Gss encodes glutathione synthetase, the ATP-dependent ligase that catalyzes the final step of glutathione biosynthesis from gamma-glutamylcysteine and glycine. The review accepts glutathione synthase activity and glutathione biosynthesis, keeps substrate/cofactor binding and homodimerization as context, modifies generic ligase activity, and marks stress/nutrient expression-response annotations as non-core over-annotations. Falcon (Edison Scientific) deep research corroborates the core catalytic and biosynthetic role and the cytosolic site of action.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004363 glutathione synthase activity | IEA GO_REF:0000120 | ACCEPT | Summary: glutathione synthase activity is retained for Gss because it matches the documented core enzymatic role or its direct pathway consequence (IEA, GO_REF:0000120). Reason: glutathione synthase activity is directly supported by the curated function of Gss and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: ATP binding is retained as contextual support for Gss, but it is not the core function (IEA, GO_REF:0000002). Reason: ATP binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0006750 glutathione biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: glutathione biosynthetic process is retained for Gss because it matches the documented core enzymatic role or its direct pathway consequence (IEA, GO_REF:0000120). Reason: glutathione biosynthetic process is directly supported by the curated function of Gss and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0016874 ligase activity | IEA GO_REF:0000002 | MODIFY | Summary: ligase activity captures part of Gss biology, but more specific replacement term(s) better represent the supported function (IEA, GO_REF:0000002). Reason: ligase activity is too broad or imprecise for Gss; replace with the more specific supported term(s): GO:0004363 glutathione synthase activity. Proposed replacements: glutathione synthase activity Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. file:rat/Gss/Gss-deep-research-falcon.md **Glutathione synthetase (GSS; EC 6.3.2.3)** catalyzes the **ATP-dependent ligation of glycine** to **Ξ³-glutamylcysteine (Ξ³-GC)** to form **glutathione (GSH)** (chen2007relationshipofglutathione pages 16-20). |
| GO:0042802 identical protein binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: identical protein binding is retained as contextual support for Gss, but it is not the core function (ISO, GO_REF:0000121). Reason: identical protein binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0004363 glutathione synthase activity | ISO GO_REF:0000121 | ACCEPT | Summary: glutathione synthase activity is retained for Gss because it matches the documented core enzymatic role or its direct pathway consequence (ISO, GO_REF:0000121). Reason: glutathione synthase activity is directly supported by the curated function of Gss and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0006750 glutathione biosynthetic process | ISO GO_REF:0000121 | ACCEPT | Summary: glutathione biosynthetic process is retained for Gss because it matches the documented core enzymatic role or its direct pathway consequence (ISO, GO_REF:0000121). Reason: glutathione biosynthetic process is directly supported by the curated function of Gss and is not merely a downstream phenotype or expression response. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0005654 nucleoplasm | ISO GO_REF:0000121 | REMOVE | Summary: nucleoplasm should not be retained for Gss based on the combined gene function and cited/source evidence (ISO, GO_REF:0000121). Reason: The available evidence supports Gss's curated activity rather than nucleoplasm; this annotation is unsupported, assigned to the wrong biological context, or too misleading to keep as non-core. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: UniProtKB:P48637 Β· human GSS SUPPORTS SOURCE BUT NOT TARGET Nucleoplasm is a localization detail on the human GSS record; it adds nothing for rat Gss, whose glutathione synthetase activity is cytosolic. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0009410 response to xenobiotic stimulus | IEP PMID:18653662 Coordinated changes in xenobiotic metabolizing enzyme gene e... | MARK AS OVER ANNOTATED | Summary: response to xenobiotic stimulus reflects an expression, phenotype, or systemic context for Gss, not a direct core gene-product function (IEP, PMID:18653662). Reason: The cited/source evidence links Gss to changes in expression or a downstream physiological state; it does not establish Gss as an effector of response to xenobiotic stimulus. Supporting Evidence: PMID:18653662 Toluene exposure decreased the expression of glutathione synthetase, and dramatically increased the number of phase III genes being downregulated. |
