ID KSS1_YEAST Reviewed; 368 AA. AC P14681; D6VUH8; Q45U43; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1990, sequence version 1. DT 27-MAR-2024, entry version 230. DE RecName: Full=Mitogen-activated protein kinase KSS1; DE Short=MAP kinase KSS1; DE EC=2.7.11.24; DE AltName: Full=Kinase suppressor of SST2; GN Name=KSS1; OrderedLocusNames=YGR040W; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2673544; DOI=10.1016/0092-8674(89)90509-6; RA Courchesne W.E., Kunisawa R., Thorner J.; RT "A putative protein kinase overcomes pheromone-induced arrest of cell RT cycling in S. cerevisiae."; RL Cell 58:1107-1119(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=SK1; RX PubMed=16273108; DOI=10.1038/ng1674; RA Deutschbauer A.M., Davis R.W.; RT "Quantitative trait loci mapped to single-nucleotide resolution in yeast."; RL Nat. Genet. 37:1333-1340(2005). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9290212; RX DOI=10.1002/(sici)1097-0061(19970915)13:11<1077::aid-yea152>3.0.co;2-y; RA Rieger M., Brueckner M., Schaefer M., Mueller-Auer S.; RT "Sequence analysis of 203 kilobases from Saccharomyces cerevisiae RT chromosome VII."; RL Yeast 13:1077-1090(1997). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169869; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H., RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [5] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J., RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., RA LaBaer J.; RT "Approaching a complete repository of sequence-verified protein-encoding RT clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [7] RP PHOSPHORYLATION. RX PubMed=1628831; DOI=10.1101/gad.6.7.1280; RA Gartner A., Nasmyth K., Ammerer G.; RT "Signal transduction in Saccharomyces cerevisiae requires tyrosine and RT threonine phosphorylation of FUS3 and KSS1."; RL Genes Dev. 6:1280-1292(1992). RN [8] RP FUNCTION, AND COMPLEX WITH DIG1; DIG2 AND STE12. RX PubMed=8918885; DOI=10.1101/gad.10.22.2831; RA Cook J.G., Bardwell L., Kron S.J., Thorner J.; RT "Two novel targets of the MAP kinase Kss1 are negative regulators of RT invasive growth in the yeast Saccharomyces cerevisiae."; RL Genes Dev. 10:2831-2848(1996). RN [9] RP FUNCTION, AND INHIBITION OF FILAMENTATION. RX PubMed=9393860; DOI=10.1016/s0092-8674(00)80454-7; RA Madhani H.D., Styles C.A., Fink G.R.; RT "MAP kinases with distinct inhibitory functions impart signaling RT specificity during yeast differentiation."; RL Cell 91:673-684(1997). RN [10] RP FUNCTION, AND INTERACTION WITH STE12. RX PubMed=9744865; DOI=10.1101/gad.12.18.2887; RA Bardwell L., Cook J.G., Voora D., Baggott D.M., Martinez A.R., Thorner J.; RT "Repression of yeast Ste12 transcription factor by direct binding of RT unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK."; RL Genes Dev. 12:2887-2898(1998). RN [11] RP FUNCTION, AND FUNCTIONAL DEPENDENCE ON DIG1/DIG2. RX PubMed=9860980; DOI=10.1073/pnas.95.26.15400; RA Bardwell L., Cook J.G., Zhu-Shimoni J.X., Voora D., Thorner J.; RT "Differential regulation of transcription: repression by unactivated RT mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 RT proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 95:15400-15405(1998). RN [12] RP FUNCTION, AND REGULATION OF ACTIVITY BY FUS3. RX PubMed=11583629; DOI=10.1016/s1097-2765(01)00322-7; RA Sabbagh W. Jr., Flatauer L.J., Bardwell A.J., Bardwell L.; RT "Specificity of MAP kinase signaling in yeast differentiation involves RT transient versus sustained MAPK activation."; RL Mol. Cell 8:683-691(2001). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=11781566; DOI=10.1038/ncb1201-1051; RA van Drogen F., Stucke V.M., Jorritsma G., Peter M.; RT "MAP kinase dynamics in response to pheromones in budding yeast."; RL Nat. Cell Biol. 3:1051-1059(2001). RN [14] RP FUNCTION, AND REGULATION OF STE12 PROMOTER SELECTIVITY. RX PubMed=12732146; DOI=10.1016/s0092-8674(03)00301-5; RA Zeitlinger J., Simon I., Harbison C.T., Hannett N.M., Volkert T.L., RA Fink G.R., Young R.A.; RT "Program-specific distribution of a transcription factor dependent on RT partner transcription factor and MAPK signaling."; RL Cell 113:395-404(2003). RN [15] RP FUNCTION, AND