NADPH-driven glutathione/glutaredoxin and thioredoxin systems with peroxide and superoxide scavenging

Cells keep their thiols reduced and remove reactive oxygen species with two parallel NADPH-driven thiol-disulfide relays and a set of thiol-independent scavengers. In the glutathione/glutaredoxin system, the FAD enzyme glutathione reductase uses NADPH to reduce glutathione disulfide to glutathione, and glutathione in turn reduces dithiol glutaredoxins, which reduce protein disulfides and glutathione-protein mixed disulfides. In the thioredoxin system, thioredoxin reductase uses NADPH to reduce thioredoxin, which reduces protein disulfides, supplies electrons to biosynthetic reductases such as ribonucleotide reductase and PAPS reductase, and reduces the thiol peroxidases. Thioredoxin reductase is a low-molecular-weight flavoenzyme in fungi, plants and bacteria and a high-molecular-weight selenoprotein related to glutathione reductase in animals. Hydrogen peroxide and organic hydroperoxides are reduced by several families of thioredoxin-dependent thiol peroxidases (typical 2-Cys peroxiredoxins, glutathione-peroxidase-like peroxiredoxins, atypical 2-Cys and BCP-type peroxiredoxins). Superoxide dismutases convert superoxide to hydrogen peroxide (Cu/Zn enzyme in the cytosol and mitochondrial intermembrane space, Mn enzyme in the mitochondrial matrix), and haem catalases dismutate hydrogen peroxide to water and oxygen without thiol reductant. The two thiol systems overlap: in budding yeast at least one cytosolic thioredoxin or dithiol glutaredoxin is required for viability.

