{"gene":"TG_219720","gene_symbol":"RAB5C","run_date":"2026-09-08T11:06:35","timeline":{"discoveries":[{"year":2013,"finding":"Overexpression of dominant-negative Rab5C in Toxoplasma gondii identifies it as a regulator of trafficking to micronemes and rhoptries; notably, not all microneme protein trafficking depends on functional Rab5C, indicating redundant microneme targeting pathways exist.","method":"Overexpression screen of Rab-GTPases (dominant-negative constructs) combined with two-colour super-resolution STED microscopy","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — overexpression/dominant-negative screen with STED imaging in a single study; multiple orthogonal methods but single lab","pmids":["23505371"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"finding":"Rab5C is implicated in the endosome-like compartment that mediates vesicular sorting and trafficking towards secretory organelles (micronemes, rhoptries, dense granules) in T. gondii, and TgVps11 (a HOPS/CORVET subunit) functions in the same pathway, placing Rab5C upstream of or co-functional with tethering complexes in secretory organelle biogenesis.","method":"Genetic epistasis via conditional knockdown of TgVps11 combined with localization studies; referenced alongside Rab5C as part of the same trafficking pathway","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — Rab5C is cited as a prior finding contextualizing TgVps11 data; no direct experiment on Rab5C performed in this paper","pmids":["25640905"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"Toxoplasma gondii RAB5C is a Rab-GTPase that regulates vesicular trafficking from endosome-like compartments to apical secretory organelles (micronemes and rhoptries), functioning as part of a pathway that partially overlaps with other redundant microneme-targeting routes and is linked to the HOPS/CORVET tethering machinery."},"narrative":{"mechanistic_narrative":"In Toxoplasma gondii, RAB5C is a Rab-GTPase that regulates vesicular trafficking toward the apical secretory organelles, the micronemes and rhoptries; overexpression of a dominant-negative Rab5C disrupts targeting to these organelles, though only a subset of microneme protein trafficking depends on functional Rab5C, revealing that redundant microneme-targeting routes operate in parallel [PMID:23505371]. Rab5C acts within an endosome-like sorting compartment that directs cargo to the secretory organelles, and it functions in a pathway that also involves the HOPS/CORVET tethering subunit TgVps11 [PMID:25640905]. Beyond this role in endosome-to-secretory-organelle trafficking, no further mechanistic detail — including direct effectors, nucleotide-cycling regulators, or structural features — has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing which Rab-GTPases govern biogenesis of the apical secretory organelles was open; a dominant-negative screen showed Rab5C is required for trafficking to micronemes and rhoptries yet dispensable for a subset of microneme cargo, defining it as one of several redundant targeting routes.","evidence":"Overexpression of dominant-negative Rab-GTPase constructs with two-colour super-resolution STED microscopy in T. gondii","pmids":["23505371"],"confidence":"Medium","gaps":["The identity of the redundant, Rab5C-independent microneme-targeting pathway is not defined","No direct Rab5C effectors or GEF/GAP regulators identified","Dominant-negative overexpression does not exclude off-target dominance effects"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2015,"claim":"Whether Rab5C connects to the endosomal tethering machinery was unresolved; conditional knockdown of the HOPS/CORVET subunit TgVps11 placed it in the same endosome-like sorting pathway that routes cargo to secretory organelles, positioning Rab5C upstream of or alongside tethering complexes.","evidence":"Conditional knockdown of TgVps11 with localization studies, referencing Rab5C as a prior pathway component (no direct Rab5C experiment)","pmids":["25640905"],"confidence":"Low","gaps":["No direct experiment on Rab5C was performed in this study; the pathway link is inferential","The order of action between Rab5C and the HOPS/CORVET complex is not established","Physical interaction between Rab5C and TgVps11 is not demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct effectors, nucleotide-cycling regulators (GEFs/GAPs), and cargo-recognition mechanism of Rab5C in secretory-organelle biogenesis remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No effector or regulator of Rab5C identified","No structural or biochemical characterization of Rab5C","The redundant microneme-targeting pathway is uncharacterized"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGVPS11 (HOPS/CORVET SUBUNIT; SAME-PATHWAY, NO DIRECT INTERACTION SHOWN)"],"other_free_text":["Regulates trafficking to micronemes and rhoptries, with redundant Rab5C-independent microneme-targeting routes coexisting [#0]","Functions within an endosome-like sorting compartment linked to HOPS/CORVET tethering machinery [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"23505371","id":"PMC_23505371","title":"An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes.","date":"2013","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/23505371","citation_count":122,"is_preprint":false},{"pmid":"25640905","id":"PMC_25640905","title":"Toxoplasma gondii Vps11, a subunit of HOPS and CORVET tethering complexes, is essential for the biogenesis of secretory organelles.","date":"2015","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25640905","citation_count":45,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3454,"output_tokens":637,"usd":0.009959,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5345,"output_tokens":1736,"usd":0.035063,"stage2_stop_reason":"end_turn"},"total_usd":0.045022,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"Overexpression of dominant-negative Rab5C in Toxoplasma gondii identifies it as a regulator of trafficking to micronemes and rhoptries; notably, not all microneme protein trafficking depends on functional Rab5C, indicating redundant microneme targeting pathways exist.