{"gene":"PF3D7_1355500","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2001,"finding":"PP5 (PfPP5) is a serine/threonine protein phosphatase with four TPR repeats at its N-terminus; recombinant PfPP5 expressed in bacteria showed phosphatase activity that was stimulated by polyunsaturated fatty acids, and the N-terminus was required for this stimulation. Co-immunoprecipitation demonstrated a physical interaction between native PfPP5 and PfHsp90.","method":"Recombinant protein expression in bacteria (in vitro phosphatase assay), N-terminal deletion analysis, co-immunoprecipitation","journal":"BMC microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro enzymatic assay with domain deletion and reciprocal Co-IP, single lab, two orthogonal methods","pmids":["11737864"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"finding":"PfPP5 exhibits phosphatase activity enhanced by arachidonic and oleic acids (but not myristic or stearic acid), is inhibited by okadaic acid with an IC50 of 4 nM, and is localized preferentially to the nucleus by immunofluorescence microscopy.","method":"Recombinant protein phosphatase assay, okadaic acid inhibition, immunofluorescence microscopy","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro enzymatic assay with inhibitor characterization plus direct localization by immunofluorescence, single lab, two orthogonal methods","pmids":["11897131"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"finding":"PfARP (SET/TAF-family protein) specifically inhibited parasitic PP2A at nanomolar concentrations with no effect on PP5, establishing that PP5 is not a target of PfARP-mediated inhibition.","method":"In vitro phosphatase inhibition assay with recombinant/native proteins","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical assay clearly distinguishing PP5 from PP2A as a substrate of PfARP inhibition, single lab; this is a NEGATIVE finding for PP5 (PfARP does not inhibit it)","pmids":["12615323"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"finding":"PfPP5 is a component of the PfHsp90 multi-chaperone complex (together with PfHsp70 and tubulin); geldanamycin disrupts this complex and inhibits parasite development, implicating PfPP5 in the temperature-dependent progression from ring to trophozoite stage.","method":"Co-immunoprecipitation of the PfHsp90 complex, geldanamycin inhibition, flow cytometry for parasite stage progression","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP of complex combined with pharmacological disruption and flow cytometry-based phenotype, single lab, two orthogonal methods","pmids":["15339915"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"In Plasmodium berghei, PP5 (PbPP5) is expressed in blood stages and ookinetes, localises to the cytoplasm and beneath the parasite plasma membrane in merozoites and ookinetes. Targeted gene deletion (Δpbpp5) had no effect on asexual blood-stage multiplication but severely impaired male gamete formation and fertility, almost completely blocking ookinete conversion and oocyst development. Genetic rescue by crossing Δpbpp5 with female-defective Δpbs47 (but not male-defective Δpbs48/45) confirmed the male-specific fertility requirement. Recombinant phosphatase domain displayed phosphatase activity sensitive to cantharidic acid (IC50=122.2 nM), cantharidin (IC50=74.3 nM), endothall (IC50=365.5 nM), and okadaic acid (IC50=1.3 nM).","method":"Targeted gene deletion (KO), genetic epistasis (crossing with sex-specific mutant lines), immunofluorescence localization, in vitro phosphatase assay with inhibitors","journal":"International journal for parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean KO with defined cellular phenotype, genetic epistasis via crossing with sex-specific lines, plus in vitro enzymatic characterization; multiple orthogonal methods in a single rigorous study","pmids":["31202684"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PP5 (PF3D7_1355500) is a TPR-containing serine/threonine protein phosphatase that physically associates with the PfHsp90 multi-chaperone complex in P. falciparum asexual stages; its phosphatase activity is stimulated by polyunsaturated fatty acids and inhibited by okadaic acid, it localises predominantly to the nucleus in P. falciparum, and the ortholog in P. berghei is dispensable for asexual blood-stage growth but is essential for male gamete fertility and ookinete conversion, as established by targeted gene deletion and genetic epistasis."