P23202 (URE2_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Transcriptional regulator URE2

Gene names

Name:	URE2
Ordered Locus Names:	YNL229C
ORF Names:	N1165

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	354 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays an important role in nitrogen catabolite repression. Down-regulates the expression of many genes involved in nitrogen utilization by inhibiting the GATA transcriptional activators GLN3 and GAT1. Under good nitrogen conditions, binds to the phosphorylated forms of GLN3 and GAT1 and sequesters them in the cytoplasm, preventing transcription of genes expressed upon nitrogen limitation. Has glutathione peroxidase activity in both native and fibrillar form. Ref.1 Ref.8 Ref.9 Ref.10 Ref.13
Subunit structure	Homodimer. Interacts with NNK1. Ref.15
Subcellular location	Cytoplasm Ref.9.
Domain	The prion domain (PrD) is a Gln/Asn (Q/N)-rich domain, which is unstructured in its native, soluble form, and which forms a parallel in-register beta-sheet in its amyloid form. Ref.7 Ref.20
Miscellaneous	[URE3] is the prion form of URE2. [URE3] is the result of a conformational change of the cellular URE2 protein that becomes self-propagating and infectious. This conformational change generates a form of URE2 that assembles into amyloid fibrils. [URE3] aggregates sequester soluble URE2, which then fails to retain GLN3 in the cytoplasm, resulting in GLN3 activation and consequently derepression of genes that are required for utilization of poor nirogen sources (Ref.6). [URE3] can be cured by GdnHCl and by deletion of the molecular chaperone HSP104, which is required for [URE3] propagation (Ref.11). Present with 7060 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the GST superfamily. Contains 1 GST C-terminal domain. Contains 1 GST N-terminal domain.

Ontologies

Keywords
Biological process	Nitrate assimilation
Cellular component	Amyloid Cytoplasm
Molecular function	Prion
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytoplasmic sequestering of transcription factor Inferred from mutant phenotype PubMed 10748041. Source: SGD nitrate assimilation Inferred from electronic annotation. Source: UniProtKB-KW protein urmylation Inferred from mutant phenotype PubMed 14551258. Source: SGD regulation of nitrogen utilization Inferred from mutant phenotype PubMed 8002570. Source: SGD response to aluminum ion Inferred from mutant phenotype PubMed 15133656. Source: SGD
Cellular_component	cytosol Inferred from direct assay PubMed 10748041. Source: SGD
Molecular_function	glutathione peroxidase activity Inferred from direct assay Ref.13. Source: SGD phosphoprotein binding Inferred from direct assay Ref.9. Source: SGD transcription corepressor activity Inferred from physical interaction Ref.8. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NNK1	P36003	4	EBI-20138,EBI-9796

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 354

354

Transcriptional regulator URE2

PRO_0000186013

Regions

Domain

112 – 196

85

GST N-terminal

Domain

205 – 354

150

GST C-terminal

Region

1 – 89

89

Prion domain (PrD)

Region

164 – 165

2

Glutathione binding

Region

180 – 181

2

Glutathione binding

Sites

Binding site

124

1

Glutathione

Binding site

151

1

Glutathione

Amino acid modifications

Modified residue

282

1

Phosphotyrosine Ref.14

Modified residue

283

1

Phosphoserine Ref.14

Modified residue

287

1

Phosphothreonine Ref.14

Experimental info

Mutagenesis

313

1

F → S: Destroys protein function.

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

354

Helix Strand Turn

Details...

