Cdc14 is the essential dual-specificity protein phosphatase of Saccharomyces cerevisiae that drives exit from mitosis by reversing phosphorylation deposited by the cyclin-dependent kinase Cdc28 (Cdk1). It belongs to the protein-tyrosine phosphatase superfamily (Cys283 forms the phosphocysteine intermediate, Asp253 is the general acid/base) but physiologically acts on CDK-phosphorylated serine-proline sites, preferring pSer-Pro-x-Lys/Arg and engaging substrates through a Pro-x-Leu docking motif. In anaphase Cdc14 dephosphorylates the APC/C activator Cdh1, the CDK inhibitor Sic1 and its transcription factor Swi5, thereby destroying mitotic cyclins and extinguishing Clb-Cdc28 activity so that cells can enter G1. From G1 through metaphase the enzyme is sequestered and inhibited in the nucleolus by Net1/Cfi1 within the RENT complex (Net1, Sir2, Cdc14). The FEAR network (separase/Esp1, Slk19, Spo12, the Polo kinase Cdc5 and inhibition of PP2A-Cdc55) releases it transiently into the nucleus in early anaphase, where it stabilizes the spindle midzone (Ase1, Fin1), promotes condensin loading and RNA polymerase I inhibition needed for rDNA condensation and segregation, and primes Top2-dependent resolution of sister-chromatid links. The mitotic exit network (Tem1 GTPase, Cdc15, Dbf2-Mob1) then drives sustained release into the cytoplasm, where Cdc14 localizes to spindle pole bodies and the bud neck and dephosphorylates cytokinesis regulators (Iqg1, Inn1, Chs2, Bud3) to couple cytokinesis to nuclear division. Cdc14 also resets SPB duplication licensing (Sfi1), is required for meiosis I spindle disassembly and the two consecutive meiotic divisions, and in meiosis or after TORC1 inactivation dephosphorylates Atg13 to stimulate autophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000183 rDNA heterochromatin formation | NAS PMID:12923057 Association of the RENT complex with nontranscribed and codi... | MARK AS OVER ANNOTATED | Summary: NAS annotation derived from the RENT-complex literature: RENT (Net1-Sir2-Cdc14) mediates rDNA silencing, but the silencing work is done by the Sir2 deacetylase recruited through Net1/Fob1; no experiment shows that Cdc14 phosphatase activity contributes to rDNA heterochromatin formation, and the cited paper does not examine Cdc14. Reason: Cdc14's membership in RENT is real (GO:0030869), but complex co-membership is not participation in the process. The cited abstract discusses only Net1 and Sir2 localisation to rDNA and Fob1-dependent silencing; the term's definition (H3K9me3-marked heterochromatin) also fits budding yeast poorly. Retain at most as a non-core, indirect association; the RENT complex annotation already captures the association. Supporting Evidence: PMID:12923057 rDNA silencing is mediated by a Sir2-containing complex called RENT (regulator of nucleolar silencing and telophase exit). |
| GO:0000226 microtubule cytoskeleton organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT-inferred role in microtubule cytoskeleton organization. In budding yeast, released Cdc14 dephosphorylates spindle proteins such as Fin1 and Ase1 to stabilize and organize the anaphase spindle midzone, and it promotes spindle disassembly at mitotic exit; this is a genuine but downstream, substrate-specific role. Reason: The phylogenetic placement is sound and supported by direct budding-yeast evidence (Cdc14 dephosphorylates Fin1, which then stabilizes the elongating spindle). However, the core function is reversal of CDK phosphorylation to drive mitotic exit; spindle organization is one of several downstream consequences, so it is kept as non-core. Supporting Evidence: PMID:17173039 In anaphase, when Clb5-Cdk1 is inactivated, Fin1 is dephosphorylated by the phosphatase Cdc14. PMID:17173039 Fin1 dephosphorylation targets it to the poles and microtubules of the elongating spindle, where it contributes to spindle integrity. |
| GO:0000278 mitotic cell cycle | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-predicted general term. Cdc14 is an essential mitotic cell-cycle regulator (mitotic exit phosphatase), so the broad term is correct though far less specific than the experimental annotations. Reason: Electronic annotation to a broad parent that is unquestionably true; the specific role (regulation of exit from mitosis, cytokinesis) is captured by other rows. Supporting Evidence: PMID:9295359 The catalytically inactive Cdc14p C283S/R289A mutant is not able to suppress the temperature sensitivity of a cdc14-1(ts) mutant nor replace the wild type gene in vivo, demonstrating that phosphatase activity is required for the cell cycle function of Cdc14p. |
| GO:0000278 mitotic cell cycle | IMP PMID:6749599 Determination of the order of gene function in the yeast nuc... | ACCEPT | Summary: Classic cdc14 conditional mutants arrest in late nuclear division; Moir and Botstein used reciprocal temperature shifts to order cdc14 relative to other nuclear-division genes. Establishes CDC14 as a mitotic cell-cycle gene. Reason: Foundational genetic evidence (abstract-only cache; the curator read the full text). The term is broad but correct; the specific process is mitotic exit, covered by GO:0007096 rows. Supporting Evidence: PMID:6749599 Cold-sensitive (cs) and heat-sensitive (ts) conditional-lethal mutations that affect specifically the cell division cycle of budding yeast (Saccharomyces cerevisiae) were used to determine the order of gene function. |
| GO:0000422 autophagy of mitochondrion | IMP PMID:29694832 Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeas... | KEEP AS NON CORE | Summary: Cdc14 is required for optimal Atg13 dephosphorylation and autophagy induction after TORC1 inactivation; SGD extends this (from the full text) to mitophagy. A stress-responsive, nutrient-dependent role distinct from mitotic exit. Reason: Supported by IMP evidence and mechanistically plausible (Atg13 is a Cdc14 substrate), but autophagy/mitophagy is a secondary role outside the core mitotic-exit function. Abstract-only cache; the mitophagy-specific data are in the full text, so the curator's call is deferred to. Supporting Evidence: PMID:29694832 Cdc14 phosphatase was required for optimal Atg13 dephosphorylation, pre-autophagosomal structure formation, and autophagy induction after TORC1 inactivation. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:17173039 Cdk and APC activities limit the spindle-stabilizing functio... | ACCEPT | Summary: Cdc14 dephosphorylates the Clb5-Cdk1 substrate Fin1 in anaphase, demonstrating phosphoprotein phosphatase activity toward a CDK site. Reason: Direct evidence of Cdc14 dephosphorylating a physiological CDK substrate; core catalytic activity. Supporting Evidence: PMID:17173039 In anaphase, when Clb5-Cdk1 is inactivated, Fin1 is dephosphorylated by the phosphatase Cdc14. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:24319056 Global analysis of cdc14 dephosphorylation sites reveals ess... | ACCEPT | Summary: Quantitative phosphoproteomics mapped 835 Cdc14-dependent dephosphorylation sites on 455 candidate substrates in vivo, and validated Smc4 and Bud3 as substrates. Reason: Direct in vivo evidence of Cdc14 phosphoprotein phosphatase activity across its substrate set; core catalytic activity. Supporting Evidence: PMID:24319056 Quantitative mass spectrometry identified a total of 835 dephosphorylation sites on 455 potential Cdc14 substrates in vivo. PMID:24319056 Cdc14-mediated dephosphorylation of Smc4 and Bud3 is essential for proper mitosis and cytokinesis, respectively. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:24954044 Molecular mechanisms that restrict yeast centrosome duplicat... | ACCEPT | Summary: Cdc14 dephosphorylates the C-terminal Cdk1/Cdc5 sites of the half-bridge protein Sfi1 to license a new round of SPB duplication. Reason: Direct evidence of phosphoprotein phosphatase activity toward a physiological substrate; core catalytic activity. Supporting Evidence: PMID:24954044 Moreover, Cdc14 dephosphorylates C-Sfi1 to prepare it for a new round of duplication, and the kinase Mps1 promotes Sfi1 extension in G1. |