MODULE:glutathione_thioredoxin_redox_systemsDRAFTCONCRETEBiological Processmodules/glutathione_thioredoxin_redox_systems.yaml
cell redox homeostasisGO:0045454 cellular oxidant detoxificationGO:0098869
YeastPathways:GLUT-REDOX2-PWY
glutathione-glutaredoxin redox reactions (S. cerevisiae, SGD YeastPathways)
YeastCyc lists GLUTATHIONE-REDUCT-NADPH-RXN (GLR1), a gene-less glutaredoxin reduction, GSHTRAN-RXN (GTT1, GTT2) and GLUTATHIONE-PEROXIDASE-RXN (GPX1, GPX2, HYR1). GLR1 was retained; the GPX1/GPX2/HYR1 proteins were retained but moved to a thioredoxin-dependent peroxiredoxin activity (PMID:16251189, PMID:12437921); the glutathione transferases were left out as conjugation enzymes rather than redox-relay components.
YeastPathways:PWY3O-592
glutathione-glutaredoxin system (S. cerevisiae, SGD YeastPathways)
YeastCyc lists GLR1 and gene-less glutaredoxin reactions; GRX1 and GRX2 were added as the dithiol glutaredoxins (PMID:9571241).
YeastPathways:THIOREDOX-PWY
thioredoxin pathway (S. cerevisiae, SGD YeastPathways)
YeastCyc lists THIOREDOXIN-REDUCT-NADPH-RXN (TRR1, TRR2) and a gene-less thioredoxin reaction; TRX1 and TRX2 were added as the cytosolic thioredoxins.
YeastPathways:DETOX1-PWY
superoxide radicals degradation (S. cerevisiae, SGD YeastPathways)
YeastCyc lists CATAL-RXN (CTA1, CTT1) and SUPEROX-DISMUT-RXN (SOD1, SOD2); all four were retained.
GO:0045454
cell redox homeostasis
Module-level process for the two NADPH-driven thiol-disulfide relays.
GO:0098869
cellular oxidant detoxification
Module-level process for peroxide and superoxide removal.
PMID:11169096
Role of the glutathione/glutaredoxin and thioredoxin systems in yeast growth and response to stress conditions.
Review of the yeast glutathione/glutaredoxin and thioredoxin systems in redox homeostasis.
PMID:2668278
Thioredoxin and glutaredoxin systems.
Classic review defining the NADPH-thioredoxin reductase-thioredoxin and NADPH-glutathione reductase-glutathione-glutaredoxin systems.
PMID:10844700
A single glutaredoxin or thioredoxin gene is essential for viability in the yeast Saccharomyces cerevisiae.
The trx1 trx2 grx1 grx2 quadruple mutant is inviable and any single remaining gene suffices; thioredoxins are the main reductants of PAPS reductase.
PMID:12612609
Non-reciprocal regulation of the redox state of the glutathione-glutaredoxin and thioredoxin systems.
Thioredoxins are kept reduced independently of the glutathione system, whereas glutaredoxin redox state follows GSSG/2GSH; Trr1 but not Glr1 is needed for normal growth.
PMID:15701801
Overlapping roles of the cytoplasmic and mitochondrial redox regulatory systems in the yeast Saccharomyces cerevisiae.
S. cerevisiae has a cytoplasmic (TRX1, TRX2, TRR1) and a mitochondrial (TRX3, TRR2) thioredoxin system; Glr1 and Trr2 overlap in keeping Trx3 reduced.
PMID:10037727
Identification and functional characterization of a novel mitochondrial thioredoxin system in Saccharomyces cerevisiae.
TRX3 and TRR2 form a mitochondrial thioredoxin system; trr2 mutants are H2O2-sensitive.
PMID:8843443
Yeast glutathione reductase is required for protection against oxidative stress and is a target gene for yAP-1 transcriptional regulation.
glr1 mutants lack glutathione reductase activity, accumulate GSSG and are oxidant-sensitive.
PMID:9571241
The yeast Saccharomyces cerevisiae contains two glutaredoxin genes that are required for protection against reactive oxygen species.
GRX1 and GRX2 encode glutathione-dependent disulfide oxidoreductases required for oxidant resistance.
PMID:7961686
Thioredoxin-dependent peroxide reductase from yeast.
Yeast TSA1 is a dimeric 2-Cys peroxidase that reduces H2O2 and alkyl hydroperoxides with electrons from thioredoxin, thioredoxin reductase and NADPH.
PMID:10681558
Distinct physiological functions of thiol peroxidase isoenzymes in Saccharomyces cerevisiae.
Five yeast thioredoxin-supported thiol peroxidases (TSA1, TSA2, AHP1, mitochondrial PRX1 and nuclear DOT5) have distinct localizations.
PMID:16251189
GPX2, encoding a phospholipid hydroperoxide glutathione peroxidase homologue, codes for an atypical 2-Cys peroxiredoxin in Saccharomyces cerevisiae.
Gpx2 reduces peroxides with thioredoxin and is far less active with glutathione/glutathione reductase.
PMID:12437921
A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation.
The GPx-like Gpx3 (HYR1/Orp1) senses H2O2 and oxidizes Yap1; thioredoxin reduces both sensor and regulator.
PMID:10480913
Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae.
GPX1, GPX2 and GPX3/HYR1 account for cellular GSH peroxidase activity; gpx3 mutants are peroxide-hypersensitive.
PMID:11445588
Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione peroxidases.
The three yeast GPx homologues are phospholipid-hydroperoxide-type enzymes that protect against lipid peroxidation.
PMID:3290902
The copper, zinc-superoxide dismutase gene of Saccharomyces cerevisiae: cloning, sequencing, and biological activity.
SOD1 encodes yeast Cu,Zn-superoxide dismutase and corrects dioxygen sensitivity of a Cu,Zn-SOD-deficient strain.
PMID:15851472
Manganese activation of superoxide dismutase 2 in the mitochondria of Saccharomyces cerevisiae.
SOD2 is the mitochondrial Mn superoxide dismutase.
PMID:8425895
Two independent peroxisomal targeting signals in catalase A of Saccharomyces cerevisiae.
Catalase A (CTA1) is targeted to peroxisomes by two independent signals.
PMID:14998369
Dual targeting of yeast catalase A to peroxisomes and mitochondria.
Catalase A is also imported into mitochondria under respiratory conditions.
UniProtKB:P06115
Catalase T (S. cerevisiae CTT1)
CTT1 encodes the cytosolic catalase T.
file:yeast/TSA1/TSA1-ai-review.yaml
TSA1 gene review (S. cerevisiae)
Core function GO:0140824 thioredoxin-dependent peroxiredoxin activity in cytosol.
file:yeast/SOD2/SOD2-ai-review.yaml
SOD2 gene review (S. cerevisiae)
Core function GO:0004784 superoxide dismutase activity in the mitochondrial matrix.
file:human/GSR/GSR-ai-review.yaml
GSR gene review (human)
Core function GO:0004362 glutathione-disulfide reductase (NADPH) activity.
file:human/TXN/TXN-ai-review.yaml
TXN gene review (human)
Core function GO:0015035 protein-disulfide reductase activity in cytosol, cell redox homeostasis.
file:human/SOD1/SOD1-ai-review.yaml
SOD1 gene review (human)
Core function GO:0004784 in cytosol and mitochondrial intermembrane space.
18Nodes
9Parts
3Variant Sets
8Variants
12Annotons
6Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:glutathione_thioredoxin_redox_systems deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

29 gene-function check(s) reflected in core functions · 0 conflict(s) · 6 evidence or coverage gap(s) (52 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

