ERO1_YEAST
ID ERO1_YEAST Reviewed; 563 AA.
AC Q03103; D6W0F5; E9P913;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Endoplasmic oxidoreductin-1;
DE EC=1.8.4.-;
DE AltName: Full=Endoplasmic reticulum oxidoreductase protein 1;
DE Flags: Precursor;
GN Name=ERO1; OrderedLocusNames=YML130C; ORFNames=YM4987.05C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169872;
RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL Nature 387:90-93(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, AND INDUCTION.
RX PubMed=9659913; DOI=10.1016/s1097-2765(00)80017-9;
RA Frand A.R., Kaiser C.A.;
RT "The ERO1 gene of yeast is required for oxidation of protein dithiols in
RT the endoplasmic reticulum.";
RL Mol. Cell 1:161-170(1998).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, INDUCTION, AND MUTAGENESIS
RP OF HIS-231.
RX PubMed=9659914; DOI=10.1016/s1097-2765(00)80018-0;
RA Pollard M.G., Travers K.J., Weissman J.S.;
RT "Ero1p: a novel and ubiquitous protein with an essential role in oxidative
RT protein folding in the endoplasmic reticulum.";
RL Mol. Cell 1:171-182(1998).
RN [6]
RP FUNCTION.
RX PubMed=10549279; DOI=10.1016/s1097-2765(00)80198-7;
RA Frand A.R., Kaiser C.A.;
RT "Ero1p oxidizes protein disulfide isomerase in a pathway for disulfide bond
RT formation in the endoplasmic reticulum.";
RL Mol. Cell 4:469-477(1999).
RN [7]
RP FUNCTION, AND COFACTOR.
RX PubMed=11090354; DOI=10.1126/science.290.5496.1571;
RA Tu B.P., Ho-Schleyer S.C., Travers K.J., Weissman J.S.;
RT "Biochemical basis of oxidative protein folding in the endoplasmic
RT reticulum.";
RL Science 290:1571-1574(2000).
RN [8]
RP MUTAGENESIS OF CYS-90; CYS-100; CYS-105; CYS-208; CYS-349; CYS-352 AND
RP CYS-355.
RX PubMed=10982384; DOI=10.1091/mbc.11.9.2833;
RA Frand A.R., Kaiser C.A.;
RT "Two pairs of conserved cysteines are required for the oxidative activity
RT of Ero1p in protein disulfide bond formation in the endoplasmic
RT reticulum.";
RL Mol. Biol. Cell 11:2833-2843(2000).
RN [9]
RP SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=11707280; DOI=10.1016/s0014-5793(01)03034-4;
RA Pagani M., Pilati S., Bertoli G., Valsasina B., Sitia R.;
RT "The C-terminal domain of yeast Ero1p mediates membrane localization and is
RT essential for function.";
RL FEBS Lett. 508:117-120(2001).
RN [10]
RP FUNCTION.
RX PubMed=12453408; DOI=10.1016/s1097-2765(02)00696-2;
RA Tu B.P., Weissman J.S.;
RT "The FAD- and O(2)-dependent reaction cycle of Ero1-mediated oxidative
RT protein folding in the endoplasmic reticulum.";
RL Mol. Cell 10:983-994(2002).
RN [11]
RP REVIEW.
RX PubMed=14757749; DOI=10.1083/jcb.200311055;
RA Tu B.P., Weissman J.S.;
RT "Oxidative protein folding in eukaryotes: mechanisms and consequences.";
RL J. Cell Biol. 164:341-346(2004).
RN [12]
RP ACTIVITY REGULATION, DISULFIDE BONDS, AND MUTAGENESIS OF CYS-90; CYS-100;
RP CYS-105; CYS-143; CYS-150; CYS-166; CYS-295; CYS-352 AND CYS-355.
RX PubMed=17448992; DOI=10.1016/j.cell.2007.02.039;
RA Sevier C.S., Qu H., Heldman N., Gross E., Fass D., Kaiser C.A.;
RT "Modulation of cellular disulfide-bond formation and the ER redox
RT environment by feedback regulation of Ero1.";
RL Cell 129:333-344(2007).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 56-424 IN COMPLEX WITH FAD,
RP POTENTIAL HOMODIMERIZATION, DISULFIDE BONDS, MUTAGENESIS OF GLY-229, AND
RP ACTIVE SITE.
