Q03103 (ERO1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Endoplasmic oxidoreductin-1
EC=1.8.4.-

Alternative name(s):
Endoplasmic oxidoreductase protein 1

Gene names

Name:	ERO1
Ordered Locus Names:	YML130C
ORF Names:	YM4987.05C

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	563 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Essential oxidoreductase that oxidizes proteins in the endoplasmic reticulum to produce disulfide bonds. Acts by oxidizing directly PDI1 isomerase through a direct disulfide exchange. Does not act as a direct oxidant of folding substrate, but relies on PDI1 to transfer oxidizing equivalent. Also able to oxidize directly the PDI related protein MPD2. Does not oxidize all PDI related proteins, suggesting that it can discriminate between PDI1 and related proteins. Reoxidation of ERO1 probably involves electron transfer to molecular oxygen via FAD. Acts independently of glutathione. May be responsible for a significant proportion of reactive oxygen species (ROS) in the cell, thereby being a source of oxidative stress. Ref.4 Ref.5 Ref.6 Ref.7 Ref.10
Cofactor	FAD. Ref.7
Enzyme regulation	Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between Cys-150 and Cys-295. Ref.12
Subunit structure	May function both as a monomer and a homodimer. Ref.13
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side Ref.4 Ref.5 Ref.9.
Induction	By unfolded protein response (UPR). Ref.4 Ref.5 Ref.12
Domain	The C-terminal part (437-563) is required for the association with the endoplasmic reticulum lumen membrane. Ref.9
Post-translational modification	The Cys-100/Cys-105 and Cys-352/Cys-355 disulfide bonds constitute the redox-active center. The Cys-100/Cys-105 disulfide bond may accept electron from PDI1 and funnel them to the active site disulfide Cys-352/Cys-355. N-glycosylated. Ref.4 Ref.5
Sequence similarities	Belongs to the EROs family.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Endoplasmic reticulum Membrane
Domain	Redox-active center Signal
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.5. Source: SGD endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor Inferred from electronic annotation. Source: InterPro protein disulfide isomerase activity Inferred from mutant phenotype Ref.8. Source: SGD thiol oxidase activity Inferred from direct assay PubMed 16407158. Source: SGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PDIA3	P30101	1	EBI-27991,EBI-979862	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 563

545

Endoplasmic oxidoreductin-1

PRO_0000008429

Sites

Active site

352

1

Nucleophile

Active site

355

1

Binding site

187

1

FAD

Binding site

189

1

FAD

Binding site

200

1

FAD

Binding site

228

1

FAD

Binding site

231

1

FAD

Binding site

260

1

FAD

Amino acid modifications

Glycosylation

21

1

N-linked (GlcNAc...) Potential

Glycosylation

35

1

N-linked (GlcNAc...) Potential

Glycosylation

53

1

N-linked (GlcNAc...) Potential

Glycosylation

130

1

N-linked (GlcNAc...) Potential

Glycosylation

342

1

N-linked (GlcNAc...) Potential

Glycosylation

425

1

N-linked (GlcNAc...) Potential

Glycosylation

458

1

N-linked (GlcNAc...) Potential

Glycosylation

468

1

N-linked (GlcNAc...) Potential

Glycosylation

491

1

N-linked (GlcNAc...) Potential

Disulfide bond

90 ↔ 349

Ref.12 Ref.13

Disulfide bond

100 ↔ 105

Redox-active Ref.12 Ref.13

Disulfide bond

143 ↔ 166

Ref.12 Ref.13

Disulfide bond

150 ↔ 295

Ref.12 Ref.13

Disulfide bond

352 ↔ 355

Redox-active Ref.12 Ref.13

Experimental info

Mutagenesis

90

1

C → A: No effect. Ref.8 Ref.12

Mutagenesis

100

1

C → A: Impairs the capture of mixed-disulfide with PDI1 thereby blocking its function. Loss of activity; when associated with A-105. Ref.8 Ref.12

Mutagenesis

105

1

C → A: Loss of activity. Ref.8 Ref.12

Mutagenesis

143

1

C → A: No effect; when associated with A-166. Ref.12

Mutagenesis

150

1

C → A: Loss of regulatory disulfide bond and strongly increased activity towards PDI; when associated with A-295. Ref.12

