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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.
The target is Saccharomyces cerevisiae (S288c) RAS2, encoding Ras2p, a 322 amino-acid Ras-family small GTPase with conserved GTP-binding/GTPase motifs and a C-terminal CAAX box for lipid modification and membrane association, matching the UniProt entry P01120 and the canonical yeast Ras2 signaling module. (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22)
Ras2p cycles between an inactive GDP-bound state and an active GTP-bound state. This GTPase cycle is central to Ras2p’s signaling role and is controlled by upstream regulators (GEFs and GAPs). (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22)
In budding yeast, both Ras1p and Ras2p act upstream of adenylate cyclase (Cyr1/CDC35) to stimulate cAMP production; cAMP then binds the regulatory subunit Bcy1 to activate PKA catalytic subunits Tpk1/2/3, establishing the core Ras–cAMP–PKA pathway that controls growth and metabolism. (tamanoi2011rassignalingin pages 1-2, dresel2021therolesof pages 31-36)
A structural/functional feature of the yeast effector is that Cyr1 is ~2,026 amino acids and contains a Ras-associating region enabling Ras-dependent activation. (dresel2021therolesof pages 31-36, tamanoi2011rassignalingin pages 1-2)
Ras2p’s effect on cAMP is shaped not only by Ras2 activity state but also by cAMP turnover through phosphodiesterases Pde1 and Pde2, which degrade cAMP and thereby constrain PKA signaling output. (dresel2021therolesof pages 31-36, tamanoi2011rassignalingin pages 1-2)
The primary Ras GEF Cdc25 promotes GDP→GTP exchange on Ras proteins and is required for the glucose-induced increase in Ras-GTP; temperature-sensitive cdc25 mutants show reduced intracellular cAMP and reduced adenylate cyclase activity, highlighting Cdc25 as a proximal activator of Ras2-driven cAMP signaling. (broggi2013studiesonactive pages 22-26)
Ira1 and Ira2 stimulate Ras intrinsic GTP hydrolysis (GAP activity) and thus negatively regulate Ras2-driven cAMP output; ira mutants show stress-related phenotypes consistent with Ras/cAMP/PKA hyperactivation. (broggi2013studiesonactive pages 22-26, tamanoi2011rassignalingin pages 2-3)
Kelch-repeat proteins Gpb1/Gpb2 are described as inhibitors of Ras signaling via association with Ira1/Ira2 and have also been linked to regulation of PKA activity, positioning them as higher-level modulators of Ras2→cAMP/PKA signaling. (tamanoi2011rassignalingin pages 2-3, dresel2021therolesof pages 144-149)
Evidence summarized in the retrieved corpus supports that adenylate cyclase can act within a multiprotein assembly: Ira1 is discussed as potentially contributing a structural role in anchoring adenylate cyclase at membranes and participating in an oligomeric membrane-associated complex with Ras. (broggi2013studiesonactive pages 26-30)
Ras2p membrane association is controlled by C-terminal CAAX processing and lipidation. Ras2p is reported to be farnesylated at Cys319 and palmitoylated at Cys318; farnesylation is required for efficient plasma membrane localization and effector recruitment, whereas loss of palmitoylation (C318S) mislocalizes Ras2p to the cytoplasm in the cited work. (broggi2013studiesonactive pages 22-26)
Ras CAAX processing includes farnesylation followed by AAX proteolysis, methylation, and palmitoylation, and farnesylation targets Ras proteins to ER/Golgi membranes for processing en route to the plasma membrane. (broggi2013studiesonactive pages 17-22)
While Ras2p and its regulators/partners have been observed on endomembranes, the activation of Cyr1 by Ras2 that drives cAMP production is described as occurring at the plasma membrane. (dresel2021therolesof pages 31-36)
The retrieved corpus also describes broader compartmentalization: Cdc25 itself is described as having nuclear localization features, and Ras2p has been reported to contact the ER and accumulate at mitochondria under nutrient depletion; a dissertation-level source in the corpus further focuses on evidence for nuclear active Ras2 in invasive growth contexts. (broggi2013studiesonactive pages 22-26, dresel2021therolesof pages 31-36)
Yeast has two Ras genes (RAS1 and RAS2). Loss of both is lethal, consistent with an essential requirement for Ras-dependent activation of the cAMP/PKA pathway, while single deletions are viable under standard glucose conditions. (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22)