RX PubMed=15163408; DOI=10.1016/s0092-8674(04)00418-0;
RA Gross E., Kastner D.B., Kaiser C.A., Fass D.;
RT "Structure of Ero1p, source of disulfide bonds for oxidative protein
RT folding in the cell.";
RL Cell 117:601-610(2004).
CC -!- FUNCTION: Essential oxidoreductase that oxidizes proteins in the
CC endoplasmic reticulum to produce disulfide bonds. Acts by oxidizing
CC directly PDI1 isomerase through a direct disulfide exchange. Does not
CC act as a direct oxidant of folding substrate, but relies on PDI1 to
CC transfer oxidizing equivalent. Also able to oxidize directly the PDI
CC related protein MPD2. Does not oxidize all PDI related proteins,
CC suggesting that it can discriminate between PDI1 and related proteins.
CC Reoxidation of ERO1 probably involves electron transfer to molecular
CC oxygen via FAD. Acts independently of glutathione. May be responsible
CC for a significant proportion of reactive oxygen species (ROS) in the
CC cell, thereby being a source of oxidative stress.
CC {ECO:0000269|PubMed:10549279, ECO:0000269|PubMed:11090354,
CC ECO:0000269|PubMed:12453408, ECO:0000269|PubMed:9659913,
CC ECO:0000269|PubMed:9659914}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:11090354};
CC -!- ACTIVITY REGULATION: Enzyme activity is tightly regulated to prevent
CC the accumulation of reactive oxygen species in the endoplasmic
CC reticulum. Reversibly down-regulated by the formation of disulfide
CC bonds between Cys-150 and Cys-295. {ECO:0000269|PubMed:17448992}.
CC -!- SUBUNIT: May function both as a monomer and a homodimer.
CC {ECO:0000269|PubMed:15163408}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11707280, ECO:0000269|PubMed:9659913,
CC ECO:0000269|PubMed:9659914}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11707280, ECO:0000269|PubMed:9659913,
CC ECO:0000269|PubMed:9659914}; Lumenal side {ECO:0000269|PubMed:11707280,
CC ECO:0000269|PubMed:9659913, ECO:0000269|PubMed:9659914}.
CC -!- INDUCTION: By unfolded protein response (UPR).
CC {ECO:0000269|PubMed:9659913, ECO:0000269|PubMed:9659914}.
CC -!- DOMAIN: The C-terminal part (437-563) is required for the association
CC with the endoplasmic reticulum lumen membrane.
CC {ECO:0000269|PubMed:11707280}.
CC -!- PTM: The Cys-100/Cys-105 and Cys-352/Cys-355 disulfide bonds constitute
CC the redox-active center. The Cys-100/Cys-105 disulfide bond may accept
CC electron from PDI1 and funnel them to the active site disulfide Cys-
CC 352/Cys-355.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9659913,
CC ECO:0000269|PubMed:9659914}.
CC -!- SIMILARITY: Belongs to the EROs family. {ECO:0000305}.
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DR EMBL; Z50178; CAA90553.1; -; Genomic_DNA.
DR EMBL; AY693050; AAT93069.1; -; Genomic_DNA.
DR EMBL; BK006946; DAA09769.1; -; Genomic_DNA.
DR PIR; S58198; S58198.
DR RefSeq; NP_013576.1; NM_001182493.1.
DR PDB; 1RP4; X-ray; 2.20 A; A=56-424.
DR PDB; 1RQ1; X-ray; 2.80 A; A=56-424.
DR PDB; 3M31; X-ray; 1.85 A; A=56-424.
DR PDB; 3NVJ; X-ray; 3.20 A; A=56-424.
DR PDBsum; 1RP4; -.
DR PDBsum; 1RQ1; -.
DR PDBsum; 3M31; -.
DR PDBsum; 3NVJ; -.
DR AlphaFoldDB; Q03103; -.
DR SMR; Q03103; -.
DR BioGRID; 35075; 356.
DR DIP; DIP-4515N; -.
