Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: cytosol is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0006979 response to oxidative stress	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Manual review: response to oxidative stress may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0008379 thioredoxin peroxidase activity	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: thioredoxin peroxidase activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0042744 hydrogen peroxide catabolic process	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: hydrogen peroxide catabolic process is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0045454 cell redox homeostasis	IBA GO_REF:0000033	ACCEPT	Summary: Manual review: cell redox homeostasis is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0000165 MAPK cascade	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Manual review: MAPK cascade may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0004601 peroxidase activity	IEA GO_REF:0000043	ACCEPT	Summary: Manual review: peroxidase activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Manual review: nucleus is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: Manual review: cytoplasm is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0016209 antioxidant activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Manual review: antioxidant activity may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0016491 oxidoreductase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Manual review: oxidoreductase activity may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0034599 cellular response to oxidative stress	IEA GO_REF:0000117	ACCEPT	Summary: Manual review: cellular response to oxidative stress is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0051920 peroxiredoxin activity	IEA GO_REF:0000002	ACCEPT	Summary: Manual review: peroxiredoxin activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0140824 thioredoxin-dependent peroxiredoxin activity	IEA GO_REF:0000120	ACCEPT	Summary: Manual review: thioredoxin-dependent peroxiredoxin activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005078 MAP kinase scaffold activity	EXP PMID:37572670 A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by...	KEEP AS NON CORE	Summary: Manual review: MAP kinase scaffold activity may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function. Supporting Evidence: PMID:37572670 We demonstrate that a P38-Prdx fusion protein compensates for loss of the yeast scaffold protein Mcs4 and MAP3K activity, driving yeast into mitosis
GO:0015035 protein-disulfide reductase activity	EXP PMID:37572670 A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by...	KEEP AS NON CORE	Summary: Manual review: protein-disulfide reductase activity may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:1900745 positive regulation of p38MAPK cascade	IMP PMID:37572670 A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by...	KEEP AS NON CORE	Summary: Manual review: positive regulation of p38MAPK cascade may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0061692 cellular detoxification of hydrogen peroxide	IMP PMID:24521463 A genetic approach to study H2O2 scavenging in fission yeast...	ACCEPT	Summary: Manual review: cellular detoxification of hydrogen peroxide is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005737 cytoplasm	IDA PMID:22344694 The transcription factors Pap1 and Prr1 collaborate to activ...	ACCEPT	Summary: Manual review: cytoplasm is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: PMID:22344694 The Crm1-dependent export of Pap1 prevails over the import, and therefore the transcription factor displays cytosolic localization prior to stress imposition (10)
GO:0051082 unfolded protein binding	IDA PMID:20356456 Distinct functional roles of peroxiredoxin isozymes and glut...	MODIFY	Summary: Manual review: unfolded protein binding is better represented by a more specific replacement term for tpx1. Reason: Modified to align with current curation guidance and improve term specificity. Proposed replacements: protein folding chaperone
GO:0140824 thioredoxin-dependent peroxiredoxin activity	IDA PMID:20356456 Distinct functional roles of peroxiredoxin isozymes and glut...	ACCEPT	Summary: Manual review: thioredoxin-dependent peroxiredoxin activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context. Supporting Evidence: PMID:20356456 TPx (thioredoxin peroxidase) exhibited a capacity for peroxide reduction with the thioredoxin system.
GO:0008379 thioredoxin peroxidase activity	IMP PMID:24268782 A peroxiredoxin promotes H2O2 signaling and oxidative stress...	ACCEPT	Summary: Manual review: thioredoxin peroxidase activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:24268782 A peroxiredoxin promotes H2O2 signaling and oxidative stress...	KEEP AS NON CORE	Summary: Manual review: positive regulation of transcription by RNA polymerase II may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0042744 hydrogen peroxide catabolic process	IMP PMID:24521463 A genetic approach to study H2O2 scavenging in fission yeast...	ACCEPT	Summary: Manual review: hydrogen peroxide catabolic process is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0045454 cell redox homeostasis	IMP PMID:24521463 A genetic approach to study H2O2 scavenging in fission yeast...	ACCEPT	Summary: Manual review: cell redox homeostasis is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0000122 negative regulation of transcription by RNA polymerase II	IMP PMID:22245228 Inactivation of a peroxiredoxin by hydrogen peroxide is crit...	KEEP AS NON CORE	Summary: Manual review: negative regulation of transcription by RNA polymerase II may be context-dependent or peripheral for tpx1. Reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
GO:0042744 hydrogen peroxide catabolic process	IMP PMID:22245228 Inactivation of a peroxiredoxin by hydrogen peroxide is crit...	ACCEPT	Summary: Manual review: hydrogen peroxide catabolic process is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005737 cytoplasm	IDA PMID:22245228 Inactivation of a peroxiredoxin by hydrogen peroxide is crit...	ACCEPT	Summary: Manual review: cytoplasm is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0004601 peroxidase activity	IDA PMID:17409354 The peroxiredoxin Tpx1 is essential as a H2O2 scavenger duri...	ACCEPT	Summary: Manual review: peroxidase activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005515 protein binding	IPI PMID:17409354 The peroxiredoxin Tpx1 is essential as a H2O2 scavenger duri...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for tpx1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.
GO:0045454 cell redox homeostasis	IMP PMID:17409354 The peroxiredoxin Tpx1 is essential as a H2O2 scavenger duri...	ACCEPT	Summary: Manual review: cell redox homeostasis is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0051920 peroxiredoxin activity	IDA PMID:17409354 The peroxiredoxin Tpx1 is essential as a H2O2 scavenger duri...	ACCEPT	Summary: Manual review: peroxiredoxin activity is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005634 nucleus	HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...	ACCEPT	Summary: Manual review: nucleus is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005829 cytosol	HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ...	ACCEPT	Summary: Manual review: cytosol is consistent with known biology of tpx1. Reason: Retained as supported or plausible for this gene and evidence context.
GO:0005515 protein binding	IPI PMID:15824112 Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular...	MARK AS OVER ANNOTATED	Summary: Manual review: protein binding is too generic or over-extended for tpx1. Reason: Marked over-annotated because more specific terms capture the biology more accurately.

