{"gene":"PF3D7_0815400","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2011,"finding":"PF3D7_0815400 (ATPTG3), along with six other epitope-tagged canonical ATP synthase subunits, was shown to localize to the mitochondrion of P. falciparum. Blue native gel electrophoresis of mitochondrial membranes indicated the ATP synthase complex (which includes ATPTG3) has a molecular mass greater than 1 million daltons, consistent with dimeric assembly, suggesting the presence of previously unknown subunits beyond the canonical set.","method":"Epitope tagging of subunits in transgenic P. falciparum lines with immunofluorescence localization; blue native gel electrophoresis of mitochondrial membranes","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by immunofluorescence in transgenic lines and native gel electrophoresis, single lab, two orthogonal methods; ATPTG3 is one of seven subunits studied collectively and is not individually distinguished in the abstract","pmids":["21984828"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Bioinformatic/proteomics-based analysis identified candidates for ATP synthase subunit a and subunit b in Plasmodium spp., noting that transmembrane helix IV of ATP synthase subunit a lacks an essential Arg residue found in canonical orthologs, and that these membrane anchor subunits are highly divergent from canonical orthologs.","method":"Computational identification based on structural fingerprints and proteomics data from other protists","journal":"Mitochondrion","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct experimental validation of ATPTG3 specifically","pmids":["19682605"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Knockout of the ATP synthase β subunit in P. berghei (a sibling subunit within the same complex that includes ATPTG3) was dispensable for asexual blood-stage growth but essential for mosquito-stage viability; ookinetes lacking the β subunit failed to produce oocysts or sporozoites. This establishes that the mitochondrial ATP synthase complex (of which ATPTG3 is a putative associated protein) is essential in the mosquito phase but not the blood stage.","method":"Genetic knockout (gene disruption) of ATP synthase β subunit in P. berghei with transmission assays in Anopheles stephensi mosquitoes and genetic complementation cross","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Low","confidence_rationale":"Tier 2 / Weak — rigorous KO experiment, but finding is about the β subunit (a different gene); ATPTG3 itself was not experimentally manipulated; relevance to ATPTG3 is indirect via complex membership","pmids":["25831536"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_0815400 (ATPTG3) is a putative ATP synthase-associated protein in P. falciparum that localizes to the mitochondrion as part of a large (>1 MDa) dimeric ATP synthase complex; beyond its mitochondrial localization and complex membership, no direct mechanistic experiments have been performed specifically on this subunit."},"narrative":{"mechanistic_narrative":"PF3D7_0815400 (ATPTG3) is a putative ATP synthase-associated protein of Plasmodium falciparum that localizes to the mitochondrion, where it is a component of a large (>1 MDa) ATP synthase complex whose mass is consistent with dimeric assembly [PMID:21984828]. Its identification alongside six canonical ATP synthase subunits by epitope tagging and blue native gel electrophoresis places it within a complex whose apparent size exceeds the canonical subunit set, indicating additional, divergent subunits [PMID:21984828]. Beyond this mitochondrial localization and complex membership, no direct mechanistic experiments have been performed on ATPTG3 itself in the available corpus; its specific molecular role within the ATP synthase complex, its interaction interfaces, and any individual functional requirement remain uncharacterized.","teleology":[{"year":2011,"claim":"To establish whether ATPTG3 is a genuine mitochondrial ATP synthase component, epitope tagging placed it, with six canonical subunits, in the mitochondrion within a >1 MDa complex, establishing both its subcellular localization and its membership in a large dimeric assembly.","evidence":"Epitope tagging with immunofluorescence localization and blue native gel electrophoresis of mitochondrial membranes in transgenic P. falciparum","pmids":["21984828"],"confidence":"Medium","gaps":["ATPTG3 was one of seven subunits studied collectively and is not individually distinguished functionally","No direct evidence of ATPTG3's specific position or role within the complex","The identity of the non-canonical subunits inferred from the >1 MDa mass was not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Computational analysis addressed the question of how the Plasmodium ATP synthase membrane sector is constituted, identifying candidate divergent subunit a and subunit b and noting loss of an otherwise essential Arg in transmembrane helix IV, framing the complex as atypical relative to canonical orthologs.","evidence":"Computational identification from structural fingerprints and proteomics data of other protists","pmids":["19682605"],"confidence":"Low","gaps":["Prediction only, with no experimental validation of ATPTG3 specifically","Does not assign ATPTG3 to any structural role","No functional consequence of the divergent features tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To determine when the ATP synthase complex is required