Ssk1 (YLR006C) is the cytoplasmic response regulator of the Sln1-Ypd1-Ssk1 multistep phosphorelay that controls the Sln1 branch of the high-osmolarity glycerol (HOG) pathway in Saccharomyces cerevisiae. It is a non-enzymatic protein whose C-terminal CheY-like receiver domain accepts a phosphoryl group on Asp554 from the histidine phosphotransfer protein Ypd1. Under normal osmolarity the active sensor kinase Sln1 keeps Ssk1 phosphorylated and inactive; hyperosmotic stress inactivates Sln1, and unphosphorylated Ssk1 accumulates, binds the N-terminal regulatory segments of the MAP kinase kinase kinases Ssk2 and Ssk22 and induces their kinase activity, which in turn activates the Pbs2-Hog1 MAPK module. Ssk1 is largely dimeric, and phosphorylated Ssk1 inhibits unphosphorylated Ssk1, buffering the pathway against spurious activation; unphosphorylated Ssk1 is also turned over by a Ubc7-dependent ubiquitin-proteasome pathway after adaptation. Through Hog1 signalling, Ssk1 also contributes to responses to other stresses such as low external pH. Because Hog1 signalling is needed for mitophagy, ssk1 deletion also partially reduces mitophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000156 phosphorelay response regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT phylogenetic inference that Ssk1 is a phosphorelay response regulator; Ssk1 is itself an experimental seed (SGD:S000003996) of the node. Reason: Ssk1 is the terminal Asp-phosphoryl acceptor of the Sln1-Ypd1-Ssk1 phosphorelay (Asp554 in its CheY-like receiver domain), and its output (Ssk2/Ssk22 activation) is controlled by this phosphorylation. This is the core molecular function; the IBA node placement is consistent with the conserved fungal Ssk1 receiver family. Supporting Evidence: PMID:8808622 This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554. PMID:18573873 In either case, unphosphorylated Ssk1 accumulates to activate Ssk2. file:yeast/SSK1/SSK1-uniprot.txt DOMAIN 505..647 |
| GO:0000156 phosphorelay response regulator activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning assignment of phosphorelay response regulator activity. Reason: Consistent with the experimental data and the receiver-domain architecture; Ssk1 receives phosphate on Asp554 from Ypd1 and this controls its signalling output. Supporting Evidence: PMID:8808622 This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554. file:yeast/SSK1/SSK1-uniprot.txt DOMAIN 505..647 |
| GO:0000156 phosphorelay response regulator activity | IMP PMID:8183345 A two-component system that regulates an osmosensing MAP kin... | ACCEPT | Summary: Maeda et al. 1994 identified Ssk1 as the response regulator of a yeast two-component system that controls the HOG osmosensing MAP kinase cascade. Reason: Foundational genetic evidence (abstract-only cache; SGD curator read the full text) establishing Ssk1 as a two-component response regulator whose activity is governed by the Sln1 sensor; later work (Posas 1996, Horie 2008) confirmed Asp554 phosphorylation and the derepression logic. Core MF. Supporting Evidence: PMID:8183345 Here we describe a two-component system in Saccharomyces cerevisiae that regulates an osmosensing MAP kinase cascade. PMID:8808622 This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554. PMID:18573873 In either case, unphosphorylated Ssk1 accumulates to activate Ssk2. |
| GO:0000160 phosphorelay signal transduction system | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (response regulator receiver domain, IPR001789) mapping to phosphorelay signal transduction system. Reason: Correct though general; the more specific child GO:0007234 osmosensory signaling via phosphorelay pathway is annotated by IDA and IBA. Ssk1 performs a step of the phosphorelay (it is the final phosphoryl acceptor), so participation is direct. Supporting Evidence: PMID:8808622 This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554. file:yeast/SSK1/SSK1-uniprot.txt DOMAIN 505..647 |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk22 (UniProtKB:P25390). Reason: Generic protein binding is uninformative. The partner Ssk22 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:11805837 high-throughput mass spectrometric protein complex identification (HMS-PCI) PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk2 (UniProtKB:P53599). Reason: Generic protein binding is uninformative. The partner Ssk2 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:11805837 high-throughput mass spectrometric protein complex identification (HMS-PCI) PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk2 (UniProtKB:P53599). Reason: Generic protein binding is uninformative. The partner Ssk2 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase kinase kinase binding 