{"gene":"PF3D7_0927000","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2010,"finding":"Recombinant P. falciparum p23 (Pfp23/PF3D7_0927000) exhibits intrinsic chaperone activity, as demonstrated by its ability to suppress citrate synthase aggregation at 45°C in vitro.","method":"In vitro aggregation suppression assay using recombinant Pfp23 and citrate synthase as substrate","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical assay with recombinant protein, single lab, single method for this specific finding","pmids":["20140477"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Recombinant Pfp23 (PF3D7_0927000) interacts directly with PfHsp90 and suppresses its ATPase activity in vitro.","method":"In vitro protein-protein interaction assay with recombinant proteins; ATPase activity assay","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical reconstitution with recombinant proteins, single lab, two orthogonal methods (interaction + ATPase inhibition)","pmids":["20140477"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"Site-directed mutagenesis of modeled Pfp23-PfHsp90 complex identified residues K91, H93, W94, and K96 in Pfp23 as crucial for binding to PfHsp90.","method":"Homology modeling of Pfp23-PfHsp90 complex combined with site-directed mutagenesis","journal":"Cellular and molecular life sciences : CMLS","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — mutagenesis with functional validation, single lab, model-guided but not crystal structure","pmids":["20140477"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Pfp23 (PF3D7_0927000) competes with PfAha1 for binding to PfHsp90 under MgCl2- and ATP-dependent conditions, as shown by GST pull-down competition assay.","method":"GST pull-down competition assay between Pfp23 and PfAha1 for PfHsp90 binding","journal":"The international journal of biochemistry & cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — reciprocal competition pull-down, single lab, single method","pmids":["22100910"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2014,"finding":"Pfp23 (PF3D7_0927000) is one of five experimentally validated co-chaperones of PfHsp90 in P. falciparum; it has been shown to interact with PfHsp90 and regulate its activity.","method":"Review summarizing experimental co-immunoprecipitation and interaction data from primary studies","journal":"Parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — review paper citing prior experimental work; no new primary data provided for Pfp23 specifically","pmids":["24560171"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"The P. falciparum genome encodes two putative p23 proteins (Pfp23A/PF3D7_0927000 and Pfp23B) with only 13% identity to each other and ~20% identity to human p23. Both recombinant proteins behaved as elongated monomers in solution, showed intrinsic chaperone activity (suppressing thermal aggregation of model substrates), and inhibited PfHsp90 ATPase activity. Pfp23A was more thermally and chemically stable than Pfp23B.","method":"Recombinant protein production; small-angle X-ray scattering (SAXS) for solution structure; thermal/chemical denaturation; in vitro aggregation suppression assays; ATPase inhibition assay","journal":"International journal of biological macromolecules","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution with recombinant proteins, multiple orthogonal methods (SAXS, thermal stability, chaperone assay, ATPase assay), single lab","pmids":["29191421"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"finding":"Mass spectrometric analysis identified an acetylation site on PfHsp90 that overlaps with the Aha1 and p23 (PF3D7_0927000) binding domain, suggesting this modification modulates Hsp90 multichaperone complex assembly including p23 binding. Treatment with a histone deacetylase inhibitor resulted in partial dissociation of the PfHsp90 complex.","method":"Mass spectrometry of PfHsp90 expressed in P. falciparum; HDAC inhibitor treatment followed by complex analysis","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 3 / Weak — MS identification of modification site, functional link to p23 binding is indirect (overlap with binding domain), single lab","pmids":["20837488"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"P. falciparum p23 (PF3D7_0927000) is a co-chaperone of PfHsp90 that exhibits intrinsic chaperone activity (suppressing substrate aggregation), directly binds PfHsp90 via residues K91, H93, W94, and K96, inhibits PfHsp90 ATPase activity, and competes with the co-chaperone PfAha1 for PfHsp90 binding; the P. falciparum genome encodes a second divergent p23 paralog (Pfp23B), and both proteins function as elongated monomers in solution."