gst-4

UniProt ID: Q21355
Organism: Caenorhabditis elegans
Review Status: COMPLETE
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Gene Description

GST-4 (K08F4.7, also called Ce-GST-p24) is a sigma-class glutathione S-transferase of C. elegans, a small cytosolic enzyme that conjugates reduced glutathione to hydrophobic electrophiles, with activity towards lipid peroxidation products. gst-4 is transcriptionally induced by oxidative stress (paraquat, pathogen-generated reactive oxygen species, light) through the transcription factor SKN-1, and its promoter-GFP fusion is a widely used reporter of SKN-1 activity. The enzyme is broadly distributed in tissues, and its abundance sets organismal resistance to oxidative stress: overexpression increases, and RNAi or deletion decreases, survival under intracellularly generated oxidative stress.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004364 glutathione transferase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA to glutathione transferase activity.
Reason: Core activity of sigma-class GSTs; experimentally assayed for GST-4.
Supporting Evidence:
file:worm/gst-4/gst-4-uniprot.txt
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles (By similarity).
PMID:12757851
The enzymatic activity of this detoxification enzyme was examined with various substrates, giving emphasis to lipid peroxidation products.
GO:0004364 glutathione transferase activity
IDA
PMID:12757851
A stress-responsive glutathione S-transferase confers resist... 		ACCEPT
Summary: Enzymatic activity of Ce-GST-p24 (K08F4.7 / GST-4) assayed with several substrates, emphasising lipid peroxidation products.
Reason: Direct biochemical evidence for the core activity.
Supporting Evidence:
PMID:12757851
The enzymatic activity of this detoxification enzyme was examined with various substrates, giving emphasis to lipid peroxidation products.
PMID:12757851
analysis of the K08F4.7 homozygous deletion mutant
GO:0004364 glutathione transferase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Automated (Rhea/EC 2.5.1.18) assignment.
Reason: Correct; duplicates the IBA/IDA.
Supporting Evidence:
file:worm/gst-4/gst-4-uniprot.txt
Reaction=RX + glutathione = an S-substituted glutathione + a halide anion + H(+)
GO:0005737 cytoplasm
IEA
GO_REF:0000117 		ACCEPT
Summary: ARBA prediction of cytoplasmic location.
Reason: Sigma-class GSTs are soluble cytosolic enzymes lacking targeting signals; the GFP fusion is widely distributed.
Supporting Evidence:
file:worm/gst-4/gst-4-uniprot.txt
Belongs to the GST superfamily. Sigma family.
PMID:12757851
The Ce-GST-p24 was also localized in BL1 C. elegans by confocal laser-scanning microscopy, revealing a wide-spread distribution profile.
GO:0006749 glutathione metabolic process
IBA
GO_REF:0000033 		ACCEPT
Summary: IBA to glutathione metabolic process.
Reason: GST-4 uses glutathione as co-substrate in conjugation reactions; appropriate general process for a GST.
Supporting Evidence:
file:worm/gst-4/gst-4-uniprot.txt
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles (By similarity).
GO:0006749 glutathione metabolic process
IDA
PMID:12757851
A stress-responsive glutathione S-transferase confers resist... 		ACCEPT
Summary: Inferred from the enzyme assays with glutathione.
Reason: Consistent with the demonstrated GST activity.
Supporting Evidence:
PMID:12757851
The enzymatic activity of this detoxification enzyme was examined with various substrates, giving emphasis to lipid peroxidation products.
GO:0043292 contractile muscle fiber
IDA
PMID:12757851
A stress-responsive glutathione S-transferase confers resist... 		KEEP AS NON CORE
Summary: Localisation of the GST-4::GFP fusion, which included muscle according to the curator's reading.
Reason: The cached abstract reports only a wide-spread distribution; the full text, read by the curator, presumably documents muscle fibre signal. Accepted as non-core; not the principal functional site.
Supporting Evidence:
PMID:12757851
The Ce-GST-p24 was also localized in BL1 C. elegans by confocal laser-scanning microscopy, revealing a wide-spread distribution profile.
GO:0006979 response to oxidative stress
IMP
PMID:12757851
A stress-responsive glutathione S-transferase confers resist... 		NEW
Summary: GST-4 levels determine oxidative stress resistance: overexpression raises it, RNAi or K08F4.7 deletion lowers it; the enzyme detoxifies lipid peroxidation products.
Reason: GST-4 performs part of the response (enzymatic conjugation/detoxification of oxidative products), satisfying the participation test; bidirectional dosage data support it. No process term beyond glutathione metabolism is currently annotated.
Supporting Evidence:
PMID:12757851
Stress experiments with BL1 demonstrated an increased resistance to intracellularly induced oxidative stress, as compared to wild type.
PMID:12757851
In both cases, the reduced Ce-GST-p24 enzyme level resulted in a significant decrease in the stress resistance of the nematodes.
PMID:12757851
The enzymatic activity of this detoxification enzyme was examined with various substrates, giving emphasis to lipid peroxidation products.

Core Functions

Sigma-class glutathione S-transferase conjugating glutathione to electrophiles including lipid peroxidation products; a SKN-1-induced enzyme whose dosage sets oxidative stress resistance.

Molecular Function:
glutathione transferase activity
Directly Involved In:
response to oxidative stress glutathione metabolic process
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:12757851
    The enzymatic activity of this detoxification enzyme was examined with various substrates, giving emphasis to lipid peroxidation products.
  • PMID:12757851
    In both cases, the reduced Ce-GST-p24 enzyme level resulted in a significant decrease in the stress resistance of the nematodes.

References

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Suggested Questions for Experts

Q: Which endogenous electrophile (e.g. 4-hydroxynonenal) is the physiologically relevant GST-4 substrate in vivo, and does GST-4 also have prostaglandin-synthase activity like some sigma-class GSTs?

Suggested Experiments

Experiment: Kinetic profiling of recombinant GST-4 against 4-HNE and other alkenals, plus HNE-glutathione conjugate measurement in gst-4 deletion versus wild-type animals.

Deep Research

WormBase

(gst-4-deep-research-wormbase.md)
WormBase gene description for gst-4 (worm) WormBase

WormBase gene description for gst-4 (worm)

gst-4 encodes a putative glutathione-requiring prostaglandin D synthase;gst-4 is required for sperm to normally migrate towards a PUFA-basedsignal exuded by oocytes; gst-4(RNAi) hermaphrodites are infertile, boththrough aberrant loss of their own sperm and through failure of males toeffectively inseminate them; in mammalian eicosanoid signalling,prostaglandin D synthase is required for the conversion of prostaglandinH2 into D2; gst-4 mRNA is expressed in adults, and accumulationincreases in response to paraquat.

📚 Additional Documentation

Notes

(gst-4-notes.md)

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