{"gene":"PF3D7_0934300","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2011,"finding":"ATP8 (PF3D7_0934300), when epitope-tagged and expressed in transgenic P. falciparum, localized to the mitochondrion. The full ATP synthase complex, including ATP8, assembles as a large dimeric complex (>1 MDa) in mitochondrial membranes, as shown by blue native gel electrophoresis. Attempts to genetically disrupt ATP8 and other subunit genes were unsuccessful, suggesting an essential role in blood-stage P. falciparum.","method":"Epitope-tagging of subunits in transgenic P. falciparum lines with immunofluorescence localization; blue native gel electrophoresis of mitochondrial membranes; attempted gene disruption","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunofluorescence with functional inference from failed knockout, two orthogonal methods in a single lab study; essentiality inference is indirect (failed disruption)","pmids":["21984828"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Bioinformatic/proteomics analysis identified PF3D7_0934300 as a candidate ATP synthase subunit 'a' (F0 sector membrane anchor) in Plasmodium spp., noting that its transmembrane helix IV lacks an essential Arg residue found in canonical orthologs, indicating divergence from canonical ATP synthase subunit a.","method":"Computational identification based on structural fingerprints and proteomics data from other protists","journal":"Mitochondrion","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic prediction only, no direct experimental validation of ATP8 function or identity","pmids":["19682605"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0934300 (ATP8) is a predicted ATP synthase subunit localized to the P. falciparum mitochondrion, where it is a component of a large (>1 MDa) dimeric ATP synthase complex; its gene appears refractory to disruption in blood-stage P. falciparum, suggesting an essential function, though its specific molecular role within the complex has not been biochemically defined."},"narrative":{"mechanistic_narrative":"PF3D7_0934300 (ATP8) is a mitochondrial protein of Plasmodium falciparum and a component of the parasite's ATP synthase, which assembles as a large dimeric complex (>1 MDa) in mitochondrial membranes [PMID:21984828]. Epitope-tagged ATP8 localizes to the mitochondrion, and its gene is refractory to disruption in blood-stage parasites, indicating an essential function [PMID:21984828]. Beyond its membership in the ATP synthase complex and this essentiality inference, the specific molecular role of ATP8 within the complex has not been biochemically defined in the available corpus; a computational analysis assigning it as a divergent subunit 'a' of the F0 sector, whose transmembrane helix IV lacks the essential Arg residue of canonical orthologs, remains a bioinformatic prediction [PMID:19682605].","teleology":[{"year":2009,"claim":"Before any experimental data, it was unknown whether Plasmodium encoded an ATP synthase subunit a; computational analysis nominated PF3D7_0934300 as a candidate F0 membrane anchor, framing the question of a divergent parasite ATP synthase.","evidence":"Bioinformatic identification from structural fingerprints and cross-protist proteomics","pmids":["19682605"],"confidence":"Low","gaps":["Prediction only, with no experimental validation of ATP8 identity or function","The functional consequence of the missing conserved Arg in transmembrane helix IV was not tested","Localization and complex membership were not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"It was unknown where ATP8 resides and whether it participates in an assembled complex; tagging and native gel analysis placed ATP8 in the mitochondrion as part of a >1 MDa dimeric ATP synthase and implied an essential role from failed disruption.","evidence":"Epitope-tagging with immunofluorescence, blue native gel electrophoresis of mitochondrial membranes, and attempted gene disruption in transgenic P. falciparum","pmids":["21984828"],"confidence":"Medium","gaps":["Essentiality is inferred from failed knockout rather than a conditional depletion","The specific molecular role of ATP8 within the complex was not defined","The predicted subunit-a assignment was not biochemically confirmed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The precise molecular function of ATP8 within the ATP synthase, and whether it functions as the predicted divergent subunit a, remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No biochemical assignment of ATP8's role in proton translocation or complex assembly","No conditional knockdown to confirm essentiality directly","No structural model of ATP8 within the P. falciparum complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ATP synthase complex (dimeric, >1 MDa) [#0]"],"partners":[],"other_free_text":["Gene refractory to disruption in blood-stage P. falciparum, implying essentiality [#0]","Computationally predicted divergent ATP synthase subunit 'a' lacking the conserved transmembrane helix IV Arg [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"19575561","id":"PMC_19575561","title":"Mitochondrial evolution and functions in malaria parasites.","date":"2009","source":"Annual review of microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/19575561","citation_count":183,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25831536","id":"PMC_25831536","title":"Mitochondrial ATP synthase is dispensable in blood-stage Plasmodium berghei rodent malaria but essential in the mosquito phase.","date":"2015","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/25831536","citation_count":91,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"15552397","id":"PMC_15552397","title":"The multiple roles of the mitochondrion of the malarial parasite.","date":"2004","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15552397","citation_count":66,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25823686","id":"PMC_25823686","title":"Triaminopyrimidine is a fast-killing and long-acting antimalarial clinical candidate.","date":"2015","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/25823686","citation_count":59,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21984828","id":"PMC_21984828","title":"ATP synthase complex of Plasmodium falciparum: dimeric assembly in mitochondrial membranes and resistance to genetic disruption.","date":"2011","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/21984828","citation_count":54,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2226706","id":"PMC_2226706","title":"Plasmodium falciparum: ATP/ADP transport across the parasitophorous vacuolar and plasma membranes.","date":"1990","source":"Experimental parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2226706","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19682605","id":"PMC_19682605","title":"Identification of mitochondrial Complex II subunits SDH3 and SDH4 and ATP synthase subunits a and b in Plasmodium spp.","date":"2009","source":"Mitochondrion","url":"https://pubmed.ncbi.nlm.nih.gov/19682605","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"2972931","id":"PMC_2972931","title":"Purification of Plasmodium falciparum digestive vacuoles and partial characterization of the vacuolar membrane ATPase.","date":"1988","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/2972931","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28875841","id":"PMC_28875841","title":"New Molecular Targets and Strategies for Antimalarial Discovery.","date":"2019","source":"Current medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28875841","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25986047","id":"PMC_25986047","title":"Molecular markers of anti-malarial drug resistance in southwest Ethiopia over time: regional surveillance from 2006 to 2013.