Gstt1 encodes rat glutathione S-transferase theta-1 (GST T1-1), a cytosolic theta-class glutathione transferase that functions as a homodimer. It conjugates reduced glutathione to small electrophiles that are poor substrates for other GST classes, including dihalomethanes and other alkyl halides; its dehalogenation of dichloromethane generates reactive glutathione-derived intermediates, so for some substrates conjugation leads to bioactivation and mutagenic DNA damage rather than detoxification. The enzyme also has selenium-independent glutathione peroxidase activity toward organic hydroperoxides such as cumene hydroperoxide. In rat it is expressed in liver (highest in centrilobular hepatocytes), lung club cells and the gastrointestinal mucosa, and its levels respond to dietary agents such as NSAIDs, selenium and vitamin E.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: cytoplasm is retained as useful context for Gstt1, but it is not the defining core function (IBA, GO_REF:0000033). Reason: cytoplasm records where Gstt1 has been observed, but localization does not define the gene product's primary activity. Supporting Evidence: UniProtKB:Q01579 SUBCELLULAR LOCATION: Cytoplasm. file:rat/Gstt1/Gstt1-deep-research-falcon.md A primary biochemical characterization purified **rat liver theta-class GSTT1-1** from **rat liver cytosol**, establishing it as a soluble enzyme (not microsomal/mitochondrial in this preparation). |
| GO:0004364 glutathione transferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione transferase activity as a direct annotation (IBA, GO_REF:0000033). Reason: glutathione transferase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: UniProtKB:Q01579 Reaction=RX + glutathione = an S-substituted glutathione + a halide anion + H(+) file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
| GO:0006749 glutathione metabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione metabolic process as a direct annotation (IBA, GO_REF:0000033). Reason: glutathione metabolic process is a direct metabolic process expected from Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: UniProtKB:Q01579 Reaction=RX + glutathione = an S-substituted glutathione + a halide anion + H(+) file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
| GO:0004364 glutathione transferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione transferase activity as a direct annotation (IEA, GO_REF:0000120). Reason: glutathione transferase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: UniProtKB:Q01579 Reaction=RX + glutathione = an S-substituted glutathione + a halide anion + H(+) file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
| GO:0004602 glutathione peroxidase activity | IEA GO_REF:0000117 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione peroxidase activity as a direct annotation (IEA, GO_REF:0000117). Reason: glutathione peroxidase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: file:rat/Gstt1/Gstt1-deep-research-falcon.md In addition, GSTT1-1 showed strong **glutathione peroxidase activity** (a glutathione-dependent reduction) toward **cumene hydroperoxide** (**24.7 mmol/min/mg**), and the study reports that theta-class GSTs have **low activity toward CDNB** compared with many other cytosolic GSTs. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: cytoplasm is retained as useful context for Gstt1, but it is not the defining core function (IEA, GO_REF:0000044). Reason: cytoplasm records where Gstt1 has been observed, but localization does not define the gene product's primary activity. Supporting Evidence: UniProtKB:Q01579 SUBCELLULAR LOCATION: Cytoplasm. file:rat/Gstt1/Gstt1-deep-research-falcon.md A primary biochemical characterization purified **rat liver theta-class GSTT1-1** from **rat liver cytosol**, establishing it as a soluble enzyme (not microsomal/mitochondrial in this preparation). |
| GO:0006749 glutathione metabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione metabolic process as a direct annotation (IEA, GO_REF:0000117). Reason: glutathione metabolic process is a direct metabolic process expected from Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: UniProtKB:Q01579 Reaction=RX + glutathione = an S-substituted glutathione + a halide anion + H(+) file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
| GO:0009751 response to salicylic acid | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: response to salicylic acid is treated as over-annotation because it reflects context or consequence rather than Gstt1's direct role (IEA, GO_REF:0000117). Reason: The salicylic-acid annotation (ARBA rule) reflects a dietary induction of GSTT1-1 protein levels by NSAIDs including acetylsalicylic acid in rat gut (PMID:9729437), i.e. stimulus-response context, rather than a direct glutathione transferase, dehalogenase, or alkylhalidase reaction. Supporting Evidence: PMID:9729437 Colonic GSTT1-1 levels were elevated by all NSAIDs tested except for relafen |
