ZDS1 (YMR273C; historical synonyms include HST1, CES1, NRC1 and OSS1) encodes a 915-residue, fungus-specific, non-catalytic regulator of the PP2A phosphatase that carries the B-type regulatory subunit Cdc55 (PP2A-Cdc55). Through its conserved C-terminal Zds_C motif, Zds1 binds Cdc55 and forms a tight stoichiometric complex with PP2A-Cdc55. Together with its paralog Zds2, it determines where the phosphatase is located and which substrates it acts on: Zds1/Zds2 keep PP2A-Cdc55 in the cytoplasm and at the bud cortex, exclude it from the nucleus, and target it to the Cdc25-family phosphatase Mih1. Through this, Zds1 promotes Cdk1 activation and mitotic entry. At anaphase onset, Zds1 acts downstream of separase to down-regulate PP2A-Cdc55 activity towards Net1, allowing Cdk-dependent Net1 phosphorylation and timely release of Cdc14 from the nucleolus (the FEAR pathway). Zds1 localizes to the cytoplasm, presumptive bud sites, the bud cortex/bud tip and, in late mitosis, the bud neck. At the bud cortex, the Zds1/Zds2-PP2A-Cdc55 complex acts as a Rho1 effector that biases Rho1 output towards polarized growth and glucan synthesis and away from cell wall integrity signalling. Additional reported roles include interaction with the mRNA export factors Dbp5 and Gfd1 at the cytoplasmic face of the nuclear pore, and effects on rDNA, mating-type and telomeric silencing and on replicative life span.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Zds1 is a cytoplasmic and cortical protein that binds Cdc55 and controls PP2A-Cdc55 localization. The cytoplasm IBA was placed by PAINT at the fungal Zds1/Zds2 node PANTHER:PTN001999034 and is supported by direct experimental evidence for both S. cerevisiae paralogs. Reason: Zds1 localizes exclusively to the cytoplasm and cortex, being excluded from the nucleus throughout the cell cycle. This is central to its function as a Cdc55 localization regulator. Multiple experimental studies confirm cytoplasmic/cortical localization via GFP-tagging and immunofluorescence. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001999034 Β· Zds1/Zds2 fungal ancestral node (PTHR28089) SUPPORTS TRANSFER PAINT places the cytoplasm IBD at the fungal Zds1/Zds2 ancestor, and both budding-yeast paralogs have direct cytoplasmic/cortical localization evidence, so ZDS1 correctly inherits this broad core localization. Supporting Evidence: PMID:21536748 Zds1-GFP and Zds2-GFP localized to the bud cortex of small to medium budded cells...Zds1 and Zds2 were excluded from the nucleus, as judged by DAPI staining of the nucleus throughout the cell cycle PMID:8816439 A glutathione S-transferase-Zds1p fusion protein that fully complemented the double mutant localized to presumptive bud sites and the tips of small buds |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IBA GO_REF:0000033 | ACCEPT | Summary: Zds1 promotes mitotic entry by regulating Cdc55 localization, enabling Cdk1 activation. PAINT places the G2/M regulation IBD at PANTHER:PTN001999034, the fungal ancestor of Zds1 and Zds2, consistent with the shared budding-yeast paralog evidence. Reason: Zds1 positively regulates G2/M transition by promoting cytoplasmic localization of Cdc55-PP2A and targeting its activity to the Cdc25-family phosphatase Mih1 (but not to the Wee1 kinase Swe1); Mih1 dephosphorylation promotes Cdk1 activation. zds1Ξ zds2Ξ mutants show prolonged G2 delay with abnormally elongated cell morphology. This positive role in mitotic entry is well-established and core to Zds1's function. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001999034 Β· Zds1/Zds2 fungal ancestral node (PTHR28089) SUPPORTS TRANSFER The PTN001999034 IBD is supported by direct budding-yeast ZDS1 and ZDS2 evidence for positive regulation of G2/M transition, and ZDS1 remains inside the clade that inherited this PP2A-Cdc55 mitotic entry role. Supporting Evidence: PMID:21536748 zds1Ξ zds2Ξ double mutant leads to abnormally elongated cell morphology as a consequence of prolonged G2 delay...Zds1/Zds2 are thought to function positively with Cdc55βPP2A to promote mitotic entry PMID:21536748 Both cdc55Ξ and zds1Ξ zds2Ξ exhibited abnormally elongated bud morphology at all the temperatures tested |
