{"gene":"PF3D7_1453700","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2010,"finding":"Recombinant P. falciparum p23 (Pfp23; PF3D7_1453700) exhibits intrinsic chaperone activity, suppressing citrate synthase aggregation at 45°C. Pfp23 directly interacts with PfHsp90 and suppresses PfHsp90 ATPase activity. Site-directed mutagenesis of modeled Pfp23–PfHsp90 complex identified residues K91, H93, W94, and K96 in Pfp23 as crucial for PfHsp90 binding.","method":"In vitro aggregation suppression assay (citrate synthase), ATPase inhibition assay, homology modeling of Pfp23–PfHsp90 complex, site-directed mutagenesis","journal":"Cellular and molecular life sciences : CMLS","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical reconstitution (chaperone assay, ATPase assay) combined with mutagenesis in a single focused study on this specific protein","pmids":["20140477"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"A gene in Plasmodium falciparum (and other Plasmodium species) encodes a homologue of cochaperone p23 (PF3D7_1453700). The protein is a relatively abundant cytoplasmic phosphoprotein of ~34–36 kDa (depending on species) and shares 44% sequence identity with the S. pombe p23 homologue. Expression of p23 mRNA and protein commences in the early ring stage and continues through the trophozoite stage, with a decline at the onset of schizogony.","method":"Gene sequencing, immunoblotting for stage-specific protein expression, mRNA expression analysis","journal":"Parasitology research","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single lab, molecular characterization and stage-specific expression by immunoblot; no functional reconstitution or mutagenesis","pmids":["12756555"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"The P. falciparum genome encodes two putative p23 proteins (Pfp23A and Pfp23B; one corresponds to PF3D7_1453700) that share only ~13% identity with each other and ~20% identity with human p23. Both recombinant proteins behave as elongated monomers in solution, display intrinsic holdase chaperone activity (suppressing thermal aggregation of model client proteins), and inhibit the ATPase activity of recombinant PfHsp90. Pfp23A is more chemically and thermally stable than Pfp23B.","method":"Recombinant protein expression and purification, small-angle X-ray scattering (SAXS), thermal/chemical stability assays, in vitro aggregation suppression assay, ATPase inhibition assay","journal":"International journal of biological macromolecules","confidence":"High","confidence_rationale":"Tier 1 / Moderate — multiple orthogonal in vitro biochemical and biophysical methods in one study, directly characterizing both p23 proteins","pmids":["29191421"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"PfAha1 (a separate PfHsp90 co-chaperone) competes with Pfp23 (PF3D7_1453700) for binding to PfHsp90 under the same MgCl2/ATP-dependent conditions, as demonstrated by GST pull-down competition assays, indicating that Pfp23 and PfAha1 share an overlapping binding interface on PfHsp90.","method":"GST pull-down competition assay between PfAha1 and Pfp23 for PfHsp90 binding","journal":"The international journal of biochemistry & cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — directed in vitro pull-down competition from a single lab; binding competition is clearly demonstrated but mechanistic depth is limited","pmids":["22100910"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Mass spectrometric analysis of PfHsp90 expressed in P. falciparum identified a site of acetylation overlapping with the Aha1 and p23 (PF3D7_1453700) binding domain of PfHsp90, suggesting this modification could modulate assembly of the PfHsp90 multi-chaperone complex. Treatment with a histone deacetylase inhibitor caused partial dissociation of the PfHsp90 complex.","method":"Mass spectrometric identification of PfHsp90 acetylation site; histone deacetylase inhibitor treatment with complex dissociation readout","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — indirect evidence; acetylation overlapping the p23 binding domain is identified by MS on the partner protein (PfHsp90), not on p23 itself; functional consequence inferred rather than directly demonstrated for p23","pmids":["20837488"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"A review of experimentally characterized PfHsp90 co-chaperones confirms that Pfp23 (PF3D7_1453700) is one of only five co-chaperones (PfHop, Pfp23, PfAha1, PfPP5, PfFKBP35) whose interaction with PfHsp90 has been experimentally validated in P. falciparum.","method":"Literature review synthesizing prior experimental co-immunoprecipitation and pull-down studies","journal":"Parasitology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — review paper citing prior experimental work; no new experiment performed","pmids":["24560171"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum p23 (PF3D7_1453700) is a cytoplasmic co-chaperone of PfHsp90 that possesses intrinsic holdase chaperone activity, directly binds PfHsp90 through key residues (K91, H93, W94, K96) in a manner competitive with co-chaperone PfAha1, and suppresses PfHsp90 ATPase activity; its mRNA and protein are expressed from the ring through trophozoite stages and decline at schizogony, and the P. falciparum genome encodes a second, structurally distinct p23 paralogue (Pfp23B) with different stability but similar PfHsp90-inhibitory function."