| GO:0004721 phosphoprotein phosphatase activity | IDA PMID:9295359 The activity of Cdc14p, an oligomeric dual specificity prote... | ACCEPT | Summary: Recombinant Cdc14p was characterized as an oligomeric dual-specificity protein phosphatase, and the catalytically inactive C283S/R289A mutant cannot support the essential cell-cycle function, showing that phosphatase activity is required in vivo. Reason: Foundational biochemical characterization of the catalytic activity; core. Supporting Evidence: PMID:9295359 Recombinant Cdc14p was produced in bacteria, characterized, and shown to be a dual specificity protein phosphatase. PMID:9295359 The catalytically inactive Cdc14p C283S/R289A mutant is not able to suppress the temperature sensitivity of a cdc14-1(ts) mutant nor replace the wild type gene in vivo, demonstrating that phosphatase activity is required for the cell cycle function of Cdc14p. |
| GO:0004721 phosphoprotein phosphatase activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-predicted phosphoprotein phosphatase activity, consistent with the extensive experimental evidence. Reason: Electronic annotation to the correct activity; supported by multiple IDA rows. Supporting Evidence: PMID:9295359 Recombinant Cdc14p was produced in bacteria, characterized, and shown to be a dual specificity protein phosphatase. |
| GO:0004722 protein serine/threonine phosphatase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT-inferred protein serine/threonine phosphatase activity for the Cdc14 family. Budding-yeast Cdc14 physiologically acts on CDK-phosphorylated pSer-Pro sites (Cdh1, Sic1, Swi5, Fin1, Iqg1, Atg13 and hundreds more), with a strong preference for phosphoserine. Reason: This is the most accurate description of Cdc14's physiological activity: although the family is dual-specificity in vitro, essentially all characterized substrates are CDK pSer-Pro sites. The IBA node is seeded by the S. cerevisiae, S. pombe and human experimental annotations. Core molecular function. Supporting Evidence: PMID:26085509 Cdc14 associated with Iqg1, dependent on several CHD-flanking Cdk sites, and efficiently dephosphorylated these sites in vitro. PMID:24319056 Quantitative mass spectrometry identified a total of 835 dephosphorylation sites on 455 potential Cdc14 substrates in vivo. file:yeast/CDC14/CDC14-deep-research-falcon.md Phosphothreonine is disfavored because its additional methyl group creates steric conflict in the active site. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:26085509 Dephosphorylation of Iqg1 by Cdc14 regulates cytokinesis in ... | ACCEPT | Summary: Cdc14 binds Iqg1 through CHD-flanking Cdk sites and efficiently dephosphorylates these serine/threonine sites in vitro; this dephosphorylation drives actin ring assembly. Reason: Direct in vitro demonstration of Ser/Thr phosphatase activity on a physiological CDK substrate; core. Supporting Evidence: PMID:26085509 Cdc14 associated with Iqg1, dependent on several CHD-flanking Cdk sites, and efficiently dephosphorylated these sites in vitro. |
| GO:0004722 protein serine/threonine phosphatase activity | IDA PMID:35238874 Cdc14 spatiotemporally dephosphorylates Atg13 to activate au... | ACCEPT | Summary: During meiotic anaphase I and II, cytoplasmic Cdc14 dephosphorylates Atg13 (a TORC1-phosphorylated Ser/Thr substrate) to activate Atg1 and autophagy; a catalytically dead Cdc14 does not. Reason: Direct demonstration of Ser/Thr phosphatase activity; the substrate is outside the CDK set but the activity is the same core catalytic function. Supporting Evidence: PMID:35238874 Cdc14 is activated in anaphase I and II, accompanying its subcellular relocation from the nucleolus to the cytoplasm, where it dephosphorylates Atg13 to stimulate Atg1 kinase activity and thus autophagy. |
| GO:0004725 protein tyrosine phosphatase activity | IEA GO_REF:0000120 | MODIFY | Summary: Electronic annotation from the EC 3.1.3.48 / RHEA:10684 mapping. Cdc14 does hydrolyze phosphotyrosine in vitro (it is a dual-specificity phosphatase), but no physiological tyrosine-phosphorylated substrate is known; its biological activity is directed at CDK pSer-Pro sites. Reason: 'Protein tyrosine phosphatase activity' alone misrepresents the enzyme: Cdc14 was shown to be a dual-specificity phosphatase, and all characterized in vivo substrates are serine/threonine (CDK) sites, with phosphothreonine and phosphotyrosine being poor substrates. The appropriate term for the biochemical activity is GO:0008138 protein tyrosine/serine/threonine phosphatase activity, and the physiological activity is already captured by GO:0004722. Proposed replacements: protein tyrosine/serine/threonine phosphatase activity Supporting Evidence: PMID:9295359 Recombinant Cdc14p was produced in bacteria, characterized, and shown to be a dual specificity protein phosphatase. file:yeast/CDC14/CDC14-deep-research-falcon.md Phosphothreonine is disfavored because its additional methyl group creates steric conflict in the active site. |
| GO:0005515 protein binding | IPI PMID:11274204 Characterization of the Net1 cell cycle-dependent regulator ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sic1, the Clb-CDK inhibitor and a physiological Cdc14 substrate, from Net1(1-600) binds Cdc14 directly and is a competitive inhibitor (Ki 3 nM) whose inhibition was measured with physiological substrates including Sic1. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. This is an enzyme-substrate relationship: the informative representation is the phosphatase activity annotation with the substrate as has_input in a GO-CAM, not a binding term on Cdc14. Removal does not assert that the interaction is false. Supporting Evidence: PMID:11274204 We show that the NH(2)-terminal fragment Net1(1-600) directly binds Cdc14 in vitro and is a highly specific competitive inhibitor of its activity (K(i) = 3 nm) with five different substrates including the physiologic targets Swi5 and Sic1. |
| GO:0005515 protein binding | IPI PMID:11274204 Characterization of the Net1 cell cycle-dependent regulator ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from Net1(1-600) binds Cdc14 directly and is a competitive inhibitor (Ki 3 nM) whose inhibition was measured with physiological substrates including Sic1. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:11274204 We show that the NH(2)-terminal fragment Net1(1-600) directly binds Cdc14 in vitro and is a highly specific competitive inhibitor of its activity (K(i) = 3 nm) with five different substrates including the physiologic targets Swi5 and Sic1. |
| GO:0005515 protein binding | IPI PMID:11805826 Functional organization of the yeast proteome by systematic ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Hsp42, a small heat-shock protein recovered in a high-throughput affinity-purification/mass-spectrometry screen, from a high-throughput TAP/mass-spectrometry proteome survey. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. Removal does not assert that the interaction is false. Supporting Evidence: PMID:11805826 We used tandem-affinity purification (TAP) and mass spectrometry in a large-scale approach to characterize multiprotein complexes in Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:14734533 Novel regulation of mitotic exit by the Cdc42 effectors Gic1... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Gic1, a Cdc42 effector that binds Cdc14 directly in vitro, from Gic1 binds Cdc14 directly in vitro but does not displace Cdc14 from Net1 and acts on mitotic exit independently of Cdc14 localization. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. Removal does not assert that the interaction is false. Supporting Evidence: PMID:14734533 Thus, Gic1 bound directly to Cdc14, Bfa1, Bub2, and Tem1. PMID:14734533 Together, these results suggest that Gic1 does not promote mitotic exit by directly regulating Cdc14 localization. |
