{"gene":"PF3D7_1007700","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2017,"finding":"PF3D7_1007700 (PfAP2-I) binds a specific DNA motif in the promoters of target genes involved in red blood cell (RBC) invasion, as determined by genome-wide ChIP-seq. Although PfAP2-I contains three AP2 DNA-binding domains, only one is required for binding target genes during blood-stage development.","method":"ChIP-seq, domain mutagenesis/deletion analysis","journal":"Cell host & microbe","confidence":"High","confidence_rationale":"Tier 1–2 / Moderate — genome-wide ChIP-seq with domain functional dissection in a single rigorous study establishing DNA-binding specificity and domain requirement","pmids":["28618269"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PF3D7_1007700 (PfAP2-I) associates with the Plasmodium bromodomain protein PfBDP1 and other chromatin-associated proteins; this complex formation is associated with transcriptional regulation of RBC invasion genes.","method":"Co-immunoprecipitation / protein interaction (ChIP-seq context)","journal":"Cell host & microbe","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — association demonstrated in single study; complex formation linked to transcriptional regulation but interaction mechanism not reconstituted in vitro","pmids":["28618269"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"PfAP2-I (PF3D7_1007700) is a key regulator of red blood cell invasion: its targets include genes encoding invasion machinery, and its activity is essential for the invasion gene expression program in blood-stage parasites.","method":"Conditional knockdown with loss-of-function phenotype, genome-wide transcriptomics","journal":"Cell host & microbe","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional knockdown combined with genome-wide ChIP-seq and transcriptomics in a single rigorous study establishing defined cellular role","pmids":["28618269"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Regulation of RBC invasion genes by PfAP2-G requires interaction with PfAP2-I (PF3D7_1007700), placing PfAP2-I as a required co-factor in the PfAP2-G transcriptional regulatory network during sexual commitment.","method":"ChIP-seq, genetic interaction / epistasis analysis","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — single lab ChIP-seq study identifying PfAP2-I as required partner of PfAP2-G; interaction mechanism not independently reconstituted","pmids":["32198457"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Jumonji demethylase inhibitor JIB-04 deregulates gene targets co-regulated by PfAP2-I (PF3D7_1007700) and PfBDP1, linking PfAP2-I target gene regulation to histone demethylase activity in the invasion gene program.","method":"Pharmacological inhibition, transcriptomics","journal":"ACS infectious diseases","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single study using pharmacological perturbation with indirect readout; PfAP2-I not directly manipulated","pmids":["32272012"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"PfAP2-I (PF3D7_1007700) target genes encoding merozoite invasion proteins are co-regulated by the PfGCN5 histone acetyltransferase complex (containing PfAP2-LT and PfBDP1); domain deletions in PfGCN5 or PfPHD1 specifically downregulate invasion genes containing the AP2-LT binding motif that overlap with PfAP2-I targets, suggesting targeted co-recruitment of the PfGCN5 complex to invasion genes by PfAP2-I.","method":"Domain deletion mutants, ChIP-seq, RNA-seq","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — PfAP2-I target overlap inferred from transcriptomic correlation, not by direct manipulation of PfAP2-I itself","pmids":["34403450"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"H3K18ac, H3K27ac, and PfH2A.Z co-localize with PfAP2-I (PF3D7_1007700) and PfBDP1 at stably positioned nucleosomes within open chromatin at active transcriptional start sites in schizont stages, and these regions possess promoter activity; this places PfAP2-I at actively acetylated regulatory regions controlling invasion gene expression.","method":"ChIP-seq, transient transfection promoter assay","journal":"Epigenetics & chromatin","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — ChIP-seq co-localization with functional promoter assay, single lab, no direct manipulation of PfAP2-I","pmids":["33225957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"finding":"An ab initio 3D structural model of PfAP2-I (PF3D7_1007700) was generated and used for in silico active site prediction and molecular docking; however, no experimental structural validation (crystallography, cryo-EM, or NMR) was performed.","method":"Computational structure prediction (ROBETTA), molecular docking (AutoDock Vina), molecular dynamics simulation","journal":"Bioinformatics and biology insights","confidence":"Low","confidence_rationale":"Tier 4 / Weak — purely computational; no experimental structural or biochemical validation of the model or predicted binding","pmids":["36704725"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1007700 (PfAP2-I) is an ApiAP2-family transcription factor that binds a specific DNA motif via one of its three AP2 domains at promoters of red blood cell invasion genes in P. falciparum blood stages, where it forms a complex with the bromodomain protein PfBDP1 and other chromatin-associated proteins to drive transcriptional regulation of the invasion gene program; additionally, PfAP2-I acts as a required co-factor for PfAP2-G-mediated transcriptional regulation, linking the invasion machinery regulatory network to the sexual commitment cascade."