},"narrative":{"mechanistic_narrative":"PP5 (PF3D7_1355500) is a TPR-repeat-containing serine/threonine protein phosphatase that couples the Plasmodium chaperone machinery to stage-specific developmental transitions [PMID:11737864, PMID:15339915]. Recombinant PfPP5 is catalytically active, and its activity is stimulated by polyunsaturated fatty acids such as arachidonic and oleic acid in an N-terminus-dependent manner, but not by saturated fatty acids, and it is inhibited by okadaic acid (IC50 ~4 nM) [PMID:11737864, PMID:11897131]. Through its N-terminal TPR repeats, native PfPP5 physically associates with PfHsp90 as a component of the PfHsp90 multi-chaperone complex (which also contains PfHsp70 and tubulin); geldanamycin disrupts this complex and blocks the temperature-dependent ring-to-trophozoite transition, placing PP5 within Hsp90-dependent asexual development [PMID:11737864, PMID:15339915]. In vitro, PP5 is not a target of the SET/TAF-family inhibitor PfARP, which selectively inhibits PP2A, distinguishing PP5 regulation from that of PP2A [PMID:12615323]. In P. falciparum, PP5 localises preferentially to the nucleus [PMID:11897131], whereas in P. berghei the ortholog localises to the cytoplasm and beneath the plasma membrane in merozoites and ookinetes; P. berghei gene deletion showed PP5 is dispensable for asexual blood-stage growth but essential for male gamete formation, fertility, and ookinete-to-oocyst conversion, a male-specific requirement confirmed by genetic crossing with sex-defective mutants [PMID:31202684].","teleology":[{"year":2001,"claim":"Established that PP5 is a genuine catalytic serine/threonine phosphatase whose activity is controlled by its N-terminal TPR region and lipid cofactors, and that it physically engages the Hsp90 chaperone.","evidence":"Recombinant bacterial expression with in vitro phosphatase assay, N-terminal deletion, and reciprocal co-immunoprecipitation in P. falciparum","pmids":["11737864"],"confidence":"Medium","gaps":["No physiological substrate identified","Functional consequence of the PfHsp90 interaction not defined","No structural model of the TPR-Hsp90 interface"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2002,"claim":"Defined the pharmacological and lipid-regulatory profile of PP5 and placed it in the nucleus, framing where and how the enzyme acts in P. falciparum.","evidence":"Recombinant phosphatase assay with fatty-acid and okadaic-acid characterization plus immunofluorescence in P. falciparum","pmids":["11897131"],"confidence":"Medium","gaps":["Nuclear substrates unidentified","Mechanism linking fatty-acid stimulation to in vivo activity unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2003,"claim":"Distinguished PP5 regulation from PP2A by showing the SET/TAF-family inhibitor PfARP does not target PP5, clarifying that PP5 sits outside the PfARP-PP2A regulatory axis.","evidence":"In vitro phosphatase inhibition assay comparing PP5 and PP2A in P. falciparum","pmids":["12615323"],"confidence":"Medium","gaps":["Does not identify any positive regulator of PP5","Negative result only"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2004,"claim":"Positioned PP5 as a functional constituent of the PfHsp90 multi-chaperone complex and linked chaperone-complex integrity to asexual stage progression.","evidence":"Co-immunoprecipitation of the PfHsp90 complex, geldanamycin disruption, and flow-cytometry stage analysis in P. falciparum","pmids":["15339915"],"confidence":"Medium","gaps":["Geldanamycin acts on Hsp90, so the direct requirement for PP5 activity in stage progression is not isolated","Stoichiometry and substrates within the complex unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Genetically defined the in vivo role of PP5, showing it is dispensable for asexual growth but essential for male gamete fertility and transmission-stage development in P. berghei.","evidence":"Targeted gene deletion, genetic epistasis by crossing with sex-defective mutants, immunofluorescence, and recombinant phosphatase-domain inhibitor assays in P. berghei","pmids":["31202684"],"confidence":"High","gaps":["Male-fertility substrates of PP5 not identified","Cytoplasmic/sub-membrane localization in P. berghei differs from reported nuclear localization in P. falciparum and is unreconciled","Whether the Hsp90 association is required for the transmission phenotype untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The physiological substrates of PP5 and the mechanistic link between its Hsp90 association, its lipid/nuclear regulation, and its male-fertility requirement remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No dephosphorylation substrate identified in any species","Species divergence in localization (nuclear in P. falciparum vs cytoplasmic/sub-membrane in P. berghei) unexplained","Whether PP5's phosphatase activity is required for gametogenesis versus a scaffolding role untested"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfHsp90 multi-chaperone complex (with PfHsp70 and tubulin) [#3]"],"partners":["PFHSP90 [#0, #3]","PFHSP70 (CO-COMPLEX MEMBER) [#3]","TUBULIN (CO-COMPLEX MEMBER) [#3]"],"other_free_text":["Phosphatase activity stimulated by arachidonic and oleic acids but not myristic or stearic acid, in an