| GO:0005515 protein binding | IPI PMID:14734533 Novel regulation of mitotic exit by the Cdc42 effectors Gic1... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from Gic1 binds Cdc14 directly in vitro but does not displace Cdc14 from Net1 and acts on mitotic exit independently of Cdc14 localization. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:14734533 Thus, Gic1 bound directly to Cdc14, Bfa1, Bub2, and Tem1. PMID:14734533 Together, these results suggest that Gic1 does not promote mitotic exit by directly regulating Cdc14 localization. |
| GO:0005515 protein binding | IPI PMID:15282295 Budding yeast silencing complexes and regulation of Sir2 act... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sir2, the NAD-dependent histone deacetylase co-subunit of the RENT complex, from purification of the native RENT silencing complex. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:15282295 we purified and characterized two budding yeast Sir2 complexes: the Sir2/Sir4 complex, which mediates silencing at mating-type loci and at telomeres, and the RENT complex, which mediates silencing at the ribosomal DNA repeats. |
| GO:0005515 protein binding | IPI PMID:15282295 Budding yeast silencing complexes and regulation of Sir2 act... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from purification of the native RENT silencing complex. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:15282295 we purified and characterized two budding yeast Sir2 complexes: the Sir2/Sir4 complex, which mediates silencing at mating-type loci and at telomeres, and the RENT complex, which mediates silencing at the ribosomal DNA repeats. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Hsp42, a small heat-shock protein recovered in a high-throughput affinity-purification/mass-spectrometry screen, from a genome-wide affinity-purification/mass-spectrometry complex survey. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. Removal does not assert that the interaction is false. Supporting Evidence: PMID:16429126 Here we report the first genome-wide screen for complexes in an organism, budding yeast, using affinity purification and mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:16713564 Downregulation of PP2A(Cdc55) phosphatase by separase initia... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from the separase/PP2A-Cdc55 study of Net1 phosphorylation and Cdc14 release. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:16713564 In metaphase, Cdc14 is kept inactive in the nucleolus by its inhibitor Net1. |
| GO:0005515 protein binding | IPI PMID:17043313 Inhibition of homologous recombination by a cohesin-associat... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sir2, the NAD-dependent histone deacetylase co-subunit of the RENT complex, from affinity purification of the RENT/Tof2/Lrs4-Csm1 rDNA silencing network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:17043313 We show that the Net1 and Sir2 subunits of the RENT (regulator of nucleolar silencing and telophase exit) silencing complex, and Fob1, which recruits RENT to the nontranscribed spacer I (NTS1) region of rDNA, are physically associated with Tof2. |
| GO:0005515 protein binding | IPI PMID:17043313 Inhibition of homologous recombination by a cohesin-associat... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from affinity purification of the RENT/Tof2/Lrs4-Csm1 rDNA silencing network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:17043313 We show that the Net1 and Sir2 subunits of the RENT (regulator of nucleolar silencing and telophase exit) silencing complex, and Fob1, which recruits RENT to the nontranscribed spacer I (NTS1) region of rDNA, are physically associated with Tof2. |
| GO:0005515 protein binding | IPI PMID:17043313 Inhibition of homologous recombination by a cohesin-associat... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Tof2, a Net1-related nucleolar protein that binds Cdc14 directly and modulates its nucleolar retention and rDNA function, from affinity purification of the RENT/Tof2/Lrs4-Csm1 rDNA silencing network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:17043313 We show that the Net1 and Sir2 subunits of the RENT (regulator of nucleolar silencing and telophase exit) silencing complex, and Fob1, which recruits RENT to the nontranscribed spacer I (NTS1) region of rDNA, are physically associated with Tof2. |
| GO:0005515 protein binding | IPI PMID:17892321 Structure-templated predictions of novel protein interaction... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Cbk1, the NDR/LATS-family protein kinase of the RAM network, from a structure-templated interaction prediction confirmed experimentally. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Cbk1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:17892321 We confirmed an unexpected predicted interaction between Cdc14 and the protein kinase Cbk1 |
| GO:0005515 protein binding | IPI PMID:18595708 A nucleolus-localized activator of Cdc14 phosphatase support... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from direct Tof2-Cdc14 binding that supports Cdc14 activity and rDNA segregation. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:18595708 Here, we report that, like Net1, Tof2 can bind to Cdc14 directly. Unlike Net1, however, Tof2 did not inhibit Cdc14 but supported Cdc14 phosphatase activity and in vivo function. |
| GO:0005515 protein binding | IPI PMID:18595708 A nucleolus-localized activator of Cdc14 phosphatase support... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Tof2, a Net1-related nucleolar protein that binds Cdc14 directly and modulates its nucleolar retention and rDNA function, from direct Tof2-Cdc14 binding that supports Cdc14 activity and rDNA segregation. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:18595708 Here, we report that, like Net1, Tof2 can bind to Cdc14 directly. Unlike Net1, however, Tof2 did not inhibit Cdc14 but supported Cdc14 phosphatase activity and in vivo function. |
| GO:0005515 protein binding | IPI PMID:18923139 Putting the brake on FEAR: Tof2 promotes the biphasic releas... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from Tof2-Cdc14 interaction that restrains full nucleolar release of Cdc14 during FEAR. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:18923139 We show that Tof2, which shares homology with the Cdc14 inhibitor Net1/Cfi1, interacts with Cdc14 phosphatase and its deletion suppresses defects in mitotic exit network (MEN) components. |
| GO:0005515 protein binding | IPI PMID:18923139 Putting the brake on FEAR: Tof2 promotes the biphasic releas... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Tof2, a Net1-related nucleolar protein that binds Cdc14 directly and modulates its nucleolar retention and rDNA function, from Tof2-Cdc14 interaction that restrains full nucleolar release of Cdc14 during FEAR. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:18923139 We show that Tof2, which shares homology with the Cdc14 inhibitor Net1/Cfi1, interacts with Cdc14 phosphatase and its deletion suppresses defects in mitotic exit network (MEN) components. |
