{"gene":"PF3D7_1223400","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2022,"finding":"PF3D7_1223400 (phospholipid-transporting ATPase 2, ATP2) forms a complex with CDC50C in P. falciparum asexual blood stages, as demonstrated by gene tagging and conditional gene disruption experiments.","method":"Gene tagging and conditional gene disruption (co-immunoprecipitation/binding partner identification implied)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — binding partner identified by gene tagging and conditional disruption in a single lab study; no reciprocal Co-IP or in vitro reconstitution reported in the abstract","pmids":["35862778"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"The CDC50C–ATP2 (PF3D7_1223400) complex influences parasite endocytosis of host cell hemoglobin and consequently hemozoin formation during trophozoite maturation; conditional disruption of CDC50C (the obligate chaperone of ATP2) is essential for blood stage trophozoite maturation.","method":"Conditional gene disruption of CDC50C with phenotypic readout (endocytosis, hemozoin formation, trophozoite maturation)","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean conditional KO with defined cellular phenotype, single lab, phenotype attributed to the CDC50C–ATP2 complex but direct functional dissection of ATP2 alone not reported","pmids":["35862778"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1223400 (ATP2) is a putative P4-ATPase that forms a complex with the CDC50C chaperone in P. falciparum asexual blood stages; this CDC50C–ATP2 complex is required for trophozoite maturation and appears to influence endocytosis of host cell hemoglobin and hemozoin formation, consistent with a phospholipid-flipping function analogous to P4-ATPases in model organisms."},"narrative":{"mechanistic_narrative":"PF3D7_1223400 (ATP2) is a putative P4-type phospholipid-transporting ATPase of P. falciparum that operates as part of a CDC50C–ATP2 complex during asexual blood-stage development [PMID:35862778]. Gene tagging and conditional disruption place ATP2 in a physical complex with the CDC50C chaperone in trophozoites [PMID:35862778], and disruption of CDC50C, the obligate chaperone of ATP2, impairs endocytosis of host-cell hemoglobin and consequent hemozoin formation, and is essential for trophozoite maturation [PMID:35862778]. Beyond its participation in the CDC50C–ATP2 complex and this maturation/endocytosis phenotype, the corpus establishes no direct biochemical characterization of ATP2 itself — its catalytic activity, lipid substrate specificity, and subcellular localization have not been dissected in the available evidence.","teleology":[{"year":2022,"claim":"It was unknown whether the putative P4-ATPase ATP2 acts alone or with a partner; identifying a stable CDC50C–ATP2 complex established the molecular context in which ATP2 functions in blood stages.","evidence":"Gene tagging and conditional gene disruption in P. falciparum asexual blood stages","pmids":["35862778"],"confidence":"Medium","gaps":["No reciprocal Co-IP or in vitro reconstitution confirming the direct ATP2–CDC50C interaction","Stoichiometry and subcellular localization of the complex not defined","ATP2's own catalytic/flippase activity not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"It was unclear what cellular process the ATP2 complex serves; conditional disruption of its chaperone CDC50C tied the complex to hemoglobin endocytosis, hemozoin formation, and trophozoite maturation.","evidence":"Conditional gene disruption of CDC50C with endocytosis, hemozoin, and maturation readouts in P. falciparum","pmids":["35862778"],"confidence":"Medium","gaps":["Phenotype was scored via CDC50C disruption; direct functional dissection of ATP2 alone not reported","Mechanistic link between putative lipid flipping and endocytosis not established","Whether ATP2 loss phenocopies CDC50C loss not shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The enzymatic activity, lipid substrate, membrane localization, and direct (ATP2-specific) contribution to endocytosis remain uncharacterized.","evidence":"No further direct experimental evidence on ATP2 in the corpus","pmids":[],"confidence":"Medium","gaps":["No in vitro or in vivo demonstration of ATP2 phospholipid-flippase activity","No lipid substrate specificity determined","No direct conditional disruption of ATP2 itself with phenotype"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["CDC50C–ATP2 complex"],"partners":["CDC50C"],"other_free_text":["ATP2 is a putative P4-type phospholipid-transporting ATPase whose enzymatic activity has not been directly demonstrated in the corpus [#0].","CDC50C is the obligate chaperone of ATP2; disruption of CDC50C impairs hemoglobin endocytosis and hemozoin formation and blocks trophozoite maturation, but a phenotype attributable to ATP2 alone has not been reported [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"15774027","id":"PMC_15774027","title":"The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum.","date":"2005","source":"Genome biology","url":"https://pubmed.ncbi.nlm.nih.gov/15774027","citation_count":146,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35862778","id":"PMC_35862778","title":"CDC50 Orthologues in Plasmodium falciparum Have Distinct Roles in Merozoite Egress and Trophozoite Maturation.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35862778","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phospholipid-transporting ATPase"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3997,"output_tokens":634,"usd":0.01075,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5200,"output_tokens":1530,"usd":0.032125,"stage2_stop_reason":"end_turn"},"total_usd":0.042875,"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\": 2022,\n      \"finding\": \"PF3D7_1223400 (phospholipid-transporting ATPase 2, ATP2) forms a complex with CDC50C in P. falciparum asexual blood stages, as demonstrated by gene tagging and conditional gene disruption experiments.