| GO:0030010 establishment of cell polarity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Zds1 contributes to cell polarity through multiple mechanisms including Cdc55-mediated regulation and Rho1 effector functions. IBA annotation is appropriate given experimental evidence for polarity defects in zds1Ξ zds2Ξ mutants. Reason: Zds1 has dual roles in cell polarity. First, as a negative regulator of Cdc42, it was originally identified in screens for polarity genes. Second, as a Rho1 effector at the bud cortex, it associates with Cdc55 to specify Rho1 output toward polarized growth. zds1Ξ zds2Ξ mutants show severe polarity defects including abnormal morphogenesis and bud morphology. The term appropriately captures Zds1's documented roles in establishing and maintaining polarized growth. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001999034 Β· Zds1/Zds2 fungal ancestral node (PTHR28089) SUPPORTS TRANSFER The fungal Zds1/Zds2 ancestor is supported by direct ZDS1 and ZDS2 polarity evidence. The transfer is sound, but the process is kept non-core because polarity phenotypes are secondary to Zds1's PP2A-Cdc55 adaptor/localization role. Supporting Evidence: PMID:8816439 A genetic screen for GTPase-activating proteins (GAPs) or other negative regulators of the Rac/Rho family GTPase Cdc42p in Saccharomyces cerevisiae identified ZDS1...the zds1 zds2 double mutant grew slowly with an apparent mitotic delay and produced elongated cells and buds with other evidence of abnormal morphogenesis PMID:21536748 Cdc55 localizes to various sites, including the bud cortex...Zds1/Zds2 interact with cell polarity proteins of the Cdc42- and the Rho1-signaling pathways both physically and genetically PMID:26728856 Zds1/Zds2-PP2A(Cdc55) promotes polarized growth and cell wall synthesis by inhibiting Rho1 GTPase-activating protein (GAP) Lrg1 but inhibits CWI pathway by stabilizing another Rho1 GAP, Sac7 file:yeast/ZDS1/ZDS1-deep-research-falcon.md As a Rho1 effector, the Zds1/Zds2βPP2A-Cdc55 complex biases Rho1 signaling toward polarized growth and Ξ²-1,3-glucan synthesis by inhibiting the GAP Lrg1, while antagonizing CWI signaling via stabilization of the GAP Sac7 |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt-derived IEA annotation for cytoplasmic localization based on subcellular location vocabulary. This is consistent with IDA and IBA annotations and experimental evidence. Reason: This IEA annotation derives from UniProt subcellular location mapping. It is consistent with and supported by direct experimental evidence (IDA and IBA annotations). UniProt correctly classifies Zds1 as cytoplasmic based on well-characterized localization studies. Supporting Evidence: PMID:21536748 Zds1, Zds2, and Cdc55 also exist in the cytoplasm and are excluded from the vacuole |
| GO:0005515 protein binding | IPI PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | REMOVE | Summary: IPI annotation for binding interactions detected with Dbp5 (P20449) and Gfd1 (Q04839) from two-hybrid and in vitro binding experiments. The interactions are real, but the generic protein binding term does not describe a molecular function. Reason: Zds1 physically interacts with Dbp5 and Gfd1 at the nuclear pore complex for mRNA export function. However, GO:0005515 is too vague and the cited paper does not establish a more specific molecular-function term for the Dbp5/Gfd1 interaction. The interaction evidence remains useful support for the mRNA export annotations, but the generic binding row should be removed rather than retained as a standalone function. Supporting Evidence: PMID:15619606 By using the two-hybrid system, we showed that Zds1p interacts in vivo with both Gfd1p and Dbp5p. In vitro binding experiments revealed that Gfd1p and Dbp5p bind directly to the C-terminal part of Zds1p |
