regulator in Toxoplasma gondii, acting at the intersection of the trans-Golgi network and endosome-like compartments [PMID:37548452]. Its conditional depletion rapidly disrupts secretory trafficking to the rhoptry bulb, establishing a direct role in exocytic sorting of rhoptry proteins [PMID:37548452]. Rab1B additionally regulates endocytic trafficking of host-derived material, and was identified through prenylated-proteome screening as one of four prenylated proteins required for this endocytic process, with prenylation required for its stability and activity [PMID:37548452]. Beyond these trafficking roles, no direct biochemical characterization of Rab1B's GTPase cycle, effectors, or guanine-nucleotide exchange machinery has been reported in the available corpus.","teleology":[{"year":2023,"claim":"It was unknown which regulator coordinates secretory sorting to the rhoptry bulb; conditional depletion of Rab1B showed it operates at the TGN/endosome intersection to control rhoptry protein sorting, defining an exocytic trafficking function.","evidence":"CRISPR/Cas9 tetracycline-inducible knockdown with confocal localization and rhoptry sorting readout in T. gondii","pmids":["37548452"],"confidence":"Medium","gaps":["No effector or GEF/GAP partners identified","GTPase cycle not directly measured","Mechanism linking Rab1B to rhoptry cargo selection unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Whether Rab1B also acts in the endocytic direction and how prenylation contributes was unknown; functional screening of prenylated candidates showed Rab1B is required for endocytic uptake of host-derived material and that prenylation regulates its stability/activity.","evidence":"Click-chemistry prenylated proteome profiling, CRISPR knockdown, and host GFP acquisition endocytic assay in T. gondii","pmids":["37548452"],"confidence":"Medium","gaps":["Prenyltransferase acting on Rab1B not defined","Whether endocytic and exocytic roles are separable is unclear","No structural basis for prenylation-dependent stability"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"The broader organellar and metabolic consequences of Rab1B loss were uncharacterized; multi-omics after depletion linked Rab1B to biogenesis of multiple secretory organelles and to fatty acid and TCA metabolism, consistent with a role in endocytic nutrient scavenging.","evidence":"Conditional knockdown with transmission electron microscopy, RNA-seq, and non-targeted metabolomics in T. gondii","pmids":["37941035"],"confidence":"Low","gaps":["Metabolic links are correlative from omics, not biochemically reconstituted","Direct versus indirect effects on organelle biogenesis not distinguished","Causal path from trafficking defect to metabolic change unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The molecular machinery of Rab1B — its GTPase cycle regulators, effectors, and direct cargo interactions — remains uncharacterized in the available corpus.","evidence":"No direct biochemical reconstitution reported","pmids":[],"confidence":"Low","gaps":["No effectors or regulators identified","No structural data","GTP/GDP cycling not measured directly"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Prenylation is required for Rab1B stability and activity [#1].","Depletion causes disorganization of endo-membranes and altered expression of rhoptry, microneme, ER, and Golgi genes, plus links to fatty acid and TCA metabolism [#2]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"37548452","id":"PMC_37548452","title":"Functional screening reveals Toxoplasma prenylated proteins required for endocytic trafficking and rhoptry protein sorting.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/37548452","citation_count":13,"is_preprint":false},{"pmid":"37941035","id":"PMC_37941035","title":"Transcriptomic and metabolomic analyses reveal the essential nature of Rab1B in Toxoplasma gondii.","date":"2023","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/37941035","citation_count":4,"is_preprint":false},{"pmid":"38407123","id":"PMC_38407123","title":"Deciphering protein prenylation in endocytic trafficking in Toxoplasma gondii.","date":"2024","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/38407123","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4966,"output_tokens":1022,"usd":0.015114,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5913,"output_tokens":2007,"usd":0.03987,"stage2_stop_reason":"end_turn"},"total_usd":0.054984,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"paper list: removed papers about other genes"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"Conditional knockdown of Rab1B in T. gondii caused a rapid defect in secretory trafficking to the rhoptry bulb, establishing a role for Rab1B at a trafficking intersection between the trans-Golgi network and endosome-like compartments for rhoptry protein sorting.\",\n      \"method\": \"CRISPR/Cas9 conditional knockdown (tetracycline-inducible TATi/Ty-Rab1B), confocal imaging localization to trans-Golgi network and endosome-like compartments, host GFP acquisition endocytic trafficking assay\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — CRISPR-based conditional knockdown with defined cellular phenotype (rhoptry sorting defect) and localization data, single lab with two orthogonal methods (imaging + functional assay)\",\n      \"pmids\": [\"37548452\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Rab1B regulates endocytic trafficking of host-derived material (GFP vesicles) in T. gondii; knockdown identified it as one of four prenylated proteins required for this process, and protein prenylation was shown to regulate the stability/activity of Rab1B.\",\n      \"method\": \"Alkyne-labeled click chemistry prenylated proteome characterization, CRISPR/Cas9 genome editing, host GFP acquisition endocytic trafficking assay, functional screening of 23 prenylated candidates\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional screening with CRISPR knockdown and endocytic assay, single lab, multiple orthogonal methods (click chemistry proteomics + genetic knockdown + imaging)\",\n      \"pmids\": [\"37548452\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Depletion of Rab1B caused strong disorganization of endo-membranes and differentially expressed genes associated with rhoptry, microneme, endoplasmic reticulum, and Golgi apparatus organelles, indicating Rab1B is involved in biogenesis of multiple secretory organelles. Multi-omics analyses also linked Rab1B to fatty acid biogenesis (myrisoleic acid, oleic acid) and TCA cycle metabolism, consistent with its role in endocytic nutrient scavenging.