Mitogen-activated protein kinase (MAPK) of the budding yeast filamentous/invasive growth pathway and a partially redundant second MAPK of the pheromone response pathway (paralog of Fus3). Kss1 is dually phosphorylated on its TEY activation-loop motif (Thr183/Tyr185) by the MAPKK Ste7, downstream of the MAPKKK Ste11, and binds Ste7 through a high-affinity docking interaction; unlike Fus3 it does not require allosteric activation by the Ste5 scaffold. Activated Kss1 is a proline-directed Ser/Thr kinase that phosphorylates Ste7, the Ste12 corepressors Dig1 and Dig2, and Ste12, driving Ste12/Tec1-dependent transcription of filamentation genes in response to nutrient limitation and contributing to pheromone-induced transcription. Unphosphorylated Kss1 has a separate, kinase-independent repressive role: it binds Ste12 directly and, with Dig1 and Dig2, keeps filamentation gene expression and invasive growth off in the absence of signal; Ste7-mediated phosphorylation weakens this interaction. Kss1 shuttles between the cytoplasm and the nucleus and accumulates in the nucleus during filamentous growth. During mating signaling, active Fus3 limits Kss1 activation to preserve pathway specificity.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000749 response to pheromone triggering conjugation with cellular fusion | IDA PMID:8668180 Signaling in the yeast pheromone response pathway: specific ... | ACCEPT | Summary: Kss1 participates in the pheromone response; it forms a pheromone-stimulated active complex with Ste7 and is activated by pheromone. Reason: Kss1 is activated by pheromone in wild-type cells and contributes to pheromone-induced gene expression, and is partially redundant with Fus3 for mating (UniProt; PMID:11583629). The Ste7-Kss1 complex phosphorylates in a pheromone-stimulated manner. Accepted, though filamentous growth rather than mating is Kss1's dominant role. Supporting Evidence: PMID:8668180 Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner PMID:11583629 we show that Kss1 is rapidly phosphorylated and potently activated by mating pheromone in wild-type cells, and that this is required for normal pheromone-induced gene expression file:yeast/KSS1/KSS1-uniprot.txt FUS3 can partially compensate for the lack of KSS1 |
| GO:0000749 response to pheromone triggering conjugation with cellular fusion | IDA PMID:8918885 Two novel targets of the MAP kinase Kss1 are negative regula... | ACCEPT | Summary: Kss1 activity toward Dig1 is pheromone-stimulated; Kss1 functions in both pheromone response and invasive growth. Reason: The paper shows pheromone-stimulated Kss1 kinase activity toward Dig1 and states that both mating and invasive growth require Kss1. Consistent with Kss1 being activated by pheromone in wild-type cells (PMID:11583629). Supporting Evidence: PMID:8918885 is phosphorylated by Kss1 in immune complexes in a pheromone-stimulated manner PMID:8918885 Both developmental alternatives to vegetative proliferation require the MAP kinase Kss1 and the transcriptional transactivator Ste12. PMID:11583629 we show that Kss1 is rapidly phosphorylated and potently activated by mating pheromone in wild-type cells, and that this is required for normal pheromone-induced gene expression |
| GO:0000749 response to pheromone triggering conjugation with cellular fusion | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning inference of involvement in pheromone response. Reason: Consistent with experimental evidence that Kss1 is activated by pheromone and contributes to pheromone-induced transcription, partially redundant with Fus3. Supporting Evidence: PMID:11583629 we show that Kss1 is rapidly phosphorylated and potently activated by mating pheromone in wild-type cells, and that this is required for normal pheromone-induced gene expression |
| GO:0001402 signal transduction involved in filamentous growth | IMP PMID:9393860 MAP kinases with distinct inhibitory functions impart signal... | ACCEPT | Summary: Kss1 is the MAPK that transmits the filamentation/invasion signal (Ste11 -> Ste7 -> Kss1 -> Ste12/Tec1). Reason: Core process. Madhani et al. showed that Kss1, not Fus3, is the MAPK of the filamentous growth pathway, with both a kinase-dependent activating and a kinase-independent inhibitory role on Ste12. Kss1 relocalizes to the nucleus during filamentous growth (PMID:18417610). Supporting Evidence: PMID:9393860 The Fus3 MAPK regulates mating, whereas the Kss1 MAPK regulates filamentation and invasion. PMID:9744865 The stimulatory function of Kss1 requires both its catalytic activity and its activation by the MAPK/ERK kinase (MEK) Ste7; in contrast, the inhibitory function of Kss1 requires neither. PMID:18417610 The proteins Bcy1p, Fus3p, Ksp1p, Kss1p, Sks1p, and Tpk2p distributed evenly over the cell under conditions of vegetative growth, but they localized predominantly to the nucleus during filamentous growth. |