| GO:0031507 heterochromatin formation | IMP PMID:10662670 Two paralogs involved in transcriptional silencing that anta... | KEEP AS NON CORE | Summary: ZDS1 deletion redistributes silencing among rDNA, a silent mating-type cassette, and telomeres, but chromatin regulation is secondary to Zds1's PP2A-Cdc55 adaptor function. Reason: The cited study directly assayed ZDS1 and found altered silencing at three heterochromatic loci. Retain the experimentally supported process while keeping it non-core because the mechanism is indirect and the principal conserved role of Zds1 is spatial regulation of PP2A-Cdc55. Supporting Evidence: PMID:10662670 deletion of the ZDS1 gene caused an increase in silencing in the rDNA and at a silent mating-type cassette at the expense of telomere silencing. |
| GO:0004864 protein phosphatase inhibitor activity | IMP PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho... | MODIFY | Summary: Ectopic Zds1 expression in metaphase-arrested cells roughly halved the specific activity of immunopurified PP2A-Cdc55 and promoted Net1 phosphorylation and Cdc14 release. This is direct experimental evidence that Zds1 can inhibit PP2A-Cdc55 in the mitotic-exit context. Reason: The measurement is real: ectopic Zds1 reduced PP2A-Cdc55 specific activity, which demonstrates that Zds1 binds and modulates the phosphatase. Inhibitor, however, captures only the context-specific (anaphase/Net1), overexpression-based output. Zds1 also activates PP2A-Cdc55 towards Mih1 and promotes its cytoplasmic function at mitotic entry, and the same group later argued that the low-abundance Zds proteins are unlikely to be direct inhibitory subunits. The parent term protein phosphatase regulator activity (GO:0019888) represents the experimentally supported activity without fixing its sign, consistent with the MODIFY of the IBA row. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:18762578 The PP2ACdc55 phosphatase-specific activity decreased to about half of its initial value in response to Zds1 induction PMID:18762578 Ectopic Zds1 expression in turn is sufficient to down-regulate PP2A(Cdc55) and promote Net1 phosphorylation. PMID:22427694 Therefore, it seems unlikely that Zds1p and Zds2p act as direct inhibitory components of the PP2ACdc55 complex. |
| GO:0004864 protein phosphatase inhibitor activity | IGI PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho... | MODIFY | Summary: Genetic interaction with CDC55 (SGD:S000003158). In cdc55 cells, Cdc14 release no longer depends on Zds1/Zds2, placing PP2A-Cdc55 downstream of Zds1 in the control of Cdc14 release. Reason: The epistasis shows that Zds1 acts through PP2A-Cdc55 and is consistent with Zds1 restraining PP2A-Cdc55 at mitotic exit. As for the IMP row, the inhibitory output is real but context-specific, and Zds1 also activates PP2A-Cdc55 towards Mih1. The broader protein phosphatase regulator activity (GO:0019888) is the appropriate molecular-function term. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:18762578 Therefore, Zds1 and Zds2 no longer influence Cdc14 release from the nucleolus in the absence of Cdc55. This is consistent with the possibility that PP2ACdc55 acts as the downstream target of Zds1 and Zds2, and that the two paralogues act in its inhibition. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IGI PMID:20980617 Zds2p regulates Swe1p-dependent polarized cell growth in Sac... | ACCEPT | Summary: Genetic interaction with CDC55 (SGD:S000003158). Deletion of CDC55 rescues zds1 zds2 bud morphology, and the ability of GAL-ZDS1 to override the Swe1 checkpoint requires CDC55. Reason: The epistasis places Zds1 upstream of PP2A-Cdc55 in promoting mitotic entry through the Swe1-dependent checkpoint. This is one of Zds1's core regulatory roles. Supporting Evidence: PMID:20980617 This negative regulation requires the CDC55 gene. PMID:21536748 Both Cdc55 and Zds1/Zds2 are important for mitotic entry |
