CDC55

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000159 protein phosphatase type 2A complex	IBA GO_REF:0000033	ACCEPT	Summary: PAINT-inferred membership of the heterotrimeric PP2A holoenzyme for the PR55/B55 family. In budding yeast Cdc55 is the B-type subunit that assembles with the Tpd3 scaffold and the Pph21/Pph22 catalytic subunits, one of only two regulatory subunits (with Rts1) in this organism. Reason: Holoenzyme membership is the defining, family-wide property of B55 subunits and the node placement is sound: every extant descendant with experimental data (human PPP2R2A, Drosophila tws, mouse Ppp2r2a/Ppp2r2d, S. pombe pab1, Dictyostelium) is a PP2A B subunit, and the S. cerevisiae protein has its own experimental evidence for the term (co-purification with Tpd3 and the catalytic subunit, competition of Tap42 with Cdc55/Tpd3 for the C subunit, and the Complex Portal entry). SGD:S000003158 appearing in the WITH/FROM list is the expected marker of that experimental grounding, not circularity. Core function. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000221745 SUPPORTS TRANSFER Ancestral PR55/B55 node; holoenzyme assembly through the WD40 propeller and beta-hairpin arm is architecturally conserved across the family with no evidence of loss in the yeast lineage. SGD:S000003158 · CDC55 SUPPORTS TRANSFER The target itself carries IDA/IMP/IPI evidence for the term; its presence among the descendant evidences is expected. UniProtKB:P63151 · PPP2R2A SUPPORTS TRANSFER Human B55-alpha has a crystal structure of the A-B55-C trimer; the orthologous relationship with Cdc55 is unambiguous. Supporting Evidence: PMID:17550305 deletion of PPE1 in an rrd1Δ/rrd2Δ strain increases holoenzyme assembly with the B-type subunit CDC55 without generation of the active C subunit PMID:10329624 phosphorylated Tap42 effectively competes with Cdc55/Tpd3 for binding to the phosphatase 2A catalytic subunit file:yeast/CDC55/CDC55-deep-research-falcon.md Pph21/Pph22 supply the metal-dependent catalytic activity, while Cdc55 governs substrate engagement and localization.
GO:0000159 protein phosphatase type 2A complex	IDA PMID:8600023 A ceramide-activated protein phosphatase mediates ceramide-i...	ACCEPT	Summary: Cdc55 was purified as a regulatory subunit (with Tpd3) of a ceramide-activated protein phosphatase; the paper assigned the catalytic partner to Sit4 rather than Pph21/Pph22. Reason: The direct evidence is that Cdc55 co-purifies with the PP2A A subunit Tpd3 in a heterotrimeric phosphatase, which is what the term asserts. The specific claim that the catalytic subunit in this preparation is Sit4 (a PP6-type catalytic subunit) has not been the mainstream view since; later biochemical work identifies Pph21/Pph22 as the catalytic partners of Tpd3-Cdc55, and Cdc55 and Tpd3 compete with Tap42 for the PP2A catalytic subunit. The term itself (PP2A holoenzyme membership) is beyond doubt on the totality of evidence, so the row is accepted with that caveat noted. Supporting Evidence: PMID:8600023 yeast cells contain a ceramide-activated protein phosphatase composed of regulatory subunits encoded by TPD3 and CDC55 and a catalytic subunit encoded by SIT4 PMID:17550305 deletion of PPE1 in an rrd1Δ/rrd2Δ strain increases holoenzyme assembly with the B-type subunit CDC55 without generation of the active C subunit PMID:10329624 phosphorylated Tap42 effectively competes with Cdc55/Tpd3 for binding to the phosphatase 2A catalytic subunit
GO:0000159 protein phosphatase type 2A complex	IEA GO_REF:0000120	ACCEPT	Summary: Automated assignment from the InterPro PP2A_PR55 signature (IPR000009) and ARBA, placing Cdc55 in the PP2A complex. Reason: An electronic call that is exactly right: the PR55 signature identifies the protein as a PP2A B subunit and the yeast protein has direct biochemical evidence for holoenzyme assembly with Tpd3 and Pph21/Pph22. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000009 · PP2A_PR55 SUPPORTS TRANSFER Family signature specific to B55/PR55 regulatory subunits; the mapping to the PP2A complex term is appropriate for every member. Supporting Evidence: PMID:17550305 deletion of PPE1 in an rrd1Δ/rrd2Δ strain increases holoenzyme assembly with the B-type subunit CDC55 without generation of the active C subunit PMID:10329624 phosphorylated Tap42 effectively competes with Cdc55/Tpd3 for binding to the phosphatase 2A catalytic subunit
GO:0000159 protein phosphatase type 2A complex	IMP PMID:8600023 A ceramide-activated protein phosphatase mediates ceramide-i...	ACCEPT	Summary: Mutation of CDC55 (like TPD3 and the catalytic-subunit gene) renders cells resistant to ceramide-induced G1 arrest, used here as genetic evidence that Cdc55 is a subunit of the ceramide-activated phosphatase. Reason: A mutant phenotype is weak evidence for a cellular-component term on its own, but it is consistent with the co-purification data in the same paper and with all later work on the Tpd3-Cdc55-Pph21/22 holoenzyme, so the term is correct. The same caveat as for the IDA row applies to the paper's assignment of Sit4 as the catalytic subunit. Supporting Evidence: PMID:8600023 Because mutation of any one of these three genes renders strains resistant to ceramide inhibition PMID:8600023 yeast cells contain a ceramide-activated protein phosphatase composed of regulatory subunits encoded by TPD3 and CDC55 and a catalytic subunit encoded by SIT4