| GO:0001403 invasive growth in response to glucose limitation | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning inference of involvement in invasive growth in response to glucose limitation. Reason: Consistent with extensive experimental evidence that Kss1 regulates haploid invasive growth. Supporting Evidence: PMID:9393860 The Fus3 MAPK regulates mating, whereas the Kss1 MAPK regulates filamentation and invasion. |
| GO:0001403 invasive growth in response to glucose limitation | IMP PMID:8001818 Elements of a single MAP kinase cascade in Saccharomyces cer... | ACCEPT | Summary: Invasive growth depends on the shared MAP kinase cascade elements; Kss1 is the MAPK of this program. Reason: Roberts and Fink established haploid invasive growth as a program using elements of the mating MAPK cascade; the curator's IMP for KSS1 is from the full text. Later work confirms Kss1 as the MAPK regulating invasion (PMID:9393860) and Dig1/Dig2-dependent control of invasive growth by Kss1 (PMID:9860980). Invasive growth is a core process for Kss1. Supporting Evidence: PMID:8001818 Thus, haploid yeast cells can enter either of two developmental pathways: mating or invasive growth, both of which depend on elements of a single MAP kinase cascade. PMID:9393860 The Fus3 MAPK regulates mating, whereas the Kss1 MAPK regulates filamentation and invasion. PMID:9860980 Dig1 and Dig2 cooperate with Kss1 to repress Ste12 action at FREs and regulate invasive growth in a naturally invasive strain. |
| GO:0004672 protein kinase activity | HDA PMID:16319894 Global analysis of protein phosphorylation in yeast. | ACCEPT | Summary: Proteome-chip in vitro kinase assays identified substrates phosphorylated by Kss1. Reason: Correct though general; Kss1 is a protein kinase. The more specific MAP kinase activity is captured by IDA rows. Supporting Evidence: PMID:16319894 we identified over 4,000 phosphorylation events involving 1,325 different proteins |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro Ser/Thr kinase active-site signature mapping to protein kinase activity. Reason: Correct, general parent of MAP kinase activity; Kss1 has a canonical kinase domain with catalytic Asp143 (UniProt). Supporting Evidence: file:yeast/KSS1/KSS1-uniprot.txt Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily. |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT phylogenetic inference of protein serine/threonine kinase activity for the MAPK family. Reason: Kss1 is a MAPK (Ser/Thr-directed, EC 2.7.11.24) that phosphorylates Ste7, Dig1, Dig2 and Ste12. The IBA is correct; the more specific MAP kinase activity is supported experimentally. Supporting Evidence: file:yeast/KSS1/KSS1-uniprot.txt KSS1 phosphorylates STE7, STE5, FAR1, DIG1, DIG2, STE12, and SST2. PMID:8668180 Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner |
| GO:0004707 MAP kinase activity | IDA PMID:8668180 Signaling in the yeast pheromone response pathway: specific ... | ACCEPT | Summary: Kss1 phosphorylates Ste7 in Ste7-Kss1 complexes isolated from yeast, in a pheromone-stimulated manner after activation by Ste7. Reason: Core MF. Kss1 is dually phosphorylated on its TEY motif by the MAPKK Ste7 and phosphorylates substrates including Ste7 itself (feedback). Supporting Evidence: PMID:8668180 Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner PMID:7579701 Catalytic activity was essential for Kss1 function in signal transmission |
| GO:0004707 MAP kinase activity | IDA PMID:8918885 Two novel targets of the MAP kinase Kss1 are negative regula... | ACCEPT | Summary: Kss1 phosphorylates Dig1 in immune complexes in a pheromone-stimulated manner. Reason: Core MF. Dig1 (and Dig2) are physiological Kss1 substrates; activated Kss1 phosphorylates them. Supporting Evidence: PMID:8918885 is phosphorylated by Kss1 in immune complexes in a pheromone-stimulated manner file:yeast/KSS1/KSS1-uniprot.txt KSS1 phosphorylates STE7, STE5, FAR1, DIG1, DIG2, STE12, and SST2. |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated inference (InterPro MAPK signature, EC 2.7.11.24) of MAP kinase activity. Reason: Consistent with experimental evidence; Kss1 is a TEY-type MAPK activated by Ste7. Supporting Evidence: PMID:8668180 Ste7 phosphorylated Kss1 (or Fus3), and Kss1 (or Fus3) phosphorylated Ste7, in a pheromone-stimulated manner |
| GO:0005515 protein binding | IPI PMID:10688190 A comprehensive analysis of protein-protein interactions in ... | MODIFY | Summary: Kss1 interaction with the MAPKK Ste7 detected by high-throughput yeast two-hybrid (Uetz et al.). Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:10688190 These approaches resulted in the detection of 957 putative interactions involving 1,004 S. cerevisiae proteins. PMID:8668180 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: Kss1 interaction with the MAPKK Ste7 detected by comprehensive yeast two-hybrid (Ito et al.). Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase 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 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: Kss1 interaction with the MAPKK Ste7 detected by high-throughput affinity purification/mass spectrometry (Ho et al.). Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. PMID:8668180 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: Kss1 interaction with the transcription factor Ste12 detected by high-throughput affinity purification/mass spectrometry (Ho et al.). Reason: Bare protein binding is uninformative. Kss1 binds Ste12 directly: unphosphorylated Kss1 binds and represses Ste12 (kinase-independent), and Ste7-mediated phosphorylation weakens the interaction (PMID:9744865, PMID:9393860). Ste12 is an RNA polymerase II-specific DNA-binding transcription factor, so the informative MF is RNA polymerase II-specific DNA-binding transcription factor binding. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. PMID:9744865 unphosphorylated Kss1 binds directly to the transcription factor Ste12, that this binding is necessary for Kss1-mediated repression of Ste12 |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Co-purification of Kss1 with the MAPKKK Ste11 in high-throughput affinity purification/mass spectrometry (Ho et al.). Reason: Bare protein binding is uninformative, and an AP-MS co-complex result does not establish direct binding; Ste11 and Kss1 are plausibly bridged by Ste7 and the Ste5 scaffold. Removal of this generic row does not mean the association is false; the relevant low-throughput two-hybrid rows are modified to MAPKKK binding. Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Co-purification of Kss1 with Bck2 in high-throughput affinity purification/mass spectrometry (Ho et al.). Reason: Bare protein binding is uninformative and the biological significance of a Kss1-Bck2 association is unknown; no informative MF can be inferred from this high-throughput co-purification. Removal does not mean the interaction is false. Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: Kss1 interaction with the Ste12 corepressor Dig1 detected by high-throughput affinity purification/mass spectrometry (Ho et al.). Reason: Bare protein binding is uninformative. Dig1 and Dig2 were identified as Kss1 two-hybrid partners and Kss1 substrates (PMID:8918885), and are the nuclear cofactors required for Kss1-imposed repression of Ste12 (PMID:9860980). Dig1 acts as a transcriptional corepressor of Ste12, so transcription corepressor binding captures the interaction. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. PMID:8918885 Kss1 binds specifically to a GST-Dig1 fusion in the absence of any other yeast protein. PMID:9860980 Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: Kss1 interaction with the Ste12 corepressor Dig2 detected by high-throughput affinity purification/mass spectrometry (Ho et al.). Reason: Bare protein binding is uninformative. Dig1 and Dig2 were identified as Kss1 two-hybrid partners and Kss1 substrates (PMID:8918885), and are the nuclear cofactors required for Kss1-imposed repression of Ste12 (PMID:9860980). Dig2 acts as a transcriptional corepressor of Ste12, so transcription corepressor binding captures the interaction. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:11805837 Beginning with 10% of predicted yeast proteins as baits, we detected 3,617 associated proteins covering 25% of the yeast proteome. PMID:8918885 Kss1 binds specifically to a GST-Dig1 fusion in the absence of any other yeast protein. PMID:9860980 Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. |
| GO:0005515 protein binding | IPI PMID:15020407 Fus1p interacts with components of the Hog1p mitogen-activat... | REMOVE | Summary: Kss1 interaction with its paralog MAPK Fus3 detected by two-hybrid matrix of fusion and pheromone pathway proteins. Reason: Bare protein binding is uninformative. A Kss1-Fus3 association has no established functional meaning (Fus3 restrains Kss1 activation, but not by a demonstrated direct binding mechanism, PMID:11583629) and may be bridged by shared partners (Ste7, Ste5, Dig1/Dig2). No informative MF can be inferred. Removal does not mean the interaction is false. 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. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MODIFY | Summary: Kss1 interaction with the transcription factor Ste12 detected by high-quality binary yeast two-hybrid map (Yu et al.). Reason: Bare protein binding is uninformative. Kss1 binds Ste12 directly: unphosphorylated Kss1 binds and represses Ste12 (kinase-independent), and Ste7-mediated phosphorylation weakens the interaction (PMID:9744865, PMID:9393860). Ste12 is an RNA polymerase II-specific DNA-binding transcription factor, so the informative MF is RNA polymerase II-specific DNA-binding transcription factor binding. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:18719252 Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions PMID:9744865 unphosphorylated Kss1 binds directly to the transcription factor Ste12, that this binding is necessary for Kss1-mediated repression of Ste12 |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MODIFY | Summary: Kss1 interaction with the Ste12 corepressor Dig1 detected by high-quality binary yeast two-hybrid map (Yu et al.). Reason: Bare protein binding is uninformative. Dig1 and Dig2 were identified as Kss1 two-hybrid partners and Kss1 substrates (PMID:8918885), and are the nuclear cofactors required for Kss1-imposed repression of Ste12 (PMID:9860980). Dig1 acts as a transcriptional corepressor of Ste12, so transcription corepressor binding captures the interaction. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:18719252 Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions PMID:8918885 Kss1 binds specifically to a GST-Dig1 fusion in the absence of any other yeast protein. PMID:9860980 Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MODIFY | Summary: Kss1 interaction with the Ste12 corepressor Dig2 detected by high-quality binary yeast two-hybrid map (Yu et al.). Reason: Bare protein binding is uninformative. Dig1 and Dig2 were identified as Kss1 two-hybrid partners and Kss1 substrates (PMID:8918885), and are the nuclear cofactors required for Kss1-imposed repression of Ste12 (PMID:9860980). Dig2 acts as a transcriptional corepressor of Ste12, so transcription corepressor binding captures the interaction. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:18719252 Compared to co-complex interactome models, this binary map is enriched for transient signaling interactions PMID:8918885 Kss1 binds specifically to a GST-Dig1 fusion in the absence of any other yeast protein. PMID:9860980 Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. |
| GO:0005515 protein binding | IPI PMID:19303851 The Ste5 scaffold directs mating signaling by catalytically ... | MODIFY | Summary: Kss1 interaction with the MAPKK Ste7 detected by in vitro reconstitution of Ste7-MAPK phosphorylation with purified proteins. Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase 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 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: Kss1 interaction with the MAPKK Ste7 detected by kinase/phosphatase interaction network AP-MS (Breitkreutz et al.). Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase 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 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: Kss1 interaction with the transcription factor Ste12 detected by kinase/phosphatase interaction network AP-MS (Breitkreutz et al.). Reason: Bare protein binding is uninformative. Kss1 binds Ste12 directly: unphosphorylated Kss1 binds and represses Ste12 (kinase-independent), and Ste7-mediated phosphorylation weakens the interaction (PMID:9744865, PMID:9393860). Ste12 is an RNA polymerase II-specific DNA-binding transcription factor, so the informative MF is RNA polymerase II-specific DNA-binding transcription factor binding. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor 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:9744865 unphosphorylated Kss1 binds directly to the transcription factor Ste12, that this binding is necessary for Kss1-mediated repression of Ste12 |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: Co-purification of Kss1 with Bck2 in kinase/phosphatase interaction network AP-MS (Breitkreutz et al.). Reason: Bare protein binding is uninformative and the biological significance of a Kss1-Bck2 association is unknown; no informative MF can be inferred from this high-throughput co-purification. Removal does not mean the 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. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Kss1 interaction with the Ste12 corepressor Dig1 detected by kinase/phosphatase interaction network AP-MS (Breitkreutz et al.). Reason: Bare protein binding is uninformative. Dig1 and Dig2 were identified as Kss1 two-hybrid partners and Kss1 substrates (PMID:8918885), and are the nuclear cofactors required for Kss1-imposed repression of Ste12 (PMID:9860980). Dig1 acts as a transcriptional corepressor of Ste12, so transcription corepressor binding captures the interaction. Proposed replacements: transcription corepressor 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:8918885 Kss1 binds specifically to a GST-Dig1 fusion in the absence of any other yeast protein. PMID:9860980 Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: Kss1 interaction with the Ste12 corepressor Dig2 detected by kinase/phosphatase interaction network AP-MS (Breitkreutz et al.). Reason: Bare protein binding is uninformative. Dig1 and Dig2 were identified as Kss1 two-hybrid partners and Kss1 substrates (PMID:8918885), and are the nuclear cofactors required for Kss1-imposed repression of Ste12 (PMID:9860980). Dig2 acts as a transcriptional corepressor of Ste12, so transcription corepressor binding captures the interaction. Proposed replacements: transcription corepressor 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:8918885 Kss1 binds specifically to a GST-Dig1 fusion in the absence of any other yeast protein. PMID:9860980 Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. |
| GO:0005515 protein binding | IPI PMID:23267104 Proteome-wide protein interaction measurements of bacterial ... | MODIFY | Summary: Kss1 interaction with the transcription factor Ste12 detected by microfluidic (MITOMI) binary interaction measurement. Reason: Bare protein binding is uninformative. Kss1 binds Ste12 directly: unphosphorylated Kss1 binds and represses Ste12 (kinase-independent), and Ste7-mediated phosphorylation weakens the interaction (PMID:9744865, PMID:9393860). Ste12 is an RNA polymerase II-specific DNA-binding transcription factor, so the informative MF is RNA polymerase II-specific DNA-binding transcription factor binding. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:9744865 unphosphorylated Kss1 binds directly to the transcription factor Ste12, that this binding is necessary for Kss1-mediated repression of Ste12 |
| GO:0005515 protein binding | IPI PMID:23953117 Exploitation of latent allostery enables the evolution of ne... | MODIFY | Summary: Kss1 interaction with the MAPKK Ste7 detected by biochemical study of Ste5/Ste7/MAPK allostery. Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:23953117 Fus3 and Kss1 are 55 % identical, are both targets of the MAPKK Ste7 PMID:8668180 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:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Kss1 interaction with its paralog MAPK Fus3 detected by proteome-wide quantitative affinity-enrichment MS (Michaelis et al.). Reason: Bare protein binding is uninformative. A Kss1-Fus3 association has no established functional meaning (Fus3 restrains Kss1 activation, but not by a demonstrated direct binding mechanism, PMID:11583629) and may be bridged by shared partners (Ste7, Ste5, Dig1/Dig2). No informative MF can be inferred. Removal does not mean the interaction is false. Supporting Evidence: PMID:37968396 Affinity purification coupled to mass spectrometry is an ideal tool for such mapping |
| GO:0005515 protein binding | IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response... | MODIFY | Summary: Kss1 interaction with the MAPKK Ste7 detected by pairwise two-hybrid analysis of pheromone pathway components. Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:7851759 We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. PMID:8668180 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: Kss1 interaction with the transcription factor Ste12 detected by pairwise two-hybrid analysis of pheromone pathway components. Reason: Bare protein binding is uninformative. Kss1 binds Ste12 directly: unphosphorylated Kss1 binds and represses Ste12 (kinase-independent), and Ste7-mediated phosphorylation weakens the interaction (PMID:9744865, PMID:9393860). Ste12 is an RNA polymerase II-specific DNA-binding transcription factor, so the informative MF is RNA polymerase II-specific DNA-binding transcription factor binding. Proposed replacements: RNA polymerase II-specific DNA-binding transcription factor binding Supporting Evidence: PMID:7851759 We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. PMID:9744865 unphosphorylated Kss1 binds directly to the transcription factor Ste12, that this binding is necessary for Kss1-mediated repression of Ste12 |