Core Functions

Thioredoxin-dependent peroxiredoxin activity that detoxifies H2O2 and maintains cellular redox balance during aerobic growth and peroxide stress.

Molecular Function:

thioredoxin-dependent peroxiredoxin activity

Directly Involved In:

hydrogen peroxide catabolic process cell redox homeostasis

Cellular Locations:

cytosol

Supporting Evidence:

PMID:17409354
The peroxiredoxin Tpx1 is essential as a H2O2 scavenger during aerobic growth in fission yeast.
PMID:20356456
TPx (thioredoxin peroxidase) exhibited a capacity for peroxide reduction with the thioredoxin system.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000108

Automatic assignment of GO terms using logical inference, based on on inter-ontology links

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:15824112

Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch controlling the transcriptional response to increasing levels of hydrogen peroxide.

PMID:16823372

ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.

PMID:17409354

The peroxiredoxin Tpx1 is essential as a H2O2 scavenger during aerobic growth in fission yeast.

PMID:20356456

Distinct functional roles of peroxiredoxin isozymes and glutathione peroxidase from fission yeast, Schizosaccharomyces pombe.

PMID:22245228

Inactivation of a peroxiredoxin by hydrogen peroxide is critical for thioredoxin-mediated repair of oxidized proteins and cell survival.

PMID:22344694

The transcription factors Pap1 and Prr1 collaborate to activate antioxidant, but not drug tolerance, genes in response to H2O2.

PMID:24268782

A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.

PMID:24521463

A genetic approach to study H2O2 scavenging in fission yeast--distinct roles of peroxiredoxin and catalase.

PMID:37572670

A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms.

📚 Additional Documentation

Deep Research Bioreason

(tpx1-deep-research-bioreason.md)

BioReason Chat Export

Exported on March 22, 2026 at 12:50 AM

Organism: Schizosaccharomyces pombe

Sequence:

MSLQIGKPAPDFKGTAVVNGAFEEIKLADYKGKWVFLGFYPLDFTFVCPTEIVAFSEAASKFAERNAQVILTSTDSEYSHLAFINTPRKEGGLGGINIPLLADPSHKVSRDYGVLIEDAGVAFRGLFLIDPKGVLRQITINDLPVGRSVDEALRLLDAFQFVEEHGEVCPANWHKGSDTIDTKNPEKYFSKH