},"narrative":{"mechanistic_narrative":"PF3D7_0927000 (p23) is a co-chaperone of the P. falciparum Hsp90 (PfHsp90) chaperone machinery that also possesses intrinsic, Hsp90-independent chaperone activity, suppressing thermal aggregation of model substrates such as citrate synthase in vitro [PMID:20140477, PMID:29191421]. It binds PfHsp90 directly and inhibits its ATPase activity, with binding mediated by residues K91, H93, W94, and K96 identified through model-guided mutagenesis [PMID:20140477]. p23 engages the same region of PfHsp90 as the co-chaperone PfAha1 and competes with it for binding in an MgCl2- and ATP-dependent manner, positioning p23 as a regulator of the composition and cycling of the PfHsp90 multichaperone complex [PMID:22100910]. The P. falciparum genome encodes two divergent p23 proteins, Pfp23A (PF3D7_0927000) and Pfp23B, sharing only ~13% identity; both behave as elongated monomers in solution, display intrinsic chaperone activity, and inhibit PfHsp90 ATPase activity, with Pfp23A being the more thermally and chemically stable of the two [PMID:29191421]. Beyond these in vitro biochemical properties, the cellular and parasite-stage functions of PF3D7_0927000 have not been characterized in the available corpus.","teleology":[{"year":2010,"claim":"Establishing whether the parasite p23 homolog is a functional chaperone and Hsp90 partner, this work showed recombinant Pfp23 both suppresses substrate aggregation on its own and binds PfHsp90 while inhibiting its ATPase activity, defining it as a bona fide co-chaperone with intrinsic activity.","evidence":"In vitro aggregation suppression, protein-protein interaction, and ATPase assays with recombinant proteins","pmids":["20140477"],"confidence":"Medium","gaps":["Single lab, in vitro reconstitution only; no cellular or parasite-based validation","No structural determination of the interaction"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"To localize the interaction interface, model-guided mutagenesis pinpointed Pfp23 residues K91, H93, W94, and K96 as required for PfHsp90 binding, giving a residue-level map of the co-chaperone contact.","evidence":"Homology modeling of the Pfp23-PfHsp90 complex with site-directed mutagenesis","pmids":["20140477"],"confidence":"Medium","gaps":["Interface inferred from a homology model, not a crystal or cryo-EM structure","Contribution of PfHsp90-side residues not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Addressing how p23 fits within the wider co-chaperone network, competition pull-downs showed Pfp23 competes with PfAha1 for PfHsp90 in an MgCl2- and ATP-dependent manner, implying p23 helps set the composition of the chaperone cycle.","evidence":"GST pull-down competition assay between Pfp23 and PfAha1 for PfHsp90","pmids":["22100910"],"confidence":"Medium","gaps":["Single method, single lab","Functional consequence of the competition for client maturation not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Resolving the paralog question, biophysical and functional characterization showed P. falciparum encodes two highly divergent p23 proteins, both of which are elongated monomers with intrinsic chaperone and PfHsp90 ATPase-inhibiting activity, with PF3D7_0927000 (Pfp23A) being the more stable.","evidence":"Recombinant protein production, SAXS, thermal/chemical denaturation, aggregation suppression and ATPase inhibition assays","pmids":["29191421"],"confidence":"High","gaps":["Distinct in vivo roles of Pfp23A versus Pfp23B not established","No structure of the p23-Hsp90 complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The cellular localization, parasite developmental role, client repertoire, and in vivo essentiality of PF3D7_0927000 remain unaddressed by the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout/knockdown phenotype reported","No in-parasite localization or expression-timing data specific to PF3D7_0927000","No identified Hsp90 client whose maturation depends on p23"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfHsp90 multichaperone complex"],"partners":["PFHSP90","PFAHA1 (COMPETING CO-CHAPERONE)"],"other_free_text":["Binds PfHsp90 via Pfp23 residues K91, H93, W94, K96 (homology-model-guided mutagenesis) [#2]","Competition with PfAha1 for PfHsp90 is MgCl2- and ATP-dependent [#3]","P. falciparum encodes two divergent p23 paralogs (Pfp23A/PF3D7_0927000 and Pfp23B, ~13% identity); both are elongated monomers in solution by SAXS [#5]","PfHsp90 acetylation overlaps the Aha1/p23 binding domain and HDAC inhibitor treatment partially dissociates the complex (indirect link) [#6]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"12584193","id":"PMC_12584193","title":"Heat shock protein 90 function is essential for Plasmodium 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aggregation suppression assay using recombinant Pfp23 and citrate synthase as substrate\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical assay with recombinant protein, single lab, single method for this specific finding\",\n      \"pmids\": [\"20140477\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Recombinant Pfp23 (PF3D7_0927000) interacts directly with PfHsp90 and suppresses its ATPase activity in vitro.