Mutagenesis

166

1

C → A: No effect; when associated with A-143. Ref.12

Mutagenesis

208

1

C → A: No effect. Ref.8

Mutagenesis

229

1

G → S in ERO1-1; induces defective folding of disulfide proteins. Ref.13

Mutagenesis

231

1

H → Y in ERO1-2; induces defective folding of disulfide proteins. Ref.5

Mutagenesis

295

1

C → A: Loss of regulatory disulfide bond and strongly increased activity towards PDI; when associated with A-150. Ref.12

Mutagenesis

349

1

C → A: Does not affect activity but increases by twofold the amount of protein found in mixed disulfide with PDI1 or MPD2. Ref.8

Mutagenesis

352

1

C → A: Loss of activity. Prevents its reoxidation thereby blocking its function. Ref.8 Ref.12

Mutagenesis

355

1

C → A: Loss of activity. Prevents its reoxidation thereby blocking its function. Ref.8 Ref.12

Sequence conflict

555

1

P → L in AAT93069. Ref.3

Secondary structure

1

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563

Helix Strand Turn

Details...

Helix

56 – 73

18

Turn

77 – 79

3

Beta strand

80 – 86

7

Beta strand

91 – 93

3

Beta strand

95 – 98

4

Turn

102 – 105

4

Beta strand

109 – 111

3

Helix

113 – 115

3

Helix

118 – 120

3

Helix

122 – 125

4

Turn

130 – 132

3

Beta strand

133 – 135

3

Beta strand

137 – 139

3

Helix

141 – 143

3

Helix

146 – 149

4

Turn

152 – 154

3

Beta strand

159 – 161

3

Helix

165 – 168

4

Beta strand

176 – 180

5

Turn

181 – 183

3

Helix

193 – 205

13

Helix

216 – 240

25

Beta strand

241 – 243

3

Turn

245 – 247

3

Helix

254 – 260

7

Turn

261 – 263

3

Helix

265 – 285

21

Helix

286 – 288

3

Helix

297 – 311

15

Helix

316 – 319

4

Turn

325 – 327

3

Helix

330 – 346

17

Helix

347 – 349

3

Helix

353 – 376

24

Helix

381 – 389

9

Helix

393 – 424

32

Sequences

	Sequence		Length	Mass (Da)
	Q03103 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 928CE700AE6137EF	FASTA	563	65,033
	10 20 30 40 50 60 MRLRTAIATL CLTAFTSATS NNSYIATDQT QNAFNDTHFC KVDRNDHVSP SCNVTFNELN 70 80 90 100 110 120 AINENIRDDL SALLKSDFFK YFRLDLYKQC SFWDANDGLC LNRACSVDVV EDWDTLPEYW 130 140 150 160 170 180 QPEILGSFNN DTMKEADDSD DECKFLDQLC QTSKKPVDIE DTINYCDVND FNGKNAVLID 190 200 210 220 230 240 LTANPERFTG YGGKQAGQIW STIYQDNCFT IGETGESLAK DAFYRLVSGF HASIGTHLSK 250 260 270 280 290 300 EYLNTKTGKW EPNLDLFMAR IGNFPDRVTN MYFNYAVVAK ALWKIQPYLP EFSFCDLVNK 310 320 330 340 350 360 EIKNKMDNVI SQLDTKIFNE DLVFANDLSL TLKDEFRSRF KNVTKIMDCV QCDRCRLWGK 370 380 390 400 410 420 IQTTGYATAL KILFEINDAD EFTKQHIVGK LTKYELIALL QTFGRLSESI ESVNMFEKMY 430 440 450 460 470 480 GKRLNGSENR LSSFFQNNFF NILKEAGKSI RYTIENINST KEGKKKTNNS QSHVFDDLKM 490 500 510 520 530 540 PKAEIVPRPS NGTVNKWKKA WNTEVNNVLE AFRFIYRSYL DLPRNIWELS LMKVYKFWNK 550 560 FIGVADYVSE ETREPISYKL DIQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII." Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T., Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K., Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P. , Skelton J., Walsh S.V., Whitehead S., Barrell B.G. Nature 387:90-93(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[2]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[3]	"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.
[4]	"The ERO1 gene of yeast is required for oxidation of protein dithiols in the endoplasmic reticulum." Frand A.R., Kaiser C.A. Mol. Cell 1:161-170(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, INDUCTION.
[5]	"Ero1p: a novel and ubiquitous protein with an essential role in oxidative protein folding in the endoplasmic reticulum." Pollard M.G., Travers K.J., Weissman J.S. Mol. Cell 1:171-182(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, INDUCTION, MUTAGENESIS OF HIS-231.
