STE7

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000165 MAPK cascade	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA placing Ste7 in the MAPK cascade from the MAP2K clade (PTN000684494). Reason: Ste7 is the MAP2K tier of the Ste11-Ste7-Fus3/Kss1 cascades; the generic MAPK cascade term is correct and consistent with the phylogenetic placement of Ste7 among MAP2Ks. More specific pathway terms (GO:0071507, GO:0001402) are annotated experimentally. Supporting Evidence: PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 file:yeast/STE7/STE7-deep-research-falcon.md Ste7 is best described as an ATP-dependent, dual-specificity MAPKK that is activated by the MAPKKK Ste11 and activates the MAPKs Fus3 and Kss1 through phosphorylation of their activation-loop threonine and tyrosine.
GO:0000196 cell integrity MAPK cascade	IGI PMID:10880465 Defects in protein glycosylation cause SHO1-dependent activa...	MODIFY	Summary: Genetic interaction (with DPM1) placing Ste7 in a Sho1-Ste11-Ste7-Kss1-Ste12 pathway activated by glycosylation defects and contributing to cell wall integrity. Reason: The paper supports Ste7 acting in a Kss1-type MAPK cascade that responds to protein-glycosylation defects and contributes to cell wall integrity. However, GO:0000196 cell integrity MAPK cascade is defined as the cascade containing the Slt2/Pmk1 MAP kinase (Pkc1-Bck1-Mkk1/2-Slt2 in yeast), in which Ste7 is not a tier; the MAP2Ks of that cascade are Mkk1/Mkk2. The essence (Ste7 functions in a MAPK cascade here) is sound, so the annotation should be expressed with the generic MAPK cascade term rather than the Slt2-specific cascade. Proposed replacements: MAPK cascade Supporting Evidence: PMID:10880465 We specifically suggest that a Sho1 --> Ste20/Ste50 --> Ste11 --> Ste7 --> Kss1 --> Ste12 pathway is responsible for activation of FUS1 transcription in these mutants. PMID:10880465 we suggest that the Sho1 --> Ste12 pathway contributes to maintenance of cell wall integrity in vegetative cells.
GO:0000749 response to pheromone triggering conjugation with cellular fusion	IDA PMID:8668180 Signaling in the yeast pheromone response pathway: specific ...	ACCEPT	Summary: Ste7-Kss1/Fus3 complexes from pheromone-treated cells show pheromone-stimulated reciprocal phosphorylation; Ste7 docking-region deletions reduce pheromone signaling in vivo. Reason: Ste7 is an essential signalling kinase of the pheromone response; this parent process term is correct. The more precise process is GO:0071507 pheromone response MAPK cascade, which is also annotated. Supporting Evidence: PMID:8668180 Kss1 and Fus3 are mitogen-activated protein kinases (MAPKs or ERKs), and Ste7 is their activating MAPK/ERK kinase (MEK), in the pheromone response pathway of Saccharomyces cerevisiae. PMID:8668180 Deletions of Ste7 in the region required for its stable association with Kss1 and Fus3 in vitro significantly decreased (but did not eliminate) signaling in vivo. PMID:8668180 Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner
GO:0001402 signal transduction involved in filamentous growth	IMP PMID:15456892 Persistent activation by constitutive Ste7 promotes Kss1-med...	ACCEPT	Summary: Constitutive Ste7 variants activate Kss1 but not Fus3 in vivo and promote filamentation gene expression and invasive growth. Reason: Ste7 is the MAP2K of the filamentous/invasive growth pathway, where it activates Kss1 largely independently of Ste5. Signal transduction involved in filamentous growth directly captures this core signalling role. Supporting Evidence: PMID:15456892 This specificity occurs because constitutive Ste7 activates Kss1, but not Fus3, in vivo and promotes filamentation gene expression while suppressing mating gene expression. PMID:15456892 Instead, we found that constitutive Ste7 promotes invasion without supporting mating responses. PMID:9363895 We show instead that Kss1 is the principal target of Ste7 in the invasive-growth response in both haploids and diploids.
