id: A0A9L0SQG9 gene_symbol: DUOX1 taxon: id: NCBITaxon:9796 label: Equus caballus status: COMPLETE description: The H2O2 catabolism prediction conflicts with DUOX1 oxidase biology. Calcium binding and hormone-related functions remain uncertain because the selected horse sequence lacks major EF-hand elements. source_documents: - projects/PROTNLM_EVALUATION/mammal-benchmark/horse40-predictions.csv - projects/PROTNLM_EVALUATION/mammal-benchmark/predictions.jsonl.gz - projects/PROTNLM_EVALUATION/mammal-benchmark/paired-sequences/DUOX1.json references: - id: PMID:33420071 title: Structures of human dual oxidase 1 complex in low-calcium and high-calcium states. full_text_unavailable: false findings: [] - id: file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md title: HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md findings: [] - id: PMID:19460756 title: 'Caenorhabditis elegans and human dual oxidase 1 (DUOX1) "peroxidase" domains: insights into heme binding and catalytic activity.' full_text_unavailable: true findings: [] predictions: - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0042446 label: hormone biosynthetic process predicted_term_type: GO_BP review: assessment: UNC confidence_score: 1 summary: Full-length mammalian DUOX1 is an H2O2-generating oxidase that can supply peroxidase chemistry; this makes a role in hormone synthesis plausible without implying that DUOX1 synthesizes hormone directly. However, the selected horse sequence deletes human residues 775–873, including major calcium-regulatory EF-hand elements. Its regulated oxidase competence and participation in the horse thyroid cannot be established from the intact human protein alone. supported_by: - &id001 reference_id: PMID:33420071 supporting_text: 'In the presence of calcium ions, intracellular EF-hand modules might enhance the catalytic activity of DUOX by stabilizing the dehydrogenase domain in a conformation that allows electron transfer.' - reference_id: file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md supporting_text: The global alignment deletes human DUOX1 residues 775–873 from the selected horse sequence. The fetched human UniProt feature table places EF-hand 1 at 815–850 and EF-hand 2 at 851–887. Thus the selected sequence lacks the first annotated EF-hand and most of the second, despite retaining the signal peptide, transmembrane oxidase region and C-terminal FAD/NADPH-binding region. Calcium-responsive activity cannot be transferred from full-length human DUOX1 without resolving this deletion. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0042744 label: hydrogen peroxide catabolic process predicted_term_type: GO_BP review: assessment: NPI confidence_score: 0 summary: The mammalian DUOX1 catalytic system generates H2O2; the isolated human peroxidase-like domain has no intrinsic peroxidase activity. Producing the substrate for a separate peroxidase is not evidence that DUOX1 carries out H2O2 catabolism. The selected horse protein retains the homologous peroxidase-like region, and no independent catabolic mechanism is supported. This prediction confuses an oxidant-generating enzyme with peroxide-consuming chemistry. supported_by: - reference_id: PMID:19460756 supporting_text: 'the isolated hDUOX1(1-593) does not bind heme and has no intrinsic peroxidase activity.' - reference_id: PMID:33420071 supporting_text: 'Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen.' - reference_id: file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md supporting_text: share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse. error_type: PSEUDOENZYME_OVERANNOTATION - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0006590 label: thyroid hormone generation predicted_term_type: GO_BP review: assessment: UNC confidence_score: 1 summary: Full-length mammalian DUOX1 is an H2O2-generating oxidase that can supply peroxidase chemistry; this makes a role in hormone synthesis plausible without implying that DUOX1 synthesizes hormone directly. However, the selected horse sequence deletes human residues 775–873, including major calcium-regulatory EF-hand elements. Its regulated oxidase competence and participation in the horse thyroid cannot be established from the intact human protein alone. supported_by: - *id001 - reference_id: file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md supporting_text: The global alignment deletes human DUOX1 residues 775–873 from the selected horse sequence. The fetched human UniProt feature table places EF-hand 1 at 815–850 and EF-hand 2 at 851–887. Thus the selected sequence lacks the first annotated EF-hand and most of the second, despite retaining the signal peptide, transmembrane oxidase region and C-terminal FAD/NADPH-binding region. Calcium-responsive activity cannot be transferred from full-length human DUOX1 without resolving this deletion. - source_method: ProtNLM2 source_version: UniProt API snapshot 2026-09-08 predicted_term: id: GO:0005509 label: calcium ion binding predicted_term_type: GO_MF review: assessment: UNC confidence_score: 1 summary: Calcium binding is directly supported in full-length human DUOX1, but the selected horse sequence lacks the first annotated EF-hand and most of the second. Remaining EF-hand-like sequence cannot establish that this shortened protein preserves the experimentally observed calcium-binding sites. Resolve the gene model or measure calcium binding before accepting this exact-sequence prediction. supported_by: - *id001 - reference_id: file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md supporting_text: The global alignment deletes human DUOX1 residues 775–873 from the selected horse sequence. The fetched human UniProt feature table places EF-hand 1 at 815–850 and EF-hand 2 at 851–887. Thus the selected sequence lacks the first annotated EF-hand and most of the second, despite retaining the signal peptide, transmembrane oxidase region and C-terminal FAD/NADPH-binding region. Calcium-responsive activity cannot be transferred from full-length human DUOX1 without resolving this deletion.