| GO:0005515 protein binding | IPI PMID:18927509 The Polo-like kinase Cdc5 interacts with FEAR network compon... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Cdc5, the Polo-like kinase whose Polo-box domain binds Cdc14, from direct binding of the Cdc5 Polo-box domain to Cdc14. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Cdc5 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:18927509 We find that Cdc5 physically associates with Cdc14, as well as with the FEAR network components Slk19 and Esp1. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sir2, the NAD-dependent histone deacetylase co-subunit of the RENT complex, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Snf1, the AMPK-family protein kinase, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Snf1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Ste7, the MAP kinase kinase of the pheromone/filamentous-growth pathways, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Ste7 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Cka1, a catalytic subunit of casein kinase II, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Cka1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Cka2, a catalytic subunit of casein kinase II, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Cka2 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Mck1, a GSK-3 family protein kinase, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Mck1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Clb3, a B-type cyclin, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Relabel the uninformative 'protein binding' as cyclin binding. Reason: Generic GO:0005515 conveys no functional information. The partner Clb3 is a B-type cyclin (Clb3-Cdc28 is one of the CDK complexes whose substrates Cdc14 reverses), so GO:0030332 cyclin binding is the informative partner-class term. The interaction comes from a single AP-MS survey and is not disputed. Proposed replacements: cyclin binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Swe1, the Wee1-family protein kinase that phosphorylates Cdc28 Tyr19, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Swe1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Boi1, a Cdc42/Bem1-associated polarity protein, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. Removal does not assert that the interaction is false. Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Chk1, the DNA damage checkpoint protein kinase, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Chk1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sic1, the Clb-CDK inhibitor and a physiological Cdc14 substrate, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. This is an enzyme-substrate relationship: the informative representation is the phosphatase activity annotation with the substrate as has_input in a GO-CAM, not a binding term on Cdc14. Removal does not assert that the interaction is false. Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Sak1, a Snf1-activating protein kinase, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Sak1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Rsp5, the NEDD4-family HECT E3 ubiquitin ligase, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Relabel the uninformative 'protein binding' as ubiquitin protein ligase binding. Reason: Generic GO:0005515 conveys no functional information. The partner Rsp5 is a HECT E3 ubiquitin ligase, so GO:0031625 ubiquitin protein ligase binding is the informative partner-class term. The functional meaning of the association (substrate, regulator, or co-complex) has not been established; the interaction itself is not disputed. Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Fmp48, a putative serine/threonine protein kinase, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Fmp48 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Cbk1, the NDR/LATS-family protein kinase of the RAM network, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Cbk1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Bck1, the MAP kinase kinase kinase of the cell-wall-integrity (PKC) pathway, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Bck1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Met14, adenylylsulfate kinase, a sulfate-assimilation enzyme (not a protein kinase), from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. Met14 is a small-molecule (APS) kinase recovered as a kinase bait in the KPI screen, so no protein-kinase-binding relabel is appropriate. Removal does not assert that the interaction is false. Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Tof2, a Net1-related nucleolar protein that binds Cdc14 directly and modulates its nucleolar retention and rDNA function, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: GOA records a physical interaction between Cdc14 and Vhs1, a serine/threonine protein kinase, from the global kinase-phosphatase interaction (KPI) affinity-purification/mass-spectrometry network. The bare 'protein binding' term is uninformative; the partner is a protein kinase, so the interaction is better expressed as protein kinase binding. Reason: Generic GO:0005515 conveys no functional information. The WITH/FROM partner Vhs1 is a protein kinase, and Cdc14's kinase interactions (Cdc5 for its release, Cbk1/RAM coordination, MAPK and checkpoint kinases as candidate substrates) are a recognised feature of its role as a signalling hub, so replace with the informative GO:0019901 protein kinase binding. The interaction itself is not disputed. Proposed replacements: protein kinase binding Supporting Evidence: PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling, the DNA damage response, and metabolism |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sir2, the NAD-dependent histone deacetylase co-subunit of the RENT complex, from the chromatin-associated (mChIP) interactome survey. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:21179020 we report a large-scale study of the protein network of 102 chromatin-related proteins from budding yeast that were analyzed by mChIP coupled to mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from the chromatin-associated (mChIP) interactome survey. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:21179020 we report a large-scale study of the protein network of 102 chromatin-related proteins from budding yeast that were analyzed by mChIP coupled to mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Tof2, a Net1-related nucleolar protein that binds Cdc14 directly and modulates its nucleolar retention and rDNA function, from the chromatin-associated (mChIP) interactome survey. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:21179020 we report a large-scale study of the protein network of 102 chromatin-related proteins from budding yeast that were analyzed by mChIP coupled to mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:22078879 A quantitative model for ordered Cdk substrate dephosphoryla... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Ask1, a DASH/Dam1 kinetochore complex subunit and CDK substrate, from in vitro dephosphorylation kinetics of Cdk substrates by Cdc14 used to model ordered mitotic exit. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. This is an enzyme-substrate relationship: the informative representation is the phosphatase activity annotation with the substrate as has_input in a GO-CAM, not a binding term on Cdc14. Removal does not assert that the interaction is false. Supporting Evidence: PMID:22078879 Here, we show, using budding yeast, that dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing. |
| GO:0005515 protein binding | IPI PMID:22078879 A quantitative model for ordered Cdk substrate dephosphoryla... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sli15, the INCENP homolog of the chromosomal passenger complex and CDK substrate, from in vitro dephosphorylation kinetics of Cdk substrates by Cdc14 used to model ordered mitotic exit. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. This is an enzyme-substrate relationship: the informative representation is the phosphatase activity annotation with the substrate as has_input in a GO-CAM, not a binding term on Cdc14. Removal does not assert that the interaction is false. Supporting Evidence: PMID:22078879 Here, we show, using budding yeast, that dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing. |
| GO:0005515 protein binding | IPI PMID:22078879 A quantitative model for ordered Cdk substrate dephosphoryla... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Orc6, an origin recognition complex subunit and CDK substrate, from in vitro dephosphorylation kinetics of Cdk substrates by Cdc14 used to model ordered mitotic exit. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. This is an enzyme-substrate relationship: the informative representation is the phosphatase activity annotation with the substrate as has_input in a GO-CAM, not a binding term on Cdc14. Removal does not assert that the interaction is false. Supporting Evidence: PMID:22078879 Here, we show, using budding yeast, that dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing. |