GO:0001403 invasive growth in response to glucose limitation	IGI PMID:9363895 Inhibitory and activating functions for MAPK Kss1 in the S. ...	KEEP AS NON CORE	Summary: Genetic interaction with KSS1 shows that Kss1 is the principal target of Ste7 in haploid and diploid invasive growth. Reason: Ste7 is required for haploid invasive growth, but its direct contribution is relaying the filamentous-growth signal to Kss1 (captured by GO:0001402). The developmental growth outcome is a valid but downstream, non-core process annotation. Supporting Evidence: PMID:9363895 We show instead that Kss1 is the principal target of Ste7 in the invasive-growth response in both haploids and diploids. PMID:9363895 Ste7 acts to relieve this negative regulation by switching Kss1 from an inhibitor to an activator.
GO:0001403 invasive growth in response to glucose limitation	IMP PMID:8001818 Elements of a single MAP kinase cascade in Saccharomyces cer...	KEEP AS NON CORE	Summary: STE7 mutants are defective in haploid filament formation and agar penetration (invasive growth). Reason: Correct loss-of-function phenotype; Ste7 acts in invasive growth as the MAP2K of the signalling pathway rather than as a morphogenetic effector, so this developmental term is kept as non-core. Supporting Evidence: PMID:8001818 We find that the same components of the MAP kinase cascade necessary for diploid pseudohyphal development (STE20, STE11, STE7, and STE12) are also required for both filament formation and agar penetration in haploids.
GO:0004672 protein kinase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro (Ser/Thr kinase active site) mapping to protein kinase activity. Reason: Ste7 is a catalytically active protein kinase. The term is general; GO:0004708 MAP kinase kinase activity is the precise function and is supported experimentally. Supporting Evidence: file:yeast/STE7/STE7-uniprot.txt protein kinase family. MAP kinase kinase subfamily. PMID:8384702 Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro.
GO:0004708 MAP kinase kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA of MAP kinase kinase activity from the MAP2K clade (PTN000684494); Ste7 (SGD:S000002318) is itself among the experimental sources, alongside Pbs2 and metazoan MEKs. Reason: Ste7 is a canonical MAP2K; its dual-specificity phosphorylation of Fus3 and Kss1 is established biochemically. Its presence among the IBA sources reflects its own experimental grounding, and the IBA adds that the activity is inherited across the MAP2K clade. Correct level of specificity. Supporting Evidence: PMID:8384702 Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro. PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 file:yeast/STE7/STE7-deep-research-falcon.md Ste7 is best described as an ATP-dependent, dual-specificity MAPKK that is activated by the MAPKKK Ste11 and activates the MAPKs Fus3 and Kss1 through phosphorylation of their activation-loop threonine and tyrosine.
GO:0004708 MAP kinase kinase activity	IDA PMID:8384702 MAP kinase-related FUS3 from S. cerevisiae is activated by S...	ACCEPT	Summary: Purified Ste7 phosphorylates Fus3 at the activating Thr/Tyr sites and stimulates its kinase activity in vitro. Reason: Direct biochemical demonstration of dual-specificity MAPKK activity toward Fus3. Core molecular function of Ste7. Supporting Evidence: PMID:8384702 Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro. PMID:8384702 we argue that STE7 is the physiological activator of FUS3
GO:0004708 MAP kinase kinase activity	IDA PMID:8668180 Signaling in the yeast pheromone response pathway: specific ...	ACCEPT	Summary: Ste7 in Ste7-Kss1/Fus3 complexes isolated from yeast phosphorylates Kss1 and Fus3 in a pheromone-stimulated manner. Reason: Direct kinase assays with Kss1 and Fus3 as substrates support MAP kinase kinase activity toward both MAPKs. Supporting Evidence: PMID:8668180 Kss1 and Fus3 are mitogen-activated protein kinases (MAPKs or ERKs), and Ste7 is their activating MAPK/ERK kinase (MEK), in the pheromone response pathway of Saccharomyces cerevisiae. PMID:8668180 Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner
GO:0004708 MAP kinase kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation (ARBA, InterPro Byr1-like catalytic domain IPR049613, EC 2.7.12.2). Reason: Consistent with experimental evidence that Ste7 is the MAP2K for Fus3 and Kss1. Supporting Evidence: file:yeast/STE7/STE7-uniprot.txt protein kinase family. MAP kinase kinase subfamily. PMID:8384702 Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro.
