{"gene":"TG_500200","gene_symbol":"ICMAP3","run_date":"2026-09-08T16:10:21","timeline":{"discoveries":[{"year":2024,"finding":"ICMAP3 exists in two isoforms that contribute to the control of intraconoidal microtubule (ICMT) length and the docking of two rhoptries at the apical vesicle (AV), respectively, as demonstrated by depletion experiments showing loss of these functions.","method":"Conditional protein depletion (loss-of-function) with ultrastructural and functional readouts of ICMT length control and rhoptry docking at the apical vesicle","journal":"Nature Communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean depletion with defined structural and functional phenotypes (ICMT length, rhoptry docking), single lab, multiple readouts","pmids":["38191574"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"ICMAP3 is an intraconoidal microtubule-associated protein that, through two distinct isoforms, regulates the length of intraconoidal microtubules and mediates docking of rhoptries to the apical vesicle, thereby enabling sustained rhoptry discharge essential for host cell invasion and virulence in Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"ICMAP3 is an intraconoidal microtubule-associated protein of Toxoplasma gondii that couples cytoskeletal organization at the apical complex to the secretory machinery required for host cell invasion. It functions through two distinct isoforms with separable roles: one contributes to the control of intraconoidal microtubule (ICMT) length, while the other mediates docking of two rhoptries at the apical vesicle, as revealed by conditional depletion causing loss of both functions [PMID:38191574]. Beyond this depletion-based characterization [PMID:38191574], no further mechanistic detail — including binding partners, structural basis of isoform specialization, or the molecular mechanism of rhoptry docking — has been characterized in the available corpus.","teleology":[{"year":2024,"claim":"It was unknown how intraconoidal microtubule length and rhoptry positioning at the apical vesicle are coordinated; depletion of ICMAP3 established that a single microtubule-associated protein, via two isoforms, governs both ICMT length control and rhoptry docking.","evidence":"Conditional protein depletion with ultrastructural and functional readouts of ICMT length and rhoptry docking at the apical vesicle in Toxoplasma gondii","pmids":["38191574"],"confidence":"Medium","gaps":["The molecular basis by which the two isoforms partition between ICMT length control and rhoptry docking is not defined","No binding partners or structural interactions with microtubules or rhoptries are identified","The mechanism linking rhoptry docking to sustained discharge and invasion is not directly demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How ICMAP3 isoforms physically associate with intraconoidal microtubules and the apical vesicle, and what partners mediate rhoptry docking, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No interactome or reciprocal binding data","No structural model of ICMAP3 or its isoforms","Strain-level generality not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Two distinct isoforms with separable functions: one controls intraconoidal microtubule (ICMT) length, the other mediates docking of two rhoptries at the apical vesicle [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"38191574","id":"PMC_38191574","title":"Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/38191574","citation_count":16,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2848,"output_tokens":361,"usd":0.006979,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4944,"output_tokens":1192,"usd":0.02726,"stage2_stop_reason":"end_turn"},"total_usd":0.034239,"stage1_batch_id":"msgbatch_01RQGfcbGqQD3GfCPaX8jpfW","stage2_batch_id":"msgbatch_019PABGEC4M9vU7v6jy6Fvwg","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2024,\n      \"finding\": \"ICMAP3 exists in two isoforms that contribute to the control of intraconoidal microtubule (ICMT) length and the docking of two rhoptries at the apical vesicle (AV), respectively, as demonstrated by depletion experiments showing loss of these functions.\",\n      \"method\": \"Conditional protein depletion (loss-of-function) with ultrastructural and functional readouts of ICMT length control and rhoptry docking at the apical vesicle\",\n      \"journal\": \"Nature Communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean depletion with defined structural and functional phenotypes (ICMT length, rhoptry docking), single lab, multiple readouts\",\n      \"pmids\": [\"38191574\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ICMAP3 is an intraconoidal microtubule-associated protein that, through two distinct isoforms, regulates the length of intraconoidal microtubules and mediates docking of rhoptries to the apical vesicle, thereby enabling sustained rhoptry discharge essential for host cell invasion and virulence in Toxoplasma gondii.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ICMAP3 is an intraconoidal microtubule-associated protein of Toxoplasma gondii that couples cytoskeletal organization at the apical complex to the secretory machinery required for host cell invasion. It functions through two distinct isoforms with separable roles: one contributes to the control of intraconoidal microtubule (ICMT) length, while the other mediates docking of two rhoptries at the apical vesicle, as revealed by conditional depletion causing loss of both functions [#0]. Beyond this depletion-based characterization [#0], no further mechanistic detail — including binding partners, structural basis of isoform specialization, or the molecular mechanism of rhoptry docking — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unknown how intraconoidal microtubule length and rhoptry positioning at the apical vesicle are coordinated; depletion of ICMAP3 established that a single microtubule-associated protein, via two isoforms, governs both ICMT length control and rhoptry docking.\",\n      \"evidence\": \"Conditional protein depletion with ultrastructural and functional readouts of ICMT length and rhoptry docking at the apical vesicle in Toxoplasma gondii\",\n      \"pmids\": [\"38191574\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular basis by which the two isoforms partition between ICMT length control and rhoptry docking is not defined\",\n        \"No binding partners or structural interactions with microtubules or rhoptries are identified\",\n        \"The mechanism linking rhoptry docking to sustained discharge and invasion is not directly demonstrated\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ICMAP3 isoforms physically associate with intraconoidal microtubules and the apical vesicle, and what partners mediate rhoptry docking, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No interactome or reciprocal binding data\",\n        \"No structural model of ICMAP3 or its isoforms\",\n        \"Strain-level generality not addressed\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005874\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Two distinct isoforms with separable functions: one controls intraconoidal microtubule (ICMT) length, the other mediates docking of two rhoptries at the apical vesicle [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_500200","name":"ICMAP3","product":"intraconoidal microtubule-associated protein ICMAP3","uniprot_acc":"S8F519","chromosome":"TGME49_chrV","start_pos":2588608},{"strain":"GT1","gene_id":"TGGT1_410070","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrV","start_pos":2452998},{"strain":"RH88","gene_id":"TGRH88_026690","name":null,"product":"putative proteophosphoglycan ppg4, related protein","uniprot_acc":null,"chromosome":"CM023086","start_pos":2626276},{"strain":"VEG","gene_id":"TGVEG_285140","name":null,"product":"hypothetical protein","uniprot_acc":"V5B444","chromosome":"TGVEG_chrV","start_pos":2558594}]}