RAS2

Existing Annotations Review

Gene Description

Existing Annotations Review

Core Functions

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.

References

Suggested Questions for Experts

Deep Research

Falcon

SGD

SGD gene description for RAS2 (yeast)

📚 Additional Documentation

Notes

Bioreason Rl Predictions

Bioreason Rl Review

Curation Analysis

Curation Summary

📄 View Raw YAML

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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000631348 · PANTHER:PTN000631348 SUPPORTS TRANSFER Current PTHR24070 IBD for Ras-family plasma-membrane localization; RAS2 descends from the node and has independent plasma-membrane localization support. 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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000631919 · PANTHER:PTN000631919 SUPPORTS TRANSFER Current opisthokont PTHR24070 IBD; the polarity term is consistent with the yeast Ras2 role in Cdc42/MAPK-dependent filamentous growth and bud-cortex localization events. Supporting Evidence: PMID:8643578 dominant negative CDC42Ala118 blocks RAS2val19 activation, placing Cdc42 downstream of Ras2. PMID:12782684 the proper localization of Lte1 to the bud cortex is dependent on active Ras
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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008393310 · PANTHER:PTN008393310 SUPPORTS TRANSFER PTHR24070 IBD node cited by the RAS2 GOA row; the inherited term matches the core Ras2 GTPase switch that drives adenylate cyclase/cAMP/PKA signaling in budding yeast and is distinct from the coexisting PTN008604616 metazoan Ras/Rap GO:0007265 IBD. 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. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000631348 · PANTHER:PTN000631348 SUPPORTS TRANSFER Current PTHR24070 IBD for conserved Ras-family GTPase activity; yeast Ras2 has direct biochemical support for guanine nucleotide binding and GTP hydrolysis. 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	ACCEPT	Summary: Electronic (ARBA) annotation to protein localization to bud neck (GO:0097271). The same term is supported for RAS2 by the IGI row from PMID:12782684, where Ras recruits the mitotic exit regulator Lte1 to the bud cortex. Reason: The claim is supported experimentally by the IGI row for the same term, which this review accepts. A duplicate electronic row for a true claim reinforces it and is not grounds for removal, so the actions are made consistent.
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 macroautophagy Supporting Evidence: PMID:15016820 The data presented here demonstrate that the Ras/PKA signaling pathway inhibits an early step in autophagy
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 Ras/PKA activity also inhibited a related process, the cytoplasm to vacuole targeting (Cvt) pathway
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 “cell 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: IMP annotation from a study of the hyperactive RAS2(val19) allele. The abstract reports that elevated Ras/PKA signalling blocks growth on galactose, partly through a defect in expression of GAL genes such as GAL1, and that the defect is suppressed by overexpressing the phosphoglucomutases PGM1 or PCM1, which the authors explain as better use of limiting glucose-1-phosphate. SGD's phenotype curation for this paper records only the RAS2-val19 activation allele (carbon-source utilization decreased on galactose), so the GO row most likely rests on that gain-of-function phenotype rather than on a ras2 loss-of-function result (SGD record consulted 2026-10-16 at https://www.yeastgenome.org/backend/reference/16292676/phenotype_details). Reason: Still unresolved after a further check, because the full text (Curr Genet 2006, paywalled, no PMC copy) could not be read. What is visible points against the annotation as worded. A hyperactive allele that lowers GAL1 expression would, if anything, place Ras signalling as an antagonist of galactose induction, not a positive contributor, and the authors' own interpretation is metabolic (glucose-1-phosphate limitation) rather than a role for Ras in the galactose transcriptional switch. But the full text may contain a ras2-null or dominant-negative result supporting a positive role, and the SGD curator read it. The row stays UNDECIDED rather than REMOVE or MODIFY until someone with the full text checks which allele and readout underlie the IMP call (see suggested_questions). Supporting Evidence: PMID:16292676 we show that a RAS2(val19) mutant that exhibits elevated levels of Ras/PKA signaling activity is unable to grow on media with galactose as the sole source of carbon. This growth defect was due, at least in part, to a defect in the expression of genes, like GAL1, that encode enzymes needed for the metabolism of galactose. PMID:16292676 these data suggest that the elevated levels of phosphoglucomutase activity allow for the more efficient utilization of the limiting levels of glucose-1-phosphate that are present in the RAS2(val19) mutant.
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.