| GO:0098869 cellular oxidant detoxification | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: cellular oxidant detoxification is retained as useful context for Gstt1, but it is not the defining core function (IEA, GO_REF:0000108). Reason: cellular oxidant detoxification is biologically compatible with Gstt1, but it is contextual or broader than the direct role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: UniProtKB:Q01579 FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Also binds steroids, bilirubin, carcinogens and numerous organic anions. Has dichloromethane dehalogenase activity. |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: cytosol is retained as useful context for Gstt1, but it is not the defining core function (IEA, GO_REF:0000107). Reason: cytosol records where Gstt1 has been observed, but localization does not define the gene product's primary activity. Supporting Evidence: UniProtKB:Q01579 SUBCELLULAR LOCATION: Cytoplasm. file:rat/Gstt1/Gstt1-deep-research-falcon.md The strongest direct evidence from retrieved primary literature places rat GSTT1-1 in the **cytosolic fraction of liver**: it was purified from **rat liver cytosol**, and its reported abundance relates to **cytosolic protein**. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: cytosol is retained as useful context for Gstt1, but it is not the defining core function (ISO, GO_REF:0000121; donor mouse Gstt1, MGI:MGI:107379). Reason: cytosol records where Gstt1 has been observed, but localization does not define the gene product's primary activity. Supporting Evidence: UniProtKB:Q01579 SUBCELLULAR LOCATION: Cytoplasm. file:rat/Gstt1/Gstt1-deep-research-falcon.md The strongest direct evidence from retrieved primary literature places rat GSTT1-1 in the **cytosolic fraction of liver**: it was purified from **rat liver cytosol**, and its reported abundance relates to **cytosolic protein**. |
| GO:0006304 DNA modification | IDA PMID:11453994 Dichloromethane mediated in vivo selection and functional ch... | MARK AS OVER ANNOTATED | Summary: DNA modification is treated as over-annotation because it reflects context or consequence rather than Gstt1's direct role (IDA, PMID:11453994). Reason: GSTT1 can bioactivate dichloromethane through glutathione-dependent chemistry, producing reactive products that damage or mutate DNA; the DNA modification term records that downstream consequence rather than the enzyme reaction itself. Supporting Evidence: PMID:11453994 the dehalogenation of dichloromethane by GST T1-1 from rat was highly mutagenic and toxic to methylotrophic bacteria. |
| GO:0009751 response to salicylic acid | IEP PMID:9729437 Nonsteroidal anti-inflammatory drugs enhance glutathione S-t... | MARK AS OVER ANNOTATED | Summary: response to salicylic acid is treated as over-annotation because it reflects context or consequence rather than Gstt1's direct role (IEP, PMID:9729437). Reason: The salicylic-acid annotation reflects source-pipeline stimulus-response provenance for Gstt1 rather than a direct glutathione transferase, dehalogenase, or alkylhalidase reaction. Supporting Evidence: PMID:9729437 Nonsteroidal anti-inflammatory drugs (NSAIDs) have been claimed to reduce cancer rates in oesophagus, stomach and colon of humans and laboratory animals. |
| GO:0010269 response to selenium ion | IEP PMID:9331086 Protection conferred by selenium deficiency against aflatoxi... | MARK AS OVER ANNOTATED | Summary: response to selenium ion is treated as over-annotation because it reflects context or consequence rather than Gstt1's direct role (IEP, PMID:9331086). Reason: response to selenium ion reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Gstt1 role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:9331086 Fischer 344 rats fed on a diet that is deficient in selenium are more resistant to the hepatocarcinogen aflatoxin B1 (AFB1) than those fed on a selenium-sufficient diet. |
| GO:0018900 dichloromethane metabolic process | IDA PMID:11453994 Dichloromethane mediated in vivo selection and functional ch... | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining dichloromethane metabolic process as a direct annotation (IDA, PMID:11453994). Reason: dichloromethane metabolic process is a direct metabolic process expected from Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:11453994 The enzymatic activity of purified His-tagged GST T1-1 variants expressed in Escherichia coli was markedly reduced with both dichloromethane and the alternative substrate 1,2-epoxy-3-(4'-nitrophenoxy)propane. |
