Sty1 (also called Spc1, Phh1; ortholog of S. cerevisiae Hog1 and human p38/JNK) is the fission yeast stress-activated MAP kinase (SAPK), the central effector of the core environmental stress response. It is a serine/threonine protein kinase of the HOG1 sub-subfamily that is activated by dual phosphorylation of its Thr-171/Tyr-173 (TGY) activation-loop motif, catalyzed by the MAP kinase kinase Wis1, and is inactivated by the tyrosine phosphatases Pyp1 and Pyp2 and by PP2C-type serine/threonine phosphatases. Sty1 is activated by a wide range of stresses including hyperosmotic shock, oxidative stress (hydrogen peroxide, menadione, methylglyoxal, arsenite), heat shock, UV, toxic cations, and nutrient/nitrogen limitation. In unstressed cells Sty1 is predominantly cytoplasmic, but upon activation it rapidly and transiently accumulates in the nucleus, where it phosphorylates the bZIP transcription factor Atf1 (and influences the Pap1 pathway) to drive transcription of stress-response genes, in part by binding and phosphorylating the RNA polymerase II C-terminal domain at stress promoters. Sty1 also phosphorylates the downstream MAPKAP kinase Srk1 and other substrates to couple the environment to the G2/M cell-cycle transition (it both promotes and, under certain conditions, delays mitotic entry), and it is required for sexual differentiation, meiosis, and meiotic recombination during nitrogen starvation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0051403 stress-activated MAPK cascade | IBA GO_REF:0000033 | ACCEPT | Summary: Sty1 is the terminal MAP kinase of the fission yeast stress-activated MAPK cascade. This phylogenetic (IBA) annotation matches a large body of experimental evidence and is a core function. Reason: Well supported by experimental and orthology evidence; Sty1 is the defining SAPK of S. pombe. Supporting Evidence: PMID:8649397 Spc1 is most closely related to Saccharomyces cerevisiae Hog1 and mammalian p38 kinases. |
| GO:0034599 cellular response to oxidative stress | IBA GO_REF:0000033 | ACCEPT | Summary: Sty1 is required for the cellular response to oxidative stress, mediating gene expression through Atf1 and the Pap1 pathway. A core function supported by extensive experimental evidence. Reason: Phylogenetic call corroborated by multiple IMP/IDA experiments in S. pombe. Supporting Evidence: PMID:9585505 the cellular response to oxidative stress and to treatment with a variety of cytotoxic agents is the result of Sty1 regulation of the Pap1 transcription factor |
| GO:0007231 osmosensory signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Sty1/Spc1 is the osmosensing MAP kinase of fission yeast, activated by hyperosmotic stress and required for growth in high osmolarity. The osmosensory signaling pathway annotation is well supported. Reason: Established osmosensing role; Sty1 is the HOG1 ortholog. Supporting Evidence: PMID:7657164 Osmotic stress induces both tyrosine phosphorylation of Sty1 and a reduction in cell size at division. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic protein kinase activity is correct but is a less informative parent of the experimentally established MAP kinase activity (GO:0004707). Better captured by the specific MF term. Reason: Subsumed by the more specific and experimentally supported MAP kinase activity annotation; the bare parent term adds little. Proposed replacements: MAP kinase activity Supporting Evidence: PMID:7657164 the sty1 gene, which encodes a MAP kinase |
| GO:0004707 MAP kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: MAP kinase activity is the core molecular function of Sty1, supported by numerous direct experimental assays. This IEA annotation is correct. Reason: Core catalytic function with abundant experimental corroboration. Supporting Evidence: PMID:9188094 Spc1 in Schizosaccharomyces pombe is a member of the stress-activated protein kinase family, an evolutionary conserved subfamily of mitogen-activated protein kinases (MAPKs). |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: As a protein kinase, Sty1 binds ATP; the InterPro-based annotation is consistent with the canonical kinase ATP-binding site (residues 26-34, 49 in UniProt). Reason: Standard, well-supported kinase cofactor/substrate binding. Supporting Evidence: PMID:7657164 the sty1 gene, which encodes a MAP kinase |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Sty1 accumulates in the nucleus upon stress, where it phosphorylates Atf1 and Pol II. This subcellular-location-derived annotation is correct and supported by direct microscopy. Reason: Stress-induced nuclear localization is well documented experimentally. Supporting Evidence: PMID:9585506 Stress induces transient nuclear localization of Spc1. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Sty1 is predominantly cytoplasmic in unstressed cells, consistent with the UniProt subcellular location. Correct. Reason: Predominant resting localization established by microscopy. Supporting Evidence: PMID:12896976 the transcription factor Pap1, and the mitogen-activated protein kinase Sty1 are excluded from the nucleus in a Crm1-dependent manner under non-stressed conditions |
| GO:0051403 stress-activated MAPK cascade | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate of the IBA stress-activated MAPK cascade annotation, here from InterPro. Correct core function. Reason: Corroborates the core stress-activated MAPK cascade function (InterPro-based computational call consistent with the IBA annotation). Supporting Evidence: PMID:9136929 Sty1 is activated by a range of environmental insults |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | KEEP AS NON CORE | Summary: Sty1 is a serine/threonine kinase; this Rhea-derived term is correct but is a less specific parent of MAP kinase activity. Reason: Correct general catalytic property; MAP kinase activity is the more informative core term. Supporting Evidence: PMID:8824588 Atf1 associates stably and is phosphorylated by the Sty1 kinase in vitro. |