AnnotonParticipantFunctionAssessment
gsr_redox_activity GLR1 (Saccharomyces cerevisiae)
UniProtKB:P41921
Family Representative 		glutathione-disulfide reductase (NADPH) activity
GO:0004362 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gsr_redox_activity pgr1 (Schizosaccharomyces pombe)
UniProtKB:P78965
Family Representative 		glutathione-disulfide reductase (NADPH) activity
GO:0004362 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gsr_redox_activity GSR (human)
UniProtKB:P00390
Family Representative 		glutathione-disulfide reductase (NADPH) activity
GO:0004362 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dithiol_grx_activity GRX1 (Saccharomyces cerevisiae)
UniProtKB:P25373
Family Representative 		glutathione disulfide oxidoreductase activity
GO:0015038 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dithiol_grx_activity GRX2 (Saccharomyces cerevisiae)
UniProtKB:P17695
Family Representative 		glutathione disulfide oxidoreductase activity
GO:0015038 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
dithiol_grx_activity GLRX (human)
UniProtKB:P35754
Family Representative 		glutathione disulfide oxidoreductase activity
GO:0015038 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
low_mr_trxr_activity TRR1 (Saccharomyces cerevisiae)
UniProtKB:P29509
Family Representative 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
low_mr_trxr_activity TRR2 (Saccharomyces cerevisiae)
UniProtKB:P38816
Family Representative 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
low_mr_trxr_activity trr1 (Schizosaccharomyces pombe)
UniProtKB:Q92375
Family Representative 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
high_mr_trxr_activity TXNRD1 (human)
UniProtKB:Q16881
Family Representative 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
cytosolic_trx_activity TRX1 (Saccharomyces cerevisiae)
UniProtKB:P22217
Family Representative 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cytosolic_trx_activity TRX2 (Saccharomyces cerevisiae)
UniProtKB:P22803
Family Representative 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cytosolic_trx_activity TXN (human)
UniProtKB:P10599
Family Representative 		protein-disulfide reductase activity
GO:0015035 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
typical_2cys_prx_activity TSA1 (Saccharomyces cerevisiae)
UniProtKB:P34760
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
typical_2cys_prx_activity TSA2 (Saccharomyces cerevisiae)
UniProtKB:Q04120
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
typical_2cys_prx_activity tpx1 (Schizosaccharomyces pombe)
UniProtKB:O74887
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
typical_2cys_prx_activity PRDX1 (human)
UniProtKB:Q06830
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
gpx_like_prx_activity HYR1 / GPX3 / ORP1 (Saccharomyces cerevisiae)
UniProtKB:P40581
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gpx_like_prx_activity GPX2 (Saccharomyces cerevisiae)
UniProtKB:P38143
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gpx_like_prx_activity GPX1 (Saccharomyces cerevisiae)
UniProtKB:P36014
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
gpx_like_prx_activity gpx1 (Schizosaccharomyces pombe)
UniProtKB:O59858
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
ahp1_activity AHP1 (Saccharomyces cerevisiae)
UniProtKB:P38013
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bcp_prx_activity DOT5 (Saccharomyces cerevisiae)
UniProtKB:P40553
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
bcp_prx_activity bcp1 (Schizosaccharomyces pombe)
UniProtKB:O94561
Family Representative 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cuzn_sod_activity SOD1 (Saccharomyces cerevisiae)
UniProtKB:P00445
Family Representative 		superoxide dismutase activity
GO:0004784 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cuzn_sod_activity sod1 (Schizosaccharomyces pombe)
UniProtKB:P28758
Family Representative 		superoxide dismutase activity
GO:0004784 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cuzn_sod_activity SOD1 (human)
UniProtKB:P00441
Family Representative 		superoxide dismutase activity
GO:0004784 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mn_sod_activity SOD2 (Saccharomyces cerevisiae)
UniProtKB:P00447
Family Representative 		superoxide dismutase activity
GO:0004784 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mn_sod_activity sod2 (Schizosaccharomyces pombe)
UniProtKB:Q9UQX0
Family Representative 		superoxide dismutase activity
GO:0004784 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
mn_sod_activity SOD2 (human)
UniProtKB:P04179
Family Representative 		superoxide dismutase activity
GO:0004784 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
catalase_activity CTA1 (Saccharomyces cerevisiae)
UniProtKB:P15202
Family Representative 		catalase activity
GO:0004096 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
catalase_activity CTT1 (Saccharomyces cerevisiae)
UniProtKB:P06115
Family Representative 		catalase activity
GO:0004096 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
catalase_activity cta1 (Schizosaccharomyces pombe)
UniProtKB:P55306
Family Representative 		catalase activity
GO:0004096 		Core Supported
The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
catalase_activity CAT (human)
UniProtKB:P04040
Family Representative 		catalase activity
GO:0004096 		Review Missing
No ai-review exists for this protein; its function and core-function coverage cannot yet be checked.
gsr_redox_activity glutathione reductase family
PANTHER:PTHR42737:SF2
Family 		glutathione-disulfide reductase (NADPH) activity
GO:0004362 		Family Supported
Family review supports GO:0004362 for PANTHER:PTHR42737:SF2. GR subfamilies; glutathione_thioredoxin_redox_systems and glutathione_synthesis_gamma_glutamyl_cycle select the base family, which also takes in the TrxRs.
