{"gene":"PF3D7_1018200","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2023,"finding":"PPP8 (PF3D7_1018200) localizes to the basal complex of P. falciparum during schizogony and is required for uniform basal complex expansion and maintenance of its integrity during daughter cell formation. Conditional depletion of PPP8 disrupts basal complex structure and segmentation. PPP8 is characterized as an 'early-departing' basal complex protein (relative to other basal complex components). By co-immunoprecipitation, PPP8 was used to identify two additional novel basal complex proteins.","method":"Multiple microscopy techniques (including fluorescence microscopy), conditional knockdown/depletion, co-immunoprecipitation","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (microscopy, conditional KO with defined phenotype, Co-IP) in a single focused study with rigorous controls","pmids":["37400439"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2008,"finding":"PPP8 (PF3D7_1018200) was identified by bioinformatic analysis of the P. falciparum genome as one of 27 putative protein phosphatase sequences, placing it within the phosphatome of the parasite.","method":"Bioinformatics / phylogenetic analysis of the P. falciparum genome","journal":"BMC genomics","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no experimental validation of PPP8 function","pmids":["18793411"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"finding":"PPP8 (PF3D7_1018200) was used as a basal complex marker in expansion microscopy (U-ExM) experiments to investigate basal complex assembly in BTP2 knockout parasites. PPP8 localized to individual basal complex units in wild-type early schizonts; in BTP2 knockout parasites, large basal complexes marked by PPP8 encompassed multiple sets of centriolar plaques and apical organelles, demonstrating that BTP2 loss disrupts basal complex individualization. These data confirmed PPP8's established basal complex localization and its utility as a marker, but the functional defects described are those of BTP2, not PPP8.","method":"Expansion microscopy (U-ExM), DNA-PAINT (PAINT), fluorescence tagging of PPP8 as a basal complex marker in a BTP2 conditional knockout background","journal":"Science advances","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — super-resolution microscopy with direct visualization of PPP8 at the basal complex, but this paper uses PPP8 as a marker rather than interrogating PPP8 function itself","pmids":["41706859"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PPP8 (PF3D7_1018200) is a PPP-type pseudophosphatase that localizes early to the basal complex of P. falciparum during schizogony and is essential for uniform basal complex expansion and integrity; its loss disrupts segmentation and daughter cell formation, and co-immunoprecipitation using PPP8 as bait identified two additional novel basal complex proteins."},"narrative":{"mechanistic_narrative":"PPP8 (PF3D7_1018200) is a PPP-type pseudophosphatase that functions as an essential structural component of the basal complex in Plasmodium falciparum during schizogony [PMID:37400439]. It localizes to the basal complex and is required for uniform basal complex expansion and for maintaining the integrity of this structure during daughter cell formation; conditional depletion of PPP8 disrupts basal complex architecture and segmentation [PMID:37400439]. PPP8 is an 'early-departing' basal complex protein relative to other components, and co-immunoprecipitation with PPP8 as bait identified two additional novel basal complex proteins [PMID:37400439]. At super-resolution, PPP8 marks individual basal complex units in wild-type early schizonts, establishing it as a reliable basal complex marker [PMID:41706859]. Beyond its structural role at the basal complex, no catalytic activity or phosphatase substrate has been characterized for PPP8 in the available corpus.","teleology":[{"year":2008,"claim":"Before any functional data existed, it was unknown which P. falciparum genes encoded phosphatase-family proteins; genome-wide bioinformatic cataloguing placed PPP8 within the parasite phosphatome as one of 27 putative protein phosphatases.","evidence":"bioinformatic and phylogenetic analysis of the P. falciparum genome","pmids":["18793411"],"confidence":"Low","gaps":["Computational prediction only, with no experimental validation of PPP8 activity or function","Does not distinguish an active phosphatase from a pseudophosphatase","No localization or cellular role addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"The cellular role of PPP8 was unknown; targeted localization, conditional depletion, and interaction mapping established it as an essential basal complex protein required for uniform basal complex expansion and daughter cell segmentation.","evidence":"fluorescence and other microscopy, conditional knockdown with defined phenotype, and co-immunoprecipitation in P. falciparum","pmids":["37400439"],"confidence":"High","gaps":["The identities and functional roles of the two co-immunoprecipitated basal complex proteins are not resolved here","Whether PPP8 acts as a catalytically dead pseudophosphatase or retains any enzymatic role is not tested","The molecular basis for its 'early-departing' behavior at the basal complex is unexplained"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2026,"claim":"It was unclear whether PPP8 marks discrete basal complex units; super-resolution imaging confirmed PPP8 labels individual basal complex units in wild-type schizonts and validated it as a basal complex marker for dissecting assembly defects in other mutants.","evidence":"expansion microscopy (U-ExM) and DNA-PAINT