},"narrative":{"mechanistic_narrative":"PF3D7_1007700 (PfAP2-I) is an ApiAP2-family transcription factor that serves as a master regulator of the red blood cell invasion gene program in Plasmodium falciparum blood stages [PMID:28618269]. It binds a specific DNA motif in the promoters of invasion machinery genes; although it carries three AP2 DNA-binding domains, only one is required for target binding during blood-stage development, and its activity is essential for the invasion gene expression program [PMID:28618269]. PfAP2-I does not act alone: it associates with the bromodomain protein PfBDP1 and other chromatin-associated proteins, and this complex operates at actively acetylated regulatory regions—marked by H3K18ac, H3K27ac, and PfH2A.Z at stably positioned nucleosomes within open chromatin at active transcriptional start sites in schizonts—to drive invasion gene transcription [PMID:28618269, PMID:33225957]. Beyond invasion regulation, PfAP2-I is a required co-factor for PfAP2-G-mediated regulation of RBC invasion genes, linking the invasion regulatory network to the sexual commitment cascade [PMID:32198457].","teleology":[{"year":2017,"claim":"Establishing what PfAP2-I does mechanistically: whether it directly binds invasion gene promoters and which of its AP2 domains is functional resolved its identity as a sequence-specific invasion gene regulator.","evidence":"Genome-wide ChIP-seq with domain mutagenesis/deletion in P. falciparum blood stages","pmids":["28618269"],"confidence":"High","gaps":["Structural basis for why only one of three AP2 domains is used is not defined","The DNA-binding affinity and specificity were not reconstituted in vitro"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Determining whether PfAP2-I acts as a stand-alone factor or within a complex: it was shown to associate with PfBDP1 and other chromatin-associated proteins, linking DNA binding to a chromatin-based regulatory apparatus.","evidence":"Co-immunoprecipitation / protein interaction analysis in P. falciparum","pmids":["28618269"],"confidence":"Medium","gaps":["Interaction with PfBDP1 not reconstituted in vitro","Direct versus indirect nature of the association within the complex not resolved","Stoichiometry and composition of the full complex undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Testing whether PfAP2-I is functionally required for invasion: conditional knockdown established it as essential for the invasion gene expression program rather than a passive DNA-binding protein.","evidence":"Conditional knockdown loss-of-function with genome-wide transcriptomics in P. falciparum","pmids":["28618269"],"confidence":"High","gaps":["Direct effect on parasite invasion phenotype versus transcriptional readout not fully separated","Whether all bound targets are functionally dependent on PfAP2-I unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Placing PfAP2-I in a chromatin context: co-localization with active histone acetylation marks and PfH2A.Z at nucleosome-defined active promoters showed it operates at open, transcriptionally active regulatory regions.","evidence":"ChIP-seq co-localization and transient transfection promoter activity assays in schizont-stage P. falciparum","pmids":["33225957"],"confidence":"Medium","gaps":["Causal order between PfAP2-I binding and acetylation mark deposition not established","PfAP2-I not directly manipulated in this study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Connecting PfAP2-I to the sexual commitment network: genetic interaction analysis showed PfAP2-G requires PfAP2-I to regulate RBC invasion genes, defining PfAP2-I as a co-factor bridging invasion and commitment programs.","evidence":"ChIP-seq and genetic interaction/epistasis analysis in P. falciparum","pmids":["32198457"],"confidence":"Medium","gaps":["Physical interaction between PfAP2-I and PfAP2-G not reconstituted","Mechanism of co-factor requirement unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Probing chromatin-modifier dependence of PfAP2-I targets: pharmacological Jumonji demethylase inhibition deregulated PfAP2-I/PfBDP1 co-regulated genes, linking their expression to histone demethylase activity.","evidence":"Pharmacological inhibition (JIB-04) with transcriptomics in P. falciparum","pmids":["32272012"],"confidence":"Low","gaps":["PfAP2-I not directly manipulated; effect is indirect","Whether demethylase acts on PfAP2-I target loci directly is not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Extending the chromatin-modifier link: overlap of PfAP2-I targets with PfGCN5/PfBDP1 complex-regulated invasion genes raised the model that PfAP2-I recruits the acetyltransferase complex to invasion promoters.","evidence":"Domain deletion mutants of PfGCN5/PfPHD1 with ChIP-seq and RNA-seq in P. falciparum","pmids":["34403450"],"confidence":"Low","gaps":["Target overlap inferred from transcriptomic correlation, not direct PfAP2-I manipulation","Physical recruitment of PfGCN5 complex by PfAP2-I not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Toward a structural understanding: a computational 3D model enabled in silico active site prediction and docking, but no experimental structure exists.","evidence":"Ab initio structure prediction (ROBETTA), docking (AutoDock Vina), and molecular dynamics; no experimental validation","pmids":["36704725"],"confidence":"Low","gaps":["No crystallography, cryo-EM, or NMR validation","Predicted binding sites biochemically untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"How PfAP2-I physically assembles with PfBDP1, PfAP2-G, and the PfGCN5 complex, and how these interactions are directed to specific invasion promoters, remains mechanistically undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No reconstituted protein-protein interaction data","No experimental structure of PfAP2-I or its complexes","Order of assembly and recruitment mechanism at target promoters unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfAP2-I / PfBDP1 chromatin-associated complex"],"partners":["PFBDP1","PFAP2-G","PFGCN5 HISTONE ACETYLTRANSFERASE COMPLEX (PFAP2-LT, PFBDP1, PFPHD1) — TARGET OVERLAP"],"other_free_text":["Binds a specific DNA motif in promoters of red blood cell invasion genes; only one of three AP2 domains is required for target binding in blood stages [#0].","Essential for the invasion gene expression program; conditional knockdown causes loss of function [#2].","Occupies active regulatory regions marked by H3K18ac, H3K27ac, and PfH2A.Z at active transcriptional start sites in schizonts [#6].","Required co-factor for PfAP2-G-mediated regulation of invasion genes, linking invasion regulation to sexual commitment [#3].","Only a computational 3D structural model exists; no experimental structure has been determined [#7]."]}},"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 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Although PfAP2-I contains three AP2 DNA-binding domains, only one is required for binding target genes during blood-stage development.\",\n      \"method\": \"ChIP-seq, domain mutagenesis/deletion analysis\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1–2 / Moderate — genome-wide ChIP-seq with domain functional dissection in a single rigorous study establishing DNA-binding specificity and domain requirement\",\n      \"pmids\": [\"28618269\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PF3D7_1007700 (PfAP2-I) associates with the Plasmodium bromodomain protein PfBDP1 and other chromatin-associated proteins; this complex formation is associated with transcriptional regulation of RBC invasion genes.\",\n      \"method\": \"Co-immunoprecipitation / protein interaction (ChIP-seq context)\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — association demonstrated in single study; complex formation linked to transcriptional regulation but interaction mechanism not reconstituted in vitro\",\n      \"pmids\": [\"28618269\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"PfAP2-I (PF3D7_1007700) is a key regulator of red blood cell invasion: its targets include genes encoding invasion machinery, and its activity is essential for the invasion gene expression program in blood-stage parasites.\",\n      \"method\": \"Conditional knockdown with loss-of-function phenotype, genome-wide transcriptomics\",\n      \"journal\": \"Cell host & microbe\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown combined with genome-wide ChIP-seq and transcriptomics in a single rigorous study establishing defined cellular role\",\n      \"pmids\": [\"28618269\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Regulation of RBC invasion genes by PfAP2-G requires interaction with PfAP2-I (PF3D7_1007700), placing PfAP2-I as a required co-factor in the PfAP2-G transcriptional regulatory network during sexual commitment.\",\n      \"method\": \"ChIP-seq, genetic interaction / epistasis analysis\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — single lab ChIP-seq study identifying PfAP2-I as required partner of PfAP2-G; interaction mechanism not independently reconstituted\",\n      \"pmids\": [\"32198457\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Jumonji demethylase inhibitor JIB-04 deregulates gene targets co-regulated by PfAP2-I (PF3D7_1007700) and PfBDP1, linking PfAP2-I target gene regulation to histone demethylase activity in the invasion gene program.\",\n      \"method\": \"Pharmacological inhibition, transcriptomics\",\n      \"journal\": \"ACS infectious diseases\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single study using pharmacological perturbation with indirect readout; PfAP2-I not directly manipulated\",\n      \"pmids\": [\"32272012\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"PfAP2-I (PF3D7_1007700) target genes encoding merozoite invasion proteins are co-regulated by the PfGCN5 histone acetyltransferase complex (containing PfAP2-LT and PfBDP1); domain deletions in PfGCN5 or PfPHD1 specifically downregulate invasion genes containing the AP2-LT binding motif that overlap with PfAP2-I targets, suggesting targeted co-recruitment of the PfGCN5 complex to invasion genes by PfAP2-I.