gsr_redox_activity glutathione reductase family
PANTHER:PTHR42737:SF5
Family 		glutathione-disulfide reductase (NADPH) activity
GO:0004362 		Family Supported
Family review supports GO:0004362 for PANTHER:PTHR42737:SF5. GR subfamilies; glutathione_thioredoxin_redox_systems and glutathione_synthesis_gamma_glutamyl_cycle select the base family, which also takes in the TrxRs.
gsr_redox_activity glutathione reductase family
PANTHER:PTHR42737:SF9
Family 		glutathione-disulfide reductase (NADPH) activity
GO:0004362 		Family Supported
Family review supports GO:0004362 for PANTHER:PTHR42737:SF9. GR subfamilies; glutathione_thioredoxin_redox_systems and glutathione_synthesis_gamma_glutamyl_cycle select the base family, which also takes in the TrxRs.
dithiol_grx_activity dithiol (CPYC) glutaredoxins
Family 		glutathione disulfide oxidoreductase activity
GO:0015038 		Family Id Missing
The family has no identifier linking it to a curated family review.
low_mr_trxr_activity low-Mr thioredoxin reductase family
PANTHER:PTHR48105:SF16
Family 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Family Supported
Family review supports GO:0004791 for PANTHER:PTHR48105:SF16. Asserted by glutathione_thioredoxin_redox_systems; accepted by TRR1, TRR2 and trr1.
high_mr_trxr_activity selenocysteine thioredoxin reductase subfamily of the glutathione reductase family
PANTHER:PTHR42737:SF8
Family 		thioredoxin-disulfide reductase (NADPH) activity
GO:0004791 		Family Supported
Family review supports GO:0004791 for PANTHER:PTHR42737:SF8. TrxR subfamilies; glutathione_thioredoxin_redox_systems selects SF8 for TXNRD1.
cytosolic_trx_activity cytosolic thioredoxin family
PANTHER:PTHR46115
Family 		protein-disulfide reductase activity
GO:0015035 		Family Supported
Family review supports GO:0015035 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by every reviewed member.
typical_2cys_prx_activity typical 2-Cys peroxiredoxin family
PANTHER:PTHR10681
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae TSA1/TSA2, S. pombe tpx1 and human PRDX4.
gpx_like_prx_activity glutathione peroxidase family (cysteine-type, fungal)
PANTHER:PTHR11592:SF78
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 for PANTHER:PTHR11592:SF78. The fungal GPX-like peroxiredoxins of SF78 (S. cerevisiae GPX1, GPX2, HYR1/GPX3 and S. pombe gpx1) use thioredoxin rather than glutathione, as glutathione_thioredoxin_redox_systems selects. Not established for the animal selenocysteine GPX subfamilies. SF78 is wider than its fungal members: it also holds plant, algal and bacterial GPX homologs (Arabidopsis GPX2, Chlamydomonas GPX5 and GPX1, Synechocystis gpx1 and gpx2, B. subtilis bsaA, Neisseria gpxA, Lactococcus gpo). Their reductant was not checked member by member here, so the scope rests on the fungal members' evidence. The bacterial BtuE subfamily SF40 is also thioredoxin-dependent: purified E. coli BtuE reduces H2O2 and organic hydroperoxides with thioredoxin A or C as the preferred electron donor (PMID:20621065), so SF40 is included.
ahp1_activity PRX5-type peroxiredoxin family
PANTHER:PTHR10430:SF16
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 for PANTHER:PTHR10430:SF16. The PRX5-type peroxiredoxins, not pmp20 (SF39). glutathione_thioredoxin_redox_systems selects the base family for AHP1.
ahp1_activity PRX5-type peroxiredoxin family
PANTHER:PTHR10430:SF8
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 for PANTHER:PTHR10430:SF8. The PRX5-type peroxiredoxins, not pmp20 (SF39). glutathione_thioredoxin_redox_systems selects the base family for AHP1.
ahp1_activity PRX5-type peroxiredoxin family
PANTHER:PTHR10430:SF30
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 for PANTHER:PTHR10430:SF30. The PRX5-type peroxiredoxins, not pmp20 (SF39). glutathione_thioredoxin_redox_systems selects the base family for AHP1.
ahp1_activity PRX5-type peroxiredoxin family
PANTHER:PTHR10430:SF33
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 for PANTHER:PTHR10430:SF33. The PRX5-type peroxiredoxins, not pmp20 (SF39). glutathione_thioredoxin_redox_systems selects the base family for AHP1.
ahp1_activity PRX5-type peroxiredoxin family
PANTHER:PTHR10430:SF34
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 for PANTHER:PTHR10430:SF34. The PRX5-type peroxiredoxins, not pmp20 (SF39). glutathione_thioredoxin_redox_systems selects the base family for AHP1.
bcp_prx_activity bacterioferritin-comigratory protein (BCP) peroxiredoxin family
PANTHER:PTHR42801
Family 		thioredoxin-dependent peroxiredoxin activity
GO:0140824 		Family Supported
Family review supports GO:0140824 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by DOT5, bcp1 and Bcp.
cuzn_sod_activity Cu/Zn superoxide dismutase family
PANTHER:PTHR10003
Family 		superoxide dismutase activity
GO:0004784 		Family Supported
Family review supports GO:0004784 FAMILY_WIDE. The glutathione_thioredoxin_redox_systems module asserts this activity for the family. It holds for the SOD1-type enzymes, which make up most of the family, but not for the CCS copper chaperones, listed as member exceptions.
mn_sod_activity Mn/Fe superoxide dismutase family
PANTHER:PTHR11404
Family 		superoxide dismutase activity
GO:0004784 		Family Supported
Family review supports GO:0004784 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by S. cerevisiae SOD2, S. pombe sod2 and C. elegans sod-2/sod-3.
catalase_activity monofunctional haem catalase family
PANTHER:PTHR11465
Family 		catalase activity
GO:0004096 		Family Supported
Family review supports GO:0004096 FAMILY_WIDE. Asserted by glutathione_thioredoxin_redox_systems; accepted by CTA1, CTT1, S. pombe cta1 and P. putida KatA.