| GO:0005515 protein binding | IPI PMID:12080074 The Srk1 protein kinase is a target for the Sty1 stress-acti... | MARK AS OVER ANNOTATED | Summary: This IPI records the Sty1-Srk1 interaction. Srk1 is a direct substrate of Sty1; the bare 'protein binding' term is uninformative and the relationship is better captured by Sty1's kinase activity acting on Srk1. Reason: Bare protein binding is uninformative per curation guidelines; the underlying interaction (Srk1 substrate) is captured by the kinase-activity and signaling annotations. Supporting Evidence: PMID:12080074 Srk1 is present in a complex with the Sty1 MAPK and is directly phosphorylated by Sty1. |
| GO:0005515 protein binding | IPI PMID:22139357 H₂O₂ stress-specific regulation of S. pombe MAPK Sty1 by mit... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Ptc4 interaction (the mitochondrial PP2C phosphatase that inactivates Sty1). Bare protein binding is uninformative. Reason: Uninformative MF term; the regulatory interaction is documented but not captured usefully by 'protein binding'. Supporting Evidence: PMID:22139357 this displays a stronger interaction with Sty1 |
| GO:0005515 protein binding | IPI PMID:23695164 Cross-species protein interactome mapping reveals species-sp... | MARK AS OVER ANNOTATED | Summary: From a high-throughput cross-species interactome map. Bare protein binding is uninformative and the interactions are not individually validated here. Reason: Uninformative MF term from a large-scale interactome screen. Supporting Evidence: PMID:23695164 Cross-species protein interactome mapping reveals species-specific wiring of stress response pathways. |
| GO:0005737 cytoplasm | IDA PMID:10233152 Active nucleocytoplasmic shuttling required for function and... | ACCEPT | Summary: Sty1 is active in and shuttles through the cytoplasm; nucleocytoplasmic shuttling is required for its function. Correctly annotated. Reason: Direct microscopy supports cytoplasmic localization/activity. Supporting Evidence: PMID:10233152 active nucleocytoplasmic shuttling is required for both the function and regulation of Spc1 during the osmotic shock response. |
| GO:0106310 protein serine kinase activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS-based serine kinase activity. Correct but a less specific parent of MAP kinase activity; duplicate of the IEA call above. Reason: Correct general catalytic property, subsumed by MAP kinase activity. Supporting Evidence: PMID:8824588 Atf1 associates stably and is phosphorylated by the Sty1 kinase in vitro. |
| GO:0090055 positive regulation of silent mating-type cassette heterochromatin formation | EXP PMID:15292231 Regulation of Swi6/HP1-dependent heterochromatin assembly by... | KEEP AS NON CORE | Summary: The MAPK pathway, via phosphorylation of Atf1/Pcr1, promotes Swi6/HP1-dependent heterochromatin assembly at the silent mating-type region. A genuine but specialized, non-core downstream role. Reason: Real but peripheral function mediated indirectly through Atf1/Pcr1; not part of the core stress-kinase function. Supporting Evidence: PMID:15292231 a phosphorylation event catalyzed by the conserved mitogen-activated protein kinase pathway is important for regulation of heterochromatin silencing by Atf1 and Pcr1 |
| GO:0005634 nucleus | IDA PMID:16141205 The glycolytic metabolite methylglyoxal activates Pap1 and S... | ACCEPT | Summary: Sty1 accumulates in the nucleus following methylglyoxal treatment. Direct evidence for stress-induced nuclear activity. Reason: Direct microscopy of stress-induced nuclear accumulation. Supporting Evidence: PMID:16141205 The mitogen-activated protein kinase Sty1 is phosphorylated and accumulates in the nucleus following methylglyoxal treatment. |
| GO:0005634 nucleus | IDA PMID:36174923 Schizosaccharomyces pombe MAP kinase Sty1 promotes survival ... | ACCEPT | Summary: Sty1 stably localizes to the nucleus in early stationary phase in cells with mitochondrial translation defects. Supports nuclear activity; redundant with other nucleus annotations. Reason: Corroborates the well-established stress-induced nuclear localization. Supporting Evidence: PMID:36174923 coincided with the stable localization of Sty1 and Pap1 in the nucleus |
| GO:0005634 nucleus | IDA PMID:9585506 Phosphorylation and association with the transcription facto... | ACCEPT | Summary: Direct demonstration of stress-induced transient nuclear localization of Sty1, where it acts on Atf1. Core localization for function. Reason: Foundational evidence that activated Sty1 acts in the nucleus. Supporting Evidence: PMID:9585506 Stress induces transient nuclear localization of Spc1. |
| GO:0005515 protein binding | IPI PMID:10428959 Sin1: an evolutionarily conserved component of the eukaryoti... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Sin1 interaction. Bare protein binding is uninformative; Sin1 is a scaffold component of the SAPK pathway. Reason: Uninformative MF term; the documented Sin1 interaction is captured by pathway-level annotations. Supporting Evidence: PMID:10428959 We have identified a protein, Sin1, that interacts with Sty1/Spc1 |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:10428959 Sin1: an evolutionarily conserved component of the eukaryoti... | ACCEPT | Summary: sty1 mutants (and sin1 mutants sharing Sty1 phenotypes) show a G2/M cell-cycle delay, consistent with Sty1 promoting mitotic entry. Core cell-cycle function. Reason: Sty1 promotes the G2/M transition; loss causes G2 delay. Supporting Evidence: PMID:10428959 Cells lacking Sin1 display many, but not all, of the phenotypes of cells lacking the Sty1/Spc1 MAP kinase including sterility, multiple stress sensitivity and a cell-cycle delay. |