},"narrative":{"mechanistic_narrative":"PF3D7_1453700 (p23) is a cytoplasmic co-chaperone of the P. falciparum Hsp90 chaperone machine that couples an intrinsic holdase activity with direct regulation of PfHsp90 [PMID:20140477, PMID:29191421]. As a purified recombinant protein it suppresses the thermal aggregation of model client proteins, establishing an ATP-independent holdase function, and it binds PfHsp90 directly to suppress its ATPase activity [PMID:20140477, PMID:29191421]. This interaction is mediated by residues K91, H93, W94, and K96 of p23, identified by mutagenesis of a modeled p23–PfHsp90 complex [PMID:20140477]. The binding interface overlaps with that of the co-chaperone PfAha1, with which p23 competes for PfHsp90 under MgCl2/ATP-dependent conditions [PMID:22100910]. p23 mRNA and protein are expressed from the early ring through the trophozoite stage and decline at the onset of schizogony [PMID:12756555]. The P. falciparum genome additionally encodes a second, structurally distinct p23 paralogue (Pfp23B) sharing only ~13% identity with PF3D7_1453700 but displaying similar PfHsp90-inhibitory and holdase activity, while PF3D7_1453700 (Pfp23A) is the more chemically and thermally stable of the two [PMID:29191421]. Beyond its role as a validated PfHsp90 co-chaperone, no in vivo function or client repertoire for PF3D7_1453700 has been characterized in the available corpus.","teleology":[{"year":2003,"claim":"Establishing that P. falciparum encodes a p23 homologue and defining when it is expressed set the stage for asking whether the parasite operates a canonical Hsp90 co-chaperone system.","evidence":"Gene sequencing, immunoblotting for stage-specific expression, and mRNA analysis in P. falciparum","pmids":["12756555"],"confidence":"Medium","gaps":["No functional reconstitution or interaction with PfHsp90 demonstrated","Subcellular localization inferred from abundance, not directly imaged","Functional role of the developmental expression decline at schizogony not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Reconstituting the recombinant protein answered whether p23 is functionally a chaperone and how it engages PfHsp90, defining both intrinsic holdase activity and the binding residues required for ATPase suppression.","evidence":"In vitro citrate synthase aggregation assay, ATPase inhibition assay, homology modeling and site-directed mutagenesis of the p23–PfHsp90 complex","pmids":["20140477"],"confidence":"High","gaps":["Binding residues identified from a modeled complex, not an experimental structure","Physiological clients of the holdase activity unknown","Function not tested in the parasite"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"Detection of a PfHsp90 acetylation site overlapping the Aha1/p23 binding domain raised the possibility that post-translational modification of the partner regulates assembly of the p23-containing complex.","evidence":"Mass spectrometric mapping of PfHsp90 acetylation and histone deacetylase inhibitor treatment with a complex-dissociation readout","pmids":["20837488"],"confidence":"Low","gaps":["Modification is on PfHsp90, not on p23 itself","Effect on p23 recruitment specifically not directly demonstrated","Functional consequence inferred rather than shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Testing p23 against another co-chaperone answered how co-chaperones are arranged on PfHsp90, showing that p23 and PfAha1 compete for an overlapping interface rather than binding simultaneously.","evidence":"GST pull-down competition assay between PfAha1 and p23 for PfHsp90 under MgCl2/ATP-dependent conditions","pmids":["22100910"],"confidence":"Medium","gaps":["Single-lab in vitro competition without structural mapping of the shared interface","Cellular relevance of the competition not tested","Order and dynamics of co-chaperone exchange on PfHsp90 unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"claim":"A synthesis of experimentally validated PfHsp90 co-chaperones confirmed p23's place within a defined set of five bona fide interactors, situating it in the parasite's chaperone network.","evidence":"Literature review consolidating prior co-immunoprecipitation and pull-down studies","pmids":["24560171"],"confidence":"Low","gaps":["No new experimental data","Does not address in vivo essentiality of p23","Client specificity within the network not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Characterizing both parasite p23 proteins answered whether the second paralogue is functionally redundant, showing that despite low sequence identity Pfp23B shares holdase and PfHsp90-inhibitory activity while PF3D7_1453700 is the more stable isoform.","evidence":"Recombinant expression, SAXS, thermal/chemical stability assays, aggregation suppression, and ATPase inhibition assays for both p23 proteins","pmids":["29191421"],"confidence":"High","gaps":["Biological rationale for two divergent p23 paralogues unknown","Whether the two paralogues occupy PfHsp90 in distinct contexts not tested","No in-parasite