RAS2 is a small GTPase that serves as a key regulator of cAMP-dependent protein kinase (PKA) signaling in Saccharomyces cerevisiae. RAS2 cycles between GTP-bound active and GDP-bound inactive states, activated by guanine nucleotide exchange factor CDC25 and inactivated by GAPs IRA1/IRA2. As a primary effector regulating adenylate cyclase activity, RAS2 controls nutrient-dependent cell growth, glucose sensing, metabolic enzyme regulation, stress response, and replicative lifespan through PKA-mediated signaling. RAS2 also functions in morphogenetic pathways including pseudohyphal growth and cell division polarity through Cdc42/MAPK signaling. The protein is farnesylated and palmitoylated, localizing to plasma membrane, ER membrane, and nucleus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Curation review of plasma membrane (GO:0005886) with IBA evidence. RAS2 is farnesylated at Cys319 and palmitoylated at Cys318; farnesylation is required for efficient plasma membrane localization, the site at which RAS2 activates Cyr1 to drive cAMP production. Reason: IBA annotation confirmed by multiple IDA annotations. RAS2 is farnesylated and palmitoylated, essential for plasma membrane anchoring. Supporting Evidence: file:yeast/RAS2/RAS2-deep-research-falcon.md Ras2p is reported to be **farnesylated at Cys319** and **palmitoylated at Cys318**; **farnesylation** is required for efficient **plasma membrane localization** and effector recruitment file:yeast/RAS2/RAS2-deep-research-falcon.md the activation of Cyr1 by Ras2 that drives cAMP production is described as occurring at the **plasma membrane**. |
| GO:0007163 establishment or maintenance of cell polarity | IBA GO_REF:0000033 | ACCEPT | Summary: Curation review of establishment or maintenance of cell polarity (GO:0007163) with IBA evidence. Reason: RAS2 regulates cell polarity through protein localization to bud neck and Cdc42/MAPK signaling pathway controlling cell division morphogenesis. |
| GO:0007265 Ras protein signal transduction | IBA GO_REF:0000033 | ACCEPT | Summary: Curation review of Ras protein signal transduction (GO:0007265) with IBA evidence. RAS2-GTP activates adenylate cyclase (Cyr1/CDC35) to raise cAMP, which binds Bcy1 to activate PKA catalytic subunits Tpk1/2/3, establishing the core Ras-cAMP-PKA pathway. Reason: Core function of RAS2. Acts as primary regulator of adenylate cyclase and PKA signaling pathway. Supporting Evidence: file:yeast/RAS2/RAS2-deep-research-falcon.md 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 **RasβcAMPβPKA** pathway that controls growth and metabolism. |
| GO:0003924 GTPase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Curation review of GTPase activity (GO:0003924) with IBA evidence. RAS2 acts as a molecular switch cycling between an inactive GDP-bound state and an active GTP-bound state; this GTPase cycle is controlled by the GEF Cdc25 and the GAPs Ira1/Ira2. Reason: Core catalytic function. RAS2 hydrolyzes GTP to GDP, enabling regulation of downstream signaling. Supporting Evidence: file:yeast/RAS2/RAS2-deep-research-falcon.md Ras2p cycles between an **inactive GDP-bound** state and an **active GTP-bound** state. file:yeast/RAS2/RAS2-deep-research-falcon.md **Ira1** and **Ira2** stimulate Ras intrinsic GTP hydrolysis (GAP activity) and thus negatively regulate Ras2-driven cAMP output |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: Curation review of nucleotide binding (GO:0000166) with IEA evidence. Reason: Appropriate computational annotation. RAS2 binds guanine nucleotides (GTP/GDP) as substrate for catalytic cycle. |
| GO:0003924 GTPase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Curation review of GTPase activity (GO:0003924) with IEA evidence. Reason: Valid InterPro-based inference. Multiple evidence types acceptable for same term. |
| GO:0003925 G protein activity | IEA GO_REF:0000003 | ACCEPT | Summary: Curation review of G protein activity (GO:0003925) with IEA evidence. Reason: Appropriate parent term. RAS2 is a GTP-binding protein with GTPase activity (G protein). |
| GO:0005525 GTP binding | IEA GO_REF:0000120 | ACCEPT | Summary: Curation review of GTP binding (GO:0005525) with IEA evidence. Reason: Appropriate computational annotation. RAS2 canonical substrate is GTP. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Curation review of plasma membrane (GO:0005886) with IEA evidence. Reason: Consistent with IBA and IDA evidence from subcellular localization mapping. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: Curation review of signal transduction (GO:0007165) with IEA evidence. Reason: Appropriate parent term for RAS2 signaling function. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Curation review of membrane (GO:0016020) with IEA evidence. Reason: Appropriate parent term. RAS2 is a membrane-anchored protein. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | ACCEPT | Summary: Curation review of hydrolase activity (GO:0016787) with IEA evidence. Reason: Appropriate parent term for GTPase activity (hydrolysis of phosphodiester bonds). |
| GO:0097271 protein localization to bud neck | IEA GO_REF:0000117 | REMOVE | Summary: Curation review of protein localization to bud neck (GO:0097271) with IEA evidence. Reason: IEA annotation for specific subcellular localization is overly detailed for computational inference. Specific experimental evidence (IGI) already provided. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Curation review of protein binding (GO:0005515) with IPI evidence. Reason: Generic protein binding term is non-informative. RAS1 interaction is properly described by signal transduction and protein localization terms. Remove per GO guidelines. Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:12782684 Ras recruits mitotic exit regulator Lte1 to the bud cortex i... | REMOVE | Summary: Curation review of protein binding (GO:0005515) with IPI evidence. Reason: Generic protein binding term is non-informative. LTE1 recruitment to bud neck is captured by specific process terms (protein localization, cell division). Supporting Evidence: PMID:12782684 Jun 2. Ras recruits mitotic exit regulator Lte1 to the bud cortex in budding yeast. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | REMOVE | Summary: Curation review of protein binding (GO:0005515) with IPI evidence. Reason: Generic protein binding term is non-informative per GO curation guidelines. Use specific process terms instead. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:21073870 Feedback regulation of Ras2 guanine nucleotide exchange fact... | REMOVE | Summary: Curation review of protein binding (GO:0005515) with IPI evidence. Reason: Generic protein binding term is non-informative. CDC25 GEF interaction is properly described through signal transduction pathways. Supporting Evidence: PMID:21073870 Epub 2010 Nov 10. Feedback regulation of Ras2 guanine nucleotide exchange factor (Ras2-GEF) activity of Cdc25p by Cdc25p phosphorylation in the yeast Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:21457714 The membrane localization of Ras2p and the association betwe... | REMOVE | Summary: Curation review of protein binding (GO:0005515) with IPI evidence. Reason: Generic protein binding term is non-informative. PKA regulation of RAS2 is captured by PKA signaling pathway terms. Supporting Evidence: PMID:21457714 Epub 2011 Mar 30. The membrane localization of Ras2p and the association between Cdc25p and Ras2-GTP are regulated by protein kinase A (PKA) in the yeast Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:23831759 Mapping the functional yeast ABC transporter interactome. | REMOVE | Summary: Curation review of protein binding (GO:0005515) with IPI evidence. Reason: Generic protein binding term is non-informative. YCF1 interaction not core to RAS2 function. Supporting Evidence: PMID:23831759 Mapping the functional yeast ABC transporter interactome. |
| GO:0005739 mitochondrion | HDA PMID:24769239 Quantitative variations of the mitochondrial proteome and ph... | KEEP AS NON CORE | Summary: Curation review of mitochondrion (GO:0005739) with HDA evidence. Reason: Minor mitochondrial localization during respiratory growth. Not primary site of RAS2 signaling. Supporting Evidence: PMID:24769239 2014 Apr 24. Quantitative variations of the mitochondrial proteome and phosphoproteome during fermentative and respiratory growth in Saccharomyces cerevisiae. |
| GO:0071944 cell periphery | HDA PMID:26928762 One library to make them all: streamlining the creation of y... | KEEP AS NON CORE | Summary: Curation review of cell periphery (GO:0071944) with HDA evidence. Reason: General cell periphery localization. Less specific than plasma membrane. Supporting Evidence: PMID:26928762 One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy. |
| GO:0005886 plasma membrane | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: Curation review of plasma membrane (GO:0005886) with HDA evidence. Reason: Proteomics evidence supporting plasma membrane localization. Supporting Evidence: PMID:11914276 Subcellular localization of the yeast proteome. |
| GO:0005886 plasma membrane | HDA PMID:16622836 The plasma membrane proteome of Saccharomyces cerevisiae and... | ACCEPT | Summary: Curation review of plasma membrane (GO:0005886) with HDA evidence. Reason: Plasma membrane proteome study confirming RAS2 localization. Supporting Evidence: PMID:16622836 The plasma membrane proteome of Saccharomyces cerevisiae and its response to the antifungal calcofluor. |
| GO:0010603 regulation of cytoplasmic mRNA processing body assembly | IMP PMID:21925385 The cAMP-dependent protein kinase signaling pathway is a key... | ACCEPT | Summary: Curation review of regulation of cytoplasmic mRNA processing body assembly (GO:0010603) with IMP evidence. Reason: RAS2/PKA pathway regulates P body formation. PMID:21925385 demonstrates cAMP/PKA controls mRNA processing body assembly. Supporting Evidence: PMID:21925385 The cAMP-dependent protein kinase signaling pathway is a key regulator of P body foci formation. |
| GO:0042149 cellular response to glucose starvation | IMP PMID:21925385 The cAMP-dependent protein kinase signaling pathway is a key... | ACCEPT | Summary: Curation review of cellular response to glucose starvation (GO:0042149) with IMP evidence. Reason: RAS2 is critical regulator of nutrient starvation response. Loss of RAS2 leads to constitutive starvation response. RAS2-driven Ras/cAMP/PKA signaling dominates glucose-responsive transcriptional reprogramming. Supporting Evidence: PMID:21925385 The cAMP-dependent protein kinase signaling pathway is a key regulator of P body foci formation. file:yeast/RAS2/RAS2-deep-research-falcon.md 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. |
| GO:0016236 macroautophagy | IGI PMID:15016820 The Ras/cAMP-dependent protein kinase signaling pathway regu... | MODIFY | Summary: Curation review of macroautophagy (GO:0016236) with IGI evidence. Reason: PMID:15016820 demonstrates RAS/PKA pathway INHIBITS autophagy during growth. Annotation reflects inhibitory relationship. Proposed replacements: negative regulation of autophagy Supporting Evidence: PMID:15016820 2004 Mar 11. The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. |
| GO:0032258 cytoplasm to vacuole targeting by the Cvt pathway | IMP PMID:15016820 The Ras/cAMP-dependent protein kinase signaling pathway regu... | MODIFY | Summary: Curation review of cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) with IMP evidence. Reason: PMID:15016820 demonstrates that the RAS/PKA pathway inhibits the Cvt pathway during growth. GO has no current negative-regulation child for this process, so the broader current Cvt-regulation term is the valid replacement. Proposed replacements: regulation of protein localization by the Cvt pathway Supporting Evidence: PMID:15016820 2004 Mar 11. The Ras/cAMP-dependent protein kinase signaling pathway regulates an early step of the autophagy process in Saccharomyces cerevisiae. |
| GO:2000222 positive regulation of pseudohyphal growth | IMP PMID:1547504 Unipolar cell divisions in the yeast S. cerevisiae lead to f... | ACCEPT | Summary: Curation review of positive regulation of pseudohyphal growth (GO:2000222) with IMP evidence. Reason: Well-documented. RAS2 (especially constitutively active RAS2val19) promotes pseudohyphal growth in response to nitrogen starvation. Supporting Evidence: PMID:1547504 Unipolar cell divisions in the yeast S. |
| GO:2000222 positive regulation of pseudohyphal growth | IMP PMID:8643578 Ras2 signals via the Cdc42/Ste20/mitogen-activated protein k... | ACCEPT | Summary: Curation review of positive regulation of pseudohyphal growth (GO:2000222) with IMP evidence. Reason: PMID:8643578 demonstrates RAS2 signals via Cdc42/MAPK pathway to induce filamentous growth. Supporting Evidence: PMID:8643578 Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. file:yeast/RAS2/RAS2-deep-research-falcon.md Ras2 influences filamentous/invasive growth and broader βcell fateβ decisions; the corpus links Ras2/cAMP/PKA signaling to differentiation outputs (including Flo8-linked programs) |
| GO:0005634 nucleus | IDA PMID:23127800 Live-cell imaging of endogenous Ras-GTP shows predominant Ra... | ACCEPT | Summary: Curation review of nucleus (GO:0005634) with IDA evidence. Reason: PMID:23127800 demonstrates RAS2-GTP localizes to nucleus, supporting transcriptional regulation functions. Supporting Evidence: PMID:23127800 Live-cell imaging of endogenous Ras-GTP shows predominant Ras activation at the plasma membrane and in the nucleus in Saccharomyces cerevisiae. file:yeast/RAS2/RAS2-deep-research-falcon.md a dissertation-level source in the corpus further focuses on evidence for **nuclear active Ras2** in invasive growth contexts. |
| GO:0005886 plasma membrane | IDA PMID:23127800 Live-cell imaging of endogenous Ras-GTP shows predominant Ra... | ACCEPT | Summary: Curation review of plasma membrane (GO:0005886) with IDA evidence. Reason: Direct experimental evidence for plasma membrane localization confirmed by fluorescence imaging. Supporting Evidence: PMID:23127800 Live-cell imaging of endogenous Ras-GTP shows predominant Ras activation at the plasma membrane and in the nucleus in Saccharomyces cerevisiae. |