Thinking Trace

I begin with the InterPro architecture. The polypeptide is built on a thioredoxin-like scaffold: IPR036249 (Thioredoxin-like superfamily, residues 1–181) encompasses the entire core and is reinforced by IPR013766 (Thioredoxin domain, residues 3–161), which defines the canonical β-sheet flanked by α-helices that houses a reversible cysteine redox center. This thioredoxin fold is specialized here by multiple peroxiredoxin signatures: IPR050217 (Thiol-specific antioxidant peroxiredoxin family, residues 3–191) and IPR024706 (Peroxiredoxin, AhpC-type family, residues 3–183) collectively specify a peroxidatic enzyme that reduces hydroperoxides. IPR000866 (Alkyl hydroperoxide reductase subunit C/Thiol-specific antioxidant domain, residues 5–137) anchors the N-terminal catalytic core that bears the peroxidatic cysteine, while IPR019479 (Peroxiredoxin, C-terminal domain, residues 158–180) supplies the flexible C-terminal tail that tunes oligomerization and catalytic cycling. The ordered layout—an N-terminal thioredoxin fold carrying the peroxidatic motif followed by a regulatory C-terminus—creates a high-efficiency peroxidase module.

This domain architecture dictates molecular function. The thioredoxin-like catalytic center, together with the peroxiredoxin/AhpC-type family assignments, causes peroxiredoxin chemistry: nucleophilic attack of a conserved cysteine on hydrogen and organic hydroperoxides to form a cysteine-sulfenic intermediate that is subsequently resolved via thiol-disulfide exchange. This establishes peroxiredoxin activity (a thiol-dependent peroxidase), matching GO:0004601 as the operative molecular function. The peroxiredoxin C-terminal region stabilizes active-state oligomers and modulates turnover, ensuring robust peroxide detoxification.

From this chemistry, the biological process follows. By reducing hydrogen peroxide and alkyl hydroperoxides, the enzyme enforces cellular redox balance and eliminates reactive oxygen species. This places the protein squarely in hydrogen peroxide catabolic pathways and oxidative stress defense. Thus, it drives hydrogen peroxide breakdown and broader ROS handling, consistent with a role in maintaining the intracellular redox environment.

Cellular location is implied by the soluble thioredoxin-like fold and absence of transmembrane or secretion signals. Peroxiredoxins of this architecture function as soluble dimers/decamers in the cytosol, where they intercept diffusible peroxides and interface with cytosolic thioredoxin systems. Therefore, the most parsimonious localization is the cytoplasm.

Mechanistically, the protein likely cycles between reduced and sulfenylated states, with electrons supplied by thioredoxin/thioredoxin reductase. The thioredoxin-like core forms the catalytic platform; the AhpC-type family identity and peroxiredoxin C-terminus promote reversible oligomerization that tunes peroxidase versus chaperone-like states under stress. I hypothesize that thioredoxin and thioredoxin reductase dock transiently to re-reduce the enzyme, while interactions with cytosolic Hsp70/Hsp90 systems and redox-sensitive client proteins facilitate recovery from oxidative insults. Together, these features define a cytoplasmic thiol-dependent peroxidase that sustains redox homeostasis in fission yeast.

Functional Summary

A soluble antioxidant enzyme in fission yeast that uses a thioredoxin-like catalytic core to reduce hydrogen and organic hydroperoxides, thereby protecting the cell from oxidative damage and stabilizing redox balance. It likely operates as a cytoplasmic dimer/decamer whose C-terminal tail regulates catalytic cycling and oligomerization. By coupling peroxide detoxification to the thioredoxin/thioredoxin-reductase system, it sustains intracellular redox homeostasis during oxidative stress.

UniProt Summary

Thiol-specific antioxidant peroxidase which catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides (By similarity).

InterPro Domains

Thioredoxin-like superfamily (IPR036249, homologous_superfamily) — residues 1-181
Thioredoxin domain (IPR013766, domain) — residues 3-161
Thiol-specific antioxidant peroxiredoxin (IPR050217, family) — residues 3-191
Peroxiredoxin, AhpC-type (IPR024706, family) — residues 3-183
Alkyl hydroperoxide reductase subunit C/ Thiol specific antioxidant (IPR000866, domain) — residues 5-137
Peroxiredoxin, C-terminal (IPR019479, domain) — residues 158-180