[6]	"Ero1p oxidizes protein disulfide isomerase in a pathway for disulfide bond formation in the endoplasmic reticulum." Frand A.R., Kaiser C.A. Mol. Cell 4:469-477(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, DIRECT OXIDATION OF PDI1 AND MPD2.
[7]	"Biochemical basis of oxidative protein folding in the endoplasmic reticulum." Tu B.P., Ho-Schleyer S.C., Travers K.J., Weissman J.S. Science 290:1571-1574(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, COFACTOR.
[8]	"Two pairs of conserved cysteines are required for the oxidative activity of Ero1p in protein disulfide bond formation in the endoplasmic reticulum." Frand A.R., Kaiser C.A. Mol. Biol. Cell 11:2833-2843(2000) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF CYS-90; CYS-100; CYS-105; CYS-208; CYS-349; CYS-352 AND CYS-355.
[9]	"The C-terminal domain of yeast Ero1p mediates membrane localization and is essential for function." Pagani M., Pilati S., Bertoli G., Valsasina B., Sitia R. FEBS Lett. 508:117-120(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, DOMAIN.
[10]	"The FAD- and O(2)-dependent reaction cycle of Ero1-mediated oxidative protein folding in the endoplasmic reticulum." Tu B.P., Weissman J.S. Mol. Cell 10:983-994(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Oxidative protein folding in eukaryotes: mechanisms and consequences." Tu B.P., Weissman J.S. J. Cell Biol. 164:341-346(2004) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[12]	"Modulation of cellular disulfide-bond formation and the ER redox environment by feedback regulation of Ero1." Sevier C.S., Qu H., Heldman N., Gross E., Fass D., Kaiser C.A. Cell 129:333-344(2007) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION, DISULFIDE BONDS, MUTAGENESIS OF CYS-90; CYS-100; CYS-105; CYS-143; CYS-150; CYS-166; CYS-295; CYS-352 AND CYS-355.
[13]	"Structure of Ero1p, source of disulfide bonds for oxidative protein folding in the cell." Gross E., Kastner D.B., Kaiser C.A., Fass D. Cell 117:601-610(2004) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 56-424 IN COMPLEX WITH FAD, POTENTIAL HOMODIMERIZATION, DISULFIDE BONDS, MUTAGENESIS OF GLY-229.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

Z50178 Genomic DNA. Translation: CAA90553.1.
AY693050 Genomic DNA. Translation: AAT93069.1.
BK006946 Genomic DNA. Translation: DAA09769.1.

PIR

S58198.

RefSeq

NP_013576.1. NM_001182493.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1RP4	X-ray	2.20	A	56-424	[»]
1RQ1	X-ray	2.80	A	56-424	[»]
3M31	X-ray	1.85	A	56-424	[»]
3NVJ	X-ray	3.20	A	56-424	[»]

ProteinModelPortal

Q03103.

SMR

Q03103. Positions 55-424.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-4515N.

IntAct

Q03103. 11 interactions.

MINT

MINT-503775.

STRING

4932.YML130C.

Proteomic databases

PaxDb

Q03103.

PeptideAtlas

Q03103.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YML130C; YML130C; YML130C.

GeneID

854909.

KEGG

sce:YML130C.

Organism-specific databases

CYGD

YML130c.

SGD

S000004599. ERO1.

Phylogenomic databases

eggNOG

COG5061.

GeneTree

ENSGT00390000007753.

HOGENOM

HOG000158050.

OMA

YEENCFG.

OrthoDB

EOG4K6KD7.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-16234.

Gene expression databases

Genevestigator

Q03103.

GermOnline

YML130C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR007266. ER_oxidoreductin-1.
[Graphical view]

PANTHER

PTHR12613. PTHR12613. 1 hit.

Pfam

PF04137. ERO1. 1 hit.
[Graphical view]

PIRSF

PIRSF017205. ERO1. 1 hit.

SUPFAM

SSF110019. ERO1. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q03103.

NextBio

977902.

Entry information

Entry name

ERO1_YEAST

Accession

Primary (citable) accession number: Q03103
Secondary accession number(s): D6W0F5, E9P913

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program