{"gene":"PF3D7_0704400","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2025,"finding":"PfPX2 (PF3D7_0704400) contains a PX domain whose in silico structural analysis revealed both canonical and non-canonical PIP-binding motifs and a positively charged binding pocket; lipid binding assays showed that the PfPX2 PX domain binds all species of phosphoinositides with a preference for PI3P, PI5P, and PI(3,5)P2.","method":"In silico structural analysis of PX domain; in vitro lipid binding assays","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 1–2 / Weak — direct in vitro lipid binding assay establishing biochemical activity, but single lab, single study, no mutagenesis validation reported","pmids":["41125830"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"PfPX2 (PF3D7_0704400) localizes to the Golgi apparatus and the micronemes in developing schizonts, as determined by immunofluorescence assays.","method":"Immunofluorescence assay (subcellular localization)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single method (IFA), localization established but functional consequence not directly demonstrated for this protein","pmids":["41125830"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"finding":"Proximity labelling identified PfSortilin, clathrin heavy chain, and PfDyn1 as potential interactors of PfPX2 (PF3D7_0704400), suggesting a role in vesicular trafficking between the Golgi apparatus and the micronemes.","method":"Proximity labelling (BioID or equivalent)","journal":"Scientific reports","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labelling identifies candidates but does not confirm direct physical interaction; single lab, single method","pmids":["41125830"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0704400 (PfPX2) is a Plasmodium falciparum PX domain-containing phosphoinositide-binding protein that preferentially binds PI3P, PI5P, and PI(3,5)P2 in vitro, localizes to the Golgi apparatus and micronemes in schizonts, and associates with vesicular trafficking machinery (PfSortilin, clathrin heavy chain, PfDyn1), suggesting a role in protein sorting/trafficking between the Golgi and micronemes."},"narrative":{"mechanistic_narrative":"PF3D7_0704400 (PfPX2) is a Plasmodium falciparum PX domain-containing protein implicated in phosphoinositide-dependent membrane trafficking during schizont development [PMID:41125830]. Its PX domain harbors both canonical and non-canonical PIP-binding motifs and a positively charged pocket, and in vitro binds all phosphoinositide species with a preference for PI3P, PI5P, and PI(3,5)P2 [PMID:41125830]. Consistent with a trafficking role, PfPX2 localizes to the Golgi apparatus and micronemes in developing schizonts [PMID:41125830]. Beyond this biochemical and localization characterization, the functional role of PfPX2 has not been established in the available corpus; its lipid-binding specificity has not been validated by mutagenesis, and its physical partners remain undefined.","teleology":[{"year":2025,"claim":"Whether PF3D7_0704400 is a functional phosphoinositide-binding protein was unknown; demonstrating that its PX domain binds specific PIP species established it as a lipid-recognition module with defined binding preferences.","evidence":"In silico structural analysis of the PX domain combined with in vitro lipid binding assays, in P. falciparum PfPX2","pmids":["41125830"],"confidence":"Medium","gaps":["No mutagenesis of the predicted binding pocket to confirm specificity","Binding shown in vitro only; in vivo lipid engagement not demonstrated","Single lab, single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"The subcellular context of PfPX2 was undefined; immunofluorescence placing it at the Golgi and micronemes in schizonts localized its activity to secretory/trafficking compartments.","evidence":"Immunofluorescence assay in P. falciparum developing schizonts","pmids":["41125830"],"confidence":"Medium","gaps":["Functional consequence of this localization not tested","Single method (IFA) without orthogonal validation","Dynamics across the intraerythrocytic cycle not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2025,"claim":"Whether PfPX2 associates with trafficking machinery was unknown; proximity labelling nominated candidate interactors consistent with Golgi-to-microneme vesicular transport.","evidence":"Proximity labelling identifying PfSortilin, clathrin heavy chain, and PfDyn1 as candidates, in P. falciparum","pmids":["41125830"],"confidence":"Low","gaps":["Proximity labelling nominates candidates but does not confirm direct physical interaction; no reciprocal or biochemical validation","No functional demonstration that PfPX2 participates in the trafficking pathway","Single lab, single method"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The cellular function of PfPX2 in parasite biology, and whether its PIP binding and putative trafficking partners are required for microneme