{"gene":"PF3D7_0622600","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2021,"finding":"QCR9 (PF3D7_0622600) was identified as a canonical subunit of the cytochrome bc1 complex (Complex III) in P. falciparum by complexome profiling, where it comigrated with other CIII subunits at an apparent molecular mass of ~730 kDa in both asexual blood stage parasites and gametocytes, establishing its physical membership in the mitochondrial Complex III.","method":"Complexome profiling (blue native PAGE coupled to mass spectrometry) across asexual blood stages and gametocyte stages","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complexome profiling with quantitative comigration analysis across two life stages in a single study; single lab but orthogonal fractionation and MS methods","pmids":["34155201"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"QCR9 (PF3D7_0622600) was specifically enriched by a photoactivatable derivative of 9-methoxystrobilurin G (9MG) in chemoproteomic target profiling, consistent with 9MG targeting cytochrome b and Complex III function; inhibition of Complex III (ubiquinone cytochrome c reductase) activity by 9MG was confirmed using P. falciparum extract.","method":"Chemoproteomic-based target profiling using a photoactivatable 9MG derivative; ubiquinone cytochrome c reductase activity assay using P. falciparum extract","journal":"Molecular omics","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — chemical proteomics enrichment plus enzymatic activity assay in a single study; single lab, enrichment does not establish direct binding to QCR9 specifically","pmids":["39262389"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"},{"species":"Plasmodium falciparum","strain":"Dd2"}]},{"year":2025,"finding":"QCR9 (PF3D7_0622600) showed significant stabilisation at 15% AEA solvent concentration in solvent proteome profiling (SPP) experiments with atovaquone, confirming its physical association within mitochondrial Complex III in P. falciparum (although it did not reach significance in the overall AUC analysis).","method":"Solvent-induced proteome profiling (SPP) with atovaquone treatment of P. falciparum lysates; individual solvent percentage analysis","journal":"International journal for parasitology. Drugs and drug resistance","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single proteomics method; QCR9 stabilisation was only significant at one solvent concentration, not in the primary AUC analysis","pmids":["41308470"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"QCR9 (PF3D7_0622600) is a canonical subunit of the P. falciparum mitochondrial cytochrome bc1 complex (Complex III), physically comigrating with other CIII components at ~730 kDa in both asexual blood stages and gametocytes, and is associated with Complex III function as shown by chemoproteomic and solvent proteome profiling experiments with Complex III inhibitors."},"narrative":{"mechanistic_narrative":"QCR9 (PF3D7_0622600) is a subunit of the mitochondrial cytochrome bc1 complex (Complex III) of P. falciparum, identified by complexome profiling as comigrating with other Complex III subunits at ~730 kDa in both asexual blood stages and gametocytes, establishing its physical membership in the complex across life stages [PMID:34155201]. Its association with Complex III is further supported by chemoproteomic enrichment with a photoactivatable derivative of the Complex III inhibitor 9-methoxystrobilurin G, in the same study that confirmed 9MG inhibits ubiquinone-cytochrome c reductase activity in P. falciparum extract [PMID:39262389]. Beyond its membership in Complex III and its co-behavior with the complex under inhibitor challenge, no QCR9-specific molecular function, structure, or phenotype has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Whether PF3D7_0622600 belongs to a defined mitochondrial complex was unresolved; complexome profiling placed it physically within Complex III across two life stages, establishing it as a canonical bc1 subunit rather than an unassigned protein.","evidence":"Complexome profiling (blue native PAGE coupled to mass spectrometry) across asexual blood stages and gametocytes","pmids":["34155201"],"confidence":"Medium","gaps":["Comigration establishes co-assembly but not the specific structural position or contacts of QCR9 within Complex III","No functional consequence of QCR9 for complex assembly or activity was tested","No direct genetic perturbation of QCR9 was performed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"It was unknown whether QCR9 co-behaves with Complex III under pharmacological targeting; chemoproteomic enrichment by a Complex III inhibitor derivative, alongside confirmed inhibition of ubiquinone-cytochrome c reductase activity, tied QCR9 to functionally engaged Complex III.","evidence":"Chemoproteomic target profiling with a photoactivatable 9MG derivative plus ubiquinone-cytochrome c reductase activity assay on P. falciparum extract","pmids":["39262389"],"confidence":"Medium","gaps":["Enrichment does not establish direct binding of the inhibitor to QCR9 specifically rather than to the complex","The catalytic subunit targeted is cytochrome b, not QCR9; QCR9's own role in inhibitor action is undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":"3D7"},{"species":"Plasmodium falciparum","strain":"Dd2"}]},{"year":2025,"claim":"Solvent proteome profiling with atovaquone tested