Reviewed, UniProtKB/Swiss-Prot P40581 (GPX3_YEAST)

Names and origin

Protein names

Recommended name:
    Peroxiredoxin HYR1
    EC=1.11.1.15
Alternative name(s):
    Hydrogen peroxide resistance protein 1
    Oxidant receptor peroxidase 1
    Glutathione peroxidase 3
    Phospholipid hydroperoxide glutathione peroxidase 3
      Short name=PHGPx3

Gene names

Name:	HYR1
Synonyms:	GPX3, ORP1
Ordered Locus Names:	YIR037W

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

General annotation (Comments)

Function	Involved in oxidative stress response and redox homeostasis. Functions as a sensor and transducer of hydroperoxide stress. In response to hydroperoxide stress it oxidizes (activates) the transcription activator YAP1, which is involved in transcription activation of genes of the oxidative stress response pathway. May also play a direct role in hydroperoxide scavenging, being the most active of three closely related S.cerevisiae peroxiredoxins (GPX1, GPX2, and HYP1/GPX3) with respect to peroxide and lipid hydroperoxide reduction. The three enzymes are not required for the glutaredoxin-mediated antioxidant function. In the presence of peroxides, HYP1 is directly oxidized at Cys-36 to form a cysteine sulfenic acid (-SOH). Cys-36-SOH then forms either an intramolecular disulfide bond (Cys-36 with Cys-82) or a transient, intermolecular disulfide bond with 'Cys-598' of YAP1, which is further resolved into a YAP1 intramolecular disulfide bond ('Cys-303' with 'Cys-598') and a reduced Cys-36 in HYP1/GPX3. Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10
Catalytic activity	2 R'-SH + ROOH = R'-S-S-R' + H2O + ROH.
Subunit structure	Interacts with YAP1 and probably YBP1. Ref.9
Subcellular location	Cytoplasm. Ref.12
Induction	In contrast to the other two peroxiredoxins, HYP1/GPX3 expression is constitutive, not stress-induced. Ref.4
Post-translational modification	Reversible disulfide bond formation between Cys-36 and Cys-82 upon peroxide reduction; probably reverted by thioredoxin (TRX2).
Miscellaneous	Present with 8000 molecules/cell in log phase SD medium. Ref.13
Sequence similarities	Belongs to the glutathione peroxidase family.
Caution	Was originally thought to be a glutathione peroxidase or a phospholipid hydroperoxide glutathione peroxidase. HYP1 does not require glutathione for hydroperoxide reduction.

Ontologies

Keywords
Cellular component	Cytoplasm
Domain	Redox-active center
Molecular function	Oxidoreductase Peroxidase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW response to oxidative stress Ref.5 Inferred from mutant phenotype. Source: SGD
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	glutathione peroxidase activity Ref.4 Ref.7 Inferred from mutant phenotype. Source: SGD phospholipid-hydroperoxide glutathione peroxidase activity Ref.5 Inferred from direct assay. Source: SGD protein binding Inferred from physical interaction. Source: IntAct thioredoxin peroxidase activity Ref.9 Traceable author statement. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADE17	P38009	1	EBI-7869,EBI-14223
ALO1	P54783	1	EBI-7869,EBI-2519
CAR2	P07991	1	EBI-7869,EBI-12430
ERG11	P10614	1	EBI-7869,EBI-5127
GAP1	P19145	1	EBI-7869,EBI-7314
GLN1	P32288	1	EBI-7869,EBI-7665
HXT7	P39004	1	EBI-7869,EBI-8790
PDR12	Q02785	1	EBI-7869,EBI-13065
PEX11	Q12462	1	EBI-7869,EBI-13198
PMP2	P40975	1	EBI-7869,EBI-2043041
PMP3	P87284	1	EBI-7869,EBI-13555
RNR2	P09938	1	EBI-7869,EBI-15240
YBL039W-B	P0C268	1	EBI-7869,EBI-2044092

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 163	163	Peroxiredoxin HYR1		PRO_0000066643
Sites
	Active site	36	1	Cysteine sulfenic acid (-SOH) intermediate
Amino acid modifications
	Disulfide bond	36 ↔ 82		Redox-active
	Disulfide bond	36		Interchain (with C-598 in YAP1); transient
Experimental info
	Mutagenesis	82	1	C → S: Loss of enzyme activity.

Sequences

	Sequence		Length	Mass (Da)
	P40581-1 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: 46C42B81E895C1A3	FASTA	163	18,641
	10 20 30 40 50 60 MSEFYKLAPV DKKGQPFPFD QLKGKVVLIV NVASKCGFTP QYKELEALYK RYKDEGFTII 70 80 90 100 110 120 GFPCNQFGHQ EPGSDEEIAQ FCQLNYGVTF PIMKKIDVNG GNEDPVYKFL KSQKSGMLGL 130 140 150 160 RGIKWNFEKF LVDKKGKVYE RYSSLTKPSS LSETIEELLK EVE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and phenotypic characterization of a glutathione-peroxidase like gene involved in the oxidative stress response of Saccharomyces cerevisiae." Budde E., Stahl U. Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 38626 / AH22 / NRRL Y-12843.
[2]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome IX." Churcher C.M., Bowman S., Badcock K., Bankier A.T., Brown D., Chillingworth T., Connor R., Devlin K., Gentles S., Hamlin N., Harris D.E., Horsnell T., Hunt S., Jagels K., Jones M., Lye G., Moule S., Odell C. , Pearson D., Rajandream M.A., Rice P., Rowley N., Skelton J., Smith V., Walsh S.V., Whitehead S., Barrell B.G. Nature 387:84-87(1997) [PubMed: 9169870] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	"Phospholipid hydroperoxide glutathione peroxidase (PHGPx): more than an antioxidant enzyme?" Ursini F., Maiorino M., Roveri A. Biomed. Environ. Sci. 10:327-332(1997) [PubMed: 9315326] [Abstract] Cited for: FUNCTION, PROTEIN OXIDATION.
[4]	"Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae." Inoue Y., Matsuda T., Sugiyama K., Izawa S., Kimura A. J. Biol. Chem. 274:27002-27009(1999) [PubMed: 10480913] [Abstract] Cited for: FUNCTION, INDUCTION.
[5]	"Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione peroxidases." Avery A.M., Avery S.V. J. Biol. Chem. 276:33730-33735(2001) [PubMed: 11445588] [Abstract] Cited for: FUNCTION, FUNCTION AS A PHGPX.
[6]	"The yeast glutaredoxins are active as glutathione peroxidases." Collinson E.J., Wheeler G.L., Garrido E.O., Avery A.M., Avery S.V., Grant C.M. J. Biol. Chem. 277:16712-16717(2002) [PubMed: 11875065] [Abstract] Cited for: FUNCTION AS A GLUTAREDOXIN.
[7]	"A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation." Delaunay A., Pflieger D., Barrault M.-B., Vinh J., Toledano M.B. Cell 111:471-481(2002) [PubMed: 12437921] [Abstract] Cited for: FUNCTION, OXIDATION OF YAP1.
[8]	"Structure, mechanism and regulation of peroxiredoxins." Wood Z.A., Schroder E., Robin Harris J., Poole L.B. Trends Biochem. Sci. 28:32-40(2003) [PubMed: 12517450] [Abstract] Cited for: FUNCTION AS A PEROXIREDOXIN.
[9]	"Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1 transcription factor." Veal E.A., Ross S.J., Malakasi P., Peacock E., Morgan B.A. J. Biol. Chem. 278:30896-30904(2003) [PubMed: 12743123] [Abstract] Cited for: FUNCTION, INTERACTION WITH YBP1.
[10]	"Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling." Azevedo D., Tacnet F., Delaunay A., Rodrigues-Pousada C., Toledano M.B. Free Radic. Biol. Med. 35:889-900(2003) [PubMed: 14556853] [Abstract] Cited for: FUNCTION, ACTIVATING SUBSTANCES.
[11]	"Roles of the glutathione- and thioredoxin-dependent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress." Carmel-Harel O., Storz G. Annu. Rev. Microbiol. 54:439-461(2000) [PubMed: 11018134] [Abstract] Cited for: REVIEW.
[12]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[13]	"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].
[14]	"Crystal structure of glutathione-dependent phospholipid peroxidase Hyr1 from the yeast Saccharomyces cerevisiae." Zhang W.J., He Y.-X., Yang Z., Yu J., Chen Y., Zhou C.-Z. Proteins 73:1058-1062(2008) [PubMed: 18767166] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS), CATALYTIC ACTIVITY, MUTAGENESIS OF CYS-82.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U22446 Genomic DNA. Translation: AAA64283.1.
Z38061 Genomic DNA. Translation: CAA86197.1.

PIR

S48499.

RefSeq

NP_012303.1.

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3CMI	X-ray	2.02	A	1-163	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:1275N.

IntAct

P40581. 30 interactions.

Protein family/group databases

PeroxiBase

3742. SceGPx03.

Proteomic databases

PeptideAtlas

P40581.

Genome annotation databases

Ensembl

YIR037W. Saccharomyces cerevisiae. [Contig view]

GeneID

854855.

GenomeReviews

Gene locus YIR037W in contig Z47047_GR.

KEGG

sce:YIR037W.

NMPDR

fig|4932.3.peg.1848.

Organism-specific databases

CYGD

YIR037w.

SGD

S000001476. HYR1.

Yeast-GFP

Search...

Phylogenomic databases

HOGENOM

P40581.

OMA

P40581. CTRFKSE.

Enzyme and pathway databases

BRENDA

1.11.1.15. 250.

Gene expression databases

ArrayExpress

P40581.

GermOnline

YIR037W. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR000889. Glutathione_peroxidase.
IPR012335. Thioredoxin_fold.
[Graphical view]

Gene3D

G3DSA:3.40.30.10. Thioredoxin_fold. 1 hit.

PANTHER

PTHR11592. Glut_peroxidase. 1 hit.

Pfam

PF00255. GSHPx. 1 hit.
[Graphical view]

PIRSF

PIRSF000303. Glutathion_perox. 1 hit.

PRINTS

PR01011. GLUTPROXDASE.

PROSITE

PS00460. GLUTATHIONE_PEROXID_1. 1 hit.
PS00763. GLUTATHIONE_PEROXID_2. 1 hit.
PS51355. GLUTATHIONE_PEROXID_3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

977764.

Entry information

Entry name

GPX3_YEAST

Accession

Primary (citable) accession number: P40581

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	June 16, 2009
This is version 77 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)