Gene-review completeness (29/34 grounded genes reviewed)

25 complete review(s) · 21 with deep research · 5 missing review · 8 reviewed but lacking deep research

Gene Review Complete Deep research
AHP1 P38013 ✓ ✓ ✓
bcp1 O94561 ✓ ✓ ✗
CTA1 P15202 ✓ ✓ ✓
cta1 P55306 ✓ ✓ ✗
CTT1 P06115 ✓ ✓ ✓
DOT5 P40553 ✓ ✓ ✓
GLR1 P41921 ✓ ✓ ✓
gpx1 O59858 ✓ ✓ ✗
GPX1 P36014 ✓ ✓ ✓
GPX2 P38143 ✓ ✓ ✓
GRX1 P25373 ✓ ✓ ✓
GRX2 P17695 ✓ ✓ ✓
GSR P00390 ✓ ✓ ✗
HYR1 P40581 ✓ 23/25 ✓
CAT (human) P04040 ✗ — —
SOD2 (human) P04179 ✗ — —
GLRX (human) P35754 ✗ — —
pgr1 P78965 ✓ ✓ ✗
PRDX1 (human) Q06830 ✗ — —
TXNRD1 (human) Q16881 ✗ — —
SOD1 P00441 ✓ ✓ ✓
SOD1 P00445 ✓ ✓ ✓
sod1 P28758 ✓ ✓ ✗
SOD2 P00447 ✓ ✓ ✓
sod2 Q9UQX0 ✓ ✓ ✗
tpx1 O74887 ✓ ✓ ✓
TRR1 P29509 ✓ ✓ ✓
trr1 Q92375 ✓ 13/14 ✗
TRR2 P38816 ✓ ✓ ✓
TRX1 P22217 ✓ ✓ ✓
TRX2 P22803 ✓ ✓ ✓
TSA1 P34760 ✓ ✓ ✓
TSA2 Q04120 ✓ 38/39 ✓
TXN P10599 ✓ 64/68 ✓

Details

Context
eukaryotesNCBITaxon:2759
Glutathione/glutaredoxin and thioredoxin systems with ROS scavengingBiological Processglutathione_thioredoxin_redox_systems
cell redox homeostasisGO:0045454 cellular oxidant detoxificationGO:0098869
Context
eukaryotesNCBITaxon:2759

