{"gene":"PF3D7_0730300","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2012,"finding":"AP2-L (PF3D7_0730300 ortholog in P. berghei) is required for liver-stage development: AP2-L-depleted parasites invaded hepatocytes normally but arrested in the middle of the liver schizont stage, reducing liver infectivity ~10,000-fold. Fluorescent protein-tagged AP2-L increased rapidly during liver schizont stage then disappeared at mature liver schizont formation. DNA microarray showed decreased expression of several genes including parasitophorous vacuole membrane proteins in early liver stage of AP2-L-depleted parasites.","method":"Reverse genetics (gene depletion), fluorescent protein tagging and live imaging, DNA microarray expression profiling, in vitro hepatocyte invasion assays","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean loss-of-function with specific cellular phenotype and expression profiling, single lab with multiple orthogonal methods","pmids":["23144823"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"finding":"PF3D7_0730300 (PfAP2-L) is identified as a component of a divergent GCN5 histone acetyltransferase complex in P. falciparum (referred to as PfAP2-LT in that study), which also contains PHD proteins PfPHD1 and PfPHD2. This complex regulates merozoite invasion genes, and its disruption causes reduced erythrocyte invasion and elevated sexual conversion.","method":"Co-immunoprecipitation/complex identification, conditional domain deletion, phenotypic assays (invasion, sexual conversion), transcriptomics","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — membership in GCN5 complex is reported but the specific mechanistic role of PfAP2-LT (PF3D7_0730300) itself within the complex is not dissected from other subunits in the abstract; single lab","pmids":["34403450"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Genome sequencing of P. falciparum vaccine and challenge strains identified variants (SNPs) in PfAP2-L (PF3D7_0730300) among strains used in whole-organism sporozoite vaccine trials, noting it as a transcription factor with sequence differences that could affect sporozoite vaccine-induced protection.","method":"Whole-genome sequencing (long-read and short-read), comparative genomics","journal":"Genome medicine","confidence":"Low","confidence_rationale":"Tier 4 / Weak — genomic/comparative analysis only, no functional experiment performed on PF3D7_0730300 itself","pmids":["31915075"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]}],"current_model":"AP2 (PF3D7_0730300, PfAP2-L) is an ApiAP2-family DNA-binding transcription factor whose P. berghei ortholog is essential for liver-stage development, where it is required for progression through the liver schizont stage and regulates expression of parasitophorous vacuole membrane protein genes; in P. falciparum it has been identified as a subunit of a divergent GCN5 histone acetyltransferase complex, but its precise molecular function within that complex remains uncharacterized."},"narrative":{"mechanistic_narrative":"PF3D7_0730300 (AP2-L) is an ApiAP2-family DNA-binding transcription factor implicated in stage-specific gene regulation across the Plasmodium life cycle [PMID:23144823, PMID:34403450]. In P. berghei, the AP2-L ortholog is essential for liver-stage development: depleted parasites invade hepatocytes normally but arrest midway through the liver schizont stage, reducing liver infectivity roughly 10,000-fold, and expression profiling links this arrest to reduced transcription of parasitophorous vacuole membrane protein genes in early liver stage [PMID:23144823]. In P. falciparum, PF3D7_0730300 has been identified as a subunit of a divergent GCN5 histone acetyltransferase complex that also contains PfPHD1 and PfPHD2 and whose disruption reduces erythrocyte invasion and elevates sexual conversion [PMID:34403450]; the specific molecular contribution of PF3D7_0730300 within this complex, as distinct from other subunits, has not been dissected in the available corpus.","teleology":[{"year":2012,"claim":"Establishing whether AP2-L has a dedicated developmental role, gene depletion revealed it is specifically required for progression through the liver schizont stage rather than for hepatocyte invasion.","evidence":"Reverse-genetic depletion with fluorescent tagging, live imaging, hepatocyte invasion assays, and DNA microarray in P. berghei","pmids":["23144823"],"confidence":"Medium","gaps":["Direct DNA-binding targets of AP2-L not defined (microarray shows downstream expression changes, not direct occupancy)","No P. falciparum functional data on liver-stage role in this study","Mechanism linking AP2-L to parasitophorous vacuole membrane protein gene regulation not resolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2020,"claim":"Addressing what molecular machinery PF3D7_0730300 acts within, it was identified as a subunit of a divergent GCN5 histone acetyltransferase complex containing PfPHD1 and PfPHD2 that governs merozoite invasion and sexual conversion.","evidence":"Co-immunoprecipitation/complex identification, conditional domain deletion, invasion and sexual-conversion assays, and transcriptomics in P. falciparum","pmids":["34403450"],"confidence":"Low","gaps":["The specific mechanistic role of PF3D7_0730300 within the complex is not dissected from other