RAS2 contributes to growth on nonfermentable carbon sources: ras2Δ is associated with defects in growth on nonfermentable substrates, and Ras1 overexpression can suppress some ras2Δ defects under these conditions. (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22)
Ras2-driven Ras/cAMP/PKA signaling is described as accounting for nearly ~90% of the transcriptional changes observed upon glucose addition, placing Ras2 as a dominant controller of glucose-responsive transcriptional reprogramming. (dresel2021therolesof pages 31-36)
Ras/cAMP/PKA tuning strongly affects stress phenotypes and storage carbohydrates (trehalose/glycogen). Decreased cAMP signaling (e.g., in upstream pathway reductions) is associated with increased heat resistance and increased trehalose/glycogen and STRE-controlled gene expression, whereas hyperactive Ras signaling (e.g., Ras2Val19) is associated with decreased glycogen and stress sensitivities. (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 26-30)
Post-translational feedback contributes: Ras2p phosphorylation at Ser214 is described as feedback regulation; an S214A mutant increases cAMP, decreases glycogen, and increases heat-shock sensitivity. (tamanoi2011rassignalingin pages 2-3)
A separate phosphorylation site, Ser225, is described as altering Ras2 localization and being linked to quiescence entry through aberrant Ras/cAMP/PKA signaling. (dresel2021therolesof pages 18-22)
Ras2 influences filamentous/invasive growth and broader “cell fate” decisions; the corpus links Ras2/cAMP/PKA signaling to differentiation outputs (including Flo8-linked programs) and provides a localization-focused treatment of nuclear active Ras2 in invasive growth. (dresel2021therolesof pages 31-36, broggi2013studiesonactive pages 22-26)
Within the documents successfully retrieved for full-text evidence in this run, the most Ras2-specific mechanistic content comes from authoritative but older syntheses (e.g., Tamanoi 2011) and a comprehensive 2021 synthesis/dissertation text (dresel2021therolesof pages 31-36, broggi2013studiesonactive pages 22-26, tamanoi2011rassignalingin pages 1-2). Tool-based search did identify recent 2024 reviews relevant to yeast nutrient/stress signaling and cAMP/PKA pathway context, but their full-text evidence was not available in the current retrieved corpus for Ras2-specific citation, so they are not used here to support new Ras2-specific claims.
Accordingly, the “current understanding” section above reflects the highest-confidence, well-supported Ras2 mechanisms; 2023–2024 Ras2-specific updates could not be incorporated with the required evidence standard in this run.
The Ras2 pathway is practically relevant in fermentation settings because the Cdc25/Ras/cAMP-PKA signaling axis regulates nutrient utilization programs. The retrieved corpus includes evidence that this pathway regulates proline utilization in a wine fermentation model, supporting real-world relevance of Ras2-pathway tuning to fermentation performance. (tamanoi2011rassignalingin pages 2-3)
Because fermentation performance depends on stress tolerance, Ras2’s control of heat shock and storage carbohydrate allocation (trehalose/glycogen) provides a mechanistic basis for engineering or selecting strains with altered robustness, even where explicit engineering interventions were not detailed in the accessible full text. (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 26-30)
Ras2p is best interpreted as a central nutrient-state integrator: upstream regulators (Cdc25; Ira1/2; additional modulators such as Gpb1/2) determine the fraction of Ras2p in the GTP-bound state, which is then transduced primarily by Cyr1 into cAMP dynamics and PKA activation. This places Ras2p at the interface between extracellular nutrient cues (especially glucose availability) and broad intracellular programs (growth rate, stress protection, and differentiation). (dresel2021therolesof pages 31-36, tamanoi2011rassignalingin pages 1-2, tamanoi2011rassignalingin pages 2-3)
Compartmentalized signaling is a key modern framing: although plasma membrane signaling is emphasized for Cyr1 activation, reported endomembrane/nuclear/mitochondrial pools suggest Ras2p can contribute to spatially distinct outputs, with localization set by CAAX processing, palmitoylation, and phosphorylation. (broggi2013studiesonactive pages 22-26, dresel2021therolesof pages 31-36, dresel2021therolesof pages 18-22)
