EC 1.11.1.15
Hydrogen peroxide resistance protein 1
Oxidant receptor peroxidase 1
Glutathione peroxidase 3
Phospholipid hydroperoxide glutathione peroxidase 3
PHGPx3

Gene name

	Name:	HYR1
	Synonyms:	GPX3, ORP1
	OrderedLocusNames:	YIR037W

From

Saccharomyces cerevisiae (Baker's yeast)

[TaxID: 4932]

Taxonomy

Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces.

Protein existence

1: Evidence at protein level;

References

[1]	NUCLEOTIDE SEQUENCE [GENOMIC DNA]. STRAIN=ATCC 38626 / AH22 / NRRL Y-12843; Budde E., Stahl U.; "Cloning and phenotypic characterization of a glutathione-peroxidase like gene involved in the oxidative stress response of Saccharomyces cerevisiae."; Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. STRAIN=ATCC 204511 / S288c / AB972; PubMed=9169870 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "The nucleotide sequence of Saccharomyces cerevisiae chromosome IX."; Nature 387:84-87(1997).
[3]	FUNCTION, AND PROTEIN OXIDATION. PubMed=9315326 [NCBI, ExPASy, EBI, Israel, Japan] Ursini F., Maiorino M., Roveri A.; "Phospholipid hydroperoxide glutathione peroxidase (PHGPx): more than an antioxidant enzyme?"; Biomed. Environ. Sci. 10:327-332(1997).
[4]	FUNCTION, AND INDUCTION. DOI=10.1074/jbc.274.38.27002; PubMed=10480913 [NCBI, ExPASy, EBI, Israel, Japan] Inoue Y., Matsuda T., Sugiyama K., Izawa S., Kimura A.; "Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae."; J. Biol. Chem. 274:27002-27009(1999).
[5]	FUNCTION, AND FUNCTION AS A PHGPX. DOI=10.1074/jbc.M105672200; PubMed=11445588 [NCBI, ExPASy, EBI, Israel, Japan] Avery A.M., Avery S.V.; "Saccharomyces cerevisiae expresses three phospholipid hydroperoxide glutathione peroxidases."; J. Biol. Chem. 276:33730-33735(2001).
[6]	FUNCTION AS A GLUTAREDOXIN. DOI=10.1074/jbc.M111686200; PubMed=11875065 [NCBI, ExPASy, EBI, Israel, Japan] Collinson E.J., Wheeler G.L., Garrido E.O., Avery A.M., Avery S.V., Grant C.M.; "The yeast glutaredoxins are active as glutathione peroxidases."; J. Biol. Chem. 277:16712-16717(2002).
[7]	FUNCTION, AND OXIDATION OF YAP1. DOI=10.1016/S0092-8674(02)01048-6; PubMed=12437921 [NCBI, ExPASy, EBI, Israel, Japan] Delaunay A., Pflieger D., Barrault M.-B., Vinh J., Toledano M.B.; "A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation."; Cell 111:471-481(2002).
[8]	FUNCTION AS A PEROXIREDOXIN. DOI=10.1016/S0968-0004(02)00003-8; PubMed=12517450 [NCBI, ExPASy, EBI, Israel, Japan] Wood Z.A., Schroder E., Robin Harris J., Poole L.B.; "Structure, mechanism and regulation of peroxiredoxins."; Trends Biochem. Sci. 28:32-40(2003).
[9]	FUNCTION, AND INTERACTION WITH YBP1. DOI=10.1074/jbc.M303542200; PubMed=12743123 [NCBI, ExPASy, EBI, Israel, Japan] Veal E.A., Ross S.J., Malakasi P., Peacock E., Morgan B.A.; "Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1 transcription factor."; J. Biol. Chem. 278:30896-30904(2003).
[10]	FUNCTION, AND ACTIVATING SUBSTANCES. DOI=10.1016/S0891-5849(03)00434-9; PubMed=14556853 [NCBI, ExPASy, EBI, Israel, Japan] Azevedo D., Tacnet F., Delaunay A., Rodrigues-Pousada C., Toledano M.B.; "Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling."; Free Radic. Biol. Med. 35:889-900(2003).
[11]	REVIEW. DOI=10.1146/annurev.micro.54.1.439; PubMed=11018134 [NCBI, ExPASy, EBI, Israel, Japan] Carmel-Harel O., Storz G.; "Roles of the glutathione- and thioredoxin-dependent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress."; Annu. Rev. Microbiol. 54:439-461(2000).
[12]	SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. DOI=10.1038/nature02026; PubMed=14562095 [NCBI, ExPASy, EBI, Israel, Japan] Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K.; "Global analysis of protein localization in budding yeast."; Nature 425:686-691(2003).
[13]	LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. DOI=10.1038/nature02046; PubMed=14562106 [NCBI, ExPASy, EBI, Israel, Japan] Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S.; "Global analysis of protein expression in yeast."; Nature 425:737-741(2003).

