Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: RIM15 is a serine/threonine protein kinase with extensive experimental validation of catalytic activity across multiple direct substrates (Igo1/2, Rph1, Hsf1, Msn2). IBA annotation based on phylogenetic inference is appropriate. Reason: Direct biochemical evidence confirms RIM15 phosphorylates Ser and Thr residues in multiple substrates. Catalytic activity is central to RIM15 mechanism of action. Supporting Evidence: PMID:24140345 Rim15 phosphorylates Hsf1 in vitro, suggesting that Rim15 might directly activate Hsf1 PMID:23273919 Rim15, analogous to the greatwall kinase in Xenopus, phosphorylates endosulfines to directly inhibit the Cdc55-protein phosphatase 2A (PP2A(Cdc55)) PMID:25660547 Rim15 mediates the phosphorylation of Rph1 upon nitrogen starvation, which causes an inhibition of its function file:yeast/RIM15/RIM15-deep-research-falcon.md Rim15 is an EC 2.7.11.1 serine/threonine-protein kinase. Direct biochemical evidence includes purified Rim15 phosphorylating substrates in vitro; a kinase-dead allele (K823Y) abrogates activity, supporting canonical ATP-dependent catalysis.
GO:0035556 intracellular signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: RIM15 integrates signals from three major nutrient-sensing kinases (TOR, PKA, Sch9) to transduce nutrient limitation signals. This is a core function central to RIM15 activation of quiescence programs. Reason: RIM15 serves as a nutrient signal integrator that receives inhibitory inputs from TOR/PKA/Sch9 and converts these into activation of G0 entry program. This is signal transduction in the strict sense - integrating multiple input signals to produce a cellular response. Supporting Evidence: PMID:14690612 Thus, Rim15 integrates signals from at least three nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control entry into G(0), a key developmental process in eukaryotic cells file:yeast/RIM15/RIM15-deep-research-falcon.md Rim15 is a central kinase in this transition, positioned downstream of major nutrient-sensing pathways including Ras/PKA and TORC1 (via Sch9), and phosphate sensing via Pho80–Pho85.
GO:0007346 regulation of mitotic cell cycle	IBA GO_REF:0000033	MODIFY	Summary: RIM15 is involved in regulation of cell cycle progression through G1/G0 transition, but phylogenetically inferred annotation may be too broad or incorrectly ancestral inferred. Reason: RIM15's role is specifically in G1 to G0 transition (quiescence entry), not general mitotic cell cycle regulation. GO:1903452 (positive regulation of G1 to G0 transition) is more specific and mechanistically accurate. The IBA annotation appears to be an over-generalization. Proposed replacements: positive regulation of G1 to G0 transition
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: RIM15 localizes to both nucleus and cytoplasm. Nuclear localization is directly demonstrated experimentally. Reason: RIM15 localizes to nucleus in response to nutrient starvation signals, which is essential for its function in activating stress response transcription factors. Supporting Evidence: PMID:14690612 Nuclear accumulation of Rim15, which is negatively regulated both by a Sit4-independent TOR effector branch and the protein kinase B (PKB/Akt) homolog Sch9 file:yeast/RIM15/RIM15-deep-research-falcon.md Upon nutrient limitation or TORC1 inhibition (e.g., rapamycin), Rim15 transiently accumulates in the nucleus, where it can activate downstream programs.
GO:0005737 cytoplasm	IBA GO_REF:0000033	ACCEPT	Summary: RIM15 localizes to cytoplasm in growing cells. Cytoplasmic sequestration is a regulatory mechanism for inactivating RIM15. Reason: RIM15 is exported to cytoplasm under favorable growth conditions (when TOR/PKA are active), which inactivates it. This is experimentally demonstrated. Supporting Evidence: PMID:16308562 Here, we show that the phosphate-sensing Pho80-Pho85 cyclin-cyclin-dependent kinase (CDK) complex also participates in Rim15 inhibition through direct phosphorylation, thereby effectively sequestering Rim15 in the cytoplasm via its association with 14-3-3 proteins file:yeast/RIM15/RIM15-deep-research-falcon.md Under glucose/nutrient-rich conditions, Rim15 is retained in the cytoplasm and inhibited. ... Pho80–Pho85 phosphorylates Rim15 at Thr1075, which promotes binding to 14-3-3 (Bmh2) and cytoplasmic retention
GO:0000160 phosphorelay signal transduction system	IEA GO_REF:0000002	REMOVE	Summary: RIM15 has a response regulatory domain (InterPro:IPR001789) detected via InterPro. However, RIM15 is not known to function as part of a classic two-component phosphorelay system in yeast. Reason: While RIM15 does contain a response regulatory domain by sequence homology, it does not participate in phosphorelay signal transduction in yeast. RIM15 is activated by inactivation of upstream kinases (TOR, PKA), not by phosphorylation as in typical phosphorelay systems. This is a false positive from InterPro domain annotation.
GO:0000166 nucleotide binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: RIM15 binds ATP as a serine/threonine kinase. This is a generic molecular function present in all kinases. Reason: While technically correct (ATP binding is required for kinase catalysis), this term is generic and uninformative for describing RIM15 function. More specific kinase activity terms (GO:0004674) are preferred.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: RIM15 is a protein kinase - this is a generic parent term to GO:0004674 (serine/threonine kinase activity). Reason: RIM15 is correctly inferred as a protein kinase via InterPro domain annotation. While GO:0004674 is more specific, this parent term is still valid and commonly annotated.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: RIM15 catalyzes phosphorylation of serine and threonine residues. Inference via InterPro and EC number is appropriate for kinase subfamily. Reason: RIM15 is confirmed to phosphorylate serine and threonine residues in multiple substrates. IEA inference via InterPro and EC:2.7.11.1 is reliable for this well-characterized kinase subfamily.
GO:0005524 ATP binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: ATP binding is a generic molecular function of all kinases. Reason: While correct, this term provides minimal functional information. Specific kinase activity terms are more informative.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: RIM15 localizes to nucleus based on UniProtKB subcellular location vocabulary mapping. Reason: Nuclear localization is directly demonstrated by multiple studies and is essential for RIM15's function in activating transcription factors. Supporting Evidence: PMID:14690612 Nuclear accumulation of Rim15, which is negatively regulated both by a Sit4-independent TOR effector branch
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: RIM15 localizes to cytoplasm based on UniProtKB subcellular location vocabulary. Reason: Dual localization to both nucleus and cytoplasm is mechanistically important for RIM15 regulation - cytoplasmic sequestration inactivates the kinase.
GO:0006950 response to stress	IEA GO_REF:0000117	ACCEPT	Summary: RIM15 is activated by various stress conditions and orchestrates stress response programs. Reason: RIM15 responds to nutrient limitation, oxidative stress, and heat stress to activate appropriate stress response genes through phosphorylation of transcription factors. Supporting Evidence: PMID:38539794 Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress Tolerance through Mediating Antioxidant Systems and Transcriptional Regulation
GO:0016301 kinase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Generic parent term for kinase activity. Reason: Correct but less specific than serine/threonine kinase activity (GO:0004674).
GO:0016740 transferase activity	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Generic parent term for all transferase activities, including kinases. Reason: Correct but extremely generic. Specific kinase terms are more informative.
GO:0051321 meiotic cell cycle	IEA GO_REF:0000043	MODIFY	Summary: RIM15 is involved in meiotic gene expression, but this is inferred from UniProtKB keyword "Meiosis" rather than direct meiotic cell cycle involvement. Reason: RIM15's role is in meiotic gene expression (stimulation of early meiotic genes via interaction with Ime1p/Ume6p), not cell cycle progression per se. GO:0045944 (positive regulation of transcription of genes involved in meiosis) would be more accurate. Proposed replacements: positive regulation of mitotic gene expression
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: RIM15 phosphorylates serine residues. Inference via Rhea mapping to EC:2.7.11.1 is appropriate. Reason: RIM15 phosphorylates both serine and threonine residues, so serine kinase activity is a subset of its activity but correctly inferred from EC number.
GO:1901992 positive regulation of mitotic cell cycle phase transition	IEA GO_REF:0000117	MODIFY	Summary: Inferred from ARBA machine learning model. RIM15 regulates G1/G0 transition, not general mitotic phase transitions. Reason: This term is misleading. RIM15 promotes G1 to G0 transition (growth arrest), not mitotic phase progression. GO:1903452 is more accurate. Proposed replacements: positive regulation of G1 to G0 transition
GO:0005515 protein binding	IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy...	REMOVE	Summary: RIM15 interacts with proteins in large-scale mass spectrometry complex identification study. Reason: Protein binding is too generic to be informative. GO:0005515 should only be used when the specific binding partner and biological consequence are documented. Without identifying which proteins RIM15 binds, this annotation conveys no functional information. Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry.
GO:0005515 protein binding	IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ...	REMOVE	Summary: RIM15 identified in chaperone interaction study. Reason: Protein binding is too generic. While RIM15 may interact with chaperones, this conveys minimal functional information without specificity. Supporting Evidence: PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell.
GO:0005515 protein binding	IPI PMID:20489023 A global protein kinase and phosphatase interaction network ...	REMOVE	Summary: RIM15 interacts with kinase/phosphatase network partners (e.g., KIN2/PHO85). Reason: Generic protein binding term without specificity. RIM15's interactions with Pho85 and other kinases/phosphatases are better captured by more specific functional annotations (substrate phosphorylation, signal transduction). Supporting Evidence: PMID:20489023 A global protein kinase and phosphatase interaction network in yeast.
GO:0034599 cellular response to oxidative stress	IMP PMID:38539794 Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative...	ACCEPT	Summary: Recent study demonstrates RIM15's role in cellular antioxidant systems and oxidative stress tolerance through transcriptional regulation. Reason: Direct experimental evidence shows RIM15 mediates response to hydrogen peroxide and oxidative stress through activation of antioxidant genes. Supporting Evidence: PMID:38539794 Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress Tolerance through Mediating Antioxidant Systems and Transcriptional Regulation
GO:0070301 cellular response to hydrogen peroxide	IMP PMID:38539794 Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative...	ACCEPT	Summary: RIM15 is required for proper cellular response to hydrogen peroxide specifically. Reason: Direct experimental evidence shows RIM15 mediates response to H2O2 as part of oxidative stress response pathway. Supporting Evidence: PMID:38539794 Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress Tolerance through Mediating Antioxidant Systems and Transcriptional Regulation
GO:0034605 cellular response to heat	IMP PMID:23861665 Budding yeast greatwall and endosulfines control activity an...	ACCEPT	Summary: RIM15 is involved in heat stress response through regulation of Hsf1 transcription factor. Reason: RIM15 phosphorylates and activates Hsf1, which is the heat shock transcription factor. This directly links RIM15 to heat stress response. Supporting Evidence: PMID:24140345 Rim15 also induces expression of Hsf1 target genes upon glucose depletion by both transcriptional activation and stabilization of the transcripts PMID:23861665 Jul 4. Budding yeast greatwall and endosulfines control activity and spatial regulation of PP2A(Cdc55) for timely mitotic progression. file:yeast/RIM15/RIM15-deep-research-falcon.md Evidence supports direct phosphorylation of Msn2 and Hsf1 by Rim15 in vitro, whereas Gis1 appears primarily regulated indirectly (via PP2A-Cdc55 inhibition through Igo1/2).
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:9111339 Stimulation of yeast meiotic gene expression by the glucose-...	ACCEPT	Summary: RIM15 stimulates transcription of meiotic genes through activation of Ime1p and interaction with Ume6p transcriptional complex. Reason: RIM15 promotes meiotic gene expression through phosphorylation and transcriptional activation pathways. Supporting Evidence: PMID:9111339 Ime1p activates early meiotic genes through its interaction with Ume6p, and analysis of Rim15p-dependent regulatory sites at the IME2 promoter indicates that activation through Ume6p is defective
GO:0051321 meiotic cell cycle	IMP PMID:9111339 Stimulation of yeast meiotic gene expression by the glucose-...	MODIFY	Summary: RIM15 was originally identified as a stimulator of meiotic gene expression, but the term conflates transcriptional activation with cell cycle progression. Reason: RIM15's role is in meiotic gene expression/transcription, not cell cycle progression per se. GO:0045959 (positive regulation of meiotic gene expression) is more mechanistically accurate. Proposed replacements: positive regulation of meiotic gene expression Supporting Evidence: PMID:9111339 Stimulation of yeast meiotic gene expression by the glucose-repressible protein kinase Rim15p. file:yeast/RIM15/RIM15-deep-research-falcon.md Igo1/2 are required for pre-meiotic autophagy, and the Rim15–Igo–PP2A-Cdc55 module regulates entry into both quiescence and gametogenesis via distinct downstream mechanisms.
GO:0004672 protein kinase activity	IDA PMID:24140345 Rim15-dependent activation of Hsf1 and Msn2/4 transcription ...	ACCEPT	Summary: Direct evidence of RIM15 protein kinase activity demonstrated through in vitro phosphorylation assays on Hsf1 and Msn2. Reason: Direct kinase activity assays demonstrate RIM15 can phosphorylate multiple substrates. IDA evidence is strong for kinase activity. Supporting Evidence: PMID:24140345 Rim15 phosphorylates Hsf1 in vitro, suggesting that Rim15 might directly activate Hsf1
GO:0004672 protein kinase activity	IDA PMID:9111339 Stimulation of yeast meiotic gene expression by the glucose-...	ACCEPT	Summary: RIM15 shows autophosphorylation activity and can phosphorylate downstream substrates. Reason: Direct biochemical evidence of protein kinase activity - autophosphorylation and substrate phosphorylation demonstrated. Supporting Evidence: PMID:9111339 Analysis of epitope-tagged derivatives indicates that Rim15p has autophosphorylation activity
GO:0004672 protein kinase activity	IDA PMID:9744870 Saccharomyces cerevisiae cAMP-dependent protein kinase contr...	ACCEPT	Summary: Direct biochemical evidence shows RIM15 has protein kinase activity and that PKA-mediated phosphorylation inhibits this activity. Reason: In vitro kinase assays confirm RIM15 phosphorylates substrates. Activity regulation by PKA demonstrates kinase activity is functionally important. Supporting Evidence: PMID:9744870 Biochemical analyses reveal that cAPK-mediated in vitro phosphorylation of Rim15p strongly inhibits its kinase activity
GO:0004674 protein serine/threonine kinase activity	IDA PMID:20471941 Initiation of the TORC1-regulated G0 program requires Igo1/2...	ACCEPT	Summary: RIM15 phosphorylates Igo1 and Igo2 endosulfines at serine/threonine residues. Reason: Direct evidence of serine/threonine kinase activity on known substrates Igo1/Igo2. Supporting Evidence: PMID:20471941 Rim15 coordinates transcription with posttranscriptional mRNA protection by phosphorylating the paralogous Igo1 and Igo2 proteins
GO:0004674 protein serine/threonine kinase activity	IMP PMID:20471941 Initiation of the TORC1-regulated G0 program requires Igo1/2...	ACCEPT	Summary: RIM15's serine/threonine kinase activity is functionally required for G0 program initiation through phosphorylation of downstream substrates. Reason: Functional evidence shows RIM15 kinase activity is essential for its biological role in quiescence entry. IMP evidence complements IDA biochemical evidence. Supporting Evidence: PMID:20471941 Initiation of the TORC1-regulated G0 program requires Igo1/2, which license specific mRNAs to evade degradation via the 5'-3' mRNA decay pathway.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:23273919 Yeast endosulfines control entry into quiescence and chronol...	ACCEPT	Summary: Direct evidence shows RIM15 phosphorylates endosulfines Igo1/Igo2. Reason: Direct biochemical evidence of serine/threonine kinase activity on characterized substrates. Multiple independent lines of IDA evidence support this annotation. Supporting Evidence: PMID:23273919 Dec 27. Yeast endosulfines control entry into quiescence and chronological life span by inhibiting protein phosphatase 2A. file:yeast/RIM15/RIM15-deep-research-falcon.md Rim15 phosphorylates Igo1 at Ser64, mapped by mass spectrometry; S64A eliminates phosphorylation.
GO:0004672 protein kinase activity	HDA PMID:16319894 Global analysis of protein phosphorylation in yeast	ACCEPT	Summary: RIM15 is phosphorylated at multiple serine/threonine residues in global phosphorylation study. Reason: HDA annotation is supported by multiple direct kinase activity assays (IDA evidence) from independent studies, confirming RIM15 is a protein kinase. Supporting Evidence: PMID:16319894 Global analysis of protein phosphorylation in yeast.
GO:0005737 cytoplasm	HDA PMID:14562095 Global analysis of protein localization in budding yeast	ACCEPT	Summary: Global protein localization study identifies RIM15 in cytoplasm. Reason: HDA evidence for localization is supported by more direct IDA evidence (PMID:14690612) that demonstrates both nuclear and cytoplasmic localization. HDA is consistent with direct evidence. Supporting Evidence: PMID:14562095 Global analysis of protein localization in budding yeast.
GO:1901992 positive regulation of mitotic cell cycle phase transition	IMP PMID:23861665 Budding yeast greatwall and endosulfines control activity an...	MODIFY	Summary: Functional evidence shows RIM15 regulates mitotic cell cycle phase transitions, specifically G1/G0 transition. Reason: RIM15's specific role is in G1 to G0 transition (quiescence, non-mitotic growth arrest), not mitotic cell cycle phase transitions. GO:1903452 is more mechanistically accurate. Proposed replacements: positive regulation of G1 to G0 transition Supporting Evidence: PMID:23861665 Jul 4. Budding yeast greatwall and endosulfines control activity and spatial regulation of PP2A(Cdc55) for timely mitotic progression.
GO:1903452 positive regulation of G1 to G0 transition	IMP PMID:20471941 Initiation of the TORC1-regulated G0 program requires Igo1/2...	ACCEPT	Summary: RIM15 is required for initiation of G0 program following nutrient limitation through direct phosphorylation of Igo1/2. Reason: This is a core function of RIM15. Direct molecular evidence shows RIM15 phosphorylates Igo1/2, which are essential for G0 program initiation. Supporting Evidence: PMID:20471941 Rim15 coordinates transcription with posttranscriptional mRNA protection by phosphorylating the paralogous Igo1 and Igo2 proteins file:yeast/RIM15/RIM15-deep-research-falcon.md A core mechanistic concept is that Rim15 acts as the yeast Greatwall kinase in a conserved module comprising Rim15 → endosulfines (Igo1/Igo2) → PP2A-B55/Cdc55. Rim15 phosphorylates Igo1/Igo2, converting them into inhibitors of PP2A-Cdc55, thereby shifting phosphorylation states of downstream effectors that control cell cycle entry/arrest and quiescence programs.
GO:1903452 positive regulation of G1 to G0 transition	IGI PMID:23273919 Yeast endosulfines control entry into quiescence and chronol...	ACCEPT	Summary: RIM15 and endosulfines (Igo1/2) function together to promote G0 entry and extend chronological lifespan. Reason: Genetic interaction evidence shows RIM15 and Igo1/2 cooperate to regulate quiescence entry. This supports the functional annotation. Supporting Evidence: PMID:23273919 The molecular elements linking Rim15 to distal readouts including the expression of Msn2/4- and Gis1-dependent genes involve the endosulfines Igo1/2
GO:1903452 positive regulation of G1 to G0 transition	IMP PMID:9744870 Saccharomyces cerevisiae cAMP-dependent protein kinase contr...	ACCEPT	Summary: RIM15 is required for proper G1 arrest in stationary phase. Deletion of RIM15 causes defects in G1 arrest. Reason: RIM15 is essential for entry into stationary phase (G0) and proper G1 growth arrest. This is a well-established primary function. Supporting Evidence: PMID:9744870 Here, we show that loss of Rim15p causes an additional pleiotropic phenotype in cells grown to stationary phase on rich medium; this phenotype includes defects in trehalose and glycogen accumulation, in transcriptional derepression of HSP12, HSP26, and SSA3, in induction of thermotolerance and starvation resistance, and in proper G1 arrest
GO:0006995 cellular response to nitrogen starvation	IMP PMID:25660547 Rph1/KDM4 mediates nutrient-limitation signaling that leads ...	ACCEPT	Summary: RIM15 is required for proper transcriptional response to nitrogen limitation through phosphorylation of Rph1. Reason: RIM15 mediates nutrient-limitation signaling in response to nitrogen starvation through Rph1 phosphorylation and autophagy induction. Supporting Evidence: PMID:25660547 Rim15 mediates the phosphorylation of Rph1 upon nitrogen starvation, which causes an inhibition of its function
GO:0006995 cellular response to nitrogen starvation	IGI PMID:25660547 Rph1/KDM4 mediates nutrient-limitation signaling that leads ...	ACCEPT	Summary: RIM15 and Rph1 function together to mediate response to nitrogen starvation and autophagy induction. Reason: Genetic interaction data show RIM15 and Rph1 cooperate in nitrogen starvation response. RIM15 phosphorylates Rph1 to relieve its repression of autophagy genes. Supporting Evidence: PMID:25660547 Preventing Rph1 phosphorylation or overexpressing the protein causes a severe block in autophagy induction
GO:0010508 positive regulation of autophagy	IMP PMID:25660547 Rph1/KDM4 mediates nutrient-limitation signaling that leads ...	ACCEPT	Summary: RIM15 promotes autophagy induction during nutrient starvation by phosphorylating Rph1, which relieves transcriptional repression of ATG genes. Reason: RIM15 phosphorylates Rph1 to inactivate its repressive function, allowing induction of autophagy genes. This is a direct mechanistic role in autophagy regulation. Supporting Evidence: PMID:25660547 Upon nutrient limitation, the inhibition of its activity is a prerequisite to the induction of ATG gene transcription and autophagy
GO:0010508 positive regulation of autophagy	IGI PMID:25660547 Rph1/KDM4 mediates nutrient-limitation signaling that leads ...	ACCEPT	Summary: RIM15 and Rph1 have antagonistic genetic interaction in autophagy regulation. Reason: Genetic interaction evidence further supports RIM15's role in autophagy induction as a downstream effector of nutrient sensing. Supporting Evidence: PMID:25660547 Preventing Rph1 phosphorylation or overexpressing the protein causes a severe block in autophagy induction
GO:0005634 nucleus	IDA PMID:14690612 TOR and PKA signaling pathways converge on the protein kinas...	ACCEPT	Summary: RIM15 localizes to the nucleus, particularly under nutrient limitation. Nuclear localization is essential for activating transcription factors. Reason: Direct experimental evidence demonstrates RIM15 nuclear accumulation as a key regulatory mechanism. This is a core aspect of RIM15 mechanism. Supporting Evidence: PMID:14690612 Nuclear accumulation of Rim15, which is negatively regulated both by a Sit4-independent TOR effector branch and the protein kinase B (PKB/Akt) homolog Sch9
GO:0005737 cytoplasm	IDA PMID:14690612 TOR and PKA signaling pathways converge on the protein kinas...	ACCEPT	Summary: RIM15 localizes to cytoplasm under nutrient-rich conditions where it is inactive. Reason: Dual localization mechanism - cytoplasmic sequestration under nutrient-rich conditions, nuclear accumulation under starvation - is essential for RIM15 regulation. Supporting Evidence: PMID:14690612 Here we demonstrate that the protein kinase Rim15 is required for entry into G(0) following inactivation of TOR and/or PKA. Induction of Rim15-dependent G(0) traits requires two discrete processes, i.e., nuclear accumulation of Rim15