N-terminus-dependent manner [#0, #1]","Inhibited by okadaic acid (IC50 ~4 nM in P. falciparum; 1.3 nM for P. berghei phosphatase domain), and by cantharidic acid, cantharidin, and endothall [#1, #4]","Not inhibited by the SET/TAF-family protein PfARP, which selectively inhibits PP2A [#2]","P. berghei gene deletion confirms dispensability for asexual blood-stage growth and a male-specific fertility/ookinete-conversion requirement via genetic crossing with sex-defective mutants [#4]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15339915","id":"PMC_15339915","title":"Recurrent fever promotes Plasmodium falciparum development in human erythrocytes.","date":"2004","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15339915","citation_count":71,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18793411","id":"PMC_18793411","title":"The protein-phosphatome of the human malaria parasite Plasmodium falciparum.","date":"2008","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/18793411","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11737864","id":"PMC_11737864","title":"A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum.","date":"2001","source":"BMC microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/11737864","citation_count":35,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PP5","PfPP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"11897131","id":"PMC_11897131","title":"Identification and biochemical characterisation of a protein phosphatase 5 homologue from Plasmodium falciparum.","date":"2002","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11897131","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PP5","PfPP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25967133","id":"PMC_25967133","title":"Exploration of new drug-like inhibitors for serine/threonine protein phosphatase 5 of Plasmodium falciparum: a docking and simulation study.","date":"2015","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/25967133","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PP5","serine/threonine protein phosphatase 5","PfPP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"12615323","id":"PMC_12615323","title":"Characterization of a unique aspartate-rich protein of the SET/TAF-family in the human malaria parasite, Plasmodium falciparum, which inhibits protein phosphatase 2A.","date":"2003","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/12615323","citation_count":21,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24560171","id":"PMC_24560171","title":"Co-chaperones of Hsp90 in Plasmodium falciparum and their concerted roles in cellular regulation.","date":"2014","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/24560171","citation_count":17,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31202684","id":"PMC_31202684","title":"Plasmodium berghei serine/threonine protein phosphatase PP5 plays a critical role in male gamete fertility.","date":"2019","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/31202684","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PP5","PbPP5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6916,"output_tokens":1602,"usd":0.022389,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6659,"output_tokens":2853,"usd":0.05231,"stage2_stop_reason":"end_turn"},"total_usd":0.074699,"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\": 2001,\n      \"finding\": \"PP5 (PfPP5) is a serine/threonine protein phosphatase with four TPR repeats at its N-terminus; recombinant PfPP5 expressed in bacteria showed phosphatase activity that was stimulated by polyunsaturated fatty acids, and the N-terminus was required for this stimulation. Co-immunoprecipitation demonstrated a physical interaction between native PfPP5 and PfHsp90.\",\n      \"method\": \"Recombinant protein expression in bacteria (in vitro phosphatase assay), N-terminal deletion analysis, co-immunoprecipitation\",\n      \"journal\": \"BMC microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro enzymatic assay with domain deletion and reciprocal Co-IP, single lab, two orthogonal methods\",\n      \"pmids\": [\"11737864\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"PfPP5 exhibits phosphatase activity enhanced by arachidonic and oleic acids (but not myristic or stearic acid), is inhibited by okadaic acid with an IC50 of 4 nM, and is localized preferentially to the nucleus by immunofluorescence microscopy.\",\n      \"method\": \"Recombinant protein phosphatase assay, okadaic acid inhibition, immunofluorescence microscopy\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro enzymatic assay with inhibitor characterization plus direct localization by immunofluorescence, single lab, two orthogonal methods\",\n      \"pmids\": [\"11897131\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"PfARP (SET/TAF-family protein) specifically inhibited parasitic PP2A at nanomolar concentrations with no effect on PP5, establishing that PP5 is not a target of PfARP-mediated inhibition.