functional comparison"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo function, essentiality, and client repertoire of PF3D7_1453700 in the parasite remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout or knockdown phenotype reported","No experimental structure of p23 or the p23–PfHsp90 complex","Physiological clients handled by p23 holdase activity unidentified"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfHsp90 multi-chaperone complex"],"partners":["PFHSP90","PFAHA1 (COMPETITIVE FOR PFHSP90 BINDING)"],"other_free_text":["Binding to PfHsp90 requires p23 residues K91, H93, W94, and K96 (identified by modeling and mutagenesis) [#0]","Behaves as an elongated monomer in solution by SAXS [#2]","P. falciparum encodes a second divergent p23 paralogue (Pfp23B); PF3D7_1453700 corresponds to the more thermally/chemically stable Pfp23A [#2]","Expressed from early ring through trophozoite stages, declining at schizogony [#1]","Acetylation of PfHsp90 overlapping the Aha1/p23 binding domain may modulate complex assembly (evidence on the partner, not on p23) [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12584193","id":"PMC_12584193","title":"Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12584193","citation_count":189,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HSP90","PfHSP90"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"20837488","id":"PMC_20837488","title":"Heat shock protein 90 as a drug target against protozoan infections: biochemical characterization of HSP90 from Plasmodium falciparum 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interactions","url":"https://pubmed.ncbi.nlm.nih.gov/39710055","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HSP90"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38131664","id":"PMC_38131664","title":"Plasmodium female gamete surface HSP90 is a key determinant for fertilization.","date":"2023","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/38131664","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HSP90"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36121150","id":"PMC_36121150","title":"Heat Shock Protein 90 Regulates the Activity of Histone Deacetylase Sir2 in Plasmodium falciparum.","date":"2022","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/36121150","citation_count":5,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfHSP90"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33689276","id":"PMC_33689276","title":"Violacein-Induced Chaperone System Collapse Underlies Multistage Antiplasmodial Activity.","date":"2021","source":"ACS infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/33689276","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfHSP90"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":48353,"output_tokens":1976,"usd":0.087349,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7082,"output_tokens":2955,"usd":0.054642,"stage2_stop_reason":"end_turn"},"total_usd":0.141991,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2010,\n      \"finding\": \"Recombinant P. falciparum p23 (Pfp23; PF3D7_1453700) exhibits intrinsic chaperone activity, suppressing citrate synthase aggregation at 45°C. Pfp23 directly interacts with PfHsp90 and suppresses PfHsp90 ATPase activity. Site-directed mutagenesis of modeled Pfp23–PfHsp90 complex identified residues K91, H93, W94, and K96 in Pfp23 as crucial for PfHsp90 binding.\",\n      \"method\": \"In vitro aggregation suppression assay (citrate synthase), ATPase inhibition assay, homology modeling of Pfp23–PfHsp90 complex, site-directed mutagenesis\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical reconstitution (chaperone assay, ATPase assay) combined with mutagenesis in a single focused study on this specific protein\",\n      \"pmids\": [\"20140477\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"A gene in Plasmodium falciparum (and other Plasmodium species) encodes a homologue of cochaperone p23 (PF3D7_1453700). The protein is a relatively abundant cytoplasmic phosphoprotein of ~34–36 kDa (depending on species) and shares 44% sequence identity with the S. pombe p23 homologue. Expression of p23 mRNA and protein commences in the early ring stage and continues through the trophozoite stage, with a decline at the onset of schizogony.\",\n      \"method\": \"Gene sequencing, immunoblotting for stage-specific protein expression, mRNA expression analysis\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single lab, molecular characterization and stage-specific expression by immunoblot; no functional reconstitution or mutagenesis\",\n      \"pmids\": [\"12756555\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The P. falciparum genome encodes two putative p23 proteins (Pfp23A and Pfp23B; one corresponds to PF3D7_1453700) that share only ~13% identity with each other and ~20% identity with human p23. Both recombinant proteins behave as elongated monomers in solution, display intrinsic holdase chaperone activity (suppressing thermal aggregation of model client proteins), and inhibit the ATPase activity of recombinant PfHsp90. Pfp23A is more chemically and thermally stable than Pfp23B.