| GO:0004707 MAP kinase activity | EXP PMID:9188094 Mcs4 mitotic catastrophe suppressor regulates the fission ye... | ACCEPT | Summary: Experimental evidence for Sty1/Spc1 MAP kinase activity within the Wik1-Wis1-Spc1 cascade. Core function (one of many supporting references). Reason: Direct experimental support for the core catalytic function. Supporting Evidence: PMID:9188094 Spc1 is activated by a MAPK kinase homologue, Wis1, and negatively regulated by Pyp1 and Pyp2 tyrosine phosphatases. |
| GO:0005515 protein binding | IPI PMID:33410907 The fission yeast Pin1 peptidyl-prolyl isomerase promotes di... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Pin1 interaction (Pin1 promotes Sty1 dissociation from Pol II). Bare protein binding is uninformative. Reason: Uninformative MF term; underlying biology captured by CTD-kinase and transcription annotations. Supporting Evidence: PMID:33410907 Pin1 binds phosphorylated CTD to promote dissociation of Sty1 from it |
| GO:0000785 chromatin | IDA PMID:33410907 The fission yeast Pin1 peptidyl-prolyl isomerase promotes di... | ACCEPT | Summary: Sty1 is recruited to stress-responsive promoters where it associates with Pol II and phosphorylates the CTD. Chromatin localization is directly supported. Reason: Sty1 acts at chromatin/promoters during stress-induced transcription. Supporting Evidence: PMID:33410907 the Atf1 transcription factor targets Sty1, the mitogen-activated protein kinase (MAPK), to specific stress-responsive promoters |
| GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity | IDA PMID:33410907 The fission yeast Pin1 peptidyl-prolyl isomerase promotes di... | ACCEPT | Summary: Sty1 directly associates with the Rpb1 CTD and phosphorylates the heptad repeat at Ser5 at stress promoters. A genuine, specific molecular function distinct from generic MAPK activity. Reason: Direct biochemical/genetic evidence for CTD Ser5 kinase activity. Supporting Evidence: PMID:33410907 Anchored Sty1 recruits Pol II through direct association with Rpb1-CTD and phosphorylates the reiterated heptad sequence at Serine 5. |
| GO:0005634 nucleus | IDA PMID:33225241 The Hsp40 Mas5 Connects Protein Quality Control and the Gene... | ACCEPT | Summary: Heat-induced inactivation of Pyp1 promotes full activation and nuclear function of the Sty1-Atf1 cascade. Supports nuclear activity; redundant with core nucleus annotation. Reason: Corroborates the well-established stress-induced nuclear localization. Supporting Evidence: PMID:33225241 to promote full activation of the anti-stress Sty1-Atf1 cascade |
| GO:0005634 nucleus | EXP PMID:12181336 Cytoplasmic localization of Wis1 MAPKK by nuclear export sig... | ACCEPT | Summary: Cytoplasmic Wis1 is required for nuclear targeting of activated Sty1. Supports stress-induced nuclear localization. Redundant with core nucleus annotation. Reason: Corroborates the well-established stress-induced nuclear localization. Supporting Evidence: PMID:12181336 Cytoplasmic localization of Wis1 MAPKK by nuclear export signal is important for nuclear targeting of Spc1/Sty1 MAPK in fission yeast. |
| GO:0005829 cytosol | EXP PMID:12181336 Cytoplasmic localization of Wis1 MAPKK by nuclear export sig... | KEEP AS NON CORE | Summary: Sty1 is present/active in the cytosol in unstressed cells (subcellular pool from which it is targeted to the nucleus). Consistent with cytoplasmic localization. Reason: Correct but redundant with the cytoplasm annotation; cytosol is the resting pool. Supporting Evidence: PMID:12181336 Cytoplasmic localization of Wis1 MAPKK by nuclear export signal is important for nuclear targeting of Spc1/Sty1 MAPK in fission yeast. |
| GO:0004707 MAP kinase activity | EXP PMID:14633985 RNA-binding protein Csx1 mediates global control of gene exp... | ACCEPT | Summary: Spc1/Sty1 MAP kinase orchestrates global gene-expression changes in response to stress. Core catalytic function (one of many supporting references). Reason: Direct experimental support for core MAP kinase function. Supporting Evidence: PMID:14633985 Fission yeast Spc1 (Sty1), a stress-activated mitogen-activated protein kinase (MAPK) homologous to human p38, orchestrates global changes in gene expression in response to diverse forms of cytotoxic stress. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:8824587 Conjugation, meiosis, and the osmotic stress response are re... | ACCEPT | Summary: Sty1 drives transcription of stress-response and meiotic genes (e.g. ste11+, gpd1+, pyp2+) via Atf1. Core downstream function. Reason: Sty1 is required for induction of stress and meiotic genes through Atf1. Supporting Evidence: PMID:8824587 Atf1 is required for induction of meiotic genes and stress-response genes, such as gpd1+ and pyp2+, that are transcriptionally regulated by Spc1. |
| GO:0038066 p38MAPK cascade | IMP PMID:11179424 Peroxide sensors for the fission yeast stress-activated mito... | ACCEPT | Summary: Sty1 is the p38-orthologous MAP kinase of the cascade, activated by peroxide via the Mcs4/Mak2/Mak3 two-component system. Core function (representative of many p38MAPK cascade annotations). Reason: Sty1 is the defining p38-type SAPK; activation via the cascade is well established. Supporting Evidence: PMID:11179424 Mcs4p, a response regulator protein, acts upstream of Sty1p by binding the Wak1p/Wis4p MAP kinase kinase kinase. |