GO Terms

Molecular Function: molecular_function (GO:0003674), binding (GO:0005488), catalytic activity (GO:0003824), antioxidant activity (GO:0016209), peroxidase activity (GO:0004601), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), unfolded protein binding (GO:0051082), oxidoreductase activity, acting on peroxide as acceptor (GO:0016684), peroxiredoxin activity (GO:0051920), thioredoxin-dependent peroxiredoxin activity (GO:0140824), thioredoxin peroxidase activity (GO:0008379)

Biological Process: biological_process (GO:0008150), metabolic process (GO:0008152), positive regulation of biological process (GO:0048518), detoxification (GO:0098754), regulation of biological process (GO:0050789), homeostatic process (GO:0042592), biological regulation (GO:0065007), response to stimulus (GO:0050896), cellular process (GO:0009987), negative regulation of biological process (GO:0048519), response to chemical (GO:0042221), regulation of metabolic process (GO:0019222), organic substance metabolic process (GO:0071704), cellular detoxification (GO:1990748), detoxification of inorganic compound (GO:0061687), catabolic process (GO:0009056), negative regulation of metabolic process (GO:0009892), cellular homeostasis (GO:0019725), cellular metabolic process (GO:0044237), positive regulation of cellular process (GO:0048522), regulation of cellular process (GO:0050794), positive regulation of metabolic process (GO:0009893), cellular response to stimulus (GO:0051716), response to stress (GO:0006950), negative regulation of cellular process (GO:0048523), negative regulation of nitrogen compound metabolic process (GO:0051172), positive regulation of macromolecule metabolic process (GO:0010604), cell redox homeostasis (GO:0045454), response to oxidative stress (GO:0006979), reactive oxygen species metabolic process (GO:0072593), cellular catabolic process (GO:0044248), response to toxic substance (GO:0009636), regulation of macromolecule metabolic process (GO:0060255), hydrogen peroxide metabolic process (GO:0042743), response to oxygen-containing compound (GO:1901700), negative regulation of cellular metabolic process (GO:0031324), response to organic substance (GO:0010033), positive regulation of biosynthetic process (GO:0009891), response to inorganic substance (GO:0010035), positive regulation of cellular metabolic process (GO:0031325), cellular oxidant detoxification (GO:0098869), cellular response to chemical stimulus (GO:0070887), cellular response to stress (GO:0033554), negative regulation of macromolecule metabolic process (GO:0010605), regulation of biosynthetic process (GO:0009889), regulation of nitrogen compound metabolic process (GO:0051171), regulation of cellular metabolic process (GO:0031323), negative regulation of biosynthetic process (GO:0009890), regulation of primary metabolic process (GO:0080090), organic substance catabolic process (GO:1901575), positive regulation of nitrogen compound metabolic process (GO:0051173), cellular response to oxidative stress (GO:0034599), regulation of macromolecule biosynthetic process (GO:0010556), hydrogen peroxide catabolic process (GO:0042744), cellular response to chemical stress (GO:0062197), regulation of gene expression (GO:0010468), positive regulation of macromolecule biosynthetic process (GO:0010557), positive regulation of nucleobase-containing compound metabolic process (GO:0045935), positive regulation of RNA metabolic process (GO:0051254), cellular response to toxic substance (GO:0097237), regulation of cellular biosynthetic process (GO:0031326), regulation of nucleobase-containing compound metabolic process (GO:0019219), negative regulation of macromolecule biosynthetic process (GO:0010558), negative regulation of cellular biosynthetic process (GO:0031327), regulation of RNA metabolic process (GO:0051252), response to hydrogen peroxide (GO:0042542), negative regulation of RNA metabolic process (GO:0051253), cellular response to oxygen-containing compound (GO:1901701), response to reactive oxygen species (GO:0000302), negative regulation of nucleobase-containing compound metabolic process (GO:0045934), positive regulation of cellular biosynthetic process (GO:0031328), regulation of RNA biosynthetic process (GO:2001141), regulation of DNA-templated transcription (GO:0006355), positive regulation of RNA biosynthetic process (GO:1902680), negative regulation of RNA biosynthetic process (GO:1902679), cellular response to reactive oxygen species (GO:0034614), cellular response to hydrogen peroxide (GO:0070301), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of DNA-templated transcription (GO:0045892), negative regulation of nucleic acid-templated transcription (GO:1903507), positive regulation of nucleic acid-templated transcription (GO:1903508), regulation of nucleic acid-templated transcription (GO:1903506), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of transcription by RNA polymerase II (GO:0000122)

