Existing Annotations Review

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. zds1Δ zds2Δ 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 zds1Δ zds2Δ double mutant leads to abnormally elongated cell morphology as a consequence of prolonged G2 delay...Zds1/Zds2 are thought to function positively with Cdc55–PP2A to promote mitotic entry PMID:21536748 Both cdc55Δ and zds1Δ zds2Δ 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 zds1Δ zds2Δ 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. zds1Δ zds2Δ 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. zds1Δ zds2Δ 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 zds1Δ zds2Δ 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 zds1Δ zds2Δ 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 zds1Δ zds2Δ 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, zds1Δ zds2Δ 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 Cdc55–PP2A

Core Functions

Zds1 is a non-catalytic adaptor for PP2A-Cdc55 that controls the phosphatase's cytoplasmic/cortical enrichment and nuclear exclusion. This spatial regulation promotes mitotic entry and timely Cdc14 release during mitotic exit.

Molecular Function:

protein phosphatase inhibitor activity

Directly Involved In:

regulation of protein localization positive regulation of G2/M transition of mitotic cell cycle

Cellular Locations:

cytoplasm

Supporting Evidence:

PMID:18762578
Ectopic Zds1 expression in turn is sufficient to down-regulate PP2A(Cdc55) and promote Net1 phosphorylation.
PMID:21536748
Thus, the cytoplasmic localization of Cdc55 mediated by Zds1/Zds2 is required and sufficient for normal mitotic entry.

References

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:10662670

Two paralogs involved in transcriptional silencing that antagonistically control yeast life span.

PMID:15619606

Physical and genetic interactions link the yeast protein Zds1p with mRNA nuclear export.

PMID:16429126

Proteome survey reveals modularity of the yeast cell machinery.

PMID:16554755

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.

PMID:18762578

Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase.

PMID:19536198

An atlas of chaperone-protein interactions in Saccharomyces cerevisiae - implications to protein folding pathways in the cell.

PMID:20980617

Zds2p regulates Swe1p-dependent polarized cell growth in Saccharomyces cerevisiae via a novel Cdc55p interaction domain.

PMID:21536748

Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitotic entry and mitotic exit in budding yeast.

PMID:37968396

The social and structural architecture of the yeast protein interactome.

PMID:8816439

ZDS1 and ZDS2, genes whose products may regulate Cdc42p in Saccharomyces cerevisiae.

file:yeast/ZDS1/ZDS1-deep-research-falcon.md

Deep research report on ZDS1

Deep Research

Falcon

(ZDS1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 19 citations 2025-12-30T22:33:05.564336

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Plan and verification
- Verified identity: ZDS1 encodes Protein Zds1 in Saccharomyces cerevisiae S288c (systematic name YMR273C), the paralog of Zds2, and functions in the Zds1/2 family that regulates the PP2A phosphatase containing regulatory subunit Cdc55. Literature cited below consistently treats Zds1/Zds2 as fungal proteins that act on PP2A-Cdc55 in budding yeast; no conflicting gene symbol usage was found for other organisms in the cited works (Rossio & Yoshida 2011; Rossio et al. 2014; Jonasson et al. 2016; Thai et al. 2017) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3, jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2, thai2017proteinkinasec pages 2-4).

1) Key concepts and definitions with current understanding
- Molecular nature: Zds1 is a non-enzymatic regulator/adaptor of the PP2A phosphatase complex that uses the B regulatory subunit Cdc55 (PP2A-Cdc55). It binds Cdc55 and helps control the subcellular localization and context-specific activity of PP2A-Cdc55, rather than acting as a catalytic enzyme itself (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3). URL/Date: J Cell Biol, May 2011, https://doi.org/10.1083/jcb.201101134; Cell Cycle, July 2014, https://doi.org/10.4161/cc.29064.
- Functional paradigm: Zds1/Zds2 promote the cytoplasmic/cortical pool of PP2A-Cdc55 and thereby promote mitotic entry while allowing proper mitotic exit by restricting nuclear PP2A-Cdc55 when needed. This spatial control links Zds1/2 to the Cdk1 control axis (Swe1/Mih1) and to mitotic exit (Cdc14 release) (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134; Cell Cycle, 2014, https://doi.org/10.4161/cc.29064.
- Cell polarity and Rho1 signaling: Zds1/Zds2 form a complex with PP2A-Cdc55 that acts as a Rho1 effector at the bud cortex to specify signaling outputs toward polarized growth and cell wall synthesis versus stress-responsive CWI signaling (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2). URL/Date: J Cell Biol, January 2016, https://doi.org/10.1083/jcb.201508119.