STE12 STABILITY. RX PubMed=12520306; DOI=10.1038/nature01243; RA Nelson C., Goto S., Lund K., Hung W., Sadowski I.; RT "Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the RT transcription factor Ste12."; RL Nature 421:187-190(2003). RN [16] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [18] RP FUNCTION, AND INTERACTION WITH POF1. RX PubMed=21460040; DOI=10.1101/gad.1998811; RA Fasolo J., Sboner A., Sun M.G., Yu H., Chen R., Sharon D., Kim P.M., RA Gerstein M., Snyder M.; RT "Diverse protein kinase interactions identified by protein microarrays RT reveal novel connections between cellular processes."; RL Genes Dev. 25:767-778(2011). CC -!- FUNCTION: Together with closely related FUS3, KSS1 is the final kinase CC in the signal transduction cascade regulating activation/repression of CC the mating and filamentation pathways, induced by pheromone and CC nitrogen/carbon limitation, respectively. Phosphorylated KSS1 activates CC both pathways, whereas activated FUS3 activates the mating but CC suppresses the filamentation pathway. KSS1 activity is down-regulated CC by FUS3 during pheromone induction to prevent inappropriate activation CC of the filamentation pathway. During induction of filamentation, KSS1 CC activates the transcription factor STE12 resulting in its binding to CC and activation of filamentation specific genes. Non-activated KSS1 has CC a kinase-independent repressive effect on STE12 transcriptional CC activity, that is mediated by direct binding to STE12 and depends on CC the presence of DIG1 and DIG2, and that is required for the suppression CC of filamentation under normal growth conditions. SSN3/SRB10 contributes CC further to the suppression of filamentation under these conditions by CC reducing STE12 stability independent of KSS1. FUS3 can partially CC compensate for the lack of KSS1 but filamentation becomes CC constitutively induced at a low level in the absence of any signal. CC KSS1 phosphorylates STE7, STE5, FAR1, DIG1, DIG2, STE12, and SST2. CC {ECO:0000269|PubMed:11583629, ECO:0000269|PubMed:12520306, CC ECO:0000269|PubMed:12732146, ECO:0000269|PubMed:21460040, CC ECO:0000269|PubMed:8918885, ECO:0000269|PubMed:9393860, CC ECO:0000269|PubMed:9744865, ECO:0000269|PubMed:9860980}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.24; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activated by tyrosine and threonine CC phosphorylation after pheromone treatment or carbon/nitrogen CC limitation. CC -!- SUBUNIT: In the nucleus, KSS1 forms a complex with DIG1, DIG2 and CC STE12; in contrast to FUS3 the interaction of KSS1 with STE12 does not CC depend on DIG1 and DIG2. Phosphorylated KSS1 shows reduced interaction CC with STE12. During pheromone activation and phosphorylation, KSS1 forms CC a membrane-associated complex with the scaffold protein STE5, the MAPKK CC STE7, the MAPKKK STE11, and the G-protein beta subunit GBB/STE4; CC interacting directly with POF1, STE7 and STE5 proteins. CC -!- INTERACTION: CC P14681; P33306: BCK2; NbExp=5; IntAct=EBI-9945, EBI-3480; CC P14681; Q03063: DIG1; NbExp=5; IntAct=EBI-9945, EBI-29752; CC P14681; Q03373: DIG2; NbExp=5; IntAct=EBI-9945, EBI-34019; CC P14681; P23561: STE11; NbExp=6; IntAct=EBI-9945, EBI-18259; CC P14681; P13574: STE12; NbExp=8; IntAct=EBI-9945, EBI-18264; CC P14681; P06784: STE7; NbExp=17; IntAct=EBI-9945, EBI-18389; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11781566}. Cytoplasm CC {ECO:0000269|PubMed:11781566}. Periplasm {ECO:0000269|PubMed:11781566}. CC Note=KSS1 shuttles rapidly between the cytoplasm and the nucleus CC independent of its activation state. CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues CC whose phosphorylation activates the MAP kinases. CC -!- PTM: Dually phosphorylated on Thr-183 and Tyr-185 by STE7 in response CC to pheromone or carbon/nitrogen limitation, which activates the enzyme. CC Activated FUS3 down-regulates KSS1 phosphorylation. CC {ECO:0000269|PubMed:1628831}. CC -!