A0A9L0SQG9

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004601 peroxidase activity	IEA GO_REF:0000002	REMOVE	Summary: peroxidase activity: The homologous mammalian N-terminal peroxidase-like domain lacks intrinsic peroxidase activity. Conservation of a peroxidase fold does not validate the electronic catalytic transfer. Reason: The homologous mammalian N-terminal peroxidase-like domain lacks intrinsic peroxidase activity. Conservation of a peroxidase fold does not validate the electronic catalytic transfer. Supporting Evidence: PMID:19460756 the isolated hDUOX1(1-593) does not bind heme and has no intrinsic peroxidase activity. file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md The downloaded human Q9NRD9 sequence (1551 residues) and selected horse A0A9L0SQG9 sequence (1452 residues) share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse.
GO:0005886 plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: plasma membrane: Human DUOX1–DUOXA1 structures and functional experiments establish a membrane oxidase complex using heme, FAD and NADPH to generate extracellular H2O2, regulated by calcium-binding EF-hand elements. These are direct components of the oxidase mechanism. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits. Reason: Human DUOX1–DUOXA1 structures and functional experiments establish a membrane oxidase complex using heme, FAD and NADPH to generate extracellular H2O2, regulated by calcium-binding EF-hand elements. These are direct components of the oxidase mechanism. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits. Supporting Evidence: PMID:33420071 Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md The downloaded human Q9NRD9 sequence (1551 residues) and selected horse A0A9L0SQG9 sequence (1452 residues) share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse.
GO:0006979 response to oxidative stress	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: response to oxidative stress: DUOX1-generated extracellular H2O2 participates in epithelial defense and redox signaling. The annotated response or tissue-level effect is a context-dependent consequence of this oxidase function, rather than an additional intrinsic molecular activity. Reason: DUOX1-generated extracellular H2O2 participates in epithelial defense and redox signaling. The annotated response or tissue-level effect is a context-dependent consequence of this oxidase function, rather than an additional intrinsic molecular activity. Supporting Evidence: PMID:33420071 Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md The downloaded human Q9NRD9 sequence (1551 residues) and selected horse A0A9L0SQG9 sequence (1452 residues) share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse.
GO:0016020 membrane	IEA GO_REF:0000044	UNDECIDED	Summary: membrane: The available evidence examined for DUOX1 does not resolve the exact claim of membrane. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000044 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for DUOX1 does not resolve the exact claim of membrane. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000044 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	UNDECIDED	Summary: oxidoreductase activity: The horse model retains oxidase machinery but lacks major EF-hand elements corresponding to human residues 775–873. Regulated enzymatic competence cannot be established solely by the intact human enzyme. Reason: The horse model retains oxidase machinery but lacks major EF-hand elements corresponding to human residues 775–873. Regulated enzymatic competence cannot be established solely by the intact human enzyme. Supporting Evidence: PMID:33420071 Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md The downloaded human Q9NRD9 sequence (1551 residues) and selected horse A0A9L0SQG9 sequence (1452 residues) share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse.
GO:0020037 heme binding	IEA GO_REF:0000002	ACCEPT	Summary: heme binding: Human DUOX1–DUOXA1 structures and functional experiments establish a membrane oxidase complex using heme, FAD and NADPH to generate extracellular H2O2, regulated by calcium-binding EF-hand elements. These are direct components of the oxidase mechanism. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits. Reason: Human DUOX1–DUOXA1 structures and functional experiments establish a membrane oxidase complex using heme, FAD and NADPH to generate extracellular H2O2, regulated by calcium-binding EF-hand elements. These are direct components of the oxidase mechanism. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits. Supporting Evidence: PMID:33420071 Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations. file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md The downloaded human Q9NRD9 sequence (1551 residues) and selected horse A0A9L0SQG9 sequence (1452 residues) share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse.
GO:0098869 cellular oxidant detoxification	IEA GO_REF:0000108	UNDECIDED	Summary: cellular oxidant detoxification: The available evidence examined for DUOX1 does not resolve the exact claim of cellular oxidant detoxification. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000108 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper. Reason: The available evidence examined for DUOX1 does not resolve the exact claim of cellular oxidant detoxification. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000108 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.

GO Term

Evidence

Action

Reason

GO:0004601 peroxidase activity

IEA
GO_REF:0000002

REMOVE

Summary: peroxidase activity: The homologous mammalian N-terminal peroxidase-like domain lacks intrinsic peroxidase activity. Conservation of a peroxidase fold does not validate the electronic catalytic transfer.

Reason: The homologous mammalian N-terminal peroxidase-like domain lacks intrinsic peroxidase activity. Conservation of a peroxidase fold does not validate the electronic catalytic transfer.

Supporting Evidence:

PMID:19460756

the isolated hDUOX1(1-593) does not bind heme and has no intrinsic peroxidase activity.

file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md

The downloaded human Q9NRD9 sequence (1551 residues) and selected horse A0A9L0SQG9 sequence (1452 residues) share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse.