Core Functions

RIM15 is a serine/threonine protein kinase that integrates signals from TOR, PKA, and Sch9 kinases to sense nutrient (glucose and nitrogen) availability. Upon nutrient limitation, RIM15 becomes active and catalyzes phosphorylation of downstream effectors (Igo1/2 endosulfines, Rph1 histone demethylase, Hsf1 and Msn2 transcription factors) to orchestrate quiescence entry and stress response programs.

Molecular Function:

protein serine/threonine kinase activity

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000116

Automatic Gene Ontology annotation based on Rhea mapping

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:11805837

Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry

PMID:14562095

Global analysis of protein localization in budding yeast

PMID:14690612

TOR and PKA signaling pathways converge on the protein kinase Rim15 to control entry into G0

PMID:16308562

Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex

PMID:16319894

Global analysis of protein phosphorylation in yeast

PMID:19536198

An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell.

PMID:20471941

Initiation of the TORC1-regulated G0 program requires Igo1/2, which license specific mRNAs to evade degradation via the 5'-3' mRNA decay pathway

PMID:20489023

A global protein kinase and phosphatase interaction network in yeast

PMID:23273919

Yeast endosulfines control entry into quiescence and chronological life span by inhibiting protein phosphatase 2A

PMID:23861665

Budding yeast greatwall and endosulfines control activity and spatial regulation of PP2A(Cdc55) for timely mitotic progression

PMID:24140345

Rim15-dependent activation of Hsf1 and Msn2/4 transcription factors by direct phosphorylation in Saccharomyces cerevisiae

PMID:25660547

Rph1/KDM4 mediates nutrient-limitation signaling that leads to the transcriptional induction of autophagy

PMID:38539794

Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress Tolerance through Mediating Antioxidant Systems and Transcriptional Regulation

PMID:9111339

Stimulation of yeast meiotic gene expression by the glucose-repressible protein kinase Rim15p

PMID:9744870

Saccharomyces cerevisiae cAMP-dependent protein kinase controls entry into stationary phase through the Rim15p protein kinase

file:yeast/RIM15/RIM15-deep-research-falcon.md

Falcon (Edison Scientific) deep research report: Functional annotation of RIM15 (UniProt P43565) in Saccharomyces cerevisiae S288c

RIM15 is the yeast Greatwall kinase: it phosphorylates the endosulfines Igo1/Igo2, converting them into inhibitors of PP2A-Cdc55/B55, thereby shifting the phosphorylation state of downstream effectors that control quiescence/G0 entry, gametogenesis, and stress programs.

"A core mechanistic concept is that Rim15 acts as the yeast Greatwall kinase in a conserved module comprising **Rim15 → endosulfines (Igo1/Igo2) → PP2A-B55/Cdc55**. Rim15 phosphorylates Igo1/Igo2, converting them into inhibitors of PP2A-Cdc55, thereby shifting phosphorylation states of downstream effectors that control cell cycle entry/arrest and quiescence programs."
The best-validated direct substrate site is Igo1 Ser64, mapped by mass spectrometry; the S64A substitution eliminates phosphorylation in vitro and Ser64 phosphorylation is required for major Rim15-dependent G0 outputs.

"Rim15 phosphorylates **Igo1 at Ser64**, mapped by mass spectrometry; **S64A** eliminates phosphorylation."
RIM15 is a ~1770-aa Ser/Thr protein kinase whose catalysis is ATP-dependent; the kinase-dead K823Y allele abrogates activity.

"Rim15 is an **EC 2.7.11.1 serine/threonine-protein kinase**. Direct biochemical evidence includes purified Rim15 phosphorylating substrates in vitro; a kinase-dead allele (**K823Y**) abrogates activity, supporting canonical ATP-dependent catalysis."
Beyond endosulfines, Rim15 directly phosphorylates the stress transcription factors Msn2 and Hsf1 in vitro, whereas Gis1 is regulated indirectly via PP2A-Cdc55 inhibition.

"Evidence supports direct phosphorylation of **Msn2** and **Hsf1** by Rim15 in vitro, whereas **Gis1** appears primarily regulated indirectly (via PP2A-Cdc55 inhibition through Igo1/2)."
Rim15 localization is nutrient-gated: cytoplasmic and inhibited in rich medium, accumulating transiently in the nucleus upon nutrient limitation or TORC1 inhibition, with nuclear export mediated by Msn5.

"Under glucose/nutrient-rich conditions, Rim15 is retained in the **cytoplasm** and inhibited. ... Upon nutrient limitation or TORC1 inhibition (e.g., rapamycin), Rim15 transiently accumulates in the **nucleus**, where it can activate downstream programs. ... Nuclear export is mediated by **Msn5**"
Rim15 activity is restrained under nutrient-rich conditions by PKA (five RRxS sites that inhibit kinase activity), TORC1-Sch9 (kinase-insert Ser1061), and Pho80-Pho85 (Thr1075 promoting 14-3-3/Bmh2 binding and cytoplasmic retention).

"PKA phosphorylates Rim15 at **five RRxS consensus sites**, strongly inhibiting Rim15 kinase activity in vitro ... Pho80–Pho85 phosphorylates Rim15 at **Thr1075**, which promotes binding to **14-3-3 (Bmh2)** and cytoplasmic retention"
The Rim15-endosulfine-PP2A axis is a fermentation brake exploited industrially: natural sake strains carry a loss-of-function 5055insA RIM15 allele giving high fermentation rates, and deleting CDC55 (PP2A-B55) abolishes the high-fermentation phenotype of Rim15-deficient strains.

"Modern sake strains carry a **loss-of-function insertion** allele (reported as **5055insA**) truncating Rim15p and linked to defective quiescence entry and **high fermentation rates**. ... deletion of **CDC55** (PP2A-B55) abolishes the"
Igo1/Igo2 (downstream of Rim15) are required for pre-meiotic autophagy, and the Rim15-Igo-PP2A-Cdc55 module governs entry into both quiescence and gametogenesis through distinct downstream mechanisms.

