{"gene":"PF3D7_MIT02100","run_date":"2026-09-08T15:24:04","timeline":{"discoveries":[{"year":1993,"finding":"Sequencing of the P. falciparum 6-kb mitochondrial element revealed that cytochrome c oxidase subunit 1 (COX1) is encoded on this extrachromosomal DNA; structural analysis of the predicted COX1 polypeptide showed overall similarity to other species, establishing it as a component of the parasite's electron transport chain.","method":"DNA sequencing and comparative structural analysis of predicted protein","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, sequencing/comparative analysis only, no direct functional assay of COX1 itself","pmids":["8459834"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":1990,"finding":"In P. yoelii, COX1 is encoded on the 6-kb extrachromosomal mitochondrial DNA and is transcribed as a discrete ~1.4 kb RNA during erythrocytic stages; primer extension and RNA sequencing identified a 12-nucleotide sequence (5'-TATTTTT TGTTT-3') at the 5' end of the cox1 transcript, and a stem-loop structure was found at the end of the cox1 open reading frame, suggesting a transcription termination signal.","method":"Primer extension, RNA sequencing, Northern blot analysis of erythrocytic-stage parasites","journal":"Molecular and cellular biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct RNA characterization with primer extension and sequencing, two orthogonal methods, single lab","pmids":["1701017"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2022,"finding":"The P. falciparum Cox11 ortholog (PfCox11) is predicted to transfer copper to the CuB site within the COX1 subunit of cytochrome c oxidase; in vitro copper-binding assays and site-directed mutagenesis of PfCox11 identified cysteine 157 (but not Cys 60) as important for copper binding, supporting a copper-delivery function toward COX1.","method":"Recombinant protein expression, in vitro copper-binding assays (bicinchoninic acid release, atomic absorption spectroscopy, bacterial growth inhibition, ascorbate oxidation inhibition, thermal shift assay), site-directed mutagenesis","journal":"Malaria journal","confidence":"Low","confidence_rationale":"Tier 3 / Weak — functional characterization is of PfCox11 (the assembly factor), not COX1 itself; the role of COX1 as the copper-recipient is inferred by analogy to yeast, not directly demonstrated for the Plasmodium protein","pmids":["35672733"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"finding":"Comparative mitochondrial genome analysis of 23 Plasmodium species confirmed that cox1 is one of only three protein-coding genes in the Plasmodium mitochondrial genome (alongside cox3 and cob), and its gene arrangement is completely conserved across all 23 species examined.","method":"Comparative genomic sequencing and bioinformatic analysis of mitochondrial genomes","journal":"Parasitology international","confidence":"Low","confidence_rationale":"Tier 4 / Strong — comparative genomics only, no direct functional assay; replicated across many species but purely sequence-based","pmids":["21329764"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_MIT02100 (COX1) is one of only three protein-coding genes on the Plasmodium mitochondrial genome, is transcribed as a discrete ~1.4 kb mRNA during erythrocytic stages (established in P. yoelii) with a defined 5′ sequence element and a 3′ stem-loop terminator, encodes a subunit of cytochrome c oxidase with overall structural conservation across species, and is predicted to receive copper at its CuB site via the assembly factor PfCox11—though direct enzymatic characterization of the COX1 subunit itself has not been demonstrated in the available literature."},"narrative":{"mechanistic_narrative":"PF3D7_MIT02100 (COX1) encodes cytochrome c oxidase subunit 1, a component of the parasite's mitochondrial electron transport chain, and is one of only three protein-coding genes carried on the Plasmodium mitochondrial genome alongside cox3 and cob, an arrangement completely conserved across 23 Plasmodium species [PMID:8459834, PMID:21329764]. The gene resides on the 6-kb extrachromosomal mitochondrial DNA and, in P. yoelii, is transcribed as a discrete ~1.4 kb RNA during erythrocytic stages, with a defined 12-nucleotide 5' sequence element and a 3' stem-loop that marks the end of the open reading frame and functions as a putative transcription termination signal [PMID:1701017]. Functionally, COX1 is predicted to be the recipient of copper at its CuB site from the assembly factor PfCox11, whose copper-binding activity was mapped to cysteine 157 in vitro [PMID:35672733]. Direct enzymatic characterization of the COX1 subunit itself has not been demonstrated in the available corpus; its structural assignment rests on sequence similarity to COX1 orthologs in other species [PMID:8459834].","teleology":[{"year":1990,"claim":"Establishing