ZDS1 (historically also called HST1) encodes a cortical/cytoplasmic adaptor protein that regulates the spatial localization and activity of the PP2A phosphatase complex containing the regulatory subunit Cdc55. Zds1 functions as a non-catalytic scaffold that binds Cdc55 and controls its nucleocytoplasmic distribution, thereby regulating two key mitotic transitions: (1) promoting mitotic entry by maintaining Cdc55-PP2A in the cytoplasm where it dephosphorylates Swe1 and activates Mih1 to enable Cdk1 activation, and (2) facilitating mitotic exit by excluding Cdc55 from the nucleus to prevent inhibition of Cdc14 release. Additionally, Zds1 serves as a Rho1 effector at the bud cortex, where it associates with Cdc55 to specify Rho1 signaling outputs toward polarized growth and cell wall synthesis while antagonizing stress-responsive CWI signaling. Zds1 also participates in mRNA export from the nucleus via interactions with Dbp5 and Gfd1 at the nuclear pore complex.
| 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. IBA annotation from phylogenetic inference is appropriate given extensive experimental evidence for cytoplasmic localization. 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. 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 file:yeast/ZDS1/ZDS1-deep-research-falcon.md model: Edison Scientific Literature |
| 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. IBA annotation is supported by multiple experimental studies demonstrating the role of Zds1 in G2/M progression. Reason: Zds1 positively regulates G2/M transition by promoting cytoplasmic localization of Cdc55-PP2A, which dephosphorylates inhibitory Swe1 kinase and activates Mih1, thereby enabling 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. 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. 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 |
| 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:0051028 mRNA transport | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: The broad mRNA transport IEA annotation reflects Zds1 interactions with Dbp5 and Gfd1 but is redundant with the more specific experimental annotations for mRNA export from the nucleus. Reason: Zds1 associates with the mRNA export machinery at the nuclear pore complex, interacting with Dbp5 (essential DEAD box helicase for mRNA export) and Gfd1. This broad parent is redundant with the directly supported, more specific GO:0006406 mRNA export from nucleus annotations and is therefore over-annotated. 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 Dbp5p and Gfd1p interact with Zds1p...In vitro binding experiments revealed that Gfd1p and Dbp5p bind directly to the C-terminal part of Zds1p |
| GO:0071555 cell wall organization | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Zds1 influences cell wall organization through Rho1 signaling and Cdc55 localization, a supported but secondary consequence of its core PP2A-Cdc55 regulatory role. Reason: Zds1 regulates cell wall organization through its role as a Rho1 effector at the bud cortex. In complex with Cdc55, Zds1 biases Rho1 signaling toward anabolic cell wall synthesis (beta-1,3-glucan synthesis) while antagonizing catabolic CWI (cell wall integrity) stress signaling. zds1Ξ zds2Ξ mutants show reduced glucan synthesis and increased chitin deposition, indicating altered cell wall composition. The term appropriately encompasses Zds1's documented role in organizing cell wall biosynthetic processes. Supporting Evidence: PMID:21536748 Cdc55 is important for mitosis, stress response, and polarized growth...Zds1/Zds2 interact with cell polarity proteins of the Cdc42- and the Rho1-signaling pathways |
| GO:0005515 protein binding | IPI PMID:15619606 Physical and genetic interactions link the yeast protein Zds... | MARK AS OVER ANNOTATED | Summary: IPI annotation for binding interactions detected with Dbp5 (P20449) and Gfd1 (Q04839) from two-hybrid and in vitro binding experiments. While protein binding is accurate, it is an overly general term that obscures the specific biochemical function. Reason: Zds1 physically interacts with Dbp5 and Gfd1 at the nuclear pore complex for mRNA export function. However, GO:0005515 (protein binding) is too vague and undescriptive. The more informative core annotations should focus on Zds1's specific binding roles, such as "Cdc55 binding" or its functional outcomes (mRNA export). Generic protein binding annotations are discouraged in modern GO curation. This IPI annotation serves as supporting evidence for specific molecular interactions but should not be considered a core functional annotation. 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:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MARK AS OVER ANNOTATED | Summary: IPI annotation from proteome survey detecting protein interactions in large-scale binding experiments. Generic protein binding annotation; see other instances for same term. Reason: This is a proteomics-derived IPI annotation from a large-scale protein interaction survey. While detecting multiple binding partners, generic protein binding annotations provide minimal functional information and are not considered informative molecular function descriptors in modern curation. Specific interaction annotations and downstream functional terms are preferred. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: IPI annotation from global yeast protein complex analysis. Generic protein binding annotation from high-throughput interaction data; see rationale for other protein binding instances. Reason: Large-scale high-throughput protein complex mapping identifies Zds1 interactors but provides minimal specificity regarding molecular function. Generic protein binding annotations from proteomics studies are too broad to be primary functional descriptors. More specific information (Cdc55-binding adaptor, mRNA export factor) is preferred. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho... | MARK AS OVER ANNOTATED | Summary: IPI annotation for binding to Tpd3, the PP2A scaffold subunit, during mitosis. This interaction supports Zds1's regulatory role but generic protein binding is not an informative molecular function. Reason: Zds1 associates with Tpd3 and Cdc55 in the PP2A-Cdc55 regulatory context, but this binding is instrumental to Zds1's primary regulatory function rather than a primary molecular function itself. Generic protein binding terminology obscures the actual mechanism. The biological process terms better capture Zds1's role. Supporting Evidence: PMID:18762578 In immunoprecipitates of Zds1 from metaphase-arrested cells, we detected Cdc55 as well as the PP2A scaffold subunit, Tpd3 by Western blotting. |