\",\n      \"method\": \"Domain deletion mutants, ChIP-seq, RNA-seq\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — PfAP2-I target overlap inferred from transcriptomic correlation, not by direct manipulation of PfAP2-I itself\",\n      \"pmids\": [\"34403450\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"H3K18ac, H3K27ac, and PfH2A.Z co-localize with PfAP2-I (PF3D7_1007700) and PfBDP1 at stably positioned nucleosomes within open chromatin at active transcriptional start sites in schizont stages, and these regions possess promoter activity; this places PfAP2-I at actively acetylated regulatory regions controlling invasion gene expression.\",\n      \"method\": \"ChIP-seq, transient transfection promoter assay\",\n      \"journal\": \"Epigenetics & chromatin\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — ChIP-seq co-localization with functional promoter assay, single lab, no direct manipulation of PfAP2-I\",\n      \"pmids\": [\"33225957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"An ab initio 3D structural model of PfAP2-I (PF3D7_1007700) was generated and used for in silico active site prediction and molecular docking; however, no experimental structural validation (crystallography, cryo-EM, or NMR) was performed.\",\n      \"method\": \"Computational structure prediction (ROBETTA), molecular docking (AutoDock Vina), molecular dynamics simulation\",\n      \"journal\": \"Bioinformatics and biology insights\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — purely computational; no experimental structural or biochemical validation of the model or predicted binding\",\n      \"pmids\": [\"36704725\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1007700 (PfAP2-I) is an ApiAP2-family transcription factor that binds a specific DNA motif via one of its three AP2 domains at promoters of red blood cell invasion genes in P. falciparum blood stages, where it forms a complex with the bromodomain protein PfBDP1 and other chromatin-associated proteins to drive transcriptional regulation of the invasion gene program; additionally, PfAP2-I acts as a required co-factor for PfAP2-G-mediated transcriptional regulation, linking the invasion machinery regulatory network to the sexual commitment cascade.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1007700 (PfAP2-I) is an ApiAP2-family transcription factor that serves as a master regulator of the red blood cell invasion gene program in Plasmodium falciparum blood stages [#2]. It binds a specific DNA motif in the promoters of invasion machinery genes; although it carries three AP2 DNA-binding domains, only one is required for target binding during blood-stage development, and its activity is essential for the invasion gene expression program [#0, #2]. PfAP2-I does not act alone: it associates with the bromodomain protein PfBDP1 and other chromatin-associated proteins, and this complex operates at actively acetylated regulatory regions—marked by H3K18ac, H3K27ac, and PfH2A.Z at stably positioned nucleosomes within open chromatin at active transcriptional start sites in schizonts—to drive invasion gene transcription [#1, #6]. Beyond invasion regulation, PfAP2-I is a required co-factor for PfAP2-G-mediated regulation of RBC invasion genes, linking the invasion regulatory network to the sexual commitment cascade [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing what PfAP2-I does mechanistically: whether it directly binds invasion gene promoters and which of its AP2 domains is functional resolved its identity as a sequence-specific invasion gene regulator.\",\n      \"evidence\": \"Genome-wide ChIP-seq with domain mutagenesis/deletion in P. falciparum blood stages\",\n      \"pmids\": [\"28618269\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural basis for why only one of three AP2 domains is used is not defined\", \"The DNA-binding affinity and specificity were not reconstituted in vitro\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Determining whether PfAP2-I acts as a stand-alone factor or within a complex: it was shown to associate with PfBDP1 and other chromatin-associated proteins, linking DNA binding to a chromatin-based regulatory apparatus.\",\n      \"evidence\": \"Co-immunoprecipitation / protein interaction analysis in P. falciparum\",\n      \"pmids\": [\"28618269\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Interaction with PfBDP1 not reconstituted in vitro\", \"Direct versus indirect nature of the association within the complex not resolved\", \"Stoichiometry and composition of the full complex undefined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Testing whether PfAP2-I is functionally required for invasion: conditional knockdown established it as essential for the invasion gene expression program rather than a passive DNA-binding protein.\",\n      \"evidence\": \"Conditional knockdown loss-of-function with genome-wide transcriptomics in P. falciparum\",\n      \"pmids\": [\"28618269\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct effect on parasite invasion phenotype versus transcriptional readout not fully separated\", \"Whether all bound targets are functionally dependent on PfAP2-I unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Placing PfAP2-I in a chromatin context: co-localization with active histone acetylation marks and PfH2A.Z at nucleosome-defined active promoters showed it operates at open, transcriptionally active regulatory regions.