The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
GTT3 (systematic name YEL017W; UniProt accession P39996) is a poorly characterized protein in Saccharomyces cerevisiae (strain ATCC 204508 / S288c). Despite extensive searching across primary literature, reviews, and high-throughput datasets, very little direct biochemical or functional characterization of Gtt3p was identified. The vast majority of research on yeast glutathione transferases focuses on the better-characterized family members GTT1 and GTT2. The following report synthesizes all available evidence, clearly distinguishing between direct evidence for GTT3 and inferences drawn from family context.
GTT3 (YEL017W) encodes a protein annotated as "Glutathione transferase 3" in S. cerevisiae. The protein is 285 amino acids in length and contains two distinctive domains: Put_GTT3 (IPR038872) and GTT3_N (PF27945). These domains are specific to GTT3 and its close homologs, and are not shared with the better-characterized yeast glutathione transferases Gtt1 and Gtt2, nor with the omega-class glutathione transferases (Gto1, Gto2, Gto3). This domain architecture suggests that Gtt3p may represent a structurally and functionally distinct class of glutathione transferase within the yeast proteome.
S. cerevisiae possesses multiple glutathione-related transferases. The best characterized are:
Gtt1 and Gtt2: These are the two canonical glutathione S-transferases (GSTs) that act on standard GST substrates such as 1-chloro-2,4-dinitrobenzene (CDNB). They catalyze the enzymatic conjugation of glutathione (GSH) with a multitude of exogenously and endogenously derived toxic compounds (mariani2008involvementofglutathione pages 2-4). Gtt1 has been described as a membrane-bound, ER-localized glutathione S-transferase, while Gtt2 has been characterized as a mitochondrial GST. Both are involved in oxidative stress defense, particularly during H₂O₂ exposure (mariani2008involvementofglutathione pages 4-6, mariani2008involvementofglutathione pages 1-2).
Gto1, Gto2, Gto3: These are omega-class glutathione transferases that display homology with human omega-class GSTs. Their enzyme activities differ from those of the Gtt isoforms, and they act as 1-Cys thiol transferases related to glutaredoxins Grx1 and Grx2 (mariani2008involvementofglutathione pages 8-9, mariani2008involvementofglutathione pages 1-2).
GTT3 (YEL017W): Grouped by name with the Gtt family but possesses unique domains (Put_GTT3, GTT3_N) that distinguish it from both Gtt1/Gtt2 and the Gto proteins. No direct biochemical characterization of Gtt3p enzymatic activity was identified in the available literature.
The following table summarizes the comparative features of the three GTT-family members:
| Gene | Systematic name | Protein / annotation | Known or reported localization | Characterized function | Evidence summary | Level of characterization |
|---|---|---|---|---|---|---|
| GTT1 | not established from gathered evidence | Glutathione transferase 1 | Endoplasmic reticulum / membrane-bound, based on review citation to earlier primary work; also treated broadly as a yeast GST acting on standard GST substrates (mariani2008involvementofglutathione pages 1-2) | Canonical GST activity: conjugates glutathione (GSH) to electrophilic substrates; implicated in oxidative-stress defense, especially during H2O2 exposure; contributes to control of protein oxidation and cell survival/apoptosis-related stress outcomes (mariani2008involvementofglutathione pages 4-6, mariani2008involvementofglutathione pages 2-4, hayes2005glutathionetransferases. pages 6-7) | Primary evidence in the gathered set focuses on oxidative-stress phenotypes and standard GST function, but not on a fully resolved substrate spectrum for yeast Gtt1 specifically (mariani2008involvementofglutathione pages 4-6, mariani2008involvementofglutathione pages 2-4, hayes2005glutathionetransferases. pages 6-7) | Moderately characterized |