| GO:0005515 protein binding | IPI PMID:22078879 A quantitative model for ordered Cdk substrate dephosphoryla... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Fin1, a spindle-stabilizing protein and CDK substrate, from in vitro dephosphorylation kinetics of Cdk substrates by Cdc14 used to model ordered mitotic exit. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. This is an enzyme-substrate relationship: the informative representation is the phosphatase activity annotation with the substrate as has_input in a GO-CAM, not a binding term on Cdc14. Removal does not assert that the interaction is false. Supporting Evidence: PMID:22078879 Here, we show, using budding yeast, that dephosphorylation of Cdk substrates involved in sequential mitotic exit events occurs with ordered timing. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Sir2, the NAD-dependent histone deacetylase co-subunit of the RENT complex, from the proteome-wide affinity-enrichment/mass-spectrometry interactome. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:37968396 Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry combined with a quantitative two-dimensional analysis strategy to comprehensively map the interactome of Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Net1/Cfi1, the nucleolar anchor and competitive inhibitor of Cdc14 in the RENT complex, from the proteome-wide affinity-enrichment/mass-spectrometry interactome. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:37968396 Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry combined with a quantitative two-dimensional analysis strategy to comprehensively map the interactome of Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: GOA records a physical interaction between Cdc14 and Tof2, a Net1-related nucleolar protein that binds Cdc14 directly and modulates its nucleolar retention and rDNA function, from the proteome-wide affinity-enrichment/mass-spectrometry interactome. Bare 'protein binding' adds no information about Cdc14's molecular function. Reason: Generic GO:0005515 is uninformative and no evidence-backed, more specific molecular-function term describes this partner relationship. The Cdc14-Net1-Sir2 (RENT) association and the Tof2/nucleolar-anchor relationship are already captured by the GO:0030869 RENT complex and GO:0005730 nucleolus annotations, which are the informative way to record it. Removal does not assert that the interaction is false. Supporting Evidence: PMID:37968396 Here we develop a sensitive high-throughput method using highly reproducible affinity enrichment coupled to mass spectrometry combined with a quantitative two-dimensional analysis strategy to comprehensively map the interactome of Saccharomyces cerevisiae. |
| GO:0005634 nucleus | HDA PMID:11914276 Subcellular localization of the yeast proteome. | ACCEPT | Summary: High-throughput immunolocalization places Cdc14 in the nucleus, consistent with its nucleolar sequestration and nucleoplasmic release during anaphase. Reason: Correct: the nucleolus is a nuclear sub-compartment and Cdc14 acts in the nucleoplasm on nuclear substrates during FEAR release. Supporting Evidence: PMID:11914276 By high-throughput immunolocalization of tagged gene products, we have determined the subcellular localization of 2744 yeast proteins. |
| GO:0005634 nucleus | IDA PMID:26090959 Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleu... | ACCEPT | Summary: Direct imaging shows Cdc14 confined to the nucleus during FEAR-mediated early-anaphase release (and during its meiosis I release), before MEN-driven export to the cytoplasm. Reason: Direct localization evidence; the nucleus is a site where Cdc14 acts on spindle, kinetochore and rDNA substrates. Supporting Evidence: PMID:26090959 We find that Cdc14 is confined to the nucleus during early mitotic anaphase release, and during its meiosis I release. |
| GO:0005730 nucleolus | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT-inferred nucleolar localization for the Cdc14 family. In budding yeast, Cdc14 resides in the nucleolus bound to Net1 for most of the cycle and, once activated in anaphase, acts on nucleolar substrates (condensin loading, Pol I inhibition, rDNA condensation), so is_active_in nucleolus is appropriate. Reason: Phylogenetic inference is corroborated by extensive direct S. cerevisiae evidence for nucleolar residence and nucleolar function (rDNA segregation via Tof2-supported activity). Supporting Evidence: PMID:12062061 Cdc14 is sequestered in the nucleolus by its inhibitor Net1/Cfi1 and is only released from the nucleolus during anaphase to inactivate mitotic CDK. PMID:18595708 Here, we report that, like Net1, Tof2 can bind to Cdc14 directly. Unlike Net1, however, Tof2 did not inhibit Cdc14 but supported Cdc14 phosphatase activity and in vivo function. |
| GO:0005730 nucleolus | IDA PMID:12062061 Mitotic exit network controls the localization of Cdc14 to t... | ACCEPT | Summary: Cdc14-5GFP is nucleolar for most of the cell cycle and is released during anaphase in a Cdc5-dependent manner. Reason: Direct localization evidence for the defining regulatory compartment of Cdc14. Supporting Evidence: PMID:12062061 Cdc14 is sequestered in the nucleolus by its inhibitor Net1/Cfi1 and is only released from the nucleolus during anaphase to inactivate mitotic CDK. |
| GO:0005730 nucleolus | IDA PMID:26090959 Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleu... | ACCEPT | Summary: Cdc14 scored as nucleolar outside anaphase in direct imaging of FEAR- and MEN-dependent release. Reason: Direct localization evidence. Supporting Evidence: PMID:26090959 We find that Cdc14 is confined to the nucleus during early mitotic anaphase release, and during its meiosis I release. |
| GO:0005730 nucleolus | IDA PMID:36259662 Phosphosites of the yeast centrosome component Spc110 contri... | ACCEPT | Summary: Cdc14-tagRFP-T is nucleolar in G1 and after cytokinesis, and re-localizes to the nucleoli as mitotic exit completes. Reason: Direct localization evidence; Cdc14 also acts on nucleolar substrates during anaphase, so is_active_in is defensible. Supporting Evidence: PMID:36259662 In telophase cells characterised by disassembled spindles, Cdc14 was localised at the bud SPB, nucleoli and bud neck (Type 3). |
| GO:0005730 nucleolus | IDA PMID:36259662 Phosphosites of the yeast centrosome component Spc110 contri... | ACCEPT | Summary: Cdc14-tagRFP-T is nucleolar in G1 and after cytokinesis, and re-localizes to the nucleoli as mitotic exit completes. Reason: Direct localization evidence. Supporting Evidence: PMID:36259662 In telophase cells characterised by disassembled spindles, Cdc14 was localised at the bud SPB, nucleoli and bud neck (Type 3). |
| GO:0005730 nucleolus | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic nucleolus annotation from UniProt subcellular-location mapping, consistent with abundant direct evidence. Reason: Correct electronic annotation. Supporting Evidence: PMID:12062061 Cdc14 is sequestered in the nucleolus by its inhibitor Net1/Cfi1 and is only released from the nucleolus during anaphase to inactivate mitotic CDK. |