where cox1 is encoded and how it is expressed was required to place COX1 within the parasite's mitochondrial genetic system; RNA-level characterization showed it is transcribed as a discrete unit with defined boundaries.","evidence":"Primer extension, RNA sequencing, and Northern blot of erythrocytic-stage P. yoelii parasites","pmids":["1701017"],"confidence":"Medium","gaps":["Whether the 5' element and 3' stem-loop mediate transcription initiation and termination was inferred from position, not tested functionally","Transcript processing and translation of the COX1 protein were not characterized","Shown in P. yoelii; not confirmed for the P. falciparum ortholog"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":1993,"claim":"Determining the coding identity of the P. falciparum 6-kb mitochondrial element assigned COX1 to the electron transport chain by sequence, establishing the gene's presumptive molecular role.","evidence":"DNA sequencing and comparative structural analysis of the predicted COX1 polypeptide from the P. falciparum 6-kb mitochondrial element","pmids":["8459834"],"confidence":"Low","gaps":["No direct functional or enzymatic assay of the COX1 subunit was performed","Assignment rests solely on sequence similarity to other species","Assembly into a cytochrome c oxidase complex was not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2011,"claim":"Comparative genomics across the genus tested whether the cox1 gene content and arrangement are conserved, establishing it as a stable, core feature of the minimal Plasmodium mitochondrial genome.","evidence":"Comparative sequencing and bioinformatic analysis of mitochondrial genomes from 23 Plasmodium species","pmids":["21329764"],"confidence":"Low","gaps":["Conservation was assessed at the sequence level only, with no functional correlate","Does not establish the enzymatic activity or essentiality of COX1"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"claim":"Characterizing the copper-delivery assembly factor PfCox11 provided indirect functional context for COX1 by identifying the presumed source of copper for its CuB catalytic site.","evidence":"Recombinant PfCox11 expression, in vitro copper-binding assays, and site-directed mutagenesis identifying Cys157 as important for copper binding","pmids":["35672733"],"confidence":"Low","gaps":["Copper transfer to COX1 itself was inferred by analogy to yeast, not directly demonstrated for the Plasmodium protein","The functional characterization is of the assembly factor, not COX1","No reconstitution of copper loading onto the COX1 CuB site"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Direct biochemical proof that the Plasmodium COX1 polypeptide is a catalytically active cytochrome c oxidase subunit remains unestablished.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct enzymatic assay of the COX1 subunit","No structural verification of copper loading at the CuB site in the parasite protein","No genetic demonstration of COX1 function or essentiality in blood-stage parasites"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Cytochrome c oxidase (Complex IV)"],"partners":["PFCOX11 (COPPER-DELIVERY ASSEMBLY FACTOR, PREDICTED TO LOAD CUB SITE)"],"other_free_text":["Encoded on the 6-kb extrachromosomal mitochondrial DNA element; one of only three protein-coding genes in the Plasmodium mitochondrial genome alongside cox3 and cob [#3]","In P. yoelii, transcribed as a discrete ~1.4 kb RNA during erythrocytic stages with a 12-nt 5' sequence element and a 3' stem-loop putative termination signal [#1]","Gene arrangement completely conserved across 23 Plasmodium species [#3]","Direct enzymatic characterization of the COX1 subunit itself has not been demonstrated in the available corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"20498054","id":"PMC_20498054","title":"African apes as reservoirs of Plasmodium falciparum and the origin and diversification of the Laverania subgenus.","date":"2010","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/20498054","citation_count":117,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"8459834","id":"PMC_8459834","title":"Structural features of Plasmodium cytochrome b that may underlie susceptibility to 8-aminoquinolines and hydroxynaphthoquinones.","date":"1993","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/8459834","citation_count":93,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cytochrome c oxidase subunit 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32687020","id":"PMC_32687020","title":"Naturally Acquired Human Plasmodium cynomolgi and P. knowlesi Infections, Malaysian Borneo.","date":"2020","source":"Emerging infectious diseases","url":"https://pubmed.ncbi.nlm.nih.gov/32687020","citation_count":62,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cytochrome c oxidase subunit 