2) Recent developments and latest research (prioritize 2023–2024)
- Direct 2023–2024 primary studies focused specifically on Zds1/Zds2 in S. cerevisiae are limited in the evidence retrieved here. However, the most recent mechanistic advance closely related to Zds1-regulated PP2A-Cdc55 is the demonstration that the cell wall integrity kinase Pkc1 remodels the PP2A-Cdc55–Zds1/2 complex and regulates binding of Igo/ENSA endosulfines to PP2A-Cdc55; this study quantified changes in complex composition and phosphorylation, including decreased phosphorylation at specific Zds1 sites upon activated PKC1, supporting multi-layered control of PP2A-Cdc55 by the CWI pathway (Thai et al. 2017) (thai2017proteinkinasec pages 2-4). URL/Date: J Biol Chem, March 2017, https://doi.org/10.1074/jbc.M116.753004.
- Partial note on recency: While high-level 2023–2024 reviews discuss PP2A-Cdc55 logic and cell-cycle phosphatase networks, the present evidence set does not contain citable 2023–2024 primary data that newly redefine Zds1’s mechanism; therefore, recent content is summarized via contextually closest mechanistic work that integrates upstream Pkc1 with PP2A-Cdc55–Zds1/2 (Thai et al. 2017) (thai2017proteinkinasec pages 2-4).

3) Current applications and real-world implementations
- Cell-cycle control models: Zds1/2 are used as genetic and biochemical tools to manipulate PP2A-Cdc55’s spatial pools and to study mitotic entry/exit switches and checkpoint pathways (e.g., using Cdc55-NLS/NES alleles to phenocopy or rescue zds1Δ zds2Δ defects) (Rossio & Yoshida 2011) (rossio2011spatialregulationof pages 6-8, rossio2011spatialregulationof pages 1-2). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134.
- Polarity/CWI pathway dissection: The Zds1/Zds2–PP2A-Cdc55 complex is applied to parse decisions in Rho1 signaling between anabolic cell-wall synthesis and stress signaling, by manipulating Zds1/2 or Cdc55 localization and assessing β-1,3-glucan synthesis and CWI output (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2, jonasson2016zds1zds2–pp2acdc55complexspecifies pages 2-3). URL/Date: J Cell Biol, 2016, https://doi.org/10.1083/jcb.201508119.
- Phosphatase regulation mapping: Proteomics of PP2A-Cdc55 complexes under Pkc1 activation—including Zds1 phosphorylation state changes and Igo/ENSA dissociation—provide a framework for chemical-genetic and systems approaches to phosphatase regulation in growth checkpoints (Thai et al. 2017) (thai2017proteinkinasec pages 2-4). URL/Date: J Biol Chem, 2017, https://doi.org/10.1074/jbc.M116.753004.

4) Expert opinions and analysis from authoritative sources
- Spatial regulation model: Expert analyses place Zds1/Zds2 as the principal determinants of cytoplasmic sequestration and cortical recruitment of PP2A-Cdc55, with ENSA-family Igo1/2 acting more prominently in the nucleus; Zds1/2 thereby enable cytoplasmic PP2A-Cdc55 to promote mitotic entry and restrict nuclear PP2A-Cdc55 to facilitate FEAR/MEN transitions (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3, rossio2014comparativegeneticanalysis pages 8-9). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134; Cell Cycle, 2014, https://doi.org/10.4161/cc.29064.
- Rho1 output specification: Zds1/Zds2–PP2A-Cdc55 are viewed as a Rho1 effector module that tunes signaling output by reciprocal regulation of Rho1 GAPs (Lrg1 and Sac7) and by mutually antagonistic dynamics with the Pkc1–Mpk1 CWI pathway; this concept reframes PP2A-Cdc55 not only as a mitotic phosphatase but as a cortical signaling effector that allocates Rho1 activity toward growth versus stress response (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2, jonasson2016zds1zds2–pp2acdc55complexspecifies pages 2-3). URL/Date: J Cell Biol, 2016, https://doi.org/10.1083/jcb.201508119.
- Cdk1/Swe1/Mih1 axis: By targeting Mih1/Cdc25 and promoting Swe1 downregulation via cytoplasmic PP2A-Cdc55, Zds1/Zds2 facilitate timely Cdk1 activation and mitotic entry; mislocalization of Cdc55 recapitulates zds1Δ zds2Δ phenotypes, underscoring the primacy of spatial control (Rossio & Yoshida 2011) (rossio2011spatialregulationof pages 6-8, rossio2011spatialregulationof pages 1-2, rossio2011spatialregulationof pages 10-10). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134.

5) Relevant statistics and data from recent studies
- Localization-function causality: Forcing Cdc55 into the nucleus (Cdc55-NLS) phenocopies zds1Δ zds2Δ (mitotic entry defects and morphology), whereas enforcing cytoplasmic localization (Cdc55-NES) rescues zds1Δ zds2Δ defects, directly quantifying the sufficiency of spatial regulation to explain functional phenotypes (Rossio & Yoshida 2011) (rossio2011spatialregulationof pages 6-8, rossio2011spatialregulationof pages 1-2). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134.
- Rho1 outputs: Loss of Zds1/Zds2 reduces β-1,3-glucan synthesis and increases chitin deposition consistent with CWI activation, providing quantitative cell wall composition readouts that map PP2A-Cdc55–Zds effects on Rho1 output (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2, jonasson2016zds1zds2–pp2acdc55complexspecifies pages 2-3). URL/Date: J Cell Biol, 2016, https://doi.org/10.1083/jcb.201508119.
- Proteomics of regulation: Quantitative mass spectrometry under activated Pkc1 shows marked reduction of Igo2 association with PP2A-Cdc55 and site-specific changes in Zds1 phosphorylation (e.g., S444/S445, S691), providing molecular readouts of CWI-dependent remodeling of the PP2A-Cdc55–Zds1/2 complex (Thai et al. 2017) (thai2017proteinkinasec pages 2-4). URL/Date: J Biol Chem, 2017, https://doi.org/10.1074/jbc.M116.753004.

