Reviewed, UniProtKB/Swiss-Prot P16892 (FUS3_YEAST)

Names and origin

Protein names

Recommended name:
    Mitogen-activated protein kinase FUS3
      Short name=MAP kinase FUS3
    EC=2.7.11.24

Gene names

Name:	FUS3
Synonyms:	DAC2
Ordered Locus Names:	YBL016W
ORF Names:	YBL0303, YBL03.21

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	353 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Together with closely related KSS1, FUS3 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 FUS3 activates the mating but suppresses the filamentation pathway, whereas activated KSS1 activates both pathways. Pheromone-activated FUS3 functions by inhibiting the binding of the transcriptional activator STE12 to filamentation specific genes while inducing its binding to and activity at mating specific genes. Non-activated FUS3 has a repressive effect on STE12 transcriptional activity. KSS1 can partially compensate for the lack of FUS3 but mating efficiency is reduced and the filamentation program is partially activated upon pheromone signaling. FUS3 phosphorylates STE7, STE5, FAR1, DIG1, DIG2 and STE12. Ref.7 Ref.8 Ref.9 Ref.11
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by tyrosine and threonine phosphorylation after pheromone treatment.
Subunit structure	In the nucleus, FUS3 forms a complex with DIG1, DIG2 and STE12. The interaction of FUS3 with STE12 depends on the presence of both DIG1 and DIG2. STE12 is lost from FUS3/DIG1/DIG2 complex after pheromone treatment. During its activation and phosphorylation, FUS3 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 STE7 and STE5.
Subcellular location	Nucleus. Cytoplasm. Periplasm. Note: FUS3 shuttles rapidly between the cytoplasm and the nucleus independent of pheromone treatment or FUS3 phosphorylation level. Activated FUS3 translocates rapidly to the nucleus. Ref.10
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Post-translational modification	Dually phosphorylated on Thr-180 and Tyr-182 by STE7 in response to pheromone induction, which activates the enzyme. Activated FUS3 initiates a feedback signal, down-regulating phosphorylation of both, FUS3 and KSS1. Ref.6 Ref.13 Ref.14
Miscellaneous	Present with 8480 molecules/cell in log phase SD medium. Ref.12
Sequence similarities	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Conjugation Mitosis
Cellular component	Cytoplasm Nucleus Periplasm
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell cycle arrest Inferred from mutant phenotype. Source: SGD cell division Inferred from electronic annotation. Source: UniProtKB-KW invasive growth in response to glucose limitation Inferred from mutant phenotype. Source: SGD mitosis Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of MAPKKK cascade Inferred from physical interaction. Source: SGD pheromone-dependent signal transduction involved in conjugation with cellular fusion Inferred from direct assay. Source: SGD protein amino acid phosphorylation Inferred from direct assay. Source: SGD
Cellular component	mating projection tip Ref.10 Inferred from direct assay. Source: SGD mitochondrion Inferred from direct assay. Source: SGD nucleus Inferred from direct assay. 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. Source: SGD protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DIG1	Q03063	1	EBI-7193,EBI-29752
DIG2	Q03373	1	EBI-7193,EBI-34019
STE11	P23561	2	EBI-7193,EBI-18259
STE5	P32917	3	EBI-7193,EBI-18373
STE7	P06784	5	EBI-7193,EBI-18389

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 353

353

Mitogen-activated protein kinase FUS3

PRO_0000186326

Regions

Domain

13 – 309

297

Protein kinase

Nucleotide binding

19 – 27

9

ATP By similarity

Motif

180 – 182

3

TXY

Sites

Active site

137

1

Proton acceptor By similarity

Binding site

42

1

ATP By similarity

Amino acid modifications

Modified residue

180

1

Phosphothreonine Ref.13 Ref.14

Modified residue

182

1

Phosphotyrosine Ref.13 Ref.14

Experimental info

Sequence conflict

334

1

Y → H in AAA34613. Ref.1

Secondary structure

1

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353

Helix Strand Turn

Details...