\",\n      \"evidence\": \"ChIP-seq co-localization and transient transfection promoter activity assays in schizont-stage P. falciparum\",\n      \"pmids\": [\"33225957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Causal order between PfAP2-I binding and acetylation mark deposition not established\", \"PfAP2-I not directly manipulated in this study\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Connecting PfAP2-I to the sexual commitment network: genetic interaction analysis showed PfAP2-G requires PfAP2-I to regulate RBC invasion genes, defining PfAP2-I as a co-factor bridging invasion and commitment programs.\",\n      \"evidence\": \"ChIP-seq and genetic interaction/epistasis analysis in P. falciparum\",\n      \"pmids\": [\"32198457\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physical interaction between PfAP2-I and PfAP2-G not reconstituted\", \"Mechanism of co-factor requirement unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Probing chromatin-modifier dependence of PfAP2-I targets: pharmacological Jumonji demethylase inhibition deregulated PfAP2-I/PfBDP1 co-regulated genes, linking their expression to histone demethylase activity.\",\n      \"evidence\": \"Pharmacological inhibition (JIB-04) with transcriptomics in P. falciparum\",\n      \"pmids\": [\"32272012\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"PfAP2-I not directly manipulated; effect is indirect\", \"Whether demethylase acts on PfAP2-I target loci directly is not shown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Extending the chromatin-modifier link: overlap of PfAP2-I targets with PfGCN5/PfBDP1 complex-regulated invasion genes raised the model that PfAP2-I recruits the acetyltransferase complex to invasion promoters.\",\n      \"evidence\": \"Domain deletion mutants of PfGCN5/PfPHD1 with ChIP-seq and RNA-seq in P. falciparum\",\n      \"pmids\": [\"34403450\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Target overlap inferred from transcriptomic correlation, not direct PfAP2-I manipulation\", \"Physical recruitment of PfGCN5 complex by PfAP2-I not demonstrated\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Toward a structural understanding: a computational 3D model enabled in silico active site prediction and docking, but no experimental structure exists.\",\n      \"evidence\": \"Ab initio structure prediction (ROBETTA), docking (AutoDock Vina), and molecular dynamics; no experimental validation\",\n      \"pmids\": [\"36704725\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No crystallography, cryo-EM, or NMR validation\", \"Predicted binding sites biochemically untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PfAP2-I physically assembles with PfBDP1, PfAP2-G, and the PfGCN5 complex, and how these interactions are directed to specific invasion promoters, remains mechanistically undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No reconstituted protein-protein interaction data\", \"No experimental structure of PfAP2-I or its complexes\", \"Order of assembly and recruitment mechanism at target promoters unresolved\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003700\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0000976\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0043565\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0, 6]},\n      {\"term_id\": \"GO:0000785\", \"supporting_discovery_ids\": [6]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006357\", \"supporting_discovery_ids\": [2, 0]},\n      {\"term_id\": \"GO:0060255\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"PfAP2-I / PfBDP1 chromatin-associated complex\"\n    ],\n    \"partners\": [\n      \"PfBDP1\",\n      \"PfAP2-G\",\n      \"PfGCN5 histone acetyltransferase complex (PfAP2-LT, PfBDP1, PfPHD1) — target overlap\"\n    ],\n    \"other_free_text\": [\n      \"Binds a specific DNA motif in promoters of red blood cell invasion genes; only one of three AP2 domains is required for target binding in blood stages [#0].\",\n      \"Essential for the invasion gene expression program; conditional knockdown causes loss of function [#2].\",\n      \"Occupies active regulatory regions marked by H3K18ac, H3K27ac, and PfH2A.Z at active transcriptional start sites in schizonts [#6].\",\n      \"Required co-factor for PfAP2-G-mediated regulation of invasion genes, linking invasion regulation to sexual commitment [#3].\",\n      \"Only a computational 3D structural model exists; no experimental structure has been determined [#7].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1007700","name":null,"product":"AP2 domain transcription factor AP2-I","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1205900","name":null,"product":"AP2 domain transcription factor AP2-I, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0806500","name":null,"product":"AP2 domain transcription factor AP2-I, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"AP2-I","evaluation":null}