| GO:0033197 response to vitamin E | IEP PMID:9855024 Effects of dietary anticarcinogens on rat gastrointestinal g... | MARK AS OVER ANNOTATED | Summary: response to vitamin E is treated as over-annotation because it reflects context or consequence rather than Gstt1's direct role (IEP, PMID:9855024). Reason: response to vitamin E reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Gstt1 role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:9855024 Several naturally occurring food components or non-steroidal anti-inflammatory drugs (NSAIDs) may reduce gastrointestinal cancer rates. |
| GO:0047651 alkylhalidase activity | IDA PMID:11453994 Dichloromethane mediated in vivo selection and functional ch... | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining alkylhalidase activity as a direct annotation (IDA, PMID:11453994). Reason: alkylhalidase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:11453994 Mammalian homologs of this bacterial enzyme are also known to catalyze this reaction. However, the dehalogenation of dichloromethane by GST T1-1 from rat was highly mutagenic and toxic to methylotrophic bacteria. |
| GO:0004364 glutathione transferase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione transferase activity as a direct annotation (ISO, GO_REF:0000121). Reason: glutathione transferase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. The donor is mouse Gstt1 (MGI:MGI:107379), the one-to-one theta-class orthologue; the activity is also directly assayed on rat GST T1-1. Supporting Evidence: UniProtKB:Q01579 Reaction=RX + glutathione = an S-substituted glutathione + a halide anion + H(+) UniProtKB:Q01579 FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
| GO:0004364 glutathione transferase activity | IDA PMID:20097269 Residue 234 is a master switch of the alternative-substrate ... | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione transferase activity as a direct annotation (IDA, PMID:20097269). Reason: glutathione transferase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:20097269 BACKGROUND: The Theta class glutathione transferase GST T1-1 is a ubiquitously occurring detoxication enzyme. The rat and mouse enzymes have high catalytic activities with numerous electrophilic compounds, but the homologous human GST T1-1 has comparatively low activity with the same substrates. |
| GO:0006749 glutathione metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione metabolic process as a direct annotation (ISO, GO_REF:0000121). Reason: glutathione metabolic process is a direct metabolic process expected from Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. The donor is mouse Gstt1 (MGI:MGI:107379); a separate row from the same donor carries the involved_in form of this term. Supporting Evidence: UniProtKB:Q01579 Reaction=RX + glutathione = an S-substituted glutathione + a halide anion + H(+) file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
| GO:0006749 glutathione metabolic process | IDA PMID:20097269 Residue 234 is a master switch of the alternative-substrate ... | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione metabolic process as a direct annotation (IDA, PMID:20097269). Reason: glutathione metabolic process is a direct metabolic process expected from Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:20097269 BACKGROUND: The Theta class glutathione transferase GST T1-1 is a ubiquitously occurring detoxication enzyme. The rat and mouse enzymes have high catalytic activities with numerous electrophilic compounds, but the homologous human GST T1-1 has comparatively low activity with the same substrates. |
| GO:0004602 glutathione peroxidase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione peroxidase activity as a direct annotation (ISO, GO_REF:0000121). Reason: glutathione peroxidase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. The donor is human GSTT1 (UniProtKB:P30711); the activity is also measured directly on rat GST T1-1 (IDA, PMID:9344408). Supporting Evidence: file:rat/Gstt1/Gstt1-deep-research-falcon.md In addition, GSTT1-1 showed strong **glutathione peroxidase activity** (a glutathione-dependent reduction) toward **cumene hydroperoxide** (**24.7 mmol/min/mg**), and the study reports that theta-class GSTs have **low activity toward CDNB** compared with many other cytosolic GSTs. |
| GO:0004364 glutathione transferase activity | IDA PMID:12588193 Glutathione transferase theta 1-1-dependent metabolism of th... | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione transferase activity as a direct annotation (IDA, PMID:12588193). Reason: glutathione transferase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:12588193 Bromodichloromethane (CHBrCl(2)), a prevalent drinking water disinfection byproduct, was previously shown to be mutagenic in Salmonella that express rat GSH transferase (GST) theta 1-1 (GST T1-1). |