Primary function of Zds1 and precise mechanistic role
- Zds1 is a scaffold/adaptor for PP2A-Cdc55. It binds Cdc55 and, with Zds2, organizes the cytoplasmic/cortical pool of PP2A-Cdc55 that promotes mitotic entry (via Mih1 activation and Swe1 inhibition) and prevents inappropriate nuclear PP2A-Cdc55 activity that would oppose mitotic exit (by affecting Net1/Cfi1 and Cdc14 release) (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134; Cell Cycle, 2014, https://doi.org/10.4161/cc.29064.
- As a Rho1 effector, the Zds1/Zds2–PP2A-Cdc55 complex biases Rho1 signaling toward polarized growth and β-1,3-glucan synthesis by inhibiting the GAP Lrg1, while antagonizing CWI signaling via stabilization of the GAP Sac7; this establishes pathway-selective dephosphorylation logic at the bud cortex (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2, jonasson2016zds1zds2–pp2acdc55complexspecifies pages 2-3). URL/Date: J Cell Biol, 2016, https://doi.org/10.1083/jcb.201508119.

Binding partners/complexes and putative direct targets
- Core complex: PP2A catalytic and scaffold subunits with regulatory B subunit Cdc55; Zds1 and Zds2 bind Cdc55 and co-exist within the PP2A-Cdc55 holoenzyme (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134; Cell Cycle, 2014, https://doi.org/10.4161/cc.29064.
- Rho1 module: Active Rho1 associates with the Zds1/Zds2–PP2A-Cdc55 complex at the bud cortex in a Zds1/2-dependent manner; Zds1’s Rho1-interacting region maps to residues 78–339 (HR2) (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 2-3). URL/Date: J Cell Biol, 2016, https://doi.org/10.1083/jcb.201508119.
- Upstream kinase pathway: Pkc1 interacts with the complex and remodels its composition and phosphorylation, including Zds1 sites, and reduces Igo/ENSA binding to PP2A-Cdc55 (Thai et al. 2017) (thai2017proteinkinasec pages 2-4). URL/Date: J Biol Chem, 2017, https://doi.org/10.1074/jbc.M116.753004.
- Targets in cell cycle: Downstream PP2A-Cdc55 substrates influenced by Zds-mediated localization include Mih1/Cdc25, Swe1, and FEAR/MEN components such as Net1/Cfi1, thereby regulating Cdk1 activation and Cdc14 release (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3).

Subcellular localization and dynamics
- Zds1/Zds2 localize predominantly to the cortex/cytoplasm at sites of polarized growth, where they recruit/maintain Cdc55 and PP2A activity; in zds1Δ zds2Δ, cortical Cdc55 is lost and Cdc55 accumulates in the nucleus (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 8-9). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134; Cell Cycle, 2014, https://doi.org/10.4161/cc.29064.
- Rho1 dependence and pathway antagonism: Cortical Zds1/Cdc55 localization is Rho1-dependent during bud growth; activation of the Rho1→Pkc1→Mpk1 CWI pathway causes Cdc55 and Zds1 to leave the bud cortex, reflecting mutual exclusivity of growth versus stress outputs (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2). URL/Date: J Cell Biol, 2016, https://doi.org/10.1083/jcb.201508119.

Pathway placement
- Cdk1/Swe1/Mih1 (morphogenesis checkpoint): Zds1-mediated cytoplasmic PP2A-Cdc55 promotes inactivation of the CDK1 inhibitor Swe1 and activation of Mih1/Cdc25, enabling mitotic entry; Zds proteins “target PP2A to Cdc25” as part of this axis (Rossio & Yoshida 2011) (rossio2011spatialregulationof pages 10-10, rossio2011spatialregulationof pages 1-2). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134.
- FEAR/MEN (mitotic exit): Downregulation of PP2A-Cdc55 by separase in early anaphase collaborates with Zds1/2 to promote Cdc14 release; nuclear exclusion of Cdc55 by Zds1/2 facilitates FEAR/MEN-driven exit (Rossio & Yoshida 2011; Rossio et al. 2014) (rossio2011spatialregulationof pages 10-10, rossio2014comparativegeneticanalysis pages 1-3). URL/Date: J Cell Biol, 2011, https://doi.org/10.1083/jcb.201101134; Cell Cycle, 2014, https://doi.org/10.4161/cc.29064.
- Rho1–Pkc1 CWI and glucan synthesis: As a Rho1 effector complex, Zds1/Zds2–PP2A-Cdc55 inhibits Lrg1 to enhance β-1,3-glucan synthase-mediated growth and stabilizes Sac7 to restrain Pkc1–Mpk1 signaling, thereby specifying Rho1 outputs (Jonasson et al. 2016) (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2, jonasson2016zds1zds2–pp2acdc55complexspecifies pages 2-3). URL/Date: J Cell Biol, 2016, https://doi.org/10.1083/jcb.201508119.

