P14681 (KSS1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Mitogen-activated protein kinase KSS1
Short name=MAP kinase KSS1
EC=2.7.11.24

Alternative name(s):
Kinase suppressor of SST2

Gene names

Name:	KSS1
Ordered Locus Names:	YGR040W

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	368 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Together with closely related FUS3, KSS1 is the final kinase in the signal transduction cascade regulating activation/repression of the mating and filamentation pathways, induced by pheromone and nitrogen/carbon limitation, respectively. Phosphorylated KSS1 activates both pathways, whereas activated FUS3 activates the mating but suppresses the filamentation pathway. KSS1 activity is down-regulated by FUS3 during pheromone induction to prevent inappropriate activation of the filamentation pathway. During induction of filamentation, KSS1 activates the transcription factor STE12 resulting in its binding to and activation of filamentation specific genes. Non-activated KSS1 has a kinase-independent repressive effect on STE12 transcriptional activity, that is mediated by direct binding to STE12 and depends on the presence of DIG1 and DIG2, and that is required for the suppression of filamentation under normal growth conditions. SSN3/SRB10 contributes further to the suppression of filamentation under these conditions by reducing STE12 stability independent of KSS1. FUS3 can partially compensate for the lack of KSS1 but filamentation becomes constitutively induced at a low level in the absence of any signal. KSS1 phosphorylates STE7, STE5, FAR1, DIG1, DIG2, STE12, and SST2. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.15 Ref.18
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by tyrosine and threonine phosphorylation after pheromone treatment or carbon/nitrogen limitation.
Subunit structure	In the nucleus, KSS1 forms a complex with DIG1, DIG2 and STE12; in contrast to FUS3 the interaction of KSS1 with STE12 does not depend on DIG1 and DIG2. Phosphorylated KSS1 shows reduced interaction with STE12. During pheromone activation and phosphorylation, KSS1 forms a membrane-associated complex with the scaffold protein STE5, the MAPKK STE7, the MAPKKK STE11, and the G-protein beta subunit GBB/STE4; interacting directly with POF1, STE7 and STE5 proteins.
Subcellular location	Nucleus. Cytoplasm. Periplasm. Note: KSS1 shuttles rapidly between the cytoplasm and the nucleus independent of its activation state. Ref.13
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-183 and Tyr-185 by STE7 in response to pheromone or carbon/nitrogen limitation, which activates the enzyme. Activated FUS3 down-regulates KSS1 phosphorylation. Ref.7
Miscellaneous	Present with 5480 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily. HOG1 sub-subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Cytoplasm Nucleus Periplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW invasive growth in response to glucose limitation Inferred from mutant phenotype PubMed 8001818. Source: SGD negative regulation of sequence-specific DNA binding transcription factor activity Inferred from mutant phenotype Ref.10. Source: SGD pheromone-dependent signal transduction involved in conjugation with cellular fusion Inferred from expression pattern Ref.12. Source: SGD signal transduction involved in filamentous growth Inferred from genetic interaction Ref.9. Source: SGD
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from direct assay PubMed 18417610PubMed 7579701. Source: SGD periplasmic space Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase activity Inferred from direct assay Ref.8. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCK2	P33306	5	EBI-9945,EBI-3480
DIG1	Q03063	6	EBI-9945,EBI-29752
DIG2	Q03373	6	EBI-9945,EBI-34019
STE11	P23561	6	EBI-9945,EBI-18259
STE12	P13574	9	EBI-9945,EBI-18264
STE7	P06784	15	EBI-9945,EBI-18389

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 368	368	Mitogen-activated protein kinase KSS1		PRO_0000186333
Regions
	Domain	13 – 313	301	Protein kinase
	Nucleotide binding	19 – 27	9	ATP By similarity
	Motif	183 – 185	3	TXY
	Compositional bias	345 – 349	5	Poly-Glu
Sites
	Active site	143	1	Proton acceptor By similarity
	Binding site	42	1	ATP By similarity
Amino acid modifications
	Modified residue	183	1	Phosphothreonine Ref.17
	Modified residue	185	1	Phosphotyrosine Ref.17

Sequences

	Sequence		Length	Mass (Da)
	P14681 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: 5FA42161B5FD51B5	FASTA	368	42,692
	10 20 30 40 50 60 MARTITFDIP SQYKLVDLIG EGAYGTVCSA IHKPSGIKVA IKKIQPFSKK LFVTRTIREI 70 80 90 100 110 120 KLLRYFHEHE NIISILDKVR PVSIDKLNAV YLVEELMETD LQKVINNQNS GFSTLSDDHV 130 140 150 160 170 180 QYFTYQILRA LKSIHSAQVI HRDIKPSNLL LNSNCDLKVC DFGLARCLAS SSDSRETLVG 190 200 210 220 230 240 FMTEYVATRW YRAPEIMLTF QEYTTAMDIW SCGCILAEMV SGKPLFPGRD YHHQLWLILE 250 260 270 280 290 300 VLGTPSFEDF NQIKSKRAKE YIANLPMRPP LPWETVWSKT DLNPDMIDLL DKMLQFNPDK 310 320 330 340 350 360 RISAAEALRH PYLAMYHDPS DEPEYPPLNL DDEFWKLDNK IMRPEEEEEV PIEMLKDMLY DELMKTME