\",\n      \"method\": \"In vitro protein-protein interaction assay with recombinant proteins; ATPase activity assay\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical reconstitution with recombinant proteins, single lab, two orthogonal methods (interaction + ATPase inhibition)\",\n      \"pmids\": [\"20140477\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Site-directed mutagenesis of modeled Pfp23-PfHsp90 complex identified residues K91, H93, W94, and K96 in Pfp23 as crucial for binding to PfHsp90.\",\n      \"method\": \"Homology modeling of Pfp23-PfHsp90 complex combined with site-directed mutagenesis\",\n      \"journal\": \"Cellular and molecular life sciences : CMLS\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — mutagenesis with functional validation, single lab, model-guided but not crystal structure\",\n      \"pmids\": [\"20140477\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Pfp23 (PF3D7_0927000) competes with PfAha1 for binding to PfHsp90 under MgCl2- and ATP-dependent conditions, as shown by GST pull-down competition assay.\",\n      \"method\": \"GST pull-down competition assay between Pfp23 and PfAha1 for PfHsp90 binding\",\n      \"journal\": \"The international journal of biochemistry & cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — reciprocal competition pull-down, single lab, single method\",\n      \"pmids\": [\"22100910\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Pfp23 (PF3D7_0927000) is one of five experimentally validated co-chaperones of PfHsp90 in P. falciparum; it has been shown to interact with PfHsp90 and regulate its activity.\",\n      \"method\": \"Review summarizing experimental co-immunoprecipitation and interaction data from primary studies\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — review paper citing prior experimental work; no new primary data provided for Pfp23 specifically\",\n      \"pmids\": [\"24560171\"],\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/PF3D7_0927000 and Pfp23B) with only 13% identity to each other and ~20% identity to human p23. Both recombinant proteins behaved as elongated monomers in solution, showed intrinsic chaperone activity (suppressing thermal aggregation of model substrates), and inhibited PfHsp90 ATPase activity. Pfp23A was more thermally and chemically stable than Pfp23B.\",\n      \"method\": \"Recombinant protein production; small-angle X-ray scattering (SAXS) for solution structure; thermal/chemical denaturation; in vitro aggregation suppression assays; ATPase inhibition assay\",\n      \"journal\": \"International journal of biological macromolecules\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution with recombinant proteins, multiple orthogonal methods (SAXS, thermal stability, chaperone assay, ATPase assay), single lab\",\n      \"pmids\": [\"29191421\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Mass spectrometric analysis identified an acetylation site on PfHsp90 that overlaps with the Aha1 and p23 (PF3D7_0927000) binding domain, suggesting this modification modulates Hsp90 multichaperone complex assembly including p23 binding. Treatment with a histone deacetylase inhibitor resulted in partial dissociation of the PfHsp90 complex.\",\n      \"method\": \"Mass spectrometry of PfHsp90 expressed in P. falciparum; HDAC inhibitor treatment followed by complex analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — MS identification of modification site, functional link to p23 binding is indirect (overlap with binding domain), single lab\",\n      \"pmids\": [\"20837488\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"P. falciparum p23 (PF3D7_0927000) is a co-chaperone of PfHsp90 that exhibits intrinsic chaperone activity (suppressing substrate aggregation), directly binds PfHsp90 via residues K91, H93, W94, and K96, inhibits PfHsp90 ATPase activity, and competes with the co-chaperone PfAha1 for PfHsp90 binding; the P. falciparum genome encodes a second divergent p23 paralog (Pfp23B), and both proteins function as elongated monomers in solution.