Limitations and open questions
- Despite substantial mechanistic clarity, high-resolution structural information for the Zds1–Cdc55 interface and comprehensive phosphosite maps controlling Zds1’s cell-cycle dynamics remain incomplete. Direct 2023–2024 primary updates specific to Zds1/2 were not retrieved in this evidence set; thus, the recency emphasis here relies on adjacent regulatory advances (Pkc1-dependent remodeling of PP2A-Cdc55–Zds1/2) (Thai et al. 2017) (thai2017proteinkinasec pages 2-4).

Embedded evidence table
| Year | Citation (authors, journal) | Focus (function/complex/pathway/localization) | Key finding (1–2 sentences) | URL / DOI |
|------|-----------------------------|-----------------------------------------------|------------------------------------------------|-----------|
| 2011 | Rossio V., Yoshida S., The Journal of Cell Biology (rossio2011spatialregulationof pages 1-2) | Spatial regulation of Cdc55–PP2A by Zds1/Zds2; mitotic entry/exit; Cdk1/Swe1/Mih1; FEAR/MEN | Zds1/Zds2 bind Cdc55–PP2A and sequester Cdc55 in the cytoplasm, promoting mitotic entry via effects on Swe1/Mih1/Cdk1 and controlling mitotic exit/FEAR by regulating nuclear Cdc55 localization. | https://doi.org/10.1083/jcb.201101134 |
| 2014 | Rossio V., Kazatskaya A., Hirabayashi M., Yoshida S., Cell Cycle (rossio2014comparativegeneticanalysis pages 1-3) | Comparative genetic analysis of PP2A-Cdc55 regulators; Zds1/2 vs Igo1/2 | Zds1/Zds2 act in the cytoplasm to sequester/exclude Cdc55 from the nucleus (distinct from nuclear Igo1/2); zds1Δ zds2Δ causes loss of cortical Cdc55 and pleiotropic mitotic/cell‑polarity defects. | https://doi.org/10.4161/cc.29064 |
| 2016 | Jonasson E.M., Rossio V., Hatakeyama R., Abe M., Ohya Y., Yoshida S., The Journal of Cell Biology (jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2) | Zds1/Zds2–PP2A–Cdc55 as Rho1 effector specifying growth vs CWI output | The Zds1/Zds2–PP2A–Cdc55 complex acts as a Rho1 effector at the bud cortex, biasing Rho1 signaling toward polarized growth (by inhibiting the Rho1 GAP Lrg1 to promote β‑1,3‑glucan synthesis) and antagonizing the Pkc1–Mpk1 CWI pathway via GAP regulation. | https://doi.org/10.1083/jcb.201508119 |
| 2017 | Thai V., Dephoure N., Weiss A., Ferguson J., Leitao R., Gygi S.P., Kellogg D.R., Journal of Biological Chemistry (thai2017proteinkinasec pages 2-4) | PKC1-dependent remodeling of PP2A–Cdc55–Zds1/2 complex and Igo/ENSA interactions | Activated Pkc1 alters PP2A–Cdc55 complex composition and phosphorylation (including Zds1 sites) and drives dissociation/reduced binding of Igo2 (ENSA homolog), linking Pkc1 signaling to dynamic regulation of PP2A activity and its associated regulators. | https://doi.org/10.1074/jbc.M116.753004 |

Table: Compact summary of key primary studies that define Zds1 (YMR273C, UniProt P50111) function, complexes, pathways, and localization; includes citations and DOIs for rapid reference.

Conclusion
Zds1 (YMR273C; UniProt P50111) is a cortical adaptor that binds the PP2A regulatory subunit Cdc55 and, with Zds2, dictates the spatial and contextual actions of PP2A-Cdc55 in budding yeast. Through localization-driven control, Zds1/2 promote mitotic entry (via Swe1/Mih1/Cdk1), enable mitotic exit (via FEAR/MEN and Cdc14 release), and act as a Rho1 effector that biases signaling toward polarized growth and β-1,3-glucan synthesis while antagonizing Pkc1–Mpk1 CWI signaling. Emerging systems-level work connects Pkc1 activity to dynamic remodeling of the PP2A-Cdc55–Zds1/2 complex and its binding partners, underscoring that Zds1 integrates growth and stress cues at the bud cortex (Rossio & Yoshida 2011; Rossio et al. 2014; Jonasson et al. 2016; Thai et al. 2017) (rossio2011spatialregulationof pages 1-2, rossio2014comparativegeneticanalysis pages 1-3, jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2, thai2017proteinkinasec pages 2-4).