GO:0000159 protein phosphatase type 2A complex	IPI PMID:10329624 Tor proteins and protein phosphatase 2A reciprocally regulat...	ACCEPT	Summary: Complex Portal-curated membership of the PP2A holoenzyme, from the demonstration that Cdc55 and Tpd3 regulate Pph21/22 and that phosphorylated Tap42 competes with Cdc55/Tpd3 for binding to the catalytic subunit. Reason: Direct evidence that Cdc55 is a subunit of the Tpd3-Pph21/22 holoenzyme and that this assembly is in competition with the Tap42-Pph21/22 dimer downstream of TOR; this row is also the origin of the TOR-pathway connection developed by later autophagy and quiescence studies. Supporting Evidence: PMID:10329624 We show that inactivation of either Cdc55 or Tpd3, which regulate Pph21/22 activity, results in rapamycin resistance and that this resistance correlates with an increased association of Tap42 with Pph21/22. PMID:10329624 phosphorylated Tap42 effectively competes with Cdc55/Tpd3 for binding to the phosphatase 2A catalytic subunit
GO:0000329 fungal-type vacuole membrane	IDA PMID:12388751 Localization of Saccharomyces cerevisiae protein phosphatase...	KEEP AS NON CORE	Summary: A functional GFP-Cdc55 fusion colocalises with the FM4-64 vacuolar-membrane stain at all cell-cycle stages; a weaker Tpd3 signal at the vacuole was also seen. Reason: The localisation is real and reproducible (Zds1 overexpression enhances the vacuolar-membrane pool, and PP2A-Cdc55 later proved to be required for ESCRT-0 recruitment to vacuolar membranes during microautophagy), but it is a minor pool relative to the nuclear and cytoplasmic pools through which the characterised mitotic functions are executed. Kept as a non-core location. Supporting Evidence: PMID:12388751 When GFP-CDC55 cells were stained with FM4-64, GFP-Cdc55p colocalized with the stain in cells in all cell cycle stages PMID:32029270 Loss of PP2A-Cdc55 compromised vacuolar localization of Hse1, but not Vps27.
GO:0000705 achiasmate meiosis I	IGI PMID:27455870 PP2A(Cdc55)'s role in reductional chromosome segregation dur...	MODIFY	Summary: cdc55 'monopolin-class' alleles (cdc55-MP) were isolated as suppressors of spo11Δ spo12Δ lethality and affect reductional segregation of sister centromeres when recombination is absent, independently of the FEAR-related function of PP2A-Cdc55; they have no effect in a wild-type (chiasmate) meiosis. Reason: The underlying finding is sound and the IGI with SPO11/SPO12 is exactly what the paper did. The term, however, describes a meiosis that occurs 'in the constitutive absence of chiasmata' (e.g. Drosophila male meiosis); a spo11Δ background is an experimentally imposed, not constitutive, loss of chiasmata, so S. cerevisiae is outside the intended scope of the term. What the genetics actually reveals is a contribution of PP2A-Cdc55 to reductional (homologous) chromosome segregation in meiosis I that is normally masked by chiasmata, which is captured by the sibling GO:0045143 row from the same paper; the replacement therefore points at that term rather than at an organism-level meiosis type. Proposed replacements: homologous chromosome segregation Supporting Evidence: PMID:27455870 We suggest that Cdc55 is required for reductional chromosome segregation during achiasmate meiosis and this is independent of its FEAR function. PMID:27455870 Although the suppressor mutations in cdc55 affect reductional chromosome segregation in the absence of recombination, they have no effect on chromosome segregation during wild type meiosis.
GO:0001100 negative regulation of exit from mitosis	IMP PMID:16314395 The role of Cdc55 in the spindle checkpoint is through regul...	ACCEPT	Summary: cdc55Δ cells prematurely release Cdc14 from the nucleolus during spindle-checkpoint activation, degrade Pds1 and lose cohesion with bub2Δ-like kinetics, and cdc55Δ suppresses lte1 spo12 synthetic lethality: Cdc55 is a negative regulator of mitotic exit acting downstream or independently of Cdc15. Reason: This is the best-established core role of PP2A-Cdc55 in budding yeast and is mechanistically explained by the Queralt/Uhlmann work: PP2A-Cdc55 keeps the Cdc14 inhibitor Net1 underphosphorylated in metaphase until separase (with Zds1/Zds2) downregulates it at anaphase onset, and nuclear-restricted Cdc55 blocks Cdc14 release. Core function. Supporting Evidence: PMID:16314395 We show that Cdc55 is a negative regulator of mitotic exit. PMID:16314395 A cdc55 mutant, like a bub2 mutant, prematurely releases Cdc14 phosphatase from the nucleolus during spindle checkpoint activation PMID:16713564 Here, we show that PP2A(Cdc55) phosphatase keeps Net1 underphosphorylated in metaphase. PMID:16713564 The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent Net1 phosphorylation. PMID:21536748 On the other hand, nuclear Cdc55 prevents mitotic exit.
