{"gene":"PF3D7_0708700","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2021,"finding":"Complexome profiling of P. falciparum identified PF3D7_0708700 (COX4) as a component of the mitochondrial respiratory chain Complex IV (cytochrome c oxidase). The complex showed remarkably divergent composition compared to canonical model organisms, with clade-specific additions, and its components were up to 40-fold more prevalent in gametocytes than in asexual blood stages.","method":"Complexome profiling (native PAGE coupled to mass spectrometry) across asexual blood stages and gametocyte stages of P. falciparum","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — complexome profiling with MS across multiple life stages in a single rigorous study; establishes complex membership and stage dynamics but no functional mutagenesis or reconstitution","pmids":["34155201"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0708700 (COX4) is a nuclear-encoded subunit of the divergently composed mitochondrial respiratory chain Complex IV in P. falciparum, with its complex showing markedly increased abundance in gametocytes relative to asexual blood stages, consistent with the metabolic switch to oxidative phosphorylation in the transmissible stage."},"narrative":{"mechanistic_narrative":"PF3D7_0708700 (COX4) is a component of the mitochondrial respiratory chain Complex IV (cytochrome c oxidase) in Plasmodium falciparum, identified by complexome profiling as part of a complex whose composition is markedly divergent from canonical model organisms, including clade-specific additions [PMID:34155201]. The Complex IV to which COX4 belongs is up to 40-fold more prevalent in gametocytes than in asexual blood stages, consistent with an increased reliance on oxidative phosphorylation in the transmissible stage [PMID:34155201]. Beyond its assignment as a Complex IV subunit and this stage-dependent abundance pattern, no function, essentiality, or mechanistic role specific to PF3D7_0708700 has been characterized in the available corpus.","teleology":[{"year":2021,"claim":"Whether PF3D7_0708700 participates in the P. falciparum respiratory chain was unknown; complexome profiling assigned it to Complex IV and revealed that this cytochrome c oxidase has a divergent, clade-specific composition and is strongly enriched in gametocytes.","evidence":"Complexome profiling (native PAGE coupled to mass spectrometry) across asexual blood stages and gametocytes of P. falciparum","pmids":["34155201"],"confidence":"Medium","gaps":["No functional mutagenesis, knockout, or reconstitution establishing the specific role of PF3D7_0708700 within Complex IV","The structural placement and interaction partners of PF3D7_0708700 within the divergent complex are not resolved","The mechanism driving the gametocyte-specific increase in complex abundance is not addressed"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether PF3D7_0708700 is individually required for Complex IV assembly or activity, and what molecular contribution it makes distinct from the complex as a whole.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No gene-specific loss-of-function or biochemical assay for PF3D7_0708700","No enzymatic activity attributed to PF3D7_0708700 itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial respiratory chain Complex IV (cytochrome c oxidase)"],"partners":[],"other_free_text":["Complex IV containing PF3D7_0708700 has a divergent, clade-specific composition relative to canonical model organisms [#0]","Complex IV components are up to 40-fold more abundant in gametocytes than asexual blood stages [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"34155201","id":"PMC_34155201","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":92,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41820854","id":"","title":"Differential expression of mitochondria-associated genes in clinical samples of Plasmodium falciparum showing severe manifestations.","date":"2026","source":"BMC genomics","url":"https://pubmed.ncbi.nlm.nih.gov/41820854","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24609083","id":"","title":"Circular RNA is expressed across the eukaryotic tree of life.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/24609083","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX4"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5023,"output_tokens":388,"usd":0.010445,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4901,"output_tokens":1164,"usd":0.026802,"stage2_stop_reason":"end_turn"},"total_usd":0.037247,"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\": \"Complexome profiling of P. falciparum identified PF3D7_0708700 (COX4) as a component of the mitochondrial respiratory chain Complex IV (cytochrome c oxidase). The complex showed remarkably divergent composition compared to canonical model organisms, with clade-specific additions, and its components were up to 40-fold more prevalent in gametocytes than in asexual blood stages.\",\n      \"method\": \"Complexome profiling (native PAGE coupled to mass spectrometry) across asexual blood stages and gametocyte stages of P. falciparum\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — complexome profiling with MS across multiple life stages in a single rigorous study; establishes complex membership and stage dynamics but no functional mutagenesis or reconstitution\",\n      \"pmids\": [\"34155201\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0708700 (COX4) is a nuclear-encoded subunit of the divergently composed mitochondrial respiratory chain Complex IV in P. falciparum, with its complex showing markedly increased abundance in gametocytes relative to asexual blood stages, consistent with the metabolic switch to oxidative phosphorylation in the transmissible stage.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0708700 (COX4) is a component of the mitochondrial respiratory chain Complex IV (cytochrome c oxidase) in Plasmodium falciparum, identified by complexome profiling as part of a complex whose composition is markedly divergent from canonical model organisms, including clade-specific additions [#0]. The Complex IV to which COX4 belongs is up to 40-fold more prevalent in gametocytes than in asexual blood stages, consistent with an increased reliance on oxidative phosphorylation in the transmissible stage [#0]. Beyond its assignment as a Complex IV subunit and this stage-dependent abundance pattern, no function, essentiality, or mechanistic role specific to PF3D7_0708700 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"Whether PF3D7_0708700 participates in the P. falciparum respiratory chain was unknown; complexome profiling assigned it to Complex IV and revealed that this cytochrome c oxidase has a divergent, clade-specific composition and is strongly enriched in gametocytes.\",\n      \"evidence\": \"Complexome profiling (native PAGE coupled to mass spectrometry) across asexual blood stages and gametocytes of P. falciparum\",\n      \"pmids\": [\n        \"34155201\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional mutagenesis, knockout, or reconstitution establishing the specific role of PF3D7_0708700 within Complex IV\",\n        \"The structural placement and interaction partners of PF3D7_0708700 within the divergent complex are not resolved\",\n        \"The mechanism driving the gametocyte-specific increase in complex abundance is not addressed\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether PF3D7_0708700 is individually required for Complex IV assembly or activity, and what molecular contribution it makes distinct from the complex as a whole.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No gene-specific loss-of-function or biochemical assay for PF3D7_0708700\",\n        \"No enzymatic activity attributed to PF3D7_0708700 itself\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006119\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"Mitochondrial respiratory chain Complex IV (cytochrome c oxidase)\"\n    ],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Complex IV containing PF3D7_0708700 has a divergent, clade-specific composition relative to canonical model organisms [#0]\",\n      \"Complex IV components are up to 40-fold more abundant in gametocytes than asexual blood stages [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0708700","name":null,"product":"cytochrome c oxidase subunit 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1219200","name":null,"product":"cytochrome c oxidase subunit 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0107300","name":null,"product":"cytochrome c oxidase subunit 4, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"COX4","evaluation":null}