\",\n      \"method\": \"Gene tagging and conditional gene disruption (co-immunoprecipitation/binding partner identification implied)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — binding partner identified by gene tagging and conditional disruption in a single lab study; no reciprocal Co-IP or in vitro reconstitution reported in the abstract\",\n      \"pmids\": [\"35862778\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The CDC50C–ATP2 (PF3D7_1223400) complex influences parasite endocytosis of host cell hemoglobin and consequently hemozoin formation during trophozoite maturation; conditional disruption of CDC50C (the obligate chaperone of ATP2) is essential for blood stage trophozoite maturation.\",\n      \"method\": \"Conditional gene disruption of CDC50C with phenotypic readout (endocytosis, hemozoin formation, trophozoite maturation)\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean conditional KO with defined cellular phenotype, single lab, phenotype attributed to the CDC50C–ATP2 complex but direct functional dissection of ATP2 alone not reported\",\n      \"pmids\": [\"35862778\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1223400 (ATP2) is a putative P4-ATPase that forms a complex with the CDC50C chaperone in P. falciparum asexual blood stages; this CDC50C–ATP2 complex is required for trophozoite maturation and appears to influence endocytosis of host cell hemoglobin and hemozoin formation, consistent with a phospholipid-flipping function analogous to P4-ATPases in model organisms.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PF3D7_1223400 (ATP2) is a putative P4-type phospholipid-transporting ATPase of P. falciparum that operates as part of a CDC50C–ATP2 complex during asexual blood-stage development [#0]. Gene tagging and conditional disruption place ATP2 in a physical complex with the CDC50C chaperone in trophozoites [#0], and disruption of CDC50C, the obligate chaperone of ATP2, impairs endocytosis of host-cell hemoglobin and consequent hemozoin formation, and is essential for trophozoite maturation [#1]. Beyond its participation in the CDC50C–ATP2 complex and this maturation/endocytosis phenotype, the corpus establishes no direct biochemical characterization of ATP2 itself — its catalytic activity, lipid substrate specificity, and subcellular localization have not been dissected in the available evidence.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"It was unknown whether the putative P4-ATPase ATP2 acts alone or with a partner; identifying a stable CDC50C–ATP2 complex established the molecular context in which ATP2 functions in blood stages.\",\n      \"evidence\": \"Gene tagging and conditional gene disruption in P. falciparum asexual blood stages\",\n      \"pmids\": [\"35862778\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No reciprocal Co-IP or in vitro reconstitution confirming the direct ATP2–CDC50C interaction\",\n        \"Stoichiometry and subcellular localization of the complex not defined\",\n        \"ATP2's own catalytic/flippase activity not measured\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"It was unclear what cellular process the ATP2 complex serves; conditional disruption of its chaperone CDC50C tied the complex to hemoglobin endocytosis, hemozoin formation, and trophozoite maturation.\",\n      \"evidence\": \"Conditional gene disruption of CDC50C with endocytosis, hemozoin, and maturation readouts in P. falciparum\",\n      \"pmids\": [\"35862778\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Phenotype was scored via CDC50C disruption; direct functional dissection of ATP2 alone not reported\",\n        \"Mechanistic link between putative lipid flipping and endocytosis not established\",\n        \"Whether ATP2 loss phenocopies CDC50C loss not shown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The enzymatic activity, lipid substrate, membrane localization, and direct (ATP2-specific) contribution to endocytosis remain uncharacterized.\",\n      \"evidence\": \"No further direct experimental evidence on ATP2 in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in vitro or in vivo demonstration of ATP2 phospholipid-flippase activity\",\n        \"No lipid substrate specificity determined\",\n        \"No direct conditional disruption of ATP2 itself with phenotype\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004012\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006897\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"CDC50C–ATP2 complex\"],\n    \"partners\": [\"CDC50C\"],\n    \"other_free_text\": [\n      \"ATP2 is a putative P4-type phospholipid-transporting ATPase whose enzymatic activity has not been directly demonstrated in the corpus [#0].\",\n      \"CDC50C is the obligate chaperone of ATP2; disruption of CDC50C impairs hemoglobin endocytosis and hemozoin formation and blocks trophozoite maturation, but a phenotype attributable to ATP2 alone has not been reported [#1].\"\n    ]\n  }\n}\n```","audit_flag":{"gene":"PF3D7_1223400","tier":"GROUNDING","verdict":"Evidence-grounding concern","subtype":"uncited_synthesis","uniprot_band":"empty","rules_fired":"R8,R12","issue":"R8: 1/3 claims uncited (33%) | No cited paper names this card; 1 of 1 cited papers name other catalogue genes (PF3D7_0719500, PF3D7_1029400, PF3D7_1133300). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1223400","name":null,"product":"phospholipid-transporting ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1438300","name":null,"product":"phospholipid-transporting ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1442600","name":null,"product":"phospholipid-transporting ATPase, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}