| GO:0005730 nucleolus | NAS PMID:10219244 Exit from mitosis is triggered by Tem1-dependent release of ... | ACCEPT | Summary: RENT (Net1-Cdc14-Sir2) localizes to the nucleolus from G1 through anaphase; Cdc14 dissociates only in late anaphase. Reason: Supported by the discovery paper for RENT; nucleolar sequestration is the central regulatory feature of Cdc14. Supporting Evidence: PMID:10219244 From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1. In late anaphase, Cdc14 dissociates from RENT, disperses throughout the cell in a Tem1-dependent manner, and ultimately triggers mitotic exit. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT-inferred cytoplasmic activity of Cdc14-family phosphatases. In budding yeast, MEN-driven release exports Cdc14 to the cytoplasm in late anaphase, where it dephosphorylates cytokinesis regulators (Inn1, Iqg1) and, in meiosis, Atg13. Reason: Consistent with direct evidence that cytoplasmic Cdc14 is required for cytokinesis and that Cdc14 dephosphorylates Atg13 in the cytoplasm. Supporting Evidence: PMID:25371407 Since the cytokinetic machinery is accessible from the cytoplasm, we postulated that Cdc14 release into this cellular compartment is required for cytokinesis. PMID:35238874 Cdc14 is activated in anaphase I and II, accompanying its subcellular relocation from the nucleolus to the cytoplasm, where it dephosphorylates Atg13 to stimulate Atg1 kinase activity and thus autophagy. |
| GO:0005737 cytoplasm | IDA PMID:26090959 Cdc14 Early Anaphase Release, FEAR, Is Limited to the Nucleu... | ACCEPT | Summary: Cdc14 is exported to the cytoplasm in late anaphase in a MEN-dependent manner. Reason: Direct localization evidence. Supporting Evidence: PMID:26090959 By late anaphase, Cdc14 had been efficiently exported to the cytoplasm (Fig 1C), indicating MEN activity. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic cytoplasm annotation from UniProt subcellular-location mapping, consistent with direct evidence for MEN-dependent cytoplasmic release. Reason: Correct electronic annotation. Supporting Evidence: PMID:26090959 By late anaphase, Cdc14 had been efficiently exported to the cytoplasm (Fig 1C), indicating MEN activity. |
| GO:0005737 cytoplasm | IMP PMID:25371407 Identification of Cdk targets that control cytokinesis. | ACCEPT | Summary: A nuclear-retained Cdc14-NLS variant fails to support cytokinesis, showing that Cdc14 must act in the cytoplasm to dephosphorylate cytokinetic Cdk targets such as Inn1. Reason: Direct functional evidence that Cdc14 is active in the cytoplasm. Supporting Evidence: PMID:25371407 Since the cytokinetic machinery is accessible from the cytoplasm, we postulated that Cdc14 release into this cellular compartment is required for cytokinesis. PMID:25371407 This confirms Inn1 as a Cdk target whose dephosphorylation by Cdc14 is crucial for successful cytokinesis. |
| GO:0005816 spindle pole body | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT-inferred SPB localization within the fungal Cdc14 clade. Budding-yeast Cdc14 is observed at the spindle pole bodies in a MEN-dependent manner, where it dephosphorylates SPB substrates (e.g. Sfi1). Reason: Corroborated by direct localization evidence and an SPB substrate (Sfi1 dephosphorylation). Supporting Evidence: PMID:12062061 We observed Cdc14-5GFP at the SPB in addition to the nucleolus. PMID:24954044 Moreover, Cdc14 dephosphorylates C-Sfi1 to prepare it for a new round of duplication, and the kinase Mps1 promotes Sfi1 extension in G1. |
| GO:0005816 spindle pole body | IDA PMID:12062061 Mitotic exit network controls the localization of Cdc14 to t... | ACCEPT | Summary: Cdc14-5GFP is observed at the SPB in addition to the nucleolus, and its SPB localization depends on MEN components and Bub2. Reason: Direct localization evidence. Supporting Evidence: PMID:12062061 We observed Cdc14-5GFP at the SPB in addition to the nucleolus. |
| GO:0005816 spindle pole body | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-predicted SPB localization, consistent with direct imaging. Reason: Correct electronic annotation. Supporting Evidence: PMID:12062061 We observed Cdc14-5GFP at the SPB in addition to the nucleolus. |
| GO:0005935 cellular bud neck | IDA PMID:36259662 Phosphosites of the yeast centrosome component Spc110 contri... | ACCEPT | Summary: In telophase cells Cdc14 localizes to the bud neck (together with the bud SPB and nucleoli), consistent with its role in dephosphorylating cytokinesis regulators at the division site. Reason: Direct localization evidence; matches the requirement for Cdc14 in Iqg1/Inn1/Chs2 dephosphorylation at the neck. Supporting Evidence: PMID:36259662 In telophase cells characterised by disassembled spindles, Cdc14 was localised at the bud SPB, nucleoli and bud neck (Type 3). |
| GO:0005935 cellular bud neck | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic bud-neck annotation from UniProt subcellular-location mapping, consistent with direct imaging. Reason: Correct electronic annotation. Supporting Evidence: PMID:36259662 In telophase cells characterised by disassembled spindles, Cdc14 was localised at the bud SPB, nucleoli and bud neck (Type 3). |
| GO:0007059 chromosome segregation | IMP PMID:16769819 Transcription of ribosomal genes can cause nondisjunction. | MODIFY | Summary: Cdc14 is required for mitotic segregation of the rDNA array: cdc14-1 cells cannot segregate full-length, highly transcribed rDNA, and the defect is suppressed by shortening the array or silencing Pol I. Cdc14 does the work by dephosphorylating condensin (Smc4) and inhibiting Pol I so that condensin can load on rDNA. Reason: The essence is correct and the mechanism is direct (Cdc14 substrates condensin and Pol I), but 'chromosome segregation' is broad; the paper studies mitotic sister-chromatid (rDNA) disjunction, so GO:0000070 mitotic sister chromatid segregation is the more accurate term. Treated as a downstream anaphase function rather than the core mitotic-exit function. Proposed replacements: mitotic sister chromatid segregation Supporting Evidence: PMID:16769819 We show that rDNA segregation requires Cdc14 partly because of its physical length but most importantly because a fraction of ribosomal RNA (rRNA) genes are transcribed at very high rates. PMID:24319056 Cdc14-mediated dephosphorylation of Smc4 and Bud3 is essential for proper mitosis and cytokinesis, respectively. |
| GO:0007096 regulation of exit from mitosis | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT-inferred regulation of exit from mitosis. This is the defining function of budding-yeast Cdc14: released by the FEAR and MEN pathways in anaphase, it reverses Cdc28 phosphorylation of Cdh1, Sic1 and Swi5 to extinguish Clb-CDK activity and reset G1. Reason: Core function, grounded by the S. cerevisiae experimental annotations that seeded the node; the term's definition (progression from anaphase/telophase to G1 associated with conversion from high to low mitotic CDK activity) describes exactly what Cdc14 does. Supporting Evidence: PMID:10219244 From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1. In late anaphase, Cdc14 dissociates from RENT, disperses throughout the cell in a Tem1-dependent manner, and ultimately triggers mitotic exit. PMID:9295359 The catalytically inactive Cdc14p C283S/R289A mutant is not able to suppress the temperature sensitivity of a cdc14-1(ts) mutant nor replace the wild type gene in vivo, demonstrating that phosphatase activity is required for the cell cycle function of Cdc14p. file:yeast/CDC14/CDC14-deep-research-falcon.md Cdc14 is essential for late-anaphase-to-G1 progression in budding yeast. |
| GO:0007096 regulation of exit from mitosis | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-predicted regulation of exit from mitosis, matching the core experimental function. Reason: Correct electronic annotation of the core function. Supporting Evidence: PMID:10219244 From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1. In late anaphase, Cdc14 dissociates from RENT, disperses throughout the cell in a Tem1-dependent manner, and ultimately triggers mitotic exit. |
| GO:0007096 regulation of exit from mitosis | IMP PMID:10219244 Exit from mitosis is triggered by Tem1-dependent release of ... | ACCEPT | Summary: Discovery of RENT and of Tem1-dependent release: Cdc14 is held inactive by Net1 in the nucleolus until late anaphase, when it disperses through the cell and triggers mitotic exit; net1-1 bypasses tem1 lethality. Reason: Core function with foundational IMP evidence. Supporting Evidence: PMID:10219244 From G1 through anaphase, RENT localizes to the nucleolus, and Cdc14 activity is inhibited by Net1. In late anaphase, Cdc14 dissociates from RENT, disperses throughout the cell in a Tem1-dependent manner, and ultimately triggers mitotic exit. |