GO:0005515 protein binding	IPI PMID:11805826 Functional organization of the yeast proteome by systematic ...	REMOVE	Summary: Cdc55 recovered with the type I myosin Myo5 in the Cellzome TAP-MS survey of yeast protein complexes. Reason: A high-throughput affinity-purification survey; the Cdc55-Myo5 pairing has no established functional consequence and does not resolve to a more informative molecular function for Cdc55, although a cortical PP2A-Cdc55 pool near actin structures is plausible. Bare "protein binding" carries no functional information about Cdc55, so the row is removed per repository curation policy; removal does not question the reported interaction, which remains recorded in IntAct and in the UniProt INTERACTION section. Supporting Evidence: PMID:11805826 We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae.
GO:0005515 protein binding	IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine...	REMOVE	Summary: Cdc55-Myo5 interaction recorded again in the genome-wide affinity-purification/mass-spectrometry screen for yeast complexes. Reason: Same interaction and same limitation as the 2002 Cellzome row: a proteome-scale co-purification without functional follow-up cannot support a specific molecular-function term for Cdc55. Bare "protein binding" carries no functional information about Cdc55, so the row is removed per repository curation policy; removal does not question the reported interaction, which remains recorded in IntAct and in the UniProt INTERACTION section. Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry.
GO:0005515 protein binding	IPI PMID:16713564 Downregulation of PP2A(Cdc55) phosphatase by separase initia...	REMOVE	Summary: Co-immunoprecipitation of Cdc55 with separase (Esp1) in the study showing that separase downregulates PP2A-Cdc55 at anaphase onset to permit Net1 phosphorylation and Cdc14 release. Reason: The interaction is biologically important, but it records Cdc55 being the target of a regulator (separase inhibits the holoenzyme) rather than an activity of Cdc55; the functional content of this paper is already captured by the negative-regulation-of-mitotic-exit row (GO:0001100) and the regulator-activity rows. Bare "protein binding" carries no functional information about Cdc55, so the row is removed per repository curation policy; removal does not question the reported interaction, which remains recorded in IntAct and in the UniProt INTERACTION section. Supporting Evidence: PMID:16713564 The sister chromatid-separating protease separase, activated at anaphase onset, interacts with and downregulates PP2A(Cdc55), thereby facilitating Cdk-dependent Net1 phosphorylation. PMID:16713564 Here, we show that PP2A(Cdc55) phosphatase keeps Net1 underphosphorylated in metaphase.
GO:0005515 protein binding	IPI PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho...	REMOVE	Summary: Separase-Cdc55 co-immunoprecipitation shown to be independent of Zds1/Zds2, in the study identifying Zds1/Zds2 as separase-cooperating PP2A-Cdc55 inhibitors that promote Cdc14 activation in early anaphase. Reason: As for the 2006 row, the interaction describes regulatory input onto PP2A-Cdc55 (separase and Zds1/Zds2 downregulate it) and is fully represented, with functional meaning, by the mitotic-exit rows. Bare "protein binding" carries no functional information about Cdc55, so the row is removed per repository curation policy; removal does not question the reported interaction, which remains recorded in IntAct and in the UniProt INTERACTION section. Supporting Evidence: PMID:18762578 Therefore separase interacts with Cdc55 independently of Zds1 and Zds2. PMID:18762578 Ectopic Zds1 expression in turn is sufficient to down-regulate PP2A(Cdc55) and promote Net1 phosphorylation.
GO:0005515 protein binding	IPI PMID:19841731 Bayesian modeling of the yeast SH3 domain interactome predic...	REMOVE	Summary: IntAct-curated Cdc55-Myo5 interaction from the yeast SH3-domain interactome study (peptide phage display, peptide arrays and Bayesian network modelling); Cdc55 is not discussed in the main text. Reason: A predicted/screen-level SH3-ligand interaction from a proteome-wide dataset, with no Cdc55-specific follow-up; it does not identify a molecular function for Cdc55. Bare "protein binding" carries no functional information about Cdc55, so the row is removed per repository curation policy; removal does not question the reported interaction, which remains recorded in IntAct and in the UniProt INTERACTION section. Supporting Evidence: PMID:19841731 We used peptide phage display to conduct a large-scale analysis of yeast SH3 domain specificity.
GO:0005634 nucleus	IDA PMID:12388751 Localization of Saccharomyces cerevisiae protein phosphatase...	ACCEPT	Summary: A fully functional, chromosomally integrated GFP-Cdc55 fusion is nuclear in more than 90% of cells at all cell-cycle stages, and this localisation does not depend on the A or C subunit. Reason: The nuclear pool is where PP2A-Cdc55 executes its core mitotic functions: it keeps Net1 underphosphorylated to retain Cdc14 in the nucleolus, and nuclear Cdc55 is essential for the spindle assembly checkpoint. Core location. Supporting Evidence: PMID:12388751 GFP-Cdc55p localized to the nucleus in >90% of all cells PMID:12388751 Cdc55p achieved its normal localization in the absence of either an A or C subunit PMID:21536748 On the other hand, nuclear Cdc55 prevents mitotic exit. PMID:23886942 we further show that nuclear Cdc55 is essential for the SAC
GO:0005634 nucleus	IMP PMID:23886942 Nuclear PP2A-Cdc55 prevents APC-Cdc20 activation during the ...	ACCEPT	Summary: SAC-specific cdc55 alleles and forced nucleocytoplasmic redistribution of Cdc55 show that the nuclear pool of PP2A-Cdc55 is the one that is active in the spindle assembly checkpoint (is_active_in nucleus). Reason: Direct functional evidence that Cdc55 acts in the nucleus, consistent with the GFP localisation and with the nuclear-restricted cdc55-NLS allele that blocks Cdc14 release. Core location. Supporting Evidence: PMID:23886942 we further show that nuclear Cdc55 is essential for the SAC PMID:23886942 APC-Cdc20 is kept inactive by dephosphorylation by nuclear PP2A-Cdc55 when spindle is damaged PMID:21536748 On the other hand, nuclear Cdc55 prevents mitotic exit.