GO:0004713 protein tyrosine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea (RHEA:10596, tyrosine phosphorylation) mapping to protein tyrosine kinase activity. Reason: Ste7 is a dual-specificity kinase that phosphorylates the activation-loop tyrosine of Fus3 and Kss1, so tyrosine kinase activity is factually correct; it is a component of the more informative GO:0004708 MAP kinase kinase activity. Supporting Evidence: PMID:8384702 Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro.
GO:0005515 protein binding	IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ...	MODIFY	Summary: Genome-wide yeast two-hybrid screen detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:11283351 A comprehensive two-hybrid analysis to explore the yeast pro...	MODIFY	Summary: Genome-wide yeast two-hybrid screen detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:11283351 Here we have completed the comprehensive analysis using this system to identify 4,549 two-hybrid interactions among 3,278 proteins. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy...	MODIFY	Summary: High-throughput affinity purification-mass spectrometry detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:11805837 Numerous protein complexes were identified, including many new interactions in various signalling pathways and in the DNA damage response. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:15020407 Fus1p interacts with components of the Hog1p mitogen-activat...	MODIFY	Summary: Two-hybrid matrix of pheromone pathway components detects Ste7 interaction with the MAP kinase Fus3, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Fus3 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:15020407 A two-hybrid matrix containing fusion proteins and pheromone response pathway signaling molecules reveals that Fus1p may participate in a complex network of interactions. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:19303851 The Ste5 scaffold directs mating signaling by catalytically ...	MODIFY	Summary: Purified-protein kinetic and binding study detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:19303851 We find that Fus3 is intrinsically a poor substrate for activated Ste7, while Kss1 is intrinsically a very good substrate. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:19303851 The Ste5 scaffold directs mating signaling by catalytically ...	MODIFY	Summary: Purified-protein kinetic and binding study detects Ste7 interaction with the MAP kinase Fus3, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Fus3 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:19303851 We find that Fus3 is intrinsically a poor substrate for activated Ste7, while Kss1 is intrinsically a very good substrate. PMID:19303851 Phosphorylation of Fus3 occurs only in the combined presence of Ste7 and Ste5, and this mechanism explains why Fus3 is only activated by mating input. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:19303851 The Ste5 scaffold directs mating signaling by catalytically ...	MODIFY	Summary: Binding assays with purified Ste5 minimal-scaffold domain detects Ste7 binding to the Ste5 scaffold protein. Reason: Bare protein binding is uninformative. Ste5 is the canonical MAPK-cascade scaffold that tethers Ste11, Ste7 and Fus3; its minimal-scaffold (VWA) domain binds Ste7 tightly and allosterically unlocks Fus3 for Ste7-catalysed phosphorylation (PMID:19303851). Scaffold protein binding (GO:0097110) describes this interaction informatively. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:19303851 The Ste5-ms domain binds tightly to Ste7, but only very weakly to Fus3.
GO:0005515 protein binding	IPI PMID:20489023 A global protein kinase and phosphatase interaction network ...	MODIFY	Summary: Kinase-phosphatase interaction network (AP-MS) detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:20489023 A global protein kinase and phosphatase interaction network ...	MODIFY	Summary: Kinase-phosphatase interaction network (AP-MS) detects Ste7 interaction with the MAP kinase Fus3, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Fus3 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:20489023 A global protein kinase and phosphatase interaction network ...	REMOVE	Summary: Kinase-phosphatase interaction network (AP-MS) co-purifies Ste7 with the HOG pathway MAPK Hog1. Reason: Bare protein binding is uninformative. Hog1 is not a Ste7 substrate (it is activated by Pbs2), and direct binding assays found no detectable association of Hog1 with Ste7, so a MAPK-binding replacement is not justified from this high-throughput co-purification. Removing the generic annotation does not mean the co-purification is false; it may reflect indirect association. Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. PMID:8668180 These complexes were specific because neither Hog1 nor Mpk1 (two other yeast MAPKs), nor mammalian Erk2, was able to associate detectably with Ste7.