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. PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk2 (UniProtKB:P53599). Reason: Generic protein binding is uninformative. The partner Ssk2 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:18467557 We identified 2770 interactions among 1124 endogenously expressed proteins. PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005515 protein binding | IPI PMID:18467557 An in vivo map of the yeast protein interactome. | REMOVE | Summary: High-throughput interaction of Ssk1 with the histidine phosphotransfer protein Ypd1 (UniProtKB:Q07688). Reason: Generic protein binding is uninformative. The Ssk1-Ypd1 interaction is real and well established (Ypd1 is the phosphoryl donor to Ssk1 Asp554; Ypd1-binding-defective Ssk1 receiver mutants are hyperactive), but binding of the phosphodonor is an integral part of the phosphorelay response regulator activity already captured by GO:0000156, and there is no more informative binding MF for Hpt-protein binding. Removal of this term does not imply the interaction is false. Supporting Evidence: PMID:18467557 We identified 2770 interactions among 1124 endogenously expressed proteins. PMID:8808622 Ypd1p binds to both Sln1p and Ssk1p and mediates the multistep phosphotransfer reaction (phosphorelay). PMID:18573873 all four of the Ssk1 mutants are completely incapable of binding to Ypd1, whereas they can bind to Ssk2. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk22 (UniProtKB:P25390). Reason: Generic protein binding is uninformative. The partner Ssk22 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:18719252 demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information. PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005515 protein binding | IPI PMID:18719252 High-quality binary protein interaction map of the yeast int... | REMOVE | Summary: High-throughput interaction of Ssk1 with the histidine phosphotransfer protein Ypd1 (UniProtKB:Q07688). Reason: Generic protein binding is uninformative. The Ssk1-Ypd1 interaction is real and well established (Ypd1 is the phosphoryl donor to Ssk1 Asp554; Ypd1-binding-defective Ssk1 receiver mutants are hyperactive), but binding of the phosphodonor is an integral part of the phosphorelay response regulator activity already captured by GO:0000156, and there is no more informative binding MF for Hpt-protein binding. Removal of this term does not imply the interaction is false. Supporting Evidence: PMID:18719252 demonstrating that high-throughput yeast two-hybrid (Y2H) screening provides high-quality binary interaction information. PMID:8808622 Ypd1p binds to both Sln1p and Ssk1p and mediates the multistep phosphotransfer reaction (phosphorelay). PMID:18573873 all four of the Ssk1 mutants are completely incapable of binding to Ypd1, whereas they can bind to Ssk2. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk22 (UniProtKB:P25390). Reason: Generic protein binding is uninformative. The partner Ssk22 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase 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:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk2 (UniProtKB:P53599). Reason: Generic protein binding is uninformative. The partner Ssk2 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase 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:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MODIFY | Summary: High-throughput interaction of Ssk1 with the MAP3K Ssk2 (UniProtKB:P53599). Reason: Generic protein binding is uninformative. The partner Ssk2 is one of the two HOG-pathway MAP3Ks that Ssk1 binds (via its C-terminal receiver domain, at the Ssk2 N-terminal regulatory segment) and activates; this interaction is independently established in low-throughput work (Posas and Saito 1998) and recorded by UniProt. The informative MF is mitogen-activated protein kinase kinase kinase binding (GO:0031435), which SGD already annotates from PMID:9482735. Proposed replacements: mitogen-activated protein kinase kinase kinase binding Supporting Evidence: PMID:37968396 The 4,159 pull-downs generated a highly structured network of 3,927 proteins connected by 31,004 interactions PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0005737 cytoplasm | IDA PMID:14665464 Saccharomyces cerevisiae histidine phosphotransferase Ypd1p ... | ACCEPT | Summary: GFP-Ssk1 localizes to the cytoplasm under all osmotic conditions tested (Lu et al. 2003). Reason: Direct localization evidence; Ssk1 is phosphorylated by Ypd1 in the cytosol and acts on the cytoplasmic MAP3Ks Ssk2/Ssk22, so cytoplasm is both where it is located and where it is active. Nuclear presence at low level was not excluded by the authors but has no known function. Supporting Evidence: PMID:14665464 GFP-Ssk1p appears to be localized to the cytoplasm PMID:14665464 since Ssk1p appears to be cytoplasmically localized under all osmotic conditions tested. |
