{"gene":"TG_226590","gene_symbol":"COX2a","run_date":"2026-09-08T11:06:45","timeline":{"discoveries":[{"year":2007,"finding":"COX2A and COX2B are subunits of the mitochondrial cytochrome c oxidase (Complex IV) in Toxoplasma gondii, as demonstrated by their co-migration with Complex IV on Blue Native/2D electrophoresis and immunochemical detection in mitochondria-enriched fractions exhibiting cyanide-sensitive oxygen uptake.","method":"Blue Native Electrophoresis followed by 2D electrophoresis, mass spectrometry, immunochemical staining with antibodies against synthetic peptide (COX2A) and hexa-histidine-tagged recombinant protein (COX2B), mitochondrial fractionation with oxygen uptake assay","journal":"Biochimica et biophysica acta","confidence":"High","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (subcellular fractionation, BN-PAGE, MS, immunochemistry, functional oxygen uptake assay) in a single study establishing direct subunit membership in Complex IV","pmids":["18036550"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2007,"finding":"The mitochondrial targeting sequence of the apicomplexan COX2A precursor is processed differently than that of its chlorophycean algal counterpart (Polytomella sp.), as indicated by a difference in apparent molecular mass of the mature COX2A subunit between the two organisms.","method":"SDS-PAGE/immunochemical comparison of mature COX2A molecular mass between T. gondii and Polytomella sp.","journal":"Biochimica et biophysica acta","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single indirect observation (molecular mass difference) from a single lab without direct mutagenesis or processing assay","pmids":["18036550"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"COX2A is a nuclear-encoded subunit of the mitochondrial cytochrome c oxidase (Complex IV) in Toxoplasma gondii, localizing to the mitochondria where it participates in cyanide-sensitive electron transport, and its precursor undergoes mitochondrial targeting sequence processing that differs from its algal ortholog."},"narrative":{"mechanistic_narrative":"COX2a is a nuclear-encoded subunit of the mitochondrial cytochrome c oxidase (Complex IV) in Toxoplasma gondii, where together with COX2B it assembles into the functional complex and supports cyanide-sensitive electron transport [PMID:18036550]. Its identity as a Complex IV component is established by co-migration with the complex on Blue Native/2D electrophoresis, mass spectrometry, and immunochemical detection in mitochondria-enriched fractions that exhibit cyanide-sensitive oxygen uptake [PMID:18036550]. Beyond its subunit membership and mitochondrial localization, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2007,"claim":"Whether the apicomplexan COX2a polypeptide is a bona fide component of respiratory Complex IV was unresolved; showing its co-migration with Complex IV in respiring mitochondria established it as a genuine subunit of cytochrome c oxidase.","evidence":"Blue Native/2D electrophoresis, mass spectrometry, and immunochemistry of mitochondria-enriched fractions with cyanide-sensitive oxygen uptake in T. gondii","pmids":["18036550"],"confidence":"High","gaps":["No structural model or stoichiometry of COX2a within Complex IV","Functional contribution of COX2a to electron transport not tested by loss-of-function","Relationship and assembly relative to COX2B not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2007,"claim":"It was unknown whether apicomplexan COX2a precursor maturation resembles that of the split-COX2 chlorophycean algae; a difference in the apparent mass of the mature protein indicated that the mitochondrial targeting sequence is processed differently between the two lineages.","evidence":"SDS-PAGE/immunochemical comparison of mature COX2a molecular mass between T. gondii and Polytomella sp.","pmids":["18036550"],"confidence":"Low","gaps":["Single indirect observation (mass difference) without direct mutagenesis or a processing assay","Processing site and responsible peptidase not identified","Functional consequence of the differential processing unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The functional requirement of COX2a for respiration, its assembly pathway with COX2B, and its structural arrangement within Complex IV remain uncharacterized.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic loss-of-function or rescue data","No structural or stoichiometric characterization","Assembly relationship with COX2B undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial cytochrome c oxidase (Complex IV)"],"partners":["COX2B"],"other_free_text":["Mitochondrial targeting sequence of the COX2a precursor is processed differently in T. gondii than in the chlorophycean alga Polytomella sp. (indirect mass evidence) [#1]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"18036550","id":"PMC_18036550","title":"The polypeptides COX2A and COX2B are essential components of the mitochondrial cytochrome c oxidase of Toxoplasma gondii.","date":"2007","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/18036550","citation_count":8,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2986,"output_tokens":657,"usd":0.009406,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5406,"output_tokens":1479,"usd":0.032003,"stage2_stop_reason":"end_turn"},"total_usd":0.041409,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2007,\n      \"finding\": \"COX2A and COX2B are subunits of the mitochondrial cytochrome c oxidase (Complex IV) in Toxoplasma gondii, as demonstrated by their co-migration with Complex IV on Blue Native/2D electrophoresis and immunochemical detection in mitochondria-enriched fractions exhibiting cyanide-sensitive oxygen uptake.