"Igo1/2 are required for **pre-meiotic autophagy**, and the Rim15–Igo–PP2A-Cdc55 module regulates entry into both quiescence and gametogenesis via distinct downstream mechanisms."
rim15Δ survival defects during quiescence are starvation-signal specific, being stronger under phosphorus and nitrogen starvation than under carbon starvation.

"rim15Δ reduced survival specifically under **phosphorus and nitrogen** starvation (not carbon)"

Deep Research

Falcon

(RIM15-deep-research-falcon.md)

Research Report: Functional Annotation of **RIM15** (UniProt **P43565**) in *Saccharomyces cerevisiae* S288c Falcon Edison Scientific Literature 46 citations 2 artifacts 2026-05-30T10:25:25.979861

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000045 I have extracted Table 1 and the relevant figure panels showing fermentation rates ($CO_2$ emission) and ethanol content comparison (image/png)

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.

Research Report: Functional Annotation of RIM15 (UniProt P43565) in Saccharomyces cerevisiae S288c

1) Target verification (gene/protein identity)

The literature retrieved consistently matches the UniProt target: S. cerevisiae RIM15 (also referenced as a Greatwall-family kinase in yeast; ordered locus YFL033C) encodes a large serine/threonine protein kinase that integrates nutrient signals to regulate entry into stationary phase/quiescence (G0) and associated stress programs. Multiple primary studies explicitly describe Rim15 as a Ser/Thr kinase downstream of nutrient signaling (PKA, TORC1-Sch9, Pho80–Pho85) and identify validated substrates (notably Igo1/Igo2 endosulfines). (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, cameroni2007structuralandfunctional pages 123-127, pedruzzi2003torandpka pages 1-2)

2) Key concepts and definitions (current understanding)

2.1 Rim15 as a nutrient-to-quiescence “integrator kinase”

In budding yeast, quiescence/stationary phase entry requires coordinated downshifts in growth programs and activation of stress-protective transcriptional and post-transcriptional programs. Rim15 is a central kinase in this transition, positioned downstream of major nutrient-sensing pathways including Ras/PKA and TORC1 (via Sch9), and phosphate sensing via Pho80–Pho85. (swinnen2006rim15andthe pages 2-4, pedruzzi2003torandpka pages 1-2)

2.2 Greatwall–Endosulfine–PP2A/B55 module (conserved logic)

A core mechanistic concept is that Rim15 acts as the yeast Greatwall kinase in a conserved module comprising Rim15 → endosulfines (Igo1/Igo2) → PP2A-B55/Cdc55. Rim15 phosphorylates Igo1/Igo2, converting them into inhibitors of PP2A-Cdc55, thereby shifting phosphorylation states of downstream effectors that control cell cycle entry/arrest and quiescence programs. (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, loewith2007structuralandfunctional pages 136-140)

2.3 Direct vs indirect control of transcription

Rim15 activates stress/quiescence transcriptional programs through transcription factors Msn2/Msn4 (STRE-element genes), Gis1 (PDS-element genes), and Hsf1 (heat shock/stress genes). Evidence supports direct phosphorylation of Msn2 and Hsf1 by Rim15 in vitro, whereas Gis1 appears primarily regulated indirectly (via PP2A-Cdc55 inhibition through Igo1/2). (lee2013rim15‐dependentactivationof pages 1-2, lee2013rim15‐dependentactivationof pages 4-6)

3) Protein features: domains, enzymatic activity, and substrate specificity

3.1 Domain architecture (structural concepts)

Rim15 is a large (~1770 aa) multidomain Ser/Thr kinase. Reported features include:
- N-terminal PAS domain, consistent with classification as a “PAS kinase” (domain contributes modestly to in vitro kinase activity). (2007; https://doi.org/10.13097/archive-ouverte/unige:2502) (loewith2007structuralandfunctional pages 1-6, loewith2007structuralandfunctional pages 66-70)
- Central protein kinase domain (AGC/Greatwall-like), containing a large insert between motifs VII and VIII that is a platform for regulatory phosphorylation and 14-3-3 binding. (cameroni2007structuralandfunctional pages 57-61, loewith2007structuralandfunctional pages 54-57)
- A C2HC zinc-finger-like module proposed to bind phosphoinositides in vitro and mediate localization/interaction functions. (loewith2007structuralandfunctional pages 1-6)
- A non-canonical receiver (REC) domain (lacking canonical phosphorylatable Asp), suggested to function in protein–protein interactions rather than classic phosphorelay. (loewith2007structuralandfunctional pages 86-90)

3.2 Kinase activity (reaction class)

Rim15 is an EC 2.7.11.1 serine/threonine-protein kinase. Direct biochemical evidence includes purified Rim15 phosphorylating substrates in vitro; a kinase-dead allele (K823Y) abrogates activity, supporting canonical ATP-dependent catalysis. (cameroni2007structuralandfunctional pages 123-127)

3.3 Validated direct substrates and what they imply about specificity

The best-supported direct substrates are the yeast endosulfines Igo1 and Igo2:
- Rim15 phosphorylates Igo1 at Ser64, mapped by mass spectrometry; S64A eliminates phosphorylation. (cameroni2007structuralandfunctional pages 123-127)
- Phospho-Ser64 can be detected in vivo under Rim15-activating conditions (nutrient limitation/rapamycin), and IGO1/2 deletion phenocopies rim15Δ for multiple G0 traits; Ser64 phosphorylation is necessary for Rim15-dependent outputs in those assays. (loewith2007structuralandfunctional pages 136-140)

In addition, Rim15 directly phosphorylates:
- Msn2 (in vitro), but not Gis1 in the same assays. (lee2013rim15‐dependentactivationof pages 4-6)
- Hsf1 (in vitro; Rim15 targets Hsf1 C-terminal region in truncation assays). (lee2013rim15‐dependentactivationof pages 4-6)

These results support a model where Rim15’s most definitive substrate “specificity” in vivo is functional (endosulfines/PP2A inhibition) rather than a fully mapped peptide motif; large-scale studies still describe Rim15-dependent sites as largely Ser/Thr and enriched in functional categories such as RNA metabolism and translation during quiescence entry. (sun2023parallelproteomicsand pages 13-17)

4) Regulation and localization: where Rim15 acts in the cell

4.1 Nutrient-dependent nucleo-cytoplasmic shuttling

A central feature of Rim15 regulation is localization control:
- Under glucose/nutrient-rich conditions, Rim15 is retained in the cytoplasm and inhibited. (swinnen2006rim15andthe pages 2-4)
- Upon nutrient limitation or TORC1 inhibition (e.g., rapamycin), Rim15 transiently accumulates in the nucleus, where it can activate downstream programs. (pedruzzi2003torandpka pages 4-5)
- Nuclear export is mediated by Msn5; Rim15 autophosphorylation has been proposed to facilitate export dynamics. (loewith2007structuralandfunctional pages 54-57, swinnen2006rim15andthe pages 2-4)

4.2 Upstream pathways and mapped phosphosites

PKA:
- PKA phosphorylates Rim15 at five RRxS consensus sites, strongly inhibiting Rim15 kinase activity in vitro and supporting cytoplasmic inactivity. (swinnen2006rim15andthe pages 2-4)

TORC1 → Sch9:
- TORC1 signaling via Sch9 promotes Rim15 cytoplasmic retention, including phosphorylation in the kinase insert region (e.g., Ser1061 by Sch9). (loewith2007structuralandfunctional pages 54-57, cameroni2007structuralandfunctional pages 54-57)

Pho80–Pho85 (phosphate/CDK pathway):
- Pho80–Pho85 phosphorylates Rim15 at Thr1075, which promotes binding to 14-3-3 (Bmh2) and cytoplasmic retention; Thr1075 is also implicated in export/retention cycles after nuclear entry. (loewith2007structuralandfunctional pages 54-57, swinnen2006rim15andthe pages 2-4)

Collectively, these pathways tune the nuclear availability and catalytic competence of Rim15 to couple nutrient status to quiescence entry. (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, swinnen2006rim15andthe pages 2-4)

5) Downstream pathways and biological functions (best-supported)

5.1 Quiescence/G0 entry and stress resistance programs

Rim15 is required for canonical G0 outputs upon nutrient limitation or TOR inhibition, including G1 arrest and activation of stress genes and reserve carbohydrate programs. Early work showed rim15 mutants fail to induce G0 transcriptional markers (e.g., SSA3/HSP genes) and metabolic changes after rapamycin, establishing Rim15 as a key effector downstream of TOR and PKA signaling. (pedruzzi2003torandpka pages 1-2)

5.2 Rim15 → Igo1/2 → PP2A-Cdc55 axis (core biochemical pathway)

The strongest mechanistic chain is:
1) Nutrient limitation relieves inhibition of Rim15 (PKA/TORC1/Sch9/Pho85 branches) and permits nuclear Rim15 activity. (swinnen2006rim15andthe pages 2-4, pedruzzi2003torandpka pages 4-5)
2) Rim15 phosphorylates Igo1/2 (Igo1 Ser64) (cameroni2007structuralandfunctional pages 123-127, loewith2007structuralandfunctional pages 136-140)
3) Phosphorylated endosulfines inhibit PP2A-Cdc55/B55, shifting phosphorylation states of downstream regulators that promote quiescence and (in diploids) gametogenesis; PP2A-Cdc55 otherwise inhibits entry into these programs. (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2)

5.3 Transcription factor branches: Msn2/4, Gis1, Hsf1

Msn2/4: Rim15 promotes STRE-dependent stress responses; Rim15 phosphorylates Msn2 in vitro, supporting direct activation potential. (lee2013rim15‐dependentactivationof pages 4-6)
Gis1: Gis1-dependent PDS transcription is positioned downstream of Rim15, often via PP2A-Cdc55 inhibition rather than direct phosphorylation by Rim15. (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4)
Hsf1: Rim15 phosphorylates Hsf1 in vitro and supports induction/stabilization of Hsf1-responsive transcripts during glucose depletion. (lee2013rim15‐dependentactivationof pages 1-2, lee2013rim15‐dependentactivationof pages 4-6)

5.4 Post-transcriptional control (mRNA stability/decapping)

Rim15 phosphorylates Igo1/2, which have been described to antagonize decapping and 5′→3′ decay of specific nutrient-regulated mRNAs, supporting translation and stress adaptation during nutrient limitation. (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4)

5.5 Autophagy and gametogenesis-associated survival

In the context of gametogenesis and starvation responses, Igo1/2 are required for pre-meiotic autophagy, and the Rim15–Igo–PP2A-Cdc55 module regulates entry into both quiescence and gametogenesis via distinct downstream mechanisms. (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2)

6) Recent developments (prioritizing 2023–2024)

6.1 2023 (peer-reviewed review): TORC1–Rim15/Igo–PP2A-Cdc55 connects nutrients to START via Whi5

A 2023 review of TORC1 control of the yeast cell cycle highlighted a specific mechanism: under nutrient-poor conditions, the Rim15–Igo1/2 pathway inhibits PP2A-Cdc55, preventing dephosphorylation of the G1 inhibitor Whi5, thereby facilitating SBF-driven transcription and promoting START commitment through increased Whi5 phosphorylation by Cln3–Cdk1. (Published Oct 2023; https://doi.org/10.3390/ijms242115745) (foltman2023torcomplex1 pages 8-11)

6.2 2023 (systems-level phosphoproteomics; preprint): starvation-signal-specific roles for Rim15

A 2023 SILAC-based temporal proteomics/phosphoproteomics study (bioRxiv; Aug 2023; https://doi.org/10.1101/2023.08.03.551843) provided quantitative, condition-specific Rim15 dependencies during quiescence entry:
- 298 proteins (carbon starvation) and 82 proteins (phosphorus starvation) showed genotype-dependent dynamics (adjusted p < 0.05), and ~75% of Rim15-dependent proteins increased in the rim15Δ background under carbon starvation (interpreted as a largely repressive role of Rim15 on protein expression in that context). (sun2023parallelproteomicsand pages 13-17)
- Proteome/phosphoproteome scale: 1,277 proteins quantified; 1,472 phosphorylation events quantified; and 46–49 starvation-induced phosphosites increased in WT depending on starvation condition. (sun2023parallelproteomicsand pages 17-22, sun2023parallelproteomicsand pages 35-40)
- Rim15-dependent phosphorylation included the known site IGO1 Ser64, and additional common Rim15-regulated phosphosites were reported across starvation contexts (enriched in RNA metabolism/translation). (sun2023parallelproteomicsand pages 13-17)
- Phenotypically, rim15Δ reduced survival specifically under phosphorus and nitrogen starvation (not carbon), reinforcing that Rim15’s contribution to “quiescence viability” is starvation-signal dependent. (sun2023parallelproteomicsand pages 1-5)

Although not all 2024 yeast papers in the retrieved set focus directly on budding yeast Rim15, the broader Greatwall-Endosulfine-PP2A/B55 axis continues to be refined in other yeast systems, reinforcing the interpretation of Rim15 as an evolutionarily conserved “kinase-to-phosphatase switch” (review/primary synthesis context). (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2)

7) Current applications and real-world implementations

7.1 Industrial fermentation: natural and engineered RIM15 loss-of-function increases fermentation rate

Sake yeast strains provide a practical demonstration of Rim15’s role as a fermentation brake:
- Modern sake strains carry a loss-of-function insertion allele (reported as 5055insA) truncating Rim15p and linked to defective quiescence entry and high fermentation rates. (Published Jun 2012; https://doi.org/10.1128/AEM.00165-12) (watanabe2012alossoffunctionmutation pages 1-2)
- In laboratory strain backgrounds, rim15 mutants display higher peak CO2 emission rates and higher ethanol output after extended fermentation.
- Example quantitative results: peak CO2 emission increased from 180.8 ± 11.5 ml/6 h (WT BY4743) to 235.3 ± 18.1 ml/6 h (BY4743 rim15); in another assay, 90.8 ± 2.5 ml/6 h to 142.7 ± 2.8 ml/6 h; ethanol reached 17.03% ± 0.44% v/v after 20 days for BY4743 rim15. (watanabe2012alossoffunctionmutation pages 5-7)
- Figures and Table evidence for these fermentation phenotypes and complementation are shown in the extracted panels (watanabe2012alossoffunctionmutation media 0df2d675, watanabe2012alossoffunctionmutation media 8dbf4238, watanabe2012alossoffunctionmutation media 4c77db42).

