Gstt1 encodes rat glutathione S-transferase theta-1, a theta-class GST with glutathione transferase, glutathione peroxidase, and dichloromethane dehalogenase activities. The review accepts these experimentally supported catalytic activities and dichloromethane/glutathione metabolism as core/direct functions, while keeping exposure-response and localization annotations non-core.
| 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 GO; GO:0005737; C:cytoplasm; IBA:GO_Central. 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 GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB. 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 GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB. 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 GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB. 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: UniProtKB:Q01579 GO; GO:0004602; F:glutathione peroxidase activity; IDA:RGD. 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 GO; GO:0005737; C:cytoplasm; IBA:GO_Central. 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 GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB. 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 reflects source-pipeline stimulus-response provenance for Gstt1 rather than a direct glutathione transferase, dehalogenase, or alkylhalidase reaction. Supporting Evidence: UniProtKB:Q01579 GO; GO:0009751; P:response to salicylic acid; IEA:GO_REF:0000117. |
| 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 GO; GO:0005829; C:cytosol; ISO:RGD. 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). Reason: cytosol records where Gstt1 has been observed, but localization does not define the gene product's primary activity. Supporting Evidence: UniProtKB:Q01579 GO; GO:0005829; C:cytosol; ISO:RGD. 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. Supporting Evidence: UniProtKB:Q01579 GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB. 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. Supporting Evidence: UniProtKB:Q01579 GO; GO:0006749; P:glutathione metabolic process; IDA:UniProtKB. 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. Supporting Evidence: UniProtKB:Q01579 GO; GO:0004602; F:glutathione peroxidase activity; IDA:RGD. 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. |
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