subunits","Whether PF3D7_0730300 provides the DNA-binding specificity for the complex is untested","Direct genomic targets of the complex versus individual subunits not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Comparative genomics of vaccine and challenge strains flagged sequence variation in PF3D7_0730300 as potentially relevant to sporozoite vaccine-induced protection, but no functional experiment tested this.","evidence":"Whole-genome (long- and short-read) sequencing and comparative genomics of P. falciparum NF54-derived strains","pmids":["31915075"],"confidence":"Low","gaps":["No functional experiment performed on PF3D7_0730300 variants","Effect of the identified SNPs on AP2-L function or vaccine protection untested","Association with protection is correlative genomic observation only"],"attribution":[{"species":"Plasmodium falciparum","strain":"NF54"}]},{"year":null,"claim":"How PF3D7_0730300 recognizes its DNA targets and whether its liver-stage regulatory role in P. berghei mechanistically corresponds to its GCN5-complex role in P. falciparum remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct DNA-binding motif or genome-wide occupancy data for PF3D7_0730300 in the corpus","No structural characterization","Cross-species reconciliation of liver-stage and blood-stage functions not established"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Divergent GCN5 histone acetyltransferase complex (with PfPHD1 and PfPHD2) [#1]"],"partners":["PFPHD1 [#1]","PFPHD2 [#1]"],"other_free_text":["In P. berghei, AP2-L is required for progression through the liver schizont stage; depletion reduces liver infectivity ~10,000-fold and lowers early liver-stage expression of parasitophorous vacuole membrane protein genes [#0].","In P. falciparum, disruption of the GCN5 complex containing PF3D7_0730300 reduces erythrocyte invasion and elevates sexual conversion [#1].","Sequence variants (SNPs) in PF3D7_0730300 were identified among whole-organism sporozoite vaccine and challenge strains, without functional testing [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"24572369","id":"PMC_24572369","title":"A transcriptional switch underlies commitment to sexual development in malaria parasites.","date":"2014","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/24572369","citation_count":397,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfAP2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"16040597","id":"PMC_16040597","title":"Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains.","date":"2005","source":"Nucleic acids 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Fluorescent protein-tagged AP2-L increased rapidly during liver schizont stage then disappeared at mature liver schizont formation. DNA microarray showed decreased expression of several genes including parasitophorous vacuole membrane proteins in early liver stage of AP2-L-depleted parasites.\",\n      \"method\": \"Reverse genetics (gene depletion), fluorescent protein tagging and live imaging, DNA microarray expression profiling, in vitro hepatocyte invasion assays\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean loss-of-function with specific cellular phenotype and expression profiling, single lab with multiple orthogonal methods\",\n      \"pmids\": [\"23144823\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_0730300 (PfAP2-L) is identified as a component of a divergent GCN5 histone acetyltransferase complex in P. falciparum (referred to as PfAP2-LT in that study), which also contains PHD proteins PfPHD1 and PfPHD2. This complex regulates merozoite invasion genes, and its disruption causes reduced erythrocyte invasion and elevated sexual conversion.\",\n      \"method\": \"Co-immunoprecipitation/complex identification, conditional domain deletion, phenotypic assays (invasion, sexual conversion), transcriptomics\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — membership in GCN5 complex is reported but the specific mechanistic role of PfAP2-LT (PF3D7_0730300) itself within the complex is not dissected from other subunits in the abstract; single lab\",\n      \"pmids\": [\"34403450\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Genome sequencing of P. falciparum vaccine and challenge strains identified variants (SNPs) in PfAP2-L (PF3D7_0730300) among strains used in whole-organism sporozoite vaccine trials, noting it as a transcription factor with sequence differences that could affect sporozoite vaccine-induced protection.\",\n      \"method\": \"Whole-genome sequencing (long-read and short-read), comparative genomics\",\n      \"journal\": \"Genome medicine\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — genomic/comparative analysis only, no functional experiment performed on PF3D7_0730300 itself\",\n      \"pmids\": [\"31915075\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    }\n  ],\n  \"current_model\": \"AP2 (PF3D7_0730300, PfAP2-L) is an ApiAP2-family DNA-binding transcription factor whose P. berghei ortholog is essential for liver-stage development, where it is required for progression through the liver schizont stage and regulates expression of parasitophorous vacuole membrane protein genes; in P. falciparum it has been identified as a subunit of a divergent GCN5 histone acetyltransferase complex, but its precise molecular function within that complex remains uncharacterized.