\",\n      \"method\": \"Recombinant protein expression and purification, small-angle X-ray scattering (SAXS), thermal/chemical stability assays, in vitro aggregation suppression assay, ATPase inhibition assay\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — multiple orthogonal in vitro biochemical and biophysical methods in one study, directly characterizing both p23 proteins\",\n      \"pmids\": [\"29191421\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"PfAha1 (a separate PfHsp90 co-chaperone) competes with Pfp23 (PF3D7_1453700) for binding to PfHsp90 under the same MgCl2/ATP-dependent conditions, as demonstrated by GST pull-down competition assays, indicating that Pfp23 and PfAha1 share an overlapping binding interface on PfHsp90.\",\n      \"method\": \"GST pull-down competition assay between PfAha1 and Pfp23 for PfHsp90 binding\",\n      \"journal\": \"The international journal of biochemistry & cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — directed in vitro pull-down competition from a single lab; binding competition is clearly demonstrated but mechanistic depth is limited\",\n      \"pmids\": [\"22100910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Mass spectrometric analysis of PfHsp90 expressed in P. falciparum identified a site of acetylation overlapping with the Aha1 and p23 (PF3D7_1453700) binding domain of PfHsp90, suggesting this modification could modulate assembly of the PfHsp90 multi-chaperone complex. Treatment with a histone deacetylase inhibitor caused partial dissociation of the PfHsp90 complex.\",\n      \"method\": \"Mass spectrometric identification of PfHsp90 acetylation site; histone deacetylase inhibitor treatment with complex dissociation readout\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — indirect evidence; acetylation overlapping the p23 binding domain is identified by MS on the partner protein (PfHsp90), not on p23 itself; functional consequence inferred rather than directly demonstrated for p23\",\n      \"pmids\": [\"20837488\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"A review of experimentally characterized PfHsp90 co-chaperones confirms that Pfp23 (PF3D7_1453700) is one of only five co-chaperones (PfHop, Pfp23, PfAha1, PfPP5, PfFKBP35) whose interaction with PfHsp90 has been experimentally validated in P. falciparum.\",\n      \"method\": \"Literature review synthesizing prior experimental co-immunoprecipitation and pull-down studies\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — review paper citing prior experimental work; no new experiment performed\",\n      \"pmids\": [\"24560171\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum p23 (PF3D7_1453700) is a cytoplasmic co-chaperone of PfHsp90 that possesses intrinsic holdase chaperone activity, directly binds PfHsp90 through key residues (K91, H93, W94, K96) in a manner competitive with co-chaperone PfAha1, and suppresses PfHsp90 ATPase activity; its mRNA and protein are expressed from the ring through trophozoite stages and decline at schizogony, and the P. falciparum genome encodes a second, structurally distinct p23 paralogue (Pfp23B) with different stability but similar PfHsp90-inhibitory function.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1453700 (p23) is a cytoplasmic co-chaperone of the P. falciparum Hsp90 chaperone machine that couples an intrinsic holdase activity with direct regulation of PfHsp90 [#0, #2]. As a purified recombinant protein it suppresses the thermal aggregation of model client proteins, establishing an ATP-independent holdase function, and it binds PfHsp90 directly to suppress its ATPase activity [#0, #2]. This interaction is mediated by residues K91, H93, W94, and K96 of p23, identified by mutagenesis of a modeled p23–PfHsp90 complex [#0]. The binding interface overlaps with that of the co-chaperone PfAha1, with which p23 competes for PfHsp90 under MgCl2/ATP-dependent conditions [#3]. p23 mRNA and protein are expressed from the early ring through the trophozoite stage and decline at the onset of schizogony [#1]. The P. falciparum genome additionally encodes a second, structurally distinct p23 paralogue (Pfp23B) sharing only ~13% identity with PF3D7_1453700 but displaying similar PfHsp90-inhibitory and holdase activity, while PF3D7_1453700 (Pfp23A) is the more chemically and thermally stable of the two [#2]. Beyond its role as a validated PfHsp90 co-chaperone, no in vivo function or client repertoire for PF3D7_1453700 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2003,\n      \"claim\": \"Establishing that P. falciparum encodes a p23 homologue and defining when it is expressed set the stage for asking whether the parasite operates a canonical Hsp90 co-chaperone system.\",\n      \"evidence\": \"Gene sequencing, immunoblotting for stage-specific expression, and mRNA analysis in P. falciparum\",\n      \"pmids\": [\"12756555\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"No functional reconstitution or interaction with PfHsp90 demonstrated\", \"Subcellular localization inferred from abundance, not directly imaged\", \"Functional role of the developmental expression decline at schizogony not tested\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Reconstituting the recombinant protein answered whether p23 is functionally a chaperone and how it engages PfHsp90, defining both intrinsic holdase activity and the binding residues required for ATPase suppression.