| GO:0004602 glutathione peroxidase activity | IDA PMID:9344408 Rat liver theta-class glutathione S-transferases T1-1 and T2... | ACCEPT | Summary: Gstt1's glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry supports retaining glutathione peroxidase activity as a direct annotation (IDA, PMID:9344408). Reason: glutathione peroxidase activity is a specific catalytic activity matching Gstt1's documented role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:9344408 The Theta-class rGSTs showed higher GSH peroxidase activity than rGSTA1-2 toward hydroperoxides of cumene, arachidonic acid, and linoleic acid. Cumene hydroperoxide was a better substrate for rGST T1-1 than for rGST T2-2, while the fatty acid hydroperoxides were the better substrates for rGST T2-2 than for rGST T1-1. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:9794803 Increased bioactivation of dihaloalkanes in rat liver due to... | MARK AS OVER ANNOTATED | Summary: response to xenobiotic stimulus is treated as over-annotation because it reflects context or consequence rather than Gstt1's direct role (IEP, PMID:9794803). Reason: response to xenobiotic stimulus reflects exposure, expression, phenotype, or downstream pathway context rather than the direct Gstt1 role in glutathione conjugation plus dichloromethane dehalogenase and alkylhalidase chemistry. Supporting Evidence: PMID:9794803 A characteristic feature of the class Theta glutathione S-transferase (GST) T1-1 is its ability to activate dichloromethane and dibromoethane by catalysing the formation of mutagenic conjugates. |
| GO:0004364 glutathione transferase activity | ISO GO_REF:0000121 | ACCEPT | Summary: Glutathione transferase activity transferred by orthology from human GSTT1 (UniProtKB:P30711); donor-split duplicate of the mouse-Gstt1-donor ISO row and consistent with the rat IDA rows for the same activity. Reason: The donor is human GSTT1 (P30711), the one-to-one theta-class orthologue of rat Gstt1. Glutathione transferase activity is the defining activity of the enzyme and is directly assayed on purified rat GST T1-1 (IDA rows from PMID:20097269 and PMID:12588193), so the transfer is sound. Supporting Evidence: UniProtKB:Q01579 FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. |
| GO:0005829 cytosol | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: Cytosol transferred by orthology from human GSTT1 (UniProtKB:P30711); donor-split duplicate of the mouse-Gstt1-donor cytosol row, kept as non-core localization context. Reason: The donor is human GSTT1 (P30711). Rat GST T1-1 was purified from liver cytosol and UniProt records a cytoplasmic location, so the transferred location is correct; localization does not define the core activity. Supporting Evidence: UniProtKB:Q01579 SUBCELLULAR LOCATION: Cytoplasm. file:rat/Gstt1/Gstt1-deep-research-falcon.md A primary biochemical characterization purified **rat liver theta-class GSTT1-1** from **rat liver cytosol**, establishing it as a soluble enzyme (not microsomal/mitochondrial in this preparation). |
| GO:0006749 glutathione metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Glutathione metabolic process transferred by orthology from mouse Gstt1 (MGI:MGI:107379), with the involved_in qualifier; companion of the acts_upstream_of_or_within row from the same donor and accepted on the same grounds. Reason: The donor is mouse Gstt1 (MGI:MGI:107379). Glutathione metabolic process is the process in which the enzyme's glutathione conjugation and glutathione-dependent peroxidase reactions consume reduced glutathione; both activities are directly measured on rat GST T1-1, and the term is also carried by IBA and IDA rows. Supporting Evidence: UniProtKB:Q01579 FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
| GO:0006749 glutathione metabolic process | ISO GO_REF:0000121 | ACCEPT | Summary: Glutathione metabolic process transferred by orthology from human GSTT1 (UniProtKB:P30711); donor-split duplicate of the mouse-Gstt1-donor row. Reason: The donor is human GSTT1 (P30711). Glutathione metabolic process is the process in which the enzyme's glutathione conjugation and glutathione-dependent peroxidase reactions consume reduced glutathione; both activities are directly measured on rat GST T1-1, and the term is also carried by IBA and IDA rows. Supporting Evidence: UniProtKB:Q01579 FUNCTION: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. file:rat/Gstt1/Gstt1-deep-research-falcon.md Its core reaction is the canonical GST reaction (**EC 2.5.1.18**): **glutathione conjugation of electrophilic substrates**; theta-class GSTT1-1 is especially notable because some conjugation reactions contribute to **bioactivation**, not just detoxification |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)