with PPP8-tagged parasites in a BTP2 knockout background in P. falciparum","pmids":["41706859"],"confidence":"Medium","gaps":["This study uses PPP8 as a marker rather than interrogating PPP8 function; the functional defects described are those of BTP2, not PPP8","PPP8's own contribution to basal complex individualization is not directly tested","No mechanistic link between PPP8 and BTP2 established beyond shared localization"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PPP8 has any residual catalytic or substrate-directed activity, and how it is recruited to and departs from the basal complex, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No phosphatase substrate or catalytic activity demonstrated","Mechanism of early-departing recruitment and release from the basal complex unknown","Structural basis of interaction with the two co-immunoprecipitated partners uncharacterized"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Basal complex"],"partners":["TWO NOVEL BASAL COMPLEX PROTEINS IDENTIFIED BY CO-IMMUNOPRECIPITATION WITH PPP8 AS BAIT [#0]"],"other_free_text":["Classified as a PPP-type pseudophosphatase and member of the P. falciparum phosphatome [#1]","Characterized as an 'early-departing' basal complex protein relative to other basal complex components [#0]","Conditional depletion disrupts basal complex expansion, integrity, and segmentation [#0]","Used as a validated basal complex marker in super-resolution imaging of BTP2 knockout parasites [#2]"]}},"prefetch_data":{},"corpus_meta":[{"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":"37400439","id":"PMC_37400439","title":"A PPP-type pseudophosphatase is required for the maintenance of basal complex integrity in Plasmodium falciparum.","date":"2023","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/37400439","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfPPP8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41706859","id":"","title":"Transmembrane proteins mediate basal complex assembly and individual daughter cell formation in malaria parasites.","date":"2026","source":"Science advances","url":"https://pubmed.ncbi.nlm.nih.gov/41706859","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PPP8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38563493","id":"","title":"The molecular mechanisms driving Plasmodium cell division.","date":"2024","source":"Biochemical Society transactions","url":"https://pubmed.ncbi.nlm.nih.gov/38563493","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PPP8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34395314","id":"","title":"Calcium in the Backstage of Malaria Parasite Biology.","date":"2021","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/34395314","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PPP8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38039338","id":"","title":"The Kelch13 compartment contains highly divergent vesicle trafficking proteins in malaria parasites.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38039338","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PPP8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7388,"output_tokens":969,"usd":0.01835,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5721,"output_tokens":1898,"usd":0.038027,"stage2_stop_reason":"end_turn"},"total_usd":0.056377,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"PPP8 (PF3D7_1018200) localizes to the basal complex of P. falciparum during schizogony and is required for uniform basal complex expansion and maintenance of its integrity during daughter cell formation. Conditional depletion of PPP8 disrupts basal complex structure and segmentation. PPP8 is characterized as an 'early-departing' basal complex protein (relative to other basal complex components). By co-immunoprecipitation, PPP8 was used to identify two additional novel basal complex proteins.\",\n      \"method\": \"Multiple microscopy techniques (including fluorescence microscopy), conditional knockdown/depletion, co-immunoprecipitation\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (microscopy, conditional KO with defined phenotype, Co-IP) in a single focused study with rigorous controls\",\n      \"pmids\": [\"37400439\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2008,\n      \"finding\": \"PPP8 (PF3D7_1018200) was identified by bioinformatic analysis of the P. falciparum genome as one of 27 putative protein phosphatase sequences, placing it within the phosphatome of the parasite.\",\n      \"method\": \"Bioinformatics / phylogenetic analysis of the P. falciparum genome\",\n      \"journal\": \"BMC genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no experimental validation of PPP8 function\",\n      \"pmids\": [\"18793411\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"PPP8 (PF3D7_1018200) was used as a basal complex marker in expansion microscopy (U-ExM) experiments to investigate basal complex assembly in BTP2 knockout parasites. PPP8 localized to individual basal complex units in wild-type early schizonts; in BTP2 knockout parasites, large basal complexes marked by PPP8 encompassed multiple sets of centriolar plaques and apical organelles, demonstrating that BTP2 loss disrupts basal complex individualization. These data confirmed PPP8's established basal complex localization and its utility as a marker, but the functional defects described are those of BTP2, not PPP8.