| GO:0005737 cytoplasm | IDA PMID:14665464 Saccharomyces cerevisiae histidine phosphotransferase Ypd1p ... | ACCEPT | Summary: GFP-Ssk1 localizes to the cytoplasm under all osmotic conditions tested (Lu et al. 2003). Reason: Direct localization evidence; Ssk1 is phosphorylated by Ypd1 in the cytosol and acts on the cytoplasmic MAP3Ks Ssk2/Ssk22, so cytoplasm is both where it is located and where it is active. Nuclear presence at low level was not excluded by the authors but has no known function. Supporting Evidence: PMID:14665464 GFP-Ssk1p appears to be localized to the cytoplasm PMID:14665464 since Ssk1p appears to be cytoplasmically localized under all osmotic conditions tested. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (Cytoplasm). Reason: Consistent with the IDA evidence from Lu et al. 2003 on which the UniProt entry is based. Supporting Evidence: file:yeast/SSK1/SSK1-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm PMID:14665464 since Ssk1p appears to be cytoplasmically localized under all osmotic conditions tested. |
| GO:0006950 response to stress | IEA GO_REF:0000117 | MODIFY | Summary: ARBA assignment of the very general term response to stress. Reason: Not wrong, but uninformative: the stress Ssk1 responds to is hyperosmotic, and it acts as the signalling input into the HOG osmostress pathway. The specific term cellular hyperosmotic response (GO:0071474) is already annotated experimentally and should be preferred. Proposed replacements: cellular hyperosmotic response Supporting Evidence: PMID:9482735 The SSK2/SSK22 MAPKKKs are activated by a 'two-component' osmosensor composed of SLN1, YPD1 and SSK1. PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. |
| GO:0007234 osmosensory signaling via phosphorelay pathway | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of involvement in osmosensory signaling via phosphorelay; supported by Ssk1 own experimental annotation and the Aspergillus homolog. Reason: Ssk1 is the response-regulator step of the Sln1-Ypd1-Ssk1 osmosensing phosphorelay; this is exactly the process the term (which names the S. cerevisiae Sln1 system) describes. Core process. Supporting Evidence: PMID:8808622 This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554. PMID:9482735 The SSK2/SSK22 MAPKKKs are activated by a 'two-component' osmosensor composed of SLN1, YPD1 and SSK1. |
| GO:0007234 osmosensory signaling via phosphorelay pathway | IDA PMID:8808622 Yeast HOG1 MAP kinase cascade is regulated by a multistep ph... | ACCEPT | Summary: Posas et al. 1996 defined the Sln1-Ypd1-Ssk1 multistep phosphorelay controlling the HOG1 cascade, with Ssk1 Asp554 as the final acceptor. Reason: Direct biochemical demonstration that Ssk1 participates in (performs the terminal step of) the osmosensing phosphorelay. Core process. Supporting Evidence: PMID:8808622 This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554. PMID:8808622 Ypd1p binds to both Sln1p and Ssk1p and mediates the multistep phosphotransfer reaction (phosphorelay). |
| GO:0030295 protein kinase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of protein kinase activator activity, seeded by Ssk1 experimental data. Reason: Ssk1 binds the N-terminal regulatory segment of the MAP3K Ssk2 and induces its latent kinase activity; dephosphorylated (inactive) Ssk2 can be re-activated by adding Ssk1 in vitro, and Ssk2 autophosphorylation upon osmostress requires Ssk1 binding. This is the output function of the response regulator, performed by unphosphorylated Ssk1. No more specific "MAP kinase kinase kinase activator" term exists in GO, so this is the appropriate MF. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:9482735 Dephosphorylation of SSK2 renders the kinase inactive, but it can be re-activated by addition of SSK1 in vitro. |
| GO:0030295 protein kinase activator activity | IDA PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: In vitro reactivation of Ssk2 kinase by Ssk1 (Posas and Saito 1998). Reason: Ssk1 binds the N-terminal regulatory segment of the MAP3K Ssk2 and induces its latent kinase activity; dephosphorylated (inactive) Ssk2 can be re-activated by adding Ssk1 in vitro, and Ssk2 autophosphorylation upon osmostress requires Ssk1 binding. This is the output function of the response regulator, performed by unphosphorylated Ssk1. No more specific "MAP kinase kinase kinase activator" term exists in GO, so this is the appropriate MF. Supporting Evidence: PMID:9482735 Dephosphorylation of SSK2 renders the kinase inactive, but it can be re-activated by addition of SSK1 in vitro. PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. |