GO:0005737 cytoplasm	IDA PMID:21536748 Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitot...	ACCEPT	Summary: Endogenously tagged Cdc55-GFP is found in the cytoplasm as well as the nucleus; the cytoplasmic and cortical pool depends on Zds1/Zds2 and is the pool that promotes mitotic entry. Reason: The cytoplasmic localisation is functionally validated by the cdc55-NES allele, which is fully competent for mitotic entry and bypasses the requirement for Zds1/Zds2, and by the swe1Δ suppression showing that the cytoplasmic pool acts on the Swe1/Mih1 axis. Core location. Supporting Evidence: PMID:21536748 Cortical and cytoplasmic localization of Cdc55 requires Zds1/Zds2, and Cdc55 accumulates in the nucleus in the absence of Zds1/Zds2. PMID:21536748 we showed that Cdc55 promotes mitotic entry when in the cytoplasm PMID:21536748 When bound to Zds1/Zds2, Cdc55 functions in the cytoplasm to promote mitotic entry by activating the Cdk.
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: PAINT-inferred cytosolic activity for the B55 family, seeded from Drosophila twins and the ancestral node. Reason: The inference is consistent with the direct yeast evidence: Cdc55 has a Zds1/Zds2-dependent cytoplasmic pool, the constitutively cytoplasmic cdc55-NES allele supports mitotic entry, and the Swe1-inactivating machinery it acts on is cytoplasmic. Cytosol is the appropriate active-in compartment for that pool alongside the nuclear pool that carries the mitotic-exit and checkpoint functions. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000221745 SUPPORTS TRANSFER Ancestral B55 node; a cytosolic pool of the holoenzyme is shared by yeast, fly and human B55 subunits. FB:FBgn0004889 · tws SUPPORTS TRANSFER Drosophila twins/B55 is a cytosolic PP2A regulatory subunit; yeast Cdc55 has its own cytoplasmic pool with a demonstrated function in mitotic entry. Supporting Evidence: PMID:21536748 Cortical and cytoplasmic localization of Cdc55 requires Zds1/Zds2, and Cdc55 accumulates in the nucleus in the absence of Zds1/Zds2. PMID:21536748 we showed that Cdc55 promotes mitotic entry when in the cytoplasm
GO:0005934 cellular bud tip	IDA PMID:12388751 Localization of Saccharomyces cerevisiae protein phosphatase...	KEEP AS NON CORE	Summary: GFP-Cdc55 concentrates at the bud tip from the smallest visible buds through medium-budded cells, and Tpd3 requires Cdc55 for its own bud-tip accumulation. Reason: A genuine, cell-cycle-regulated cortical pool: Cdc55 recruits the scaffold subunit to the bud tip, the Zds1/Zds2 proteins that anchor Cdc55 in the cytoplasm are themselves bud-cortex proteins, and cdc55 mutants have polarised-growth and morphogenesis defects. The functional consequence at this site is not resolved at the substrate level, so it is kept as a non-core location. Supporting Evidence: PMID:12388751 GFP-Cdc55p localized to the bud tip of the smallest visible buds, to the bud tip of small/medium budded cells, and to some buds that were nearly as large as the mother PMID:12388751 Most strikingly, in cdc55Δ cells, GFP-Tpd3p was rarely found at bud tips, being seen in <5% of small/medium budded cells compared with 70% in wild-type cells
GO:0005935 cellular bud neck	IDA PMID:12388751 Localization of Saccharomyces cerevisiae protein phosphatase...	KEEP AS NON CORE	Summary: GFP-Cdc55 localises to the bud neck in about half of post-telophase cells, progressing from the daughter side to single and double rings and to the new cell wall, mirroring Tpd3. Reason: The late-mitotic bud-neck pool is consistent with the cytokinesis and septation defects of cdc55 mutants and with the bud-neck localisation of Zds1/Zds2, but the substrates acted on there are not defined, so it is a non-core location. Supporting Evidence: PMID:12388751 It also localized to the bud neck (Figure 4 A, open arrowheads) in 53% of post-telophase cells
GO:0010971 positive regulation of G2/M transition of mitotic cell cycle	IMP PMID:21536748 Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitot...	ACCEPT	Summary: cdc55Δ, zds1Δ zds2Δ and nuclear-restricted cdc55-NLS cells show a Swe1-dependent G2 delay with elongated buds and accumulate Tyr19-phosphorylated Cdc28, whereas cytoplasmic cdc55-NES is fully competent for mitotic entry: cytoplasmic PP2A-Cdc55 promotes mitotic entry by opposing Swe1 and activating Mih1. Reason: In budding yeast, unlike metazoa, PP2A-Cdc55 promotes rather than prevents mitotic entry, feeding the positive feedback loop of Cdk1 activation through Mih1 dephosphorylation/activation and by opposing the initial Cdk1 phosphorylation of Swe1; the term's definition (a pathway that activates a cell-cycle CDK at the G2/M switch) fits this precisely. Core function. Supporting Evidence: PMID:21536748 we showed that Cdc55 promotes mitotic entry when in the cytoplasm PMID:21536748 Our genetic data suggest that the critical target of Cdc55 in mitotic entry is Swe1 because mitotic entry defects of cdc55Δ, zds1Δ zds2Δ, and cdc55-NLS are almost fully rescued by deletion of SWE1. PMID:23861665 In stark contrast to other organisms, budding yeast PP2ACdc55 promotes, rather than prevents, timely entry into mitosis by participating in the positive feedback loop for Cdk1 activation PMID:23861665 In addition, PP2ACdc55 dephosphorylates and activates Mih1