| GTT2 | not established from gathered evidence | Glutathione transferase 2 | Often described as mitochondrial in the literature context gathered; direct localization evidence was not independently retrieved here, so this should be treated cautiously (auchere2008glutathionedependentredoxstatus pages 3-4) | Canonical GST activity with major role in oxidative-stress defense; especially important for detoxifying lipid peroxides / oxidized products and limiting lipid peroxidation and protein carbonylation during H2O2 stress (mariani2008involvementofglutathione pages 6-8, mariani2008involvementofglutathione pages 1-2, mariani2008involvementofglutathione pages 2-4) | Best-supported functional member in the gathered evidence set; repeatedly linked to peroxide stress and detoxification of oxidized cellular components (mariani2008involvementofglutathione pages 6-8, mariani2008involvementofglutathione pages 1-2, sha2013thegenomewideearly pages 9-11) | Moderately to well characterized |
| GTT3 | YEL017W | Glutathione transferase 3; UniProt target P39996 | Unknown from the gathered primary evidence; no direct localization study for YEL017W/Gtt3 was found in the retrieved literature | Specific biochemical activity remains unclear. By annotation and family context, Gtt3 is expected to be a GST-like protein, but no direct enzymatic assay, substrate specificity, or catalytic mechanism for the specific YEL017W protein was retrieved. Expression was measured in frataxin-deficient yeast and showed no major change (relative expression ~1.14 in YNB; ~0.86 in iron-supplemented YNB) (auchere2008glutathionedependentredoxstatus pages 5-6, auchere2008glutathionedependentredoxstatus pages 4-5) | The strongest direct evidence retrieved is that GTT3 transcription was not detectably altered in the frataxin-deficient oxidative-stress model, unlike some other glutathione-related genes (auchere2008glutathionedependentredoxstatus pages 5-6, auchere2008glutathionedependentredoxstatus pages 4-5). A deletion including YEL017W was associated with increased prodeoxyviolacein production in SCRaMbLE experiments, but mechanism was not resolved (wang2018ringsyntheticchromosome pages 5-6) | Poorly characterized / largely uncharacterized |
Table: This table compares the three Saccharomyces cerevisiae glutathione transferase genes discussed in the evidence, highlighting that GTT1 and GTT2 are functionally better supported, whereas GTT3/YEL017W remains poorly characterized with little direct biochemical or localization evidence.
Based on its annotation as a glutathione transferase, Gtt3p is predicted to catalyze the conjugation of the tripeptide glutathione (γ-L-glutamyl-L-cysteinyl-glycine) with electrophilic substrates. The general mechanism of GSTs involves nucleophilic attack by the thiol group of reduced glutathione (GSH) on nonpolar compounds containing electrophilic carbon, nitrogen, or sulfur atoms (hayes2005glutathionetransferases. pages 1-3). This reaction produces less reactive, more water-soluble conjugates that can be further processed and excreted. Substrates for GSTs broadly include α,β-unsaturated carbonyls (such as 4-hydroxynonenal from lipid peroxidation), epoxides, quinones, and various xenobiotics (hayes2005glutathionetransferases. pages 6-7, hayes2005glutathionetransferases. pages 4-6). In yeast specifically, Gtt1 and Gtt2 have been shown to protect cells from lipid peroxidation and protein carbonylation during oxidative stress (mariani2008involvementofglutathione pages 6-8, mariani2008involvementofglutathione pages 4-6).
However, no direct enzymatic assay data for Gtt3p was identified. Its substrate specificity, catalytic efficiency, and whether it acts on the canonical GST substrate CDNB or on alternative substrates remain unknown. The unique domain architecture (Put_GTT3, GTT3_N) suggests that Gtt3p may have a distinct substrate preference or catalytic activity compared to Gtt1 and Gtt2.
No direct experimental localization of Gtt3p was found in the retrieved literature. The global yeast GFP localization study by Huh et al. (2003, Nature 425:686–691) is the standard reference for yeast protein localization, but the Huh et al. paper was unobtainable in this search, and no specific localization data for YEL017W/Gtt3p was retrieved from secondary sources. By contrast, Gtt1p has been described as an endoplasmic reticulum (ER)-localized, membrane-bound glutathione S-transferase, and Gtt2p has been associated with mitochondria (mariani2008involvementofglutathione pages 1-2). The localization of Gtt3p remains an open question.