| GO:0031667 response to nutrient levels | IEP PMID:19212806 High fat feeding and dietary L-arginine supplementation diff... | MARK AS OVER ANNOTATED | Summary: response to nutrient levels reflects an expression, phenotype, or systemic context for Gss, not a direct core gene-product function (IEP, PMID:19212806). Reason: The cited/source evidence links Gss to changes in expression or a downstream physiological state; it does not establish Gss as an effector of response to nutrient levels. Supporting Evidence: PMID:19212806 In contrast, Arg supplementation reduced mRNA levels for fatty acid binding protein 1, glycogenin, protein phosphates 1B, caspases 1 and 2, and hepatic lipase, but increased expression of PPARgamma, heme oxygenase 3, glutathione synthetase, insulin-like growth factor II, sphingosine-1-phosphate receptor, and stress-induced protein. |
| GO:0034612 response to tumor necrosis factor | IEP PMID:16011481 Tumour necrosis factor alpha induces co-ordinated activation... | MARK AS OVER ANNOTATED | Summary: response to tumor necrosis factor reflects an expression, phenotype, or systemic context for Gss, not a direct core gene-product function (IEP, PMID:16011481). Reason: The cited/source evidence links Gss to changes in expression or a downstream physiological state; it does not establish Gss as an effector of response to tumor necrosis factor. Supporting Evidence: PMID:16011481 TNFalpha induces the expression and recombinant promoter activities of GCLC, GCLM and GSS in H4IIE cells. |
| GO:0043200 response to amino acid | IEP PMID:19212806 High fat feeding and dietary L-arginine supplementation diff... | MARK AS OVER ANNOTATED | Summary: response to amino acid reflects an expression, phenotype, or systemic context for Gss, not a direct core gene-product function (IEP, PMID:19212806). Reason: The cited/source evidence links Gss to changes in expression or a downstream physiological state; it does not establish Gss as an effector of response to amino acid. Supporting Evidence: PMID:19212806 In contrast, Arg supplementation reduced mRNA levels for fatty acid binding protein 1, glycogenin, protein phosphates 1B, caspases 1 and 2, and hepatic lipase, but increased expression of PPARgamma, heme oxygenase 3, glutathione synthetase, insulin-like growth factor II, sphingosine-1-phosphate receptor, and stress-induced protein. |
| GO:0000287 magnesium ion binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: magnesium ion binding is retained as contextual support for Gss, but it is not the core function (ISS, GO_REF:0000024). Reason: magnesium ion binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0000287 magnesium ion binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: magnesium ion binding is retained as contextual support for Gss, but it is not the core function (ISO, GO_REF:0000121). Reason: magnesium ion binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0005524 ATP binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ATP binding is retained as contextual support for Gss, but it is not the core function (ISS, GO_REF:0000024). Reason: ATP binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0005524 ATP binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: ATP binding is retained as contextual support for Gss, but it is not the core function (ISO, GO_REF:0000121). Reason: ATP binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: protein homodimerization activity is retained as contextual support for Gss, but it is not the core function (ISS, GO_REF:0000024). Reason: protein homodimerization activity records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0042803 protein homodimerization activity | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: protein homodimerization activity is retained as contextual support for Gss, but it is not the core function (ISO, GO_REF:0000121). Reason: protein homodimerization activity records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0043295 glutathione binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: glutathione binding is retained as contextual support for Gss, but it is not the core function (ISS, GO_REF:0000024). Reason: glutathione binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0043295 glutathione binding | ISO GO_REF:0000121 | KEEP AS NON CORE | Summary: glutathione binding is retained as contextual support for Gss, but it is not the core function (ISO, GO_REF:0000121). Reason: glutathione binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0046686 response to cadmium ion | ISO GO_REF:0000121 | MARK AS OVER ANNOTATED | Summary: response to cadmium ion reflects an expression, phenotype, or systemic context for Gss, not a direct core gene-product function (ISO, GO_REF:0000121). Reason: The cited/source evidence links Gss to changes in expression or a downstream physiological state; it does not establish Gss as an effector of response to cadmium ion. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH ROLE CONFLATION Sources checked: MGI:MGI:95852 Β· mouse Gss SUPPORTS SOURCE BUT NOT TARGET The mouse Gss donor evidence is exposure/expression-based (cadmium induces glutathione-pathway genes) and does not establish Gss as an effector of the cadmium response in rat. Supporting Evidence: UniProtKB:P46413 FUNCTION: Catalyzes the production of glutathione from gamma-glutamylcysteine and glycine in an ATP-dependent manner. |