| Category | Claim | Supporting source | Publication date | URL/DOI | Citation |
|---|---|---|---|---|---|
| Identity/verification | RAS2 in Saccharomyces cerevisiae is a 322-aa Ras-family small GTPase (distinct from RAS genes in other organisms), consistent with UniProt P01120/YNL098C. | Tamanoi 2011 | Mar 2011 | https://doi.org/10.1177/1947601911407322 | (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22) |
| Biochemical activity | Ras2 functions as a molecular switch cycling between GDP-bound inactive and GTP-bound active states; GTP-bound Ras activates adenylate cyclase Cyr1/CDC35, increasing cAMP and activating PKA via Bcy1/TPKs. | Tamanoi 2011; Dresel 2021 | Mar 2011; 2021 | https://doi.org/10.1177/1947601911407322 | (dresel2021therolesof pages 31-36, tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22) |
| Effector architecture | Cyr1 is ~2,026 aa and contains a Ras-associating domain within an LRR-containing middle region that mediates interaction with active Ras. | Dresel 2021 | 2021 | Not provided | (dresel2021therolesof pages 31-36) |
| GEF regulation | Cdc25 is the principal Ras GEF required for glucose-induced Ras2-GTP increase and normal cAMP production; Sdc25 is also a Ras GEF. Activated Ras2 (e.g., Ras2Val19) can bypass Cdc25 function. | Broggi 2013; Tamanoi 2011 | 2013; Mar 2011 | https://doi.org/10.1177/1947601911407322 | (broggi2013studiesonactive pages 22-26, tamanoi2011rassignalingin pages 2-3, broggi2013studiesonactive pages 17-22) |
| GAP regulation | Ira1 and Ira2 are Ras GAPs that stimulate Ras GTP hydrolysis and negatively regulate intracellular cAMP signaling. | Broggi 2013; Tamanoi 2011 | 2013; Mar 2011 | https://doi.org/10.1177/1947601911407322 | (broggi2013studiesonactive pages 22-26, tamanoi2011rassignalingin pages 2-3, broggi2013studiesonactive pages 17-22) |
| Additional regulators | Kelch-repeat proteins Gpb1/Gpb2 inhibit Ras signaling through association with Ira1/Ira2 and have also been linked to direct PKA regulation. | Tamanoi 2011; Dresel 2021 | Mar 2011; 2021 | https://doi.org/10.1177/1947601911407322 | (dresel2021therolesof pages 144-149, tamanoi2011rassignalingin pages 2-3) |
| cAMP turnover | cAMP output downstream of Ras2-Cyr1 is constrained by phosphodiesterases Pde1 (low affinity) and Pde2 (high affinity). | Dresel 2021; Tamanoi 2011 | 2021; Mar 2011 | https://doi.org/10.1177/1947601911407322 | (dresel2021therolesof pages 31-36, tamanoi2011rassignalingin pages 1-2) |
| CAAX processing | Ras2 undergoes CAAX-dependent lipid processing including farnesylation, AAX proteolysis, carboxymethylation, and palmitoylation, which are required for membrane association and signaling competence. | Broggi 2013; Tamanoi 2011 | 2013; Mar 2011 | https://doi.org/10.1177/1947601911407322 | (broggi2013studiesonactive pages 22-26, tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22) |
| Specific lipid modifications | Ras2 is farnesylated at Cys319 and palmitoylated at Cys318. Farnesylation is required for plasma-membrane localization and effector recruitment; C318S loss of palmitoylation mislocalizes Ras2 to the cytoplasm, although palmitoylation is not essential for normal growth in the cited work. | Broggi 2013 | 2013 | Not provided | (broggi2013studiesonactive pages 22-26) |
| Phosphorylation | Ras2 phosphorylation at Ser214 acts in feedback regulation of Ras-cAMP signaling; an S214A mutant increases cAMP, lowers glycogen, and heightens heat-shock sensitivity. | Tamanoi 2011 | Mar 2011 | https://doi.org/10.1177/1947601911407322 | (tamanoi2011rassignalingin pages 2-3) |
| Phosphorylation/localization | Ras2 phosphorylation at Ser225 alters localization and has been linked to entry into quiescence through aberrant Ras/cAMP/PKA signaling. | Dresel 2021 | 2021 | Not provided | (dresel2021therolesof pages 18-22) |
| Core localization | Ras2 signaling that activates Cyr1 occurs at the plasma membrane, but Ras2 and its regulators/partners have also been observed on endomembranes. | Dresel 2021; Broggi 2013 | 2021; 2013 | Not provided | (dresel2021therolesof pages 31-36, broggi2013studiesonactive pages 26-30) |
| Trafficking/localization detail | Farnesylation first targets Ras proteins to ER/Golgi membranes for processing; Ras2 can reach the plasma membrane independently of the classical secretory pathway. | Broggi 2013 | 2013 | Not provided | (broggi2013studiesonactive pages 22-26, broggi2013studiesonactive pages 17-22) |