GO:0010972 negative regulation of G2/M transition of mitotic cell cycle	IEA GO_REF:0000117	MODIFY	Summary: ARBA machine-learning transfer of the metazoan B55 role in restraining mitotic entry (PP2A-B55 dephosphorylates Cdk1 substrates and is inhibited by Greatwall-phosphorylated endosulfines at mitotic entry). Reason: The sign of this transfer is wrong for budding yeast. The experimental literature is explicit that PP2A-Cdc55 promotes, rather than prevents, timely entry into mitosis, by dephosphorylating and activating Mih1 and by opposing Swe1 activation; cdc55Δ cells accumulate Tyr19-phosphorylated Cdk1 and delay G2/M. The only sense in which Cdc55 restrains entry is as the Zds1/Zds2-controlled component required for the Swe1-dependent morphogenesis-checkpoint delay (the IGI rows below), a context-dependent effect that is not what the ARBA rule is describing. Rather than remove the row outright, it is generalised to the sign-neutral parent so that the machine annotation stops asserting the metazoan direction; the positive-regulation IMP row remains the core statement. Propagation Review Root cause: PROPAGATION BAD Failure modes: REGULATORY SIGN INVERSION LINEAGE OR TAXON MISMATCH Sources checked: ARBA:ARBA00084549 SUPPORTS SOURCE BUT NOT TARGET The rule generalises the metazoan PP2A-B55 behaviour (restraint of mitotic entry, relieved by cyclin B-CDK1 and Greatwall-ENSA) to the family; in S. cerevisiae the endosulfine-PP2A-Cdc55 module is wired the other way, with PP2A-Cdc55 promoting Cdk1 activation. Proposed replacements: regulation of G2/M transition of mitotic cell cycle Supporting Evidence: PMID:23861665 In stark contrast to other organisms, budding yeast PP2ACdc55 promotes, rather than prevents, timely entry into mitosis by participating in the positive feedback loop for Cdk1 activation PMID:23861665 In addition, PP2ACdc55 dephosphorylates and activates Mih1 PMID:21536748 we showed that Cdc55 promotes mitotic entry when in the cytoplasm PMID:21536748 Our genetic data suggest that the critical target of Cdc55 in mitotic entry is Swe1 because mitotic entry defects of cdc55Δ, zds1Δ zds2Δ, and cdc55-NLS are almost fully rescued by deletion of SWE1.
GO:0016237 microautophagy	IMP PMID:32029270 PP2A promotes ESCRT-0 complex formation on vacuolar membrane...	KEEP AS NON CORE	Summary: After TORC1 inactivation, loss of PP2A-Cdc55 compromises vacuolar recruitment of the ESCRT-0 subunit Hse1 (but not Vps27) and impairs microautophagy induction. Reason: PP2A-Cdc55 acts here as a TORC1-downstream phosphatase that licenses ESCRT-0 assembly on the vacuolar membrane; it is an upstream regulatory input rather than part of the membrane-deformation machinery of microautophagy itself, but GO has no regulation-of-microautophagy child to move it to. The cached record is abstract-only and the SGD curator read the full text, so the term is kept and graded non-core (nutrient-signalling branch of PP2A-Cdc55 function). Supporting Evidence: PMID:32029270 Here, we show that the TORC1-downstream protein phosphatase PP2A-Cdc55 is important for these events after TORC1 inactivation in budding yeast. PMID:32029270 Loss of PP2A-Cdc55 compromised vacuolar localization of Hse1, but not Vps27.
GO:0019888 protein phosphatase regulator activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT-inferred protein phosphatase regulator activity for the PR55/B55 family: the B subunit has no catalytic centre and instead determines the substrate specificity, localisation and inhibitor sensitivity of the PP2A holoenzyme. Reason: This is the correct molecular-function statement for Cdc55 and the node placement is sound across the family. In yeast, Cdc55 confers histone H1/Net1-directed activity on the holoenzyme, is the subunit through which Rim15-phosphorylated Igo1/Igo2, separase and Zds1/Zds2 regulate the enzyme, and is required for the phosphatase to be targeted to its cortical, cytoplasmic and nuclear sites of action. Core molecular function. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000221745 SUPPORTS TRANSFER Ancestral B55 node; regulatory-subunit activity is the family-defining function. SGD:S000003158 · CDC55 SUPPORTS TRANSFER The target carries its own IGI evidence for this term; expected marker of experimental grounding. Supporting Evidence: PMID:17550305 The B-type subunits are responsible for the substrate specificity and intracellular localization of the PP2A holoenzymes. PMID:23861665 Phosphorylated Igo1 inhibits PP2A(Cdc55) activity in vitro and induces mitotic entry in Xenopus egg extracts PMID:23861665 Here we show that budding yeast endosulfines (Igo1 and Igo2) bind to PP2A(Cdc55) in a cell cycle-regulated manner upon Greatwall (Rim15)-dependent phosphorylation. file:yeast/CDC55/CDC55-deep-research-falcon.md Pph21/Pph22 supply the metal-dependent catalytic activity, while Cdc55 governs substrate engagement and localization.