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"1701017","id":"PMC_1701017","title":"Complex transcription from the extrachromosomal DNA encoding mitochondrial functions of Plasmodium yoelii.","date":"1990","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/1701017","citation_count":57,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"22633951","id":"PMC_22633951","title":"Plasmodium ovale in Bangladesh: genetic diversity and the first known evidence of the sympatric distribution of Plasmodium ovale curtisi and Plasmodium ovale wallikeri in southern Asia.","date":"2012","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/22633951","citation_count":50,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21329764","id":"PMC_21329764","title":"Highly conserved gene arrangement of the mitochondrial genomes of 23 Plasmodium species.","date":"2011","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/21329764","citation_count":45,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34971372","id":"PMC_34971372","title":"Cryptic Plasmodium inui and Plasmodium fieldi Infections Among Symptomatic Malaria Patients in Thailand.","date":"2022","source":"Clinical infectious diseases : an official publication of the Infectious Diseases Society of America","url":"https://pubmed.ncbi.nlm.nih.gov/34971372","citation_count":43,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32933567","id":"PMC_32933567","title":"New vectors in northern Sarawak, Malaysian Borneo, for the zoonotic malaria parasite, Plasmodium knowlesi.","date":"2020","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/32933567","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1","cytochrome c oxidase subunit 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26577930","id":"PMC_26577930","title":"Molecular characterization of misidentified Plasmodium ovale imported cases in Singapore.","date":"2015","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/26577930","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19840032","id":"PMC_19840032","title":"Comparison of three real-time PCR methods with blood smears and rapid diagnostic test in Plasmodium sp. infection.","date":"2009","source":"Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases","url":"https://pubmed.ncbi.nlm.nih.gov/19840032","citation_count":33,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34011373","id":"PMC_34011373","title":"Multicopy targets for Plasmodium vivax and Plasmodium falciparum detection by colorimetric LAMP.","date":"2021","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/34011373","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1","PvCOX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"24004956","id":"PMC_24004956","title":"Plasmodium falciparum mitochondrial genetic diversity exhibits isolation-by-distance patterns supporting a sub-Saharan African origin.","date":"2013","source":"Mitochondrion","url":"https://pubmed.ncbi.nlm.nih.gov/24004956","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37742788","id":"PMC_37742788","title":"Zoonotic simian malaria parasites in free-ranging Macaca fascicularis macaques and human malaria patients in Thailand, with a note on genetic characterization of recent isolates.","date":"2023","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/37742788","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35077516","id":"PMC_35077516","title":"Placental malaria caused by Plasmodium vivax or P. falciparum in Colombia: Histopathology and mediators in placental processes.","date":"2022","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/35077516","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35672733","id":"PMC_35672733","title":"Expression and copper binding characteristics of Plasmodium falciparum cytochrome c oxidase assembly factor 11, Cox11.","date":"2022","source":"Malaria journal","url":"https://pubmed.ncbi.nlm.nih.gov/35672733","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37348640","id":"PMC_37348640","title":"Expression and copper binding studies of a Plasmodium falciparum protein with Cox19 copper binding motifs.","date":"2023","source":"Experimental 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falciparum.","date":"2026","source":"iScience","url":"https://pubmed.ncbi.nlm.nih.gov/42375531","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["cytochrome c oxidase subunit 1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"39878187","id":"PMC_39878187","title":"[Investigation of Molecular Differences in Plasmodium spp. Isolates Obtained from Malaria Patients].","date":"2025","source":"Mikrobiyoloji bulteni","url":"https://pubmed.ncbi.nlm.nih.gov/39878187","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["COX1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":13211,"output_tokens":1224,"usd":0.028997,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":11995,"output_tokens":4580,"usd":0.131528,"resynth_parse_fail":true},"total_usd":0.160525,"stage1_batch_id":"msgbatch_01S4WrhSkksYHeZXxqf3za3o","stage2_batch_id":"msgbatch_019VBBeuW6G52X8gZfsFDfb5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1993,\n      \"finding\": \"Sequencing of the P. falciparum 6-kb mitochondrial element revealed that cytochrome c oxidase subunit 1 (COX1) is encoded on this extrachromosomal DNA; structural analysis of the predicted COX1 polypeptide showed overall similarity to other species, establishing it as a component of the parasite's electron transport chain.