whether QCR9 shows drug-linked thermodynamic behavior consistent with Complex III association, adding orthogonal support for its physical membership.","evidence":"Solvent-induced proteome profiling (SPP) of atovaquone-treated P. falciparum lysates, individual solvent-percentage analysis","pmids":["41308470"],"confidence":"Low","gaps":["Stabilisation was significant only at a single solvent concentration and did not reach significance in the primary AUC analysis","Single lab and single method; does not demonstrate direct atovaquone binding to QCR9"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific molecular contribution of QCR9 to Complex III — its role in complex assembly, stability, or electron transfer, and the phenotypic consequence of its loss — remains unaddressed in the corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout, knockdown, or rescue of QCR9 reported","No structural model localizing QCR9 within Complex III","No QCR9-specific (as opposed to complex-level) biochemical function established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial cytochrome bc1 complex (Complex III), ~730 kDa"],"partners":["OTHER CYTOCHROME BC1 COMPLEX (COMPLEX III) SUBUNITS (CO-MIGRATING; INDIVIDUAL PARTNERS NOT SPECIFIED IN CORPUS)"],"other_free_text":["QCR9 (PF3D7_0622600) is characterized in the corpus only as a physical member of P. falciparum mitochondrial Complex III; no QCR9-specific molecular function, structure, or loss-of-function phenotype has been established.","Association with Complex III is supported across asexual blood stages and gametocytes and under challenge with Complex III inhibitors 9-methoxystrobilurin G and atovaquone [#0, #1, #2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"39262389","id":"PMC_39262389","title":"Antimalarial mechanism of action of the natural product 9-methoxystrobilurin G.","date":"2024","source":"Molecular omics","url":"https://pubmed.ncbi.nlm.nih.gov/39262389","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41308470","id":"","title":"Validation of solvent proteome profiling for antimalarial drug target deconvolution.","date":"2025","source":"International journal for parasitology. Drugs and drug resistance","url":"https://pubmed.ncbi.nlm.nih.gov/41308470","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36624300","id":"","title":"Protein KIC5 is a novel regulator of artemisinin stress response in the malaria parasite Plasmodium falciparum.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36624300","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34155201","id":"","title":"Composition and stage dynamics of mitochondrial complexes in Plasmodium falciparum.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34155201","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["QCR9"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7363,"output_tokens":1002,"usd":0.018559,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5738,"output_tokens":1962,"usd":0.03887,"stage2_stop_reason":"end_turn"},"total_usd":0.057429,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2021,\n      \"finding\": \"QCR9 (PF3D7_0622600) was identified as a canonical subunit of the cytochrome bc1 complex (Complex III) in P. falciparum by complexome profiling, where it comigrated with other CIII subunits at an apparent molecular mass of ~730 kDa in both asexual blood stage parasites and gametocytes, establishing its physical membership in the mitochondrial Complex III.\",\n      \"method\": \"Complexome profiling (blue native PAGE coupled to mass spectrometry) across asexual blood stages and gametocyte stages\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complexome profiling with quantitative comigration analysis across two life stages in a single study; single lab but orthogonal fractionation and MS methods\",\n      \"pmids\": [\"34155201\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"QCR9 (PF3D7_0622600) was specifically enriched by a photoactivatable derivative of 9-methoxystrobilurin G (9MG) in chemoproteomic target profiling, consistent with 9MG targeting cytochrome b and Complex III function; inhibition of Complex III (ubiquinone cytochrome c reductase) activity by 9MG was confirmed using P. falciparum extract.\",\n      \"method\": \"Chemoproteomic-based target profiling using a photoactivatable 9MG derivative; ubiquinone cytochrome c reductase activity assay using P. falciparum extract\",\n      \"journal\": \"Molecular omics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — chemical proteomics enrichment plus enzymatic activity assay in a single study; single lab, enrichment does not establish direct binding to QCR9 specifically\",\n      \"pmids\": [\"39262389\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"QCR9 (PF3D7_0622600) showed significant stabilisation at 15% AEA solvent concentration in solvent proteome profiling (SPP) experiments with atovaquone, confirming its physical association within mitochondrial Complex III in P. falciparum (although it did not reach significance in the overall AUC analysis).