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