{"gene":"PF3D7_0611300","run_date":"2026-09-08T12:51:26","timeline":{"discoveries":[{"year":2011,"finding":"PF3D7_0611300 (ATPTG2), 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 has a molecular mass greater than 1 million daltons, consistent with dimeric assembly, implying the presence of previously unknown subunits beyond the canonical ones. Attempts to disrupt the β and γ subunit genes were unsuccessful, suggesting the complex is essential in blood stages.","method":"Epitope tagging and immunolocalization; 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 and native gel electrophoresis in a single lab with multiple orthogonal methods, but ATPTG2 specifically is one of seven subunits studied and its individual role is not distinguished from the complex as a whole","pmids":["21984828"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Bioinformatic and proteomics-based analysis identified candidate 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, indicating these membrane anchor subunits are divergent from canonical eukaryotic counterparts.","method":"Computational structural fingerprint analysis and proteomics data comparison","journal":"Mitochondrion","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic prediction with proteomics support from other protists; no direct experimental validation of ATPTG2 specifically","pmids":["19682605"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0611300 (ATPTG2) is an ATP synthase-associated subunit that localizes to the P. falciparum mitochondrion and is incorporated into a large (>1 MDa) dimeric ATP synthase complex; beyond its membership in this complex, no specific catalytic or regulatory mechanism has been experimentally established for ATPTG2 itself."},"narrative":{"mechanistic_narrative":"PF3D7_0611300 (ATPTG2) is a mitochondrial ATP synthase-associated subunit of Plasmodium falciparum, identified as a component of the parasite's ATP synthase complex through epitope tagging and immunolocalization to the mitochondrion [PMID:21984828]. Blue native gel electrophoresis of mitochondrial membranes places this complex at greater than 1 MDa, consistent with a dimeric assembly and implying additional, non-canonical subunits beyond the seven canonical ones studied [PMID:21984828]. Although disruption of the β and γ subunits was unsuccessful, indicating the complex is essential in blood stages, this essentiality was established for those catalytic subunits and not for ATPTG2 itself [PMID:21984828]. Beyond its membership in this mitochondrial ATP synthase complex [PMID:21984828], no specific catalytic or regulatory function has been experimentally established for ATPTG2 in the available corpus.","teleology":[{"year":2011,"claim":"It was unknown whether P. falciparum assembles a canonical mitochondrial ATP synthase and which proteins constitute it; tagging and native gel analysis established that ATPTG2 co-localizes to the mitochondrion within a >1 MDa dimeric complex, placing it among the subunits of the parasite ATP synthase.","evidence":"Epitope tagging with immunolocalization and blue native gel electrophoresis of mitochondrial membranes, plus attempted gene disruption of β and γ subunits, in P. falciparum","pmids":["21984828"],"confidence":"Medium","gaps":["ATPTG2's individual catalytic or structural role is not distinguished from the complex as a whole","Essentiality was tested for the β and γ subunits, not for ATPTG2","No stoichiometry, topology, or interaction map for ATPTG2 within the complex"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"claim":"Whether the membrane-anchor subunits of the Plasmodium ATP synthase are conserved was uncertain; computational and proteomic analysis showed subunit a lacks an essential Arg in transmembrane helix IV, indicating these membrane subunits are divergent from canonical eukaryotic orthologs.","evidence":"Computational structural fingerprint analysis and comparison against proteomics data in Plasmodium spp.","pmids":["19682605"],"confidence":"Low","gaps":["Bioinformatic prediction without direct experimental validation, and not specific to ATPTG2","Does not establish whether ATPTG2 is one of the divergent membrane subunits","No functional consequence of the divergence tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular contribution of ATPTG2 to ATP synthase assembly, catalysis, or dimerization, and whether ATPTG2 itself is essential, remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No ATPTG2-specific knockout or knockdown phenotype","No structural placement of ATPTG2 within the dimeric complex","No defined biochemical activity for ATPTG2"],"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 INCLUDING Β AND Γ SUBUNITS (CO-MEMBERS OF THE SAME COMPLEX) [#0]"],"other_free_text":["ATPTG2 is characterized in the corpus only as a mitochondrion-localized member of the P. falciparum ATP synthase complex; no catalytic or regulatory role specific to ATPTG2 has been established [#0].","Bioinformatic analysis of Plasmodium ATP synthase membrane-anchor subunits found them divergent from canonical eukaryotic orthologs, but this was not shown for ATPTG2 specifically [#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":"31812035","id":"PMC_31812035","title":"Harmicines - harmine and cinnamic acid hybrids as novel antiplasmodial hits.","date":"2019","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/31812035","citation_count":29,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35551033","id":"PMC_35551033","title":"Design and synthesis of harmiquins, harmine and chloroquine hybrids as potent antiplasmodial agents.","date":"2022","source":"European journal of medicinal chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/35551033","citation_count":28,"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":6909,"output_tokens":689,"usd":0.015531,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5359,"output_tokens":1624,"usd":0.033697,"stage2_stop_reason":"end_turn"},"total_usd":0.049228,"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_0611300 (ATPTG2), 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 has a molecular mass greater than 1 million daltons, consistent with dimeric assembly, implying the presence of previously unknown subunits beyond the canonical ones. Attempts to disrupt the β and γ subunit genes were unsuccessful, suggesting the complex is essential in blood stages.