7.2 Mechanistic strain design: TORC1–Greatwall(Rim15)–PP2A-B55/Cdc55 pathway as an engineering handle

A 2019 applied microbiology study connected fermentation-rate control mechanistically to a nutrient-signaling pathway:
- Disruption of RIM15 increases fermentation rates across non-sake strains, and deletion of CDC55 (PP2A-B55) abolishes the “high fermentation” phenotype of Rim15-deficient strains, supporting that PP2A-B55 mediates TORC1–Rim15 control of fermentation. (Published Jan 2019; https://doi.org/10.1128/AEM.02083-18) (watanabe2019nutrientsignalingvia pages 1-2)
- The authors explicitly frame these results as a rational basis for designing/breeding industrial yeasts with optimized fermentation performance, while noting potential fitness trade-offs. (watanabe2019nutrientsignalingvia pages 1-2)

7.3 Trade-offs: fermentation speed vs stress tolerance/quiescence robustness

Restoring functional ScRIM15 in a sake background improved stress-related brewing traits (e.g., reduced cell death in high-ethanol mash) while modestly decreasing fermentation performance, illustrating a common industrial trade-off between rapid fermentation and robustness/survival programs governed by Rim15. (watanabe2012alossoffunctionmutation pages 8-9)

8) Expert opinions and analysis (authoritative synthesis)

8.1 Rim15 as a “crossroads” node of nutrient signaling

A widely cited review described Rim15 as a focal integrator of at least four nutrient-responsive pathways, emphasizing that Rim15 integrates kinase signaling through phosphorylation-dependent localization and activity control to coordinate entry into stationary phase. (Published Apr 2006; https://doi.org/10.1186/1747-1028-1-3) (swinnen2006rim15andthe pages 2-4)

8.2 Rim15 in lifespan/quiescence frameworks

Review literature on TORC1-Sch9-longevity places Rim15 in the canonical downstream effector layer for quiescence/stress resistance programs, emphasizing the Rim15→Igo→PP2A-Cdc55→Gis1 logic and highlighting that multiple mechanistic links remain an active area (e.g., details of Rim15–Msn2/4 regulation). (Published Feb 2014; https://doi.org/10.1111/1567-1364.12097) (swinnen2014molecularmechanismslinking pages 4-5)

9) Key statistics and data points (recent and classic)

9.1 Validated phosphorylation target with residue-level mapping

Igo1 Ser64 is a validated Rim15 phosphorylation site mapped by mass spectrometry; S64A abolishes phosphorylation in vitro (and Ser64 phosphorylation is required for major Rim15-dependent G0 outputs in follow-up studies). (cameroni2007structuralandfunctional pages 123-127, loewith2007structuralandfunctional pages 136-140)

9.2 Quantitative industrial phenotypes (2012)

Increased peak CO2 emission rates in rim15 mutants (examples: 180.8 ± 11.5 → 235.3 ± 18.1 ml/6 h; 90.8 ± 2.5 → 142.7 ± 2.8 ml/6 h) and ethanol reaching 17.03% ± 0.44% v/v after 20 days in one rim15 mutant condition. (watanabe2012alossoffunctionmutation pages 5-7)
Visual evidence for fermentation kinetics and complementation is provided in extracted figure/table panels. (watanabe2012alossoffunctionmutation media 0df2d675, watanabe2012alossoffunctionmutation media 8dbf4238, watanabe2012alossoffunctionmutation media 4c77db42)

9.3 Quantitative omics (2023; preprint)

1,277 proteins quantified and 1,472 phosphorylation events quantified during quiescence entry; Rim15-dependent dynamics observed for 298 (carbon) and 82 (phosphorus) proteins; ~75% of Rim15-dependent proteins increased in rim15Δ under carbon starvation. (sun2023parallelproteomicsand pages 13-17, sun2023parallelproteomicsand pages 17-22)
Rim15-dependent common phosphorylation events include IGO1 Ser64 and other sites spanning RNA/translation/proteostasis-related factors. (sun2023parallelproteomicsand pages 13-17)

10) Consolidated functional annotation summary

The table below consolidates (i) domains and enzymatic evidence, (ii) upstream regulatory logic and localization, (iii) validated direct substrates, (iv) downstream pathways and applications, and (v) DOI-linked sources.

Module/Process	Upstream regulators	Mechanism (phosphosites/localization)	Direct Rim15 substrates/targets	Downstream outcomes	Key evidence (brief)	Primary citations with year+DOI URL
Nutrient-sensing hub controlling G0/quiescence entry	PKA; TORC1→Sch9; Pho80–Pho85	PKA phosphorylates Rim15 at five RRxS sites and inhibits kinase activity; TORC1/Sch9 and Pho80–Pho85 promote cytoplasmic retention via kinase-insert phosphosites including S1061 and T1075; T1075 promotes Bmh2/14-3-3 binding; nutrient limitation/rapamycin/phosphate withdrawal trigger nuclear accumulation; export requires Msn5 (loewith2007structuralandfunctional pages 54-57, swinnen2006rim15andthe pages 2-4, cameroni2007structuralandfunctional pages 54-57, swinnen2014molecularmechanismslinking pages 4-5, pedruzzi2003torandpka pages 4-5)	Rim15 itself is regulated rather than acting as substrate in this row	Entry into G0/stationary phase, G1 arrest, activation of starvation-responsive transcriptional program (swinnen2006rim15andthe pages 2-4, pedruzzi2003torandpka pages 1-2)	Genetics and localization assays showed rim15 mutants fail to mount rapamycin-induced G0 responses; phosphatase-sensitive mobility shifts and GFP localization linked TOR/Sch9 to Rim15 phosphorylation and nuclear exclusion (pedruzzi2003torandpka pages 4-5, pedruzzi2003torandpka pages 1-2)	Pedruzzi et al. 2003, https://doi.org/10.1016/S1097-2765(03)00485-4; Swinnen et al. 2006, https://doi.org/10.1186/1747-1028-1-3
Rim15 structural/enzymatic annotation	Nutrient pathways modulate activity but not basic domain architecture	Large 1770-aa AGC/Greatwall-like Ser/Thr kinase with N-terminal PAS domain, central kinase domain with large insert between motifs VII–VIII, C2HC zinc-finger-like region, and non-canonical REC domain; autophosphorylates; catalytic Lys823 required for activity (cameroni2007structuralandfunctional pages 57-61, loewith2007structuralandfunctional pages 86-90, loewith2007structuralandfunctional pages 1-6, cameroni2007structuralandfunctional pages 123-127)	Igo1/Igo2 are validated direct phospho-targets; broader consensus remains incompletely defined (cameroni2007structuralandfunctional pages 123-127)	Provides biochemical basis for central signaling role and regulated substrate phosphorylation during nutrient limitation	Purified wild-type but not kinase-dead Rim15 phosphorylated substrates on protein arrays/in vitro; domain analyses support multidomain signaling/scaffolding functions (cameroni2007structuralandfunctional pages 57-61, cameroni2007structuralandfunctional pages 123-127)	Cameroni/Loewith 2007 thesis/archive, https://doi.org/10.13097/archive-ouverte/unige:2502
Greatwall–Endosulfine–PP2A-Cdc55 module	Relief of PKA, TORC1-Sch9, and Pho80–Pho85 inhibition activates Rim15	Upon activation/nuclear function, Rim15 phosphorylates endosulfines Igo1/Igo2; Igo1 Ser64 is validated; phospho-Igo1/2 inhibit PP2A-Cdc55/B55 (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, cameroni2007structuralandfunctional pages 123-127, loewith2007structuralandfunctional pages 136-140)	Igo1 Ser64; Igo2 corresponding conserved site (cameroni2007structuralandfunctional pages 123-127, sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, loewith2007structuralandfunctional pages 136-140)	PP2A-Cdc55 inhibition; preservation of phosphorylated targets such as Gis1/Sic1-related outputs; promotion of quiescence and gametogenesis; contribution to mRNA protection (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, swinnen2014molecularmechanismslinking pages 3-4, deprez2018thetorc1sch9pathway pages 5-6)	Protein microarray + in vitro kinase assays + MS mapped Igo1 Ser64; phospho-Ser64 antibodies and mutational analysis showed Ser64 is necessary for Rim15-dependent G0 traits; genetic studies linked Rim15-Igo1/2 to PP2A-Cdc55 inhibition (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, cameroni2007structuralandfunctional pages 123-127, loewith2007structuralandfunctional pages 136-140)	Sarkar et al. 2014, https://doi.org/10.1371/journal.pgen.1004456; Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004
Stress-responsive transcription via Msn2/4	Upstream inhibition by PKA and TORC1-Sch9 is relieved during starvation	Rim15 enters nucleus and stimulates Msn2/Msn4-dependent STRE genes; Msn2 is directly phosphorylated by Rim15 in vitro, while the precise mechanism for Msn4 remains less direct/fully resolved (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4, deprez2018thetorc1sch9pathway pages 5-6)	Msn2 direct in vitro substrate; Msn4 functional downstream effector (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4)	Environmental stress response, antioxidant defense genes, reserve carbohydrate accumulation, quiescence-associated survival (swinnen2014molecularmechanismslinking pages 4-5, swinnen2014molecularmechanismslinking pages 3-4, deprez2018thetorc1sch9pathway pages 5-6)	In vitro kinase assays demonstrated Rim15→Msn2 phosphorylation; classic genetics placed Msn2/4 downstream of Rim15 in G0/stress programs (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4)	Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004; Pedruzzi et al. 2003, https://doi.org/10.1016/S1097-2765(03)00485-4
Heat-shock/stress transcription via Hsf1	Rim15 activated when PKA/TORC1 repression is relieved by glucose depletion/starvation	Rim15 directly phosphorylates Hsf1 in vitro; supports induction and stabilization of some Hsf1 target transcripts during glucose depletion (lee2013rim15‐dependentactivationof pages 1-2, lee2013rim15‐dependentactivationof pages 4-6)	Hsf1 (direct in vitro substrate) (lee2013rim15‐dependentactivationof pages 1-2, lee2013rim15‐dependentactivationof pages 4-6)	Heat-shock/stress gene expression, including HSP26-linked responses, contributing to stress resistance (lee2013rim15‐dependentactivationof pages 1-2, deprez2018thetorc1sch9pathway pages 5-6)	Purified Rim15 phosphorylated Hsf1 fragments in vitro; transcript assays showed Rim15-dependent induction/stabilization of Hsf1 targets under glucose depletion (lee2013rim15‐dependentactivationof pages 1-2, lee2013rim15‐dependentactivationof pages 4-6)	Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004
Gis1/PDS transcriptional branch	Activated indirectly downstream of Rim15 and antagonism of PP2A-Cdc55	Rim15 does not directly phosphorylate Gis1 detectably in vitro; instead phospho-Igo1/2 inhibit PP2A-Cdc55, helping maintain Gis1 in an active phosphorylated state and/or promoter recruitment (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4, cameroni2007structuralandfunctional pages 123-127)	No strong evidence for direct Rim15→Gis1 phosphorylation; indirect regulation via Igo1/2–PP2A-Cdc55 (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4)	Post-diauxic shift (PDS) gene expression, stationary-phase transcriptional remodeling, oxidative/stress adaptation (swinnen2014molecularmechanismslinking pages 4-5, swinnen2014molecularmechanismslinking pages 3-4)	Genetic epistasis supports Gis1 downstream of Rim15; biochemical work supports the indirect Igo1/2→PP2A-Cdc55 route rather than direct phosphorylation (lee2013rim15‐dependentactivationof pages 1-2, cameroni2007structuralandfunctional pages 123-127)	Swinnen et al. 2014, https://doi.org/10.1111/1567-1364.12097; Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004
mRNA stability / decapping control	Rim15 activation under nutrient limitation	Rim15-phosphorylated Igo1/2 antagonize 5′→3′ mRNA decay, in part via association with decapping factor Dhh1; this is downstream of Rim15 kinase action on Igo proteins (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4, deprez2018thetorc1sch9pathway pages 5-6)	Igo1/Igo2 are direct Rim15 substrates mediating this branch (lee2013rim15‐dependentactivationof pages 1-2, loewith2007structuralandfunctional pages 136-140)	Stabilization/translation of nutrient-regulated mRNAs during starvation/quiescence entry (lee2013rim15‐dependentactivationof pages 1-2, swinnen2014molecularmechanismslinking pages 3-4, deprez2018thetorc1sch9pathway pages 5-6)	Review synthesis and primary data indicate phospho-Igo proteins protect mRNAs from decapping-dependent degradation; IGO1/2 deletion reduces induction of Rim15-responsive genes such as BTN2/HSP26 (lee2013rim15‐dependentactivationof pages 1-2, lee2013rim15‐dependentactivationof pages 4-6)	Lee et al. 2013, https://doi.org/10.1016/j.febslet.2013.10.004; Swinnen et al. 2014, https://doi.org/10.1111/1567-1364.12097
Autophagy/gametogenesis-linked survival program	Nutrient starvation activates Rim15 module	Rim15 phosphorylates Igo1/Igo2 to oppose PP2A-Cdc55; Igo1/2 are required for pre-meiotic autophagy, though autophagy defect alone does not fully explain sporulation defect (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2)	Igo1/Igo2 (direct); downstream autophagy effectors not fully resolved here (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2)	Entry into gametogenesis and starvation survival; quiescence and sporulation via distinct downstream mechanisms (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2)	Genetic deletion of IGO1/2 impaired pre-meiotic autophagy and sporulation; authors concluded the Rim15-Endosulfine-PP2A-Cdc55 module governs quiescence and gametogenesis through distinct mechanisms (sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2)	Sarkar et al. 2014, https://doi.org/10.1371/journal.pgen.1004456
Quiescence phosphoproteome and recent 2023 systems-level updates	Starvation signal context (carbon vs phosphorus vs nitrogen) intersects with Rim15 dependence	Temporal SILAC proteomics/phosphoproteomics in WT vs rim15Δ during starvation identified 1,277 proteins and 1,472 phosphorylation events; 11 common phosphorylation targets increased in WT vs rim15Δ; IGO1 S64 detected before starvation as Rim15-dependent (sun2023parallelproteomicsand pages 13-17, sun2023parallelproteomicsand pages 35-40, sun2023parallelproteomicsand pages 17-22, sun2023parallelproteomicsand pages 25-29)	Confirmed/implicated: IGO1 S64 plus candidate broader targets enriched in RNA metabolism, translation, proteostasis, glycogen metabolism (sun2023parallelproteomicsand pages 13-17, sun2023parallelproteomicsand pages 17-22)	Rim15 contributes to quiescence survival especially under phosphorus and nitrogen starvation; regulates mitochondrial/proteostasis and RNA/translation functions (sun2023parallelproteomicsand pages 13-17, sun2023parallelproteomicsand pages 1-5)	Quantitative study found 298 proteins (carbon) and 82 proteins (phosphorus) with genotype-dependent dynamics; survival defects were stronger in phosphorus/nitrogen starvation than carbon starvation (sun2023parallelproteomicsand pages 13-17, sun2023parallelproteomicsand pages 1-5)	Sun et al. 2023 preprint, https://doi.org/10.1101/2023.08.03.551843
Fermentation control / industrial implementation	TORC1–Rim15–PP2A-B55 axis; natural/engineered RIM15 loss-of-function	Natural sake-yeast frameshift rim15^5055insA truncates Rim15; RIM15 loss increases fermentation rate, while restoring functional RIM15 improves stress tolerance and some brewing traits; CDC55/PP2A-B55 mediates much of the effect downstream (watanabe2012alossoffunctionmutation pages 3-5, watanabe2019nutrientsignalingvia pages 1-2, watanabe2012alossoffunctionmutation pages 5-7)	Rim15 pathway outputs involve Igo1/2 and PP2A-B55/Cdc55; direct fermentation substrate not defined (watanabe2019nutrientsignalingvia pages 1-2, watanabe2012alossoffunctionmutation pages 5-7)	Faster alcoholic fermentation, higher early CO2 evolution and ethanol production, but trade-offs in quiescence entry/stress tolerance/cell survival (watanabe2012alossoffunctionmutation pages 3-5, watanabe2012alossoffunctionmutation pages 8-9, watanabe2012alossoffunctionmutation pages 5-7)	In laboratory strains, rim15 mutants showed higher peak CO2 emission (e.g., 180.8 ± 11.5 vs 235.3 ± 18.1 ml/6 h) and higher ethanol after 20 days (17.03% ± 0.44% v/v); restoring ScRIM15 in K701 improved stress tolerance and reduced cell death in high-ethanol mash (watanabe2012alossoffunctionmutation pages 8-9, watanabe2012alossoffunctionmutation pages 5-7, watanabe2012alossoffunctionmutation media 0df2d675)	Watanabe et al. 2012, https://doi.org/10.1128/AEM.00165-12; Watanabe et al. 2019, https://doi.org/10.1128/AEM.02083-18