GO:0019888 protein phosphatase regulator activity	IEA GO_REF:0000120	ACCEPT	Summary: InterPro/ARBA automated assignment of protein phosphatase regulator activity from the PP2A_PR55 signature. Reason: Correct: the PR55 family signature identifies a non-catalytic PP2A regulatory subunit, and the yeast protein has genetic and biochemical evidence for the same activity. Supporting Evidence: PMID:17550305 The B-type subunits are responsible for the substrate specificity and intracellular localization of the PP2A holoenzymes. PMID:23861665 Phosphorylated Igo1 inhibits PP2A(Cdc55) activity in vitro and induces mitotic entry in Xenopus egg extracts
GO:0019888 protein phosphatase regulator activity	IGI PMID:17550305 Generation of active protein phosphatase 2A is coupled to ho...	ACCEPT	Summary: A cdc55Δ rts1Δ double mutant lacking both yeast B-type subunits was used, alongside tpd3Δ and rrd1Δ rrd2Δ, to dissect how active and substrate-specific PP2A is generated; B-subunit assembly with Cdc55 is coupled to Rrd2/Tpd3-dependent maturation of the catalytic subunit. Reason: The paper's headline concerns Rrd2 and Tpd3, but the full text assays holoenzyme composition with anti-Cdc55 antibodies and uses the B-subunit-less double mutant as a comparator, which is a legitimate IGI basis for Cdc55 (with Rts1) regulating PP2A activity. Consistent with all other evidence for the term. Supporting Evidence: PMID:17550305 a cdc55Δ/rts1Δ strain, which lacks the known B-type subunits of yeast PMID:17550305 deletion of PPE1 in an rrd1Δ/rrd2Δ strain increases holoenzyme assembly with the B-type subunit CDC55 without generation of the active C subunit PMID:17550305 Complex formation with the regulatory A and B-type subunits suppresses nonspecific C subunit activity, but increases the substrate affinity
GO:0043332 mating projection tip	IDA PMID:12388751 Localization of Saccharomyces cerevisiae protein phosphatase...	KEEP AS NON CORE	Summary: In pheromone-treated cells GFP-Cdc55 accumulates as a crescent at the shmoo tip, as does Tpd3; tpd3Δ cells form abnormal mating projections. Reason: A real localisation that parallels the bud-tip pool during polarised growth; the mating-projection role is a context-specific extension of the polarity-site localisation rather than a core function, and no substrate at this site is defined. Supporting Evidence: PMID:12388751 GFP-Cdc55p also localized to the shmoo tip in a pattern identical to that shown by Tpd3p
GO:0044818 mitotic G2/M transition checkpoint	IGI PMID:20980617 Zds2p regulates Swe1p-dependent polarized cell growth in Sac...	KEEP AS NON CORE	Summary: Deletion of CDC55 rescues the Swe1-dependent elongated-bud phenotype of zds1Δ zds2Δ cells, and galactose-induced ZDS2 cannot drive mitosis past an actin-perturbation (cdc24-1) checkpoint arrest without CDC55; Zds2 binds Cdc55 directly through its C-terminal ZH4 domain. Reason: The genetics genuinely place Cdc55 in the Swe1-dependent morphogenesis checkpoint circuit: the checkpoint delay of zds1Δ zds2Δ requires CDC55 and the Zds proteins act on the checkpoint through Cdc55. The sign, however, is context-dependent. In the same circuit PP2A-Cdc55 is the phosphatase that dephosphorylates and activates Mih1 and opposes Swe1, i.e. it normally promotes the G2/M transition, and the later Rossio/Yoshida work explains the zds1Δ zds2Δ phenotype by mislocalisation of Cdc55 to the nucleus. Cdc55 is therefore better understood as the Zds-regulated effector on the Swe1/Mih1 axis than as a checkpoint sensor. The curator's reading of the genetic data is defensible and the full text was read, so the row is kept, but graded non-core; the positive-regulation IMP row is the core statement of this function. Supporting Evidence: PMID:20980617 deletion of CDC55 rescues the aberrant bud morphology of a zds1Δzds2Δ strain PMID:20980617 This negative regulation requires the CDC55 gene. PMID:20980617 ZH4 is shown by protein affinity assays to be necessary and sufficient for interaction with Cdc55p, a regulatory subunit of protein phosphatase 2A (PP2A). PMID:23861665 In stark contrast to other organisms, budding yeast PP2ACdc55 promotes, rather than prevents, timely entry into mitosis by participating in the positive feedback loop for Cdk1 activation
GO:0044818 mitotic G2/M transition checkpoint	IGI PMID:20980617 Zds2p regulates Swe1p-dependent polarized cell growth in Sac...	KEEP AS NON CORE	Summary: Same experiments as the ZDS2 row, with ZDS1 as the interacting gene: cdc55Δ suppresses the zds1Δ zds2Δ checkpoint-dependent bud elongation and GAL-ZDS1 cannot override the Swe1 checkpoint in a cdc55Δ background. Reason: As for the ZDS2 row: the requirement for CDC55 in the Zds-regulated Swe1 checkpoint response is real, but PP2A-Cdc55 normally promotes G2/M through Mih1/Swe1, and the checkpoint-delay phenotype reflects Cdc55 mislocalised to the nucleus in the absence of Zds1/Zds2. Kept, non-core. Supporting Evidence: PMID:20980617 deletion of CDC55 rescues the aberrant bud morphology of a zds1Δzds2Δ strain PMID:20980617 This negative regulation requires the CDC55 gene. PMID:21536748 Cortical and cytoplasmic localization of Cdc55 requires Zds1/Zds2, and Cdc55 accumulates in the nucleus in the absence of Zds1/Zds2.
