{"gene":"TG_253380","gene_symbol":"AP2III2","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2024,"finding":"TgAP2III-2 has only a minor impact on tachyzoite proliferation as determined by genetic knockout analysis; in contrast, TgAP2XII-9 (studied in the same paper as a paired factor) regulates daughter cell assembly and IMC formation, and a double mutant of TgAP2XII-9 and TgAP2III-2 showed TgAP2XII-9 had the prominent role, indicating TgAP2III-2 plays at most a minor, non-essential role in the tachyzoite cell cycle.","method":"Genetic knockout (single and double mutant), transcriptomics, CUT&Tag chromatin binding analysis, immunofluorescence with cell cycle/IMC markers","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype and transcriptomic/CUT&Tag analysis in single lab; TgAP2III-2 phenotype is specifically described as minor, limiting mechanistic resolution","pmids":["39774584"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgAP2III-2 (AP2III2) is a Toxoplasma gondii ApiAP2 transcription factor that participates in tachyzoite cell cycle regulation but has only a minor impact on tachyzoite proliferation; it was studied alongside TgAP2XII-9 in a cascading AP2 expression program controlling daughter cell assembly, where TgAP2XII-9 rather than TgAP2III-2 was found to be the dominant regulator."},"narrative":{"mechanistic_narrative":"TgAP2III-2 (AP2III2) is a Toxoplasma gondii ApiAP2 transcription factor implicated in tachyzoite cell cycle regulation, but genetic knockout establishes that it has only a minor, non-essential impact on tachyzoite proliferation [PMID:39774584]. Studied alongside the paired factor TgAP2XII-9, single- and double-mutant analysis with transcriptomics and CUT&Tag chromatin binding showed that TgAP2XII-9 — not TgAP2III-2 — is the dominant regulator of daughter cell assembly and IMC formation [PMID:39774584]. Beyond this single characterization, no distinct genomic targets, cofactors, or mechanistic role specific to TgAP2III-2 have been resolved in the available corpus.","teleology":[{"year":2024,"claim":"To determine whether TgAP2III-2 contributes to the AP2 expression program governing tachyzoite cell division, knockout analysis was performed and showed it plays at most a minor, non-essential role, with the paired factor TgAP2XII-9 dominating daughter cell assembly.","evidence":"Single and double genetic knockouts with transcriptomics, CUT&Tag chromatin binding, and immunofluorescence using cell cycle/IMC markers in Toxoplasma gondii","pmids":["39774584"],"confidence":"Medium","gaps":["The specific chromatin targets and any direct regulatory function unique to TgAP2III-2 were not resolved because its knockout phenotype is minor","No cofactors or protein partners of TgAP2III-2 identified","Its role, if any, in life-cycle stages other than the tachyzoite was not examined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"It remains unknown what direct genomic targets, binding motif, or non-redundant biological function TgAP2III-2 possesses beyond its minor contribution to tachyzoite division.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No dedicated characterization of TgAP2III-2 chromatin occupancy independent of TgAP2XII-9","No identified condition under which TgAP2III-2 loss produces a strong phenotype"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGAP2XII-9 (STUDIED AS PAIRED FACTOR; DOMINANT REGULATOR IN DOUBLE-MUTANT ANALYSIS) [#0]"],"other_free_text":["Genetic knockout indicates TgAP2III-2 is non-essential for tachyzoite proliferation [#0]","TgAP2XII-9, not TgAP2III-2, regulates daughter cell assembly and IMC formation [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"20865045","id":"PMC_20865045","title":"Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/20865045","citation_count":234,"is_preprint":false},{"pmid":"29932347","id":"PMC_29932347","title":"The Epigenome, Cell Cycle, and Development in Toxoplasma.","date":"2018","source":"Annual review of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29932347","citation_count":51,"is_preprint":false},{"pmid":"20657661","id":"PMC_20657661","title":"The construction and use of log-odds substitution scores for multiple sequence alignment.","date":"2010","source":"PLoS computational biology","url":"https://pubmed.ncbi.nlm.nih.gov/20657661","citation_count":48,"is_preprint":false},{"pmid":"19146987","id":"PMC_19146987","title":"Repeated secondary loss of adaptin complex genes in the Apicomplexa.","date":"2008","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/19146987","citation_count":36,"is_preprint":false},{"pmid":"22486860","id":"PMC_22486860","title":"Cactin is essential for G1 progression in Toxoplasma gondii.","date":"2012","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/22486860","citation_count":23,"is_preprint":false},{"pmid":"25393307","id":"PMC_25393307","title":"Distinct strains of Toxoplasma gondii feature divergent transcriptomes regardless of developmental stage.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25393307","citation_count":22,"is_preprint":false},{"pmid":"18983845","id":"PMC_18983845","title":"New eukaryotic systematics: a phylogenetic perspective of developmental gene expression in the Apicomplexa.","date":"2008","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/18983845","citation_count":12,"is_preprint":false},{"pmid":"39690155","id":"PMC_39690155","title":"Apicomplexan mitoribosome from highly fragmented rRNAs to a functional machine.","date":"2024","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/39690155","citation_count":9,"is_preprint":false},{"pmid":"39774584","id":"PMC_39774584","title":"Cascading expression of ApiAP2 transcription factors controls daughter cell assembly in Toxoplasma gondii.","date":"2024","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/39774584","citation_count":3,"is_preprint":false},{"pmid":"36178892","id":"PMC_36178892","title":"Genomic insights into host and parasite interactions during intracellular infection by Toxoplasma gondii.