Helix

103 – 107

5

Beta strand

111 – 118

8

Helix

123 – 134

12

Beta strand

139 – 143

5

Turn

146 – 149

4

Helix

150 – 152

3

Helix

154 – 157

4

Beta strand

167 – 170

4

Turn

171 – 175

5

Beta strand

176 – 180

5

Helix

181 – 196

16

Helix

206 – 222

17

Helix

224 – 235

12

Beta strand

237 – 239

3

Helix

242 – 271

30

Helix

279 – 284

6

Beta strand

285 – 287

3

Helix

289 – 291

3

Beta strand

295 – 297

3

Helix

308 – 311

4

Helix

314 – 317

4

Helix

320 – 323

4

Helix

327 – 330

4

Helix

332 – 342

11

Helix

345 – 350

6

Sequences

	Sequence		Length	Mass (Da)
	P23202 [UniParc]. Last modified November 1, 1991. Version 1. Checksum: 2C628976034B0F1C	FASTA	354	40,271
	10 20 30 40 50 60 MMNNNGNQVS NLSNALRQVN IGNRNSNTTT DQSNINFEFS TGVNNNNNNN SSSNNNNVQN 70 80 90 100 110 120 NNSGRNGSQN NDNENNIKNT LEQHRQQQQA FSDMSHVEYS RITKFFQEQP LEGYTLFSHR 130 140 150 160 170 180 SAPNGFKVAI VLSELGFHYN TIFLDFNLGE HRAPEFVSVN PNARVPALID HGMDNLSIWE 190 200 210 220 230 240 SGAILLHLVN KYYKETGNPL LWSDDLADQS QINAWLFFQT SGHAPMIGQA LHFRYFHSQK 250 260 270 280 290 300 IASAVERYTD EVRRVYGVVE MALAERREAL VMELDTENAA AYSAGTTPMS QSRFFDYPVW 310 320 330 340 350 LVGDKLTIAD LAFVPWNNVV DRIGINIKIE FPEVYKWTKH MMRRPAVIKA LRGE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The URE2 gene product of Saccharomyces cerevisiae plays an important role in the cellular response to the nitrogen source and has homology to glutathione s-transferases." Coschigano P.W., Magasanik B. Mol. Cell. Biol. 11:822-832(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION.
[2]	"Conservation of a portion of the S. cerevisiae Ure2p prion domain that interacts with the full-length protein." Edskes H.K., Wickner R.B. Proc. Natl. Acad. Sci. U.S.A. 99:16384-16391(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 14085 / CBS 3093 / IFO 1997 / NRRL Y-12657, ATCC 9804 / CBS 400 / DSM 70478 / IFO 0210 / JCM 2220, Boots, CBS 2087, CBS 4734, CBS 5112, CBS 5287, CBS 7957, Chevalieri / ATCC 10604 / CBS 405 / IFO 0258 / NRRL Y-1546, Fleischmann, McPhie Sourdough, SAF, Sigma 1278B, Wyeast#1007, YJM 143, YJM 280, YJM 320, YJM 326 and YJM 415.
[3]	"The DNA sequence of cosmid 14-5 from chromosome XIV reveals 21 open reading frames including a novel gene encoding a globin-like domain." Pandolfo D., de Antoni A., Lanfranchi G., Valle G. Yeast 12:1071-1076(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XIV and its evolutionary implications." Philippsen P., Kleine K., Poehlmann R., Duesterhoeft A., Hamberg K., Hegemann J.H., Obermaier B., Urrestarazu L.A., Aert R., Albermann K., Altmann R., Andre B., Baladron V., Ballesta J.P.G., Becam A.-M., Beinhauer J.D., Boskovic J., Buitrago M.J. , Bussereau F., Coster F., Crouzet M., D'Angelo M., Dal Pero F., De Antoni A., del Rey F., Doignon F., Domdey H., Dubois E., Fiedler T.A., Fleig U., Floeth M., Fritz C., Gaillardin C., Garcia-Cantalejo J.M., Glansdorff N., Goffeau A., Gueldener U., Herbert C.J., Heumann K., Heuss-Neitzel D., Hilbert H., Hinni K., Iraqui Houssaini I., Jacquet M., Jimenez A., Jonniaux J.-L., Karpfinger-Hartl L., Lanfranchi G., Lepingle A., Levesque H., Lyck R., Maftahi M., Mallet L., Maurer C.T.C., Messenguy F., Mewes H.-W., Moestl D., Nasr F., Nicaud J.-M., Niedenthal R.K., Pandolfo D., Pierard A., Piravandi E., Planta R.J., Pohl T.M., Purnelle B., Rebischung C., Remacha M.A., Revuelta J.L., Rinke M., Saiz J.E., Sartorello F., Scherens B., Sen-Gupta M., Soler-Mira A., Urbanus J.H.M., Valle G., Van Dyck L., Verhasselt P., Vierendeels F., Vissers S., Voet M., Volckaert G., Wach A., Wambutt R., Wedler H., Zollner A., Hani J. Nature 387:93-98(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[5]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[6]	"[URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae." Wickner R.B. Science 264:566-569(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION.