| GO:1903500 negative regulation of mitotic actomyosin contractile ring assembly | EXP PMID:32915139 Stress-activated MAPK signaling controls fission yeast actom... | KEEP AS NON CORE | Summary: The SAPK effector Sty1 downregulates contractile actomyosin ring assembly by reducing formin For3 levels upon cytoskeletal damage and stress. A genuine but specialized, non-core downstream role. Reason: Real stress-adaptive cytokinesis control, but peripheral to the core kinase/signaling function. Supporting Evidence: PMID:32915139 the stress-activated protein kinase pathway (SAPK) and its effector, MAPK Sty1, downregulates CAR assembly in S. pombe when its integrity becomes compromised during cytoskeletal damage and stress by reducing For3 levels. |
| GO:0004707 MAP kinase activity | IDA PMID:31911490 RNA-Binding Protein Rnc1 Regulates Cell Length at Division a... | ACCEPT | Summary: Direct evidence for Sty1 MAP kinase activity (here in the context of Rnc1 negative feedback). Core function; redundant with other MAP kinase activity calls. Reason: Direct support for the core catalytic function. Supporting Evidence: PMID:31911490 Rnc1 downregulates the activity of Sty1, the MAPK of the stress-activated MAPK pathway (SAPK) |
| GO:0005515 protein binding | IPI PMID:31911490 RNA-Binding Protein Rnc1 Regulates Cell Length at Division a... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Rnc1 interaction (negative-feedback RNA-binding protein). Bare protein binding is uninformative. Reason: Uninformative MF term; regulatory relationship captured by pathway annotations. Supporting Evidence: PMID:31911490 Rnc1 downregulates the activity of Sty1, the MAPK of the stress-activated MAPK pathway (SAPK) |
| GO:0010494 cytoplasmic stress granule | EXP PMID:32071154 Fission Yeast Puf2, a Pumilio and FBF Family RNA-Binding Pro... | KEEP AS NON CORE | Summary: Sty1 is detected in cytoplasmic stress granules formed upon glucose deprivation. A specialized, non-core localization. Reason: Minor stress-induced localization pool; not central to the kinase's signaling function. Supporting Evidence: PMID:32071154 Stress granules (SGs) are cytoplasmic aggregates formed upon stress when untranslated messenger ribonucleoproteins accumulate in the cells. |
| GO:0010972 negative regulation of G2/M transition of mitotic cell cycle | IMP PMID:29065217 The fission yeast MAPK Spc1 senses perturbations in Cdc25 an... | ACCEPT | Summary: Spc1/Sty1 acts as a mitotic inhibitor by targeting the 14-3-3 protein Rad24, relocalizing Cdc25 and delaying mitosis. Genuine context-dependent function complementing its positive G2/M role. Reason: Direct genetic evidence that Sty1 can delay mitotic entry via Rad24/Cdc25. Supporting Evidence: PMID:29065217 Spc1 targets the 14-3-3 protein, Rad24, independently of Srk1, leading to relocalization of Cdc25 and mitotic inhibition. |
| GO:0005515 protein binding | IPI PMID:31477575 Modulation of TOR complex 2 signaling by the stress-activate... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Sin1 interaction in the TORC2 context (Spc1 CD domain binds Sin1). Bare protein binding is uninformative. Reason: Uninformative MF term; the Sin1/TORC2 interaction is captured by signaling annotations. Supporting Evidence: PMID:31477575 the common docking (CD) domain of Spc1 interacts with a cluster of basic amino acid residues in Sin1 |
| GO:0005737 cytoplasm | IDA PMID:12896976 Schizosaccharomyces pombe cells lacking the Ran-binding prot... | ACCEPT | Summary: Sty1 is excluded from the nucleus (cytoplasmic) under non-stressed conditions in a Crm1-dependent manner. Supports cytoplasmic localization. Reason: Direct microscopy of resting cytoplasmic localization. Supporting Evidence: PMID:12896976 the transcription factor Pap1, and the mitogen-activated protein kinase Sty1 are excluded from the nucleus in a Crm1-dependent manner under non-stressed conditions |
| GO:0004707 MAP kinase activity | IDA PMID:28924043 Dynamic regulation of Cdr1 kinase localization and phosphory... | ACCEPT | Summary: Direct evidence for Sty1 kinase activity (osmotic-stress-induced Cdr1 hyperphosphorylation requires Sty1). Core function; redundant. Reason: Direct support for the core catalytic function. Supporting Evidence: PMID:28924043 This stress-induced hyperphosphorylation required both Cdr1 autophosphorylation and the stress-activated protein kinase Sty1. |
| GO:0004707 MAP kinase activity | IDA PMID:18272791 Activation of Srk1 by the mitogen-activated protein kinase S... | ACCEPT | Summary: Sty1 directly phosphorylates Srk1 at Thr-463; direct kinase activity. Core function; redundant with other MAP kinase activity calls. Reason: Direct biochemical demonstration of Sty1 kinase activity on a substrate. Supporting Evidence: PMID:18272791 Sty1/Spc1 phosphorylates Srk1 at threonine 463 of the regulatory domain |
| GO:0010972 negative regulation of G2/M transition of mitotic cell cycle | IPI PMID:18272791 Activation of Srk1 by the mitogen-activated protein kinase S... | ACCEPT | Summary: Via phosphorylation/activation of Srk1, which inhibits Cdc25, Sty1 negatively regulates the G2/M transition. Genuine context-dependent role. Reason: Mechanistic evidence for Sty1-Srk1-Cdc25 mitotic inhibition. Supporting Evidence: PMID:18272791 inducing both activation of Srk1 kinase, which negatively regulates cell cycle progression by inhibiting Cdc25 |
| GO:1990625 negative regulation of cytoplasmic translational initiation in response to stress | IPI PMID:18065650 Fission yeast mitogen-activated protein kinase Sty1 interact... | KEEP AS NON CORE | Summary: Sty1 binds translation factors eEF2 and eIF3a and is required for translational adaptation/recovery after stress. A genuine but specialized, non-core role. Reason: Real translational adaptation function, peripheral to the core stress-signaling role. Supporting Evidence: PMID:18065650 We find Sty1, but not Mkp1, to bind to the translation elongation factor eukaryotic elongation factor 2 (eEF2) and the translation initiation factor eukaryotic initiation factor 3a (eIF3a). |