GO:0005515 protein binding	IPI PMID:20489023 A global protein kinase and phosphatase interaction network ...	REMOVE	Summary: Kinase-phosphatase interaction network (AP-MS) co-purifies Ste7 with the phosphatase Cdc14. Reason: Bare protein binding is uninformative, and the cached (abstract-only) evidence does not establish a functional consequence of Cdc14 association for Ste7 that would justify a specific MF term. Removal does not imply the reported interaction is false. Supporting Evidence: PMID:20489023 We identified a kinase and phosphatase interaction (KPI) network of 1844 interactions in budding yeast by mass spectrometric analysis of protein complexes. PMID:20489023 Notably, the cell cycle phosphatase Cdc14 associated with multiple kinases that revealed roles for Cdc14 in mitogen-activated protein kinase signaling
GO:0005515 protein binding	IPI PMID:23953117 Exploitation of latent allostery enables the evolution of ne...	MODIFY	Summary: In vitro kinase/binding study of Fus3/Kss1 orthologs detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:23953117 This VWA allosteric co-activation is essential for the transmission of the mating signal but has no influence on activation of the paralagous starvation-specific MAP kinase Kss1, which is also a substrate for the MAPKK Ste7 PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:23953117 Exploitation of latent allostery enables the evolution of ne...	MODIFY	Summary: In vitro kinase/binding study of Fus3/Kss1 orthologs detects Ste7 interaction with the MAP kinase Fus3, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Fus3 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:23953117 This VWA allosteric co-activation is essential for the transmission of the mating signal but has no influence on activation of the paralagous starvation-specific MAP kinase Kss1, which is also a substrate for the MAPKK Ste7 PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response...	MODIFY	Summary: Pairwise two-hybrid analysis of pheromone pathway components detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:7851759 We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response...	MODIFY	Summary: Pairwise two-hybrid analysis of pheromone pathway components detects Ste7 interaction with the MAP kinase Fus3, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Fus3 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:7851759 We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response...	MODIFY	Summary: Pairwise two-hybrid analysis detects Ste7 binding to the Ste5 scaffold protein. Reason: Bare protein binding is uninformative. Ste5 is the canonical MAPK-cascade scaffold that tethers Ste11, Ste7 and Fus3; its minimal-scaffold (VWA) domain binds Ste7 tightly and allosterically unlocks Fus3 for Ste7-catalysed phosphorylation (PMID:19303851). Scaffold protein binding (GO:0097110) describes this interaction informatively. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:7851759 Ste5p, a protein of unknown biochemical function, interacted with protein kinases that operate at each step of the MAP kinase cascade, specifically with Ste11p (an MEKK), Ste7p (an MEK), and Fus3p (a MAP kinase). PMID:19303851 The Ste5-ms domain binds tightly to Ste7, but only very weakly to Fus3.
GO:0005515 protein binding	IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc...	MODIFY	Summary: Two-hybrid and co-purification analysis of the Ste5 complex detects Ste7 interaction with the MAP kinase Kss1, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Kss1 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:8062390 By two-hybrid analysis, Ste11, Ste7, and Fus3 associate with different domains of Ste5, while Kss1, another MAPK, associates with the same domain as Fus3, thus implying that Ste5 simultaneously binds a MEKK, MEK, and MAPK. PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc...	MODIFY	Summary: Two-hybrid and co-purification analysis of the Ste5 complex detects Ste7 interaction with the MAP kinase Fus3, one of the two direct substrates of Ste7. Reason: Bare protein binding is uninformative. Fus3 is a MAP kinase that Ste7 docks with high affinity (Kd ~5 nM) through a site outside its catalytic core, and then dually phosphorylates (PMID:8668180). The informative replacement is mitogen-activated protein kinase binding, which captures the MAPKK-MAPK docking interaction that underlies Ste7 substrate selection. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:8062390 Ste5 also increases the amount of Ste11 complexed to Ste7 and Fus3 PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins.
GO:0005515 protein binding	IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc...	MODIFY	Summary: Two-hybrid and co-purification detects Ste7 binding to the Ste5 scaffold protein. Reason: Bare protein binding is uninformative. Ste5 is the canonical MAPK-cascade scaffold that tethers Ste11, Ste7 and Fus3; its minimal-scaffold (VWA) domain binds Ste7 tightly and allosterically unlocks Fus3 for Ste7-catalysed phosphorylation (PMID:19303851). Scaffold protein binding (GO:0097110) describes this interaction informatively. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:8062390 By two-hybrid analysis, Ste11, Ste7, and Fus3 associate with different domains of Ste5, while Kss1, another MAPK, associates with the same domain as Fus3, thus implying that Ste5 simultaneously binds a MEKK, MEK, and MAPK. PMID:19303851 The Ste5-ms domain binds tightly to Ste7, but only very weakly to Fus3.