| GO:0005515 protein binding | IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ... | MARK AS OVER ANNOTATED | Summary: IPI annotation from chaperone-protein interaction atlas. Generic protein binding from large-scale interaction mapping; consistent with other instances of this term. Reason: Large-scale chaperone interaction studies identify Zds1 as a protein interaction hub, but generic "protein binding" is insufficiently specific. Zds1's functional interactions (Cdc55 binding, Dbp5/Gfd1 interaction) are better characterized through more specific molecular functions and biological processes. Supporting Evidence: PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces cerevisiae: implications to protein folding pathways in the cell. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: IPI annotation from recent structural and functional analysis of yeast protein interactome architecture. Generic binding annotation from modern interaction mapping. Reason: Recent high-resolution interactome study identifies Zds1 protein interactions but provides minimal functional specificity. Modern protein interaction data is better expressed through specific molecular function terms or biological process annotations that capture functional context. Supporting Evidence: PMID:37968396 Nov 15. The social and structural architecture of the yeast protein interactome. |
| 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... | ACCEPT | Summary: Zds1 down-regulates PP2A-Cdc55 at anaphase onset, although spatial redistribution is also central to its broader mechanism. Reason: PMID:18762578 directly shows that ectopic Zds1 is sufficient to down-regulate PP2A-Cdc55 and frames Zds1/Zds2 as PP2A-Cdc55 inhibitors downstream of separase. Later localization work refines rather than negates this experimentally supported inhibitory activity. Supporting Evidence: PMID:18762578 Ectopic Zds1 expression in turn is sufficient to down-regulate PP2A(Cdc55) and promote Net1 phosphorylation. |
| GO:0004864 protein phosphatase inhibitor activity | IGI PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho... | ACCEPT | Summary: Genetic interaction with separase supports Zds1-dependent inhibition of PP2A-Cdc55 during early anaphase. Reason: The genetic evidence complements the direct perturbation result in the same paper. Zds1 acts downstream of separase to down-regulate PP2A-Cdc55 and permit Cdc14 release. Supporting Evidence: PMID:18762578 Zds1 and Zds2 are required downstream of separase to facilitate nucleolar Cdc14 release. |
| 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: IGI annotation for positive regulation of G2/M transition based on genetic interactions with Cdc55. This captures one of Zds1's core regulatory functions with appropriate evidence type. Reason: Zds1 positively regulates G2/M transition through spatial control of Cdc55-PP2A. The IGI evidence from genetic interaction studies with Cdc55 is appropriate for confirming this biological role. This annotation appropriately captures the positive regulatory function of Zds1 in promoting mitotic entry. Supporting Evidence: PMID:21536748 Both Cdc55 and Zds1/Zds2 are important for mitotic entry PMID:20980617 2010 Oct 27. Zds2p regulates Swe1p-dependent polarized cell growth in Saccharomyces cerevisiae via a novel Cdc55p interaction domain. |
| 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: IGI annotation for mRNA export based on genetic interaction with Dbp5 and other export factors. Supports the IMP annotation for this function. Reason: Genetic interactions between ZDS1 and key mRNA export genes (DBP5, MEX67) confirm Zds1's role in mRNA export machinery. The IGI evidence corroborates the IMP findings and demonstrates Zds1 functions in a coordinated complex with established export factors. 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: IPI annotation for mRNA export based on direct physical interactions of Zds1 with Dbp5 and Gfd1 at the NPC. Multiple lines of evidence converge on this function. Reason: Direct protein-protein interactions (two-hybrid and in vitro binding) between Zds1 and Dbp5/Gfd1 establish Zds1 as a physical component of the mRNA export machinery. The converging evidence from IMP, IGI, and IPI annotations all support this functional role. 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... | ACCEPT | Summary: IMP annotation for regulation of protein localization capturing Zds1's central function in controlling Cdc55 nucleocytoplasmic distribution. This is a core mechanistic function. Reason: Zds1's primary molecular mechanism is spatial regulation of Cdc55-PP2A localization. Zds1 binds Cdc55 and controls its subcellular distribution, promoting cytoplasmic/cortical localization while excluding Cdc55 from the nucleus. This nucleocytoplasmic regulation of Cdc55 is the fundamental mechanism underlying Zds1's roles in mitotic entry, mitotic exit, and signaling output specification. The term "regulation of protein localization" accurately and appropriately describes this core function. This is one of Zds1's most important and well-characterized biological process annotations. Supporting Evidence: PMID:21536748 Cortical and cytoplasmic localization of Cdc55 requires Zds1/Zds2 because Cdc55 accumulates in the nucleus in the absence of Zds1/Zds2...Zds1/Zds2 primarily control Cdc55 localization PMID:21536748 By genetically manipulating nucleocytoplasmic distribution of Cdc55, we show that Zds1/Zds2 act as positive regulators for cytoplasmic Cdc55βPP2A |
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