\",\n      \"evidence\": \"In vitro citrate synthase aggregation assay, ATPase inhibition assay, homology modeling and site-directed mutagenesis of the p23–PfHsp90 complex\",\n      \"pmids\": [\"20140477\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Binding residues identified from a modeled complex, not an experimental structure\", \"Physiological clients of the holdase activity unknown\", \"Function not tested in the parasite\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Detection of a PfHsp90 acetylation site overlapping the Aha1/p23 binding domain raised the possibility that post-translational modification of the partner regulates assembly of the p23-containing complex.\",\n      \"evidence\": \"Mass spectrometric mapping of PfHsp90 acetylation and histone deacetylase inhibitor treatment with a complex-dissociation readout\",\n      \"pmids\": [\"20837488\"],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Modification is on PfHsp90, not on p23 itself\", \"Effect on p23 recruitment specifically not directly demonstrated\", \"Functional consequence inferred rather than shown\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Testing p23 against another co-chaperone answered how co-chaperones are arranged on PfHsp90, showing that p23 and PfAha1 compete for an overlapping interface rather than binding simultaneously.\",\n      \"evidence\": \"GST pull-down competition assay between PfAha1 and p23 for PfHsp90 under MgCl2/ATP-dependent conditions\",\n      \"pmids\": [\"22100910\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Single-lab in vitro competition without structural mapping of the shared interface\", \"Cellular relevance of the competition not tested\", \"Order and dynamics of co-chaperone exchange on PfHsp90 unresolved\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"A synthesis of experimentally validated PfHsp90 co-chaperones confirmed p23's place within a defined set of five bona fide interactors, situating it in the parasite's chaperone network.\",\n      \"evidence\": \"Literature review consolidating prior co-immunoprecipitation and pull-down studies\",\n      \"pmids\": [\"24560171\"],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"No new experimental data\", \"Does not address in vivo essentiality of p23\", \"Client specificity within the network not resolved\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Characterizing both parasite p23 proteins answered whether the second paralogue is functionally redundant, showing that despite low sequence identity Pfp23B shares holdase and PfHsp90-inhibitory activity while PF3D7_1453700 is the more stable isoform.\",\n      \"evidence\": \"Recombinant expression, SAXS, thermal/chemical stability assays, aggregation suppression, and ATPase inhibition assays for both p23 proteins\",\n      \"pmids\": [\"29191421\"],\n      \"confidence\": \"High\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Biological rationale for two divergent p23 paralogues unknown\", \"Whether the two paralogues occupy PfHsp90 in distinct contexts not tested\", \"No in-parasite functional comparison\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo function, essentiality, and client repertoire of PF3D7_1453700 in the parasite remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"No genetic knockout or knockdown phenotype reported\", \"No experimental structure of p23 or the p23–PfHsp90 complex\", \"Physiological clients handled by p23 holdase activity unidentified\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0051087\", \"supporting_discovery_ids\": [0, 3, 5]},\n      {\"term_id\": \"GO:0001671\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0061077\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"complexes\": [\n      \"PfHsp90 multi-chaperone complex\"\n    ],\n    \"partners\": [\n      \"PfHsp90\",\n      \"PfAha1 (competitive for PfHsp90 binding)\"\n    ],\n    \"other_free_text\": [\n      \"Binding to PfHsp90 requires p23 residues K91, H93, W94, and K96 (identified by modeling and mutagenesis) [#0]\",\n      \"Behaves as an elongated monomer in solution by SAXS [#2]\",\n      \"P. falciparum encodes a second divergent p23 paralogue (Pfp23B); PF3D7_1453700 corresponds to the more thermally/chemically stable Pfp23A [#2]\",\n      \"Expressed from early ring through trophozoite stages, declining at schizogony [#1]\",\n      \"Acetylation of PfHsp90 overlapping the Aha1/p23 binding domain may modulate complex assembly (evidence on the partner, not on p23) [#4]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1453700","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 5 of 6 cited papers name other catalogue genes (PF3D7_0708400, PF3D7_0306200, PF3D7_1247400). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1453700","name":null,"product":"HSP90 co-chaperone p23","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1317400","name":null,"product":"HSP90 co-chaperone p23, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1228400","name":null,"product":"HSP90 co-chaperone p23, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}