across the parasite life cycle, knockout of the β subunit (a sibling subunit of the same complex, not ATPTG3) showed the complex is dispensable for asexual blood-stage growth but essential for mosquito-stage viability.","evidence":"Genetic knockout of the ATP synthase β subunit in P. berghei with mosquito transmission assays and complementation cross","pmids":["25831536"],"confidence":"Low","gaps":["Finding concerns the β subunit, not ATPTG3; relevance is indirect via complex membership","ATPTG3 was not genetically manipulated in this study","Whether ATPTG3 is individually required for complex assembly or stage-specific function is untested"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Whether ATPTG3 is individually essential, its precise structural position within the dimeric ATP synthase, and its molecular contribution to complex assembly or function remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No gene disruption or knockdown of ATPTG3 itself has been reported","No structural placement of ATPTG3 within the complex","No biochemical characterization of ATPTG3's interactions distinct from bulk complex isolation"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ATP synthase complex (>1 MDa, dimeric) [#0]"],"partners":["CANONICAL ATP SYNTHASE SUBUNITS CO-LOCALIZED WITHIN THE SAME COMPLEX [#0]"],"other_free_text":["ATPTG3 is characterized only as a putative ATP synthase-associated protein and mitochondrial ATP synthase complex member; no direct functional experiments have been performed on this subunit itself.","Findings on the ATP synthase β subunit (dispensable in blood stage, essential in mosquito stage in P. berghei) [#2] and computational analysis of divergent membrane subunits [#1] concern other components of the complex, not ATPTG3 directly."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"2536737","id":"PMC_2536737","title":"Metabolic interconnection between the human malarial parasite Plasmodium falciparum and its host erythrocyte. Regulation of ATP levels by means of an adenylate translocator and adenylate kinase.","date":"1989","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2536737","citation_count":95,"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":"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":"2171868","id":"PMC_2171868","title":"Effect of mitochondrial inhibitors on adenosinetriphosphate levels in Plasmodium falciparum.","date":"1990","source":"Comparative biochemistry and physiology. B, Comparative biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/2171868","citation_count":47,"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":"22001249","id":"PMC_22001249","title":"The mechanism of erythrocyte invasion by the malarial parasite, Plasmodium falciparum.","date":"2011","source":"Seminars in cell & developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/22001249","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":"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}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6164,"output_tokens":1001,"usd":0.016754,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5795,"output_tokens":1839,"usd":0.037475,"stage2_stop_reason":"end_turn"},"total_usd":0.054229,"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\": \"PF3D7_0815400 (ATPTG3), along with six other epitope-tagged canonical ATP synthase subunits, was shown to localize to the mitochondrion of P. falciparum. Blue native gel electrophoresis of mitochondrial membranes indicated the ATP synthase complex (which includes ATPTG3) has a molecular mass greater than 1 million daltons, consistent with dimeric assembly, suggesting the presence of previously unknown subunits beyond the canonical set.\",\n      \"method\": \"Epitope tagging of subunits in transgenic P. falciparum lines with immunofluorescence localization; blue native gel electrophoresis of mitochondrial membranes\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by immunofluorescence in transgenic lines and native gel electrophoresis, single lab, two orthogonal methods; ATPTG3 is one of seven subunits studied collectively and is not individually distinguished in the abstract\",\n      \"pmids\": [\"21984828\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Bioinformatic/proteomics-based analysis identified candidates for ATP synthase subunit a and subunit b in Plasmodium spp., noting that transmembrane helix IV of ATP synthase subunit a lacks an essential Arg residue found in canonical orthologs, and that these membrane anchor subunits are highly divergent from canonical orthologs.\",\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 prediction only, no direct experimental validation of ATPTG3 specifically\",\n      \"pmids\": [\"19682605\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Knockout of the ATP synthase β subunit in P. berghei (a sibling subunit within the same complex that includes ATPTG3) was dispensable for asexual blood-stage growth but essential for mosquito-stage viability; ookinetes lacking the β subunit failed to produce oocysts or sporozoites. This establishes that the mitochondrial ATP synthase complex (of which ATPTG3 is a putative associated protein) is essential in the mosquito phase but not the blood stage.