| GO:0000131 incipient cellular bud site | IDA PMID:8816439 ZDS1 and ZDS2, genes whose products may regulate Cdc42p in S... | KEEP AS NON CORE | Summary: IDA annotation for Zds1 localization to incipient bud sites in G1 phase cells. This is supported by direct observation of GST-Zds1 fusion protein localization. Reason: Zds1 localizes to presumptive bud sites in unbudded cells and to bud tips in early budding cells. This localization is consistent with its role in cell polarity establishment and cortical signaling. Direct evidence from GST-Zds1 localization studies confirms this subcellular compartmentalization. Supporting Evidence: PMID:8816439 A glutathione S-transferase-Zds1p fusion protein that fully complemented the double mutant localized to presumptive bud sites and the tips of small buds |
| GO:0005737 cytoplasm | IDA PMID:21536748 Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitot... | ACCEPT | Summary: IDA annotation for cytoplasmic localization from direct observation of endogenous Zds1-GFP throughout the cell cycle. Consistent with all other localization evidence. Reason: Direct fluorescence microscopy confirms Zds1-GFP localizes to the cytoplasm throughout the cell cycle. This is core evidence supporting Zds1's function as a cytoplasmic regulator of Cdc55 localization. The IDA evidence type is appropriate for direct visualization. Supporting Evidence: PMID:21536748 Zds1-GFP and Zds2-GFP localized to the bud cortex of small to medium budded cells...Zds1, Zds2, and Cdc55 also exist in the cytoplasm and are excluded from the vacuole |
| GO:0005934 cellular bud tip | IDA PMID:8816439 ZDS1 and ZDS2, genes whose products may regulate Cdc42p in S... | KEEP AS NON CORE | Summary: IDA annotation for Zds1 localization to bud tips in developing buds. Direct evidence from GST-Zds1 fusion protein imaging confirms bud tip enrichment. Reason: Zds1 concentrates at bud tips, especially in small to medium-sized buds, which is consistent with its role in cell polarity and polarized growth regulation. This subcellular localization is relevant to understanding where Zds1 exerts its regulatory functions on the Rho1 and Cdc42 signaling pathways. Supporting Evidence: PMID:8816439 A glutathione S-transferase-Zds1p fusion protein that fully complemented the double mutant localized to presumptive bud sites and the tips of small buds PMID:21536748 We also observed bud neck localization of Zds1-GFP and Zds2-GFP in late mitotic cells |
| GO:0005935 cellular bud neck | IDA PMID:21536748 Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitot... | KEEP AS NON CORE | Summary: IDA annotation for Zds1 localization to the bud neck in late mitotic cells. Direct fluorescence imaging confirms this dynamic localization change. Reason: Zds1 relocates to the bud neck during late mitosis, coinciding with its roles in regulating mitotic exit and cytokinesis. This dynamic localization pattern reflects Zds1's cell cycle-dependent functions in controlling Cdc55 localization during different mitotic phases. The IDA evidence from endogenous Zds1-GFP is solid. Supporting Evidence: PMID:21536748 We also observed bud neck localization of Zds1-GFP and Zds2-GFP in late mitotic cells PMID:21536748 Cdc55-GFP localized to the bud cortex of small to medium budded cells and to the bud neck in late mitotic cells |
| GO:0006406 mRNA export from nucleus | IMP PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | KEEP AS NON CORE | Summary: IMP annotation for Zds1 requirement in mRNA export based on genetic analysis of export-deficient mutants. Zds1 is part of the mRNA export machinery at the NPC. Reason: Zds1 is a functional component of the mRNA export machinery, associating with Dbp5 and Gfd1 at the cytoplasmic fibrils of the nuclear pore complex. Deletion of ZDS1 exacerbates mRNA export defects in dbp5 and mex67 mutants, indicating Zds1 is required for optimal mRNA export. While this is a secondary function of Zds1 compared to its primary cell cycle role, it is well-documented and appropriately characterized as a biological process. Supporting Evidence: PMID:15619606 Zds1p associates with the complex formed by Dbp5p, Gfd1p, and nucleoporins at the cytosolic fibrils of the nuclear pore complex and is required for optimal mRNA export PMID:15619606 deletion of ZDS1 or of both ZDS1 and the closely related ZDS2 exacerbated the poly(A)+ export defects shown by dbp5-2 and mex67-5 mutants |
| GO:0006406 mRNA export from nucleus | IGI PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | KEEP AS NON CORE | Summary: Genetic interaction with GFD1 (SGD:S000004868), a Dbp5-associated mRNA export factor. It supports the IMP evidence that Zds1 contributes to optimal mRNA export. Reason: Genetic interactions between ZDS1 and mRNA export genes, together with direct binding of Gfd1 and Dbp5 to the Zds1 C terminus, support a contributory role in mRNA export. The role is secondary to Zds1's PP2A-Cdc55 regulatory function. Supporting Evidence: PMID:15619606 ZDS1 interacted genetically with mutant alleles of genes encoding key factors in mRNA export, including DBP5 and MEX67 |
| GO:0006406 mRNA export from nucleus | IPI PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | KEEP AS NON CORE | Summary: Physical interaction with Gfd1 (SGD:S000004868) by two-hybrid and in vitro binding to the Zds1 C terminus. Reason: Direct binding of Gfd1 to Zds1 supports Zds1 association with the Dbp5-Gfd1-nucleoporin complex at the cytoplasmic face of the nuclear pore. This role is non-core relative to PP2A-Cdc55 regulation. Supporting Evidence: PMID:15619606 By using the two-hybrid system, we showed that Zds1p interacts in vivo with both Gfd1p and Dbp5p. In vitro binding experiments revealed that Gfd1p and Dbp5p bind directly to the C-terminal part of Zds1p |
| 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: IMP annotation for positive regulation of G2/M transition from detailed experimental analysis of mitotic entry defects. This represents definitive evidence for Zds1's core function. Reason: Experimental studies directly demonstrate that Zds1 promotes G2/M transition through spatial control of Cdc55. The zds1Ξ zds2Ξ mutant exhibits severe G2 delay, abnormal morphology, and elevated Cdc28-Y19 phosphorylation. Introduction of a cytoplasm-localized Cdc55-NES fully rescues these defects, proving the sufficiency and necessity of Zds1-mediated Cdc55 cytoplasmic localization for mitotic entry. This is a definitional core function of Zds1. Supporting Evidence: PMID:21536748 zds1Ξ zds2Ξ double mutant leads to abnormally elongated cell morphology as a consequence of prolonged G2 delay |
| GO:0030010 establishment of cell polarity | IMP PMID:8816439 ZDS1 and ZDS2, genes whose products may regulate Cdc42p in S... | KEEP AS NON CORE | Summary: IMP annotation for cell polarity based on morphological and genetic analysis of zds1Ξ zds2Ξ mutants showing severe polarity defects and abnormal cell shape. Reason: Zds1 is established as important for cell polarity establishment through multiple lines of evidence: first, it was identified as a negative regulator of the Cdc42 GTPase in polarity screens; second, zds1Ξ zds2Ξ mutants show severe abnormal morphology indicating polarity defects; and third, it functions as a Rho1 effector at the bud cortex to specify growth outputs. The IMP annotation appropriately captures this documented role. Supporting Evidence: PMID:8816439 However, the zds1 zds2 double mutant grew slowly with an apparent mitotic delay and produced elongated cells and buds with other evidence of abnormal morphogenesis PMID:21536748 Zds1/Zds2 interact with cell polarity proteins of the Cdc42- and the Rho1-signaling pathways both physically and genetically |