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-310' with 'Cys-598') and a reduced Cys-36 in HYP1/GPX3.
CATALYTIC ACTIVITY: 2 R'-SH + ROOH = R'-S-S-R' + H₂O + ROH.
SUBUNIT: Interacts with YAP1 and probably YBP1.
SUBCELLULAR LOCATION: Cytoplasm.
INDUCTION: In contrast to the other two peroxiredoxins, HYP1/GPX3 expression is constitutive, not stress-induced.
PTM: 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.
SIMILARITY: 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.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

U22446; AAA64283.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
Z38061; CAA86197.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

PIR

S48499; S48499.

RefSeq

NP_012303.1; -.

3D structure databases

PDB

3CMI; X-ray; 2.02 A; A=1-163.

[ExPASy / RCSB / EBI]

PDBsum

3CMI; -.

ModBase

P40581.

Protein-protein interaction databases

DIP

DIP:1275N; -.

IntAct

P40581; -.

Protein family/group databases

PeroxiBase

3742; SceGPx03.

Organism-specific databases

YIR037w; -.

S000001476; HYR1.

Gene expression databases

ArrayExpress

P40581; -.

GermOnline

YIR037W; Saccharomyces cerevisiae.

Ontologies

GO:0005737;	Cellular component: cytoplasm (inferred from electronic annotation from UniProtKB-KW).
GO:0004602;	Molecular function: glutathione peroxidase activity (inferred from electronic annotation from InterPro).
GO:0047066;	Molecular function: phospholipid-hydroperoxide glutathione peroxidase activity (inferred from direct assay from SGD).
GO:0008379;	Molecular function: thioredoxin peroxidase activity (traceable author statement from SGD).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
GO:0006979;	Biological process: response to oxidative stress (inferred from electronic annotation from InterPro).
QuickGo view.

Family and domain databases

InterPro

IPR000889; Glut_peroxidase.
IPR012335; Thioredoxin_fold.
Graphical view of domain structure.

Gene3D

G3DSA:3.40.30.10; Thioredoxin_fold; 1.

PANTHER

PTHR11592; Glut_peroxidase; 1.

Pfam

PF00255; GSHPx; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF000303; Glutathion_perox; 1.

PRINTS

PR01011; GLUTPROXDASE.

PROSITE

PS00460; GLUTATHIONE_PEROXID_1; 1.
PS00763; GLUTATHIONE_PEROXID_2; 1.
PS51355; GLUTATHIONE_PEROXID_3; 1.
PROSITE graphical view of domain structure (profiles).

ProtoNet

P40581.

Proteomic databases

PeptideAtlas

P40581; -.

Genome annotation databases

Ensembl

YIR037W; Saccharomyces cerevisiae. [Contig view]

854855; -.

Z47047_GR; YIR037W.

sce:YIR037W; -.

fig|4932.3.peg.1848; -.

Phylogenomic databases

HOGENOM

P40581; -.

Other

LinkHub

P40581; -.

NextBio

977764; -.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Complete proteome; Cytoplasm; Oxidoreductase; Peroxidase; Redox-active center.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 163`	`163`	`Peroxiredoxin HYR1.`	`PRO_0000066643`
`ACT_SITE`	`36 36`		`Cysteine sulfenic acid (-SOH) intermediate.`
`DISULFID`	`36 82`		`Redox-active.`
`DISULFID`	`36 36`		`Interchain (with C-598 in YAP1); transient.`

Sequence information

Length: 163 AA [This is the length of the unprocessed precursor]

Molecular weight: 18641 Da [This is the MW of the unprocessed precursor]

CRC64: 46C42B81E895C1A3 [This is a checksum on the sequence]

        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

P40581 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools