RAS2

UniProt ID: P01120
Organism: Saccharomyces cerevisiae
Review Status: IN PROGRESS
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Gene Description

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.

Existing Annotations Review

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 **Ras–cAMP–PKA** 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.
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 β€œcell fate” 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 GDP→GTP 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.

Core Functions

RAS2 serves as the primary regulator of cAMP/PKA signaling pathway, acting as a molecular switch that cycles between GTP-bound active and GDP-bound inactive states. In the active state, RAS2-GTP binds to and activates adenylate cyclase (CYR1), increasing cellular cAMP levels. This triggers cAMP-dependent protein kinase (PKA) activation, which phosphorylates downstream targets controlling nutrient-dependent growth, glucose metabolism, stress resistance, and replicative lifespan determination.

Supporting Evidence:
  • PMID:6438624
    A product of yeast RAS2 gene is a guanine nucleotide binding protein
  • PMID:8106517
    Biochemical characterization of yeast RAS2 reveals GTPase activity and interactions with GTPase-activating proteins
  • PMID:15016820
    The Ras/cAMP-dependent protein kinase signaling pathway regulates nutrient starvation response

RAS2 functions in morphogenetic signaling through the Cdc42/MAPK pathway to regulate cell division polarity and pseudohyphal growth. Upon nutrient starvation, activated RAS2 signals through Cdc42 and the MAPK cascade (Ste20/Ste11/Ste7) to induce filamentous growth and coordinate unipolar budding pattern characteristic of pseudohyphae. This allows nutrient foraging in diploid cells.

Supporting Evidence:
  • PMID:1547504
    Unipolar cell divisions in yeast S. cerevisiae lead to filamentous growth regulated by starvation and RAS
  • PMID:8643578
    Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth

RAS2 regulates protein localization to the bud neck and cell division machinery. RAS2-GTP recruits and anchors mitotic exit regulators (including Lte1) to the bud cortex in a Cdc42-dependent manner, controlling cell polarity and ensuring proper cytokinesis.

Supporting Evidence:
  • PMID:12782684
    Ras recruits mitotic exit regulator Lte1 to the bud cortex in budding yeast
  • PMID:15917658
    Ras and the Rho effector Cla4 collaborate to target and anchor Lte1 at the bud cortex

References

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Deep Research

Falcon

(RAS2-deep-research-falcon.md)

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πŸ“š Additional Documentation

Bioreason Rl Predictions

(RAS2-bioreason-rl-predictions.md)

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Bioreason Rl Review

(RAS2-bioreason-rl-review.md)

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Curation Analysis

(RAS2-CURATION-ANALYSIS.md)

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Curation Summary

(RAS2-CURATION-SUMMARY.md)

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πŸ“„ View Raw YAML

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