| GO:0030010 establishment of cell polarity | IGI PMID:8816439 ZDS1 and ZDS2, genes whose products may regulate Cdc42p in S... | KEEP AS NON CORE | Summary: IGI annotation for cell polarity based on genetic interactions with Cdc42, Rho1, and other polarity proteins. Multiple genetic interactions confirm Zds1's polarity role. Reason: Genetic interaction studies establish Zds1 as a functional component of cell polarity networks, particularly through interactions with Cdc42 and Rho1 signaling pathways. These genetic interactions corroborate the IMP findings and demonstrate Zds1 works coordinately with known polarity regulators. Supporting Evidence: PMID:8816439 The similarity of this localization to that of Cdc42p suggests that Zds1p may interact directly with Cdc42p PMID:21536748 Zds1/Zds2 interact with cell polarity proteins of the Cdc42- and the Rho1-signaling pathways both physically and genetically |
| GO:0032880 regulation of protein localization | IMP PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho... | MODIFY | Summary: zds1 cells show delayed nucleolar release of Cdc14 in early anaphase. Later work showed that Zds1/Zds2 also control the nucleocytoplasmic distribution of Cdc55 itself, and Zds1 regulates Cdc55 localization through its Zds_C motif. Reason: Regulating where proteins are located is central to how Zds1 works, but this parent term is broader than its two readouts. Zds1 keeps PP2A-Cdc55 in the cytoplasm/cortex and out of the nucleus, and it promotes timely release of Cdc14 from the nucleolus in early anaphase. Both are captured by negative regulation of protein localization to nucleus; the nucleolar term (GO:1904750) is a subclass of it and is not added separately. Both readouts are direct consequences of Zds1's PP2A-Cdc55 regulatory activity. Proposed replacements: negative regulation of protein localization to nucleus Supporting Evidence: PMID:18762578 In contrast, in zds1Ξ cells, Cdc14 release from the nucleolus was retarded by 10 min PMID:21536748 Cortical and cytoplasmic localization of Cdc55 requires Zds1/Zds2, and Cdc55 accumulates in the nucleus in the absence of Zds1/Zds2. PMID:22427694 Zds1p physically interacts with, and regulates the localization of, Cdc55p through the Zds_C motif. |
| GO:0004864 protein phosphatase inhibitor activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBD at the fungal Zds node PTN001999034, seeded only by ZDS1 itself (SGD:S000004886). The seed is ZDS1's own experimental evidence that ectopic Zds1 halves the specific activity of immunopurified PP2A-Cdc55 in metaphase-arrested cells. That ZDS1 is among its own sources is expected and is not circular. The inhibitor term describes only one context-dependent output of Zds1's regulation of PP2A-Cdc55. Reason: Zds1 clearly binds and modulates PP2A-Cdc55, but the inhibitor label is too narrow and partly contradicted. Zds1/Zds2 are strictly required for PP2A-Cdc55-dependent dephosphorylation of Mih1, an activating, substrate-targeting role. They maintain the cytoplasmic pool of PP2A-Cdc55 that promotes mitotic entry, and the Queralt lab later concluded that Zds proteins are unlikely to be direct inhibitory components of PP2A-Cdc55. Their effect is better described by the parent term protein phosphatase regulator activity (GO:0019888), which covers both the activating and the inhibitory outputs. The context-specific inhibitory evidence is retained on the experimental IMP row as non-core. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001999034 SUPPORTS TRANSFER The node correctly places a PP2A-Cdc55 regulatory function at the fungal Zds ancestor, and ZDS1 is the seed. The inhibitor-specific term reflects only the mitotic-exit (Net1/Cdc14) output of the overexpression experiment, not the Mih1-targeting and cytoplasmic-retention outputs, so the parent regulator term is the safer ancestral assertion. Proposed replacements: protein phosphatase regulator activity Supporting Evidence: PMID:18762578 The PP2ACdc55 phosphatase-specific activity decreased to about half of its initial value in response to Zds1 induction PMID:21119008 Thus, Zds1/2 activate PP2ACdc55-dependent dephosphorylation of Mih1. PMID:21536748 Zds1/Zds2 promote Cdc55-PP2A function for mitotic entry, whereas Zds1/Zds2 inhibit Cdc55-PP2A function during mitotic exit. PMID:22427694 Therefore, it seems unlikely that Zds1p and Zds2p act as direct inhibitory components of the PP2ACdc55 complex. |