- MISCELLANEOUS: Present with 5480 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. MAP kinase subfamily. HOG1 sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M26398; AAA34882.1; -; Genomic_DNA. DR EMBL; DQ115391; AAZ22456.1; -; Genomic_DNA. DR EMBL; Z72825; CAA97038.1; -; Genomic_DNA. DR EMBL; AY557773; AAS56099.1; -; Genomic_DNA. DR EMBL; BK006941; DAA08139.1; -; Genomic_DNA. DR PIR; A33297; A33297. DR RefSeq; NP_011554.3; NM_001181169.3. DR AlphaFoldDB; P14681; -. DR SMR; P14681; -. DR BioGRID; 33287; 221. DR DIP; DIP-60N; -. DR ELM; P14681; -. DR IntAct; P14681; 78. DR MINT; P14681; -. DR STRING; 4932.YGR040W; -. DR iPTMnet; P14681; -. DR MaxQB; P14681; -. DR PaxDb; 4932-YGR040W; -. DR PeptideAtlas; P14681; -. DR EnsemblFungi; YGR040W_mRNA; YGR040W; YGR040W. DR GeneID; 852931; -. DR KEGG; sce:YGR040W; -. DR AGR; SGD:S000003272; -. DR SGD; S000003272; KSS1. DR VEuPathDB; FungiDB:YGR040W; -. DR eggNOG; KOG0660; Eukaryota. DR HOGENOM; CLU_000288_181_1_1; -. DR InParanoid; P14681; -. DR OMA; CYFLYQM; -. DR OrthoDB; 158564at2759; -. DR BioCyc; YEAST:G3O-30760-MONOMER; -. DR BRENDA; 2.7.11.24; 984. DR Reactome; R-SCE-110056; MAPK3 (ERK1) activation. DR Reactome; R-SCE-111995; phospho-PLA2 pathway. DR Reactome; R-SCE-112409; RAF-independent MAPK1/3 activation. DR Reactome; R-SCE-112411; MAPK1 (ERK2) activation. DR Reactome; R-SCE-170968; Frs2-mediated activation. DR Reactome; R-SCE-198753; ERK/MAPK targets. DR Reactome; R-SCE-202670; ERKs are inactivated. DR Reactome; R-SCE-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-SCE-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-SCE-375165; NCAM signaling for neurite out-growth. DR Reactome; R-SCE-437239; Recycling pathway of L1. DR Reactome; R-SCE-445144; Signal transduction by L1. DR Reactome; R-SCE-450341; Activation of the AP-1 family of transcription factors. DR Reactome; R-SCE-5673001; RAF/MAP kinase cascade. DR Reactome; R-SCE-5674135; MAP2K and MAPK activation. DR Reactome; R-SCE-5674499; Negative feedback regulation of MAPK pathway. DR Reactome; R-SCE-5675221; Negative regulation of MAPK pathway. DR Reactome; R-SCE-6798695; Neutrophil degranulation. DR Reactome; R-SCE-881907; Gastrin-CREB signalling pathway via PKC and MAPK. DR Reactome; R-SCE-9634635; Estrogen-stimulated signaling through PRKCZ. DR BioGRID-ORCS; 852931; 1 hit in 13 CRISPR screens. DR PRO; PR:P14681; -. DR Proteomes; UP000002311; Chromosome VII. DR RNAct; P14681; Protein. DR GO; GO:0005935; C:cellular bud neck; IDA:SGD. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004707; F:MAP kinase activity; IDA:SGD. DR GO; GO:0004672; F:protein kinase activity; HDA:SGD. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0001403; P:invasive growth in response to glucose limitation; IMP:SGD. DR GO; GO:0000750; P:pheromone-dependent signal transduction involved in conjugation with cellular fusion; IMP:SGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0010973; P:positive regulation of division septum assembly; IGI:SGD. DR GO; GO:0001402; P:signal transduction involved in filamentous growth; IMP:SGD. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF590; MITOGEN-ACTIVATED PROTEIN KINASE KSS1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS01351; MAPK; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW ATP-binding; Cell cycle; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; KW Periplasm; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1..368 FT /note="Mitogen-activated protein kinase KSS1" FT /id="PRO_0000186333" FT DOMAIN 13..313 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOTIF 183..185 FT /note="TXY" FT ACT_SITE 143 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 19..27 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 42 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 183 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:17330950" FT MOD_RES 185 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:17330950" SQ SEQUENCE 368 AA; 42692 MW; 5FA42161B5FD51B5 CRC64; MARTITFDIP SQYKLVDLIG EGAYGTVCSA IHKPSGIKVA IKKIQPFSKK LFVTRTIREI KLLRYFHEHE NIISILDKVR PVSIDKLNAV YLVEELMETD LQKVINNQNS GFSTLSDDHV QYFTYQILRA LKSIHSAQVI HRDIKPSNLL LNSNCDLKVC DFGLARCLAS SSDSRETLVG FMTEYVATRW YRAPEIMLTF QEYTTAMDIW SCGCILAEMV SGKPLFPGRD YHHQLWLILE VLGTPSFEDF NQIKSKRAKE YIANLPMRPP LPWETVWSKT DLNPDMIDLL DKMLQFNPDK RISAAEALRH PYLAMYHDPS DEPEYPPLNL DDEFWKLDNK IMRPEEEEEV PIEMLKDMLY DELMKTME //