DR IntAct; Q03103; 11.
DR STRING; 4932.YML130C; -.
DR MaxQB; Q03103; -.
DR PaxDb; Q03103; -.
DR PRIDE; Q03103; -.
DR EnsemblFungi; YML130C_mRNA; YML130C; YML130C.
DR GeneID; 854909; -.
DR KEGG; sce:YML130C; -.
DR SGD; S000004599; ERO1.
DR VEuPathDB; FungiDB:YML130C; -.
DR eggNOG; KOG2608; Eukaryota.
DR GeneTree; ENSGT00390000007753; -.
DR HOGENOM; CLU_023061_1_0_1; -.
DR InParanoid; Q03103; -.
DR OMA; RDYCVPD; -.
DR BioCyc; MetaCyc:G3O-32708-MON; -.
DR BioCyc; YEAST:G3O-32708-MON; -.
DR EvolutionaryTrace; Q03103; -.
DR PRO; PR:Q03103; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; Q03103; protein.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:SGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IBA:GO_Central.
DR GO; GO:0016972; F:thiol oxidase activity; IDA:SGD.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; IMP:SGD.
DR InterPro; IPR007266; Ero1.
DR InterPro; IPR037192; ERO1-like_sf.
DR PANTHER; PTHR12613; PTHR12613; 1.
DR Pfam; PF04137; ERO1; 1.
DR PIRSF; PIRSF017205; ERO1; 1.
DR SUPFAM; SSF110019; SSF110019; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Electron transport; Endoplasmic reticulum;
KW FAD; Flavoprotein; Glycoprotein; Membrane; Oxidoreductase;
KW Redox-active center; Reference proteome; Signal; Transport.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..563
FT /note="Endoplasmic oxidoreductin-1"
FT /id="PRO_0000008429"
FT ACT_SITE 352
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:15163408"
FT ACT_SITE 355
FT /evidence="ECO:0000269|PubMed:15163408"
FT BINDING 187
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15163408"
FT BINDING 189
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15163408"
FT BINDING 200
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15163408"
FT BINDING 228
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15163408"
FT BINDING 231
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15163408"
FT BINDING 260
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:15163408"
FT CARBOHYD 21
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 35
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 53
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 342
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 425
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 458
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 468
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 90..349
FT /evidence="ECO:0000269|PubMed:15163408,
FT ECO:0007744|PDB:1RP4, ECO:0007744|PDB:1RQ1"
FT DISULFID 100..105
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:15163408,
FT ECO:0007744|PDB:1RP4, ECO:0007744|PDB:1RQ1"
FT DISULFID 143..166
FT /evidence="ECO:0000269|PubMed:15163408,
FT ECO:0007744|PDB:1RP4, ECO:0007744|PDB:1RQ1"
FT DISULFID 150..295
FT /evidence="ECO:0000269|PubMed:15163408,
FT ECO:0007744|PDB:1RP4, ECO:0007744|PDB:1RQ1"
FT DISULFID 352..355
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:15163408,
FT ECO:0007744|PDB:1RP4, ECO:0007744|PDB:1RQ1"
FT MUTAGEN 90
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:10982384,
FT ECO:0000269|PubMed:17448992"
FT MUTAGEN 100
FT /note="C->A: Impairs the capture of mixed-disulfide with
FT PDI1 thereby blocking its function. Loss of activity; when
FT associated with A-105."
FT /evidence="ECO:0000269|PubMed:10982384,
FT ECO:0000269|PubMed:17448992"
FT MUTAGEN 105
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:10982384,
FT ECO:0000269|PubMed:17448992"
FT MUTAGEN 143
FT /note="C->A: No effect; when associated with A-166."
FT /evidence="ECO:0000269|PubMed:17448992"
FT MUTAGEN 150
FT /note="C->A: Loss of regulatory disulfide bond and strongly
FT increased activity towards PDI; when associated with A-
FT 295."
FT /evidence="ECO:0000269|PubMed:17448992"
FT MUTAGEN 166
FT /note="C->A: No effect; when associated with A-143."
FT /evidence="ECO:0000269|PubMed:17448992"
FT MUTAGEN 208
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:10982384"
FT MUTAGEN 229
FT /note="G->S: In ERO1-1; induces defective folding of
FT disulfide proteins."