| GO:0005515 protein binding | IPI PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | REMOVE | Summary: Two-hybrid and in vitro binding of Zds1 to the mRNA export factor Gfd1 (Q04839) through the Zds1 C-terminal region. Reason: The interaction is real and supports the mRNA-export process rows, but generic protein binding is not an informative molecular function, and the paper does not establish a more specific activity for Zds1 in this complex. Removing the row does not dispute the interaction. Supporting Evidence: PMID:15619606 In vitro binding experiments revealed that Gfd1p and Dbp5p bind directly to the C-terminal part of Zds1p. |
| GO:0006406 mRNA export from nucleus | IGI PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | KEEP AS NON CORE | Summary: Genetic interaction with DBP5 (SGD:S000005572). Deletion of ZDS1 exacerbates the poly(A)+ RNA export defect of dbp5-2 cells. Reason: The genetic interaction is experimentally documented (abstract-only cache; deferring to the curator's full-text reading) and supports a contributory role of Zds1 in optimal mRNA export. This role is peripheral to Zds1's main function as a PP2A-Cdc55 regulator, and whether it is mediated by PP2A-Cdc55 is unknown. Supporting Evidence: PMID:15619606 deletion of ZDS1 or of both ZDS1 and the closely related ZDS2 exacerbated the poly(A)+ export defects shown by dbp5-2 and mex67-5 mutants |
| GO:0006406 mRNA export from nucleus | IPI PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | KEEP AS NON CORE | Summary: Physical interaction with Dbp5 (SGD:S000005572), the DEAD-box mRNA export helicase, by two-hybrid and in vitro binding to the Zds1 C terminus. Reason: Direct binding to Dbp5, together with the genetic data, supports a role for Zds1 at the cytoplasmic face of the nuclear pore in optimal mRNA export. This role is non-core relative to PP2A-Cdc55 regulation. Supporting Evidence: PMID:15619606 We proposed that Zds1p associates with the complex formed by Dbp5p, Gfd1p, and nucleoporins at the cytosolic fibrils of the nuclear pore complex and is required for optimal mRNA export. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IGI PMID:20980617 Zds2p regulates Swe1p-dependent polarized cell growth in Sac... | ACCEPT | Summary: Genetic interaction with the paralog ZDS2 (SGD:S000004577). The aberrant bud morphology and G2/M phenotype appear only in zds1 zds2 double mutants, and GAL-ZDS1 can force mitotic entry when the Swe1 checkpoint is active. Reason: The ZDS1/ZDS2 redundancy is the basis of the IGI. Together with the CDC55 epistasis from the same paper, it supports a positive regulatory role for Zds1 in the G2/M transition via PP2A-Cdc55. Supporting Evidence: PMID:20980617 We also show that expression of ZDS1 or ZDS2 from a strong galactose-inducible promoter can induce mitosis even when the Swe1p-dependent G2/M checkpoint is activated by mis-organization of the actin cytoskeleton. PMID:20980617 deletion of CDC55 rescues the aberrant bud morphology of a zds1Ξzds2Ξ strain |
| GO:0030010 establishment of cell polarity | IGI PMID:8816439 ZDS1 and ZDS2, genes whose products may regulate Cdc42p in S... | KEEP AS NON CORE | Summary: Genetic interaction with CDC42 (SGD:S000004219). Zds1 was isolated in a screen for negative regulators of Cdc42, and its overexpression lowers Cdc42 activity. Reason: The genetic relationship with CDC42 is documented (abstract-only cache; deferring to the curator's reading). Zds1 has no Rho-GAP homology, and its polarity effects are now understood to be mediated largely through PP2A-Cdc55, the Swe1 checkpoint and Rho1 effector output. The polarity process is therefore secondary. Supporting Evidence: PMID:8816439 it appears that overexpression of either Zds1p or Zds2p decreases the level of Cdc42p activity |