[7]	"Prion-inducing domain of yeast Ure2p and protease resistance of Ure2p in prion-containing cells." Masison D.C., Wickner R.B. Science 270:93-95(1995) [PubMed] [Europe PMC] [Abstract] Cited for: DOMAIN PRION.
[8]	"Interaction of the GATA factor Gln3p with the nitrogen regulator Ure2p in Saccharomyces cerevisiae." Blinder D., Coschigano P.W., Magasanik B. J. Bacteriol. 178:4734-4736(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"The TOR signalling pathway controls nuclear localization of nutrient-regulated transcription factors." Beck T., Hall M.N. Nature 402:689-692(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"Nitrogen catabolite repression of DAL80 expression depends on the relative levels of Gat1p and Ure2p production in Saccharomyces cerevisiae." Cunningham T.S., Andhare R., Cooper T.G. J. Biol. Chem. 275:14408-14414(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"[URE3] prion propagation in Saccharomyces cerevisiae: requirement for chaperone Hsp104 and curing by overexpressed chaperone Ydj1p." Moriyama H., Edskes H.K., Wickner R.B. Mol. Cell. Biol. 20:8916-8922(2000) [PubMed] [Europe PMC] [Abstract] Cited for: PRION FORMATION, PRION CURING.
[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] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[13]	"The yeast prion protein Ure2 shows glutathione peroxidase activity in both native and fibrillar forms." Bai M., Zhou J.M., Perrett S. J. Biol. Chem. 279:50025-50030(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-282; SER-283 AND THR-287, MASS SPECTROMETRY.
[15]	"A global protein kinase and phosphatase interaction network in yeast." Breitkreutz A., Choi H., Sharom J.R., Boucher L., Neduva V., Larsen B., Lin Z.Y., Breitkreutz B.J., Stark C., Liu G., Ahn J., Dewar-Darch D., Reguly T., Tang X., Almeida R., Qin Z.S., Pawson T., Gingras A.C., Nesvizhskii A.I., Tyers M. Science 328:1043-1046(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NNK1.
[16]	"Crystal structures of the yeast prion Ure2p functional region in complex with glutathione and related compounds." Bousset L., Belrhali H., Melki R., Morera S. Biochemistry 40:13564-13573(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 95-354 IN COMPLEX WITH GLUTATHIONE AND INHIBITORS.
[17]	"The crystal structure of the nitrogen regulation fragment of the yeast prion protein Ure2p." Umland T.C., Taylor K.L., Rhee S., Wickner R.B., Davies D.R. Proc. Natl. Acad. Sci. U.S.A. 98:1459-1464(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 97-354.
[18]	"Structure of the globular region of the prion protein Ure2 from the yeast Saccharomyces cerevisiae." Bousset L., Belrhali H., Janin J., Melki R., Morera S. Structure 9:39-46(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 100-353.
[19]	"Parallel beta-sheets and polar zippers in amyloid fibrils formed by residues 10-39 of the yeast prion protein Ure2p." Chan J.C., Oyler N.A., Yau W.M., Tycko R. Biochemistry 44:10669-10680(2005) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 10-39.
[20]	"Characterization of beta-sheet structure in Ure2p(1-89) yeast prion fibrils by solid-state nuclear magnetic resonance." Baxa U., Wickner R.B., Steven A.C., Anderson D.E., Marekov L.N., Yau W.M., Tycko R. Biochemistry 46:13149-13162(2007) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 1-89, DOMAIN PRION.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Mad yeast disease - Issue 47 of June 2004