\",\n      \"method\": \"Expansion microscopy (U-ExM), DNA-PAINT (PAINT), fluorescence tagging of PPP8 as a basal complex marker in a BTP2 conditional knockout background\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — super-resolution microscopy with direct visualization of PPP8 at the basal complex, but this paper uses PPP8 as a marker rather than interrogating PPP8 function itself\",\n      \"pmids\": [\"41706859\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PPP8 (PF3D7_1018200) is a PPP-type pseudophosphatase that localizes early to the basal complex of P. falciparum during schizogony and is essential for uniform basal complex expansion and integrity; its loss disrupts segmentation and daughter cell formation, and co-immunoprecipitation using PPP8 as bait identified two additional novel basal complex proteins.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PPP8 (PF3D7_1018200) is a PPP-type pseudophosphatase that functions as an essential structural component of the basal complex in Plasmodium falciparum during schizogony [#0]. It localizes to the basal complex and is required for uniform basal complex expansion and for maintaining the integrity of this structure during daughter cell formation; conditional depletion of PPP8 disrupts basal complex architecture and segmentation [#0]. PPP8 is an 'early-departing' basal complex protein relative to other components, and co-immunoprecipitation with PPP8 as bait identified two additional novel basal complex proteins [#0]. At super-resolution, PPP8 marks individual basal complex units in wild-type early schizonts, establishing it as a reliable basal complex marker [#2]. Beyond its structural role at the basal complex, no catalytic activity or phosphatase substrate has been characterized for PPP8 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2008,\n      \"claim\": \"Before any functional data existed, it was unknown which P. falciparum genes encoded phosphatase-family proteins; genome-wide bioinformatic cataloguing placed PPP8 within the parasite phosphatome as one of 27 putative protein phosphatases.\",\n      \"evidence\": \"bioinformatic and phylogenetic analysis of the P. falciparum genome\",\n      \"pmids\": [\"18793411\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only, with no experimental validation of PPP8 activity or function\",\n        \"Does not distinguish an active phosphatase from a pseudophosphatase\",\n        \"No localization or cellular role addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"The cellular role of PPP8 was unknown; targeted localization, conditional depletion, and interaction mapping established it as an essential basal complex protein required for uniform basal complex expansion and daughter cell segmentation.\",\n      \"evidence\": \"fluorescence and other microscopy, conditional knockdown with defined phenotype, and co-immunoprecipitation in P. falciparum\",\n      \"pmids\": [\"37400439\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The identities and functional roles of the two co-immunoprecipitated basal complex proteins are not resolved here\",\n        \"Whether PPP8 acts as a catalytically dead pseudophosphatase or retains any enzymatic role is not tested\",\n        \"The molecular basis for its 'early-departing' behavior at the basal complex is unexplained\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"It was unclear whether PPP8 marks discrete basal complex units; super-resolution imaging confirmed PPP8 labels individual basal complex units in wild-type schizonts and validated it as a basal complex marker for dissecting assembly defects in other mutants.\",\n      \"evidence\": \"expansion microscopy (U-ExM) and DNA-PAINT with PPP8-tagged parasites in a BTP2 knockout background in P. falciparum\",\n      \"pmids\": [\"41706859\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"This study uses PPP8 as a marker rather than interrogating PPP8 function; the functional defects described are those of BTP2, not PPP8\",\n        \"PPP8's own contribution to basal complex individualization is not directly tested\",\n        \"No mechanistic link between PPP8 and BTP2 established beyond shared localization\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PPP8 has any residual catalytic or substrate-directed activity, and how it is recruited to and departs from the basal complex, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No phosphatase substrate or catalytic activity demonstrated\",\n        \"Mechanism of early-departing recruitment and release from the basal complex unknown\",\n        \"Structural basis of interaction with the two co-immunoprecipitated partners uncharacterized\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"basal complex\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"schizogony / daughter cell segmentation\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"Basal complex\"],\n    \"partners\": [\"Two novel basal complex proteins identified by co-immunoprecipitation with PPP8 as bait [#0]\"],\n    \"other_free_text\": [\n      \"Classified as a PPP-type pseudophosphatase and member of the P. falciparum phosphatome [#1]\",\n      \"Characterized as an 'early-departing' basal complex protein relative to other basal complex components [#0]\",\n      \"Conditional depletion disrupts basal complex expansion, integrity, and segmentation [#0]\",\n      \"Used as a validated basal complex marker in super-resolution imaging of BTP2 knockout parasites [#2]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1018200","name":null,"product":"pseudophosphatase PPP8","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0502500","name":null,"product":"serine/threonine protein phosphatase 8","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0602400","name":null,"product":"serine/threonine protein phosphatase 8, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PPP8","evaluation":null}