GO:0045143 homologous chromosome segregation	IGI PMID:27455870 PP2A(Cdc55)'s role in reductional chromosome segregation dur...	KEEP AS NON CORE	Summary: cdc55-MP alleles impair reductional segregation of sister centromeres in spo11Δ spo12Δ (achiasmate) meiosis, an effect separable from the FEAR-related function of PP2A-Cdc55, without affecting segregation in a wild-type meiosis. Reason: A meiosis-specific contribution to homologue (reductional) segregation that is only revealed in the absence of recombination; the molecular mechanism (candidates include sister-kinetochore mono-orientation or centromeric cohesion protection) is not defined. Biologically genuine but peripheral to the core mitotic and nutrient-signalling functions of the holoenzyme. Supporting Evidence: PMID:27455870 We suggest that Cdc55 is required for reductional chromosome segregation during achiasmate meiosis and this is independent of its FEAR function. PMID:27455870 Although the suppressor mutations in cdc55 affect reductional chromosome segregation in the absence of recombination, they have no effect on chromosome segregation during wild type meiosis.
GO:0061586 positive regulation of transcription by transcription factor localization	IMP PMID:23275436 Yeast protein phosphatase 2A-Cdc55 regulates the transcripti...	KEEP AS NON CORE	Summary: PP2A-Cdc55 (not PP2A-Rts1) is required for full induction of Msn2/4-dependent stress genes: it sustains nuclear accumulation of Msn2 and Msn4 during hyperosmotic stress and enhances Msn2 chromatin recruitment, without altering Hog1 signalling or the stress-induced dephosphorylation of the mapped Msn2 sites. Reason: The term fits the data (transcriptional activation through transcription-factor localisation/retention), and the phenotype is specific to Cdc55 and to Msn2/4-driven promoters. The mechanism is indirect (Msn2 itself is not detectably a PP2A-Cdc55 substrate at the sites examined), and the stress-transcription role is a secondary output of the nutrient/stress branch of PP2A-Cdc55 function rather than a core function, so it is kept as non-core. Supporting Evidence: PMID:23275436 We show that PP2A-Cdc55 contributes to sustained nuclear accumulation of Msn2 and Msn4 during hyperosmolarity stress. PMID:23275436 PP2A-Cdc55 also enhances Msn2-dependent transactivation, required for extended chromatin recruitment of the transcription factor. PMID:23275436 Thus, based on our analyses, the initial dephosphorylation of Msn2 is not controlled by PP2A-Cdc55.
GO:0071475 cellular hyperosmotic salinity response	IMP PMID:23275436 Yeast protein phosphatase 2A-Cdc55 regulates the transcripti...	KEEP AS NON CORE	Summary: cdc55Δ cells show reduced hyperosmotic (NaCl) induction of many Msn2/4 target genes, while Msn2/4-independent responses (copper, calcium) are unaffected. Reason: A response-to term that correctly records a reproducible mutant phenotype in the environmental stress response. It is downstream of the transcription-factor-retention role above and is not a core function of the phosphatase regulatory subunit. Supporting Evidence: PMID:23275436 We have identified Cdc55, a regulatory B subunit of protein phosphatase 2A (PP2A), as an essential activating factor for stress gene transcription in Saccharomyces cerevisiae. PMID:23275436 Furthermore, the Hog1 mitogen-activated protein kinase pathway activity is not influenced by PP2A-Cdc55.
GO:0090266 regulation of mitotic cell cycle spindle assembly checkpoint	IMP PMID:23886942 Nuclear PP2A-Cdc55 prevents APC-Cdc20 activation during the ...	ACCEPT	Summary: Cdc55 is essential for the spindle assembly checkpoint; SAC-specific cdc55 alleles and nucleocytoplasmic manipulation show that nuclear PP2A-Cdc55 keeps APC-Cdc20 dephosphorylated and inactive when the spindle is damaged, and Zds1/Zds2 restrain the SAC by excluding Cdc55 from the nucleus. Reason: CDC55 was recovered in two independent spindle-checkpoint screens and cdc55 mutants fail to arrest in nocodazole; this paper adds a nuclear target (APC-Cdc20) and separation-of-function alleles. Together with the Yellman/Burke demonstration that Cdc55 restrains Cdc14 release during checkpoint arrest, this is a core function. The 'regulation of' term is appropriate because Cdc55 is not part of the Mad/Bub signalling cascade but sustains the arrest it produces. Supporting Evidence: PMID:23886942 Cdc55, a regulatory B-subunit of protein phosphatase 2A (PP2A) complex, is essential for the spindle assembly checkpoint (SAC) in budding yeast PMID:23886942 APC-Cdc20 is kept inactive by dephosphorylation by nuclear PP2A-Cdc55 when spindle is damaged PMID:23886942 the Cdc55-binding proteins Zds1 and Zds2 inhibit both nuclear accumulation of Cdc55 and SAC activity PMID:16314395 This suggested that the checkpoint role of Cdc55 was not direct inhibition of APC Cdc20 as it is for Mad2.