Cellular Component: cellular_component (GO:0005575), cellular anatomical entity (GO:0110165), cytosol (GO:0005829), intracellular anatomical structure (GO:0005622), organelle (GO:0043226), cytoplasm (GO:0005737), intracellular organelle (GO:0043229), membrane-bounded organelle (GO:0043227), intracellular membrane-bounded organelle (GO:0043231), nucleus (GO:0005634)

Generated by BioReason

Deep Research Bioreason Rl

(tpx1-deep-research-bioreason-rl.md)

BioReason Chat Export

Exported on March 22, 2026 at 12:50 AM

Organism: Schizosaccharomyces pombe

Sequence:

MSLQIGKPAPDFKGTAVVNGAFEEIKLADYKGKWVFLGFYPLDFTFVCPTEIVAFSEAASKFAERNAQVILTSTDSEYSHLAFINTPRKEGGLGGINIPLLADPSHKVSRDYGVLIEDAGVAFRGLFLIDPKGVLRQITINDLPVGRSVDEALRLLDAFQFVEEHGEVCPANWHKGSDTIDTKNPEKYFSKH

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

Thioredoxin-like superfamily (IPR036249, homologous_superfamily) — residues 1-181
Thioredoxin domain (IPR013766, domain) — residues 3-161
Thiol-specific antioxidant peroxiredoxin (IPR050217, family) — residues 3-191
Peroxiredoxin, AhpC-type (IPR024706, family) — residues 3-183
Alkyl hydroperoxide reductase subunit C/ Thiol specific antioxidant (IPR000866, domain) — residues 5-137
Peroxiredoxin, C-terminal (IPR019479, domain) — residues 158-180

GO Terms

Generated by BioReason

Bioreason Rl Review

(tpx1-bioreason-rl-review.md)

BioReason-Pro RL Review: tpx1 (S. pombe)

Source: tpx1-deep-research-bioreason-rl.md

Correctness: 5/5
Completeness: 3/5

Functional Summary Review

BioReason's functional summary is accurate:

A soluble antioxidant enzyme in fission yeast that uses a thioredoxin-like catalytic core to reduce hydrogen and organic hydroperoxides, thereby protecting the cell from oxidative damage and stabilizing redox balance. It likely operates as a cytoplasmic dimer/decamer whose C-terminal tail regulates catalytic cycling and oligomerization. By coupling peroxide detoxification to the thioredoxin/thioredoxin-reductase system, it sustains intracellular redox homeostasis during oxidative stress.

This correctly identifies tpx1 as a thioredoxin-dependent peroxiredoxin with peroxidase activity. The curated review confirms:
- Thioredoxin-dependent peroxiredoxin activity (GO:0140824, IDA from PMID:20356456)
- Peroxidase activity (GO:0004601, IDA from PMID:17409354)
- Hydrogen peroxide catabolic process (GO:0042744, IMP)
- Cell redox homeostasis (GO:0045454, IMP)
- Cytosol/cytoplasm localization (IDA from PMID:22344694, HDA from PMID:16823372)

The domain architecture is correctly described -- tpx1 has the full complement of peroxiredoxin domains including the AhpC-type family (IPR024706) and the C-terminal domain (IPR019479).

The mention of oligomerization states (dimer/decamer) is consistent with typical 2-Cys peroxiredoxin biology, and the thioredoxin/thioredoxin-reductase regeneration system is correct.

What BioReason misses:
- The signaling role of tpx1 -- it acts as a MAP kinase scaffold (GO:0005078, EXP from PMID:37572670), which is a notable non-core function
- The role in transcriptional regulation (positive and negative regulation of transcription by RNA polymerase II)
- The protein-disulfide reductase activity (GO:0015035)
- The chaperone activity (GO:0051082/GO:0044183) -- tpx1 also has holdase-type chaperone function (PMID:20356456), similar to but stronger than pmp20
- The fact that tpx1 is described as "essential as a H2O2 scavenger during aerobic growth" (PMID:17409354), not just during oxidative stress

Comparison with interpro2go:

The interpro2go annotation (GO_REF:0000002) assigns peroxiredoxin activity (GO:0051920), which is correct and accepted in the curated review. BioReason correctly recapitulates and elaborates on this interpro2go annotation, providing a well-grounded functional narrative. Unlike the pmp20 case where BioReason incorrectly assumed peroxidase activity from the domain, here tpx1 actually does have the full catalytic apparatus (including resolving cysteine), making the domain-to-function inference valid. BioReason and interpro2go are aligned and both correct for the core peroxidase function.

