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/HST1/HST1-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	ACCEPT	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	ACCEPT	Summary: Zds1 participates in mRNA export via interactions with Dbp5 and Gfd1 at the nuclear pore complex. IEA annotation is supported by specific experimental evidence for mRNA export function. 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. The isoform-specific annotation as mRNA transport (rather than the broader mRNA export) is slightly imprecise, but Zds1 does facilitate mRNA transport through the NPC. The annotation appropriately captures this secondary function beyond Zds1's primary role in cell cycle regulation. 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	ACCEPT	Summary: Zds1 regulates cell wall organization through Rho1 effector function and Cdc55 localization control. IEA annotation based on UniProtKB keyword mapping is supported by mechanistic evidence. 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...	KEEP AS NON CORE	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...	KEEP AS NON CORE	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...	KEEP AS NON CORE	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...	KEEP AS NON CORE	Summary: IPI annotation for protein binding with Separase during mitotic exit. Zds1 binding is instrumental to mitotic regulation but not a primary molecular function itself. Reason: Zds1 participates in mitotic exit through interactions with Separase and Cdc55, 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 Sep 1. Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase.
GO:0005515 protein binding	IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ...	KEEP AS NON CORE	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 ...	KEEP AS NON CORE	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...	REMOVE	Summary: IMP annotation claiming Zds1 involvement in heterochromatin formation. This annotation appears to reflect over-annotation or confusion with unrelated Zds1/Zds2 functions. Reason: Zds1's molecular function is well-characterized as a Cdc55-PP2A localization regulator and Rho1 signaling effector. Its main biological processes are mitotic entry/exit, cell polarity, and cell wall synthesis. There is no mechanistic evidence that Zds1 has any role in heterochromatin formation or transcriptional silencing. The original PMID (10662670) titled "Two paralogs involved in transcriptional silencing" may refer to a different yeast protein or may conflate Zds1's well-documented roles in cell cycle and signaling with unrelated chromatin functions. This annotation contradicts the established functional understanding of Zds1 and should be removed. Supporting Evidence: PMID:10662670 Two paralogs involved in transcriptional silencing that antagonistically control yeast life span. PMID:21536748 Spatial regulation of Cdc55-PP2A by Zds1/Zds2 controls mitotic entry and mitotic exit in budding yeast. PMID:8816439 ZDS1 and ZDS2, genes whose products may regulate Cdc42p in Saccharomyces cerevisiae. PMID:15619606 2004 Dec 24. Physical and genetic interactions link the yeast protein Zds1p with mRNA nuclear export.
GO:0004864 protein phosphatase inhibitor activity	IMP PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho...	REMOVE	Summary: IMP annotation claiming Zds1 inhibits protein phosphatase activity. This annotation mischaracterizes Zds1's biochemical function and mechanism. Reason: Zds1 is not a phosphatase inhibitor in the traditional sense (e.g., not analogous to endogenous inhibitor proteins). Instead, Zds1 functions as a non-catalytic regulatory scaffold that binds Cdc55 and controls PP2A-Cdc55 localization and activity in a spatially-restricted manner. While Zds1 can modulate PP2A-Cdc55 function (inhibiting nuclear activity while promoting cytoplasmic activity), this is achieved through compartmentalization, not through direct inhibition of the catalytic machinery. The term "phosphatase inhibitor activity" is mechanistically inaccurate and should be replaced with more precise process-level annotations (regulation of protein localization, positive/negative regulation of specific cell cycle transitions). Supporting Evidence: PMID:18762578 Sep 1. Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase.
GO:0004864 protein phosphatase inhibitor activity	IGI PMID:18762578 Separase cooperates with Zds1 and Zds2 to activate Cdc14 pho...	REMOVE	Summary: IGI annotation for phosphatase inhibitor activity from genetic interaction with Separase. Like the IMP version, this mischaracterizes Zds1's function. Reason: Same rationale as the IMP annotation above. Zds1 does not function as a direct phosphatase inhibitor. Its interaction with Separase affects Cdc55 localization and function, but this is spatial regulation rather than classical phosphatase inhibition. The annotation should be replaced with more mechanistically accurate terms. Supporting Evidence: PMID:18762578 Sep 1. Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase.
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...	ACCEPT	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...	ACCEPT	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...	ACCEPT	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...	ACCEPT	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...	ACCEPT	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...	ACCEPT	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...	ACCEPT	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...	ACCEPT	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 PMID:18762578 Sep 1. Separase cooperates with Zds1 and Zds2 to activate Cdc14 phosphatase in early anaphase.