References

(rossio2011spatialregulationof pages 1-2): Valentina Rossio and Satoshi Yoshida. Spatial regulation of cdc55–pp2a by zds1/zds2 controls mitotic entry and mitotic exit in budding yeast. The Journal of Cell Biology, 193:445-454, May 2011. URL: https://doi.org/10.1083/jcb.201101134, doi:10.1083/jcb.201101134. This article has 76 citations.
(rossio2014comparativegeneticanalysis pages 1-3): Valentina Rossio, Anna Kazatskaya, Mayo Hirabayashi, and Satoshi Yoshida. Comparative genetic analysis of pp2a-cdc55 regulators in budding yeast. Cell Cycle, 13:2073-2083, Jul 2014. URL: https://doi.org/10.4161/cc.29064, doi:10.4161/cc.29064. This article has 15 citations and is from a peer-reviewed journal.
(jonasson2016zds1zds2–pp2acdc55complexspecifies pages 1-2): Erin M. Jonasson, Valentina Rossio, Riko Hatakeyama, Mitsuhiro Abe, Yoshikazu Ohya, and Satoshi Yoshida. Zds1/zds2–pp2acdc55 complex specifies signaling output from rho1 gtpase. The Journal of Cell Biology, 212:51-61, Jan 2016. URL: https://doi.org/10.1083/jcb.201508119, doi:10.1083/jcb.201508119. This article has 23 citations.
(thai2017proteinkinasec pages 2-4): Vu Thai, Noah Dephoure, Amit Weiss, Jacqueline Ferguson, Ricardo Leitao, Steven P. Gygi, and Douglas R. Kellogg. Protein kinase c controls binding of igo/ensa proteins to protein phosphatase 2a in budding yeast. Journal of Biological Chemistry, 292:4925-4941, Mar 2017. URL: https://doi.org/10.1074/jbc.m116.753004, doi:10.1074/jbc.m116.753004. This article has 23 citations and is from a domain leading peer-reviewed journal.
(rossio2011spatialregulationof pages 6-8): Valentina Rossio and Satoshi Yoshida. Spatial regulation of cdc55–pp2a by zds1/zds2 controls mitotic entry and mitotic exit in budding yeast. The Journal of Cell Biology, 193:445-454, May 2011. URL: https://doi.org/10.1083/jcb.201101134, doi:10.1083/jcb.201101134. This article has 76 citations.
(jonasson2016zds1zds2–pp2acdc55complexspecifies pages 2-3): Erin M. Jonasson, Valentina Rossio, Riko Hatakeyama, Mitsuhiro Abe, Yoshikazu Ohya, and Satoshi Yoshida. Zds1/zds2–pp2acdc55 complex specifies signaling output from rho1 gtpase. The Journal of Cell Biology, 212:51-61, Jan 2016. URL: https://doi.org/10.1083/jcb.201508119, doi:10.1083/jcb.201508119. This article has 23 citations.
(rossio2014comparativegeneticanalysis pages 8-9): Valentina Rossio, Anna Kazatskaya, Mayo Hirabayashi, and Satoshi Yoshida. Comparative genetic analysis of pp2a-cdc55 regulators in budding yeast. Cell Cycle, 13:2073-2083, Jul 2014. URL: https://doi.org/10.4161/cc.29064, doi:10.4161/cc.29064. This article has 15 citations and is from a peer-reviewed journal.
(rossio2011spatialregulationof pages 10-10): Valentina Rossio and Satoshi Yoshida. Spatial regulation of cdc55–pp2a by zds1/zds2 controls mitotic entry and mitotic exit in budding yeast. The Journal of Cell Biology, 193:445-454, May 2011. URL: https://doi.org/10.1083/jcb.201101134, doi:10.1083/jcb.201101134. This article has 76 citations.

Citations

thai2017proteinkinasec pages 2-4
rossio2011spatialregulationof pages 1-2
rossio2014comparativegeneticanalysis pages 1-3
rossio2011spatialregulationof pages 6-8
rossio2014comparativegeneticanalysis pages 8-9
rossio2011spatialregulationof pages 10-10
https://doi.org/10.1083/jcb.201101134;
https://doi.org/10.4161/cc.29064.
https://doi.org/10.1083/jcb.201508119.
https://doi.org/10.1074/jbc.M116.753004.
https://doi.org/10.1083/jcb.201101134.
https://doi.org/10.1083/jcb.201101134
https://doi.org/10.4161/cc.29064
https://doi.org/10.1083/jcb.201508119
https://doi.org/10.1074/jbc.M116.753004
https://doi.org/10.1083/jcb.201101134,
https://doi.org/10.4161/cc.29064,
https://doi.org/10.1083/jcb.201508119,
https://doi.org/10.1074/jbc.m116.753004,

📚 Additional Documentation

Notes

(ZDS1-notes.md)

ZDS1 review notes

Identity and research provenance

Canonical target: ZDS1/YMR273C, UniProt P50111. HST1 is a legacy synonym of
ZDS1 and caused the earlier directory collision with canonical sirtuin HST1
(YOL068C/P53685).
The existing Falcon report is correctly grounded on P50111/ZDS1, although its
recorded request metadata still contains the former gene_id: HST1 value.
just deep-research-openscientist yeast ZDS1 was attempted twice on
2026-08-12. Both jobs resolved P50111/ZDS1 correctly but failed while polling
the provider (first ConnectTimeout, then DNS ConnectError). No provider
artifact was written or fabricated.