GO:0090266 regulation of mitotic cell cycle spindle assembly checkpoint	IMP PMID:27191586 Identification of a mutation causing a defective spindle ass...	ACCEPT	Summary: The spindle-assembly-checkpoint defect of the sake yeast strain K1801 maps to a single Cdc55 R48P substitution, confirmed by molecular genetics. Reason: An independent, allele-level confirmation of the checkpoint requirement for Cdc55 in a natural isolate; the abstract-only cache states the result explicitly. Supporting Evidence: PMID:27191586 found 1 mutation, R48P of Cdc55, the PP2A regulatory B subunit that is important for the SAC PMID:27191586 we confirmed that the Cdc55-R48P mutation was responsible for the SAC-defect in K1801 by molecular genetic analyses
GO:1900182 positive regulation of protein localization to nucleus	IMP PMID:23275436 Yeast protein phosphatase 2A-Cdc55 regulates the transcripti...	KEEP AS NON CORE	Summary: PP2A-Cdc55 is needed for sustained nuclear accumulation of Msn2/Msn4 during hyperosmotic stress; an Msn2 allele lacking its NES is constitutively nuclear in cdc55Δ but still needs Cdc55 for full target-gene induction. Reason: Correct description of one of the two Msn2-directed effects in the paper (nuclear retention, plus an intranuclear chromatin-recruitment effect). Indirect at the substrate level and part of the stress-response branch, so non-core. Supporting Evidence: PMID:23275436 We show that PP2A-Cdc55 contributes to sustained nuclear accumulation of Msn2 and Msn4 during hyperosmolarity stress.
GO:1902531 regulation of intracellular signal transduction	IEA GO_REF:0000117	MODIFY	Summary: ARBA-predicted generic 'regulation of intracellular signal transduction'. Reason: Not wrong, but too general to be informative. The concrete signalling pathway PP2A-Cdc55 is known to regulate in budding yeast is the spindle assembly checkpoint (GO:0090266, an experimentally supported descendant of this term via the IMP rows), so the row should be resolved to that descendant rather than kept as a bare ancestor. Its other regulatory roles (Cdk1 activation at G2/M, Cdc14 release at mitotic exit) are already carried by specific experimental rows. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: ARBA:ARBA00027126 SUPPORTS TRANSFER The rule is biologically compatible with Cdc55 (it does regulate an intracellular signalling pathway) but stops at a level that conveys nothing about which one. Proposed replacements: regulation of mitotic cell cycle spindle assembly checkpoint Supporting Evidence: PMID:23886942 Cdc55, a regulatory B-subunit of protein phosphatase 2A (PP2A) complex, is essential for the spindle assembly checkpoint (SAC) in budding yeast PMID:23886942 APC-Cdc20 is kept inactive by dephosphorylation by nuclear PP2A-Cdc55 when spindle is damaged
GO:1905477 positive regulation of protein localization to membrane	IMP PMID:32029270 PP2A promotes ESCRT-0 complex formation on vacuolar membrane...	KEEP AS NON CORE	Summary: PP2A-Cdc55 promotes recruitment of the ESCRT-0 subunit Hse1 to vacuolar membranes after TORC1 inactivation (Vps27 localisation is unaffected). Reason: Accurately captures the paper's localisation result; a more specific child (positive regulation of protein localization to vacuolar membrane) does not exist in GO, so the general membrane term is the right available one. Part of the TORC1-downstream nutrient-signalling branch, non-core. Supporting Evidence: PMID:32029270 Loss of PP2A-Cdc55 compromised vacuolar localization of Hse1, but not Vps27.
GO:2000786 positive regulation of autophagosome assembly	IGI PMID:27973551 Orchestrated Action of PP2A Antagonizes Atg13 Phosphorylatio...	KEEP AS NON CORE	Summary: PP2A-Cdc55 and PP2A-Rts1 act redundantly downstream of TORC1 inactivation to dephosphorylate Atg13, activate Atg1 and permit PAS formation; the cdc55Δ rts1Δ double mutant is defective in rapamycin-induced non-selective autophagy while the Cvt pathway is intact. Reason: The IGI with RTS1 is exactly what was shown (single deletions have little effect; the double is defective). PP2A-Cdc55 does contribute directly to the initiating step (Atg13 dephosphorylation that licenses Atg1 activation), so a positive-regulation term is appropriate. It is one of several nutrient-signalling outputs of the holoenzyme and is graded non-core. Supporting Evidence: PMID:27973551 two protein phosphatase 2A (PP2A) phosphatases, PP2A-Cdc55 and PP2A-Rts1, which are activated by inactivation of TORC1, are required for sufficient Atg13 dephosphorylation and autophagy induction after TORC1 inactivation in budding yeast PMID:27973551 These indicated that PP2A-Cdc55 and PP2A-Rts1 have a redundant function in induction of TORC1 inactivation-induced (nonselective) autophagy.

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