protein sorting or parasite viability, remains unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout/knockdown phenotype reported","No confirmed direct interaction partner","Contribution to microneme biogenesis or invasion untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFSORTILIN (CANDIDATE, PROXIMITY LABELLING)","CLATHRIN HEAVY CHAIN (CANDIDATE, PROXIMITY LABELLING)","PFDYN1 (CANDIDATE, PROXIMITY LABELLING)"],"other_free_text":["PfPX2 PX domain contains both canonical and non-canonical PIP-binding motifs with a positively charged binding pocket [#0].","Binds all phosphoinositide species in vitro with preference for PI3P, PI5P, and PI(3,5)P2 [#0].","Partner identifications are candidate-level from proximity labelling and are not confirmed direct interactions [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"28068997","id":"PMC_28068997","title":"Absence of in vivo selection for K13 mutations after artemether-lumefantrine treatment in Uganda.","date":"2017","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/28068997","citation_count":28,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoinositide-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"31097469","id":"PMC_31097469","title":"A pan-apicomplexan phosphoinositide-binding protein acts in malarial microneme exocytosis.","date":"2019","source":"EMBO reports","url":"https://pubmed.ncbi.nlm.nih.gov/31097469","citation_count":22,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoinositide-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35038916","id":"PMC_35038916","title":"A Phosphoinositide-Binding Protein Acts in the Trafficking Pathway of Hemoglobin in the Malaria Parasite Plasmodium falciparum.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/35038916","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoinositide-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"40766679","id":"PMC_40766679","title":"A novel locus associated with decreased susceptibility of Plasmodium falciparum to lumefantrine and dihydroartemisinin has emerged and spread in Uganda.","date":"2025","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/40766679","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoinositide-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42182324","id":"PMC_42182324","title":"A Plasmodium falciparum PX1 haplotype is associated with reduced susceptibility to artemisinin and lumefantrine.","date":"2026","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/42182324","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoinositide-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41125830","id":"PMC_41125830","title":"Characterization of a phosphoinositide-binding protein containing a PHOX homology domain in the malaria parasite Plasmodium falciparum.","date":"2025","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/41125830","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["phosphoinositide-binding protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6122,"output_tokens":810,"usd":0.015258,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5441,"output_tokens":1844,"usd":0.036652,"stage2_stop_reason":"end_turn"},"total_usd":0.05191,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2025,\n      \"finding\": \"PfPX2 (PF3D7_0704400) contains a PX domain whose in silico structural analysis revealed both canonical and non-canonical PIP-binding motifs and a positively charged binding pocket; lipid binding assays showed that the PfPX2 PX domain binds all species of phosphoinositides with a preference for PI3P, PI5P, and PI(3,5)P2.\",\n      \"method\": \"In silico structural analysis of PX domain; in vitro lipid binding assays\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1–2 / Weak — direct in vitro lipid binding assay establishing biochemical activity, but single lab, single study, no mutagenesis validation reported\",\n      \"pmids\": [\"41125830\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"PfPX2 (PF3D7_0704400) localizes to the Golgi apparatus and the micronemes in developing schizonts, as determined by immunofluorescence assays.\",\n      \"method\": \"Immunofluorescence assay (subcellular localization)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (IFA), localization established but functional consequence not directly demonstrated for this protein\",\n      \"pmids\": [\"41125830\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Proximity labelling identified PfSortilin, clathrin heavy chain, and PfDyn1 as potential interactors of PfPX2 (PF3D7_0704400), suggesting a role in vesicular trafficking between the Golgi apparatus and the micronemes.