Notes on thinking trace

The trace provides a thorough and accurate analysis of the domain architecture. The reasoning from thioredoxin-like fold through peroxiredoxin/AhpC-type identity to peroxidase function is sound and well-calibrated for this protein. The C-terminal domain discussion about oligomerization regulation is a nice mechanistic detail.

📄 View Raw YAML

id: O74887
gene_symbol: tpx1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:284812
  label: Schizosaccharomyces pombe (strain 972 / ATCC 24843)
description: >-
  Tpx1 is the major thioredoxin-dependent peroxiredoxin in Schizosaccharomyces
  pombe, catalyzing peroxide reduction to maintain low intracellular H2O2 and
  supporting oxidative-stress adaptation through redox signaling.
existing_annotations:
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: cytosol is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0006979
    label: response to oxidative stress
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: response to oxidative stress may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0008379
    label: thioredoxin peroxidase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: thioredoxin peroxidase activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0042744
    label: hydrogen peroxide catabolic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: hydrogen peroxide catabolic process is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0045454
    label: cell redox homeostasis
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: cell redox homeostasis is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0000165
    label: MAPK cascade
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  review:
    summary: 'Manual review: MAPK cascade may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0004601
    label: peroxidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: 'Manual review: peroxidase activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: 'Manual review: nucleus is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Manual review: cytoplasm is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0016209
    label: antioxidant activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Manual review: antioxidant activity may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0016491
    label: oxidoreductase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Manual review: oxidoreductase activity may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0034599
    label: cellular response to oxidative stress
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Manual review: cellular response to oxidative stress is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0051920
    label: peroxiredoxin activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: 'Manual review: peroxiredoxin activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0140824
    label: thioredoxin-dependent peroxiredoxin activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Manual review: thioredoxin-dependent peroxiredoxin activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005078
    label: MAP kinase scaffold activity
  evidence_type: EXP
  original_reference_id: PMID:37572670
  review:
    summary: 'Manual review: MAP kinase scaffold activity may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    supported_by:
    - reference_id: PMID:37572670
      supporting_text: >-
        We demonstrate that a P38-Prdx fusion protein compensates for loss of the
        yeast scaffold protein Mcs4 and MAP3K activity, driving yeast into mitosis
- term:
    id: GO:0015035
    label: protein-disulfide reductase activity
  evidence_type: EXP
  original_reference_id: PMID:37572670
  review:
    summary: 'Manual review: protein-disulfide reductase activity may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:1900745
    label: positive regulation of p38MAPK cascade
  evidence_type: IMP
  original_reference_id: PMID:37572670
  review:
    summary: 'Manual review: positive regulation of p38MAPK cascade may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0061692
    label: cellular detoxification of hydrogen peroxide
  evidence_type: IMP
  original_reference_id: PMID:24521463
  review:
    summary: 'Manual review: cellular detoxification of hydrogen peroxide is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:22344694
  review:
    summary: 'Manual review: cytoplasm is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
    - reference_id: PMID:22344694
      supporting_text: >-
        The Crm1-dependent export of Pap1 prevails over the import, and therefore
        the transcription factor displays cytosolic localization prior to stress
        imposition (10)
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:20356456
  review:
    summary: 'Manual review: unfolded protein binding is better represented by a more specific replacement term for tpx1.'
    action: MODIFY
    reason: Modified to align with current curation guidance and improve term specificity.
    proposed_replacement_terms:
    - id: GO:0044183
      label: protein folding chaperone
- term:
    id: GO:0140824
    label: thioredoxin-dependent peroxiredoxin activity
  evidence_type: IDA
  original_reference_id: PMID:20356456
  review:
    summary: 'Manual review: thioredoxin-dependent peroxiredoxin activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
    - reference_id: PMID:20356456
      supporting_text: >-
        TPx (thioredoxin peroxidase) exhibited a capacity for peroxide reduction