\",\n      \"method\": \"Overexpression screen of Rab-GTPases (dominant-negative constructs) combined with two-colour super-resolution STED microscopy\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — overexpression/dominant-negative screen with STED imaging in a single study; multiple orthogonal methods but single lab\",\n      \"pmids\": [\"23505371\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Rab5C is implicated in the endosome-like compartment that mediates vesicular sorting and trafficking towards secretory organelles (micronemes, rhoptries, dense granules) in T. gondii, and TgVps11 (a HOPS/CORVET subunit) functions in the same pathway, placing Rab5C upstream of or co-functional with tethering complexes in secretory organelle biogenesis.\",\n      \"method\": \"Genetic epistasis via conditional knockdown of TgVps11 combined with localization studies; referenced alongside Rab5C as part of the same trafficking pathway\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — Rab5C is cited as a prior finding contextualizing TgVps11 data; no direct experiment on Rab5C performed in this paper\",\n      \"pmids\": [\"25640905\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"Toxoplasma gondii RAB5C is a Rab-GTPase that regulates vesicular trafficking from endosome-like compartments to apical secretory organelles (micronemes and rhoptries), functioning as part of a pathway that partially overlaps with other redundant microneme-targeting routes and is linked to the HOPS/CORVET tethering machinery.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"In Toxoplasma gondii, RAB5C is a Rab-GTPase that regulates vesicular trafficking toward the apical secretory organelles, the micronemes and rhoptries; overexpression of a dominant-negative Rab5C disrupts targeting to these organelles, though only a subset of microneme protein trafficking depends on functional Rab5C, revealing that redundant microneme-targeting routes operate in parallel [#0]. Rab5C acts within an endosome-like sorting compartment that directs cargo to the secretory organelles, and it functions in a pathway that also involves the HOPS/CORVET tethering subunit TgVps11 [#1]. Beyond this role in endosome-to-secretory-organelle trafficking, no further mechanistic detail — including direct effectors, nucleotide-cycling regulators, or structural features — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing which Rab-GTPases govern biogenesis of the apical secretory organelles was open; a dominant-negative screen showed Rab5C is required for trafficking to micronemes and rhoptries yet dispensable for a subset of microneme cargo, defining it as one of several redundant targeting routes.\",\n      \"evidence\": \"Overexpression of dominant-negative Rab-GTPase constructs with two-colour super-resolution STED microscopy in T. gondii\",\n      \"pmids\": [\"23505371\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"single lab, dominant-negative overexpression\",\n      \"gaps\": [\n        \"The identity of the redundant, Rab5C-independent microneme-targeting pathway is not defined\",\n        \"No direct Rab5C effectors or GEF/GAP regulators identified\",\n        \"Dominant-negative overexpression does not exclude off-target dominance effects\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether Rab5C connects to the endosomal tethering machinery was unresolved; conditional knockdown of the HOPS/CORVET subunit TgVps11 placed it in the same endosome-like sorting pathway that routes cargo to secretory organelles, positioning Rab5C upstream of or alongside tethering complexes.\",\n      \"evidence\": \"Conditional knockdown of TgVps11 with localization studies, referencing Rab5C as a prior pathway component (no direct Rab5C experiment)\",\n      \"pmids\": [\"25640905\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Rab5C cited contextually, not directly tested here\",\n      \"gaps\": [\n        \"No direct experiment on Rab5C was performed in this study; the pathway link is inferential\",\n        \"The order of action between Rab5C and the HOPS/CORVET complex is not established\",\n        \"Physical interaction between Rab5C and TgVps11 is not demonstrated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct effectors, nucleotide-cycling regulators (GEFs/GAPs), and cargo-recognition mechanism of Rab5C in secretory-organelle biogenesis remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No effector or regulator of Rab5C identified\",\n        \"No structural or biochemical characterization of Rab5C\",\n        \"The redundant microneme-targeting pathway is uncharacterized\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005768\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgVps11 (HOPS/CORVET subunit; same-pathway, no direct interaction shown)\"],\n    \"other_free_text\": [\n      \"Regulates trafficking to micronemes and rhoptries, with redundant Rab5C-independent microneme-targeting routes coexisting [#0]\",\n      \"Functions within an endosome-like sorting compartment linked to HOPS/CORVET tethering machinery [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_219720","name":"RAB5C","product":"ras-related protein RAB5C","uniprot_acc":"S8G8J6","chromosome":"TGME49_chrXII","start_pos":688712},{"strain":"GT1","gene_id":"TGGT1_219720","name":null,"product":"putative Ras-related protein Rab-5C","uniprot_acc":null,"chromosome":"TGGT1_chrXII","start_pos":628976},{"strain":"RH88","gene_id":"TGRH88_057930","name":null,"product":"putative Ras-related protein Rab-5C","uniprot_acc":null,"chromosome":"CM023093","start_pos":701299},{"strain":"VEG","gene_id":"TGVEG_219720","name":null,"product":"putative Ras-related protein Rab-5C","uniprot_acc":"A0A125YVT5","chromosome":"TGVEG_chrXII","start_pos":662180}]}