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M35268 Genomic DNA. Translation: AAA35201.1.
AF525174 Genomic DNA. Translation: AAM93167.1.
AF525175 Genomic DNA. Translation: AAM93168.1.
AF525176 Genomic DNA. Translation: AAM93169.1.
AF525177 Genomic DNA. Translation: AAM93170.1.
AF525178 Genomic DNA. Translation: AAM93171.1.
AF525179 Genomic DNA. Translation: AAM93172.1.
AF525180 Genomic DNA. Translation: AAM93173.1.
AF525181 Genomic DNA. Translation: AAM93174.1.
AF525182 Genomic DNA. Translation: AAM93175.1.
AF525183 Genomic DNA. Translation: AAM93176.1.
AF525184 Genomic DNA. Translation: AAM93177.1.
AF525185 Genomic DNA. Translation: AAM93178.1.
AF525186 Genomic DNA. Translation: AAM93179.1.
AF525187 Genomic DNA. Translation: AAM93180.1.
AF525188 Genomic DNA. Translation: AAM93181.1.
AF525189 Genomic DNA. Translation: AAM93182.1.
AF525190 Genomic DNA. Translation: AAM93183.1.
AF525191 Genomic DNA. Translation: AAM93184.1.
AF525192 Genomic DNA. Translation: AAM93185.1.
Z69381 Genomic DNA. Translation: CAA93369.1.
Z71505 Genomic DNA. Translation: CAA96134.1.
BK006947 Genomic DNA. Translation: DAA10329.1.

PIR

A39609.

RefSeq

NP_014170.1. NM_001183067.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1G6W	X-ray	2.50	A/B/C/D	94-354	[»]
1G6Y	X-ray	2.80	A/B	94-354	[»]
1HQO	X-ray	2.30	A/B	97-354	[»]
1JZR	X-ray	2.90	A/B/C/D	95-354	[»]
1K0A	X-ray	2.50	A/B	95-354	[»]
1K0B	X-ray	2.50	A/B/C/D	95-354	[»]
1K0C	X-ray	2.50	A/B/C/D	95-354	[»]
1K0D	X-ray	2.20	A/B/C/D	95-354	[»]

DisProt

DP00353.

ProteinModelPortal

P23202.

SMR

P23202. Positions 96-354.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1308N.

IntAct

P23202. 28 interactions.

MINT

MINT-393865.

STRING

4932.YNL229C.

Proteomic databases

PaxDb

P23202.

PeptideAtlas

P23202.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YNL229C; YNL229C; YNL229C.

GeneID

855492.

KEGG

sce:YNL229C.

Organism-specific databases

CYGD

YNL229c.

SGD

S000005173. URE2.

Phylogenomic databases

eggNOG

COG0625.

HOGENOM

HOG000125742.

KO

K00799.

OMA

KWTKHMM.

OrthoDB

EOG4X0R27.

Gene expression databases

ArrayExpress

P23202.

Genevestigator

P23202.

GermOnline

YNL229C. Saccharomyces cerevisiae.

Family and domain databases

Gene3D

1.20.1050.10. 1 hit.
3.40.30.10. 1 hit.

InterPro

IPR010987. Glutathione-S-Trfase_C-like.
IPR004045. Glutathione_S-Trfase_N.
IPR017933. Glutathione_S_Trfase/Cl_chnl_C.
IPR004046. GST_C.
IPR017298. Prion_URE2.
IPR012336. Thioredoxin-like_fold.
[Graphical view]

Pfam

PF00043. GST_C. 1 hit.
PF02798. GST_N. 1 hit.
[Graphical view]

PIRSF

PIRSF037861. Prion_URE2. 1 hit.

SUPFAM

SSF47616. GST_C_like. 1 hit.
SSF52833. Thiordxn-like_fd. 1 hit.

PROSITE

PS50405. GST_CTER. 1 hit.
PS50404. GST_NTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P23202.

NextBio

979478.

Entry information

Entry name

URE2_YEAST

Accession

Primary (citable) accession number: P23202
Secondary accession number(s): D6W0W3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1991
Last sequence update:	November 1, 1991
Last modified:	May 1, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program