\",\n      \"method\": \"Tetracycline-inducible conditional knockdown, transmission electron microscopy, high-throughput transcriptomics (RNA-seq), non-targeted metabolomics, qRT-PCR validation, correlation analysis of DEMs and DEGs\",\n      \"journal\": \"Parasites & vectors\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — multi-omics correlative approach with conditional knockdown; mechanistic pathway placement is inferred from transcriptomic/metabolomic changes rather than direct biochemical reconstitution; single lab\",\n      \"pmids\": [\"37941035\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgRab1B is a prenylated small GTPase that localizes to the trans-Golgi network and endosome-like compartments in Toxoplasma gondii, where it plays a dual role as a key vesicular regulator: its conditional depletion rapidly disrupts rhoptry bulb protein sorting (exocytic pathway) and impairs endocytic trafficking of host-derived material, with protein prenylation required for Rab1B stability and activity.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgRab1B is a prenylated small GTPase that functions as a vesicular trafficking regulator in Toxoplasma gondii, acting at the intersection of the trans-Golgi network and endosome-like compartments [#0]. Its conditional depletion rapidly disrupts secretory trafficking to the rhoptry bulb, establishing a direct role in exocytic sorting of rhoptry proteins [#0]. Rab1B additionally regulates endocytic trafficking of host-derived material, and was identified through prenylated-proteome screening as one of four prenylated proteins required for this endocytic process, with prenylation required for its stability and activity [#1]. Beyond these trafficking roles, no direct biochemical characterization of Rab1B's GTPase cycle, effectors, or guanine-nucleotide exchange machinery has been reported in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"It was unknown which regulator coordinates secretory sorting to the rhoptry bulb; conditional depletion of Rab1B showed it operates at the TGN/endosome intersection to control rhoptry protein sorting, defining an exocytic trafficking function.\",\n      \"evidence\": \"CRISPR/Cas9 tetracycline-inducible knockdown with confocal localization and rhoptry sorting readout in T. gondii\",\n      \"pmids\": [\"37548452\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No effector or GEF/GAP partners identified\", \"GTPase cycle not directly measured\", \"Mechanism linking Rab1B to rhoptry cargo selection unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether Rab1B also acts in the endocytic direction and how prenylation contributes was unknown; functional screening of prenylated candidates showed Rab1B is required for endocytic uptake of host-derived material and that prenylation regulates its stability/activity.\",\n      \"evidence\": \"Click-chemistry prenylated proteome profiling, CRISPR knockdown, and host GFP acquisition endocytic assay in T. gondii\",\n      \"pmids\": [\"37548452\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Prenyltransferase acting on Rab1B not defined\", \"Whether endocytic and exocytic roles are separable is unclear\", \"No structural basis for prenylation-dependent stability\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The broader organellar and metabolic consequences of Rab1B loss were uncharacterized; multi-omics after depletion linked Rab1B to biogenesis of multiple secretory organelles and to fatty acid and TCA metabolism, consistent with a role in endocytic nutrient scavenging.\",\n      \"evidence\": \"Conditional knockdown with transmission electron microscopy, RNA-seq, and non-targeted metabolomics in T. gondii\",\n      \"pmids\": [\"37941035\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Metabolic links are correlative from omics, not biochemically reconstituted\", \"Direct versus indirect effects on organelle biogenesis not distinguished\", \"Causal path from trafficking defect to metabolic change unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The molecular machinery of Rab1B — its GTPase cycle regulators, effectors, and direct cargo interactions — remains uncharacterized in the available corpus.\",\n      \"evidence\": \"No direct biochemical reconstitution reported\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No effectors or regulators identified\", \"No structural data\", \"GTP/GDP cycling not measured directly\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GTPase activity\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"trans-Golgi network\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"endosome\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"exocytic secretory trafficking (rhoptry protein sorting)\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"endocytic trafficking of host-derived material\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"secretory organelle biogenesis\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Prenylation is required for Rab1B stability and activity [#1].\",\n      \"Depletion causes disorganization of endo-membranes and altered expression of rhoptry, microneme, ER, and Golgi genes, plus links to fatty acid and TCA metabolism [#2].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_214770","name":"RAB1B","product":"ras-related protein RAB1B","uniprot_acc":"A0A125YLS2","chromosome":"TGME49_chrX","start_pos":6485819},{"strain":"GT1","gene_id":"TGGT1_214770","name":null,"product":"putative small GTP binding protein rab1a","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":6376684},{"strain":"RH88","gene_id":"TGRH88_039840","name":null,"product":"putative small GTP binding protein rab1a","uniprot_acc":null,"chromosome":"CM023091","start_pos":1047894},{"strain":"VEG","gene_id":"TGVEG_214770","name":null,"product":"putative small GTP binding protein rab1a","uniprot_acc":"V4ZB03","chromosome":"TGVEG_chrX","start_pos":6415370}]}