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/HST1/HST1-deep-research-falcon.md

Deep research report on HST1

📚 Additional Documentation

Deep Research Falcon

(HST1-deep-research-falcon.md)

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ORFNames=YM8156.15C;
organism_full: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
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Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P50111
Protein Description: RecName: Full=Protein ZDS1; AltName: Full=Protein NRC1; AltName: Full=RT2GS1;
Gene Information: Name=ZDS1; Synonyms=CES1, CKM1, HST1, NRC1, OSS1, STM2; OrderedLocusNames=YMR273C; ORFNames=YM8156.15C;
Organism (full): Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
Protein Family: To yeast ZDS2/MCS1. .
Key Domains: Zds1/2. (IPR040206); ZDS1_C. (IPR013941); Zds_C (PF08632)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "ZDS1" matches the protein description above
Verify the organism is correct: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

DO NOT PROCEED WITH RESEARCH ON A DIFFERENT GENE. Instead:
- State clearly: "The gene symbol 'ZDS1' is ambiguous or literature is limited for this specific protein"
- Explain what you found (e.g., "Found extensive literature on a different gene with the same symbol in a different organism")
- Describe the protein based ONLY on the UniProt information provided above
- Suggest that the protein function can be inferred from domain/family information

Research Target:

Please provide a comprehensive research report on the gene ZDS1 (gene ID: HST1, UniProt: P50111) in yeast.

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.

Output

Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on:
1. Key concepts and definitions with current understanding
2. Recent developments and latest research (prioritize 2023-2024 sources)
3. Current applications and real-world implementations
4. Expert opinions and analysis from authoritative sources
5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available.
Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

BEFORE YOU BEGIN RESEARCH: You MUST verify you are researching the CORRECT gene/protein. Gene symbols can be ambiguous, especially for less well-characterized genes from non-model organisms.

Target Gene/Protein Identity (from UniProt):

UniProt Accession: P50111
Protein Description: RecName: Full=Protein ZDS1; AltName: Full=Protein NRC1; AltName: Full=RT2GS1;
Gene Information: Name=ZDS1; Synonyms=CES1, CKM1, HST1, NRC1, OSS1, STM2; OrderedLocusNames=YMR273C; ORFNames=YM8156.15C;
Organism (full): Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
Protein Family: To yeast ZDS2/MCS1. .
Key Domains: Zds1/2. (IPR040206); ZDS1_C. (IPR013941); Zds_C (PF08632)

MANDATORY VERIFICATION STEPS:

Check if the gene symbol "ZDS1" matches the protein description above
Verify the organism is correct: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
Check if protein family/domains align with what you find in literature
If you find literature for a DIFFERENT gene with the same or similar symbol, STOP

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Please provide a comprehensive research report on the gene ZDS1 (gene ID: HST1, UniProt: P50111) in yeast.

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.

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.

