{"gene":"PF3D7_1433300","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2020,"finding":"PF3D7_1433300 (RBAP46) was expressed in all three asexual blood stages and exhibited nuclear localization in P. falciparum, as determined by cloning, recombinant expression, and microscopy.","method":"Cloning, recombinant expression in E. coli, subcellular localization by direct imaging","journal":"Parasitology research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment with expression characterization across life stages, single lab, but no functional consequence explicitly tied to localization","pmids":["32363442"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Purified recombinant PF3D7_1433300 (RBAP46) directly interacts with histone H4, as shown by in vitro binding assay with purified protein.","method":"In vitro binding assay with purified recombinant protein and histone H4","journal":"Parasitology research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — direct in vitro binding assay establishing substrate interaction, but single lab and single method","pmids":["32363442"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"In silico structural analysis of PF3D7_1433300 (RBAP46) revealed conservation of the seven-bladed WD40 β-propeller conformation and histone H4 binding interface relative to human RBBP7, with species-specific differences in the histone binding pocket residues.","method":"Comparative in silico sequence and structural analysis (homology modeling)","journal":"Parasitology research","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/structural prediction only, no experimental mutagenesis or structural determination","pmids":["32363442"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1433300 (RBAP46) is a WD40-repeat histone chaperone that localizes to the nucleus in asexual blood-stage P. falciparum and directly binds histone H4 in vitro, consistent with a role in chromatin maintenance, though its precise placement within specific chromatin-regulatory complexes in the parasite has not yet been experimentally established."},"narrative":{"mechanistic_narrative":"PF3D7_1433300 (RBAP46) is a putative histone chaperone of asexual blood-stage Plasmodium falciparum that is expressed across all three asexual blood stages and localizes to the nucleus [PMID:32363442]. Purified recombinant PF3D7_1433300 directly binds histone H4 in vitro, identifying histone H4 as a physical interaction partner and pointing to a role in chromatin maintenance [PMID:32363442]. Beyond its nuclear localization and direct H4 binding, no functional role, complex membership, or in vivo phenotype for PF3D7_1433300 has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Whether PF3D7_1433300 is expressed and where it acts in the parasite was unknown; establishing stage-specific expression and nuclear localization positioned it as a candidate chromatin-associated factor in blood-stage parasites.","evidence":"Cloning, recombinant expression in E. coli, and subcellular localization by direct imaging in P. falciparum","pmids":["32363442"],"confidence":"Medium","gaps":["No functional consequence tied to the nuclear localization","No identification of the chromatin-regulatory complex it associates with in vivo","Single-lab observation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether PF3D7_1433300 physically engages histones was unknown; demonstrating direct binding to histone H4 established a candidate molecular substrate and supported a histone-chaperone function.","evidence":"In vitro binding assay with purified recombinant protein and histone H4","pmids":["32363442"],"confidence":"Medium","gaps":["Single method and single lab, no reciprocal or in-cell validation of the interaction","Binding affinity and stoichiometry not determined","No demonstration that H4 binding matters for any parasite chromatin process"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether the parasite protein retains the structural features underlying histone recognition was addressed by modeling its predicted fold against human RBBP7.","evidence":"Comparative in silico sequence and homology structural analysis","pmids":["32363442"],"confidence":"Low","gaps":["Computational prediction only; no experimental structure or mutagenesis of the predicted histone-binding pocket","Species-specific pocket residue differences not functionally tested","Fold not confirmed by structural determination"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific chromatin-regulatory complex(es) PF3D7_1433300 operates within in P. falciparum, and its in vivo function and essentiality, remain unestablished.","evidence":"","pmids":[],"confidence":"Low","gaps":["No complex membership defined for PF3D7_1433300 itself","No genetic knockdown/knockout phenotype reported","No demonstrated role in a defined chromatin process"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["HISTONE H4"],"other_free_text":["Expressed across all three asexual blood stages of P. falciparum [#0]","Predicted seven-bladed WD40 beta-propeller fold with a histone H4 binding interface, by homology modeling against human RBBP7, with species-specific histone-pocket residue differences [#2]","No experimentally defined chromatin-regulatory complex membership for PF3D7_1433300 in the available corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"32363442","id":"PMC_32363442","title":"The multifaceted histone chaperone RbAp46/48 in Plasmodium falciparum: structural insights, production, and characterization.","date":"2020","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/32363442","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RBAP46","RBBP7","PfRBAP46"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35923798","id":"","title":"The WD40-Protein PfWLP1 Ensures Stability of the PfCCp-Based Adhesion Protein Complex in Plasmodium falciparum Gametocytes.","date":"2022","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/35923798","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RBAP46"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26043001","id":"","title":"Genome-Wide Collation of the Plasmodium falciparum WDR Protein Superfamily Reveals Malarial Parasite-Specific Features.