{"gene":"PF3D7_0107400","run_date":"2026-09-07T10:55:51","timeline":{"discoveries":[{"year":2011,"finding":"ATPk (PF3D7_0107400), identified as a predicted ATP synthase subunit, was shown by epitope-tagging and immunofluorescence to localize to the mitochondrion of P. falciparum blood-stage parasites. Blue native gel electrophoresis of mitochondrial membranes indicated the ATP synthase complex exceeds 1 million daltons and is assembled as a dimer, consistent with the presence of previously unknown subunits beyond the canonical set. Attempts to disrupt the genes encoding the β and γ subunits were unsuccessful, suggesting the complex is essential in blood stages.","method":"Epitope-tagging of seven canonical ATP synthase subunits in transgenic P. falciparum lines; 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 experiment with epitope-tagged subunits and blue native gel electrophoresis in a single lab; gene disruption attempts provide functional inference but are negative results","pmids":["21984828"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2009,"finding":"Bioinformatic and proteomics-based analysis identified PF3D7_0107400 (ATPk) as a candidate subunit of the Fo sector of the ATP synthase in Plasmodium spp. The predicted transmembrane helix IV of the ATP synthase subunit a (a candidate corresponding to this locus) was noted to lack an essential Arg residue found in canonical orthologs, suggesting divergence from canonical ATP synthase architecture.","method":"Bioinformatic identification based on structural fingerprints and proteomics data from related protists","journal":"Mitochondrion","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic prediction with no direct experimental validation in Plasmodium","pmids":["19682605"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"ATPk (PF3D7_0107400) is a putative ATP synthase-associated subunit in P. falciparum that localizes to the parasite mitochondrion and is a component of a large (>1 MDa) dimeric ATP synthase complex assembled in the mitochondrial membrane; its precise catalytic or structural role within the complex has not been experimentally defined beyond complex membership."},"narrative":{"mechanistic_narrative":"ATPk (PF3D7_0107400) is a putative subunit of the mitochondrial ATP synthase in Plasmodium falciparum, established as a component of the complex rather than as an independently characterized enzyme [PMID:21984828]. Epitope-tagging and immunofluorescence localize ATPk to the mitochondrion of blood-stage parasites, and blue native gel electrophoresis of mitochondrial membranes shows the ATP synthase it belongs to exceeds 1 MDa and assembles as a dimer, consistent with a divergent complex containing subunits beyond the canonical set [PMID:21984828]. Failure to disrupt the genes encoding the catalytic β and γ subunits indicates the complex is essential in blood stages, though this evidence concerns those subunits rather than ATPk itself [PMID:21984828]. Beyond membership in this complex and its mitochondrial localization [PMID:21984828], and an earlier bioinformatic placement of the locus in the Fo sector [PMID:19682605], no catalytic or structural role for ATPk has been experimentally defined in the available corpus.","teleology":[{"year":2009,"claim":"Before any experimental work, it was unknown whether PF3D7_0107400 was part of the Plasmodium ATP synthase; bioinformatic and proteomic analysis first nominated it as a candidate Fo-sector subunit and flagged divergence from canonical architecture.","evidence":"Bioinformatic identification from structural fingerprints and proteomics data of related protists, noting loss of an essential Arg in a predicted transmembrane helix","pmids":["19682605"],"confidence":"Low","gaps":["Purely computational prediction with no direct experimental validation in Plasmodium","Assignment to the Fo sector and the subunit-a correspondence not confirmed biochemically","No evidence distinguishing ATPk's role from other predicted subunits"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"It was unknown where ATPk resides and how the parasite ATP synthase is organized; tagging and native-gel analysis placed ATPk in the mitochondrion within a >1 MDa dimeric complex, establishing it as a bona fide component of an unusually large ATP synthase.","evidence":"Epitope-tagging and immunofluorescence localization plus blue native gel electrophoresis of mitochondrial membranes in transgenic P. falciparum; attempted disruption of β and γ subunit genes","pmids":["21984828"],"confidence":"Medium","gaps":["ATPk's specific catalytic or structural function within the complex not defined","Essentiality demonstrated only for β and γ subunits, not directly for ATPk","Stoichiometry and position of ATPk in the dimer not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The precise role of ATPk within the ATP synthase — whether it contributes to catalysis, proton translocation, dimerization, or complex assembly — remains undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct genetic knockout/knockdown of ATPk to test essentiality","No structural model placing ATPk within the complex","No biochemical assignment of ATPk to a functional module (Fo vs F1)"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ATP synthase complex (>1 MDa, dimeric)"],"partners":[],"other_free_text":["ATPk (PF3D7_0107400) is established only as a component of the P. falciparum mitochondrial ATP synthase complex; its individual catalytic or structural role is not experimentally defined in the corpus.","Bioinformatic prediction placed the locus in the Fo sector and noted loss of a conserved Arg in a predicted transmembrane helix, indicating divergence from canonical ATP synthase architecture [#1].","Essentiality of the complex in blood stages was inferred from failed disruption of the β and γ subunit genes, not from direct targeting of ATPk [#0]."]