Curation corrections

PMID:10662670 directly studies ZDS1 deletion and reports redistribution of
silencing among rDNA, a silent mating-type cassette, and telomeres. The
experimental heterochromatin annotation is therefore retained as non-core;
the initialized review's claim that the paper concerned a different protein
was incorrect.
PMID:18762578 directly reports that ectopic Zds1 down-regulates PP2A-Cdc55 and
suggests that Zds1/Zds2 act as separase-regulated PP2A-Cdc55 inhibitors.
Later spatial-localization work refines this mechanism but does not justify
removing the experimental molecular-function annotations.
Generic protein binding annotations are marked over-annotated because they
are true interaction observations but do not describe Zds1's adaptor/regulator
function.
Coimmunoprecipitation with Cdc55 and Tpd3 demonstrates association with
PP2A-Cdc55, not part_of membership in the heterotrimeric PP2A holoenzyme;
no new GO:0000159 annotation is proposed.

Core synthesis

Zds1 is a non-catalytic PP2A-Cdc55 adaptor/regulator. Its principal conserved
role is to establish the cytoplasmic and cortical pool of PP2A-Cdc55 and limit
nuclear Cdc55, thereby coordinating mitotic entry and exit. Cell-polarity,
cell-wall, mRNA-export, and chromatin-silencing phenotypes are retained where
experimentally supported but are secondary to this core mechanism; the broad
mRNA-transport parent is marked over-annotated because the more specific
nuclear-export term is already supported.