Quantitative PCR analysis in a yeast model of Friedreich's ataxia (frataxin-deficient S. cerevisiae) measured GTT3 expression alongside other glutathione-related genes. The relative expression ratio of GTT3 in frataxin-deficient versus wild-type cells was 1.14 ± 0.45 on standard YNB medium and 0.86 ± 0.17 on iron-supplemented YNB medium, indicating that GTT3 transcription was not significantly altered under these oxidative stress conditions (auchere2008glutathionedependentredoxstatus pages 5-6, auchere2008glutathionedependentredoxstatus pages 4-5). The authors concluded that there was "no evidence of a change in transcription of... the glutathione transferase GTT1-3" in frataxin-deficient cells, even though these cells exhibited severe oxidative stress with elevated glutathione peroxidase activity, depleted NADPH, and increased G6PDH activity (auchere2008glutathionedependentredoxstatus pages 4-5).
This is in contrast to GTT1 and GTT2, which are both transcriptionally upregulated in response to cumene hydroperoxide (CHP) and H₂O₂ stress (sha2013thegenomewideearly pages 9-11). The lack of GTT3 induction under oxidative stress conditions suggests either that GTT3 is constitutively expressed, that it responds to different stress signals, or that it has a distinct physiological role from GTT1/GTT2.
In SCRaMbLE (Synthetic Chromosome Recombination and Modification by LoxP-mediated Evolution) experiments using a ring synthetic chromosome V, deletion of YEL017W was identified among a set of gene deletions (along with YEL017C-A, YER151C, and YER182W) that contributed to increased production of prodeoxyviolacein (PDV), a chromogenic compound used as a phenotypic marker (wang2018ringsyntheticchromosome pages 5-6). The SCRaMbLEd strain showed approximately 3.48-fold increased PDV production compared to the control strain (zhou2021directedgenomeevolution pages 9-10). However, the exact mechanism by which YEL017W deletion increases PDV productivity was not elucidated, and the deletion was identified in combination with other genetic changes, making it difficult to attribute the phenotype solely to loss of GTT3 (wang2018ringsyntheticchromosome pages 5-6).
Given its annotation as a glutathione transferase, Gtt3p is expected to participate in glutathione metabolism and potentially in cellular detoxification pathways. The yeast glutathione system is a major component of the antioxidant defense network, involved in:
However, the specific pathway in which Gtt3p operates cannot be definitively assigned from current evidence. The fact that GTT3 expression is not induced by oxidative stress in the frataxin-deficiency model, unlike GTT2, may suggest a role distinct from canonical oxidative stress defense.
Gtt3p contains two domains unique to this protein family: Put_GTT3 (IPR038872) and GTT3_N (PF27945). These domains are not found in the canonical cytosolic GST superfamily classes (alpha, mu, pi, sigma, theta, omega, zeta) that have been extensively characterized in mammals (hayes2005glutathionetransferases. pages 9-12). The distinctive domain architecture suggests that Gtt3p may represent a fungal-specific or Saccharomyces-specific variation of the glutathione transferase fold. Recent work using AI-based structure prediction (AlphaFold) has revealed "hidden" glutathione transferases in the human genome that share the cytosolic GST fold but have divergent sequences, suggesting that GST-fold proteins are more diverse than previously appreciated. Similar analysis could potentially illuminate the structural relationship of Gtt3p to other GST-fold proteins, but such analysis specific to Gtt3p was not identified in the literature.
GTT3 (YEL017W) encodes a putative glutathione transferase in S. cerevisiae that remains largely uncharacterized at the biochemical level. While it is named alongside the better-characterized Gtt1 and Gtt2 as part of the yeast glutathione transferase family, Gtt3p possesses unique domains (Put_GTT3, GTT3_N) that distinguish it from these paralogs and from other GST classes. No direct enzymatic activity, substrate specificity, or subcellular localization data for Gtt3p were identified in the available literature. Its transcription is not induced under oxidative stress conditions that activate other glutathione-related genes, and its deletion has been associated with altered secondary metabolite production in synthetic biology experiments but without a resolved mechanism. The function of Gtt3p can currently only be inferred by analogy to the broader glutathione transferase superfamily: it is predicted to catalyze the conjugation of glutathione with electrophilic substrates, but its specific biological role, substrates, and cellular compartment of action remain open questions requiring future experimental investigation.