| GO:0005515 protein binding | IPI PMID:15870269 Response of fission yeast to toxic cations involves cooperat... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Hal4 interaction in the toxic-cation response. Bare protein binding is uninformative. Reason: Uninformative MF term; the Hal4 interaction is captured by the cation-resistance biology. Supporting Evidence: PMID:15870269 we have identified a novel Spc1-interacting protein, Hal4 |
| GO:0031138 negative regulation of conjugation with cellular fusion | IMP PMID:12080074 The Srk1 protein kinase is a target for the Sty1 stress-acti... | KEEP AS NON CORE | Summary: Through its substrate Srk1, Sty1 restrains entry into sexual development; overexpression of srk1+ inhibits the nitrogen-starvation-induced G1 arrest required for mating. A genuine non-core regulatory role. Reason: Negative regulation of conjugation via Srk1 is real but secondary to Sty1's core stress functions. Supporting Evidence: PMID:12080074 overexpression of srk1(+) inhibits the nitrogen starvation-induced arrest in G(1). |
| GO:0034599 cellular response to oxidative stress | IMP PMID:12080074 The Srk1 protein kinase is a target for the Sty1 stress-acti... | ACCEPT | Summary: Sty1 mediates the response to oxidative and other cytotoxic stresses; this IMP corroborates the core oxidative-stress role. Reason: Core stress-response function with direct genetic support. Supporting Evidence: PMID:12080074 The fission yeast stress-activated Sty1/Spc1 MAPK pathway responds to a similar range of stresses as do the mammalian p38 and SAPK/JNK MAPK pathways. |
| GO:0071470 cellular response to osmotic stress | IMP PMID:12080074 The Srk1 protein kinase is a target for the Sty1 stress-acti... | ACCEPT | Summary: Sty1 is the central kinase mediating the cellular response to osmotic stress. Core function with strong genetic support across many studies. Reason: Core osmotic-stress-response role; sty1 mutants are osmosensitive. Supporting Evidence: PMID:7657164 delta sty1 and delta wis1 cells are unable to grow in high osmolarity medium. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:7657164 Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kin... | ACCEPT | Summary: sty1 mutants are delayed in mitotic initiation and reduced in cell size at division, consistent with Sty1 promoting the G2/M transition. Core cell-cycle function. Reason: Foundational genetic evidence that Sty1 promotes mitotic entry. Supporting Evidence: PMID:7657164 sty1- and sty2- mutant cells are substantially delayed in the timing of mitotic initiation. |
| GO:0034599 cellular response to oxidative stress | IMP PMID:11886858 The serine/threonine kinase Cmk2 is required for oxidative s... | ACCEPT | Summary: Sty1 phosphorylates Cmk2, which acts downstream in the oxidative-stress response. Corroborates the core oxidative-stress role. Reason: Direct evidence linking Sty1 to oxidative-stress response via Cmk2. Supporting Evidence: PMID:11886858 Cmk2 acts downstream of Sty1 and is an essential kinase for oxidative stress responses. |
| GO:0034599 cellular response to oxidative stress | IMP PMID:22139357 H₂O₂ stress-specific regulation of S. pombe MAPK Sty1 by mit... | ACCEPT | Summary: Sty1 activity upon H2O2 stress is regulated by the mitochondrial PP2C Ptc4; supports the core oxidative-stress role. Reason: Corroborates the oxidative-stress-response function with H2O2-specific regulation. Supporting Evidence: PMID:22139357 the stress-activated MAP kinase, Sty1, is activated via phosphorylation upon exposure to stress and orchestrates an appropriate response. |
| GO:0038066 p38MAPK cascade | IMP PMID:7657164 Pyp1 and Pyp2 PTPases dephosphorylate an osmosensing MAP kin... | ACCEPT | Summary: Sty1 is the p38/HOG1-orthologous MAP kinase of the cascade. Core function; redundant with other p38MAPK cascade annotations. Reason: Foundational characterization of Sty1 as the p38-type SAPK. Supporting Evidence: PMID:7657164 a MAP kinase that is closely related to a subfamily of MAP kinases regulated by osmotic stress including Saccharomyces cervisiae HOG1 and human CSBP1 |
| GO:0038066 p38MAPK cascade | IMP PMID:8824588 The Atf1 transcription factor is a target for the Sty1 stres... | ACCEPT | Summary: Sty1 is the stress-activated p38-type kinase phosphorylating Atf1. Core function; redundant with other p38MAPK cascade annotations. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:8824588 ATF-2 is regulated through phosphorylation in mammalian cells by the stress-activated mitogen-activated protein (MAP) kinases SAPK/JNK and p38. |
| GO:1903715 regulation of aerobic respiration | IMP PMID:22139357 H₂O₂ stress-specific regulation of S. pombe MAPK Sty1 by mit... | KEEP AS NON CORE | Summary: A mitochondrial pool of Sty1 (regulated by Ptc4) links the kinase to mitochondrial function; a specialized, non-core role. Reason: Real but peripheral mitochondrial connection; not a core stress-kinase function. Supporting Evidence: PMID:22139357 A fraction of Sty1 also localizes to the mitochondria suggesting that Ptc4 attenuates the activity of a mitochondrial pool of this MAPK. |
| GO:0004707 MAP kinase activity | IDA PMID:11886858 The serine/threonine kinase Cmk2 is required for oxidative s... | ACCEPT | Summary: Direct evidence that activated Sty1 phosphorylates Cmk2. Core catalytic function; redundant. Reason: Direct support for the core kinase activity. Supporting Evidence: PMID:11886858 in vivo or in vitro activated Sty1 was able to phosphorylate Cmk2 |