| GO:0030295 protein kinase activator activity | IMP PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Genetic evidence that Ssk1 interaction is required for Ssk2 autophosphorylation/activation upon osmostress (Posas and Saito 1998). Reason: Ssk1 binds the N-terminal regulatory segment of the MAP3K Ssk2 and induces its latent kinase activity; dephosphorylated (inactive) Ssk2 can be re-activated by adding Ssk1 in vitro, and Ssk2 autophosphorylation upon osmostress requires Ssk1 binding. This is the output function of the response regulator, performed by unphosphorylated Ssk1. No more specific "MAP kinase kinase kinase activator" term exists in GO, so this is the appropriate MF. Supporting Evidence: PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 Thus, Ssk1-OH is indeed necessary for Ssk2 activation. |
| GO:0031435 mitogen-activated protein kinase kinase kinase binding | IPI PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Ssk1 receiver domain binds the N-terminal segment of the MAP3K Ssk2 (Posas and Saito 1998). Reason: Informative binding MF directly supported by the cited paper and by Horie et al. 2008 (two-hybrid and co-precipitation). The binding is the mechanistic basis of Ssk2 activation; it is subsumed by, and supports, the protein kinase activator activity core function. Supporting Evidence: PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. PMID:18573873 In vivo coprecipitation assays corroborated the finding that Ssk1-D628G does not bind to Ssk2 file:yeast/SSK1/SSK1-uniprot.txt SUBUNIT: Interacts with SSK2, SSK22 and YPD1. |
| GO:0032956 regulation of actin cytoskeleton organization | IMP PMID:19633059 Importance of polarisome proteins in reorganization of actin... | KEEP AS NON CORE | Summary: Sln1-branch (including SSK1) deletion blocks the transient actin depolarization triggered by low-pH (pH 3.0) stress (Motizuki and Xu 2009). Reason: Abstract-only cache; the SGD curator attributed an IMP to SSK1 from the full text, which is consistent with the abstract statement about Sln1-branch deletions. Ssk1 acts here as the upstream signalling input to Hog1 activation; the actin reorganization is executed by Hog1 and polarisome proteins. The regulation term is acceptable for an upstream signalling component but is a peripheral, context-specific consequence, not a core function. Supporting Evidence: PMID:19633059 Gene deletions on the Sln1p branch of the HOG pathway completely blocked actin depolarization, suggesting that Hog1p activation depends mainly on the osmosensor Sln1p. PMID:19633059 S. cerevisiae responds to low-pH stress by transiently depolarizing its actin cytoskeleton, and that this step requires a mitogen-activated protein kinase, high osmolarity glycerol 1 (Hog1p). file:yeast/SSK1/SSK1-deep-research-falcon.md These are downstream consequences of Ssk1 signaling rather than direct biochemical activities of Ssk1 itself. |
| GO:0071467 cellular response to pH | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA assignment of cellular response to pH, presumably mirroring the SGD IMP for cellular response to acidic pH. Reason: Broader parent of the experimentally supported cellular response to acidic pH (GO:0071468). Acceptable as a peripheral role of the Sln1-branch HOG signalling input, not a core function. Supporting Evidence: PMID:19633059 Gene deletions on the Sln1p branch of the HOG pathway completely blocked actin depolarization, suggesting that Hog1p activation depends mainly on the osmosensor Sln1p. |
| GO:0071468 cellular response to acidic pH | IMP PMID:19633059 Importance of polarisome proteins in reorganization of actin... | KEEP AS NON CORE | Summary: Ssk1 (Sln1 branch) is required for the Hog1-dependent actin depolarization response to pH 3.0 stress. Reason: Supported by the SGD curator reading of the full text (abstract-only cache). Ssk1 signals low-pH stress into the HOG pathway, but this is a secondary context of its general role as the Sln1-branch response regulator; kept as non-core. Supporting Evidence: PMID:19633059 Gene deletions on the Sln1p branch of the HOG pathway completely blocked actin depolarization, suggesting that Hog1p activation depends mainly on the osmosensor Sln1p. PMID:19633059 S. cerevisiae responds to low-pH stress by transiently depolarizing its actin cytoskeleton, and that this step requires a mitogen-activated protein kinase, high osmolarity glycerol 1 (Hog1p). |
| GO:0071474 cellular hyperosmotic response | IDA PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Ssk1 is required for, and directly signals, osmostress-induced Ssk2 activation (Posas and Saito 1998). Reason: Ssk1 performs the signal-transducing step that couples osmosensing to the HOG MAPK cascade, which executes the cellular hyperosmotic response. Accepted as a core process at the level SGD annotates it. Supporting Evidence: PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. PMID:9482735 The SSK2/SSK22 MAPKKKs are activated by a 'two-component' osmosensor composed of SLN1, YPD1 and SSK1. |