| GO:0005515 protein binding | IPI PMID:7851759 Protein-protein interactions in the yeast pheromone response... | MODIFY | Summary: Kss1 interaction with the MAPKKK Ste11 detected by pairwise two-hybrid analysis of pheromone pathway components. Reason: Bare protein binding is uninformative. Ste11 is the MAPKKK of the Kss1 cascade (order Ste11 -> Ste7 -> Kss1, PMID:7579701); the two-hybrid signal supports mitogen-activated protein kinase kinase kinase binding, although it may be bridged by endogenous Ste7/Ste5 and has not been shown to be direct with purified proteins. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:7851759 We also found that both Ste11p and Ste7p interact with Fus3p and Kss1p. PMID:7579701 suggesting an order of function: Ste11-->Ste7-->Kss1 |
| GO:0005515 protein binding | IPI PMID:8062390 Ste5 tethers multiple protein kinases in the MAP kinase casc... | MODIFY | Summary: Kss1 interaction with the MAPKK Ste7 detected by two-hybrid analysis of Ste5 and cascade kinases. Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:8062390 while Kss1, another MAPK, associates with the same domain as Fus3 PMID:8668180 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: Kss1 interaction with the MAPKKK Ste11 detected by two-hybrid analysis of Ste5 and cascade kinases. Reason: Bare protein binding is uninformative. Ste11 is the MAPKKK of the Kss1 cascade (order Ste11 -> Ste7 -> Kss1, PMID:7579701); the two-hybrid signal supports mitogen-activated protein kinase kinase kinase binding, although it may be bridged by endogenous Ste7/Ste5 and has not been shown to be direct with purified proteins. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:8062390 while Kss1, another MAPK, associates with the same domain as Fus3 PMID:7579701 suggesting an order of function: Ste11-->Ste7-->Kss1 |
| GO:0005515 protein binding | IPI PMID:8668180 Signaling in the yeast pheromone response pathway: specific ... | MODIFY | Summary: Kss1 interaction with the MAPKK Ste7 detected by in vitro binding and co-immunoprecipitation of Ste7-MAPK complexes. Reason: Bare protein binding is uninformative. Ste7 is the MAPKK that dually phosphorylates Kss1, and Kss1 forms a specific, high-affinity docking complex with Ste7 (Kd ~5 nM) that forms independently of Ste5 and outside the catalytic core (PMID:8668180). The informative MF is mitogen-activated protein kinase kinase binding. Proposed replacements: mitogen-activated protein kinase kinase binding Supporting Evidence: PMID:8668180 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:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro protein-kinase ATP-binding signature mapping to ATP binding. Reason: Correct; Kss1 has the canonical kinase ATP-binding site (Gly-rich loop 19-27, Lys42). Not informative beyond kinase activity but accurate. Supporting Evidence: file:yeast/KSS1/KSS1-uniprot.txt ATP-binding; Cell cycle; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT phylogenetic inference that MAPKs act in the nucleus. Reason: Kss1 is concentrated in the nucleus, where it binds and regulates Ste12 with Dig1/Dig2. Supporting Evidence: PMID:7579701 Indirect immunofluorescence demonstrated that Kss1 is concentrated in the nucleus and that its distribution is not altered detectably during signaling. PMID:9860980 Herein we show that two nuclear proteins, Dig1 and Dig2, are required cofactors in Kss1-imposed repression. |
| GO:0005634 nucleus | IDA PMID:18417610 Analysis of the yeast kinome reveals a network of regulated ... | ACCEPT | Summary: Kss1-vYFP localizes predominantly to the nucleus during filamentous growth. Reason: Direct localization evidence with a functional fusion; nucleus is where Kss1 regulates Ste12/Tec1. Supporting Evidence: PMID:18417610 The proteins Bcy1p, Fus3p, Ksp1p, Kss1p, Sks1p, and Tpk2p distributed evenly over the cell under conditions of vegetative growth, but they localized predominantly to the nucleus during filamentous growth. |