| GO:0005515 protein binding | IPI PMID:11886858 The serine/threonine kinase Cmk2 is required for oxidative s... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Cmk2 interaction. Bare protein binding is uninformative; Cmk2 is a substrate of Sty1. Reason: Uninformative MF term; the Cmk2 substrate relationship is captured by kinase-activity annotations. Supporting Evidence: PMID:11886858 Co-precipitation assays demonstrated that Cmk2 binds Sty1. |
| GO:0038066 p38MAPK cascade | IMP PMID:9693384 The fission yeast mitotic regulator win1+ encodes an MAP kin... | ACCEPT | Summary: Sty1 is activated through Win1-Wis1 in the cascade in response to high osmolarity. Core function; redundant duplicate. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:9693384 Win1 is a MAP kinase kinase kinase that phosphorylates and activates Wis1. |
| GO:0010972 negative regulation of G2/M transition of mitotic cell cycle | IMP PMID:21965528 Aurora promotes cell division during recovery from TOR-media... | ACCEPT | Summary: TOR and MAPK signaling contribute to a transient block to cell division upon increased nutrient provision. Supports a negative G2/M role in a specific nutrient context. Reason: Corroborates the context-dependent negative regulation of the G2/M transition. Supporting Evidence: PMID:21965528 this block to cell division relies upon TOR and MAPK signalling |
| GO:0038066 p38MAPK cascade | IMP PMID:20919928 Two-component mediated peroxide sensing and signal transduct... | ACCEPT | Summary: Two-component (Mak2/Mak3) peroxide sensing activates the Sty1 cascade. Core function; redundant duplicate. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:20919928 the peroxide-sensing Mak2 and Mak3 histidine kinases regulate H(2)O(2)-induced activation of the Sty1 stress-activated protein kinase pathway |
| GO:0004707 MAP kinase activity | IDA PMID:22144909 The fission yeast stress-responsive MAPK pathway promotes me... | ACCEPT | Summary: Sty1 phosphorylates Lsk1 (CTDK-I) to promote CTD Ser-2 phosphorylation during meiosis. Direct kinase activity; core function. Reason: Direct biochemical evidence for Sty1 kinase activity on a substrate. Supporting Evidence: PMID:22144909 Sty1 phosphorylates Lsk1, the catalytic subunit of CTDK-I. |
| GO:0005758 mitochondrial intermembrane space | IDA PMID:22139357 H₂O₂ stress-specific regulation of S. pombe MAPK Sty1 by mit... | KEEP AS NON CORE | Summary: A fraction of Sty1 localizes to mitochondria, where mitochondrial Ptc4 regulates it. A minor, specialized localization pool. Reason: Minor mitochondrial pool; peripheral to the predominant cytoplasmic/nuclear function. Supporting Evidence: PMID:22139357 A fraction of Sty1 also localizes to the mitochondria suggesting that Ptc4 attenuates the activity of a mitochondrial pool of this MAPK. |
| GO:0004707 MAP kinase activity | IDA PMID:9136929 The Mcs4 response regulator coordinately controls the stress... | ACCEPT | Summary: Direct evidence for Sty1 MAP kinase activity within the Wak1-Wis1-Sty1 cascade. Core function; redundant. Reason: Direct support for the core catalytic function. Supporting Evidence: PMID:9136929 The fission yeast Sty1 MAP kinase is required for cell cycle control, initiation of sexual differentiation, and protection against cellular stress. |
| GO:0004707 MAP kinase activity | IDA PMID:8824588 The Atf1 transcription factor is a target for the Sty1 stres... | ACCEPT | Summary: Sty1 phosphorylates Atf1 in vitro; direct demonstration of MAP kinase activity on its key substrate. Core function. Reason: Foundational biochemical evidence for the core kinase activity. Supporting Evidence: PMID:8824588 Atf1 associates stably and is phosphorylated by the Sty1 kinase in vitro. |
| GO:0004707 MAP kinase activity | IDA PMID:9450957 The Win1 mitotic regulator is a component of the fission yea... | ACCEPT | Summary: Direct evidence for Sty1 MAP kinase activity, activated by Win1/Wak1. Core function; redundant. Reason: Direct support for the core catalytic function. Supporting Evidence: PMID:9450957 Like the mammalian JNK/SAPK and p38/CSBP1 MAPKs, Sty1 is activated by a range of environmental insults |
| GO:0038066 p38MAPK cascade | IMP PMID:9450957 The Win1 mitotic regulator is a component of the fission yea... | ACCEPT | Summary: Win1 and Wak1 coordinately activate Sty1 in the cascade. Core function; redundant duplicate. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:9450957 Wak1 and Win1 coordinately control activation of Sty1 in response to multiple environmental stresses |
| GO:0004707 MAP kinase activity | IDA PMID:12080074 The Srk1 protein kinase is a target for the Sty1 stress-acti... | ACCEPT | Summary: Sty1 directly phosphorylates Srk1; direct demonstration of MAP kinase activity. Core function; redundant. Reason: Direct biochemical evidence for the core kinase activity. Supporting Evidence: PMID:12080074 Srk1 is present in a complex with the Sty1 MAPK and is directly phosphorylated by Sty1. |
| GO:0005634 nucleus | IDA PMID:10233152 Active nucleocytoplasmic shuttling required for function and... | ACCEPT | Summary: Active nucleocytoplasmic shuttling brings Sty1 into the nucleus during osmotic stress, where it functions. Core localization for function. Reason: Direct evidence for stress-induced nuclear activity. Supporting Evidence: PMID:10233152 nuclear accumulation of the SAPK Spc1 (also known as StyI) requires activating phosphorylation catalyzed by the SAPK kinase Wis1 |
| GO:0005515 protein binding | IPI PMID:9585506 Phosphorylation and association with the transcription facto... | MARK AS OVER ANNOTATED | Summary: Records the Sty1-Atf1 interaction. Atf1 is the key nuclear substrate of Sty1; bare protein binding is uninformative. Reason: Uninformative MF term; the Atf1 substrate relationship is captured by the kinase-activity and transcription annotations. Supporting Evidence: PMID:9585506 Nuclear retention of Spc1 requires Atf1, a transcription factor that is the key nuclear substrate of Spc1. |
| GO:0005737 cytoplasm | IDA PMID:9585506 Phosphorylation and association with the transcription facto... | ACCEPT | Summary: Sty1 is cytoplasmic in unstressed cells. Core localization; direct microscopy. Reason: Foundational evidence for resting cytoplasmic localization. Supporting Evidence: PMID:9585506 Stress induces transient nuclear localization of Spc1. |
| GO:0004707 MAP kinase activity | IDA PMID:10398679 Heat-shock-induced activation of stress MAP kinase is regula... | ACCEPT | Summary: Sty1 activity (Thr-171/Tyr-173 phosphorylation) measured directly upon heat shock. Core kinase function; redundant. Reason: Direct support for the core catalytic function. Supporting Evidence: PMID:10398679 Although osmostress and oxidative stress induce strong activation of the Wis1 MAPK kinase (MEK), which activates Spc1 through Thr-171/Tyr-173 phosphorylation, activation of Wis1 upon heat shock is relatively weak and transient. |
| GO:0038066 p38MAPK cascade | IDA PMID:10398679 Heat-shock-induced activation of stress MAP kinase is regula... | ACCEPT | Summary: Heat-shock activation of Sty1 in the cascade, with PP2C-mediated attenuation. Core function; redundant duplicate. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:10398679 stress-activated protein kinases (SAPKs), members of a MAP kinase (MAPK) subfamily, regulate the transcriptional response to various environmental stress |
| GO:0038066 p38MAPK cascade | IMP PMID:10398679 Heat-shock-induced activation of stress MAP kinase is regula... | ACCEPT | Summary: Duplicate p38MAPK cascade annotation (IMP) from the same heat-shock study. Redundant. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:10398679 transient activation of Spc1 upon heat shock is ensured by differential regulation of threonine and tyrosine phosphorylation. |
| GO:0004707 MAP kinase activity | IDA PMID:8824587 Conjugation, meiosis, and the osmotic stress response are re... | ACCEPT | Summary: Direct evidence for Sty1/Spc1 kinase activity (stress-induced Atf1 phosphorylation). Core function; redundant. Reason: Direct support for the core catalytic function. Supporting Evidence: PMID:8824587 Spc1 is required for stress-induced phosphorylation of Atf1. |
| GO:0038066 p38MAPK cascade | IMP PMID:9718372 Evidence for a novel MAPKKK-independent pathway controlling ... | ACCEPT | Summary: Characterizes activation of the Sty1 cascade (including a MAPKKK-independent route). Core function; redundant duplicate. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:9718372 a novel MAPKKK-independent pathway by which the Wis1 MAPKK can activate the Sty1 MAPK in response to stress in fission yeast. |
| GO:0004707 MAP kinase activity | IDA PMID:7501024 Cell-cycle control linked to extracellular environment by MA... | ACCEPT | Summary: Spc1/Sty1 MAP kinase activity, activated by Wis1 in response to osmotic stress. Foundational core function. Reason: Foundational evidence for the core catalytic function. Supporting Evidence: PMID:7501024 Spc1 is a MAP kinase homologue that is activated by Wis1 kinase in response to osmotic stress and nutrient limitation. |
| GO:0010971 positive regulation of G2/M transition of mitotic cell cycle | IMP PMID:7501024 Cell-cycle control linked to extracellular environment by MA... | ACCEPT | Summary: Spc1 promotes the onset of mitosis; spc1-cdc25 synthetic lethality demonstrates its positive role in G2/M. Core cell-cycle function. Reason: Foundational genetic evidence that Sty1 promotes mitotic entry. Supporting Evidence: PMID:7501024 A lethal interaction of spc1 and cdc25 mutations shows that Spc1 promotes the onset of mitosis. |
| GO:0038066 p38MAPK cascade | IMP PMID:7501024 Cell-cycle control linked to extracellular environment by MA... | ACCEPT | Summary: Spc1 is the MAP kinase of the cascade linking environment to cell cycle. Core function; redundant duplicate. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:7501024 a fission yeast MAP kinase pathway links the cell-cycle G2/M control with changes in the extracellular environment |
| GO:0005634 nucleus | IDA PMID:19672306 Genome-wide screen of genes required for caffeine tolerance ... | ACCEPT | Summary: From a caffeine-tolerance screen implicating the Sty1 pathway. Supports nuclear activity; redundant with core nucleus annotation. Reason: Corroborates the well-established stress-induced nuclear localization. Supporting Evidence: PMID:19672306 The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. |
| GO:0005515 protein binding | IPI PMID:8649397 Activation and regulation of the Spc1 stress-activated prote... | MARK AS OVER ANNOTATED | Summary: Records the Spc1-Pyp2 interaction (the negative-feedback tyrosine phosphatase). Bare protein binding is uninformative. Reason: Uninformative MF term; the Pyp2 regulatory interaction is captured by activity-regulation annotations. Supporting Evidence: PMID:8649397 Spc1 associates with Pyp2 in vivo |
| GO:0038066 p38MAPK cascade | IMP PMID:8649397 Activation and regulation of the Spc1 stress-activated prote... | ACCEPT | Summary: Spc1 is the p38-related kinase activated by Wis1 and inhibited by Pyp1/Pyp2. Core function; redundant duplicate. Reason: Corroborates the core p38-type stress-activated MAPK cascade function. Supporting Evidence: PMID:8649397 Spc1 is most closely related to Saccharomyces cerevisiae Hog1 and mammalian p38 kinases. |
| GO:0042307 positive regulation of protein import into nucleus | IMP PMID:9585505 Regulation of the fission yeast transcription factor Pap1 by... | KEEP AS NON CORE | Summary: Sty1 is required for the oxidative-stress-induced nuclear accumulation of the Pap1 transcription factor (via regulated nuclear export). A genuine but specialized downstream role. Reason: Real role in driving Pap1 nuclear accumulation, but secondary to the core kinase/transcription functions. Supporting Evidence: PMID:9585505 the Pap1 protein relocalizes from the cytoplasm to the nucleus in a process that is dependent on the Sty1 kinase |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:9585505 Regulation of the fission yeast transcription factor Pap1 by... | ACCEPT | Summary: Sty1 and Pap1 are required for expression of oxidative-stress and multidrug-resistance genes. Core downstream transcriptional function; redundant with the Atf1-based call. Reason: Sty1 is required for stress-gene transcription via Pap1/Atf1. Supporting Evidence: PMID:9585505 both Sty1 and Pap1 are required for the expression of a number of genes involved in the oxidative stress response |
| GO:0004707 MAP kinase activity | IDA PMID:12135491 Rum1, an inhibitor of cyclin-dependent kinase in fission yea... | ACCEPT | Summary: This study uses an in vitro kinase assay to show that MAPK phosphorylates the fission-yeast CDK inhibitor Rum1 (at Thr13/Ser19), reducing its Cdc2-inhibitory activity. The cached abstract does not specify the source of the MAPK used, so it cannot be determined from the abstract whether the assay used Sty1 directly; PomBase assigned this as Sty1 MAP kinase activity (IDA). MAP kinase activity is in any case the core, amply-supported function of Sty1. Reason: MAP kinase activity is the core function of Sty1 and is well supported. This PomBase IDA is retained; we defer to the curator on the specifics of the in vitro assay, which are not resolvable from the cached abstract. (An earlier note asserting the assay used a "mammalian/heterologous MAPK" is not supported by the abstract and has been removed.) Supporting Evidence: PMID:12135491 MAPK phosphorylates the N-terminal portion of p25(rum1) and residues Thr13 and Ser19 are major phosphorylation sites for MAPK. |
| GO:0004707 MAP kinase activity | IDA PMID:9251044 Stress-activated protein kinase pathway in cell cycle contro... | ACCEPT | Summary: Methods/review reference for the Spc1/Sty1 SAPK pathway and its kinase activity in cell-cycle control. Core function; redundant. Reason: Supports the core catalytic function. Supporting Evidence: PMID:9251044 Stress-activated protein kinase pathway in cell cycle control of fission yeast. |
| GO:0005634 nucleus | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: High-throughput localization study detecting Sty1 in the nucleus. Consistent with stress-induced nuclear pool; redundant with curated nucleus annotations. Reason: High-throughput corroboration of nuclear localization. Supporting Evidence: PMID:16823372 ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe. |
| GO:0005829 cytosol | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | KEEP AS NON CORE | Summary: High-throughput localization detecting Sty1 in the cytosol, consistent with the predominant resting cytoplasmic pool. Reason: High-throughput corroboration; redundant with the cytoplasm annotation. Supporting Evidence: PMID:16823372 ORFeome cloning and global analysis of protein localization in the fission yeast Schizosaccharomyces pombe. |
| GO:0010520 regulation of reciprocal meiotic recombination | IMP PMID:9819443 Regulation of the Mts1-Mts2-dependent ade6-M26 meiotic recom... | KEEP AS NON CORE | Summary: Spc1 phosphorylates Atf1/Mts1, regulating its occupancy of the ade6-M26 meiotic recombination hotspot. A genuine but specialized non-core role. Reason: Real meiotic-recombination regulation via Atf1, peripheral to the core stress-kinase function. Supporting Evidence: PMID:9819443 the Spc1 kinase helps regulate the effector activities of the Mts1-Mts2 heterodimer in part by modulating its ability to occupy the M26 DNA site in vivo. |
| GO:0051445 regulation of meiotic cell cycle | IMP PMID:9819443 Regulation of the Mts1-Mts2-dependent ade6-M26 meiotic recom... | KEEP AS NON CORE | Summary: Spc1 regulates developmental decisions including meiosis via Atf1/Pcr1. A genuine but specialized non-core role. Reason: Real role in meiotic developmental control, peripheral to the core stress-signaling function. Supporting Evidence: PMID:9819443 The first class (osmoregulation, spore viability, and spore quiescence) requires the Spc1 MAP kinase and the Mts1 protein |
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Download this section (compressed HTML)Q: How is the dual (positive vs negative) regulation of the G2/M transition by Sty1 partitioned between conditions, and what determines whether Sty1 promotes or delays mitotic entry?
Q: What is the full in vivo substrate repertoire of Sty1 beyond Atf1, Srk1, Cmk2, Lsk1, Rum1 and the Pol II CTD, and how is substrate selection achieved between the cytoplasmic, nuclear, and mitochondrial pools?
Q: What is the functional significance of the mitochondrial and stress-granule pools of Sty1 relative to its dominant cytoplasmic-to-nuclear signaling role?
Experiment: Quantitative phosphoproteomics of wild-type versus analog-sensitive sty1 (sty1-as) cells across distinct stresses (osmotic, oxidative, heat, nitrogen starvation) to define the stress-specific in vivo substrate landscape.
Experiment: Compartment-restricted Sty1 alleles (forced cytoplasmic, nuclear, or mitochondrial targeting) to dissect which functions require each subcellular pool.
Experiment: ChIP-seq of Sty1 and phospho-CTD (Ser5) across the genome under oxidative versus osmotic stress to map direct chromatin recruitment and its dependence on Atf1 versus Pap1.
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