NEW (YeastPathways project, 2026-10), built from YeastCyc GLUT-REDOX2-PWY, PWY3O-592, THIOREDOX-PWY and DETOX1-PWY. Boundary: the two NADPH-driven thiol-disulfide relays (glutathione reductase -> glutathione -> dithiol glutaredoxin; thioredoxin reductase -> thioredoxin) plus the peroxide and superoxide scavengers that they or no thiol feed (thiol peroxidases, superoxide dismutases, catalases). Glutathione synthesis and turnover are in glutathione_synthesis_gamma_glutamyl_cycle, which also lists glutathione reductase; glutathione S-transferases (GTT1, GTT2) and vacuolar GS-X pumps (YCF1) are conjugation/transport and are left out; monothiol glutaredoxins (GRX3/4/5) act mainly in iron-sulfur cluster and iron-regulation pathways; thioredoxin-reduced biosynthetic enzymes (PAPS reductase MET16, ribonucleotide reductase) are consumers in other modules. YeastCyc corrections: the frames have no gene for glutaredoxin or thioredoxin reactions (GRX1/GRX2, TRX1/TRX2 added); GPX1, GPX2 and HYR1 are thioredoxin-dependent cysteine peroxiredoxins, not glutathione peroxidases (PMID:16251189, PMID:12437921); the "superoxide radicals degradation" frame does list SOD1 and SOD2 in addition to the catalases. The peroxiredoxins TSA1, TSA2, AHP1 and DOT5 are absent from the YeastCyc frames and were added. Mitochondria have their own thioredoxin system (TRR2 included under the low-Mr reductase; TRX3 is in PANTHER PTHR10438, not PTHR46115, so it is described here rather than listed under the cytosolic thioredoxin selector) and a 1-Cys peroxiredoxin (PRX1) that is not modelled. GO-CAM disagreements: all four SGD models place every activity in cytosol (SOD2 and TRR2 are mitochondrial, CTA1 peroxisomal), THIOREDOX-PWY is part of the obsolete GO:0006125, and GLUT-REDOX2-PWY types the GPx-like enzymes with GO:0004602 glutathione peroxidase activity. Thioredoxin reductase is an EXACTLY_ONE variant set (low-Mr PTHR48105 in fungi vs high-Mr selenoprotein PTHR42737:SF8 in animals). No PomBase GO-CAM is linked for this group, but S. pombe exemplars are included where the ortholog is clear.

Connections

trx_step -> thiol_peroxidase_step Provides Input For
Reduced thioredoxin regenerates the oxidized thiol peroxidases.
sod_step -> thiol_peroxidase_step Provides Input For
Hydrogen peroxide made by superoxide dismutase is reduced by thiol peroxidases.
sod_step -> catalase_step Provides Input For
Hydrogen peroxide made by superoxide dismutase is dismutated by catalase.
The two relays back each other up (one cytosolic thioredoxin or dithiol glutaredoxin is required for viability), but the thioredoxin redox state is maintained independently of glutathione (PMID:12612609); represented as functional overlap, not electron transfer.
Part 1: glutathione/glutaredoxin system
NADPH - glutathione reductase - glutathione - glutaredoxin relayBiological Processglutathione_glutaredoxin_system

Connections

gsr_step -> grx_step Provides Input For
Reduced glutathione made by glutathione reductase reduces glutaredoxins.
Part 1: GSSG reduction by NADPH
Glutathione reductaseReactiongsr_step

Annotons

Glutathione-disulfide reductase (GLR1/GSR)
gsr_redox_activity
Participant: Family: glutathione reductase family
Family:
glutathione reductase family
Representative Members: GLR1 (Saccharomyces cerevisiae)UniProtKB:P41921 pgr1 (Schizosaccharomyces pombe)UniProtKB:P78965 GSR (human)UniProtKB:P00390

Function

glutathione-disulfide reductase (NADPH) activityGO:0004362
Substrates: glutathione disulfide NADPH
Products: glutathione (2 GSH) NADP+

Processes

cell redox homeostasisGO:0045454

Locations

cytosolGO:0005829

Keeps the glutathione pool reduced; also acts in mitochondria, where it overlaps with TRR2 in keeping TRX3 reduced.

Part 2: glutathione-dependent disulfide reduction by dithiol glutaredoxins
Dithiol glutaredoxinReactiongrx_step

Annotons

Dithiol glutaredoxin (GRX1/GRX2)
dithiol_grx_activity
Participant: Family: dithiol (CPYC) glutaredoxins
Family:
dithiol (CPYC) glutaredoxins Yeast GRX1/GRX2 are in PANTHER PTHR45694:SF18 and human GLRX in PTHR46185, so no single family id is asserted. Monothiol (CGFS) glutaredoxins function mainly in iron-sulfur cluster trafficking and are not included.
Representative Members: GRX1 (Saccharomyces cerevisiae)UniProtKB:P25373 GRX2 (Saccharomyces cerevisiae)UniProtKB:P17695 GLRX (human)UniProtKB:P35754

Function

glutathione disulfide oxidoreductase activityGO:0015038
Substrates: glutathione protein disulfide or glutathione-protein mixed disulfide
Products: glutathione disulfide reduced protein thiols

Processes

cell redox homeostasisGO:0045454

Locations

cytosolGO:0005829

Transfers glutathione reducing power to protein disulfides and glutathione mixed disulfides.

