{"gene":"TG_283510","gene_symbol":"IAP1","run_date":"2026-09-08T16:59:59+00:00","timeline":{"discoveries":[{"year":2014,"finding":"IAP1 (IMC-associated protein 1) acts as the key determinant for the restricted localization of myosin C (MyoC) to the posterior pole of Toxoplasma gondii, functioning as a central component of the MyoC-glideosome that also includes GAP80, GAP50, GAP40, and shared myosin light chains with MyoA.","method":"Genetic deletion of glideosome components, localization studies, and functional complementation/invasion assays","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean genetic deletion with defined localization and invasion phenotype, single lab, multiple components validated","pmids":["25393004"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"TgIAP1 membrane association depends on palmitoylation catalyzed by TgDHHC2 (but not TgDHHC14); depletion of TgDHHC2 causes TgIAP1 to lose its membrane association, identifying it as a likely substrate of TgDHHC2.","method":"Conditional knockdown of TgDHHC2 and TgDHHC14 combined with localization analysis of TgIAP1 by fluorescence microscopy","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function depletion with defined localization readout, single lab, two TgDHHCs compared orthogonally","pmids":["32329212"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"IAP1 is an IMC-associated protein in Toxoplasma gondii whose membrane association depends on palmitoylation by the acyltransferase TgDHHC2, and which acts as the key determinant for restricting myosin C (MyoC) localization to the basal posterior pole as a central structural component of the MyoC-glideosome."},"narrative":{"mechanistic_narrative":"IAP1 (IMC-associated protein 1) is an inner membrane complex-associated protein of Toxoplasma gondii that serves as the key determinant restricting myosin C (MyoC) to the parasite's posterior pole, acting as a central structural component of the MyoC-glideosome alongside GAP80, GAP50, GAP40, and light chains shared with MyoA [PMID:25393004]. Its membrane association is conferred by palmitoylation catalyzed by the acyltransferase TgDHHC2 (but not TgDHHC14), and depletion of TgDHHC2 abolishes IAP1 membrane targeting, identifying IAP1 as a likely TgDHHC2 substrate [PMID:32329212]. Beyond these two findings, no further mechanistic detail on IAP1 has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"It was unknown what confined MyoC to the parasite posterior; genetic dissection established IAP1 as the determinant of restricted MyoC localization and a core component of the distinct MyoC-glideosome.","evidence":"Genetic deletion of glideosome components with localization and invasion assays in T. gondii","pmids":["25393004"],"confidence":"Medium","gaps":["Molecular mechanism by which IAP1 anchors or restricts MyoC is not defined","Direct physical interaction between IAP1 and MyoC not biochemically resolved","Contribution of IAP1 to parasite motility or fitness beyond localization not quantified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"How IAP1 achieves membrane association was unresolved; conditional depletion showed its membrane targeting requires palmitoylation by TgDHHC2, placing IAP1 downstream of a specific acyltransferase.","evidence":"Conditional knockdown of TgDHHC2 and TgDHHC14 with fluorescence localization of TgIAP1 in T. gondii","pmids":["32329212"],"confidence":"Medium","gaps":["Direct palmitoylation of IAP1 by TgDHHC2 not shown biochemically (identified as likely substrate via depletion)","Palmitoylation site(s) on IAP1 not mapped","Whether loss of IAP1 palmitoylation disrupts MyoC-glideosome assembly not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"Whether IAP1 directly binds MyoC and how its palmitoylation-dependent membrane anchoring couples to MyoC restriction remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural or direct binding data for the IAP1-MyoC interaction","Causal link between TgDHHC2-dependent membrane targeting and MyoC posterior restriction untested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["MyoC-glideosome (IAP1, MyoC, GAP80, GAP50, GAP40, shared myosin light chains)"],"partners":["MYOC","GAP80","GAP50","GAP40","TGDHHC2 (PALMITOYLATING ENZYME)"],"other_free_text":["Membrane association of IAP1 depends on palmitoylation by TgDHHC2 but not TgDHHC14, identifying IAP1 as a likely TgDHHC2 substrate."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"25393004","id":"PMC_25393004","title":"Plasticity between MyoC- and MyoA-glideosomes: an example of functional compensation in Toxoplasma gondii invasion.","date":"2014","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/25393004","citation_count":77,"is_preprint":false},{"pmid":"23248260","id":"PMC_23248260","title":"Balance between NF-κB p100 and p52 regulates T cell costimulation dependence.","date":"2012","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/23248260","citation_count":24,"is_preprint":false},{"pmid":"32329212","id":"PMC_32329212","title":"Two palmitoyl acyltransferases involved sequentially in the biogenesis of the inner membrane complex of Toxoplasma gondii.","date":"2020","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/32329212","citation_count":7,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3978,"output_tokens":621,"usd":0.010625,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5283,"output_tokens":1676,"usd":0.034158,"stage2_stop_reason":"end_turn"},"total_usd":0.0,"stage1_batch_id":"msgbatch_01WgHz6kceqm573AGLyz57at","stage2_batch_id":"msgbatch_01LK4wDYj5zYquahv7gi9893","note":"batch pricing = 50% of standard","skipped":true},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"IAP1 (IMC-associated protein 1) acts as the key determinant for the restricted localization of myosin C (MyoC) to the posterior pole of Toxoplasma gondii, functioning as a central component of the MyoC-glideosome that also includes GAP80, GAP50, GAP40, and shared myosin light chains with MyoA.