| GO:0005634 nucleus | IDA PMID:7579701 Phosphorylation and localization of Kss1, a MAP kinase of th... | ACCEPT | Summary: Indirect immunofluorescence shows Kss1 concentrated in the nucleus. Reason: Direct localization evidence; consistent with the nuclear Ste12-Dig1/Dig2 regulatory function. Supporting Evidence: PMID:7579701 Indirect immunofluorescence demonstrated that Kss1 is concentrated in the nucleus and that its distribution is not altered detectably during signaling. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to nucleus. Reason: Supported by experimental localization. Supporting Evidence: PMID:7579701 Indirect immunofluorescence demonstrated that Kss1 is concentrated in the nucleus and that its distribution is not altered detectably during signaling. file:yeast/KSS1/KSS1-uniprot.txt KSS1 shuttles rapidly between the cytoplasm and the nucleus independent of its activation state. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT phylogenetic inference that MAPKs act in the cytoplasm. Reason: Kss1 shuttles between cytoplasm and nucleus, and is activated by Ste7/Ste11, which are predominantly cytoplasmic. Accepted. Supporting Evidence: file:yeast/KSS1/KSS1-uniprot.txt KSS1 shuttles rapidly between the cytoplasm and the nucleus independent of its activation state. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping to cytoplasm. Reason: Kss1 shuttles between cytoplasm and nucleus (UniProt). Supporting Evidence: file:yeast/KSS1/KSS1-uniprot.txt KSS1 shuttles rapidly between the cytoplasm and the nucleus independent of its activation state. |
| GO:0005935 cellular bud neck | IDA PMID:27400980 Phosphorylation of Bni4 by MAP kinases contributes to septum... | KEEP AS NON CORE | Summary: Kss1 observed at the bud neck in a study of multicopy suppression of slt2 rim101 lethality via Bni4. Reason: Experimental localization by the curator from the full text (abstract only cached). The bud-neck pool relates to a multicopy-suppression/septum-assembly context rather than to Kss1's core signaling role; kept as non-core. Supporting Evidence: PMID:27400980 Here, we identify new multicopy suppressors of this lethality including Kss1, Pcl1 and Sph1 PMID:27400980 Bni4 interacts physically with both kinases, and its levels of phosphorylation are reduced in the slt2Ξ mutant but increased after Kss1 overexpression. |
| GO:0010973 positive regulation of division septum assembly | IGI PMID:27400980 Phosphorylation of Bni4 by MAP kinases contributes to septum... | KEEP AS NON CORE | Summary: Kss1 overexpression suppresses slt2 rim101 synthetic lethality and restores Bni4 localization and phosphorylation, supporting septum assembly. Reason: Genetic interaction evidence (IGI) from multicopy suppression; Kss1 increases Bni4 phosphorylation. This is a peripheral, overexpression-revealed role and not part of Kss1's core MAPK signaling functions; deferring to the curator, kept as non-core. Supporting Evidence: PMID:27400980 Here, we identify new multicopy suppressors of this lethality including Kss1, Pcl1 and Sph1 PMID:27400980 Bni4 interacts physically with both kinases, and its levels of phosphorylation are reduced in the slt2Ξ mutant but increased after Kss1 overexpression. |
| GO:0010973 positive regulation of division septum assembly | IGI PMID:27400980 Phosphorylation of Bni4 by MAP kinases contributes to septum... | KEEP AS NON CORE | Summary: Same study as the other septum-assembly IGI row (different WITH/FROM gene). Reason: As for the companion row: multicopy suppression by Kss1 of slt2 rim101 lethality via Bni4 phosphorylation; peripheral, non-core. Supporting Evidence: PMID:27400980 Here, we identify new multicopy suppressors of this lethality including Kss1, Pcl1 and Sph1 PMID:27400980 Bni4 interacts physically with both kinases, and its levels of phosphorylation are reduced in the slt2Ξ mutant but increased after Kss1 overexpression. |
| GO:0042597 periplasmic space | IEA GO_REF:0000044 | REMOVE | Summary: UniProt subcellular location 'Periplasm' mapped to periplasmic space. Reason: Kss1 is a soluble intracellular MAP kinase without a signal peptide that acts in the cytoplasm and nucleus. The UniProt 'Periplasm' location is cited to PMID:11781566, whose abstract concerns cytoplasmic/nuclear Fus3 and cortical Ste5/Ste7/Fus3 at mating projection tips, not a periplasmic (cell wall-plasma membrane) compartment. The mapping is not biologically plausible and should be removed. Supporting Evidence: PMID:7579701 Indirect immunofluorescence demonstrated that Kss1 is concentrated in the nucleus and that its distribution is not altered detectably during signaling. file:yeast/KSS1/KSS1-uniprot.txt KSS1 shuttles rapidly between the cytoplasm and the nucleus independent of its activation state. PMID:11781566 Ste5p, Ste7p and Fus3p also localized to tips of mating projections in pheromone-treated cells. |