Table: This table summarizes validated functional annotation for Saccharomyces cerevisiae Rim15 (UniProt P43565), including upstream regulation, localization and phosphosite mechanisms, direct substrates, downstream biological roles, and key primary literature supporting each module.

11) Practical functional annotation (concise “database-style” statement)

Rim15 (P43565) is a nutrient-regulated Ser/Thr protein kinase that functions as a yeast Greatwall kinase to promote entry into quiescence/stationary phase by (1) translocating to the nucleus upon nutrient limitation and (2) phosphorylating Igo1/Igo2 endosulfines (Igo1 Ser64) to inhibit PP2A-Cdc55/B55, thereby sustaining phosphorylation-dependent states of downstream regulators controlling stress transcription, mRNA stability, and cell-cycle/quiescence decisions. Rim15 also directly phosphorylates stress regulators Msn2 and Hsf1 in vitro and supports starvation-induced stress gene programs. Rim15 activity is restrained under nutrient-rich conditions by PKA, TORC1→Sch9, and Pho80–Pho85 through phosphoregulation that enforces cytoplasmic retention (including Thr1075 and Ser1061) and inhibits catalytic activity. (loewith2007structuralandfunctional pages 54-57, sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, lee2013rim15‐dependentactivationof pages 4-6)

12) Notes on evidence quality and recency

Core Rim15 mechanisms (Igo1 Ser64 phosphorylation; upstream nutrient control; PP2A-Cdc55 inhibition) are supported by robust primary literature from 2003–2014 and remain foundational. (pedruzzi2003torandpka pages 1-2, sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2, loewith2007structuralandfunctional pages 136-140)
2023–2024 updates are mostly (i) synthesis/reviews placing Rim15 into cell-cycle control logic and (ii) omics-scale studies refining starvation-signal-specific dependencies; some of the newest quantitative phosphoproteomics evidence is currently available as a preprint and should be interpreted accordingly. (foltman2023torcomplex1 pages 8-11, sun2023parallelproteomicsand pages 13-17)

References

(sarkar2014therim15endosulfinepp2acdc55signalling pages 1-2): Sourav Sarkar, Jacob Z. Dalgaard, Jonathan B. A. Millar, and Prakash Arumugam. The rim15-endosulfine-pp2acdc55 signalling module regulates entry into gametogenesis and quiescence via distinct mechanisms in budding yeast. PLoS Genetics, 10:e1004456, Jun 2014. URL: https://doi.org/10.1371/journal.pgen.1004456, doi:10.1371/journal.pgen.1004456. This article has 61 citations and is from a domain leading peer-reviewed journal.
(cameroni2007structuralandfunctional pages 123-127): Structural and functional characterization of the novel yeast PAS kinase Rim 15, a central regulator of the G0 program in yeast
(pedruzzi2003torandpka pages 1-2): Ivo Pedruzzi, Frédérique Dubouloz, Elisabetta Cameroni, Valeria Wanke, Johnny Roosen, Joris Winderickx, and Claudio De Virgilio. Tor and pka signaling pathways converge on the protein kinase rim15 to control entry into g0. Molecular cell, 12 6:1607-13, Dec 2003. URL: https://doi.org/10.1016/s1097-2765(03)00485-4, doi:10.1016/s1097-2765(03)00485-4. This article has 406 citations and is from a highest quality peer-reviewed journal.
(swinnen2006rim15andthe pages 2-4): Erwin Swinnen, Valeria Wanke, Johnny Roosen, Bart Smets, Frédérique Dubouloz, Ivo Pedruzzi, Elisabetta Cameroni, Claudio De Virgilio, and Joris Winderickx. Rim15 and the crossroads of nutrient signalling pathways in saccharomyces cerevisiae. Cell Division, 1:3-3, Apr 2006. URL: https://doi.org/10.1186/1747-1028-1-3, doi:10.1186/1747-1028-1-3. This article has 197 citations and is from a peer-reviewed journal.
(loewith2007structuralandfunctional pages 136-140): R Loewith. Structural and functional characterization of the novel yeast pas kinase rim15, a central regulator of the g0 program in yeast. Unknown journal, 2007.
(lee2013rim15‐dependentactivationof pages 1-2): Peter Lee, Myunghye Kim, S. Paik, Seung-Hwan Choi, Boram Cho, and J. Hahn. Rim15‐dependent activation of hsf1 and msn2/4 transcription factors by direct phosphorylation in saccharomyces cerevisiae. FEBS Letters, Nov 2013. URL: https://doi.org/10.1016/j.febslet.2013.10.004, doi:10.1016/j.febslet.2013.10.004. This article has 109 citations and is from a peer-reviewed journal.
(lee2013rim15‐dependentactivationof pages 4-6): Peter Lee, Myunghye Kim, S. Paik, Seung-Hwan Choi, Boram Cho, and J. Hahn. Rim15‐dependent activation of hsf1 and msn2/4 transcription factors by direct phosphorylation in saccharomyces cerevisiae. FEBS Letters, Nov 2013. URL: https://doi.org/10.1016/j.febslet.2013.10.004, doi:10.1016/j.febslet.2013.10.004. This article has 109 citations and is from a peer-reviewed journal.
(loewith2007structuralandfunctional pages 1-6): R Loewith. Structural and functional characterization of the novel yeast pas kinase rim15, a central regulator of the g0 program in yeast. Unknown journal, 2007.
(loewith2007structuralandfunctional pages 66-70): R Loewith. Structural and functional characterization of the novel yeast pas kinase rim15, a central regulator of the g0 program in yeast. Unknown journal, 2007.
(cameroni2007structuralandfunctional pages 57-61): Structural and functional characterization of the novel yeast PAS kinase Rim 15, a central regulator of the G0 program in yeast
(loewith2007structuralandfunctional pages 54-57): R Loewith. Structural and functional characterization of the novel yeast pas kinase rim15, a central regulator of the g0 program in yeast. Unknown journal, 2007.
(loewith2007structuralandfunctional pages 86-90): R Loewith. Structural and functional characterization of the novel yeast pas kinase rim15, a central regulator of the g0 program in yeast. Unknown journal, 2007.
(sun2023parallelproteomicsand pages 13-17): Siyu Sun, Daniel Tranchina, and David Gresham. Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.03.551843, doi:10.1101/2023.08.03.551843. This article has 1 citations.
(pedruzzi2003torandpka pages 4-5): Ivo Pedruzzi, Frédérique Dubouloz, Elisabetta Cameroni, Valeria Wanke, Johnny Roosen, Joris Winderickx, and Claudio De Virgilio. Tor and pka signaling pathways converge on the protein kinase rim15 to control entry into g0. Molecular cell, 12 6:1607-13, Dec 2003. URL: https://doi.org/10.1016/s1097-2765(03)00485-4, doi:10.1016/s1097-2765(03)00485-4. This article has 406 citations and is from a highest quality peer-reviewed journal.
(cameroni2007structuralandfunctional pages 54-57): Structural and functional characterization of the novel yeast PAS kinase Rim 15, a central regulator of the G0 program in yeast
(swinnen2014molecularmechanismslinking pages 3-4): Erwin Swinnen, Ruben Ghillebert, Tobias Wilms, and Joris Winderickx. Molecular mechanisms linking the evolutionary conserved torc1-sch9 nutrient signalling branch to lifespan regulation in saccharomyces cerevisiae. FEMS yeast research, 14 1:17-32, Feb 2014. URL: https://doi.org/10.1111/1567-1364.12097, doi:10.1111/1567-1364.12097. This article has 99 citations and is from a peer-reviewed journal.
(foltman2023torcomplex1 pages 8-11): Magdalena Foltman and Alberto Sanchez-Diaz. Tor complex 1: orchestrating nutrient signaling and cell cycle progression. International Journal of Molecular Sciences, 24:15745, Oct 2023. URL: https://doi.org/10.3390/ijms242115745, doi:10.3390/ijms242115745. This article has 18 citations.
(sun2023parallelproteomicsand pages 17-22): Siyu Sun, Daniel Tranchina, and David Gresham. Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.03.551843, doi:10.1101/2023.08.03.551843. This article has 1 citations.
(sun2023parallelproteomicsand pages 35-40): Siyu Sun, Daniel Tranchina, and David Gresham. Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.03.551843, doi:10.1101/2023.08.03.551843. This article has 1 citations.
(sun2023parallelproteomicsand pages 1-5): Siyu Sun, Daniel Tranchina, and David Gresham. Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.03.551843, doi:10.1101/2023.08.03.551843. This article has 1 citations.
(watanabe2012alossoffunctionmutation pages 1-2): Daisuke Watanabe, Yuya Araki, Yan Zhou, Naoki Maeya, Takeshi Akao, and Hitoshi Shimoi. A loss-of-function mutation in the pas kinase rim15p is related to defective quiescence entry and high fermentation rates of saccharomyces cerevisiae sake yeast strains. Applied and Environmental Microbiology, 78:4008-4016, Jun 2012. URL: https://doi.org/10.1128/aem.00165-12, doi:10.1128/aem.00165-12. This article has 121 citations and is from a peer-reviewed journal.
(watanabe2012alossoffunctionmutation pages 5-7): Daisuke Watanabe, Yuya Araki, Yan Zhou, Naoki Maeya, Takeshi Akao, and Hitoshi Shimoi. A loss-of-function mutation in the pas kinase rim15p is related to defective quiescence entry and high fermentation rates of saccharomyces cerevisiae sake yeast strains. Applied and Environmental Microbiology, 78:4008-4016, Jun 2012. URL: https://doi.org/10.1128/aem.00165-12, doi:10.1128/aem.00165-12. This article has 121 citations and is from a peer-reviewed journal.
(watanabe2012alossoffunctionmutation media 0df2d675): Daisuke Watanabe, Yuya Araki, Yan Zhou, Naoki Maeya, Takeshi Akao, and Hitoshi Shimoi. A loss-of-function mutation in the pas kinase rim15p is related to defective quiescence entry and high fermentation rates of saccharomyces cerevisiae sake yeast strains. Applied and Environmental Microbiology, 78:4008-4016, Jun 2012. URL: https://doi.org/10.1128/aem.00165-12, doi:10.1128/aem.00165-12. This article has 121 citations and is from a peer-reviewed journal.
(watanabe2012alossoffunctionmutation media 8dbf4238): Daisuke Watanabe, Yuya Araki, Yan Zhou, Naoki Maeya, Takeshi Akao, and Hitoshi Shimoi. A loss-of-function mutation in the pas kinase rim15p is related to defective quiescence entry and high fermentation rates of saccharomyces cerevisiae sake yeast strains. Applied and Environmental Microbiology, 78:4008-4016, Jun 2012. URL: https://doi.org/10.1128/aem.00165-12, doi:10.1128/aem.00165-12. This article has 121 citations and is from a peer-reviewed journal.
(watanabe2012alossoffunctionmutation media 4c77db42): Daisuke Watanabe, Yuya Araki, Yan Zhou, Naoki Maeya, Takeshi Akao, and Hitoshi Shimoi. A loss-of-function mutation in the pas kinase rim15p is related to defective quiescence entry and high fermentation rates of saccharomyces cerevisiae sake yeast strains. Applied and Environmental Microbiology, 78:4008-4016, Jun 2012. URL: https://doi.org/10.1128/aem.00165-12, doi:10.1128/aem.00165-12. This article has 121 citations and is from a peer-reviewed journal.
(watanabe2019nutrientsignalingvia pages 1-2): Daisuke Watanabe, Takuma Kajihara, Yukiko Sugimoto, Kenichi Takagi, Megumi Mizuno, Yan Zhou, Jiawen Chen, Kojiro Takeda, Hisashi Tatebe, Kazuhiro Shiozaki, Nobushige Nakazawa, Shingo Izawa, Takeshi Akao, Hitoshi Shimoi, Tatsuya Maeda, and Hiroshi Takagi. Nutrient signaling via the torc1-greatwall-pp2a ^b55δ pathway is responsible for the high initial rates of alcoholic fermentation in sake yeast strains of saccharomyces cerevisiae. Applied and Environmental Microbiology, Jan 2019. URL: https://doi.org/10.1128/aem.02083-18, doi:10.1128/aem.02083-18. This article has 35 citations and is from a peer-reviewed journal.
(watanabe2012alossoffunctionmutation pages 8-9): Daisuke Watanabe, Yuya Araki, Yan Zhou, Naoki Maeya, Takeshi Akao, and Hitoshi Shimoi. A loss-of-function mutation in the pas kinase rim15p is related to defective quiescence entry and high fermentation rates of saccharomyces cerevisiae sake yeast strains. Applied and Environmental Microbiology, 78:4008-4016, Jun 2012. URL: https://doi.org/10.1128/aem.00165-12, doi:10.1128/aem.00165-12. This article has 121 citations and is from a peer-reviewed journal.
(swinnen2014molecularmechanismslinking pages 4-5): Erwin Swinnen, Ruben Ghillebert, Tobias Wilms, and Joris Winderickx. Molecular mechanisms linking the evolutionary conserved torc1-sch9 nutrient signalling branch to lifespan regulation in saccharomyces cerevisiae. FEMS yeast research, 14 1:17-32, Feb 2014. URL: https://doi.org/10.1111/1567-1364.12097, doi:10.1111/1567-1364.12097. This article has 99 citations and is from a peer-reviewed journal.
(deprez2018thetorc1sch9pathway pages 5-6): Marie-Anne Deprez, Elja Eskes, Joris Winderickx, and Tobias Wilms. The torc1-sch9 pathway as a crucial mediator of chronological lifespan in the yeast saccharomyces cerevisiae. FEMS yeast research, Aug 2018. URL: https://doi.org/10.1093/femsyr/foy048, doi:10.1093/femsyr/foy048. This article has 79 citations and is from a peer-reviewed journal.
(sun2023parallelproteomicsand pages 25-29): Siyu Sun, Daniel Tranchina, and David Gresham. Parallel proteomics and phosphoproteomics defines starvation signal specific processes in cell quiescence. bioRxiv, Aug 2023. URL: https://doi.org/10.1101/2023.08.03.551843, doi:10.1101/2023.08.03.551843. This article has 1 citations.
(watanabe2012alossoffunctionmutation pages 3-5): Daisuke Watanabe, Yuya Araki, Yan Zhou, Naoki Maeya, Takeshi Akao, and Hitoshi Shimoi. A loss-of-function mutation in the pas kinase rim15p is related to defective quiescence entry and high fermentation rates of saccharomyces cerevisiae sake yeast strains. Applied and Environmental Microbiology, 78:4008-4016, Jun 2012. URL: https://doi.org/10.1128/aem.00165-12, doi:10.1128/aem.00165-12. This article has 121 citations and is from a peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