\",\n      \"method\": \"DNA sequencing and comparative structural analysis of predicted protein\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, sequencing/comparative analysis only, no direct functional assay of COX1 itself\",\n      \"pmids\": [\"8459834\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1990,\n      \"finding\": \"In P. yoelii, COX1 is encoded on the 6-kb extrachromosomal mitochondrial DNA and is transcribed as a discrete ~1.4 kb RNA during erythrocytic stages; primer extension and RNA sequencing identified a 12-nucleotide sequence (5'-TATTTTT TGTTT-3') at the 5' end of the cox1 transcript, and a stem-loop structure was found at the end of the cox1 open reading frame, suggesting a transcription termination signal.\",\n      \"method\": \"Primer extension, RNA sequencing, Northern blot analysis of erythrocytic-stage parasites\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct RNA characterization with primer extension and sequencing, two orthogonal methods, single lab\",\n      \"pmids\": [\"1701017\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"The P. falciparum Cox11 ortholog (PfCox11) is predicted to transfer copper to the CuB site within the COX1 subunit of cytochrome c oxidase; in vitro copper-binding assays and site-directed mutagenesis of PfCox11 identified cysteine 157 (but not Cys 60) as important for copper binding, supporting a copper-delivery function toward COX1.\",\n      \"method\": \"Recombinant protein expression, in vitro copper-binding assays (bicinchoninic acid release, atomic absorption spectroscopy, bacterial growth inhibition, ascorbate oxidation inhibition, thermal shift assay), site-directed mutagenesis\",\n      \"journal\": \"Malaria journal\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — functional characterization is of PfCox11 (the assembly factor), not COX1 itself; the role of COX1 as the copper-recipient is inferred by analogy to yeast, not directly demonstrated for the Plasmodium protein\",\n      \"pmids\": [\"35672733\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Comparative mitochondrial genome analysis of 23 Plasmodium species confirmed that cox1 is one of only three protein-coding genes in the Plasmodium mitochondrial genome (alongside cox3 and cob), and its gene arrangement is completely conserved across all 23 species examined.\",\n      \"method\": \"Comparative genomic sequencing and bioinformatic analysis of mitochondrial genomes\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Strong — comparative genomics only, no direct functional assay; replicated across many species but purely sequence-based\",\n      \"pmids\": [\"21329764\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_MIT02100 (COX1) is one of only three protein-coding genes on the Plasmodium mitochondrial genome, is transcribed as a discrete ~1.4 kb mRNA during erythrocytic stages (established in P. yoelii) with a defined 5′ sequence element and a 3′ stem-loop terminator, encodes a subunit of cytochrome c oxidase with overall structural conservation across species, and is predicted to receive copper at its CuB site via the assembly factor PfCox11—though direct enzymatic characterization of the COX1 subunit itself has not been demonstrated in the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_MIT02100 (COX1) encodes cytochrome c oxidase subunit 1, a component of the parasite's mitochondrial electron transport chain, and is one of only three protein-coding genes carried on the Plasmodium mitochondrial genome alongside cox3 and cob, an arrangement completely conserved across 23 Plasmodium species [#0, #3]. The gene resides on the 6-kb extrachromosomal mitochondrial DNA and, in P. yoelii, is transcribed as a discrete ~1.4 kb RNA during erythrocytic stages, with a defined 12-nucleotide 5' sequence element and a 3' stem-loop that marks the end of the open reading frame and functions as a putative transcription termination signal [#1]. Functionally, COX1 is predicted to be the recipient of copper at its CuB site from the assembly factor PfCox11, whose copper-binding activity was mapped to cysteine 157 in vitro [#2]. Direct enzymatic characterization of the COX1 subunit itself has not been demonstrated in the available corpus; its structural assignment rests on sequence similarity to COX1 orthologs in other species [#0].