| GO:0030010 establishment of cell polarity | IGI PMID:8816439 ZDS1 and ZDS2, genes whose products may regulate Cdc42p in S... | KEEP AS NON CORE | Summary: Genetic interaction with ZDS2 (SGD:S000004577). Single mutants have mild or no phenotypes, whereas zds1 zds2 double mutants have elongated cells and buds with abnormal morphogenesis. Reason: The redundant requirement is experimentally documented. Polarity defects are a downstream consequence of PP2A-Cdc55 dysregulation (the Swe1-dependent G2 delay and Rho1 output), so the process is retained as non-core. Supporting Evidence: PMID:8816439 Deletion analysis also suggests that Zds1p and Zds2p are at least partially overlapping in function. PMID:8816439 However, the zds1 zds2 double mutant grew slowly with an apparent mitotic delay and produced elongated cells and buds with other evidence of abnormal morphogenesis. |
| GO:0031536 positive regulation of exit from mitosis | IMP PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho... | NEW | Summary: Proposed process annotation. Zds1 is required downstream of separase for timely early-anaphase (FEAR) release of Cdc14 from the nucleolus. Ectopic Zds1 is sufficient to release Cdc14 and rescues the MEN mutant cdc15-2. Reason: Participation test: Zds1 does regulatory work in this process. It binds Cdc55 through the Zds_C motif and down-regulates nuclear PP2A-Cdc55 activity towards Net1, which permits Cdk-dependent Net1 phosphorylation and Cdc14 release. This is a regulator role, matching the "regulation of" term. Comparator check: other FEAR-pathway and phosphatase regulators of mitotic exit in S. cerevisiae carry this term (ESP1 IMP/IGI, LTE1 IMP, GLC7 IGI), and CDC55 carries the opposing negative regulation of exit from mitosis. ZDS1, which occupies the same regulator role, currently has no mitotic-exit term. Supporting Evidence: PMID:18762578 Zds1 and Zds2 are required downstream of separase to facilitate nucleolar Cdc14 release. PMID:22427694 Zds1p is required for timely Cdc14p activation during anaphase. PMID:22427694 Strikingly, the fusion construct containing the Zds1p N-terminal region from residues 1 to 460 fused to the Zds_C motif (zds1Ξ461β802) induces timely nucleolar Cdc14 release at endogenous levels and can suppress the synthetic growth defect of the cdc15-2 and zds1Ξ zds2Ξ mutations. |
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Download this section (compressed HTML)Q: Should the PAINT IBD at PANTHER:PTN001999034 assert protein phosphatase regulator activity (GO:0019888) rather than protein phosphatase inhibitor activity (GO:0004864)? The only seed is the ZDS1 overexpression IMP, while Zds1/Zds2 also activate PP2A-Cdc55 towards Mih1 and promote its cytoplasmic function.
Q: How does separase convert Zds1 from a PP2A-Cdc55 targeting factor into a down-regulator at anaphase onset? Do cell-cycle-dependent phosphorylation sites on Zds1 switch its effect on substrate selection?
Experiment: Purify PP2A-Cdc55 with and without stoichiometric Zds1 (or the Zds_C fragment) and measure dephosphorylation kinetics of Cdk1-phosphorylated Mih1, Net1 and Swe1 and of a generic phosphopeptide. Include phosphomimetic/non-phosphorylatable Zds1 mutants at the cell-cycle-regulated sites.
Hypothesis: Zds1 changes PP2A-Cdc55 activity in a substrate-selective way rather than inhibiting catalysis globally.
Type: in vitro reconstitution and phosphatase kinetics
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Download this section (compressed HTML)Protein with a role in regulating Swe1p-dependent polarized growth; involved in maintaining Cdc55p in the cytoplasm where it promotes mitotic entry; involved in mitotic exit through Cdc14p regulation; interacts with silencing proteins at telomeres; has a role in Bcy1p localization; implicated in mRNA nuclear export; ZDS1 has a paralog, ZDS2, that arose from the whole genome duplication
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