GO:0005515 protein binding	IPI PMID:8668180 Signaling in the yeast pheromone response pathway: specific ...	MODIFY	Summary: In vitro translated Kss1 forms a tight (Kd ~5 nM), specific complex with Ste7 via a docking site outside the Ste7 catalytic core; complexes exist in yeast extracts. Reason: Bare protein binding is uninformative. This is the defining evidence for high-affinity MAPKK-MAPK docking, best captured as mitogen-activated protein kinase binding. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins. PMID:8668180 Deletions of Ste7 in the region required for its stable association with Kss1 and Fus3 in vitro significantly decreased (but did not eliminate) signaling in vivo.
GO:0005515 protein binding	IPI PMID:8668180 Signaling in the yeast pheromone response pathway: specific ...	MODIFY	Summary: In vitro translated Fus3 forms a tight (Kd ~5 nM), specific complex with Ste7; the complex is present in yeast extracts independent of Ste5 and Ste11. Reason: Bare protein binding is uninformative. High-affinity docking of the MAPK Fus3 to Ste7 is best captured as mitogen-activated protein kinase binding. Proposed replacements: mitogen-activated protein kinase binding Supporting Evidence: PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins. PMID:8668180 Deletions of Ste7 in the region required for its stable association with Kss1 and Fus3 in vitro significantly decreased (but did not eliminate) signaling in vivo.
GO:0005515 protein binding	IPI PMID:9311911 Ste5 RING-H2 domain: role in Ste4-promoted oligomerization f...	MODIFY	Summary: In vitro binding with wild-type and RING-H2 mutant Ste5 detects Ste7 binding to the Ste5 scaffold protein. Reason: Bare protein binding is uninformative. Ste5 is the canonical MAPK-cascade scaffold that tethers Ste11, Ste7 and Fus3; its minimal-scaffold (VWA) domain binds Ste7 tightly and allosterically unlocks Fus3 for Ste7-catalysed phosphorylation (PMID:19303851). Scaffold protein binding (GO:0097110) describes this interaction informatively. Proposed replacements: scaffold protein binding Supporting Evidence: PMID:9311911 In vitro Ste5(C177A C180A) bound each component of the MAPK cascade, but not Ste4. PMID:19303851 The Ste5-ms domain binds tightly to Ste7, but only very weakly to Fus3.
GO:0005524 ATP binding	IEA GO_REF:0000002	ACCEPT	Summary: InterPro (protein kinase domain, ATP-binding site) mapping to ATP binding. Reason: Ste7 has a canonical kinase ATP-binding site and uses ATP as phosphate donor; correct supporting MF for its MAPKK activity. Supporting Evidence: file:yeast/STE7/STE7-uniprot.txt /note="Proton acceptor" file:yeast/STE7/STE7-deep-research-falcon.md Ste7 is best described as an ATP-dependent, dual-specificity MAPKK that is activated by the MAPKKK Ste11 and activates the MAPKs Fus3 and Kss1 through phosphorylation of their activation-loop threonine and tyrosine.
GO:0005737 cytoplasm	IDA PMID:11781566 MAP kinase dynamics in response to pheromones in budding yea...	ACCEPT	Summary: GFP-tagged Ste7 is predominantly cytoplasmic. Reason: Direct localization evidence; the cytoplasm (and cytoplasmic Ste5 complexes) is where Ste7 acts on Fus3 and Kss1. Supporting Evidence: PMID:11781566 Here we show that Ste11p and Ste7p were predominantly cytoplasmic proteins, while Ste5p and Fus3p were found in the nucleus and the cytoplasm.
GO:0007124 pseudohyphal growth	IMP PMID:8643578 Ras2 signals via the Cdc42/Ste20/mitogen-activated protein k...	KEEP AS NON CORE	Summary: Ras2-induced filamentous (pseudohyphal) growth and FG(TyA)::lacZ induction require Ste7. Reason: Ste7 is required for diploid pseudohyphal growth as the MAP2K of the filamentous growth MAPK pathway; the developmental outcome is kept as a non-core process, with the signalling role captured by GO:0001402. Supporting Evidence: PMID:8643578 Ste7 (MEK or MAPK kinase), and the transcription factor Ste12 PMID:8643578 Our results suggest that filamentous growth in budding yeast is regulated by an evolutionarily conserved signaling pathway that controls cell morphology. PMID:8001818 We find that the same components of the MAP kinase cascade necessary for diploid pseudohyphal development (STE20, STE11, STE7, and STE12) are also required for both filament formation and agar penetration in haploids.
