RIM15

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
  - 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
  - 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
  - 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
  - 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.
  - 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.
  - 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.
  - 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
  - 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
    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: []
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: []