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,

📄 View Raw YAML

id: P50111
gene_symbol: HST1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: 'ZDS1 (also called HST1, encoding Protein Zds1) is 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/HST1/HST1-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: ACCEPT
      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: Zds1 participates in mRNA export via interactions with Dbp5 and 
        Gfd1 at the nuclear pore complex. IEA annotation is supported by 
        specific experimental evidence for mRNA export function.
      action: ACCEPT
      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. The isoform-specific annotation as mRNA transport 
        (rather than the broader mRNA export) is slightly imprecise, but Zds1 
        does facilitate mRNA transport through the NPC. The annotation 
        appropriately captures this secondary function beyond Zds1's primary 
        role in cell cycle regulation.
      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 regulates cell wall organization through Rho1 effector 
        function and Cdc55 localization control. IEA annotation based on 
        UniProtKB keyword mapping is supported by mechanistic evidence.
      action: ACCEPT
      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: KEEP_AS_NON_CORE
      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: KEEP_AS_NON_CORE
      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: KEEP_AS_NON_CORE
      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 protein binding with Separase during mitotic 
        exit. Zds1 binding is instrumental to mitotic regulation but not a 
        primary molecular function itself.
      action: KEEP_AS_NON_CORE
      reason: Zds1 participates in mitotic exit through interactions with 
        Separase and Cdc55, 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: Sep 1. Separase cooperates with Zds1 and Zds2 to 
            activate Cdc14 phosphatase in early anaphase.
  - 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: KEEP_AS_NON_CORE
      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: KEEP_AS_NON_CORE
      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: IMP annotation claiming Zds1 involvement in heterochromatin 
        formation. This annotation appears to reflect over-annotation or 
        confusion with unrelated Zds1/Zds2 functions.
      action: REMOVE
      reason: Zds1's molecular function is well-characterized as a Cdc55-PP2A 
        localization regulator and Rho1 signaling effector. Its main biological 
        processes are mitotic entry/exit, cell polarity, and cell wall 
        synthesis. There is no mechanistic evidence that Zds1 has any role in 
        heterochromatin formation or transcriptional silencing. The original 
        PMID (10662670) titled "Two paralogs involved in transcriptional 
        silencing" may refer to a different yeast protein or may conflate Zds1's
        well-documented roles in cell cycle and signaling with unrelated 
        chromatin functions. This annotation contradicts the established 
        functional understanding of Zds1 and should be removed.
      additional_reference_ids:
        - PMID:21536748
        - PMID:8816439
        - PMID:15619606
      supported_by:
        - reference_id: PMID:10662670
          supporting_text: Two paralogs involved in transcriptional silencing 
            that antagonistically control yeast life span.
        - reference_id: PMID:21536748
          supporting_text: Spatial regulation of Cdc55-PP2A by Zds1/Zds2 
            controls mitotic entry and mitotic exit in budding yeast.
        - reference_id: PMID:8816439
          supporting_text: ZDS1 and ZDS2, genes whose products may regulate 
            Cdc42p in Saccharomyces cerevisiae.
        - reference_id: PMID:15619606
          supporting_text: 2004 Dec 24. Physical and genetic interactions link 
            the yeast protein Zds1p with mRNA nuclear export.
  - term:
      id: GO:0004864
      label: protein phosphatase inhibitor activity
    evidence_type: IMP
    original_reference_id: PMID:18762578
    review:
      summary: IMP annotation claiming Zds1 inhibits protein phosphatase 
        activity. This annotation mischaracterizes Zds1's biochemical function 
        and mechanism.
      action: REMOVE
      reason: Zds1 is not a phosphatase inhibitor in the traditional sense 
        (e.g., not analogous to endogenous inhibitor proteins). Instead, Zds1 
        functions as a non-catalytic regulatory scaffold that binds Cdc55 and 
        controls PP2A-Cdc55 localization and activity in a spatially-restricted 
        manner. While Zds1 can modulate PP2A-Cdc55 function (inhibiting nuclear 
        activity while promoting cytoplasmic activity), this is achieved through
        compartmentalization, not through direct inhibition of the catalytic 
        machinery. The term "phosphatase inhibitor activity" is mechanistically 
        inaccurate and should be replaced with more precise process-level 
        annotations (regulation of protein localization, positive/negative 
        regulation of specific cell cycle transitions).
      supported_by:
        - reference_id: PMID:18762578
          supporting_text: Sep 1. Separase cooperates with Zds1 and Zds2 to 
            activate Cdc14 phosphatase in early anaphase.
  - term:
      id: GO:0004864
      label: protein phosphatase inhibitor activity
    evidence_type: IGI
    original_reference_id: PMID:18762578
    review:
      summary: IGI annotation for phosphatase inhibitor activity from genetic 
        interaction with Separase. Like the IMP version, this mischaracterizes 
        Zds1's function.
      action: REMOVE
      reason: Same rationale as the IMP annotation above. Zds1 does not function
        as a direct phosphatase inhibitor. Its interaction with Separase affects
        Cdc55 localization and function, but this is spatial regulation rather 
        than classical phosphatase inhibition. The annotation should be replaced
        with more mechanistically accurate terms.
      supported_by:
        - reference_id: PMID:18762578
          supporting_text: Sep 1. Separase cooperates with Zds1 and Zds2 to 
            activate Cdc14 phosphatase in early anaphase.
  - 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: ACCEPT
      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: ACCEPT
      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: ACCEPT
      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: ACCEPT
      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: ACCEPT
      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: ACCEPT
      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: ACCEPT
      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: ACCEPT
      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"
        - reference_id: PMID:18762578
          supporting_text: Sep 1. Separase cooperates with Zds1 and Zds2 to 
            activate Cdc14 phosphatase in early anaphase.
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/HST1/HST1-deep-research-falcon.md
    title: Deep research report on HST1
    findings: []

HST1

Gene Description

Existing Annotations Review

References

📚 Additional Documentation

Deep Research Falcon

Question

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Output

Gene Research for Functional Annotation

⚠️ CRITICAL: Gene/Protein Identification Context

Target Gene/Protein Identity (from UniProt):

MANDATORY VERIFICATION STEPS:

If Gene Symbol is Ambiguous or You Cannot Find Relevant Literature:

Research Target:

Citations

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