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0927000 (p23) is a co-chaperone of the P. falciparum Hsp90 (PfHsp90) chaperone machinery that also possesses intrinsic, Hsp90-independent chaperone activity, suppressing thermal aggregation of model substrates such as citrate synthase in vitro [#0, #5]. It binds PfHsp90 directly and inhibits its ATPase activity, with binding mediated by residues K91, H93, W94, and K96 identified through model-guided mutagenesis [#1, #2]. p23 engages the same region of PfHsp90 as the co-chaperone PfAha1 and competes with it for binding in an MgCl2- and ATP-dependent manner, positioning p23 as a regulator of the composition and cycling of the PfHsp90 multichaperone complex [#3]. The P. falciparum genome encodes two divergent p23 proteins, Pfp23A (PF3D7_0927000) and Pfp23B, sharing only ~13% identity; both behave as elongated monomers in solution, display intrinsic chaperone activity, and inhibit PfHsp90 ATPase activity, with Pfp23A being the more thermally and chemically stable of the two [#5]. Beyond these in vitro biochemical properties, the cellular and parasite-stage functions of PF3D7_0927000 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2010,\n      \"claim\": \"Establishing whether the parasite p23 homolog is a functional chaperone and Hsp90 partner, this work showed recombinant Pfp23 both suppresses substrate aggregation on its own and binds PfHsp90 while inhibiting its ATPase activity, defining it as a bona fide co-chaperone with intrinsic activity.\",\n      \"evidence\": \"In vitro aggregation suppression, protein-protein interaction, and ATPase assays with recombinant proteins\",\n      \"pmids\": [\"20140477\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single lab, in vitro reconstitution only; no cellular or parasite-based validation\", \"No structural determination of the interaction\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"To localize the interaction interface, model-guided mutagenesis pinpointed Pfp23 residues K91, H93, W94, and K96 as required for PfHsp90 binding, giving a residue-level map of the co-chaperone contact.\",\n      \"evidence\": \"Homology modeling of the Pfp23-PfHsp90 complex with site-directed mutagenesis\",\n      \"pmids\": [\"20140477\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Interface inferred from a homology model, not a crystal or cryo-EM structure\", \"Contribution of PfHsp90-side residues not defined\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Addressing how p23 fits within the wider co-chaperone network, competition pull-downs showed Pfp23 competes with PfAha1 for PfHsp90 in an MgCl2- and ATP-dependent manner, implying p23 helps set the composition of the chaperone cycle.\",\n      \"evidence\": \"GST pull-down competition assay between Pfp23 and PfAha1 for PfHsp90\",\n      \"pmids\": [\"22100910\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Single method, single lab\", \"Functional consequence of the competition for client maturation not tested\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Resolving the paralog question, biophysical and functional characterization showed P. falciparum encodes two highly divergent p23 proteins, both of which are elongated monomers with intrinsic chaperone and PfHsp90 ATPase-inhibiting activity, with PF3D7_0927000 (Pfp23A) being the more stable.\",\n      \"evidence\": \"Recombinant protein production, SAXS, thermal/chemical denaturation, aggregation suppression and ATPase inhibition assays\",\n      \"pmids\": [\"29191421\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Distinct in vivo roles of Pfp23A versus Pfp23B not established\", \"No structure of the p23-Hsp90 complex\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The cellular localization, parasite developmental role, client repertoire, and in vivo essentiality of PF3D7_0927000 remain unaddressed by the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No genetic knockout/knockdown phenotype reported\", \"No in-parasite localization or expression-timing data specific to PF3D7_0927000\", \"No identified Hsp90 client whose maturation depends on p23\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [0, 5]},\n      {\"term_id\": \"GO:0051087\", \"supporting_discovery_ids\": [1, 3, 4]},\n      {\"term_id\": \"GO:0001671\", \"supporting_discovery_ids\": [1, 5]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006457\", \"supporting_discovery_ids\": [0, 5]}\n    ],\n    \"complexes\": [\"PfHsp90 multichaperone complex\"],\n    \"partners\": [\"PfHsp90\", \"PfAha1 (competing co-chaperone)\"],\n    \"other_free_text\": [\n      \"Binds PfHsp90 via Pfp23 residues K91, H93, W94, K96 (homology-model-guided mutagenesis) [#2]\",\n      \"Competition with PfAha1 for PfHsp90 is MgCl2- and ATP-dependent [#3]\",\n      \"P. falciparum encodes two divergent p23 paralogs (Pfp23A/PF3D7_0927000 and Pfp23B, ~13% identity); both are elongated monomers in solution by SAXS [#5]\",\n      \"PfHsp90 acetylation overlaps the Aha1/p23 binding domain and HDAC inhibitor treatment partially dissociates the complex (indirect link) [#6]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0927000","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 5 of 5 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_0927000","name":null,"product":"HSP90 co-chaperone p23","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0827800","name":null,"product":"HSP90 co-chaperone p23, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0725300","name":null,"product":"HSP90 co-chaperone p23, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}