References
(mariani2008involvementofglutathione pages 2-4): Diana Mariani, Cristiane J. Mathias, Carmelita G. da Silva, Ricardo da Silva Herdeiro, Ricardo Pereira, Anita D. Panek, Elis C.A. Eleutherio, and Marcos Dias Pereira. Involvement of glutathione transferases, gtt1and gtt2, with oxidative stress response generated by h2o2 during growth of saccharomyces cerevisiae. Redox Report, 13:246-254, Dec 2008. URL: https://doi.org/10.1179/135100008x309028, doi:10.1179/135100008x309028. This article has 42 citations and is from a peer-reviewed journal.
(mariani2008involvementofglutathione pages 4-6): Diana Mariani, Cristiane J. Mathias, Carmelita G. da Silva, Ricardo da Silva Herdeiro, Ricardo Pereira, Anita D. Panek, Elis C.A. Eleutherio, and Marcos Dias Pereira. Involvement of glutathione transferases, gtt1and gtt2, with oxidative stress response generated by h2o2 during growth of saccharomyces cerevisiae. Redox Report, 13:246-254, Dec 2008. URL: https://doi.org/10.1179/135100008x309028, doi:10.1179/135100008x309028. This article has 42 citations and is from a peer-reviewed journal.
(mariani2008involvementofglutathione pages 1-2): Diana Mariani, Cristiane J. Mathias, Carmelita G. da Silva, Ricardo da Silva Herdeiro, Ricardo Pereira, Anita D. Panek, Elis C.A. Eleutherio, and Marcos Dias Pereira. Involvement of glutathione transferases, gtt1and gtt2, with oxidative stress response generated by h2o2 during growth of saccharomyces cerevisiae. Redox Report, 13:246-254, Dec 2008. URL: https://doi.org/10.1179/135100008x309028, doi:10.1179/135100008x309028. This article has 42 citations and is from a peer-reviewed journal.
(mariani2008involvementofglutathione pages 8-9): Diana Mariani, Cristiane J. Mathias, Carmelita G. da Silva, Ricardo da Silva Herdeiro, Ricardo Pereira, Anita D. Panek, Elis C.A. Eleutherio, and Marcos Dias Pereira. Involvement of glutathione transferases, gtt1and gtt2, with oxidative stress response generated by h2o2 during growth of saccharomyces cerevisiae. Redox Report, 13:246-254, Dec 2008. URL: https://doi.org/10.1179/135100008x309028, doi:10.1179/135100008x309028. This article has 42 citations and is from a peer-reviewed journal.
(hayes2005glutathionetransferases. pages 6-7): John D. Hayes, Jack U. Flanagan, and Ian R. Jowsey. Glutathione transferases. Annual review of pharmacology and toxicology, 45:51-88, Sep 2005. URL: https://doi.org/10.1146/annurev.pharmtox.45.120403.095857, doi:10.1146/annurev.pharmtox.45.120403.095857. This article has 5256 citations and is from a highest quality peer-reviewed journal.
(auchere2008glutathionedependentredoxstatus pages 3-4): F. Auchère, Renata Santos, S. Planamente, E. Lesuisse, and J. Camadro. Glutathione-dependent redox status of frataxin-deficient cells in a yeast model of friedreich's ataxia. Human molecular genetics, 17 18:2790-802, Sep 2008. URL: https://doi.org/10.1093/hmg/ddn178, doi:10.1093/hmg/ddn178. This article has 101 citations and is from a domain leading peer-reviewed journal.
(mariani2008involvementofglutathione pages 6-8): Diana Mariani, Cristiane J. Mathias, Carmelita G. da Silva, Ricardo da Silva Herdeiro, Ricardo Pereira, Anita D. Panek, Elis C.A. Eleutherio, and Marcos Dias Pereira. Involvement of glutathione transferases, gtt1and gtt2, with oxidative stress response generated by h2o2 during growth of saccharomyces cerevisiae. Redox Report, 13:246-254, Dec 2008. URL: https://doi.org/10.1179/135100008x309028, doi:10.1179/135100008x309028. This article has 42 citations and is from a peer-reviewed journal.