| GO:0004363 glutathione synthase activity | IDA PMID:10964706 Novel kinetics of mammalian glutathione synthetase: characte... | ACCEPT | Summary: glutathione synthase activity is retained for Gss because it matches the documented core enzymatic role or its direct pathway consequence (IDA, PMID:10964706). Reason: glutathione synthase activity is directly supported by the curated function of Gss and is not merely a downstream phenotype or expression response. Supporting Evidence: PMID:10964706 Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP-forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. |
| GO:0005524 ATP binding | IDA PMID:10964706 Novel kinetics of mammalian glutathione synthetase: characte... | KEEP AS NON CORE | Summary: ATP binding is retained as contextual support for Gss, but it is not the core function (IDA, PMID:10964706). Reason: ATP binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: PMID:10964706 Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP-forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. |
| GO:0006750 glutathione biosynthetic process | IDA PMID:10964706 Novel kinetics of mammalian glutathione synthetase: characte... | ACCEPT | Summary: glutathione biosynthetic process is retained for Gss because it matches the documented core enzymatic role or its direct pathway consequence (IDA, PMID:10964706). Reason: glutathione biosynthetic process is directly supported by the curated function of Gss and is not merely a downstream phenotype or expression response. Supporting Evidence: PMID:10964706 Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP-forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. file:rat/Gss/Gss-deep-research-falcon.md **Glutathione synthetase (GSS; gene symbol Gss)** is the **second (final) enzyme** in the canonical two-step de novo biosynthesis of glutathione (GSH), a major low-molecular-weight cellular thiol antioxidant (chen2007relationshipofglutathione pages 16-20, tandon2024unravelingthemultifaceted pages 1-2). |
| GO:0016594 glycine binding | IDA PMID:10964706 Novel kinetics of mammalian glutathione synthetase: characte... | KEEP AS NON CORE | Summary: glycine binding is retained as contextual support for Gss, but it is not the core function (IDA, PMID:10964706). Reason: glycine binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: PMID:10964706 Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP-forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. file:rat/Gss/Gss-deep-research-falcon.md β’ Core substrates are Ξ³-glutamylcysteine, glycine, and ATP. β’ Product is glutathione (GSH), the major low-molecular-weight cellular thiol antioxidant. β’ Literature supports strong substrate specificity for glycine ligation to Ξ³-glutamylcysteine. |
| GO:0042277 peptide binding | IPI PMID:10964706 Novel kinetics of mammalian glutathione synthetase: characte... | KEEP AS NON CORE | Summary: peptide binding is retained as contextual support for Gss, but it is not the core function (IPI, PMID:10964706). Reason: peptide binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: PMID:10964706 Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP-forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. |
| GO:0042802 identical protein binding | IPI PMID:7862666 Amino acid sequence of rat kidney glutathione synthetase. | KEEP AS NON CORE | Summary: identical protein binding is retained as contextual support for Gss, but it is not the core function (IPI, PMID:7862666). Reason: identical protein binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: PMID:7862666 Glutathione (GSH) synthetase [gamma-L-glutamyl-L-cysteine:glycine ligase (ADP-forming), EC 6.3.2.3], an enzyme present in almost all cells, catalyzes the ATP-dependent synthesis of GSH from gamma-L-glutamyl-L-cysteine and glycine. file:rat/Gss/Gss-deep-research-falcon.md **Glutathione synthetase (GSS; EC 6.3.2.3)** catalyzes the **ATP-dependent ligation of glycine** to **Ξ³-glutamylcysteine (Ξ³-GC)** to form **glutathione (GSH)** (chen2007relationshipofglutathione pages 16-20). |
| GO:0043295 glutathione binding | IDA PMID:10964706 Novel kinetics of mammalian glutathione synthetase: characte... | KEEP AS NON CORE | Summary: glutathione binding is retained as contextual support for Gss, but it is not the core function (IDA, PMID:10964706). Reason: glutathione binding records localization, cofactor/substrate binding, oligomeric state, or physiological context rather than the defining molecular activity of Gss. Supporting Evidence: PMID:10964706 Glutathione (GSH) synthetase [L-gamma-glutamyl-L-cysteinyl:glycine ligase (ADP-forming), EC 6.3.2.3] catalyzes the final step in GSH biosynthesis. |
| GO:0004363 glutathione synthase activity | IDA PMID:7862666 Amino acid sequence of rat kidney glutathione synthetase. | ACCEPT | Summary: glutathione synthase activity is retained for Gss because it matches the documented core enzymatic role or its direct pathway consequence (IDA, PMID:7862666). Reason: glutathione synthase activity is directly supported by the curated function of Gss and is not merely a downstream phenotype or expression response. Supporting Evidence: PMID:7862666 Glutathione (GSH) synthetase [gamma-L-glutamyl-L-cysteine:glycine ligase (ADP-forming), EC 6.3.2.3], an enzyme present in almost all cells, catalyzes the ATP-dependent synthesis of GSH from gamma-L-glutamyl-L-cysteine and glycine. |
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