{"gene":"PF3D7_0110700","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2020,"finding":"PF3D7_0110700 (CAF1C/PfRbAp46/48) directly interacts with histone H4, as demonstrated by pulldown assay using purified recombinant protein.","method":"Direct binding assay with purified recombinant PF3D7_0110700 and histone H4 (in vitro interaction); protein expressed and purified from E. coli","journal":"Parasitology research","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single pulldown method with purified recombinant protein; no orthogonal validation or mutagenesis","pmids":["32363442"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PF3D7_0110700 (CAF1C/PfRbAp46/48) localizes to the nucleus and is expressed in all three asexual blood stages (ring, trophozoite, schizont), as shown by cellular fractionation/localization experiments.","method":"Nuclear localization determined by direct experiment (subcellular localization assay); expression across asexual blood stages detected by western blot or equivalent","journal":"Parasitology research","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, localization without functional consequence demonstrated, no orthogonal methods reported in abstract","pmids":["32363442"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"In silico structural analysis of PF3D7_0110700 revealed conservation of the seven-bladed WD40 β-propeller conformation and characteristic binding interfaces found in RbAp46/48 homologs, with species-specific features distinguishing it from yeast, Drosophila, and human orthologs.","method":"Comparative in silico sequence and structural analysis","journal":"Parasitology research","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/in silico analysis only, no experimental structural or functional validation reported","pmids":["32363442"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0110700 (CAF1C) is a nuclear WD40-repeat histone chaperone expressed across asexual blood stages of P. falciparum that directly binds histone H4, consistent with a role as the RbAp46/48-like subunit of the chromatin assembly factor-1 complex, though its precise molecular mechanism and in vivo function remain uncharacterized."},"narrative":{"mechanistic_narrative":"PF3D7_0110700 (CAF1C) is a Plasmodium falciparum histone chaperone that directly binds histone H4, established by a pulldown assay with purified recombinant protein and consistent with a role as the RbAp46/48-like subunit of the chromatin assembly factor-1 complex [PMID:32363442]. The protein localizes to the nucleus and is expressed across all three asexual blood stages (ring, trophozoite, schizont) [PMID:32363442]. Beyond this direct H4-binding activity and nuclear localization, the molecular mechanism and in vivo function of PF3D7_0110700 have not been characterized in the available corpus; its assignment to the CAF-1 complex and its seven-bladed WD40 β-propeller architecture rest on in silico comparison to RbAp46/48 homologs rather than on experimental structural or functional validation [PMID:32363442].","teleology":[{"year":2020,"claim":"To test whether PF3D7_0110700 acts as a histone chaperone, its physical association with core histones was probed, establishing a direct H4-binding activity that anchors its candidate chromatin-assembly role.","evidence":"In vitro pulldown assay with purified recombinant PF3D7_0110700 and histone H4 (protein from E. coli)","pmids":["32363442"],"confidence":"Medium","gaps":["Single pulldown method without orthogonal validation or binding-interface mutagenesis","Binding to other histones and to assembled nucleosomes not tested","Whether the interaction occurs in vivo or within an intact CAF-1 complex is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To place the H4-binding activity in a cellular context, subcellular localization and stage expression were assessed, showing nuclear residence throughout asexual blood-stage development consistent with a chromatin function.","evidence":"Subcellular localization/fractionation assay and stage expression detection (western blot or equivalent) across ring, trophozoite, and schizont stages","pmids":["32363442"],"confidence":"Low","gaps":["Localization reported without demonstrated functional consequence and without orthogonal methods","No evidence linking nuclear presence to chromatin assembly activity in vivo","Gametocyte and other life-cycle stages not examined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To classify PF3D7_0110700 structurally, comparative modeling was used, inferring a conserved seven-bladed WD40 β-propeller and RbAp46/48-like binding interfaces with species-specific features distinguishing it from yeast, Drosophila, and human orthologs.","evidence":"Comparative in silico sequence and structural analysis","pmids":["32363442"],"confidence":"Low","gaps":["Computational inference only, with no experimental structure","CAF-1 complex membership predicted by homology, not demonstrated biochemically","Functional significance of the species-specific features untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo function of PF3D7_0110700, its assembly into and role within a Plasmodium CAF-1 complex, and its contribution to parasite chromatin assembly and viability remain unresolved.","evidence":"No genetic, complex-reconstitution, or loss-of-function evidence present in the corpus","pmids":[],"confidence":"Low","gaps":["No knockout, knockdown, or conditional-depletion phenotype reported","CAF-1 complex partners not experimentally identified for this subunit","No experimental structure or nucleosome-assembly assay"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Chromatin assembly factor-1 (CAF-1) complex — inferred by homology only [#2]"],"partners":["HISTONE H4 (DIRECT IN VITRO BINDING) [#0]"],"other_free_text":["Predicted seven-bladed WD40 β-propeller with RbAp46/48-like binding interfaces and species-specific features versus yeast, Drosophila, and human orthologs (in silico only) [#2]","Expressed across ring, trophozoite, and schizont asexual blood stages [#1]","In vivo function and CAF-1 complex membership not experimentally established 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":["CAF1C"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3406,"output_tokens":809,"usd":0.011177,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5459,"output_tokens":1867,"usd":0.036985,"stage2_stop_reason":"end_turn"},"total_usd":0.048162,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_0110700 (CAF1C/PfRbAp46/48) directly interacts with histone H4, as demonstrated by pulldown assay using purified recombinant protein.