| GO:0097271 protein localization to bud neck | IGI PMID:12782684 Ras recruits mitotic exit regulator Lte1 to the bud cortex i... | ACCEPT | Summary: Curation review of protein localization to bud neck (GO:0097271) with IGI evidence. Reason: PMID:12782684 demonstrates RAS2 recruits mitotic exit regulator Lte1 to bud cortex. Supporting Evidence: PMID:12782684 Jun 2. Ras recruits mitotic exit regulator Lte1 to the bud cortex in budding yeast. |
| GO:0000411 positive regulation of transcription by galactose | IMP PMID:16292676 Increased phosphoglucomutase activity suppresses the galacto... | UNDECIDED | Summary: Curation review of positive regulation of transcription by galactose (GO:0000411) with IMP evidence. Reason: Insufficient information on mechanism. Paper addresses phosphoglucomutase activity and metabolic effects rather than direct transcriptional regulation. Supporting Evidence: PMID:16292676 Increased phosphoglucomutase activity suppresses the galactose growth defect associated with elevated levels of Ras signaling in S. |
| GO:0003924 GTPase activity | IDA PMID:8106517 Biochemical characterization of yeast RAS2 mutants reveals a... | ACCEPT | Summary: Curation review of GTPase activity (GO:0003924) with IDA evidence from biochemical characterization study. Reason: PMID:8106517 biochemically characterizes RAS2 GTPase activity, measuring intrinsic GTPase rates and GDP dissociation. Core catalytic function of RAS2. Supporting Evidence: PMID:8106517 Biochemical characterization of yeast RAS2 mutants reveals a new region of ras protein involved in the interaction with GTPase-activating proteins. file:yeast/RAS2/RAS2-deep-research-falcon.md The primary Ras GEF **Cdc25** promotes GDPβGTP exchange on Ras proteins and is required for the **glucose-induced increase in Ras-GTP** |
| GO:0005525 GTP binding | IDA PMID:6438624 A product of yeast RAS2 gene is a guanine nucleotide binding... | ACCEPT | Summary: Curation review of GTP binding (GO:0005525) with IDA evidence from foundational biochemical study. Reason: PMID:6438624 demonstrates RAS2 binds guanine nucleotides (GTP/GDP) with specificity characteristic of Ras proteins. Foundational evidence for RAS2 as GTPase. Supporting Evidence: PMID:6438624 A product of yeast RAS2 gene is a guanine nucleotide binding protein. file:yeast/RAS2/RAS2-deep-research-falcon.md Ras2p cycles between an **inactive GDP-bound** state and an **active GTP-bound** state. |
| GO:0005739 mitochondrion | IDA PMID:22575457 Localization of Ras signaling complex in budding yeast. | KEEP AS NON CORE | Summary: Curation review of mitochondrion (GO:0005739) with IDA evidence. Reason: PMID:22575457 shows minor mitochondrial localization. Not primary site of RAS2 signaling function. Falcon notes mitochondrial accumulation is enhanced under nutrient depletion. Supporting Evidence: PMID:22575457 Localization of Ras signaling complex in budding yeast. file:yeast/RAS2/RAS2-deep-research-falcon.md Ras2p has been reported to contact the ER and accumulate at mitochondria under nutrient depletion |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:22575457 Localization of Ras signaling complex in budding yeast. | ACCEPT | Summary: Curation review of endoplasmic reticulum membrane (GO:0005789) with IDA evidence. Reason: PMID:22575457 demonstrates RAS2 localizes to ER membrane during lipid modification and trafficking to plasma membrane. Supporting Evidence: PMID:22575457 Localization of Ras signaling complex in budding yeast. file:yeast/RAS2/RAS2-deep-research-falcon.md 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. |
| GO:0005886 plasma membrane | IDA PMID:20162532 Chemical inhibition of CaaX protease activity disrupts yeast... | ACCEPT | Summary: Curation review of plasma membrane (GO:0005886) with IDA evidence. Reason: Direct experimental evidence. Chemical inhibition of CaaX protease disrupts RAS2 localization. Supporting Evidence: PMID:20162532 Chemical inhibition of CaaX protease activity disrupts yeast Ras localization. |
| GO:0030437 ascospore formation | IMP PMID:2558958 Isolation and characterization of temperature-sensitive muta... | KEEP AS NON CORE | Summary: Curation review of ascospore formation (GO:0030437) with IMP evidence. Reason: RAS2 plays permissive role in sporulation response to nutrient starvation. Not primary regulator of meiosis. Supporting Evidence: PMID:2558958 Isolation and characterization of temperature-sensitive mutations in the RAS2 and CYR1 genes of Saccharomyces cerevisiae. |
| GO:0032880 regulation of protein localization | IMP PMID:15917658 Ras and the Rho effector Cla4 collaborate to target and anch... | ACCEPT | Summary: Curation review of regulation of protein localization (GO:0032880) with IMP evidence. Reason: PMID:15917658 demonstrates RAS2 collaborates with Cdc42/Cla4 to target and anchor Lte1 at bud cortex. Supporting Evidence: PMID:15917658 Ras and the Rho effector Cla4 collaborate to target and anchor Lte1 at the bud cortex. |
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