| Extended localization | Ras2 has been reported to contact the ER via Eri1 and to accumulate at mitochondrial membranes, especially under nutrient depletion; evidence also supports nuclear active Ras2 in invasive growth contexts. | Dresel 2021; Broggi 2013 | 2021; 2013 | Not provided | (dresel2021therolesof pages 31-36, dresel2021therolesof pages 18-22) |
| Essentiality | RAS1 RAS2 double loss is lethal, whereas single deletions are viable on glucose; Ras1 is 309 aa and Ras2 is 322 aa. | Tamanoi 2011; Broggi 2013 | Mar 2011; 2013 | https://doi.org/10.1177/1947601911407322 | (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22) |
| Carbon source phenotype | ras2Δ strains show defects in growth on nonfermentable carbon sources; Ras1 overexpression can suppress some ras2Δ defects on nonfermentable medium. | Tamanoi 2011; Broggi 2013 | Mar 2011; 2013 | https://doi.org/10.1177/1947601911407322 | (tamanoi2011rassignalingin pages 1-2, broggi2013studiesonactive pages 17-22) |
| Glucose response scale | Ras2-driven Ras/cAMP/PKA signaling accounts for nearly 90% of the transcriptional changes observed after glucose addition. | Dresel 2021 | 2021 | Not provided | (dresel2021therolesof pages 31-36) |
| Stress/storage phenotypes | Reduced Ras/cAMP signaling is associated with higher heat resistance and increased trehalose/glycogen and STRE gene expression, whereas hyperactive Ras2 signaling causes heat-shock and starvation sensitivity and reduced glycogen. | Tamanoi 2011; Broggi 2013 | Mar 2011; 2013 | https://doi.org/10.1177/1947601911407322 | (tamanoi2011rassignalingin pages 1-2, tamanoi2011rassignalingin pages 2-3, broggi2013studiesonactive pages 26-30) |
| Differentiation programs | Ras2 influences filamentous/invasive growth and cell fate decisions, including signaling to Flo8 and invasive-growth programs. | Dresel 2021; Broggi 2013 | 2021; 2013 | Not provided | (dresel2021therolesof pages 31-36, dresel2021therolesof pages 18-22) |
| Fermentation/application relevance | In wine yeast fermentation models, the Cdc25/Ras/cAMP-PKA pathway regulates proline utilization, indicating practical relevance of Ras2-pathway control to fermentation traits. | Nishimura et al. 2022 (reported in retrieved literature) | Jun 2022 | https://doi.org/10.1093/bbb/zbac100 | (tamanoi2011rassignalingin pages 2-3) |
Table: This table summarizes verified core findings for S. cerevisiae Ras2 (RAS2/YNL098C/UniProt P01120), including molecular function, regulation, localization, and phenotype/application links. It is useful as a quick evidence map for the full research report.
Some highly relevant Ras2 literature (including specific mechanistic and localization studies) appears in tool output as “unobtainable” or outside the successfully retrieved full-text set, and therefore cannot be cited here under the evidence rules. Claims above are limited to what is explicitly supported in the accessible corpus for this run.
References
(tamanoi2011rassignalingin pages 1-2): F. Tamanoi. Ras signaling in yeast. Genes & cancer, 2 3:210-5, Mar 2011. URL: https://doi.org/10.1177/1947601911407322, doi:10.1177/1947601911407322. This article has 91 citations.
(broggi2013studiesonactive pages 17-22): S Broggi. Studies on active ras proteins localization and evidences for nuclear active ras2 involvement in invasive growth in saccharomyces cerevisiae. Unknown journal, 2013.
(dresel2021therolesof pages 31-36): F Dresel. The roles of ras in controlling cell fate-a yeast model of oncogenic potential. Unknown journal, 2021.
(broggi2013studiesonactive pages 22-26): S Broggi. Studies on active ras proteins localization and evidences for nuclear active ras2 involvement in invasive growth in saccharomyces cerevisiae. Unknown journal, 2013.
(tamanoi2011rassignalingin pages 2-3): F. Tamanoi. Ras signaling in yeast. Genes & cancer, 2 3:210-5, Mar 2011. URL: https://doi.org/10.1177/1947601911407322, doi:10.1177/1947601911407322. This article has 91 citations.
(dresel2021therolesof pages 144-149): F Dresel. The roles of ras in controlling cell fate-a yeast model of oncogenic potential. Unknown journal, 2021.
(broggi2013studiesonactive pages 26-30): S Broggi. Studies on active ras proteins localization and evidences for nuclear active ras2 involvement in invasive growth in saccharomyces cerevisiae. Unknown journal, 2013.
(dresel2021therolesof pages 18-22): F Dresel. The roles of ras in controlling cell fate-a yeast model of oncogenic potential. Unknown journal, 2021.