Part 2: thioredoxin system
NADPH - thioredoxin reductase - thioredoxin relayBiological Processthioredoxin_system

Connections

trxr_step -> trx_step Provides Input For
Reduced thioredoxin is generated by thioredoxin reductase.
Part 1: thioredoxin reduction by NADPH
Thioredoxin reductaseReactiontrxr_step
Variant set: Thioredoxin reductase type by enzyme family (lineage) (Exactly One)
Low-molecular-weight thioredoxin reductase (fungi, plants, bacteria)Reactionlow_mr_trxr

Annotons

Low-Mr thioredoxin reductase (TRR1/TRR2)
low_mr_trxr_activity
Participant: Family: low-Mr thioredoxin reductase family
Family:
low-Mr thioredoxin reductase family
Representative Members: TRR1 (Saccharomyces cerevisiae)UniProtKB:P29509 TRR2 (Saccharomyces cerevisiae)UniProtKB:P38816 trr1 (Schizosaccharomyces pombe)UniProtKB:Q92375

Function

thioredoxin-disulfide reductase (NADPH) activityGO:0004791
Substrates: oxidized thioredoxin NADPH
Products: reduced thioredoxin NADP+

Processes

cell redox homeostasisGO:0045454

FAD enzyme reducing thioredoxin; cytosolic TRR1 and mitochondrial TRR2 in budding yeast.

High-molecular-weight selenoprotein thioredoxin reductase (animals)Reactionhigh_mr_trxr

Annotons

High-Mr thioredoxin reductase (TXNRD1)
high_mr_trxr_activity
Participant: Family: selenocysteine thioredoxin reductase subfamily of the glutathione reductase family
Family:
selenocysteine thioredoxin reductase subfamily of the glutathione reductase familyPANTHER:PTHR42737:SF8
Representative Members: TXNRD1 (human)UniProtKB:Q16881

Function

thioredoxin-disulfide reductase (NADPH) activityGO:0004791
Substrates: oxidized thioredoxin NADPH
Products: reduced thioredoxin NADP+

Processes

cell redox homeostasisGO:0045454

Animal selenoprotein thioredoxin reductase, homologous to glutathione reductase.

Part 2: protein disulfide reduction by thioredoxin
ThioredoxinReactiontrx_step

Annotons

Cytosolic thioredoxin (TRX1/TRX2/TXN)
cytosolic_trx_activity
Participant: Family: cytosolic thioredoxin family
Family:
cytosolic thioredoxin familyPANTHER:PTHR46115
Representative Members: TRX1 (Saccharomyces cerevisiae)UniProtKB:P22217 TRX2 (Saccharomyces cerevisiae)UniProtKB:P22803 TXN (human)UniProtKB:P10599

Function

protein-disulfide reductase activityGO:0015035
Substrates: protein disulfide (including oxidized peroxiredoxins, PAPS reductase and ribonucleotide reductase)
Products: reduced protein dithiol

Processes

cell redox homeostasisGO:0045454

Locations

cytosolGO:0005829

Reduces protein disulfides and supplies electrons to PAPS reductase, ribonucleotide reductase and thiol peroxidases.

Part 3: hydroperoxide reduction by thiol peroxidases
Thioredoxin-dependent thiol peroxidasesReactionthiol_peroxidase_step

Several non-homologous peroxiredoxin families reduce H2O2 and organic hydroperoxides with electrons from thioredoxin. In fungi the glutathione-peroxidase-like enzymes are cysteine (not selenocysteine) peroxiredoxins that use thioredoxin rather than glutathione.

Variant set: Thiol peroxidase families by enzyme family (One Or More)
Typical 2-Cys peroxiredoxins (TSA1/TSA2, PRDX1)Reactiontypical_2cys_prx

Annotons

Typical 2-Cys peroxiredoxin
typical_2cys_prx_activity
Participant: Family: typical 2-Cys peroxiredoxin family
Family:
typical 2-Cys peroxiredoxin familyPANTHER:PTHR10681
Representative Members: TSA1 (Saccharomyces cerevisiae)UniProtKB:P34760 TSA2 (Saccharomyces cerevisiae)UniProtKB:Q04120 tpx1 (Schizosaccharomyces pombe)UniProtKB:O74887 PRDX1 (human)UniProtKB:Q06830

Function

thioredoxin-dependent peroxiredoxin activityGO:0140824
Substrates: hydrogen peroxide or alkyl hydroperoxide reduced thioredoxin
Products: water or alcohol oxidized thioredoxin

Processes

hydrogen peroxide catabolic processGO:0042744

Locations

cytosolGO:0005829

Abundant cytosolic H2O2 scavengers; TSA1 is also a molecular chaperone (outside this module).