| GO:0010508 positive regulation of autophagy | IDA PMID:35238874 Cdc14 spatiotemporally dephosphorylates Atg13 to activate au... | KEEP AS NON CORE | Summary: Cdc14 released to the cytoplasm in meiotic anaphase I and II dephosphorylates Atg13, activating Atg1 and stimulating autophagy required for efficient meiotic progression and sporulation. Reason: Direct, substrate-level evidence (Atg13 dephosphorylation), but autophagy regulation is a context-specific meiotic/starvation role secondary to the core mitotic-exit function. Supporting Evidence: PMID:35238874 Cdc14 is activated in anaphase I and II, accompanying its subcellular relocation from the nucleolus to the cytoplasm, where it dephosphorylates Atg13 to stimulate Atg1 kinase activity and thus autophagy. |
| GO:0016479 negative regulation of transcription by RNA polymerase I | IMP PMID:19158678 Cdc14 inhibits transcription by RNA polymerase I during anap... | KEEP AS NON CORE | Summary: Cdc14 inhibits RNA polymerase I transcription of rDNA during anaphase; its phosphatase activity is required for Pol I inhibition in vitro and in vivo, and this inhibition is a prerequisite for condensin loading and rDNA disjunction. Reason: Direct evidence that Cdc14 does the work (phosphatase-dependent Pol I inhibition), but this is an anaphase-specific downstream function serving rDNA segregation rather than the core mitotic-exit switch. Supporting Evidence: PMID:19158678 Here we show that Cdc14, a protein phosphatase required for nucleolar segregation and mitotic exit, inhibits transcription of yeast ribosomal genes (rDNA) during anaphase. The phosphatase activity of Cdc14 is required for RNA polymerase I (Pol I) inhibition in vitro and in vivo. |
| GO:0030869 RENT complex | IDA PMID:10219244 Exit from mitosis is triggered by Tem1-dependent release of ... | ACCEPT | Summary: Mass-spectrometric analysis of Net1 purifications identified RENT (Net1, Cdc14, Sir2) as a nucleolar complex in which Net1 inhibits Cdc14 until late anaphase. Reason: Cdc14 is a defining subunit of RENT; the complex is the sequestration/inhibition mechanism central to Cdc14 regulation. Supporting Evidence: PMID:10219244 mass spectrometric analysis reveals that it is a key component of a multifunctional complex, denoted RENT (for regulator of nucleolar silencing and telophase), that also contains Cdc14 and the silencing regulator Sir2. |
| GO:0030869 RENT complex | IPI PMID:12923057 Association of the RENT complex with nontranscribed and codi... | ACCEPT | Summary: RENT (Net1-Sir2-Cdc14) is the nucleolar silencing complex whose Net1 and Sir2 subunits were mapped to rDNA; Cdc14 co-purifies as a RENT subunit. Reason: Consistent with the RENT discovery paper; Cdc14 is a bona fide RENT subunit. Supporting Evidence: PMID:12923057 rDNA silencing is mediated by a Sir2-containing complex called RENT (regulator of nucleolar silencing and telophase exit). PMID:10219244 mass spectrometric analysis reveals that it is a key component of a multifunctional complex, denoted RENT (for regulator of nucleolar silencing and telophase), that also contains Cdc14 and the silencing regulator Sir2. |
| GO:0032467 positive regulation of cytokinesis | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT-inferred positive regulation of cytokinesis within the fungal Cdc14 clade. Budding-yeast Cdc14 couples cytokinesis to mitotic exit by dephosphorylating cytokinetic Cdk targets (Iqg1, Inn1, Chs2, Bud3, Aip1, Ede1) after its cytoplasmic release. Reason: Strongly corroborated by direct S. cerevisiae evidence; coordinating cytokinesis with nuclear division is an integral part of Cdc14's mitotic-exit function. Supporting Evidence: PMID:25371407 downregulation of cyclin-dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. PMID:26085509 Overexpression of Cdc14 resulted in premature actin ring assembly, whereas inhibition of Cdc14 function prevented actin ring formation. |
| GO:0032467 positive regulation of cytokinesis | IMP PMID:25371407 Identification of Cdk targets that control cytokinesis. | ACCEPT | Summary: Cdk downregulation together with Cdc14 activation controls each step of cytokinesis; nuclear-retained Cdc14 fails to support cytokinesis, and Cdc14-mediated dephosphorylation of Inn1 is required. Reason: Direct IMP evidence with substrate-level mechanism; core coupling of cytokinesis to mitotic exit. Supporting Evidence: PMID:25371407 downregulation of cyclin-dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. PMID:25371407 This confirms Inn1 as a Cdk target whose dephosphorylation by Cdc14 is crucial for successful cytokinesis. |
| GO:0032954 regulation of cytokinetic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA-predicted regulation of cytokinetic process, consistent with the experimental evidence for Cdc14 control of actomyosin ring assembly, furrow ingression and cell separation. Reason: Correct, if generic, electronic annotation. Supporting Evidence: PMID:25371407 downregulation of cyclin-dependent kinase (Cdk) activity, together with upregulation of its counteracting phosphatase Cdc14, controls each of the sequential steps of cytokinesis, including furrow ingression, membrane resolution and cell separation in budding yeast. |
| GO:0033554 cellular response to stress | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA-predicted generic stress-response term. Cdc14 does participate in stress responses (NaCl/osmotic response coordination, TORC1-inactivation-induced autophagy), but these are secondary to its cell-cycle role. Reason: Supported in broad terms by experimental work on the osmotic-stress and starvation responses, but generic and clearly non-core. Supporting Evidence: PMID:25411400 Cdc14 is critical for coordinating distinct facets of the NaCl response PMID:29694832 Cdc14 phosphatase was required for optimal Atg13 dephosphorylation, pre-autophagosomal structure formation, and autophagy induction after TORC1 inactivation. |
| GO:0044732 mitotic spindle pole body | IDA PMID:36259662 Phosphosites of the yeast centrosome component Spc110 contri... | ACCEPT | Summary: Cdc14 localizes to the mitotic SPBs in late anaphase, in a MEN-dependent manner. Reason: Direct localization evidence. Supporting Evidence: PMID:36259662 By contrast, in late-anaphase cells with long spindles, where the bud SPB had reached the bud cortex, Cdc14 was predominantly found at both SPBs (Type 1) or at the bud SPB (Type 2). |
| GO:0051229 meiotic spindle disassembly | IMP PMID:12737806 The Cdc14 phosphatase and the FEAR network control meiotic s... | KEEP AS NON CORE | Summary: cdc14-1, slk19 and spo12 mutants fail to disassemble the meiosis I spindle in a timely fashion, so both meiotic segregation phases occur on the persisting MI spindle; Cdc14 and the FEAR network are required for meiosis I spindle disassembly and for two consecutive segregation phases. Reason: Solid IMP evidence for a meiotic role; a context-specific (meiotic) function outside the core mitotic-exit activity. Supporting Evidence: PMID:12737806 Our results show that Cdc14, Slk19, and Spo12 are not only required for meiosis I spindle disassembly but also play a pivotal role in establishing two consecutive chromosome segregation phases, a key feature of the meiotic cell cycle. |
| GO:0070550 rDNA chromatin condensation | IMP PMID:35477092 Interphase chromosome condensation in nutrient-starved condi... | KEEP AS NON CORE | Summary: Cdc14 (with Rpd3, Hmo1, CLIP and cohibin, but not condensin) is required for TORC1-inactivation-induced rDNA condensation in interphase G1 cells; Cdc14 also drives anaphase rDNA condensation through condensin. Reason: IMP evidence for a nutrient-stress rDNA condensation role, consistent with Cdc14's known repression of rRNA transcription and condensin regulation; a downstream nucleolar function, not the core. Supporting Evidence: PMID:35477092 The histone deacetylase Rpd3 and Cdc14, which repress rRNA transcription, were both required for the interphase rDNA condensation. |