📄 View Raw YAML

id: P50111
gene_symbol: ZDS1
aliases:
- HST1
- CES1
- CKM1
- NRC1
- OSS1
- STM2
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: '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.'
existing_annotations:
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "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"
        - reference_id: PMID:8816439
          supporting_text: "A glutathione S-transferase-Zds1p fusion protein that
            fully complemented the double mutant localized to presumptive bud sites
            and the tips of small buds"
        - reference_id: file:yeast/ZDS1/ZDS1-deep-research-falcon.md
          supporting_text: 'model: Edison Scientific Literature'
  - term:
      id: GO:0010971
      label: positive regulation of G2/M transition of mitotic cell cycle
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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. zds1Δ zds2Δ
        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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "zds1Δ zds2Δ double mutant leads to abnormally elongated
            cell morphology as a consequence of prolonged G2 delay...Zds1/Zds2 are
            thought to function positively with Cdc55–PP2A to promote mitotic entry"
        - reference_id: PMID:21536748
          supporting_text: "Both cdc55Δ and zds1Δ zds2Δ exhibited abnormally elongated
            bud morphology at all the temperatures tested"
  - term:
      id: GO:0030010
      label: establishment of cell polarity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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 zds1Δ zds2Δ mutants.
      action: KEEP_AS_NON_CORE
      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. zds1Δ zds2Δ
        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.
      supported_by:
        - reference_id: PMID:8816439
          supporting_text: "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"
        - reference_id: PMID:21536748
          supporting_text: "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"
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: UniProt-derived IEA annotation for cytoplasmic localization based
        on subcellular location vocabulary. This is consistent with IDA and IBA
        annotations and experimental evidence.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "Zds1, Zds2, and Cdc55 also exist in the cytoplasm and
            are excluded from the vacuole"
  - term:
      id: GO:0051028
      label: mRNA transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:15619606
          supporting_text: "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"
        - reference_id: PMID:15619606
          supporting_text: "Dbp5p and Gfd1p interact with Zds1p...In vitro binding
            experiments revealed that Gfd1p and Dbp5p bind directly to the C-terminal
            part of Zds1p"
  - term:
      id: GO:0071555
      label: cell wall organization
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: Zds1 influences cell wall organization through Rho1 signaling and
        Cdc55 localization, a supported but secondary consequence of its core
        PP2A-Cdc55 regulatory role.
      action: KEEP_AS_NON_CORE
      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. zds1Δ zds2Δ 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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "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"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:15619606
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:15619606
          supporting_text: "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"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16429126
    review:
      summary: IPI annotation from proteome survey detecting protein
        interactions in large-scale binding experiments. Generic protein binding
        annotation; see other instances for same term.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:16429126
          supporting_text: Proteome survey reveals modularity of the yeast cell
            machinery.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16554755
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:16554755
          supporting_text: Global landscape of protein complexes in the yeast
            Saccharomyces cerevisiae.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18762578
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:18762578
          supporting_text: In immunoprecipitates of Zds1 from metaphase-arrested cells,
            we detected Cdc55 as well as the PP2A scaffold subunit, Tpd3 by Western
            blotting.
          reference_section_type: RESULTS
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:19536198
    review:
      summary: IPI annotation from chaperone-protein interaction atlas. Generic
        protein binding from large-scale interaction mapping; consistent with
        other instances of this term.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:19536198
          supporting_text: 'An atlas of chaperone-protein interactions in Saccharomyces
            cerevisiae: implications to protein folding pathways in the cell.'
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:37968396
    review:
      summary: IPI annotation from recent structural and functional analysis of
        yeast protein interactome architecture. Generic binding annotation from
        modern interaction mapping.
      action: MARK_AS_OVER_ANNOTATED
      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.
      supported_by:
        - reference_id: PMID:37968396
          supporting_text: Nov 15. The social and structural architecture of the
            yeast protein interactome.
  - term:
      id: GO:0031507
      label: heterochromatin formation
    evidence_type: IMP
    original_reference_id: PMID:10662670
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:10662670
          supporting_text: 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.
          reference_section_type: ABSTRACT
  - term:
      id: GO:0004864
      label: protein phosphatase inhibitor activity
    evidence_type: IMP
    original_reference_id: PMID:18762578
    review:
      summary: Zds1 down-regulates PP2A-Cdc55 at anaphase onset, although spatial
        redistribution is also central to its broader mechanism.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18762578
          supporting_text: Ectopic Zds1 expression in turn is sufficient to down-regulate
            PP2A(Cdc55) and promote Net1 phosphorylation.
          reference_section_type: ABSTRACT
  - term:
      id: GO:0004864
      label: protein phosphatase inhibitor activity
    evidence_type: IGI
    original_reference_id: PMID:18762578
    review:
      summary: Genetic interaction with separase supports Zds1-dependent inhibition
        of PP2A-Cdc55 during early anaphase.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:18762578
          supporting_text: Zds1 and Zds2 are required downstream of separase to facilitate
            nucleolar Cdc14 release.
          reference_section_type: ABSTRACT
  - term:
      id: GO:0010971
      label: positive regulation of G2/M transition of mitotic cell cycle
    evidence_type: IGI
    original_reference_id: PMID:20980617
    review:
      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.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "Both Cdc55 and Zds1/Zds2 are important for mitotic entry"
        - reference_id: PMID:20980617
          supporting_text: 2010 Oct 27. Zds2p regulates Swe1p-dependent
            polarized cell growth in Saccharomyces cerevisiae via a novel Cdc55p
            interaction domain.
  - term:
      id: GO:0000131
      label: incipient cellular bud site
    evidence_type: IDA
    original_reference_id: PMID:8816439
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:8816439
          supporting_text: "A glutathione S-transferase-Zds1p fusion protein that
            fully complemented the double mutant localized to presumptive bud sites
            and the tips of small buds"
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:21536748
    review:
      summary: IDA annotation for cytoplasmic localization from direct
        observation of endogenous Zds1-GFP throughout the cell cycle. Consistent
        with all other localization evidence.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "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"
  - term:
      id: GO:0005934
      label: cellular bud tip
    evidence_type: IDA
    original_reference_id: PMID:8816439
    review:
      summary: IDA annotation for Zds1 localization to bud tips in developing