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/25986047","citation_count":20,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7153,"output_tokens":686,"usd":0.015874,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5316,"output_tokens":1588,"usd":0.03314,"stage2_stop_reason":"end_turn"},"total_usd":0.049014,"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\": 2011,\n      \"finding\": \"ATP8 (PF3D7_0934300), when epitope-tagged and expressed in transgenic P. falciparum, localized to the mitochondrion. The full ATP synthase complex, including ATP8, assembles as a large dimeric complex (>1 MDa) in mitochondrial membranes, as shown by blue native gel electrophoresis. Attempts to genetically disrupt ATP8 and other subunit genes were unsuccessful, suggesting an essential role in blood-stage P. falciparum.\",\n      \"method\": \"Epitope-tagging of subunits in transgenic P. falciparum lines with immunofluorescence localization; blue native gel electrophoresis of mitochondrial membranes; attempted gene disruption\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunofluorescence with functional inference from failed knockout, two orthogonal methods in a single lab study; essentiality inference is indirect (failed disruption)\",\n      \"pmids\": [\"21984828\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Bioinformatic/proteomics analysis identified PF3D7_0934300 as a candidate ATP synthase subunit 'a' (F0 sector membrane anchor) in Plasmodium spp., noting that its transmembrane helix IV lacks an essential Arg residue found in canonical orthologs, indicating divergence from canonical ATP synthase subunit a.\",\n      \"method\": \"Computational identification based on structural fingerprints and proteomics data from other protists\",\n      \"journal\": \"Mitochondrion\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic prediction only, no direct experimental validation of ATP8 function or identity\",\n      \"pmids\": [\"19682605\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0934300 (ATP8) is a predicted ATP synthase subunit localized to the P. falciparum mitochondrion, where it is a component of a large (>1 MDa) dimeric ATP synthase complex; its gene appears refractory to disruption in blood-stage P. falciparum, suggesting an essential function, though its specific molecular role within the complex has not been biochemically defined.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0934300 (ATP8) is a mitochondrial protein of Plasmodium falciparum and a component of the parasite's ATP synthase, which assembles as a large dimeric complex (>1 MDa) in mitochondrial membranes [#0]. Epitope-tagged ATP8 localizes to the mitochondrion, and its gene is refractory to disruption in blood-stage parasites, indicating an essential function [#0]. Beyond its membership in the ATP synthase complex and this essentiality inference, the specific molecular role of ATP8 within the complex has not been biochemically defined in the available corpus; a computational analysis assigning it as a divergent subunit 'a' of the F0 sector, whose transmembrane helix IV lacks the essential Arg residue of canonical orthologs, remains a bioinformatic prediction [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Before any experimental data, it was unknown whether Plasmodium encoded an ATP synthase subunit a; computational analysis nominated PF3D7_0934300 as a candidate F0 membrane anchor, framing the question of a divergent parasite ATP synthase.\",\n      \"evidence\": \"Bioinformatic identification from structural fingerprints and cross-protist proteomics\",\n      \"pmids\": [\n        \"19682605\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Prediction only, with no experimental validation of ATP8 identity or function\",\n        \"The functional consequence of the missing conserved Arg in transmembrane helix IV was not tested\",\n        \"Localization and complex membership were not established\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"It was unknown where ATP8 resides and whether it participates in an assembled complex; tagging and native gel analysis placed ATP8 in the mitochondrion as part of a >1 MDa dimeric ATP synthase and implied an essential role from failed disruption.\",\n      \"evidence\": \"Epitope-tagging with immunofluorescence, blue native gel electrophoresis of mitochondrial membranes, and attempted gene disruption in transgenic P. falciparum\",\n      \"pmids\": [\n        \"21984828\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Essentiality is inferred from failed knockout rather than a conditional depletion\",\n        \"The specific molecular role of ATP8 within the complex was not defined\",\n        \"The predicted subunit-a assignment was not biochemically confirmed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise molecular function of ATP8 within the ATP synthase, and whether it functions as the predicted divergent subunit a, remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical assignment of ATP8's role in proton translocation or complex assembly\",\n        \"No conditional knockdown to confirm essentiality directly\",\n        \"No structural model of ATP8 within the P. falciparum complex\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0046933\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0005739\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      },\n      {\n        \"term_id\": \"GO:0005743\",\n        \"supporting_discovery_ids\": [\n          0\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0015986\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"Mitochondrial ATP synthase complex (dimeric, >1 MDa) [#0]\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Gene refractory to disruption in blood-stage P. falciparum, implying essentiality [#0]\",\n      \"Computationally predicted divergent ATP synthase subunit 'a' lacking the conserved transmembrane helix IV Arg [#1]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0934300","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_0611100, PF3D7_1010300). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0934300","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0835100","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0733000","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATP8","evaluation":null}