Glutathione-peroxidase-like peroxiredoxins (GPX1/GPX2/HYR1)Reactiongpx_like_prx

Annotons

GPx-like thioredoxin peroxidase
gpx_like_prx_activity
Participant: Family: glutathione peroxidase family (cysteine-type, fungal)
Family:
glutathione peroxidase family (cysteine-type, fungal)PANTHER:PTHR11592:SF78
Representative Members: HYR1 / GPX3 / ORP1 (Saccharomyces cerevisiae)UniProtKB:P40581 GPX2 (Saccharomyces cerevisiae)UniProtKB:P38143 GPX1 (Saccharomyces cerevisiae)UniProtKB:P36014 gpx1 (Schizosaccharomyces pombe)UniProtKB:O59858

Function

thioredoxin-dependent peroxiredoxin activityGO:0140824
Substrates: hydrogen peroxide, alkyl or phospholipid hydroperoxide reduced thioredoxin
Products: water or alcohol oxidized thioredoxin

Processes

hydrogen peroxide catabolic processGO:0042744

Lipid hydroperoxide and H2O2 reduction; HYR1 doubles as the Yap1 H2O2 sensor.

Atypical 2-Cys peroxiredoxin (AHP1)Reactionatypical_2cys_prx

Annotons

AHP1 alkyl hydroperoxide reductase
ahp1_activity
Participant: Family: PRX5-type peroxiredoxin family
Family:
PRX5-type peroxiredoxin family
Representative Members: AHP1 (Saccharomyces cerevisiae)UniProtKB:P38013

Function

thioredoxin-dependent peroxiredoxin activityGO:0140824

Processes

hydrogen peroxide catabolic processGO:0042744

Locations

cytosolGO:0005829

Cytosolic alkyl hydroperoxide reductase.

BCP-type peroxiredoxin (DOT5, bcp1)Reactionbcp_prx

Annotons

BCP-type nuclear thiol peroxidase
bcp_prx_activity
Participant: Family: bacterioferritin-comigratory protein (BCP) peroxiredoxin family
Family:
bacterioferritin-comigratory protein (BCP) peroxiredoxin familyPANTHER:PTHR42801
Representative Members: DOT5 (Saccharomyces cerevisiae)UniProtKB:P40553 bcp1 (Schizosaccharomyces pombe)UniProtKB:O94561

Function

thioredoxin-dependent peroxiredoxin activityGO:0140824

Processes

hydrogen peroxide catabolic processGO:0042744

Locations

nucleusGO:0005634

Nuclear thiol peroxidase.

Part 4: superoxide dismutation
Superoxide dismutaseReactionsod_step
Variant set: Superoxide dismutase metal and compartment by metal cofactor / compartment (One Or More)
Cu/Zn superoxide dismutase (cytosol and intermembrane space)Reactioncuzn_sod

Annotons

Cu/Zn superoxide dismutase (SOD1)
cuzn_sod_activity
Participant: Family: Cu/Zn superoxide dismutase family
Family:
Cu/Zn superoxide dismutase familyPANTHER:PTHR10003
Representative Members: SOD1 (Saccharomyces cerevisiae)UniProtKB:P00445 sod1 (Schizosaccharomyces pombe)UniProtKB:P28758 SOD1 (human)UniProtKB:P00441

Function

superoxide dismutase activityGO:0004784
Substrates: superoxide
Products: hydrogen peroxide dioxygen

Processes

removal of superoxide radicalsGO:0019430

Locations

cytosolGO:0005829 mitochondrial intermembrane spaceGO:0005758

Cytosolic and intermembrane-space superoxide dismutase.

Mn superoxide dismutase (mitochondrial matrix)Reactionmn_sod

Annotons

Mn superoxide dismutase (SOD2)
mn_sod_activity
Participant: Family: Mn/Fe superoxide dismutase family
Family:
Mn/Fe superoxide dismutase familyPANTHER:PTHR11404
Representative Members: SOD2 (Saccharomyces cerevisiae)UniProtKB:P00447 sod2 (Schizosaccharomyces pombe)UniProtKB:Q9UQX0 SOD2 (human)UniProtKB:P04179

Function

superoxide dismutase activityGO:0004784
Substrates: superoxide
Products: hydrogen peroxide dioxygen

Processes

removal of superoxide radicalsGO:0019430

Locations

mitochondrial matrixGO:0005759

Matrix superoxide dismutase.

Part 5: hydrogen peroxide dismutation (thiol-independent)
CatalaseReactioncatalase_step

Annotons

Haem catalase (CTA1/CTT1/CAT)
catalase_activity
Participant: Family: monofunctional haem catalase family
Family:
monofunctional haem catalase familyPANTHER:PTHR11465
Representative Members: CTA1 (Saccharomyces cerevisiae)UniProtKB:P15202 CTT1 (Saccharomyces cerevisiae)UniProtKB:P06115 cta1 (Schizosaccharomyces pombe)UniProtKB:P55306 CAT (human)UniProtKB:P04040

Function

catalase activityGO:0004096
Substrates: hydrogen peroxide (2)
Products: water (2) dioxygen

Processes

hydrogen peroxide catabolic processGO:0042744

Thiol-independent H2O2 sink; peroxisomal (CTA1) and cytosolic (CTT1) isozymes in budding yeast, so no single location is asserted.