\",\n      \"method\": \"Blue Native Electrophoresis followed by 2D electrophoresis, mass spectrometry, immunochemical staining with antibodies against synthetic peptide (COX2A) and hexa-histidine-tagged recombinant protein (COX2B), mitochondrial fractionation with oxygen uptake assay\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (subcellular fractionation, BN-PAGE, MS, immunochemistry, functional oxygen uptake assay) in a single study establishing direct subunit membership in Complex IV\",\n      \"pmids\": [\"18036550\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"The mitochondrial targeting sequence of the apicomplexan COX2A precursor is processed differently than that of its chlorophycean algal counterpart (Polytomella sp.), as indicated by a difference in apparent molecular mass of the mature COX2A subunit between the two organisms.\",\n      \"method\": \"SDS-PAGE/immunochemical comparison of mature COX2A molecular mass between T. gondii and Polytomella sp.\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single indirect observation (molecular mass difference) from a single lab without direct mutagenesis or processing assay\",\n      \"pmids\": [\"18036550\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"COX2A is a nuclear-encoded subunit of the mitochondrial cytochrome c oxidase (Complex IV) in Toxoplasma gondii, localizing to the mitochondria where it participates in cyanide-sensitive electron transport, and its precursor undergoes mitochondrial targeting sequence processing that differs from its algal ortholog.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"COX2a is a nuclear-encoded subunit of the mitochondrial cytochrome c oxidase (Complex IV) in Toxoplasma gondii, where together with COX2B it assembles into the functional complex and supports cyanide-sensitive electron transport [#0]. Its identity as a Complex IV component is established by co-migration with the complex on Blue Native/2D electrophoresis, mass spectrometry, and immunochemical detection in mitochondria-enriched fractions that exhibit cyanide-sensitive oxygen uptake [#0]. Beyond its subunit membership and mitochondrial localization, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2007,\n      \"claim\": \"Whether the apicomplexan COX2a polypeptide is a bona fide component of respiratory Complex IV was unresolved; showing its co-migration with Complex IV in respiring mitochondria established it as a genuine subunit of cytochrome c oxidase.\",\n      \"evidence\": \"Blue Native/2D electrophoresis, mass spectrometry, and immunochemistry of mitochondria-enriched fractions with cyanide-sensitive oxygen uptake in T. gondii\",\n      \"pmids\": [\"18036550\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model or stoichiometry of COX2a within Complex IV\",\n        \"Functional contribution of COX2a to electron transport not tested by loss-of-function\",\n        \"Relationship and assembly relative to COX2B not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"It was unknown whether apicomplexan COX2a precursor maturation resembles that of the split-COX2 chlorophycean algae; a difference in the apparent mass of the mature protein indicated that the mitochondrial targeting sequence is processed differently between the two lineages.\",\n      \"evidence\": \"SDS-PAGE/immunochemical comparison of mature COX2a molecular mass between T. gondii and Polytomella sp.\",\n      \"pmids\": [\"18036550\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single indirect observation (mass difference) without direct mutagenesis or a processing assay\",\n        \"Processing site and responsible peptidase not identified\",\n        \"Functional consequence of the differential processing unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The functional requirement of COX2a for respiration, its assembly pathway with COX2B, and its structural arrangement within Complex IV remain uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic loss-of-function or rescue data\",\n        \"No structural or stoichiometric characterization\",\n        \"Assembly relationship with COX2B undefined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004129\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006119\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Mitochondrial cytochrome c oxidase (Complex IV)\"],\n    \"partners\": [\"COX2B\"],\n    \"other_free_text\": [\n      \"Mitochondrial targeting sequence of the COX2a precursor is processed differently in T. gondii than in the chlorophycean alga Polytomella sp. (indirect mass evidence) [#1]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_226590","name":"COX2a","product":"cytochrome c oxidase subunit COX2a","uniprot_acc":"S8EUP1","chromosome":"TGME49_chrX","start_pos":1517322},{"strain":"GT1","gene_id":"TGGT1_226590","name":null,"product":"putative cytochrome C oxidase subunit IIa","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":1425019},{"strain":"RH88","gene_id":"TGRH88_046190","name":null,"product":"putative cytochrome C oxidase subunit IIa","uniprot_acc":null,"chromosome":"CM023091","start_pos":6053202},{"strain":"VEG","gene_id":"TGVEG_226590","name":null,"product":"putative cytochrome C oxidase subunit IIa","uniprot_acc":"A0A0F7V207","chromosome":"TGVEG_chrX","start_pos":1409937}]}