        buds. Direct evidence from GST-Zds1 fusion protein imaging confirms bud
        tip enrichment.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:8816439
          supporting_text: "A glutathione S-transferase-Zds1p fusion protein that
            fully complemented the double mutant localized to presumptive bud sites
            and the tips of small buds"
        - reference_id: PMID:21536748
          supporting_text: "We also observed bud neck localization of Zds1-GFP and
            Zds2-GFP in late mitotic cells"
  - term:
      id: GO:0005935
      label: cellular bud neck
    evidence_type: IDA
    original_reference_id: PMID:21536748
    review:
      summary: IDA annotation for Zds1 localization to the bud neck in late
        mitotic cells. Direct fluorescence imaging confirms this dynamic
        localization change.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "We also observed bud neck localization of Zds1-GFP and
            Zds2-GFP in late mitotic cells"
        - reference_id: PMID:21536748
          supporting_text: "Cdc55-GFP localized to the bud cortex of small to medium
            budded cells and to the bud neck in late mitotic cells"
  - term:
      id: GO:0006406
      label: mRNA export from nucleus
    evidence_type: IMP
    original_reference_id: PMID:15619606
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:15619606
          supporting_text: "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"
        - reference_id: PMID:15619606
          supporting_text: "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"
  - term:
      id: GO:0006406
      label: mRNA export from nucleus
    evidence_type: IGI
    original_reference_id: PMID:15619606
    review:
      summary: IGI annotation for mRNA export based on genetic interaction with
        Dbp5 and other export factors. Supports the IMP annotation for this
        function.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:15619606
          supporting_text: "ZDS1 interacted genetically with mutant alleles of genes
            encoding key factors in mRNA export, including DBP5 and MEX67"
  - term:
      id: GO:0006406
      label: mRNA export from nucleus
    evidence_type: IPI
    original_reference_id: PMID:15619606
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:15619606
          supporting_text: "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"
  - term:
      id: GO:0010971
      label: positive regulation of G2/M transition of mitotic cell cycle
    evidence_type: IMP
    original_reference_id: PMID:21536748
    review:
      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.
      action: ACCEPT
      reason: Experimental studies directly demonstrate that Zds1 promotes G2/M
        transition through spatial control of Cdc55. The zds1Δ zds2Δ 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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "zds1Δ zds2Δ double mutant leads to abnormally elongated
            cell morphology as a consequence of prolonged G2 delay"
  - term:
      id: GO:0030010
      label: establishment of cell polarity
    evidence_type: IMP
    original_reference_id: PMID:8816439
    review:
      summary: IMP annotation for cell polarity based on morphological and
        genetic analysis of zds1Δ zds2Δ mutants showing severe polarity defects
        and abnormal cell shape.
      action: KEEP_AS_NON_CORE
      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, zds1Δ zds2Δ 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.'
      supported_by:
        - reference_id: PMID:8816439
          supporting_text: "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"
        - reference_id: PMID:21536748
          supporting_text: "Zds1/Zds2 interact with cell polarity proteins of the
            Cdc42- and the Rho1-signaling pathways both physically and genetically"
  - term:
      id: GO:0030010
      label: establishment of cell polarity
    evidence_type: IGI
    original_reference_id: PMID:8816439
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:8816439
          supporting_text: "The similarity of this localization to that of Cdc42p
            suggests that Zds1p may interact directly with Cdc42p"
        - reference_id: PMID:21536748
          supporting_text: "Zds1/Zds2 interact with cell polarity proteins of the
            Cdc42- and the Rho1-signaling pathways both physically and genetically"
  - term:
      id: GO:0032880
      label: regulation of protein localization
    evidence_type: IMP
    original_reference_id: PMID:18762578
    review:
      summary: IMP annotation for regulation of protein localization capturing
        Zds1's central function in controlling Cdc55 nucleocytoplasmic
        distribution. This is a core mechanistic function.
      action: ACCEPT
      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.
      supported_by:
        - reference_id: PMID:21536748
          supporting_text: "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"
        - reference_id: PMID:21536748
          supporting_text: "By genetically manipulating nucleocytoplasmic distribution
            of Cdc55, we show that Zds1/Zds2 act as positive regulators for cytoplasmic
            Cdc55–PP2A"
core_functions:
  - description: >-
      Zds1 is a non-catalytic adaptor for PP2A-Cdc55 that controls the phosphatase's
      cytoplasmic/cortical enrichment and nuclear exclusion. This spatial regulation
      promotes mitotic entry and timely Cdc14 release during mitotic exit.
    molecular_function:
      id: GO:0004864
      label: protein phosphatase inhibitor activity
    directly_involved_in:
      - id: GO:0032880
        label: regulation of protein localization
      - id: GO:0010971
        label: positive regulation of G2/M transition of mitotic cell cycle
    locations:
      - id: GO:0005737
        label: cytoplasm
    supported_by:
      - reference_id: PMID:18762578
        supporting_text: Ectopic Zds1 expression in turn is sufficient to down-regulate
          PP2A(Cdc55) and promote Net1 phosphorylation.
        reference_section_type: ABSTRACT
      - reference_id: PMID:21536748
        supporting_text: Thus, the cytoplasmic localization of Cdc55 mediated by Zds1/Zds2
          is required and sufficient for normal mitotic entry.
        reference_section_type: RESULTS
references:
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword
      mapping
    findings: []
  - id: GO_REF:0000044
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular
      Location vocabulary mapping, accompanied by conservative changes to GO
      terms applied by UniProt
    findings: []
  - id: PMID:10662670
    title: Two paralogs involved in transcriptional silencing that
      antagonistically control yeast life span.
    findings: []
  - id: PMID:15619606
    title: Physical and genetic interactions link the yeast protein Zds1p with
      mRNA nuclear export.
    findings: []
  - id: PMID:16429126
    title: Proteome survey reveals modularity of the yeast cell machinery.
    findings: []
  - id: PMID:16554755
    title: Global landscape of protein complexes in the yeast Saccharomyces
      cerevisiae.
    findings: []
  - id: PMID:18762578
    title: Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase
      in early anaphase.
    findings: []
  - id: PMID:19536198
    title: An atlas of chaperone-protein interactions in Saccharomyces
      cerevisiae - implications to protein folding pathways in the cell.
    findings: []
  - id: PMID:20980617
    title: Zds2p regulates Swe1p-dependent polarized cell growth in
      Saccharomyces cerevisiae via a novel Cdc55p interaction domain.
    findings: []
  - id: PMID:21536748
    title: Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitotic entry
      and mitotic exit in budding yeast.
    findings: []
  - id: PMID:37968396
    title: The social and structural architecture of the yeast protein
      interactome.
    findings: []
  - id: PMID:8816439
    title: ZDS1 and ZDS2, genes whose products may regulate Cdc42p in
      Saccharomyces cerevisiae.
    findings: []
  - id: file:yeast/ZDS1/ZDS1-deep-research-falcon.md
    title: Deep research report on ZDS1
    findings: []

ZDS1

Gene Description

Existing Annotations Review

Core Functions

Zds1 is a non-catalytic adaptor for PP2A-Cdc55 that controls the phosphatase's cytoplasmic/cortical enrichment and nuclear exclusion. This spatial regulation promotes mitotic entry and timely Cdc14 release during mitotic exit.

References

Deep Research

Falcon

Citations

📚 Additional Documentation

Notes

ZDS1 review notes

Identity and research provenance

Curation corrections

Core synthesis

📄 View Raw YAML