\",\n      \"method\": \"In vitro phosphatase inhibition assay with recombinant/native proteins\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical assay clearly distinguishing PP5 from PP2A as a substrate of PfARP inhibition, single lab; this is a NEGATIVE finding for PP5 (PfARP does not inhibit it)\",\n      \"pmids\": [\"12615323\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"PfPP5 is a component of the PfHsp90 multi-chaperone complex (together with PfHsp70 and tubulin); geldanamycin disrupts this complex and inhibits parasite development, implicating PfPP5 in the temperature-dependent progression from ring to trophozoite stage.\",\n      \"method\": \"Co-immunoprecipitation of the PfHsp90 complex, geldanamycin inhibition, flow cytometry for parasite stage progression\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP of complex combined with pharmacological disruption and flow cytometry-based phenotype, single lab, two orthogonal methods\",\n      \"pmids\": [\"15339915\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"In Plasmodium berghei, PP5 (PbPP5) is expressed in blood stages and ookinetes, localises to the cytoplasm and beneath the parasite plasma membrane in merozoites and ookinetes. Targeted gene deletion (Δpbpp5) had no effect on asexual blood-stage multiplication but severely impaired male gamete formation and fertility, almost completely blocking ookinete conversion and oocyst development. Genetic rescue by crossing Δpbpp5 with female-defective Δpbs47 (but not male-defective Δpbs48/45) confirmed the male-specific fertility requirement. Recombinant phosphatase domain displayed phosphatase activity sensitive to cantharidic acid (IC50=122.2 nM), cantharidin (IC50=74.3 nM), endothall (IC50=365.5 nM), and okadaic acid (IC50=1.3 nM).\",\n      \"method\": \"Targeted gene deletion (KO), genetic epistasis (crossing with sex-specific mutant lines), immunofluorescence localization, in vitro phosphatase assay with inhibitors\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean KO with defined cellular phenotype, genetic epistasis via crossing with sex-specific lines, plus in vitro enzymatic characterization; multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"31202684\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PP5 (PF3D7_1355500) is a TPR-containing serine/threonine protein phosphatase that physically associates with the PfHsp90 multi-chaperone complex in P. falciparum asexual stages; its phosphatase activity is stimulated by polyunsaturated fatty acids and inhibited by okadaic acid, it localises predominantly to the nucleus in P. falciparum, and the ortholog in P. berghei is dispensable for asexual blood-stage growth but is essential for male gamete fertility and ookinete conversion, as established by targeted gene deletion and genetic epistasis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PP5 (PF3D7_1355500) is a TPR-repeat-containing serine/threonine protein phosphatase that couples the Plasmodium chaperone machinery to stage-specific developmental transitions [#0, #3]. Recombinant PfPP5 is catalytically active, and its activity is stimulated by polyunsaturated fatty acids such as arachidonic and oleic acid in an N-terminus-dependent manner, but not by saturated fatty acids, and it is inhibited by okadaic acid (IC50 ~4 nM) [#0, #1]. Through its N-terminal TPR repeats, native PfPP5 physically associates with PfHsp90 as a component of the PfHsp90 multi-chaperone complex (which also contains PfHsp70 and tubulin); geldanamycin disrupts this complex and blocks the temperature-dependent ring-to-trophozoite transition, placing PP5 within Hsp90-dependent asexual development [#0, #3]. In vitro, PP5 is not a target of the SET/TAF-family inhibitor PfARP, which selectively inhibits PP2A, distinguishing PP5 regulation from that of PP2A [#2]. In P. falciparum, PP5 localises preferentially to the nucleus [#1], whereas in P. berghei the ortholog localises to the cytoplasm and beneath the plasma membrane in merozoites and ookinetes; P. berghei gene deletion showed PP5 is dispensable for asexual blood-stage growth but essential for male gamete formation, fertility, and ookinete-to-oocyst conversion, a male-specific requirement confirmed by genetic crossing with sex-defective mutants [#4].\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"Established that PP5 is a genuine catalytic serine/threonine phosphatase whose activity is controlled by its N-terminal TPR region and lipid cofactors, and that it physically engages the Hsp90 chaperone.