GO:0043332 mating projection tip	IDA PMID:11781566 MAP kinase dynamics in response to pheromones in budding yea...	ACCEPT	Summary: Ste7 localizes to the tips of mating projections in pheromone-treated cells. Reason: Direct localization evidence; consistent with the Ste5-organized kinase module acting at the shmoo tip during mating signalling. Supporting Evidence: PMID:11781566 Ste5p, Ste7p and Fus3p also localized to tips of mating projections in pheromone-treated cells.
GO:0043332 mating projection tip	IDA PMID:17952059 Spatial regulation of Fus3 MAP kinase activity through a rea...	ACCEPT	Summary: FCCS/FLIM study showing Fus3-activating kinases are partitioned to the mating projection tip, from which a gradient of active Fus3 emanates. Reason: Consistent with the independent van Drogen et al. observation; Ste7 is one of the Fus3-activating kinases localized at the shmoo tip. Supporting Evidence: PMID:17952059 Spatial partitioning of Fus3 activating kinases to this site and deactivating phosphatases in the cytoplasm maintain this Fus3(PP)-activity distribution. PMID:17952059 revealed a gradient of Fus3(PP) activity emanating from the tip of the mating projection
GO:0051286 cell tip	IEA GO_REF:0000117	ACCEPT	Summary: ARBA mapping to cell tip. Reason: Mating projection tip is_a cell tip, and Ste7 has direct experimental localization to the mating projection tip; the broader IEA term is correct. Supporting Evidence: PMID:11781566 Ste5p, Ste7p and Fus3p also localized to tips of mating projections in pheromone-treated cells.
GO:0071507 pheromone response MAPK cascade	IDA PMID:8159759 Reconstitution of a yeast protein kinase cascade in vitro: a...	ACCEPT	Summary: In vitro reconstitution: Ste11 phosphorylates and activates Ste7, which phosphorylates Fus3. Reason: Direct biochemical reconstitution of the Ste11-Ste7-Fus3 tiers of the pheromone response MAPK cascade; this is the core process of Ste7. Supporting Evidence: PMID:8159759 reconstituted a kinase cascade in which STE11 phosphorylates and activates STE7, which in turn phosphorylates the mitogen-activated protein kinase FUS3 PMID:8159759 We also identify a STE11-dependent phosphorylation site in STE7 which is required for activity of STE7.
GO:0071507 pheromone response MAPK cascade	IDA PMID:8384702 MAP kinase-related FUS3 from S. cerevisiae is activated by S...	ACCEPT	Summary: Ste7 dual-phosphorylates and activates Fus3 in vitro. Reason: Ste7 performs the MAP2K step of the pheromone response MAPK cascade (GO:0071507 definition names Ste7 as the MAP2K). Supporting Evidence: PMID:8384702 Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro. PMID:8384702 we argue that STE7 is the physiological activator of FUS3
GO:0071507 pheromone response MAPK cascade	IDA PMID:8455599 Pheromone-induced signal transduction in Saccharomyces cerev...	ACCEPT	Summary: Pheromone activates Ste7 (assayed by Fus3 phosphorylation) and Fus3/Kss1 activation is Ste7-dependent. Reason: Direct evidence that Ste7 is activated by pheromone and acts between Ste11 and Fus3/Kss1. Supporting Evidence: PMID:8455599 FUS3 and presumably KSS1 are phosphorylated and activated during pheromone induction by a STE7-dependent mechanism. PMID:8455599 Using in vitro assays for FUS3 phosphorylation, we show that pheromone activates STE7 even in the absence of FUS3 and KSS1.
GO:0071507 pheromone response MAPK cascade	IEA GO_REF:0000117	ACCEPT	Summary: ARBA mapping to pheromone response MAPK cascade. Reason: Consistent with extensive experimental evidence for this core process. Supporting Evidence: PMID:8455599 FUS3 and presumably KSS1 are phosphorylated and activated during pheromone induction by a STE7-dependent mechanism.
