KSS1_YEAST
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 03-AUG-2022, entry version 223.
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}.
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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; 218.
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; P14681; -.
DR PRIDE; P14681; -.
DR EnsemblFungi; YGR040W_mRNA; YGR040W; YGR040W.
DR GeneID; 852931; -.
DR KEGG; sce:YGR040W; -.
DR SGD; S000003272; KSS1.
DR VEuPathDB; FungiDB:YGR040W; -.
DR eggNOG; KOG0660; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P14681; -.
DR OMA; EIMTFRP; -.
DR BioCyc; YEAST:G3O-30760-MON; -.
DR BRENDA; 2.7.11.24; 984.
DR Reactome; R-SCE-110056; MAPK3 (ERK1) activation.
DR Reactome; R-SCE-112409; RAF-independent MAPK1/3 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-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-SCE-375165; NCAM signaling for neurite out-growth.
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 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:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:SGD.
DR GO; GO:0000750; P:pheromone-dependent signal transduction involved in conjugation with cellular fusion; IMP:SGD.
DR GO; GO:0010973; P:positive regulation of division septum assembly; IGI:SGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:SGD.
DR GO; GO:0001402; P:signal transduction involved in filamentous growth; IMP:SGD.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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