\",\n      \"method\": \"Solvent-induced proteome profiling (SPP) with atovaquone treatment of P. falciparum lysates; individual solvent percentage analysis\",\n      \"journal\": \"International journal for parasitology. Drugs and drug resistance\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single proteomics method; QCR9 stabilisation was only significant at one solvent concentration, not in the primary AUC analysis\",\n      \"pmids\": [\"41308470\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"QCR9 (PF3D7_0622600) is a canonical subunit of the P. falciparum mitochondrial cytochrome bc1 complex (Complex III), physically comigrating with other CIII components at ~730 kDa in both asexual blood stages and gametocytes, and is associated with Complex III function as shown by chemoproteomic and solvent proteome profiling experiments with Complex III inhibitors.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"QCR9 (PF3D7_0622600) is a subunit of the mitochondrial cytochrome bc1 complex (Complex III) of P. falciparum, identified by complexome profiling as comigrating with other Complex III subunits at ~730 kDa in both asexual blood stages and gametocytes, establishing its physical membership in the complex across life stages [#0]. Its association with Complex III is further supported by chemoproteomic enrichment with a photoactivatable derivative of the Complex III inhibitor 9-methoxystrobilurin G, in the same study that confirmed 9MG inhibits ubiquinone-cytochrome c reductase activity in P. falciparum extract [#1]. Beyond its membership in Complex III and its co-behavior with the complex under inhibitor challenge, no QCR9-specific molecular function, structure, or phenotype has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PF3D7_0622600 belongs to a defined mitochondrial complex was unresolved; complexome profiling placed it physically within Complex III across two life stages, establishing it as a canonical bc1 subunit rather than an unassigned protein.\",\n      \"evidence\": \"Complexome profiling (blue native PAGE coupled to mass spectrometry) across asexual blood stages and gametocytes\",\n      \"pmids\": [\"34155201\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Comigration establishes co-assembly but not the specific structural position or contacts of QCR9 within Complex III\",\n        \"No functional consequence of QCR9 for complex assembly or activity was tested\",\n        \"No direct genetic perturbation of QCR9 was performed\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"It was unknown whether QCR9 co-behaves with Complex III under pharmacological targeting; chemoproteomic enrichment by a Complex III inhibitor derivative, alongside confirmed inhibition of ubiquinone-cytochrome c reductase activity, tied QCR9 to functionally engaged Complex III.\",\n      \"evidence\": \"Chemoproteomic target profiling with a photoactivatable 9MG derivative plus ubiquinone-cytochrome c reductase activity assay on P. falciparum extract\",\n      \"pmids\": [\"39262389\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Enrichment does not establish direct binding of the inhibitor to QCR9 specifically rather than to the complex\",\n        \"The catalytic subunit targeted is cytochrome b, not QCR9; QCR9's own role in inhibitor action is undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"3D7\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Solvent proteome profiling with atovaquone tested whether QCR9 shows drug-linked thermodynamic behavior consistent with Complex III association, adding orthogonal support for its physical membership.\",\n      \"evidence\": \"Solvent-induced proteome profiling (SPP) of atovaquone-treated P. falciparum lysates, individual solvent-percentage analysis\",\n      \"pmids\": [\"41308470\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Stabilisation was significant only at a single solvent concentration and did not reach significance in the primary AUC analysis\",\n        \"Single lab and single method; does not demonstrate direct atovaquone binding to QCR9\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular contribution of QCR9 to Complex III — its role in complex assembly, stability, or electron transfer, and the phenotypic consequence of its loss — remains unaddressed in the corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout, knockdown, or rescue of QCR9 reported\",\n        \"No structural model localizing QCR9 within Complex III\",\n        \"No QCR9-specific (as opposed to complex-level) biochemical function established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0022904\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\"Mitochondrial cytochrome bc1 complex (Complex III), ~730 kDa\"],\n    \"partners\": [\"Other cytochrome bc1 complex (Complex III) subunits (co-migrating; individual partners not specified in corpus)\"],\n    \"other_free_text\": [\n      \"QCR9 (PF3D7_0622600) is characterized in the corpus only as a physical member of P. falciparum mitochondrial Complex III; no QCR9-specific molecular function, structure, or loss-of-function phenotype has been established.\",\n      \"Association with Complex III is supported across asexual blood stages and gametocytes and under challenge with Complex III inhibitors 9-methoxystrobilurin G and atovaquone [#0, #1, #2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0622600","name":null,"product":"cytochrome b-c1 complex subunit 9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1121500","name":null,"product":"cytochrome b-c1 complex subunit 9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1127600","name":null,"product":"cytochrome b-c1 complex subunit 9, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"QCR9","evaluation":null}