\",\n  \"teleology\": [\n    {\n      \"year\": 1990,\n      \"claim\": \"Establishing where cox1 is encoded and how it is expressed was required to place COX1 within the parasite's mitochondrial genetic system; RNA-level characterization showed it is transcribed as a discrete unit with defined boundaries.\",\n      \"evidence\": \"Primer extension, RNA sequencing, and Northern blot of erythrocytic-stage P. yoelii parasites\",\n      \"pmids\": [\"1701017\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the 5' element and 3' stem-loop mediate transcription initiation and termination was inferred from position, not tested functionally\",\n        \"Transcript processing and translation of the COX1 protein were not characterized\",\n        \"Shown in P. yoelii; not confirmed for the P. falciparum ortholog\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 1993,\n      \"claim\": \"Determining the coding identity of the P. falciparum 6-kb mitochondrial element assigned COX1 to the electron transport chain by sequence, establishing the gene's presumptive molecular role.\",\n      \"evidence\": \"DNA sequencing and comparative structural analysis of the predicted COX1 polypeptide from the P. falciparum 6-kb mitochondrial element\",\n      \"pmids\": [\"8459834\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct functional or enzymatic assay of the COX1 subunit was performed\",\n        \"Assignment rests solely on sequence similarity to other species\",\n        \"Assembly into a cytochrome c oxidase complex was not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Comparative genomics across the genus tested whether the cox1 gene content and arrangement are conserved, establishing it as a stable, core feature of the minimal Plasmodium mitochondrial genome.\",\n      \"evidence\": \"Comparative sequencing and bioinformatic analysis of mitochondrial genomes from 23 Plasmodium species\",\n      \"pmids\": [\"21329764\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Conservation was assessed at the sequence level only, with no functional correlate\",\n        \"Does not establish the enzymatic activity or essentiality of COX1\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Characterizing the copper-delivery assembly factor PfCox11 provided indirect functional context for COX1 by identifying the presumed source of copper for its CuB catalytic site.\",\n      \"evidence\": \"Recombinant PfCox11 expression, in vitro copper-binding assays, and site-directed mutagenesis identifying Cys157 as important for copper binding\",\n      \"pmids\": [\"35672733\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Copper transfer to COX1 itself was inferred by analogy to yeast, not directly demonstrated for the Plasmodium protein\",\n        \"The functional characterization is of the assembly factor, not COX1\",\n        \"No reconstitution of copper loading onto the COX1 CuB site\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Direct biochemical proof that the Plasmodium COX1 polypeptide is a catalytically active cytochrome c oxidase subunit remains unestablished.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct enzymatic assay of the COX1 subunit\",\n        \"No structural verification of copper loading at the CuB site in the parasite protein\",\n        \"No genetic demonstration of COX1 function or essentiality in blood-stage parasites\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004129\", \"supporting_discovery_ids\": [0, 2]},\n      {\"term_id\": \"GO:0005507\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005743\", \"supporting_discovery_ids\": [0, 1, 3]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006119\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0022904\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\n      \"Cytochrome c oxidase (Complex IV)\"\n    ],\n    \"partners\": [\n      \"PfCox11 (copper-delivery assembly factor, predicted to load CuB site)\"\n    ],\n    \"other_free_text\": [\n      \"Encoded on the 6-kb extrachromosomal mitochondrial DNA element; one of only three protein-coding genes in the Plasmodium mitochondrial genome alongside cox3 and cob [#3]\",\n      \"In P. yoelii, transcribed as a discrete ~1.4 kb RNA during erythrocytic stages with a 12-nt 5' sequence element and a 3' stem-loop putative termination signal [#1]\",\n      \"Gene arrangement completely conserved across 23 Plasmodium species [#3]\",\n      \"Direct enzymatic characterization of the COX1 subunit itself has not been demonstrated in the available corpus\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_MIT02100","name":null,"product":"cytochrome c oxidase subunit 1","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"COX1","evaluation":null}