        with the thioredoxin system.
- term:
    id: GO:0008379
    label: thioredoxin peroxidase activity
  evidence_type: IMP
  original_reference_id: PMID:24268782
  review:
    summary: 'Manual review: thioredoxin peroxidase activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:24268782
  review:
    summary: 'Manual review: positive regulation of transcription by RNA polymerase II may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0042744
    label: hydrogen peroxide catabolic process
  evidence_type: IMP
  original_reference_id: PMID:24521463
  review:
    summary: 'Manual review: hydrogen peroxide catabolic process is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0045454
    label: cell redox homeostasis
  evidence_type: IMP
  original_reference_id: PMID:24521463
  review:
    summary: 'Manual review: cell redox homeostasis is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0000122
    label: negative regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:22245228
  review:
    summary: 'Manual review: negative regulation of transcription by RNA polymerase II may be context-dependent or peripheral for tpx1.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0042744
    label: hydrogen peroxide catabolic process
  evidence_type: IMP
  original_reference_id: PMID:22245228
  review:
    summary: 'Manual review: hydrogen peroxide catabolic process is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:22245228
  review:
    summary: 'Manual review: cytoplasm is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0004601
    label: peroxidase activity
  evidence_type: IDA
  original_reference_id: PMID:17409354
  review:
    summary: 'Manual review: peroxidase activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17409354
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for tpx1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
- term:
    id: GO:0045454
    label: cell redox homeostasis
  evidence_type: IMP
  original_reference_id: PMID:17409354
  review:
    summary: 'Manual review: cell redox homeostasis is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0051920
    label: peroxiredoxin activity
  evidence_type: IDA
  original_reference_id: PMID:17409354
  review:
    summary: 'Manual review: peroxiredoxin activity is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:16823372
  review:
    summary: 'Manual review: nucleus is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:16823372
  review:
    summary: 'Manual review: cytosol is consistent with known biology of tpx1.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:15824112
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for tpx1.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:15824112
  title: Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch controlling the transcriptional response to increasing levels of hydrogen peroxide.
  findings: []
- id: PMID:16823372
  title: ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe.
  findings: []
- id: PMID:17409354
  title: The peroxiredoxin Tpx1 is essential as a H2O2 scavenger during aerobic growth in fission yeast.
  findings: []
- id: PMID:20356456
  title: Distinct functional roles of peroxiredoxin isozymes and glutathione peroxidase from fission yeast, Schizosaccharomyces pombe.
  findings: []
- id: PMID:22245228
  title: Inactivation of a peroxiredoxin by hydrogen peroxide is critical for thioredoxin-mediated repair of oxidized proteins and cell survival.
  findings: []
- id: PMID:22344694
  title: The transcription factors Pap1 and Prr1 collaborate to activate antioxidant, but not drug tolerance, genes in response to H2O2.
  findings: []
- id: PMID:24268782
  title: A peroxiredoxin promotes H2O2 signaling and oxidative stress resistance by oxidizing a thioredoxin family protein.
  findings: []
- id: PMID:24521463
  title: A genetic approach to study H2O2 scavenging in fission yeast--distinct roles of peroxiredoxin and catalase.
  findings: []
- id: PMID:37572670
  title: A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms.
  findings: []
core_functions:
- description: >-
    Thioredoxin-dependent peroxiredoxin activity that detoxifies H2O2 and
    maintains cellular redox balance during aerobic growth and peroxide stress.
  supported_by:
  - reference_id: PMID:17409354
    supporting_text: >-
      The peroxiredoxin Tpx1 is essential as a H2O2 scavenger during aerobic
      growth in fission yeast.
  - reference_id: PMID:20356456
    supporting_text: >-
      TPx (thioredoxin peroxidase) exhibited a capacity for peroxide reduction
      with the thioredoxin system.
  molecular_function:
    id: GO:0140824
    label: thioredoxin-dependent peroxiredoxin activity
  directly_involved_in:
  - id: GO:0042744
    label: hydrogen peroxide catabolic process
  - id: GO:0045454
    label: cell redox homeostasis
  locations:
  - id: GO:0005829
    label: cytosol

tpx1

Gene Description

Existing Annotations Review

Core Functions

Thioredoxin-dependent peroxiredoxin activity that detoxifies H2O2 and maintains cellular redox balance during aerobic growth and peroxide stress.

References

📚 Additional Documentation

Deep Research Bioreason

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Deep Research Bioreason Rl

BioReason Chat Export

Thinking Trace

Functional Summary

UniProt Summary

InterPro Domains

GO Terms

Bioreason Rl Review

BioReason-Pro RL Review: tpx1 (S. pombe)

Functional Summary Review

Notes on thinking trace

📄 View Raw YAML