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26043001","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["RBAP46"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5359,"output_tokens":743,"usd":0.013611,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5386,"output_tokens":1552,"usd":0.032865,"stage2_stop_reason":"end_turn"},"total_usd":0.046476,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_1433300 (RBAP46) was expressed in all three asexual blood stages and exhibited nuclear localization in P. falciparum, as determined by cloning, recombinant expression, and microscopy.\",\n      \"method\": \"Cloning, recombinant expression in E. coli, subcellular localization by direct imaging\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment with expression characterization across life stages, single lab, but no functional consequence explicitly tied to localization\",\n      \"pmids\": [\"32363442\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Purified recombinant PF3D7_1433300 (RBAP46) directly interacts with histone H4, as shown by in vitro binding assay with purified protein.\",\n      \"method\": \"In vitro binding assay with purified recombinant protein and histone H4\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — direct in vitro binding assay establishing substrate interaction, but single lab and single method\",\n      \"pmids\": [\"32363442\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In silico structural analysis of PF3D7_1433300 (RBAP46) revealed conservation of the seven-bladed WD40 β-propeller conformation and histone H4 binding interface relative to human RBBP7, with species-specific differences in the histone binding pocket residues.\",\n      \"method\": \"Comparative in silico sequence and structural analysis (homology modeling)\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/structural prediction only, no experimental mutagenesis or structural determination\",\n      \"pmids\": [\"32363442\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1433300 (RBAP46) is a WD40-repeat histone chaperone that localizes to the nucleus in asexual blood-stage P. falciparum and directly binds histone H4 in vitro, consistent with a role in chromatin maintenance, though its precise placement within specific chromatin-regulatory complexes in the parasite has not yet been experimentally established.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1433300 (RBAP46) is a putative histone chaperone of asexual blood-stage Plasmodium falciparum that is expressed across all three asexual blood stages and localizes to the nucleus [#0]. Purified recombinant PF3D7_1433300 directly binds histone H4 in vitro, identifying histone H4 as a physical interaction partner and pointing to a role in chromatin maintenance [#1]. Beyond its nuclear localization and direct H4 binding, no functional role, complex membership, or in vivo phenotype for PF3D7_1433300 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether PF3D7_1433300 is expressed and where it acts in the parasite was unknown; establishing stage-specific expression and nuclear localization positioned it as a candidate chromatin-associated factor in blood-stage parasites.\",\n      \"evidence\": \"Cloning, recombinant expression in E. coli, and subcellular localization by direct imaging in P. falciparum\",\n      \"pmids\": [\"32363442\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional consequence tied to the nuclear localization\",\n        \"No identification of the chromatin-regulatory complex it associates with in vivo\",\n        \"Single-lab observation\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether PF3D7_1433300 physically engages histones was unknown; demonstrating direct binding to histone H4 established a candidate molecular substrate and supported a histone-chaperone function.\",\n      \"evidence\": \"In vitro binding assay with purified recombinant protein and histone H4\",\n      \"pmids\": [\"32363442\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method and single lab, no reciprocal or in-cell validation of the interaction\",\n        \"Binding affinity and stoichiometry not determined\",\n        \"No demonstration that H4 binding matters for any parasite chromatin process\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether the parasite protein retains the structural features underlying histone recognition was addressed by modeling its predicted fold against human RBBP7.\",\n      \"evidence\": \"Comparative in silico sequence and homology structural analysis\",\n      \"pmids\": [\"32363442\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only; no experimental structure or mutagenesis of the predicted histone-binding pocket\",\n        \"Species-specific pocket residue differences not functionally tested\",\n        \"Fold not confirmed by structural determination\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific chromatin-regulatory complex(es) PF3D7_1433300 operates within in P. falciparum, and its in vivo function and essentiality, remain unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No complex membership defined for PF3D7_1433300 itself\",\n        \"No genetic knockdown/knockout phenotype reported\",\n        \"No demonstrated role in a defined chromatin process\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042393\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\"histone H4\"],\n    \"other_free_text\": [\n      \"Expressed across all three asexual blood stages of P. falciparum [#0]\",\n      \"Predicted seven-bladed WD40 beta-propeller fold with a histone H4 binding interface, by homology modeling against human RBBP7, with species-specific histone-pocket residue differences [#2]\",\n      \"No experimentally defined chromatin-regulatory complex membership for PF3D7_1433300 in the available corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1433300","name":null,"product":"histone-binding protein RBBP7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1011600","name":null,"product":"histone-binding protein RBBP7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0419900","name":null,"product":"histone-binding protein RBBP7, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RBAP46","evaluation":null}