GO_REF:0000033

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gstt1 annotations including cytoplasm; glutathione metabolic process; glutathione transferase activity.

"GO_REF entry used only to trace the source annotation method; biological support was assessed against UniProt and cached literature where available."

GO_REF:0000044

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gstt1 annotations including cytoplasm.

"GO_REF entry used only to trace the source annotation method; biological support was assessed against UniProt and cached literature where available."

GO_REF:0000107

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gstt1 annotations including cytosol.

"GO_REF entry used only to trace the source annotation method; biological support was assessed against UniProt and cached literature where available."

GO_REF:0000108

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gstt1 annotations including cellular oxidant detoxification.

"GO_REF entry used only to trace the source annotation method; biological support was assessed against UniProt and cached literature where available."

GO_REF:0000117

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gstt1 annotations including glutathione metabolic process; glutathione peroxidase activity; response to salicylic acid.

"GO_REF entry used only to trace the source annotation method; biological support was assessed against UniProt and cached literature where available."

GO_REF:0000120

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gstt1 annotations including glutathione transferase activity.

"GO_REF entry used only to trace the source annotation method; biological support was assessed against UniProt and cached literature where available."

GO_REF:0000121

GO reference used by source annotation pipeline

Source annotation pipeline provenance for Gstt1 annotations including cytosol; glutathione metabolic process; glutathione peroxidase activity; glutathione transferase activity.

"GO_REF entry used only to trace the source annotation method; biological support was assessed against UniProt and cached literature where available."

PMID:11453994

Dichloromethane mediated in vivo selection and functional characterization of rat glutathione S-transferase theta 1-1 variants

For Gstt1, this publication provides direct evidence that rat GST T1-1 dehalogenates dichloromethane (supporting alkylhalidase activity and dichloromethane metabolic process), and that this dehalogenation is mutagenic (supporting the DNA modification over-annotation as a downstream consequence rather than the direct enzyme reaction).

"the dehalogenation of dichloromethane by GST T1-1 from rat was highly mutagenic and toxic to methylotrophic bacteria."

PMID:12588193

Glutathione transferase theta 1-1-dependent metabolism of the water disinfection byproduct bromodichloromethane

For Gstt1, this publication supports direct annotations to glutathione transferase activity.

"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)."

PMID:20097269

Residue 234 is a master switch of the alternative-substrate activity profile of human and rodent theta class glutathione transferase T1-1

For Gstt1, this publication supports direct annotations to glutathione metabolic process; glutathione transferase activity.

"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."

PMID:9331086

Protection conferred by selenium deficiency against aflatoxin B1 in the rat is associated with the hepatic expression of an aldo-keto reductase and a glutathione S-transferase subunit that metabolize the mycotoxin

For Gstt1, this publication was reviewed as context for response to selenium ion.

"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."

PMID:9344408

Rat liver theta-class glutathione S-transferases T1-1 and T2-2: their chromatographic, electrophoretic, immunochemical, and functional properties

For Gstt1, this publication supports direct annotations to glutathione peroxidase activity; purified rat GST T1-1 had higher GSH peroxidase activity than rGSTA1-2, with cumene hydroperoxide a preferred substrate for rGST T1-1.

"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."

PMID:9729437

Nonsteroidal anti-inflammatory drugs enhance glutathione S-transferase theta levels in rat colon

For Gstt1, this publication was reviewed as context for response to salicylic acid.

"Nonsteroidal anti-inflammatory drugs (NSAIDs) have been claimed to reduce cancer rates in oesophagus, stomach and colon of humans and laboratory animals."

PMID:9794803

Increased bioactivation of dihaloalkanes in rat liver due to induction of class theta glutathione S-transferase T1-1

For Gstt1, this publication was reviewed as context for response to xenobiotic stimulus.

"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."

PMID:9855024

Effects of dietary anticarcinogens on rat gastrointestinal glutathione S-transferase theta 1-1 levels

For Gstt1, this publication was reviewed as context for response to vitamin E.

"Several naturally occurring food components or non-steroidal anti-inflammatory drugs (NSAIDs) may reduce gastrointestinal cancer rates."

file:rat/Gstt1/Gstt1-deep-research-falcon.md

Falcon (Edison Scientific) deep research report: rat Gstt1 (UniProt Q01579), glutathione S-transferase theta-1

Falcon confirms gene identity - rat Gstt1/GSTT1-1 is the historical theta-class cytosolic GST 5-5, purified as a homodimer from rat liver cytosol, distinct from the related theta enzyme GSTT2-2.

"Rat **Gstt1/GSTT1-1** corresponds to the historical rat **GST 5-5** enzyme: a **theta-class, soluble cytosolic glutathione S-transferase** purified from rat liver cytosol as a homodimer with an apparent subunit size of about **28 kDa**"
Falcon corroborates the canonical glutathione transferase reaction (EC 2.5.1.18) as the core function of rat GSTT1-1.

"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"
Falcon corroborates rat GSTT1-1 dichloromethane (DCM) transferase activity with direct rat biochemical specific-activity measurements, supporting the dichloromethane metabolic process and alkylhalidase annotations.

"In rat biochemical assays, GSTT1-1 shows substantial activity toward **dichloromethane (DCM)** and model substrates including **EPNP** and **4-nitrobenzyl chloride**, with reported specific activities of **7.8, 35.2, and 7.8 mmol/min/mg**, respectively; it also has **glutathione peroxidase activity** toward **cumene hydroperoxide** (**24.7 mmol/min/mg**)"
Falcon directly supports rat GSTT1-1 glutathione peroxidase activity toward cumene hydroperoxide.

"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."
Falcon corroborates cytosolic localization - rat GSTT1-1 was purified from rat liver cytosol as a soluble (not microsomal/mitochondrial) enzyme.

"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)."
Falcon explains that DCM/dihaloalkane DNA damage and mutagenicity is a downstream consequence of GST-catalyzed bioactivation to reactive intermediates, not the direct enzyme reaction - supporting the over-annotation call on DNA modification and xenobiotic-response context terms.

"A review summarizing theta-class function states that rat GSTT1-1 (form 5-5) conjugates **ethylene dibromide**, generating an electrophilic intermediate capable of forming adducts, and also describes **Ames-test–detectable mutagenicity** when rat GSTT1-1 is expressed in bacteria and incubated with dihaloalkanes."
CAVEAT (paralog): Falcon notes substrate-preference differences between GSTT1-1 and the distinct rat theta enzyme GSTT2-2 (e.g., GSTT2-2 prefers fatty-acid hydroperoxides) - GSTT2-2-specific substrate claims must not be imported onto Gstt1.

"GSTT1-1 preferred cumene hydroperoxide; GSTT2-2 preferred fatty-acid hydroperoxides; theta-class GSTs together ~0.5% of total cytosolic protein"