| GO:0071103 DNA conformation change | IGI PMID:41533572 Safeguarding genome integrity: Polo-like kinase Cdc5 and pho... | KEEP AS NON CORE | Summary: Cdc14 and Cdc5 jointly promote Top2-mediated resolution of sister-chromatid catenanes in anaphase, by regulating Top2 phosphorylation (Cdc14 opposes Top2 phosphorylation) and SUMOylation/localization. The IGI partner is CDC5. Reason: Genetic evidence is sound, but the conformation change itself is performed by Top2; Cdc14 contributes by dephosphorylating and thereby tuning Top2, so its involvement is regulatory and downstream of its core function. Retained as non-core; a regulation-of term would be more precise if one becomes available. Supporting Evidence: PMID:41533572 We show that Cdc14 and Cdc5 collaborate to facilitate the resolution of DNA catenanes, the predominant species of DNA intertwines in mitosis, by regulating Topoisomerase II (Top2) function, both through SUMOylation and phosphorylation. PMID:41533572 Cdc5 promotes, whereas Cdc14 opposes, Top2 phosphorylation, defining an antagonistic regulatory axis that ensures the precise tuning of Top2 activity required for faithful chromosome segregation. |
| GO:0071470 cellular response to osmotic stress | IMP PMID:25411400 Pathway connectivity and signaling coordination in the yeast... | KEEP AS NON CORE | Summary: In a phosphoproteomic/transcriptomic dissection of the NaCl response, cdc14-3 cells show defective osmo-responsive transcription overlapping the Hog1 program and aberrant Hog1 nuclear localization, identifying Cdc14 as a hub coordinating facets of the osmotic-stress response. Reason: IMP evidence for a stress-response role; largely indirect (no direct Cdc14-Hog1 interaction) and clearly secondary to the cell-cycle function. Supporting Evidence: PMID:25411400 Cdc14 is critical for coordinating distinct facets of the NaCl response |
| GO:0071958 new mitotic spindle pole body | IDA PMID:36259662 Phosphosites of the yeast centrosome component Spc110 contri... | ACCEPT | Summary: In late anaphase and telophase Cdc14 is found preferentially at the bud (daughter) SPB, the new SPB that receives the MEN signal. Reason: Direct localization evidence; asymmetric enrichment at the bud-directed SPB matches MEN localization. Supporting Evidence: PMID:36259662 By contrast, in late-anaphase cells with long spindles, where the bud SPB had reached the bud cortex, Cdc14 was predominantly found at both SPBs (Type 1) or at the bud SPB (Type 2). |
| GO:0072686 mitotic spindle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT-inferred mitotic spindle localization (donors: S. pombe Clp1 and C. elegans CDC-14). Budding-yeast Cdc14 associates with the anaphase spindle/midzone and SPBs, where it dephosphorylates spindle substrates such as Fin1 and Ase1. Reason: Consistent with S. cerevisiae substrate data (Fin1 dephosphorylation targets it to spindle poles and microtubules) and with SPB/spindle localization; the family-level inference is sound. Supporting Evidence: PMID:17173039 In anaphase, when Clb5-Cdk1 is inactivated, Fin1 is dephosphorylated by the phosphatase Cdc14. PMID:17173039 Fin1 dephosphorylation targets it to the poles and microtubules of the elongating spindle, where it contributes to spindle integrity. PMID:36259662 By contrast, in late-anaphase cells with long spindles, where the bud SPB had reached the bud cortex, Cdc14 was predominantly found at both SPBs (Type 1) or at the bud SPB (Type 2). |
| GO:0140013 meiotic nuclear division | IDA PMID:35238874 Cdc14 spatiotemporally dephosphorylates Atg13 to activate au... | KEEP AS NON CORE | Summary: Cdc14 is activated in meiotic anaphase I and II, relocating from the nucleolus to the cytoplasm, and its activity promotes meiotic progression, exit and sporulation. Reason: Direct evidence of a meiotic role; a context-specific function outside the core mitotic-exit activity. Supporting Evidence: PMID:35238874 Cdc14 is activated in anaphase I and II, accompanying its subcellular relocation from the nucleolus to the cytoplasm, where it dephosphorylates Atg13 to stimulate Atg1 kinase activity and thus autophagy. |
| GO:1903501 positive regulation of mitotic actomyosin contractile ring assembly | IGI PMID:26085509 Dephosphorylation of Iqg1 by Cdc14 regulates cytokinesis in ... | ACCEPT | Summary: The nonphosphorylatable iqg1-4A allele rescues the failure of cdc14-1 cells to form actin rings, placing Cdc14-mediated Iqg1 dephosphorylation upstream of actomyosin ring assembly. Reason: Direct genetic (IGI with IQG1) and biochemical evidence that Cdc14 promotes actin ring assembly by dephosphorylating Iqg1; part of Cdc14's core cytokinesis-coupling function. Supporting Evidence: PMID:26085509 Of importance, the iqg1-4A mutant rescued the inability of cdc14-1 cells to form actin rings. PMID:26085509 Cdc14 associated with Iqg1, dependent on several CHD-flanking Cdk sites, and efficiently dephosphorylated these sites in vitro. |
| GO:1903501 positive regulation of mitotic actomyosin contractile ring assembly | IMP PMID:26085509 Dephosphorylation of Iqg1 by Cdc14 regulates cytokinesis in ... | ACCEPT | Summary: Cdc14 overexpression causes premature actin ring assembly whereas loss of Cdc14 function prevents it, and Cdc14 dephosphorylates the CHD-flanking Cdk sites of Iqg1. Reason: Direct IMP evidence with substrate-level mechanism; part of Cdc14's core cytokinesis-coupling function. Supporting Evidence: PMID:26085509 Overexpression of Cdc14 resulted in premature actin ring assembly, whereas inhibition of Cdc14 function prevented actin ring formation. PMID:26085509 Cdc14 associated with Iqg1, dependent on several CHD-flanking Cdk sites, and efficiently dephosphorylated these sites in vitro. |
| GO:2000786 positive regulation of autophagosome assembly | IMP PMID:29694832 Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeas... | KEEP AS NON CORE | Summary: Cdc14 is required for optimal Atg13 dephosphorylation, pre-autophagosomal structure formation and autophagy induction after TORC1 inactivation, and Cdc14 activation provokes autophagy even in nutrient-rich conditions. Reason: Direct IMP evidence for a starvation-response role acting through the Atg13 substrate; secondary to the core mitotic-exit function. Supporting Evidence: PMID:29694832 Cdc14 phosphatase was required for optimal Atg13 dephosphorylation, pre-autophagosomal structure formation, and autophagy induction after TORC1 inactivation. |
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Download this section (compressed HTML)Q: Which of the 455 candidate Cdc14 substrates identified by phosphoproteomics are direct, PxL-docked targets versus indirect consequences of CDK inactivation or Fin1-PP1/PP2A relays, and how does substrate docking set the ordered timing of dephosphorylation during mitotic exit?
Q: Is there any physiological phosphotyrosine substrate of Cdc14 that would justify retaining a protein tyrosine phosphatase annotation, or is its in vivo activity exclusively directed at CDK pSer-Pro sites?
Q: What is the direct substrate through which Cdc14 coordinates the osmotic-stress (Hog1) transcriptional response, given that no direct Cdc14-Hog1 interaction was detected?
Experiment: Substrate-trapping (C283S/D253A) Cdc14 pull-downs combined with PxL-motif mutagenesis and in vitro dephosphorylation kinetics to distinguish direct from indirect substrates among the phosphoproteomic candidates, especially Top2, Hog1-pathway components and Atg13.
Experiment: Phosphotyrosine-specific phosphoproteomics comparing wild-type and cdc14-ts cells at mitotic exit to test whether any tyrosine-phosphorylated proteins are Cdc14-dependent in vivo.
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