| GO:0071474 cellular hyperosmotic response | IMP PMID:18573873 Phosphorylated Ssk1 prevents unphosphorylated Ssk1 from acti... | ACCEPT | Summary: Ssk1 phosphorylation-site and Ypd1-binding mutants constitutively activate Ssk2/Hog1; Ssk1 is required for the Sln1-branch osmostress response (Horie et al. 2008). Reason: Consistent mutant evidence that unphosphorylated Ssk1 is the active signal of the Sln1 branch of the hyperosmotic response. Core process. Supporting Evidence: PMID:18573873 Thus, Ssk1-OH is indeed necessary for Ssk2 activation. PMID:18573873 In either case, unphosphorylated Ssk1 accumulates to activate Ssk2. |
| GO:1900744 regulation of p38MAPK cascade | IDA PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Ssk1 directly reactivates Ssk2 MAP3K in vitro (Posas and Saito 1998). Reason: SGD uses the p38MAPK cascade terms for the Hog1 cascade. Ssk1 is not a component of the kinase tiers but directly regulates the cascade at its entry point: unphosphorylated Ssk1 activates the MAP3K Ssk2, while phosphorylated Ssk1 inhibits Ssk1-OH, giving a dual regulatory role that the non-directional "regulation" term captures well. Supporting Evidence: PMID:9482735 Dephosphorylation of SSK2 renders the kinase inactive, but it can be re-activated by addition of SSK1 in vitro. PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. |
| GO:1900744 regulation of p38MAPK cascade | IGI PMID:9482735 Activation of the yeast SSK2 MAP kinase kinase kinase by the... | ACCEPT | Summary: Genetic interaction between SSK1 and SSK2 in control of the Hog1 cascade (Posas and Saito 1998). Reason: SGD uses the p38MAPK cascade terms for the Hog1 cascade. Ssk1 is not a component of the kinase tiers but directly regulates the cascade at its entry point: unphosphorylated Ssk1 activates the MAP3K Ssk2, while phosphorylated Ssk1 inhibits Ssk1-OH, giving a dual regulatory role that the non-directional "regulation" term captures well. Supporting Evidence: PMID:9482735 Upon hyperosmotic treatment, SSK2 is autophosphorylated rapidly, and this reaction requires the interaction of SSK1 with SSK2. PMID:9482735 The SSK1 C-terminal receiver domain interacts with an N-terminal segment of SSK2. |
| GO:1900744 regulation of p38MAPK cascade | IMP PMID:18573873 Phosphorylated Ssk1 prevents unphosphorylated Ssk1 from acti... | ACCEPT | Summary: Horie et al. 2008 show Ssk1 acts both as an activator of Ssk2 and, when phosphorylated, as an inhibitor of unphosphorylated Ssk1. Reason: SGD uses the p38MAPK cascade terms for the Hog1 cascade. Ssk1 is not a component of the kinase tiers but directly regulates the cascade at its entry point: unphosphorylated Ssk1 activates the MAP3K Ssk2, while phosphorylated Ssk1 inhibits Ssk1-OH, giving a dual regulatory role that the non-directional "regulation" term captures well. Supporting Evidence: PMID:18573873 Therefore, Ssk1 has a dual function as both an activator of Ssk2 and an inhibitor of Ssk1 itself. PMID:18573873 Thus, Ssk1-OH is indeed necessary for Ssk2 activation. |
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Download this section (compressed HTML)Q: Should Ssk1 homodimerization (GO:0042803 protein homodimerization activity), shown by gel filtration and co-precipitation of receiver domains in Horie et al. 2008 and central to the Ssk1~P/Ssk1-OH inhibition model, be annotated, given SGD curated that paper without adding it?
Q: Is Ssk22 activated by Ssk1 by the same two-step mechanism as Ssk2, and is the Ssk1-Ssk22 interaction direct? Current evidence for Ssk22 is largely high-throughput interaction data and pathway genetics.
Q: In a HOG GO-CAM, should Ssk1 be modelled with GO:0000156 (input from Ypd1) causally upstream of Ssk2/Ssk22 MAP3K activity, with GO:0030295 carrying has_input Ssk2/Ssk22, rather than as a generic binding node?
Experiment: Reconstitute Ssk2 and Ssk22 activation in vitro with purified Ssk1-OH, Ssk1~P (via Ypd1 phosphotransfer) and mixed dimers to test quantitatively whether only Ssk1-OH/Ssk1-OH dimers activate the MAP3Ks and whether Ssk1 bridges Ssk2 dimerization.
Experiment: Determine a structure of the Ssk1 receiver domain in complex with the Ssk2 N-terminal regulatory segment to define the Ssk2-binding surface (including the D628 region) and how Asp554 phosphorylation blocks it.
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Download this section (compressed HTML)Cytoplasmic phosphorelay intermediate osmosensor and regulator; part of a two-component signal transducer that mediates osmosensing via a phosphorelay mechanism; required for mitophagy; dephosphorylated form is degraded by the ubiquitin-proteasome system; potential Cdc28p substrate
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