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/36178892","citation_count":2,"is_preprint":false},{"pmid":"42087241","id":"PMC_42087241","title":"Host-cell dependent epigenetic profiles associated with survival outcomes in T. gondii infection.","date":"2026","source":"Epigenetics & chromatin","url":"https://pubmed.ncbi.nlm.nih.gov/42087241","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":18625,"output_tokens":469,"usd":0.031455,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5101,"output_tokens":1397,"usd":0.030215,"stage2_stop_reason":"end_turn"},"total_usd":0.06167,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","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\": 2024,\n      \"finding\": \"TgAP2III-2 has only a minor impact on tachyzoite proliferation as determined by genetic knockout analysis; in contrast, TgAP2XII-9 (studied in the same paper as a paired factor) regulates daughter cell assembly and IMC formation, and a double mutant of TgAP2XII-9 and TgAP2III-2 showed TgAP2XII-9 had the prominent role, indicating TgAP2III-2 plays at most a minor, non-essential role in the tachyzoite cell cycle.\",\n      \"method\": \"Genetic knockout (single and double mutant), transcriptomics, CUT&Tag chromatin binding analysis, immunofluorescence with cell cycle/IMC markers\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype and transcriptomic/CUT&Tag analysis in single lab; TgAP2III-2 phenotype is specifically described as minor, limiting mechanistic resolution\",\n      \"pmids\": [\"39774584\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgAP2III-2 (AP2III2) is a Toxoplasma gondii ApiAP2 transcription factor that participates in tachyzoite cell cycle regulation but has only a minor impact on tachyzoite proliferation; it was studied alongside TgAP2XII-9 in a cascading AP2 expression program controlling daughter cell assembly, where TgAP2XII-9 rather than TgAP2III-2 was found to be the dominant regulator.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgAP2III-2 (AP2III2) is a Toxoplasma gondii ApiAP2 transcription factor implicated in tachyzoite cell cycle regulation, but genetic knockout establishes that it has only a minor, non-essential impact on tachyzoite proliferation [#0]. Studied alongside the paired factor TgAP2XII-9, single- and double-mutant analysis with transcriptomics and CUT&Tag chromatin binding showed that TgAP2XII-9 — not TgAP2III-2 — is the dominant regulator of daughter cell assembly and IMC formation [#0]. Beyond this single characterization, no distinct genomic targets, cofactors, or mechanistic role specific to TgAP2III-2 have been resolved in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2024,\n      \"claim\": \"To determine whether TgAP2III-2 contributes to the AP2 expression program governing tachyzoite cell division, knockout analysis was performed and showed it plays at most a minor, non-essential role, with the paired factor TgAP2XII-9 dominating daughter cell assembly.\",\n      \"evidence\": \"Single and double genetic knockouts with transcriptomics, CUT&Tag chromatin binding, and immunofluorescence using cell cycle/IMC markers in Toxoplasma gondii\",\n      \"pmids\": [\"39774584\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate\",\n      \"gaps\": [\n        \"The specific chromatin targets and any direct regulatory function unique to TgAP2III-2 were not resolved because its knockout phenotype is minor\",\n        \"No cofactors or protein partners of TgAP2III-2 identified\",\n        \"Its role, if any, in life-cycle stages other than the tachyzoite was not examined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what direct genomic targets, binding motif, or non-redundant biological function TgAP2III-2 possesses beyond its minor contribution to tachyzoite division.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No dedicated characterization of TgAP2III-2 chromatin occupancy independent of TgAP2XII-9\",\n        \"No identified condition under which TgAP2III-2 loss produces a strong phenotype\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003700\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007049\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006355\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"TgAP2XII-9 (studied as paired factor; dominant regulator in double-mutant analysis) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Genetic knockout indicates TgAP2III-2 is non-essential for tachyzoite proliferation [#0]\",\n      \"TgAP2XII-9, not TgAP2III-2, regulates daughter cell assembly and IMC formation [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_253380","name":"AP2III2","product":"AP2 domain transcription factor AP2III-2","uniprot_acc":"S8FDR0","chromosome":"TGME49_chrIII","start_pos":904923},{"strain":"GT1","gene_id":"TGGT1_253380","name":null,"product":"AP2 domain transcription factor AP2III-2","uniprot_acc":null,"chromosome":"TGGT1_chrIII","start_pos":889944},{"strain":"RH88","gene_id":"TGRH88_004930","name":null,"product":"AP2 domain transcription factor AP2III-2","uniprot_acc":null,"chromosome":"CM023084","start_pos":1692751},{"strain":"VEG","gene_id":"TGVEG_253380","name":null,"product":"AP2 domain transcription factor AP2III-2","uniprot_acc":"B9QIW3","chromosome":"TGVEG_chrIII","start_pos":917369}]}