\",\n      \"method\": \"Epitope tagging and immunolocalization; 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 and native gel electrophoresis in a single lab with multiple orthogonal methods, but ATPTG2 specifically is one of seven subunits studied and its individual role is not distinguished from the complex as a whole\",\n      \"pmids\": [\"21984828\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Bioinformatic and proteomics-based analysis identified candidate 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, indicating these membrane anchor subunits are divergent from canonical eukaryotic counterparts.\",\n      \"method\": \"Computational structural fingerprint analysis and proteomics data comparison\",\n      \"journal\": \"Mitochondrion\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic prediction with proteomics support from other protists; no direct experimental validation of ATPTG2 specifically\",\n      \"pmids\": [\"19682605\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0611300 (ATPTG2) is an ATP synthase-associated subunit that localizes to the P. falciparum mitochondrion and is incorporated into a large (>1 MDa) dimeric ATP synthase complex; beyond its membership in this complex, no specific catalytic or regulatory mechanism has been experimentally established for ATPTG2 itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0611300 (ATPTG2) is a mitochondrial ATP synthase-associated subunit of Plasmodium falciparum, identified as a component of the parasite's ATP synthase complex through epitope tagging and immunolocalization to the mitochondrion [#0]. Blue native gel electrophoresis of mitochondrial membranes places this complex at greater than 1 MDa, consistent with a dimeric assembly and implying additional, non-canonical subunits beyond the seven canonical ones studied [#0]. Although disruption of the β and γ subunits was unsuccessful, indicating the complex is essential in blood stages, this essentiality was established for those catalytic subunits and not for ATPTG2 itself [#0]. Beyond its membership in this mitochondrial ATP synthase complex [#0], no specific catalytic or regulatory function has been experimentally established for ATPTG2 in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"It was unknown whether P. falciparum assembles a canonical mitochondrial ATP synthase and which proteins constitute it; tagging and native gel analysis established that ATPTG2 co-localizes to the mitochondrion within a >1 MDa dimeric complex, placing it among the subunits of the parasite ATP synthase.\",\n      \"evidence\": \"Epitope tagging with immunolocalization and blue native gel electrophoresis of mitochondrial membranes, plus attempted gene disruption of β and γ subunits, in P. falciparum\",\n      \"pmids\": [\"21984828\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ATPTG2's individual catalytic or structural role is not distinguished from the complex as a whole\",\n        \"Essentiality was tested for the β and γ subunits, not for ATPTG2\",\n        \"No stoichiometry, topology, or interaction map for ATPTG2 within the complex\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Whether the membrane-anchor subunits of the Plasmodium ATP synthase are conserved was uncertain; computational and proteomic analysis showed subunit a lacks an essential Arg in transmembrane helix IV, indicating these membrane subunits are divergent from canonical eukaryotic orthologs.\",\n      \"evidence\": \"Computational structural fingerprint analysis and comparison against proteomics data in Plasmodium spp.\",\n      \"pmids\": [\"19682605\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Bioinformatic prediction without direct experimental validation, and not specific to ATPTG2\",\n        \"Does not establish whether ATPTG2 is one of the divergent membrane subunits\",\n        \"No functional consequence of the divergence tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular contribution of ATPTG2 to ATP synthase assembly, catalysis, or dimerization, and whether ATPTG2 itself is essential, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No ATPTG2-specific knockout or knockdown phenotype\",\n        \"No structural placement of ATPTG2 within the dimeric complex\",\n        \"No defined biochemical activity for ATPTG2\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\n      \"Mitochondrial ATP synthase complex (>1 MDa, dimeric) [#0]\"\n    ],\n    \"partners\": [\n      \"Canonical ATP synthase subunits including β and γ subunits (co-members of the same complex) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"ATPTG2 is characterized in the corpus only as a mitochondrion-localized member of the P. falciparum ATP synthase complex; no catalytic or regulatory role specific to ATPTG2 has been established [#0].\",\n      \"Bioinformatic analysis of Plasmodium ATP synthase membrane-anchor subunits found them divergent from canonical eukaryotic orthologs, but this was not shown for ATPTG2 specifically [#1].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0611300","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_0611300","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0109600","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1139100","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATPTG2","evaluation":null}