GO:0071507 pheromone response MAPK cascade	IGI PMID:8455599 Pheromone-induced signal transduction in Saccharomyces cerev...	ACCEPT	Summary: Genetic interaction with STE11: Ste7 hyperphosphorylation requires Ste11, placing Ste11 upstream of Ste7. Reason: Epistasis supports the Ste11 -> Ste7 -> Fus3/Kss1 order of the pheromone response cascade. Supporting Evidence: PMID:8455599 This modification of STE7 requires the STE11 kinase, which is proposed to act before STE7 during signal transmission. PMID:8455599 Using in vitro assays for FUS3 phosphorylation, we show that pheromone activates STE7 even in the absence of FUS3 and KSS1.
GO:0071507 pheromone response MAPK cascade	IMP PMID:8159759 Reconstitution of a yeast protein kinase cascade in vitro: a...	ACCEPT	Summary: Mutation of the Ste11-dependent phosphorylation site in Ste7 abolishes Ste7 activity. Reason: Loss-of-function evidence for Ste7 activation-loop phosphorylation being required for pheromone cascade signalling. Supporting Evidence: PMID:8159759 We also identify a STE11-dependent phosphorylation site in STE7 which is required for activity of STE7.
GO:0071507 pheromone response MAPK cascade	IMP PMID:8384702 MAP kinase-related FUS3 from S. cerevisiae is activated by S...	ACCEPT	Summary: Genetic data place Ste7 as the physiological activator of Fus3 in pheromone signalling. Reason: Core process; supported jointly by genetics and in vitro kinase data. Supporting Evidence: PMID:8384702 we argue that STE7 is the physiological activator of FUS3
GO:0071507 pheromone response MAPK cascade	IPI PMID:8668180 Signaling in the yeast pheromone response pathway: specific ...	ACCEPT	Summary: Physical interaction of Ste7 with Fus3 (high-affinity docking complex) supports participation in the pheromone response MAPK cascade. Reason: Ste7 binds Fus3 directly and phosphorylates it in pheromone-stimulated complexes; docking-region deletions reduce signalling in vivo. Supporting Evidence: PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins. PMID:8668180 Deletions of Ste7 in the region required for its stable association with Kss1 and Fus3 in vitro significantly decreased (but did not eliminate) signaling in vivo.
GO:0071507 pheromone response MAPK cascade	IPI PMID:8668180 Signaling in the yeast pheromone response pathway: specific ...	ACCEPT	Summary: Physical interaction of Ste7 with Kss1 (high-affinity docking complex) supports participation in the pheromone response MAPK cascade. Reason: Ste7 binds Kss1 directly and phosphorylates it in pheromone-stimulated complexes; Kss1 acts redundantly with Fus3 in mating signalling. Supporting Evidence: PMID:8668180 When synthesized by in vitro translation, Kss1 and Fus3 could each form a tight complex (Kd of approximately 5 nM) with Ste7 in the absence of any additional yeast proteins. PMID:8668180 Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	MARK AS OVER ANNOTATED	Summary: Rhea (RHEA:17989, serine phosphorylation) mapping to protein serine kinase activity, derived from the EC 2.7.12.2 reaction set. Reason: The characterized Ste7 phosphoacceptors are the threonine and tyrosine of the MAPK activation loop (GO:0004708 definition: T-X-Y motif). The serine reaction is inherited from the generic EC 2.7.12.2 reaction set rather than from Ste7-specific evidence; no physiological serine substrate of Ste7 is documented in the reviewed literature. Not impossible, but an over-annotation relative to the evidence. Supporting Evidence: PMID:8384702 Here we report that STE7 is a dual-specificity kinase that modifies FUS3 at the appropriate sites and stimulates its catalytic activity in vitro. file:yeast/STE7/STE7-deep-research-falcon.md This evidence supports a restricted primary substrate set: Fus3 and Kss1 are the established direct physiological substrates.

Gene Description

Existing Annotations Review

Core Functions

MAP2K of the pheromone response cascade: activated by Ste11 on the Ste5 scaffold, Ste7 dually phosphorylates the Fus3 (and Kss1) activation loop, a step that for Fus3 requires allosteric unlocking by the Ste5 scaffold.

MAP2K of the filamentous/invasive growth pathway: Ste7 activates Kss1, an intrinsically good substrate, largely independently of Ste5, switching Kss1 from an inhibitor to an activator of invasive growth.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

SGD

SGD gene description for STE7 (yeast)

📚 Additional Documentation

Notes

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