\",\n      \"method\": \"Genetic deletion of glideosome components, localization studies, and functional complementation/invasion assays\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic deletion with defined localization and invasion phenotype, single lab, multiple components validated\",\n      \"pmids\": [\"25393004\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"TgIAP1 membrane association depends on palmitoylation catalyzed by TgDHHC2 (but not TgDHHC14); depletion of TgDHHC2 causes TgIAP1 to lose its membrane association, identifying it as a likely substrate of TgDHHC2.\",\n      \"method\": \"Conditional knockdown of TgDHHC2 and TgDHHC14 combined with localization analysis of TgIAP1 by fluorescence microscopy\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function depletion with defined localization readout, single lab, two TgDHHCs compared orthogonally\",\n      \"pmids\": [\"32329212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"IAP1 is an IMC-associated protein in Toxoplasma gondii whose membrane association depends on palmitoylation by the acyltransferase TgDHHC2, and which acts as the key determinant for restricting myosin C (MyoC) localization to the basal posterior pole as a central structural component of the MyoC-glideosome.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"IAP1 (IMC-associated protein 1) is an inner membrane complex-associated protein of Toxoplasma gondii that serves as the key determinant restricting myosin C (MyoC) to the parasite's posterior pole, acting as a central structural component of the MyoC-glideosome alongside GAP80, GAP50, GAP40, and light chains shared with MyoA [#0]. Its membrane association is conferred by palmitoylation catalyzed by the acyltransferase TgDHHC2 (but not TgDHHC14), and depletion of TgDHHC2 abolishes IAP1 membrane targeting, identifying IAP1 as a likely TgDHHC2 substrate [#1]. Beyond these two findings, no further mechanistic detail on IAP1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"It was unknown what confined MyoC to the parasite posterior; genetic dissection established IAP1 as the determinant of restricted MyoC localization and a core component of the distinct MyoC-glideosome.\",\n      \"evidence\": \"Genetic deletion of glideosome components with localization and invasion assays in T. gondii\",\n      \"pmids\": [\"25393004\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Molecular mechanism by which IAP1 anchors or restricts MyoC is not defined\",\n        \"Direct physical interaction between IAP1 and MyoC not biochemically resolved\",\n        \"Contribution of IAP1 to parasite motility or fitness beyond localization not quantified\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"How IAP1 achieves membrane association was unresolved; conditional depletion showed its membrane targeting requires palmitoylation by TgDHHC2, placing IAP1 downstream of a specific acyltransferase.\",\n      \"evidence\": \"Conditional knockdown of TgDHHC2 and TgDHHC14 with fluorescence localization of TgIAP1 in T. gondii\",\n      \"pmids\": [\"32329212\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct palmitoylation of IAP1 by TgDHHC2 not shown biochemically (identified as likely substrate via depletion)\",\n        \"Palmitoylation site(s) on IAP1 not mapped\",\n        \"Whether loss of IAP1 palmitoylation disrupts MyoC-glideosome assembly not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether IAP1 directly binds MyoC and how its palmitoylation-dependent membrane anchoring couples to MyoC restriction remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or direct binding data for the IAP1-MyoC interaction\",\n        \"Causal link between TgDHHC2-dependent membrane targeting and MyoC posterior restriction untested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"inner membrane complex\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"posterior/basal pole\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"MyoC-glideosome assembly\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"protein palmitoylation-dependent membrane targeting\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"MyoC-glideosome (IAP1, MyoC, GAP80, GAP50, GAP40, shared myosin light chains)\"],\n    \"partners\": [\"MyoC\", \"GAP80\", \"GAP50\", \"GAP40\", \"TgDHHC2 (palmitoylating enzyme)\"],\n    \"other_free_text\": [\n      \"Membrane association of IAP1 depends on palmitoylation by TgDHHC2 but not TgDHHC14, identifying IAP1 as a likely TgDHHC2 substrate.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_283510","name":"IAP1","product":"IMC-associated protein IAP1","uniprot_acc":"S8F567","chromosome":"TGME49_chrV","start_pos":3106265},{"strain":"GT1","gene_id":"TGGT1_283510","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrV","start_pos":2942804},{"strain":"RH88","gene_id":"TGRH88_027320","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023086","start_pos":3145266},{"strain":"VEG","gene_id":"TGVEG_283510","name":null,"product":"hypothetical protein","uniprot_acc":"B9QGN3","chromosome":"TGVEG_chrV","start_pos":3062545}]}