\",\n      \"method\": \"Direct binding assay with purified recombinant PF3D7_0110700 and histone H4 (in vitro interaction); protein expressed and purified from E. coli\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single pulldown method with purified recombinant protein; no orthogonal validation or mutagenesis\",\n      \"pmids\": [\"32363442\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_0110700 (CAF1C/PfRbAp46/48) localizes to the nucleus and is expressed in all three asexual blood stages (ring, trophozoite, schizont), as shown by cellular fractionation/localization experiments.\",\n      \"method\": \"Nuclear localization determined by direct experiment (subcellular localization assay); expression across asexual blood stages detected by western blot or equivalent\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, localization without functional consequence demonstrated, no orthogonal methods reported in abstract\",\n      \"pmids\": [\"32363442\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In silico structural analysis of PF3D7_0110700 revealed conservation of the seven-bladed WD40 β-propeller conformation and characteristic binding interfaces found in RbAp46/48 homologs, with species-specific features distinguishing it from yeast, Drosophila, and human orthologs.\",\n      \"method\": \"Comparative in silico sequence and structural analysis\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/in silico analysis only, no experimental structural or functional validation reported\",\n      \"pmids\": [\"32363442\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0110700 (CAF1C) is a nuclear WD40-repeat histone chaperone expressed across asexual blood stages of P. falciparum that directly binds histone H4, consistent with a role as the RbAp46/48-like subunit of the chromatin assembly factor-1 complex, though its precise molecular mechanism and in vivo function remain uncharacterized.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0110700 (CAF1C) is a Plasmodium falciparum histone chaperone that directly binds histone H4, established by a pulldown assay with purified recombinant protein and consistent with a role as the RbAp46/48-like subunit of the chromatin assembly factor-1 complex [#0]. The protein localizes to the nucleus and is expressed across all three asexual blood stages (ring, trophozoite, schizont) [#1]. Beyond this direct H4-binding activity and nuclear localization, the molecular mechanism and in vivo function of PF3D7_0110700 have not been characterized in the available corpus; its assignment to the CAF-1 complex and its seven-bladed WD40 β-propeller architecture rest on in silico comparison to RbAp46/48 homologs rather than on experimental structural or functional validation [#2].\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"To test whether PF3D7_0110700 acts as a histone chaperone, its physical association with core histones was probed, establishing a direct H4-binding activity that anchors its candidate chromatin-assembly role.\",\n      \"evidence\": \"In vitro pulldown assay with purified recombinant PF3D7_0110700 and histone H4 (protein from E. coli)\",\n      \"pmids\": [\"32363442\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single pulldown method without orthogonal validation or binding-interface mutagenesis\",\n        \"Binding to other histones and to assembled nucleosomes not tested\",\n        \"Whether the interaction occurs in vivo or within an intact CAF-1 complex is unresolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To place the H4-binding activity in a cellular context, subcellular localization and stage expression were assessed, showing nuclear residence throughout asexual blood-stage development consistent with a chromatin function.\",\n      \"evidence\": \"Subcellular localization/fractionation assay and stage expression detection (western blot or equivalent) across ring, trophozoite, and schizont stages\",\n      \"pmids\": [\"32363442\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Localization reported without demonstrated functional consequence and without orthogonal methods\",\n        \"No evidence linking nuclear presence to chromatin assembly activity in vivo\",\n        \"Gametocyte and other life-cycle stages not examined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To classify PF3D7_0110700 structurally, comparative modeling was used, inferring a conserved seven-bladed WD40 β-propeller and RbAp46/48-like binding interfaces with species-specific features distinguishing it from yeast, Drosophila, and human orthologs.\",\n      \"evidence\": \"Comparative in silico sequence and structural analysis\",\n      \"pmids\": [\"32363442\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational inference only, with no experimental structure\",\n        \"CAF-1 complex membership predicted by homology, not demonstrated biochemically\",\n        \"Functional significance of the species-specific features untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo function of PF3D7_0110700, its assembly into and role within a Plasmodium CAF-1 complex, and its contribution to parasite chromatin assembly and viability remain unresolved.\",\n      \"evidence\": \"No genetic, complex-reconstitution, or loss-of-function evidence present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockout, knockdown, or conditional-depletion phenotype reported\",\n        \"CAF-1 complex partners not experimentally identified for this subunit\",\n        \"No experimental structure or nucleosome-assembly assay\"\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\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006335\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"Chromatin assembly factor-1 (CAF-1) complex — inferred by homology only [#2]\"\n    ],\n    \"partners\": [\n      \"Histone H4 (direct in vitro binding) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"Predicted seven-bladed WD40 β-propeller with RbAp46/48-like binding interfaces and species-specific features versus yeast, Drosophila, and human orthologs (in silico only) [#2]\",\n      \"Expressed across ring, trophozoite, and schizont asexual blood stages [#1]\",\n      \"In vivo function and CAF-1 complex membership not experimentally established in the available corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0110700","name":null,"product":"chromatin assembly factor 1 subunit C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0203000","name":null,"product":"chromatin assembly factor 1 subunit C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0203200","name":null,"product":"chromatin assembly factor 1 subunit C, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CAF1C","evaluation":null}