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PF3D7_0730300 (AP2-L) is an ApiAP2-family DNA-binding transcription factor implicated in stage-specific gene regulation across the Plasmodium life cycle [#0, #1]. In P. berghei, the AP2-L ortholog is essential for liver-stage development: depleted parasites invade hepatocytes normally but arrest midway through the liver schizont stage, reducing liver infectivity roughly 10,000-fold, and expression profiling links this arrest to reduced transcription of parasitophorous vacuole membrane protein genes in early liver stage [#0]. In P. falciparum, PF3D7_0730300 has been identified as a subunit of a divergent GCN5 histone acetyltransferase complex that also contains PfPHD1 and PfPHD2 and whose disruption reduces erythrocyte invasion and elevates sexual conversion [#1]; the specific molecular contribution of PF3D7_0730300 within this complex, as distinct from other subunits, has not been dissected in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"Establishing whether AP2-L has a dedicated developmental role, gene depletion revealed it is specifically required for progression through the liver schizont stage rather than for hepatocyte invasion.\",\n      \"evidence\": \"Reverse-genetic depletion with fluorescent tagging, live imaging, hepatocyte invasion assays, and DNA microarray in P. berghei\",\n      \"pmids\": [\"23144823\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct DNA-binding targets of AP2-L not defined (microarray shows downstream expression changes, not direct occupancy)\",\n        \"No P. falciparum functional data on liver-stage role in this study\",\n        \"Mechanism linking AP2-L to parasitophorous vacuole membrane protein gene regulation not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Addressing what molecular machinery PF3D7_0730300 acts within, it was identified as a subunit of a divergent GCN5 histone acetyltransferase complex containing PfPHD1 and PfPHD2 that governs merozoite invasion and sexual conversion.\",\n      \"evidence\": \"Co-immunoprecipitation/complex identification, conditional domain deletion, invasion and sexual-conversion assays, and transcriptomics in P. falciparum\",\n      \"pmids\": [\"34403450\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"The specific mechanistic role of PF3D7_0730300 within the complex is not dissected from other subunits\",\n        \"Whether PF3D7_0730300 provides the DNA-binding specificity for the complex is untested\",\n        \"Direct genomic targets of the complex versus individual subunits not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Comparative genomics of vaccine and challenge strains flagged sequence variation in PF3D7_0730300 as potentially relevant to sporozoite vaccine-induced protection, but no functional experiment tested this.\",\n      \"evidence\": \"Whole-genome (long- and short-read) sequencing and comparative genomics of P. falciparum NF54-derived strains\",\n      \"pmids\": [\"31915075\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No functional experiment performed on PF3D7_0730300 variants\",\n        \"Effect of the identified SNPs on AP2-L function or vaccine protection untested\",\n        \"Association with protection is correlative genomic observation only\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"NF54\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PF3D7_0730300 recognizes its DNA targets and whether its liver-stage regulatory role in P. berghei mechanistically corresponds to its GCN5-complex role in P. falciparum remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct DNA-binding motif or genome-wide occupancy data for PF3D7_0730300 in the corpus\",\n        \"No structural characterization\",\n        \"Cross-species reconciliation of liver-stage and blood-stage functions not established\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003700\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0003677\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006357\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"Divergent GCN5 histone acetyltransferase complex (with PfPHD1 and PfPHD2) [#1]\"\n    ],\n    \"partners\": [\n      \"PfPHD1 [#1]\",\n      \"PfPHD2 [#1]\"\n    ],\n    \"other_free_text\": [\n      \"In P. berghei, AP2-L is required for progression through the liver schizont stage; depletion reduces liver infectivity ~10,000-fold and lowers early liver-stage expression of parasitophorous vacuole membrane protein genes [#0].\",\n      \"In P. falciparum, disruption of the GCN5 complex containing PF3D7_0730300 reduces erythrocyte invasion and elevates sexual conversion [#1].\",\n      \"Sequence variants (SNPs) in PF3D7_0730300 were identified among whole-organism sporozoite vaccine and challenge strains, without functional testing [#2].\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0730300","name":null,"product":"AP2 domain transcription factor AP2-L, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0214400","name":null,"product":"AP2 domain transcription factor AP2-L","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0215200","name":null,"product":"AP2 domain transcription factor AP2-L, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"AP2-L","evaluation":null}