GO:0005886 plasma membrane

IEA
GO_REF:0000044

Summary: plasma membrane: Human DUOX1–DUOXA1 structures and functional experiments establish a membrane oxidase complex using heme, FAD and NADPH to generate extracellular H2O2, regulated by calcium-binding EF-hand elements. These are direct components of the oxidase mechanism. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.

Reason: Human DUOX1–DUOXA1 structures and functional experiments establish a membrane oxidase complex using heme, FAD and NADPH to generate extracellular H2O2, regulated by calcium-binding EF-hand elements. These are direct components of the oxidase mechanism. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.

Supporting Evidence:

PMID:33420071

Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen. They are involved in many crucial biological processes and human diseases, especially in thyroid diseases. DUOXs are protein complexes co-assembled from the catalytic DUOX subunits and the auxiliary DUOXA subunits and their activities are regulated by intracellular calcium concentrations.

file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md

GO:0006979 response to oxidative stress

IEA
GO_REF:0000002

KEEP AS NON CORE

Summary: response to oxidative stress: DUOX1-generated extracellular H2O2 participates in epithelial defense and redox signaling. The annotated response or tissue-level effect is a context-dependent consequence of this oxidase function, rather than an additional intrinsic molecular activity.

Reason: DUOX1-generated extracellular H2O2 participates in epithelial defense and redox signaling. The annotated response or tissue-level effect is a context-dependent consequence of this oxidase function, rather than an additional intrinsic molecular activity.

Supporting Evidence:

PMID:33420071

file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md

GO:0016020 membrane

IEA
GO_REF:0000044

UNDECIDED

Summary: membrane: The available evidence examined for DUOX1 does not resolve the exact claim of membrane. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000044 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.

Reason: The available evidence examined for DUOX1 does not resolve the exact claim of membrane. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000044 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.

GO:0016491 oxidoreductase activity

IEA
GO_REF:0000002

UNDECIDED

Summary: oxidoreductase activity: The horse model retains oxidase machinery but lacks major EF-hand elements corresponding to human residues 775–873. Regulated enzymatic competence cannot be established solely by the intact human enzyme.

Reason: The horse model retains oxidase machinery but lacks major EF-hand elements corresponding to human residues 775–873. Regulated enzymatic competence cannot be established solely by the intact human enzyme.

Supporting Evidence:

PMID:33420071

file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md

GO:0020037 heme binding

IEA
GO_REF:0000002

Summary: heme binding: Human DUOX1–DUOXA1 structures and functional experiments establish a membrane oxidase complex using heme, FAD and NADPH to generate extracellular H2O2, regulated by calcium-binding EF-hand elements. These are direct components of the oxidase mechanism. Transfer to horse is an inference; the paired-sequence report records model-specific gaps and limits.

Supporting Evidence:

PMID:33420071

file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md

GO:0098869 cellular oxidant detoxification

IEA
GO_REF:0000108

UNDECIDED

Summary: cellular oxidant detoxification: The available evidence examined for DUOX1 does not resolve the exact claim of cellular oxidant detoxification. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000108 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.

Reason: The available evidence examined for DUOX1 does not resolve the exact claim of cellular oxidant detoxification. The specific experiment or traced orthology/phylogenetic inference behind GO_REF:0000108 is needed; the annotation is not rejected from absence in a summary or from a different main focus of the paper.

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · DUOX1-protnlm-predictions-review.yaml · Review status: COMPLETE

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

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0042446 hormone biosynthetic process GO_BP

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08

Review rationale: 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.

Supporting Evidence:

PMID:33420071: "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."
file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md: "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."

GO:0042744 hydrogen peroxide catabolic process GO_BP

NPI — Nonparalog incorrect Review score: 0/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08

PSEUDOENZYME OVERANNOTATION

Review rationale: 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.

Supporting Evidence:

PMID:19460756: "the isolated hDUOX1(1-593) does not bind heme and has no intrinsic peroxidase activity."
PMID:33420071: "Dual oxidases (DUOXs) produce hydrogen peroxide by transferring electrons from intracellular NADPH to extracellular oxygen."
file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md: "share 91.4% identity among 1452 paired residues. Paired coverage is 93.6% of human and 100.0% of horse."

GO:0006590 thyroid hormone generation GO_BP

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08

Supporting Evidence:

PMID:33420071: "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."
file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md: "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."

GO:0005509 calcium ion binding GO_MF

UNC — Uncertain Review score: 1/2

Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-09-08

Review rationale: 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.

Supporting Evidence:

PMID:33420071: "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."
file:HORSE/DUOX1/DUOX1-bioinformatics/RESULTS.md: "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."

📚 Additional Documentation

Bioinformatics Results

(RESULTS.md)

Loading supporting content…

Download this section (compressed HTML)

Protnlm Function Review

(DUOX1-protnlm-function-review.md)

Loading supporting content…

Download this section (compressed HTML)

Gene Description

Existing Annotations Review

References

External Prediction Reviews

ProtNLM2 External predictions

📚 Additional Documentation

Notes

Bioinformatics Results

Protnlm Function Review

📄 View Raw YAML