loewith2007structuralandfunctional pages 1-6
loewith2007structuralandfunctional pages 86-90
cameroni2007structuralandfunctional pages 123-127
loewith2007structuralandfunctional pages 136-140
sun2023parallelproteomicsand pages 13-17
pedruzzi2003torandpka pages 4-5
pedruzzi2003torandpka pages 1-2
sun2023parallelproteomicsand pages 1-5
watanabe2012alossoffunctionmutation pages 1-2
watanabe2012alossoffunctionmutation pages 5-7
watanabe2019nutrientsignalingvia pages 1-2
watanabe2012alossoffunctionmutation pages 8-9
swinnen2014molecularmechanismslinking pages 4-5
loewith2007structuralandfunctional pages 66-70
cameroni2007structuralandfunctional pages 57-61
loewith2007structuralandfunctional pages 54-57
cameroni2007structuralandfunctional pages 54-57
swinnen2014molecularmechanismslinking pages 3-4
sun2023parallelproteomicsand pages 17-22
sun2023parallelproteomicsand pages 35-40
sun2023parallelproteomicsand pages 25-29
watanabe2012alossoffunctionmutation pages 3-5
https://doi.org/10.13097/archive-ouverte/unige:2502
https://doi.org/10.3390/ijms242115745
https://doi.org/10.1101/2023.08.03.551843
https://doi.org/10.1128/AEM.00165-12
https://doi.org/10.1128/AEM.02083-18
https://doi.org/10.1186/1747-1028-1-3
https://doi.org/10.1111/1567-1364.12097
https://doi.org/10.1016/S1097-2765(03
https://doi.org/10.1371/journal.pgen.1004456;
https://doi.org/10.1016/j.febslet.2013.10.004
https://doi.org/10.1016/j.febslet.2013.10.004;
https://doi.org/10.1111/1567-1364.12097;
https://doi.org/10.1371/journal.pgen.1004456
https://doi.org/10.1128/AEM.00165-12;
https://doi.org/10.1371/journal.pgen.1004456,
https://doi.org/10.1016/s1097-2765(03
https://doi.org/10.1186/1747-1028-1-3,
https://doi.org/10.1016/j.febslet.2013.10.004,
https://doi.org/10.1101/2023.08.03.551843,
https://doi.org/10.1111/1567-1364.12097,
https://doi.org/10.3390/ijms242115745,
https://doi.org/10.1128/aem.00165-12,
https://doi.org/10.1128/aem.02083-18,
https://doi.org/10.1093/femsyr/foy048,

📄 View Raw YAML

id: P43565
gene_symbol: RIM15
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: RIM15 encodes a serine/threonine protein kinase that integrates 
  nutrient signals (TOR, PKA, Sch9) to orchestrate entry into quiescence (G0 
  arrest). RIM15 directly phosphorylates key substrates including Igo1/2 
  (endosulfines), Rph1 (histone demethylase), and transcription factors Hsf1, 
  Msn2 to regulate stress response genes, autophagy induction, and chronological
  lifespan. Also promotes meiotic gene expression in response to glucose 
  depletion.
existing_annotations:
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: RIM15 is a serine/threonine protein kinase with extensive 
        experimental validation of catalytic activity across multiple direct 
        substrates (Igo1/2, Rph1, Hsf1, Msn2). IBA annotation based on 
        phylogenetic inference is appropriate.
      action: ACCEPT
      reason: Direct biochemical evidence confirms RIM15 phosphorylates Ser and 
        Thr residues in multiple substrates. Catalytic activity is central to 
        RIM15 mechanism of action.
      supported_by:
        - reference_id: PMID:24140345
          supporting_text: Rim15 phosphorylates Hsf1 in vitro, suggesting that 
            Rim15 might directly activate Hsf1
        - reference_id: PMID:23273919
          supporting_text: Rim15, analogous to the greatwall kinase in Xenopus, 
            phosphorylates endosulfines to directly inhibit the Cdc55-protein 
            phosphatase 2A (PP2A(Cdc55))
        - reference_id: PMID:25660547
          supporting_text: Rim15 mediates the phosphorylation of Rph1 upon
            nitrogen starvation, which causes an inhibition of its function
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            Rim15 is an **EC 2.7.11.1 serine/threonine-protein kinase**. Direct
            biochemical evidence includes purified Rim15 phosphorylating
            substrates in vitro; a kinase-dead allele (**K823Y**) abrogates
            activity, supporting canonical ATP-dependent catalysis.
  - term:
      id: GO:0035556
      label: intracellular signal transduction
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: RIM15 integrates signals from three major nutrient-sensing 
        kinases (TOR, PKA, Sch9) to transduce nutrient limitation signals. This 
        is a core function central to RIM15 activation of quiescence programs.
      action: ACCEPT
      reason: RIM15 serves as a nutrient signal integrator that receives 
        inhibitory inputs from TOR/PKA/Sch9 and converts these into activation 
        of G0 entry program. This is signal transduction in the strict sense - 
        integrating multiple input signals to produce a cellular response.
      supported_by:
        - reference_id: PMID:14690612
          supporting_text: Thus, Rim15 integrates signals from at least three
            nutrient-sensory kinases (TOR, PKA, and Sch9) to properly control
            entry into G(0), a key developmental process in eukaryotic cells
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            Rim15 is a central kinase in this transition, positioned downstream
            of major nutrient-sensing pathways including Ras/PKA and TORC1 (via
            Sch9), and phosphate sensing via Pho80–Pho85.
  - term:
      id: GO:0007346
      label: regulation of mitotic cell cycle
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: RIM15 is involved in regulation of cell cycle progression through
        G1/G0 transition, but phylogenetically inferred annotation may be too 
        broad or incorrectly ancestral inferred.
      action: MODIFY
      reason: RIM15's role is specifically in G1 to G0 transition (quiescence 
        entry), not general mitotic cell cycle regulation. GO:1903452 (positive 
        regulation of G1 to G0 transition) is more specific and mechanistically 
        accurate. The IBA annotation appears to be an over-generalization.
      proposed_replacement_terms:
        - id: GO:1903452
          label: positive regulation of G1 to G0 transition
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: RIM15 localizes to both nucleus and cytoplasm. Nuclear 
        localization is directly demonstrated experimentally.
      action: ACCEPT
      reason: RIM15 localizes to nucleus in response to nutrient starvation 
        signals, which is essential for its function in activating stress 
        response transcription factors.
      supported_by:
        - reference_id: PMID:14690612
          supporting_text: Nuclear accumulation of Rim15, which is negatively
            regulated both by a Sit4-independent TOR effector branch and the
            protein kinase B (PKB/Akt) homolog Sch9
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            Upon nutrient limitation or TORC1 inhibition (e.g., rapamycin),
            Rim15 transiently accumulates in the **nucleus**, where it can
            activate downstream programs.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: RIM15 localizes to cytoplasm in growing cells. Cytoplasmic 
        sequestration is a regulatory mechanism for inactivating RIM15.
      action: ACCEPT
      reason: RIM15 is exported to cytoplasm under favorable growth conditions 
        (when TOR/PKA are active), which inactivates it. This is experimentally 
        demonstrated.
      supported_by:
        - reference_id: PMID:16308562
          supporting_text: Here, we show that the phosphate-sensing Pho80-Pho85
            cyclin-cyclin-dependent kinase (CDK) complex also participates in
            Rim15 inhibition through direct phosphorylation, thereby effectively
            sequestering Rim15 in the cytoplasm via its association with 14-3-3
            proteins
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            Under glucose/nutrient-rich conditions, Rim15 is retained in the
            **cytoplasm** and inhibited.
            ...
            Pho80–Pho85 phosphorylates Rim15 at **Thr1075**, which promotes
            binding to **14-3-3 (Bmh2)** and cytoplasmic retention
  - term:
      id: GO:0000160
      label: phosphorelay signal transduction system
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: RIM15 has a response regulatory domain (InterPro:IPR001789) 
        detected via InterPro. However, RIM15 is not known to function as part 
        of a classic two-component phosphorelay system in yeast.
      action: REMOVE
      reason: While RIM15 does contain a response regulatory domain by sequence 
        homology, it does not participate in phosphorelay signal transduction in
        yeast. RIM15 is activated by inactivation of upstream kinases (TOR, 
        PKA), not by phosphorylation as in typical phosphorelay systems. This is
        a false positive from InterPro domain annotation.
  - term:
      id: GO:0000166
      label: nucleotide binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: RIM15 binds ATP as a serine/threonine kinase. This is a generic 
        molecular function present in all kinases.
      action: KEEP_AS_NON_CORE
      reason: While technically correct (ATP binding is required for kinase 
        catalysis), this term is generic and uninformative for describing RIM15 
        function. More specific kinase activity terms (GO:0004674) are 
        preferred.
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: RIM15 is a protein kinase - this is a generic parent term to 
        GO:0004674 (serine/threonine kinase activity).
      action: ACCEPT
      reason: RIM15 is correctly inferred as a protein kinase via InterPro 
        domain annotation. While GO:0004674 is more specific, this parent term 
        is still valid and commonly annotated.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: RIM15 catalyzes phosphorylation of serine and threonine residues.
        Inference via InterPro and EC number is appropriate for kinase 
        subfamily.
      action: ACCEPT
      reason: RIM15 is confirmed to phosphorylate serine and threonine residues 
        in multiple substrates. IEA inference via InterPro and EC:2.7.11.1 is 
        reliable for this well-characterized kinase subfamily.
  - term:
      id: GO:0005524
      label: ATP binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: ATP binding is a generic molecular function of all kinases.
      action: KEEP_AS_NON_CORE
      reason: While correct, this term provides minimal functional information. 
        Specific kinase activity terms are more informative.
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: RIM15 localizes to nucleus based on UniProtKB subcellular 
        location vocabulary mapping.
      action: ACCEPT
      reason: Nuclear localization is directly demonstrated by multiple studies 
        and is essential for RIM15's function in activating transcription 
        factors.
      supported_by:
        - reference_id: PMID:14690612
          supporting_text: Nuclear accumulation of Rim15, which is negatively 
            regulated both by a Sit4-independent TOR effector branch
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: RIM15 localizes to cytoplasm based on UniProtKB subcellular 
        location vocabulary.
      action: ACCEPT
      reason: Dual localization to both nucleus and cytoplasm is mechanistically
        important for RIM15 regulation - cytoplasmic sequestration inactivates 
        the kinase.
  - term:
      id: GO:0006950
      label: response to stress
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: RIM15 is activated by various stress conditions and orchestrates 
        stress response programs.
      action: ACCEPT
      reason: RIM15 responds to nutrient limitation, oxidative stress, and heat 
        stress to activate appropriate stress response genes through 
        phosphorylation of transcription factors.
      supported_by:
        - reference_id: PMID:38539794
          supporting_text: Novel Roles of the Greatwall Kinase Rim15 in Yeast 
            Oxidative Stress Tolerance through Mediating Antioxidant Systems and
            Transcriptional Regulation
  - term:
      id: GO:0016301
      label: kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Generic parent term for kinase activity.
      action: KEEP_AS_NON_CORE
      reason: Correct but less specific than serine/threonine kinase activity 
        (GO:0004674).
  - term:
      id: GO:0016740
      label: transferase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Generic parent term for all transferase activities, including 
        kinases.
      action: KEEP_AS_NON_CORE
      reason: Correct but extremely generic. Specific kinase terms are more 
        informative.
  - term:
      id: GO:0051321
      label: meiotic cell cycle
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: RIM15 is involved in meiotic gene expression, but this is 
        inferred from UniProtKB keyword "Meiosis" rather than direct meiotic 
        cell cycle involvement.
      action: MODIFY
      reason: RIM15's role is in meiotic gene expression (stimulation of early 
        meiotic genes via interaction with Ime1p/Ume6p), not cell cycle 
        progression per se. GO:0045944 (positive regulation of transcription of 
        genes involved in meiosis) would be more accurate.
      proposed_replacement_terms:
        - id: GO:0045959
          label: positive regulation of mitotic gene expression
  - term:
      id: GO:0106310
      label: protein serine kinase activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000116
    review:
      summary: RIM15 phosphorylates serine residues. Inference via Rhea mapping 
        to EC:2.7.11.1 is appropriate.
      action: ACCEPT
      reason: RIM15 phosphorylates both serine and threonine residues, so serine
        kinase activity is a subset of its activity but correctly inferred from 
        EC number.
  - term:
      id: GO:1901992
      label: positive regulation of mitotic cell cycle phase transition
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: Inferred from ARBA machine learning model. RIM15 regulates G1/G0 
        transition, not general mitotic phase transitions.
      action: MODIFY
      reason: This term is misleading. RIM15 promotes G1 to G0 transition 
        (growth arrest), not mitotic phase progression. GO:1903452 is more 
        accurate.
      proposed_replacement_terms:
        - id: GO:1903452
          label: positive regulation of G1 to G0 transition
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11805837
    review:
      summary: RIM15 interacts with proteins in large-scale mass spectrometry 
        complex identification study.
      action: REMOVE
      reason: Protein binding is too generic to be informative. GO:0005515 
        should only be used when the specific binding partner and biological 
        consequence are documented. Without identifying which proteins RIM15 
        binds, this annotation conveys no functional information.
      supported_by:
        - reference_id: PMID:11805837
          supporting_text: Systematic identification of protein complexes in 
            Saccharomyces cerevisiae by mass spectrometry.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19536198
    review:
      summary: RIM15 identified in chaperone interaction study.
      action: REMOVE
      reason: Protein binding is too generic. While RIM15 may interact with 
        chaperones, this conveys minimal functional information without 
        specificity.
      supported_by:
        - reference_id: PMID:19536198
          supporting_text: 'An atlas of chaperone-protein interactions in Saccharomyces
            cerevisiae: implications to protein folding pathways in the cell.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20489023
    review:
      summary: RIM15 interacts with kinase/phosphatase network partners (e.g., 
        KIN2/PHO85).
      action: REMOVE
      reason: Generic protein binding term without specificity. RIM15's 
        interactions with Pho85 and other kinases/phosphatases are better 
        captured by more specific functional annotations (substrate 
        phosphorylation, signal transduction).
      supported_by:
        - reference_id: PMID:20489023
          supporting_text: A global protein kinase and phosphatase interaction 
            network in yeast.
  - term:
      id: GO:0034599
      label: cellular response to oxidative stress
    evidence_type: IMP
    original_reference_id: PMID:38539794
    review:
      summary: Recent study demonstrates RIM15's role in cellular antioxidant 
        systems and oxidative stress tolerance through transcriptional 
        regulation.
      action: ACCEPT
      reason: Direct experimental evidence shows RIM15 mediates response to 
        hydrogen peroxide and oxidative stress through activation of antioxidant
        genes.
      supported_by:
        - reference_id: PMID:38539794
          supporting_text: Novel Roles of the Greatwall Kinase Rim15 in Yeast 
            Oxidative Stress Tolerance through Mediating Antioxidant Systems and
            Transcriptional Regulation
  - term:
      id: GO:0070301
      label: cellular response to hydrogen peroxide
    evidence_type: IMP
    original_reference_id: PMID:38539794
    review:
      summary: RIM15 is required for proper cellular response to hydrogen 
        peroxide specifically.
      action: ACCEPT
      reason: Direct experimental evidence shows RIM15 mediates response to H2O2
        as part of oxidative stress response pathway.
      supported_by:
        - reference_id: PMID:38539794
          supporting_text: Novel Roles of the Greatwall Kinase Rim15 in Yeast 
            Oxidative Stress Tolerance through Mediating Antioxidant Systems and
            Transcriptional Regulation
  - term:
      id: GO:0034605
      label: cellular response to heat
    evidence_type: IMP
    original_reference_id: PMID:23861665
    review:
      summary: RIM15 is involved in heat stress response through regulation of 
        Hsf1 transcription factor.
      action: ACCEPT
      reason: RIM15 phosphorylates and activates Hsf1, which is the heat shock 
        transcription factor. This directly links RIM15 to heat stress response.
      supported_by:
        - reference_id: PMID:24140345
          supporting_text: Rim15 also induces expression of Hsf1 target genes 
            upon glucose depletion by both transcriptional activation and 
            stabilization of the transcripts
        - reference_id: PMID:23861665
          supporting_text: Jul 4. Budding yeast greatwall and endosulfines
            control activity and spatial regulation of PP2A(Cdc55) for timely
            mitotic progression.
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            Evidence supports direct phosphorylation of **Msn2** and **Hsf1** by
            Rim15 in vitro, whereas **Gis1** appears primarily regulated
            indirectly (via PP2A-Cdc55 inhibition through Igo1/2).
  - term:
      id: GO:0045944
      label: positive regulation of transcription by RNA polymerase II
    evidence_type: IMP
    original_reference_id: PMID:9111339
    review:
      summary: RIM15 stimulates transcription of meiotic genes through 
        activation of Ime1p and interaction with Ume6p transcriptional complex.
      action: ACCEPT
      reason: RIM15 promotes meiotic gene expression through phosphorylation and
        transcriptional activation pathways.
      supported_by:
        - reference_id: PMID:9111339
          supporting_text: Ime1p activates early meiotic genes through its 
            interaction with Ume6p, and analysis of Rim15p-dependent regulatory 
            sites at the IME2 promoter indicates that activation through Ume6p 
            is defective
  - term:
      id: GO:0051321
      label: meiotic cell cycle
    evidence_type: IMP
    original_reference_id: PMID:9111339
    review:
      summary: RIM15 was originally identified as a stimulator of meiotic gene 
        expression, but the term conflates transcriptional activation with cell 
        cycle progression.
      action: MODIFY
      reason: RIM15's role is in meiotic gene expression/transcription, not cell
        cycle progression per se. GO:0045959 (positive regulation of meiotic 
        gene expression) is more mechanistically accurate.
      proposed_replacement_terms:
        - id: GO:0045959
          label: positive regulation of meiotic gene expression
      supported_by:
        - reference_id: PMID:9111339
          supporting_text: Stimulation of yeast meiotic gene expression by the
            glucose-repressible protein kinase Rim15p.
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            Igo1/2 are required for **pre-meiotic autophagy**, and the
            Rim15–Igo–PP2A-Cdc55 module regulates entry into both quiescence and
            gametogenesis via distinct downstream mechanisms.
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IDA
    original_reference_id: PMID:24140345
    review:
      summary: Direct evidence of RIM15 protein kinase activity demonstrated 
        through in vitro phosphorylation assays on Hsf1 and Msn2.
      action: ACCEPT
      reason: Direct kinase activity assays demonstrate RIM15 can phosphorylate 
        multiple substrates. IDA evidence is strong for kinase activity.
      supported_by:
        - reference_id: PMID:24140345
          supporting_text: Rim15 phosphorylates Hsf1 in vitro, suggesting that 
            Rim15 might directly activate Hsf1
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IDA
    original_reference_id: PMID:9111339
    review:
      summary: RIM15 shows autophosphorylation activity and can phosphorylate 
        downstream substrates.
      action: ACCEPT
      reason: Direct biochemical evidence of protein kinase activity - 
        autophosphorylation and substrate phosphorylation demonstrated.
      supported_by:
        - reference_id: PMID:9111339
          supporting_text: Analysis of epitope-tagged derivatives indicates that
            Rim15p has autophosphorylation activity
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: IDA
    original_reference_id: PMID:9744870
    review:
      summary: Direct biochemical evidence shows RIM15 has protein kinase 
        activity and that PKA-mediated phosphorylation inhibits this activity.
      action: ACCEPT
      reason: In vitro kinase assays confirm RIM15 phosphorylates substrates. 
        Activity regulation by PKA demonstrates kinase activity is functionally 
        important.
      supported_by:
        - reference_id: PMID:9744870
          supporting_text: Biochemical analyses reveal that cAPK-mediated in 
            vitro phosphorylation of Rim15p strongly inhibits its kinase 
            activity
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:20471941
    review:
      summary: RIM15 phosphorylates Igo1 and Igo2 endosulfines at 
        serine/threonine residues.
      action: ACCEPT
      reason: Direct evidence of serine/threonine kinase activity on known 
        substrates Igo1/Igo2.
      supported_by:
        - reference_id: PMID:20471941
          supporting_text: Rim15 coordinates transcription with 
            posttranscriptional mRNA protection by phosphorylating the 
            paralogous Igo1 and Igo2 proteins
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IMP
    original_reference_id: PMID:20471941
    review:
      summary: RIM15's serine/threonine kinase activity is functionally required
        for G0 program initiation through phosphorylation of downstream 
        substrates.
      action: ACCEPT
      reason: Functional evidence shows RIM15 kinase activity is essential for 
        its biological role in quiescence entry. IMP evidence complements IDA 
        biochemical evidence.
      supported_by:
        - reference_id: PMID:20471941
          supporting_text: Initiation of the TORC1-regulated G0 program requires
            Igo1/2, which license specific mRNAs to evade degradation via the 
            5'-3' mRNA decay pathway.
  - term:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    evidence_type: IDA
    original_reference_id: PMID:23273919
    review:
      summary: Direct evidence shows RIM15 phosphorylates endosulfines 
        Igo1/Igo2.
      action: ACCEPT
      reason: Direct biochemical evidence of serine/threonine kinase activity on
        characterized substrates. Multiple independent lines of IDA evidence 
        support this annotation.
      supported_by:
        - reference_id: PMID:23273919
          supporting_text: Dec 27. Yeast endosulfines control entry into
            quiescence and chronological life span by inhibiting protein
            phosphatase 2A.
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            Rim15 phosphorylates **Igo1 at Ser64**, mapped by mass spectrometry;
            **S64A** eliminates phosphorylation.
  - term:
      id: GO:0004672
      label: protein kinase activity
    evidence_type: HDA
    original_reference_id: PMID:16319894
    review:
      summary: RIM15 is phosphorylated at multiple serine/threonine residues in 
        global phosphorylation study.
      action: ACCEPT
      reason: HDA annotation is supported by multiple direct kinase activity 
        assays (IDA evidence) from independent studies, confirming RIM15 is a 
        protein kinase.
      supported_by:
        - reference_id: PMID:16319894
          supporting_text: Global analysis of protein phosphorylation in yeast.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: HDA
    original_reference_id: PMID:14562095
    review:
      summary: Global protein localization study identifies RIM15 in cytoplasm.
      action: ACCEPT
      reason: HDA evidence for localization is supported by more direct IDA 
        evidence (PMID:14690612) that demonstrates both nuclear and cytoplasmic 
        localization. HDA is consistent with direct evidence.
      supported_by:
        - reference_id: PMID:14562095
          supporting_text: Global analysis of protein localization in budding 
            yeast.
  - term:
      id: GO:1901992
      label: positive regulation of mitotic cell cycle phase transition
    evidence_type: IMP
    original_reference_id: PMID:23861665
    review:
      summary: Functional evidence shows RIM15 regulates mitotic cell cycle 
        phase transitions, specifically G1/G0 transition.
      action: MODIFY
      reason: RIM15's specific role is in G1 to G0 transition (quiescence, 
        non-mitotic growth arrest), not mitotic cell cycle phase transitions. 
        GO:1903452 is more mechanistically accurate.
      proposed_replacement_terms:
        - id: GO:1903452
          label: positive regulation of G1 to G0 transition
      supported_by:
        - reference_id: PMID:23861665
          supporting_text: Jul 4. Budding yeast greatwall and endosulfines 
            control activity and spatial regulation of PP2A(Cdc55) for timely 
            mitotic progression.
  - term:
      id: GO:1903452
      label: positive regulation of G1 to G0 transition
    evidence_type: IMP
    original_reference_id: PMID:20471941
    review:
      summary: RIM15 is required for initiation of G0 program following nutrient
        limitation through direct phosphorylation of Igo1/2.
      action: ACCEPT
      reason: This is a core function of RIM15. Direct molecular evidence shows 
        RIM15 phosphorylates Igo1/2, which are essential for G0 program 
        initiation.
      supported_by:
        - reference_id: PMID:20471941
          supporting_text: Rim15 coordinates transcription with
            posttranscriptional mRNA protection by phosphorylating the
            paralogous Igo1 and Igo2 proteins
        - reference_id: file:yeast/RIM15/RIM15-deep-research-falcon.md
          supporting_text: |-
            A core mechanistic concept is that Rim15 acts as the yeast Greatwall
            kinase in a conserved module comprising **Rim15 → endosulfines
            (Igo1/Igo2) → PP2A-B55/Cdc55**. Rim15 phosphorylates Igo1/Igo2,
            converting them into inhibitors of PP2A-Cdc55, thereby shifting
            phosphorylation states of downstream effectors that control cell
            cycle entry/arrest and quiescence programs.
  - term:
      id: GO:1903452
      label: positive regulation of G1 to G0 transition
    evidence_type: IGI
    original_reference_id: PMID:23273919
    review:
      summary: RIM15 and endosulfines (Igo1/2) function together to promote G0 
        entry and extend chronological lifespan.
      action: ACCEPT
      reason: Genetic interaction evidence shows RIM15 and Igo1/2 cooperate to 
        regulate quiescence entry. This supports the functional annotation.
      supported_by:
        - reference_id: PMID:23273919
          supporting_text: The molecular elements linking Rim15 to distal 
            readouts including the expression of Msn2/4- and Gis1-dependent 
            genes involve the endosulfines Igo1/2
  - term:
      id: GO:1903452
      label: positive regulation of G1 to G0 transition
    evidence_type: IMP
    original_reference_id: PMID:9744870
    review:
      summary: RIM15 is required for proper G1 arrest in stationary phase. 
        Deletion of RIM15 causes defects in G1 arrest.
      action: ACCEPT
      reason: RIM15 is essential for entry into stationary phase (G0) and proper
        G1 growth arrest. This is a well-established primary function.
      supported_by:
        - reference_id: PMID:9744870
          supporting_text: Here, we show that loss of Rim15p causes an 
            additional pleiotropic phenotype in cells grown to stationary phase 
            on rich medium; this phenotype includes defects in trehalose and 
            glycogen accumulation, in transcriptional derepression of HSP12, 
            HSP26, and SSA3, in induction of thermotolerance and starvation 
            resistance, and in proper G1 arrest
  - term:
      id: GO:0006995
      label: cellular response to nitrogen starvation
    evidence_type: IMP
    original_reference_id: PMID:25660547
    review:
      summary: RIM15 is required for proper transcriptional response to nitrogen
        limitation through phosphorylation of Rph1.
      action: ACCEPT
      reason: RIM15 mediates nutrient-limitation signaling in response to 
        nitrogen starvation through Rph1 phosphorylation and autophagy 
        induction.
      supported_by:
        - reference_id: PMID:25660547
          supporting_text: Rim15 mediates the phosphorylation of Rph1 upon 
            nitrogen starvation, which causes an inhibition of its function
  - term:
      id: GO:0006995
      label: cellular response to nitrogen starvation
    evidence_type: IGI
    original_reference_id: PMID:25660547
    review:
      summary: RIM15 and Rph1 function together to mediate response to nitrogen 
        starvation and autophagy induction.
      action: ACCEPT
      reason: Genetic interaction data show RIM15 and Rph1 cooperate in nitrogen
        starvation response. RIM15 phosphorylates Rph1 to relieve its repression
        of autophagy genes.
      supported_by:
        - reference_id: PMID:25660547
          supporting_text: Preventing Rph1 phosphorylation or overexpressing the
            protein causes a severe block in autophagy induction
  - term:
      id: GO:0010508
      label: positive regulation of autophagy
    evidence_type: IMP
    original_reference_id: PMID:25660547
    review:
      summary: RIM15 promotes autophagy induction during nutrient starvation by 
        phosphorylating Rph1, which relieves transcriptional repression of ATG 
        genes.
      action: ACCEPT
      reason: RIM15 phosphorylates Rph1 to inactivate its repressive function, 
        allowing induction of autophagy genes. This is a direct mechanistic role
        in autophagy regulation.
      supported_by:
        - reference_id: PMID:25660547
          supporting_text: Upon nutrient limitation, the inhibition of its 
            activity is a prerequisite to the induction of ATG gene 
            transcription and autophagy
  - term:
      id: GO:0010508
      label: positive regulation of autophagy
    evidence_type: IGI
    original_reference_id: PMID:25660547
    review:
      summary: RIM15 and Rph1 have antagonistic genetic interaction in autophagy
        regulation.
      action: ACCEPT
      reason: Genetic interaction evidence further supports RIM15's role in 
        autophagy induction as a downstream effector of nutrient sensing.
      supported_by:
        - reference_id: PMID:25660547
          supporting_text: Preventing Rph1 phosphorylation or overexpressing the
            protein causes a severe block in autophagy induction
  - term:
      id: GO:0005634
      label: nucleus
    evidence_type: IDA
    original_reference_id: PMID:14690612
    review:
      summary: RIM15 localizes to the nucleus, particularly under nutrient 
        limitation. Nuclear localization is essential for activating 
        transcription factors.
      action: ACCEPT
      reason: Direct experimental evidence demonstrates RIM15 nuclear 
        accumulation as a key regulatory mechanism. This is a core aspect of 
        RIM15 mechanism.
      supported_by:
        - reference_id: PMID:14690612
          supporting_text: Nuclear accumulation of Rim15, which is negatively 
            regulated both by a Sit4-independent TOR effector branch and the 
            protein kinase B (PKB/Akt) homolog Sch9
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:14690612
    review:
      summary: RIM15 localizes to cytoplasm under nutrient-rich conditions where
        it is inactive.
      action: ACCEPT
      reason: Dual localization mechanism - cytoplasmic sequestration under 
        nutrient-rich conditions, nuclear accumulation under starvation - is 
        essential for RIM15 regulation.
      supported_by:
        - reference_id: PMID:14690612
          supporting_text: Here we demonstrate that the protein kinase Rim15 is 
            required for entry into G(0) following inactivation of TOR and/or 
            PKA. Induction of Rim15-dependent G(0) traits requires two discrete 
            processes, i.e., nuclear accumulation of Rim15
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular 
      Location vocabulary mapping, accompanied by conservative changes to GO 
      terms applied by UniProt
    findings: []
  - id: GO_REF:0000116
    title: Automatic Gene Ontology annotation based on Rhea mapping
    findings: []
  - id: GO_REF:0000117
    title: Electronic Gene Ontology annotations created by ARBA machine learning
      models
    findings: []
  - id: GO_REF:0000120
    title: Combined Automated Annotation using Multiple IEA Methods
    findings: []
  - id: PMID:11805837
    title: Systematic identification of protein complexes in Saccharomyces 
      cerevisiae by mass spectrometry
    findings: []
  - id: PMID:14562095
    title: Global analysis of protein localization in budding yeast
    findings: []
  - id: PMID:14690612
    title: TOR and PKA signaling pathways converge on the protein kinase Rim15 
      to control entry into G0
    findings: []
  - id: PMID:16308562
    title: Regulation of G0 entry by the Pho80-Pho85 cyclin-CDK complex
    findings: []
  - id: PMID:16319894
    title: Global analysis of protein phosphorylation in yeast
    findings: []
  - id: PMID:19536198
    title: "An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell."
    findings: []
  - id: PMID:20471941
    title: Initiation of the TORC1-regulated G0 program requires Igo1/2, which 
      license specific mRNAs to evade degradation via the 5'-3' mRNA decay 
      pathway
    findings: []
  - id: PMID:20489023
    title: A global protein kinase and phosphatase interaction network in yeast
    findings: []
  - id: PMID:23273919
    title: Yeast endosulfines control entry into quiescence and chronological 
      life span by inhibiting protein phosphatase 2A
    findings: []
  - id: PMID:23861665
    title: Budding yeast greatwall and endosulfines control activity and spatial
      regulation of PP2A(Cdc55) for timely mitotic progression
    findings: []
  - id: PMID:24140345
    title: Rim15-dependent activation of Hsf1 and Msn2/4 transcription factors 
      by direct phosphorylation in Saccharomyces cerevisiae
    findings: []
  - id: PMID:25660547
    title: Rph1/KDM4 mediates nutrient-limitation signaling that leads to the 
      transcriptional induction of autophagy
    findings: []
  - id: PMID:38539794
    title: Novel Roles of the Greatwall Kinase Rim15 in Yeast Oxidative Stress 
      Tolerance through Mediating Antioxidant Systems and Transcriptional 
      Regulation
    findings: []
  - id: PMID:9111339
    title: Stimulation of yeast meiotic gene expression by the 
      glucose-repressible protein kinase Rim15p
    findings: []
  - id: PMID:9744870
    title: Saccharomyces cerevisiae cAMP-dependent protein kinase controls entry
      into stationary phase through the Rim15p protein kinase
    findings: []
  - id: file:yeast/RIM15/RIM15-deep-research-falcon.md
    title: |-
      Falcon (Edison Scientific) deep research report: Functional annotation of
      RIM15 (UniProt P43565) in Saccharomyces cerevisiae S288c
    findings:
      - statement: |-
          RIM15 is the yeast Greatwall kinase: it phosphorylates the endosulfines
          Igo1/Igo2, converting them into inhibitors of PP2A-Cdc55/B55, thereby
          shifting the phosphorylation state of downstream effectors that control
          quiescence/G0 entry, gametogenesis, and stress programs.
        supporting_text: |-
          A core mechanistic concept is that Rim15 acts as the yeast Greatwall
          kinase in a conserved module comprising **Rim15 → endosulfines
          (Igo1/Igo2) → PP2A-B55/Cdc55**. Rim15 phosphorylates Igo1/Igo2,
          converting them into inhibitors of PP2A-Cdc55, thereby shifting
          phosphorylation states of downstream effectors that control cell cycle
          entry/arrest and quiescence programs.
        reference_section_type: OTHER
      - statement: |-
          The best-validated direct substrate site is Igo1 Ser64, mapped by mass
          spectrometry; the S64A substitution eliminates phosphorylation in vitro
          and Ser64 phosphorylation is required for major Rim15-dependent G0
          outputs.
        supporting_text: |-
          Rim15 phosphorylates **Igo1 at Ser64**, mapped by mass spectrometry;
          **S64A** eliminates phosphorylation.
        reference_section_type: OTHER
      - statement: |-
          RIM15 is a ~1770-aa Ser/Thr protein kinase whose catalysis is
          ATP-dependent; the kinase-dead K823Y allele abrogates activity.
        supporting_text: |-
          Rim15 is an **EC 2.7.11.1 serine/threonine-protein kinase**. Direct
          biochemical evidence includes purified Rim15 phosphorylating substrates
          in vitro; a kinase-dead allele (**K823Y**) abrogates activity,
          supporting canonical ATP-dependent catalysis.
        reference_section_type: OTHER
      - statement: |-
          Beyond endosulfines, Rim15 directly phosphorylates the stress
          transcription factors Msn2 and Hsf1 in vitro, whereas Gis1 is regulated
          indirectly via PP2A-Cdc55 inhibition.
        supporting_text: |-
          Evidence supports direct phosphorylation of **Msn2** and **Hsf1** by
          Rim15 in vitro, whereas **Gis1** appears primarily regulated indirectly
          (via PP2A-Cdc55 inhibition through Igo1/2).
        reference_section_type: OTHER
      - statement: |-
          Rim15 localization is nutrient-gated: cytoplasmic and inhibited in rich
          medium, accumulating transiently in the nucleus upon nutrient
          limitation or TORC1 inhibition, with nuclear export mediated by Msn5.
        supporting_text: |-
          Under glucose/nutrient-rich conditions, Rim15 is retained in the
          **cytoplasm** and inhibited.
          ...
          Upon nutrient limitation or TORC1 inhibition (e.g., rapamycin), Rim15
          transiently accumulates in the **nucleus**, where it can activate
          downstream programs.
          ...
          Nuclear export is mediated by **Msn5**
        reference_section_type: OTHER
      - statement: |-
          Rim15 activity is restrained under nutrient-rich conditions by PKA
          (five RRxS sites that inhibit kinase activity), TORC1-Sch9
          (kinase-insert Ser1061), and Pho80-Pho85 (Thr1075 promoting 14-3-3/Bmh2
          binding and cytoplasmic retention).
        supporting_text: |-
          PKA phosphorylates Rim15 at **five RRxS consensus sites**, strongly
          inhibiting Rim15 kinase activity in vitro
          ...
          Pho80–Pho85 phosphorylates Rim15 at **Thr1075**, which promotes binding
          to **14-3-3 (Bmh2)** and cytoplasmic retention
        reference_section_type: OTHER
      - statement: |-
          The Rim15-endosulfine-PP2A axis is a fermentation brake exploited
          industrially: natural sake strains carry a loss-of-function 5055insA
          RIM15 allele giving high fermentation rates, and deleting CDC55
          (PP2A-B55) abolishes the high-fermentation phenotype of
          Rim15-deficient strains.
        supporting_text: |-
          Modern sake strains carry a **loss-of-function insertion** allele
          (reported as **5055insA**) truncating Rim15p and linked to defective
          quiescence entry and **high fermentation rates**.
          ...
          deletion of **CDC55** (PP2A-B55) abolishes the
        reference_section_type: OTHER
      - statement: |-
          Igo1/Igo2 (downstream of Rim15) are required for pre-meiotic autophagy,
          and the Rim15-Igo-PP2A-Cdc55 module governs entry into both quiescence
          and gametogenesis through distinct downstream mechanisms.
        supporting_text: |-
          Igo1/2 are required for **pre-meiotic autophagy**, and the
          Rim15–Igo–PP2A-Cdc55 module regulates entry into both quiescence and
          gametogenesis via distinct downstream mechanisms.
        reference_section_type: OTHER
      - statement: |-
          rim15Δ survival defects during quiescence are starvation-signal
          specific, being stronger under phosphorus and nitrogen starvation than
          under carbon starvation.
        supporting_text: |-
          rim15Δ reduced survival specifically under **phosphorus and nitrogen**
          starvation (not carbon)
        reference_section_type: OTHER
core_functions:
  - molecular_function:
      id: GO:0004674
      label: protein serine/threonine kinase activity
    description: RIM15 is a serine/threonine protein kinase that integrates 
      signals from TOR, PKA, and Sch9 kinases to sense nutrient (glucose and 
      nitrogen) availability. Upon nutrient limitation, RIM15 becomes active and
      catalyzes phosphorylation of downstream effectors (Igo1/2 endosulfines, 
      Rph1 histone demethylase, Hsf1 and Msn2 transcription factors) to 
      orchestrate quiescence entry and stress response programs.
proposed_new_terms: []
suggested_questions:
  - question: Does RIM15 directly phosphorylate other transcription factors 
      besides Hsf1, Msn2, and Gis1?
  - question: What are the kinetic parameters (Km, kcat) of RIM15 
      phosphorylation of different substrates?
  - question: How does RIM15 selectivity/specificity among substrates function 
      mechanistically?
  - question: Does RIM15 have scaffold functions independent of its catalytic 
      kinase activity?
suggested_experiments: []

RIM15

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Deep Research

Falcon

Research Report: Functional Annotation of RIM15 (UniProt P43565) in Saccharomyces cerevisiae S288c

1) Target verification (gene/protein identity)

2) Key concepts and definitions (current understanding)

2.1 Rim15 as a nutrient-to-quiescence “integrator kinase”

2.2 Greatwall–Endosulfine–PP2A/B55 module (conserved logic)

2.3 Direct vs indirect control of transcription

3) Protein features: domains, enzymatic activity, and substrate specificity

3.1 Domain architecture (structural concepts)

3.2 Kinase activity (reaction class)

3.3 Validated direct substrates and what they imply about specificity

4) Regulation and localization: where Rim15 acts in the cell

4.1 Nutrient-dependent nucleo-cytoplasmic shuttling

4.2 Upstream pathways and mapped phosphosites

5) Downstream pathways and biological functions (best-supported)

5.1 Quiescence/G0 entry and stress resistance programs

5.2 Rim15 → Igo1/2 → PP2A-Cdc55 axis (core biochemical pathway)

5.3 Transcription factor branches: Msn2/4, Gis1, Hsf1

5.4 Post-transcriptional control (mRNA stability/decapping)

5.5 Autophagy and gametogenesis-associated survival

6) Recent developments (prioritizing 2023–2024)

6.1 2023 (peer-reviewed review): TORC1–Rim15/Igo–PP2A-Cdc55 connects nutrients to START via Whi5

6.2 2023 (systems-level phosphoproteomics; preprint): starvation-signal-specific roles for Rim15

6.3 2024: mechanistic refinement in related conserved modules

7) Current applications and real-world implementations

7.1 Industrial fermentation: natural and engineered RIM15 loss-of-function increases fermentation rate

7.2 Mechanistic strain design: TORC1–Greatwall(Rim15)–PP2A-B55/Cdc55 pathway as an engineering handle

7.3 Trade-offs: fermentation speed vs stress tolerance/quiescence robustness

8) Expert opinions and analysis (authoritative synthesis)

8.1 Rim15 as a “crossroads” node of nutrient signaling

8.2 Rim15 in lifespan/quiescence frameworks

9) Key statistics and data points (recent and classic)

9.1 Validated phosphorylation target with residue-level mapping

9.2 Quantitative industrial phenotypes (2012)

9.3 Quantitative omics (2023; preprint)

10) Consolidated functional annotation summary

11) Practical functional annotation (concise “database-style” statement)

12) Notes on evidence quality and recency

Artifacts

Citations

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