\",\n      \"evidence\": \"Recombinant bacterial expression with in vitro phosphatase assay, N-terminal deletion, and reciprocal co-immunoprecipitation in P. falciparum\",\n      \"pmids\": [\"11737864\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No physiological substrate identified\", \"Functional consequence of the PfHsp90 interaction not defined\", \"No structural model of the TPR-Hsp90 interface\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Defined the pharmacological and lipid-regulatory profile of PP5 and placed it in the nucleus, framing where and how the enzyme acts in P. falciparum.\",\n      \"evidence\": \"Recombinant phosphatase assay with fatty-acid and okadaic-acid characterization plus immunofluorescence in P. falciparum\",\n      \"pmids\": [\"11897131\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Nuclear substrates unidentified\", \"Mechanism linking fatty-acid stimulation to in vivo activity unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Distinguished PP5 regulation from PP2A by showing the SET/TAF-family inhibitor PfARP does not target PP5, clarifying that PP5 sits outside the PfARP-PP2A regulatory axis.\",\n      \"evidence\": \"In vitro phosphatase inhibition assay comparing PP5 and PP2A in P. falciparum\",\n      \"pmids\": [\"12615323\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Does not identify any positive regulator of PP5\", \"Negative result only\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Positioned PP5 as a functional constituent of the PfHsp90 multi-chaperone complex and linked chaperone-complex integrity to asexual stage progression.\",\n      \"evidence\": \"Co-immunoprecipitation of the PfHsp90 complex, geldanamycin disruption, and flow-cytometry stage analysis in P. falciparum\",\n      \"pmids\": [\"15339915\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Geldanamycin acts on Hsp90, so the direct requirement for PP5 activity in stage progression is not isolated\", \"Stoichiometry and substrates within the complex unknown\"],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Genetically defined the in vivo role of PP5, showing it is dispensable for asexual growth but essential for male gamete fertility and transmission-stage development in P. berghei.\",\n      \"evidence\": \"Targeted gene deletion, genetic epistasis by crossing with sex-defective mutants, immunofluorescence, and recombinant phosphatase-domain inhibitor assays in P. berghei\",\n      \"pmids\": [\"31202684\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Male-fertility substrates of PP5 not identified\", \"Cytoplasmic/sub-membrane localization in P. berghei differs from reported nuclear localization in P. falciparum and is unreconciled\", \"Whether the Hsp90 association is required for the transmission phenotype untested\"],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological substrates of PP5 and the mechanistic link between its Hsp90 association, its lipid/nuclear regulation, and its male-fertility requirement remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No dephosphorylation substrate identified in any species\", \"Species divergence in localization (nuclear in P. falciparum vs cytoplasmic/sub-membrane in P. berghei) unexplained\", \"Whether PP5's phosphatase activity is required for gametogenesis versus a scaffolding role untested\"],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004722\", \"supporting_discovery_ids\": [0, 1, 4]},\n      {\"term_id\": \"GO:0051879\", \"supporting_discovery_ids\": [0, 3]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007140\", \"supporting_discovery_ids\": [4]},\n      {\"term_id\": \"GO:0090114\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"complexes\": [\n      \"PfHsp90 multi-chaperone complex (with PfHsp70 and tubulin) [#3]\"\n    ],\n    \"partners\": [\n      \"PfHsp90 [#0, #3]\",\n      \"PfHsp70 (co-complex member) [#3]\",\n      \"tubulin (co-complex member) [#3]\"\n    ],\n    \"other_free_text\": [\n      \"Phosphatase activity stimulated by arachidonic and oleic acids but not myristic or stearic acid, in an N-terminus-dependent manner [#0, #1]\",\n      \"Inhibited by okadaic acid (IC50 ~4 nM in P. falciparum; 1.3 nM for P. berghei phosphatase domain), and by cantharidic acid, cantharidin, and endothall [#1, #4]\",\n      \"Not inhibited by the SET/TAF-family protein PfARP, which selectively inhibits PP2A [#2]\",\n      \"P. berghei gene deletion confirms dispensability for asexual blood-stage growth and a male-specific fertility/ookinete-conversion requirement via genetic crossing with sex-defective mutants [#4]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1355500","name":null,"product":"serine/threonine protein phosphatase 5","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1131900","name":null,"product":"serine/threonine protein phosphatase 5","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1116000","name":null,"product":"serine/threonine protein phosphatase 5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PP5","evaluation":null}