\",\n      \"method\": \"Proximity labelling (BioID or equivalent)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labelling identifies candidates but does not confirm direct physical interaction; single lab, single method\",\n      \"pmids\": [\"41125830\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0704400 (PfPX2) is a Plasmodium falciparum PX domain-containing phosphoinositide-binding protein that preferentially binds PI3P, PI5P, and PI(3,5)P2 in vitro, localizes to the Golgi apparatus and micronemes in schizonts, and associates with vesicular trafficking machinery (PfSortilin, clathrin heavy chain, PfDyn1), suggesting a role in protein sorting/trafficking between the Golgi and micronemes.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0704400 (PfPX2) is a Plasmodium falciparum PX domain-containing protein implicated in phosphoinositide-dependent membrane trafficking during schizont development [#0, #1]. Its PX domain harbors both canonical and non-canonical PIP-binding motifs and a positively charged pocket, and in vitro binds all phosphoinositide species with a preference for PI3P, PI5P, and PI(3,5)P2 [#0]. Consistent with a trafficking role, PfPX2 localizes to the Golgi apparatus and micronemes in developing schizonts [#1]. Beyond this biochemical and localization characterization, the functional role of PfPX2 has not been established in the available corpus; its lipid-binding specificity has not been validated by mutagenesis, and its physical partners remain undefined.\",\n  \"teleology\": [\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether PF3D7_0704400 is a functional phosphoinositide-binding protein was unknown; demonstrating that its PX domain binds specific PIP species established it as a lipid-recognition module with defined binding preferences.\",\n      \"evidence\": \"In silico structural analysis of the PX domain combined with in vitro lipid binding assays, in P. falciparum PfPX2\",\n      \"pmids\": [\"41125830\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No mutagenesis of the predicted binding pocket to confirm specificity\",\n        \"Binding shown in vitro only; in vivo lipid engagement not demonstrated\",\n        \"Single lab, single study\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"The subcellular context of PfPX2 was undefined; immunofluorescence placing it at the Golgi and micronemes in schizonts localized its activity to secretory/trafficking compartments.\",\n      \"evidence\": \"Immunofluorescence assay in P. falciparum developing schizonts\",\n      \"pmids\": [\"41125830\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Functional consequence of this localization not tested\",\n        \"Single method (IFA) without orthogonal validation\",\n        \"Dynamics across the intraerythrocytic cycle not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether PfPX2 associates with trafficking machinery was unknown; proximity labelling nominated candidate interactors consistent with Golgi-to-microneme vesicular transport.\",\n      \"evidence\": \"Proximity labelling identifying PfSortilin, clathrin heavy chain, and PfDyn1 as candidates, in P. falciparum\",\n      \"pmids\": [\"41125830\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Proximity labelling nominates candidates but does not confirm direct physical interaction; no reciprocal or biochemical validation\",\n        \"No functional demonstration that PfPX2 participates in the trafficking pathway\",\n        \"Single lab, single method\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The cellular function of PfPX2 in parasite biology, and whether its PIP binding and putative trafficking partners are required for microneme protein sorting or parasite viability, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout/knockdown phenotype reported\",\n        \"No confirmed direct interaction partner\",\n        \"Contribution to microneme biogenesis or invasion untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0035091\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0032266\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0080025\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005794\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0016192\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfSortilin (candidate, proximity labelling)\",\n      \"clathrin heavy chain (candidate, proximity labelling)\",\n      \"PfDyn1 (candidate, proximity labelling)\"\n    ],\n    \"other_free_text\": [\n      \"PfPX2 PX domain contains both canonical and non-canonical PIP-binding motifs with a positively charged binding pocket [#0].\",\n      \"Binds all phosphoinositide species in vitro with preference for PI3P, PI5P, and PI(3,5)P2 [#0].\",\n      \"Partner identifications are candidate-level from proximity labelling and are not confirmed direct interactions [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0704400","name":null,"product":"phosphoinositide-binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0802100","name":null,"product":"phosphoinositide-binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0102600","name":null,"product":"phosphoinositide-binding protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}