| GO:0071507 pheromone response MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference that Kss1 participates in the pheromone response MAPK cascade. Reason: Kss1 is phosphorylated and activated by Ste7 in response to pheromone in wild-type cells and contributes to pheromone-induced gene expression, partially redundant with Fus3; it is a bona fide MAPK tier member of the pheromone cascade (grounded in the scer_mating_fus3_cascade module as a Fus3/Kss1 mating MAPK). Supporting Evidence: PMID:11583629 we show that Kss1 is rapidly phosphorylated and potently activated by mating pheromone in wild-type cells, and that this is required for normal pheromone-induced gene expression PMID:7579701 suggesting an order of function: Ste11-->Ste7-->Kss1 file:yeast/KSS1/KSS1-uniprot.txt FUS3 can partially compensate for the lack of KSS1 |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-based mapping (RHEA:17989) of protein serine kinase activity. Reason: Kss1 is a Ser/Thr MAPK; serine phosphorylation of substrates is part of its activity. Supporting Evidence: file:yeast/KSS1/KSS1-uniprot.txt Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + |
| GO:2000218 negative regulation of invasive growth in response to glucose limitation | IMP PMID:9744865 Repression of yeast Ste12 transcription factor by direct bin... | NEW | Summary: Unphosphorylated Kss1 binds Ste12 directly and, together with Dig1/Dig2, represses Ste12-dependent filamentation gene expression and invasive growth in the absence of signal, independently of its kinase activity. Reason: Kss1 itself does the work: its direct, activation-loop-controlled binding to Ste12 is necessary for repression, and the inhibitory function requires neither catalytic activity nor Ste7 activation (PMID:9744865, PMID:9393860). Dig1/Dig2 cooperate with Kss1 to regulate invasive growth (PMID:9860980). Comparator check: DIG1, the partner repressor in the same Ste12-repression role, carries GO:2000218 by IGI from PMID:8918885. The term is not an ancestor or descendant of the positive filamentation terms already on Kss1. Supporting Evidence: PMID:9744865 unphosphorylated Kss1 binds directly to the transcription factor Ste12, that this binding is necessary for Kss1-mediated repression of Ste12 PMID:9744865 The stimulatory function of Kss1 requires both its catalytic activity and its activation by the MAPK/ERK kinase (MEK) Ste7; in contrast, the inhibitory function of Kss1 requires neither. PMID:9393860 Kss1 inhibits the filamentation pathway by interacting with its target transcription factor Ste12. PMID:9860980 Dig1 and Dig2 cooperate with Kss1 to repress Ste12 action at FREs and regulate invasive growth in a naturally invasive strain. |
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Download this section (compressed HTML)Q: Does unphosphorylated Kss1 repress Ste12 while bound at FRE/PRE promoters (which would justify transcription corepressor activity, GO:0003714), or by sequestering Ste12 off DNA?
Q: Is the UniProt 'Periplasm' subcellular location for Kss1 (cited to PMID:11781566) an error, e.g. a mis-mapping of cell cortex/cell periphery, and should the GO:0042597 IEA be withdrawn at source?
Q: Is Kss1-dependent Bni4 phosphorylation and bud-neck localization physiological at endogenous Kss1 levels, or only revealed by overexpression in slt2 mutants?
Experiment: ChIP of kinase-dead and wild-type Kss1 at FRE-containing promoters (e.g. FLO11 regulators, TEC1) in the presence and absence of Dig1/Dig2 to test whether repressive Kss1 is promoter-associated.
Hypothesis: Repressive, unphosphorylated Kss1 is recruited with Ste12-Dig1/Dig2 to FRE promoters.
Type: chromatin immunoprecipitation
Experiment: Endogenously tagged Kss1 imaging and subcellular fractionation to test for any cell-surface/cortical pool and resolve the UniProt periplasm assignment.
Hypothesis: Kss1 has no periplasmic pool; any peripheral signal reflects cortical association with Ste5/Ste7.
Type: fluorescence microscopy
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Download this section (compressed HTML)Mitogen-activated protein kinase (MAPK); involved in signal transduction pathways that control filamentous growth and pheromone response; regulates septum assembly, and may directly phosphorylate Bni4p; the KSS1 gene is nonfunctional in some S288C-related strains and functional in W303a strains
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