FT /evidence="ECO:0000269|PubMed:15163408"
FT MUTAGEN 231
FT /note="H->Y: In ERO1-2; induces defective folding of
FT disulfide proteins."
FT /evidence="ECO:0000269|PubMed:9659914"
FT MUTAGEN 295
FT /note="C->A: Loss of regulatory disulfide bond and strongly
FT increased activity towards PDI; when associated with A-
FT 150."
FT /evidence="ECO:0000269|PubMed:17448992"
FT MUTAGEN 349
FT /note="C->A: Does not affect activity but increases by
FT twofold the amount of protein found in mixed disulfide with
FT PDI1 or MPD2."
FT /evidence="ECO:0000269|PubMed:10982384"
FT MUTAGEN 352
FT /note="C->A: Loss of activity. Prevents its reoxidation
FT thereby blocking its function."
FT /evidence="ECO:0000269|PubMed:10982384,
FT ECO:0000269|PubMed:17448992"
FT MUTAGEN 355
FT /note="C->A: Loss of activity. Prevents its reoxidation
FT thereby blocking its function."
FT /evidence="ECO:0000269|PubMed:10982384,
FT ECO:0000269|PubMed:17448992"
FT CONFLICT 555
FT /note="P -> L (in Ref. 3; AAT93069)"
FT /evidence="ECO:0000305"
FT HELIX 56..73
FT /evidence="ECO:0007829|PDB:3M31"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:3M31"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:3M31"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:3M31"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:1RP4"
FT TURN 102..105
FT /evidence="ECO:0007829|PDB:3M31"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:3NVJ"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:1RP4"
FT HELIX 118..120
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 122..125
FT /evidence="ECO:0007829|PDB:3M31"
FT TURN 130..132
FT /evidence="ECO:0007829|PDB:3M31"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:1RQ1"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:1RQ1"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:3M31"
FT TURN 152..154
FT /evidence="ECO:0007829|PDB:1RP4"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:1RP4"
FT HELIX 165..168
FT /evidence="ECO:0007829|PDB:3M31"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:3M31"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 193..205
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 216..240
FT /evidence="ECO:0007829|PDB:3M31"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:3M31"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 254..260
FT /evidence="ECO:0007829|PDB:3M31"
FT TURN 261..263
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 265..285
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 286..288
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 297..311
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 316..319
FT /evidence="ECO:0007829|PDB:3M31"
FT TURN 325..327
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 330..346
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 347..349
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 353..376
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 381..389
FT /evidence="ECO:0007829|PDB:3M31"
FT HELIX 393..424
FT /evidence="ECO:0007829|PDB:3M31"
SQ SEQUENCE 563 AA; 65033 MW; 928CE700AE6137EF CRC64;
MRLRTAIATL CLTAFTSATS NNSYIATDQT QNAFNDTHFC KVDRNDHVSP SCNVTFNELN
AINENIRDDL SALLKSDFFK YFRLDLYKQC SFWDANDGLC LNRACSVDVV EDWDTLPEYW
QPEILGSFNN DTMKEADDSD DECKFLDQLC QTSKKPVDIE DTINYCDVND FNGKNAVLID
LTANPERFTG YGGKQAGQIW STIYQDNCFT IGETGESLAK DAFYRLVSGF HASIGTHLSK
EYLNTKTGKW EPNLDLFMAR IGNFPDRVTN MYFNYAVVAK ALWKIQPYLP EFSFCDLVNK
EIKNKMDNVI SQLDTKIFNE DLVFANDLSL TLKDEFRSRF KNVTKIMDCV QCDRCRLWGK
IQTTGYATAL KILFEINDAD EFTKQHIVGK LTKYELIALL QTFGRLSESI ESVNMFEKMY
GKRLNGSENR LSSFFQNNFF NILKEAGKSI RYTIENINST KEGKKKTNNS QSHVFDDLKM
PKAEIVPRPS NGTVNKWKKA WNTEVNNVLE AFRFIYRSYL DLPRNIWELS LMKVYKFWNK
FIGVADYVSE ETREPISYKL DIQ
