{"gene":"TG_244040","gene_symbol":"ArPIKfyve","run_date":"2026-09-08T12:58:25","timeline":{"discoveries":[{"year":2014,"finding":"Conditional knockdown of ArPIKfyve, the regulatory protein of PIKfyve lipid kinase, causes enlarged apicoplasts, phenocopying loss of PIKfyve and PI(3)P depletion, establishing that ArPIKfyve is required for apicoplast homeostasis as part of the PIKfyve regulatory complex that produces PI(3,5)P2 from PI(3)P.","method":"Conditional gene knockdown (inducible depletion) with apicoplast morphology readout","journal":"Cellular Microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean conditional knockdown with defined organelle phenotype, single lab, single method","pmids":["25329540"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"ArPIKfyve is a regulatory protein of the PIKfyve lipid kinase complex in Toxoplasma gondii that is required for apicoplast homeostasis, likely by facilitating PIKfyve-mediated synthesis of PI(3,5)P2 from PI(3)P; its absence (like loss of PIKfyve itself) causes abnormal apicoplast enlargement and disrupts organelle inheritance."},"narrative":{"mechanistic_narrative":"ArPIKfyve is a regulatory component of the PIKfyve lipid kinase complex in Toxoplasma gondii required for apicoplast homeostasis [PMID:25329540]. Conditional depletion of ArPIKfyve causes enlarged apicoplasts, phenocopying loss of PIKfyve itself and PI(3)P depletion, indicating that ArPIKfyve acts as part of a regulatory complex that supports PIKfyve-mediated synthesis of PI(3,5)P2 from PI(3)P [PMID:25329540]. Beyond this genetic phenotype, no further biochemical or structural detail of ArPIKfyve has been characterized in the available corpus.","teleology":[{"year":2014,"claim":"It was unknown whether the PIKfyve regulatory subunit contributes to organelle maintenance in Toxoplasma; conditional knockdown showed ArPIKfyve loss enlarges apicoplasts, establishing it as a required regulator of apicoplast homeostasis within the PIKfyve lipid kinase complex.","evidence":"Conditional inducible knockdown with apicoplast morphology readout in T. gondii","pmids":["25329540"],"confidence":"Medium","gaps":["Direct biochemical demonstration that ArPIKfyve stimulates PIKfyve-mediated PI(3,5)P2 synthesis is not shown","The physical interaction between ArPIKfyve and PIKfyve is inferred from phenocopy, not demonstrated","The mechanism linking PI(3,5)P2 levels to apicoplast size and inheritance is not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How ArPIKfyve activates PIKfyve at the molecular level, and how the resulting PI(3,5)P2 pool controls apicoplast size and organelle inheritance, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No direct binding or reconstitution data for the ArPIKfyve–PIKfyve complex","No measurement of PI(3,5)P2 levels upon ArPIKfyve depletion","Subcellular localization of ArPIKfyve not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PIKfyve lipid kinase regulatory complex"],"partners":["PIKFYVE"],"other_free_text":["Required for apicoplast homeostasis; conditional depletion causes apicoplast enlargement, phenocopying PIKfyve loss and PI(3)P depletion."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"25329540","id":"PMC_25329540","title":"Lipid kinases are essential for apicoplast homeostasis in Toxoplasma gondii.","date":"2014","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25329540","citation_count":35,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3067,"output_tokens":388,"usd":0.00751,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4985,"output_tokens":1277,"usd":0.028425,"stage2_stop_reason":"end_turn"},"total_usd":0.035935,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2014,\n      \"finding\": \"Conditional knockdown of ArPIKfyve, the regulatory protein of PIKfyve lipid kinase, causes enlarged apicoplasts, phenocopying loss of PIKfyve and PI(3)P depletion, establishing that ArPIKfyve is required for apicoplast homeostasis as part of the PIKfyve regulatory complex that produces PI(3,5)P2 from PI(3)P.\",\n      \"method\": \"Conditional gene knockdown (inducible depletion) with apicoplast morphology readout\",\n      \"journal\": \"Cellular Microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean conditional knockdown with defined organelle phenotype, single lab, single method\",\n      \"pmids\": [\"25329540\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ArPIKfyve is a regulatory protein of the PIKfyve lipid kinase complex in Toxoplasma gondii that is required for apicoplast homeostasis, likely by facilitating PIKfyve-mediated synthesis of PI(3,5)P2 from PI(3)P; its absence (like loss of PIKfyve itself) causes abnormal apicoplast enlargement and disrupts organelle inheritance.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ArPIKfyve is a regulatory component of the PIKfyve lipid kinase complex in Toxoplasma gondii required for apicoplast homeostasis [#0]. Conditional depletion of ArPIKfyve causes enlarged apicoplasts, phenocopying loss of PIKfyve itself and PI(3)P depletion, indicating that ArPIKfyve acts as part of a regulatory complex that supports PIKfyve-mediated synthesis of PI(3,5)P2 from PI(3)P [#0]. Beyond this genetic phenotype, no further biochemical or structural detail of ArPIKfyve has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2014,\n      \"claim\": \"It was unknown whether the PIKfyve regulatory subunit contributes to organelle maintenance in Toxoplasma; conditional knockdown showed ArPIKfyve loss enlarges apicoplasts, establishing it as a required regulator of apicoplast homeostasis within the PIKfyve lipid kinase complex.\",\n      \"evidence\": \"Conditional inducible knockdown with apicoplast morphology readout in T. gondii\",\n      \"pmids\": [\n        \"25329540\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct biochemical demonstration that ArPIKfyve stimulates PIKfyve-mediated PI(3,5)P2 synthesis is not shown\",\n        \"The physical interaction between ArPIKfyve and PIKfyve is inferred from phenocopy, not demonstrated\",\n        \"The mechanism linking PI(3,5)P2 levels to apicoplast size and inheritance is not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ArPIKfyve activates PIKfyve at the molecular level, and how the resulting PI(3,5)P2 pool controls apicoplast size and organelle inheritance, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No direct binding or reconstitution data for the ArPIKfyve\\u2013PIKfyve complex\",\n        \"No measurement of PI(3,5)P2 levels upon ArPIKfyve depletion\",\n        \"Subcellular localization of ArPIKfyve not established\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0019904\",\n        \"supporting_discovery_ids\": [\n          0\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0046854\",\n        \"supporting_discovery_ids\": [\n          0\n        ],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"PIKfyve lipid kinase regulatory complex\"\n    ],\n    \"partners\": [\n      \"PIKfyve\"\n    ],\n    \"other_free_text\": [\n      \"Required for apicoplast homeostasis; conditional depletion causes apicoplast enlargement, phenocopying PIKfyve loss and PI(3)P depletion.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_244040","name":"ArPIKfyve","product":"PIKfyve regulatory protein","uniprot_acc":"S8GPL9","chromosome":"TGME49_chrVI","start_pos":2971952},{"strain":"GT1","gene_id":"TGGT1_244040","name":null,"product":"HEAT repeat-containing protein","uniprot_acc":null,"chromosome":"TGGT1_chrVI","start_pos":2886249},{"strain":"RH88","gene_id":"TGRH88_028460","name":null,"product":"HEAT repeat-containing protein","uniprot_acc":null,"chromosome":"CM023087","start_pos":730791},{"strain":"VEG","gene_id":"TGVEG_244040","name":null,"product":"HEAT repeat-containing protein","uniprot_acc":"V4Z8K9","chromosome":"TGVEG_chrVI","start_pos":2975917}]}