Beta strand

13 – 21

9

Beta strand

23 – 32

10

Turn

33 – 35

3

Beta strand

38 – 44

7

Helix

50 – 65

16

Beta strand

74 – 77

4

Turn

83 – 85

3

Beta strand

89 – 94

6

Beta strand

97 – 99

3

Helix

100 – 106

7

Helix

111 – 130

20

Helix

140 – 142

3

Beta strand

143 – 145

3

Beta strand

151 – 153

3

Helix

156 – 158

3

Helix

186 – 188

3

Helix

191 – 195

5

Helix

202 – 218

17

Helix

228 – 239

12

Helix

245 – 248

4

Helix

254 – 260

7

Helix

271 – 274

4

Helix

280 – 289

10

Helix

294 – 296

3

Helix

300 – 304

5

Helix

307 – 309

3

Turn

310 – 312

3

Helix

326 – 333

8

Helix

340 – 351

12

Sequences

	Sequence		Length	Mass (Da)
	P16892-1 [UniParc]. Last modified October 1, 1993. Version 2. Checksum: 5117980D20A1E7E2	FASTA	353	40,772
	10 20 30 40 50 60 MPKRIVYNIS SDFQLKSLLG EGAYGVVCSA THKPTGEIVA IKKIEPFDKP LFALRTLREI 70 80 90 100 110 120 KILKHFKHEN IITIFNIQRP DSFENFNEVY IIQELMQTDL HRVISTQMLS DDHIQYFIYQ 130 140 150 160 170 180 TLRAVKVLHG SNVIHRDLKP SNLLINSNCD LKVCDFGLAR IIDESAADNS EPTGQQSGMT 190 200 210 220 230 240 EYVATRWYRA PEVMLTSAKY SRAMDVWSCG CILAELFLRR PIFPGRDYRH QLLLIFGIIG 250 260 270 280 290 300 TPHSDNDLRC IESPRAREYI KSLPMYPAAP LEKMFPRVNP KGIDLLQRML VFDPAKRITA 310 320 330 340 350 KEALEHPYLQ TYHDPNDEPE GEPIPPSFFE FDHYKEALTT KDLKKLIWNE IFS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation." Elion E.A., Grisafi P.L., Fink G.R. Cell 60:649-664(1990) [PubMed: 2406028] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The DAC2/FUS3 protein kinase is not essential for transcriptional activation of the mating pheromone response pathway in Saccharomyces cerevisiae." Fujimura H.A. Mol. Gen. Genet. 235:450-452(1992) [PubMed: 1465115] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"An 11.4 kb DNA segment on the left arm of yeast chromosome II carries the carboxypeptidase Y sorting gene PEP1, as well as ACH1, FUS3 and a putative ARS." van Dyck L., Purnelle B., Skala J., Goffeau A. Yeast 8:769-776(1992) [PubMed: 1441754] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[4]	"Complete DNA sequence of yeast chromosome II." Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C., Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M., Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M., Cziepluch C. , Demolis N., Delaveau T., Doignon F., Domdey H., Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D., Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N., Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J., Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C., Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P., Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y., Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F., Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E., Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M., Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B., Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L., Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M., Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S., Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K., Mewes H.-W., Kleine K. EMBO J. 13:5795-5809(1994) [PubMed: 7813418] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	"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: 17322287] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[6]	"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: 1628831] [Abstract] Cited for: PHOSPHORYLATION.
[7]	"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: 9393860] [Abstract] Cited for: FUNCTION, REGULATION OF STE12 ACTIVITY.
[8]	"Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates." Tedford K., Kim S., Sa D., Stevens K., Tyers M. Curr. Biol. 7:228-238(1997) [PubMed: 9094309] [Abstract] Cited for: FUNCTION, COMPLEX WITH DIG1; DIG2 AND STE12.
[9]	"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: 11583629] [Abstract] Cited for: FUNCTION, REGULATION OF KSS1 ACTIVITY.
[10]	"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: 11781566] [Abstract] Cited for: SUBCELLULAR LOCATION.
[11]	"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: 12732146] [Abstract] Cited for: FUNCTION, REGULATION OF STE12 PROMOTER SELECTIVITY.
[12]	"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: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[13]	"Quantitative phosphoproteomics applied to the yeast pheromone signaling pathway." Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M., Jensen O.N. Mol. Cell. Proteomics 4:310-327(2005) [PubMed: 15665377] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY.
[14]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-180 AND TYR-182, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M31132 Genomic DNA. Translation: AAA34613.1.
X69572 Genomic DNA. Translation: CAA49292.1.
X68577 Genomic DNA. Translation: CAA48569.1.
Z35777 Genomic DNA. Translation: CAA84835.1.
AY693096 Genomic DNA. Translation: AAT93115.1.

PIR

S28548.

RefSeq

NP_009537.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2B9F	X-ray	1.80	A	1-353	[»]
2B9H	X-ray	1.55	A	1-353	[»]
2B9I	X-ray	2.50	A	1-353	[»]
2B9J	X-ray	2.30	A	1-353	[»]
2F49	X-ray	1.90	A/B	1-353	[»]
2F9G	X-ray	2.10	A	1-353	[»]
2FA2	X-ray	2.85	A/B	1-353	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:714N.

IntAct

P16892. 11 interactions.

STRING

P16892.

Proteomic databases

PeptideAtlas

P16892.

Genome annotation databases

Ensembl

YBL016W; YBL016W; YBL016W; Saccharomyces cerevisiae. [Genome view]

GeneID

852265.

GenomeReviews

Gene locus YBL016W in contig Y13134_GR.

KEGG

sce:YBL016W.

NMPDR

fig|4932.3.peg.230.

Organism-specific databases

CYGD

YBL016w.

SGD

S000000112. FUS3.

Phylogenomic databases

HOGENOM

P16892.

OMA

HDINDEP.

Enzyme and pathway databases

BRENDA

2.7.11.24. 250.

Gene expression databases

ArrayExpress

P16892.

Genevestigator

P16892.

GermOnline

YBL016W. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR003527. MAP_kinase_CS.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 2 hits.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

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 Resources

NextBio

970865.

Entry information

Entry name

FUS3_YEAST

Accession

Primary (citable) accession number: P16892

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	October 1, 1993
Last modified:	November 3, 2009
This is version 118 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)