(sha2013thegenomewideearly pages 9-11): Wei Sha, Ana M. Martins, Reinhard Laubenbacher, Pedro Mendes, and Vladimir Shulaev. The genome-wide early temporal response of saccharomyces cerevisiae to oxidative stress induced by cumene hydroperoxide. PLoS ONE, 8:e74939, Sep 2013. URL: https://doi.org/10.1371/journal.pone.0074939, doi:10.1371/journal.pone.0074939. This article has 42 citations and is from a peer-reviewed journal.
(auchere2008glutathionedependentredoxstatus pages 5-6): F. Auchère, Renata Santos, S. Planamente, E. Lesuisse, and J. Camadro. Glutathione-dependent redox status of frataxin-deficient cells in a yeast model of friedreich's ataxia. Human molecular genetics, 17 18:2790-802, Sep 2008. URL: https://doi.org/10.1093/hmg/ddn178, doi:10.1093/hmg/ddn178. This article has 101 citations and is from a domain leading peer-reviewed journal.
(auchere2008glutathionedependentredoxstatus pages 4-5): F. Auchère, Renata Santos, S. Planamente, E. Lesuisse, and J. Camadro. Glutathione-dependent redox status of frataxin-deficient cells in a yeast model of friedreich's ataxia. Human molecular genetics, 17 18:2790-802, Sep 2008. URL: https://doi.org/10.1093/hmg/ddn178, doi:10.1093/hmg/ddn178. This article has 101 citations and is from a domain leading peer-reviewed journal.
(wang2018ringsyntheticchromosome pages 5-6): Juan Wang, Ze-Xiong Xie, Yuan Ma, Xiang-Rong Chen, Yao-Qing Huang, Bo He, Bin Jia, Bing-Zhi Li, and Ying-Jin Yuan. Ring synthetic chromosome v scramble. Nature Communications, Sep 2018. URL: https://doi.org/10.1038/s41467-018-06216-y, doi:10.1038/s41467-018-06216-y. This article has 90 citations and is from a highest quality peer-reviewed journal.
(hayes2005glutathionetransferases. pages 1-3): John D. Hayes, Jack U. Flanagan, and Ian R. Jowsey. Glutathione transferases. Annual review of pharmacology and toxicology, 45:51-88, Sep 2005. URL: https://doi.org/10.1146/annurev.pharmtox.45.120403.095857, doi:10.1146/annurev.pharmtox.45.120403.095857. This article has 5256 citations and is from a highest quality peer-reviewed journal.
(hayes2005glutathionetransferases. pages 4-6): John D. Hayes, Jack U. Flanagan, and Ian R. Jowsey. Glutathione transferases. Annual review of pharmacology and toxicology, 45:51-88, Sep 2005. URL: https://doi.org/10.1146/annurev.pharmtox.45.120403.095857, doi:10.1146/annurev.pharmtox.45.120403.095857. This article has 5256 citations and is from a highest quality peer-reviewed journal.
(zhou2021directedgenomeevolution pages 9-10): Sijie Zhou, Yi Wu, Ze-Xiong Xie, Bin Jia, and Ying-Jin Yuan. Directed genome evolution driven by structural rearrangement techniques. Chemical Society reviews, 50:12788-12807, Oct 2021. URL: https://doi.org/10.1039/d1cs00722j, doi:10.1039/d1cs00722j. This article has 26 citations and is from a highest quality peer-reviewed journal.
(hayes2005glutathionetransferases. pages 9-12): John D. Hayes, Jack U. Flanagan, and Ian R. Jowsey. Glutathione transferases. Annual review of pharmacology and toxicology, 45:51-88, Sep 2005. URL: https://doi.org/10.1146/annurev.pharmtox.45.120403.095857, doi:10.1146/annurev.pharmtox.45.120403.095857. This article has 5256 citations and is from a highest quality peer-reviewed journal.