\",\n      \"method\": \"Genetic knockout (gene disruption) of ATP synthase β subunit in P. berghei with transmission assays in Anopheles stephensi mosquitoes and genetic complementation cross\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 2 / Weak — rigorous KO experiment, but finding is about the β subunit (a different gene); ATPTG3 itself was not experimentally manipulated; relevance to ATPTG3 is indirect via complex membership\",\n      \"pmids\": [\"25831536\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0815400 (ATPTG3) is a putative ATP synthase-associated protein in P. falciparum that localizes to the mitochondrion as part of a large (>1 MDa) dimeric ATP synthase complex; beyond its mitochondrial localization and complex membership, no direct mechanistic experiments have been performed specifically on this subunit.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0815400 (ATPTG3) is a putative ATP synthase-associated protein of Plasmodium falciparum that localizes to the mitochondrion, where it is a component of a large (>1 MDa) ATP synthase complex whose mass is consistent with dimeric assembly [#0]. Its identification alongside six canonical ATP synthase subunits by epitope tagging and blue native gel electrophoresis places it within a complex whose apparent size exceeds the canonical subunit set, indicating additional, divergent subunits [#0]. Beyond this mitochondrial localization and complex membership, no direct mechanistic experiments have been performed on ATPTG3 itself in the available corpus; its specific molecular role within the ATP synthase complex, its interaction interfaces, and any individual functional requirement remain uncharacterized.\",\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"To establish whether ATPTG3 is a genuine mitochondrial ATP synthase component, epitope tagging placed it, with six canonical subunits, in the mitochondrion within a >1 MDa complex, establishing both its subcellular localization and its membership in a large dimeric assembly.\",\n      \"evidence\": \"Epitope tagging with immunofluorescence localization and blue native gel electrophoresis of mitochondrial membranes in transgenic P. falciparum\",\n      \"pmids\": [\"21984828\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ATPTG3 was one of seven subunits studied collectively and is not individually distinguished functionally\",\n        \"No direct evidence of ATPTG3's specific position or role within the complex\",\n        \"The identity of the non-canonical subunits inferred from the >1 MDa mass was not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Computational analysis addressed the question of how the Plasmodium ATP synthase membrane sector is constituted, identifying candidate divergent subunit a and subunit b and noting loss of an otherwise essential Arg in transmembrane helix IV, framing the complex as atypical relative to canonical orthologs.\",\n      \"evidence\": \"Computational identification from structural fingerprints and proteomics data of other protists\",\n      \"pmids\": [\"19682605\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Prediction only, with no experimental validation of ATPTG3 specifically\",\n        \"Does not assign ATPTG3 to any structural role\",\n        \"No functional consequence of the divergent features tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To determine when the ATP synthase complex is required across the parasite life cycle, knockout of the β subunit (a sibling subunit of the same complex, not ATPTG3) showed the complex is dispensable for asexual blood-stage growth but essential for mosquito-stage viability.\",\n      \"evidence\": \"Genetic knockout of the ATP synthase β subunit in P. berghei with mosquito transmission assays and complementation cross\",\n      \"pmids\": [\"25831536\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Finding concerns the β subunit, not ATPTG3; relevance is indirect via complex membership\",\n        \"ATPTG3 was not genetically manipulated in this study\",\n        \"Whether ATPTG3 is individually required for complex assembly or stage-specific function is untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether ATPTG3 is individually essential, its precise structural position within the dimeric ATP synthase, and its molecular contribution to complex assembly or function remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No gene disruption or knockdown of ATPTG3 itself has been reported\",\n        \"No structural placement of ATPTG3 within the complex\",\n        \"No biochemical characterization of ATPTG3's interactions distinct from bulk complex isolation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"Mitochondrial ATP synthase complex (>1 MDa, dimeric) [#0]\"],\n    \"partners\": [\"Canonical ATP synthase subunits co-localized within the same complex [#0]\"],\n    \"other_free_text\": [\n      \"ATPTG3 is characterized only as a putative ATP synthase-associated protein and mitochondrial ATP synthase complex member; no direct functional experiments have been performed on this subunit itself.\",\n      \"Findings on the ATP synthase β subunit (dispensable in blood stage, essential in mosquito stage in P. berghei) [#2] and computational analysis of divergent membrane subunits [#1] concern other components of the complex, not ATPTG3 directly.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0815400","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0715400","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0505000","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATPTG3","evaluation":null}