}},"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":"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":"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":"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":"35626703","id":"PMC_35626703","title":"The Plasmodium falciparum CCCH Zinc Finger Protein ZNF4 Plays an Important Role in Gametocyte Exflagellation through the Regulation of Male Enriched Transcripts.","date":"2022","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/35626703","citation_count":20,"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":5451,"output_tokens":722,"usd":0.013591,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5396,"output_tokens":1652,"usd":0.03414,"stage2_stop_reason":"end_turn"},"total_usd":0.047731,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2011,\n      \"finding\": \"ATPk (PF3D7_0107400), identified as a predicted ATP synthase subunit, was shown by epitope-tagging and immunofluorescence to localize to the mitochondrion of P. falciparum blood-stage parasites. Blue native gel electrophoresis of mitochondrial membranes indicated the ATP synthase complex exceeds 1 million daltons and is assembled as a dimer, consistent with the presence of previously unknown subunits beyond the canonical set. Attempts to disrupt the genes encoding the β and γ subunits were unsuccessful, suggesting the complex is essential in blood stages.\",\n      \"method\": \"Epitope-tagging of seven canonical ATP synthase subunits in transgenic P. falciparum lines; 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 experiment with epitope-tagged subunits and blue native gel electrophoresis in a single lab; gene disruption attempts provide functional inference but are negative results\",\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 PF3D7_0107400 (ATPk) as a candidate subunit of the Fo sector of the ATP synthase in Plasmodium spp. The predicted transmembrane helix IV of the ATP synthase subunit a (a candidate corresponding to this locus) was noted to lack an essential Arg residue found in canonical orthologs, suggesting divergence from canonical ATP synthase architecture.\",\n      \"method\": \"Bioinformatic identification based on structural fingerprints and proteomics data from related protists\",\n      \"journal\": \"Mitochondrion\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic prediction with no direct experimental validation in Plasmodium\",\n      \"pmids\": [\"19682605\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"ATPk (PF3D7_0107400) is a putative ATP synthase-associated subunit in P. falciparum that localizes to the parasite mitochondrion and is a component of a large (>1 MDa) dimeric ATP synthase complex assembled in the mitochondrial membrane; its precise catalytic or structural role within the complex has not been experimentally defined beyond complex membership.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ATPk (PF3D7_0107400) is a putative subunit of the mitochondrial ATP synthase in Plasmodium falciparum, established as a component of the complex rather than as an independently characterized enzyme [#0]. Epitope-tagging and immunofluorescence localize ATPk to the mitochondrion of blood-stage parasites, and blue native gel electrophoresis of mitochondrial membranes shows the ATP synthase it belongs to exceeds 1 MDa and assembles as a dimer, consistent with a divergent complex containing subunits beyond the canonical set [#0]. Failure to disrupt the genes encoding the catalytic β and γ subunits indicates the complex is essential in blood stages, though this evidence concerns those subunits rather than ATPk itself [#0]. Beyond membership in this complex and its mitochondrial localization [#0], and an earlier bioinformatic placement of the locus in the Fo sector [#1], no catalytic or structural role for ATPk has been experimentally defined in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Before any experimental work, it was unknown whether PF3D7_0107400 was part of the Plasmodium ATP synthase; bioinformatic and proteomic analysis first nominated it as a candidate Fo-sector subunit and flagged divergence from canonical architecture.\",\n      \"evidence\": \"Bioinformatic identification from structural fingerprints and proteomics data of related protists, noting loss of an essential Arg in a predicted transmembrane helix\",\n      \"pmids\": [\"19682605\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Purely computational prediction with no direct experimental validation in Plasmodium\",\n        \"Assignment to the Fo sector and the subunit-a correspondence not confirmed biochemically\",\n        \"No evidence distinguishing ATPk's role from other predicted subunits\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"It was unknown where ATPk resides and how the parasite ATP synthase is organized; tagging and native-gel analysis placed ATPk in the mitochondrion within a >1 MDa dimeric complex, establishing it as a bona fide component of an unusually large ATP synthase.\",\n      \"evidence\": \"Epitope-tagging and immunofluorescence localization plus blue native gel electrophoresis of mitochondrial membranes in transgenic P. falciparum; attempted disruption of β and γ subunit genes\",\n      \"pmids\": [\"21984828\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"ATPk's specific catalytic or structural function within the complex not defined\",\n        \"Essentiality demonstrated only for β and γ subunits, not directly for ATPk\",\n        \"Stoichiometry and position of ATPk in the dimer not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise role of ATPk within the ATP synthase — whether it contributes to catalysis, proton translocation, dimerization, or complex assembly — remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct genetic knockout/knockdown of ATPk to test essentiality\",\n        \"No structural model placing ATPk within the complex\",\n        \"No biochemical assignment of ATPk to a functional module (Fo vs F1)\"\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\": [\"Mitochondrial ATP synthase complex (>1 MDa, dimeric)\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"ATPk (PF3D7_0107400) is established only as a component of the P. falciparum mitochondrial ATP synthase complex; its individual catalytic or structural role is not experimentally defined in the corpus.\",\n      \"Bioinformatic prediction placed the locus in the Fo sector and noted loss of a conserved Arg in a predicted transmembrane helix, indicating divergence from canonical ATP synthase architecture [#1].\",\n      \"Essentiality of the complex in blood stages was inferred from failed disruption of the β and γ subunit genes, not from direct targeting of ATPk [#0].\"\n    ]\n  }\n}\n```","audit_flag":{"gene":"PF3D7_0107400","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_0107400","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0206000","name":null,"product":"ATP synthase-associated protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATPk","evaluation":null}