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae." Courchesne W.E., Kunisawa R., Thorner J. Cell 58:1107-1119(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Quantitative trait loci mapped to single-nucleotide resolution in yeast." Deutschbauer A.M., Davis R.W. Nat. Genet. 37:1333-1340(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: SK1.
[3]	"Sequence analysis of 203 kilobases from Saccharomyces cerevisiae chromosome VII." Rieger M., Brueckner M., Schaefer M., Mueller-Auer S. Yeast 13:1077-1090(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome VII." Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., Coblenz A., Coglievina M., Coissac E. , Defoor E., Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., Zollner A., Kleine K. Nature 387:81-84(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[5]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[6]	"Approaching a complete repository of sequence-verified protein-encoding clones for Saccharomyces cerevisiae." Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J. , Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D., LaBaer J. Genome Res. 17:536-543(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[7]	"Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1." Gartner A., Nasmyth K., Ammerer G. Genes Dev. 6:1280-1292(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION.
[8]	"Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae." Cook J.G., Bardwell L., Kron S.J., Thorner J. Genes Dev. 10:2831-2848(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COMPLEX WITH DIG1; DIG2 AND STE12.
[9]	"MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation." Madhani H.D., Styles C.A., Fink G.R. Cell 91:673-684(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INHIBITION OF FILAMENTATION.
[10]	"Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK." Bardwell L., Cook J.G., Voora D., Baggott D.M., Martinez A.R., Thorner J. Genes Dev. 12:2887-2898(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH STE12.
[11]	"Differential regulation of transcription: repression by unactivated mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 proteins." Bardwell L., Cook J.G., Zhu-Shimoni J.X., Voora D., Thorner J. Proc. Natl. Acad. Sci. U.S.A. 95:15400-15405(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, FUNCTIONAL DEPENDENCE ON DIG1/DIG2.
[12]	"Specificity of MAP kinase signaling in yeast differentiation involves transient versus sustained MAPK activation." Sabbagh W. Jr., Flatauer L.J., Bardwell A.J., Bardwell L. Mol. Cell 8:683-691(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, REGULATION OF ACTIVITY BY FUS3.
[13]	"MAP kinase dynamics in response to pheromones in budding yeast." van Drogen F., Stucke V.M., Jorritsma G., Peter M. Nat. Cell Biol. 3:1051-1059(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[14]	"Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling." Zeitlinger J., Simon I., Harbison C.T., Hannett N.M., Volkert T.L., Fink G.R., Young R.A. Cell 113:395-404(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, REGULATION OF STE12 PROMOTER SELECTIVITY.
[15]	"Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12." Nelson C., Goto S., Lund K., Hung W., Sadowski I. Nature 421:187-190(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, STE12 STABILITY.
[16]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[17]	"Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae." Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., Elias J.E., Gygi S.P. J. Proteome Res. 6:1190-1197(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-183 AND TYR-185, MASS SPECTROMETRY. Strain: ADR376.
[18]	"Diverse protein kinase interactions identified by protein microarrays reveal novel connections between cellular processes." Fasolo J., Sboner A., Sun M.G., Yu H., Chen R., Sharon D., Kim P.M., Gerstein M., Snyder M. Genes Dev. 25:767-778(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH POF1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M26398 Genomic DNA. Translation: AAA34882.1. DQ115391 Genomic DNA. Translation: AAZ22456.1. Z72825 Genomic DNA. Translation: CAA97038.1. AY557773 Genomic DNA. Translation: AAS56099.1. BK006941 Genomic DNA. Translation: DAA08139.1.
PIR	A33297.
RefSeq	NP_011554.3. NM_001181169.3.
3D structure databases
ProteinModelPortal	P14681.
SMR	P14681. Positions 1-364.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-60N.
IntAct	P14681. 44 interactions.
MINT	MINT-411417.
STRING	4932.YGR040W.
Proteomic databases
PaxDb	P14681.
PeptideAtlas	P14681.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YGR040W; YGR040W; YGR040W.
GeneID	852931.
KEGG	sce:YGR040W. sce:YGR046W.
Organism-specific databases
CYGD	YGR040w.
SGD	S000003272. KSS1.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00550000074298.
HOGENOM	HOG000233024.
KO	K04371.
OMA	DHYQILE.
OrthoDB	EOG4P8JSR.
Enzyme and pathway databases
BRENDA	2.7.11.24. 984.
Gene expression databases
Genevestigator	P14681.
GermOnline	YGR040W. Saccharomyces cerevisiae.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR003527. MAP_kinase_CS. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
SMART	SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS01351. MAPK. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	972657.

Entry information

Entry name

KSS1_YEAST

Accession

Primary (citable) accession number: P14681
Secondary accession number(s): D6VUH8, Q45U43

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	May 1, 2013
This is version 149 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program