ERO1A_RAT
ID ERO1A_RAT Reviewed; 464 AA.
AC Q8R4A1; Q8VH29; Q8VH30;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=ERO1-like protein alpha;
DE Short=ERO1-L;
DE Short=ERO1-L-alpha;
DE EC=1.8.4.- {ECO:0000250|UniProtKB:Q96HE7};
DE AltName: Full=Endoplasmic reticulum oxidoreductase alpha {ECO:0000312|RGD:621713};
DE AltName: Full=Endoplasmic reticulum oxidoreductin-1-like protein;
DE AltName: Full=Global ischemia-induced protein 11;
DE AltName: Full=Oxidoreductin-1-L-alpha;
DE Flags: Precursor;
GN Name=Ero1a {ECO:0000312|RGD:621713}; Synonyms=Ero1l, Giig11;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), SUBCELLULAR LOCATION, AND
RP INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=12694393; DOI=10.1046/j.1471-4159.2003.01699.x;
RA Chen D., Jin K., Kawaguchi K., Nakayama M., Zhou X., Xiong Z., Zhou A.,
RA Mao X.O., Greenberg D.A., Graham S.H., Simon R.P.;
RT "Ero1-L, an ischemia-inducible gene from rat brain with homology to global
RT ischemia-induced gene 11 (Giig11), is localized to neuronal dendrites by a
RT dispersed identifier (ID) element-dependent mechanism.";
RL J. Neurochem. 85:670-679(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Thyroid;
RA Li B., Abplanalp W.A., Kim P.S.;
RT "Cloning of the two forms of Ero1, alpha and beta and their regulation in
RT cultured thyrocytes.";
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND INDUCTION.
RX PubMed=12752442; DOI=10.1046/j.1432-1033.2003.03590.x;
RA Gess B., Hofbauer K.H., Wenger R.H., Lohaus C., Meyer H.E., Kurtz A.;
RT "The cellular oxygen tension regulates expression of the endoplasmic
RT oxidoreductase ERO1-Lalpha.";
RL Eur. J. Biochem. 270:2228-2235(2003).
RN [4]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-276, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24090084; DOI=10.1021/pr400783j;
RA Parker B.L., Thaysen-Andersen M., Solis N., Scott N.E., Larsen M.R.,
RA Graham M.E., Packer N.H., Cordwell S.J.;
RT "Site-specific glycan-peptide analysis for determination of N-glycoproteome
RT heterogeneity.";
RL J. Proteome Res. 12:5791-5800(2013).
CC -!- FUNCTION: Oxidoreductase involved in disulfide bond formation in the
CC endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme
CC catalyzing protein disulfide formation, in order to allow P4HB to
CC sustain additional rounds of disulfide formation. Following P4HB
CC reoxidation, passes its electrons to molecular oxygen via FAD, leading
CC to the production of reactive oxygen species (ROS) in the cell.
CC Required for the proper folding of immunoglobulins. Plays an important
CC role in ER stress-induced, CHOP-dependent apoptosis by activating the
CC inositol 1,4,5-trisphosphate receptor IP3R1.
CC {ECO:0000250|UniProtKB:Q96HE7}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000250|UniProtKB:Q96HE7};
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 the active site Cys-94 and Cys-130, and between Cys-99
CC and Cys-104. Glutathione may be required to regulate its activity in
CC the endoplasmic reticulum (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Predominantly monomer. May function both as a monomer and a
CC homodimer. Interacts with PDILT. Interacts with ERP44; the interaction
CC results in retention of ERO1A in the endoplasmic reticulum.
CC {ECO:0000250|UniProtKB:Q96HE7}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q96HE7}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q96HE7}; Lumenal side
CC {ECO:0000250|UniProtKB:Q96HE7}. Golgi apparatus lumen
CC {ECO:0000250|UniProtKB:Q96HE7}. Secreted
CC {ECO:0000250|UniProtKB:Q96HE7}. Cell projection, dendrite
CC {ECO:0000269|PubMed:12694393}. Note=The association with ERP44 is
CC essential for its retention in the endoplasmic reticulum (By
CC similarity). In neurons, it localizes to dendrites (PubMed:12694393).
CC {ECO:0000250|UniProtKB:Q96HE7, ECO:0000269|PubMed:12694393}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8R4A1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R4A1-2; Sequence=VSP_011023;
CC -!- INDUCTION: Stimulated by hypoxia; suggesting that it is regulated via
CC the HIF-pathway. Increased expression in brain after global cerebral
CC ischemia. {ECO:0000269|PubMed:12694393, ECO:0000269|PubMed:12752442}.
CC -!- PTM: N-glycosylated.
CC -!- PTM: The Cys-94/Cys-99 and Cys-390/Cys-393 disulfide bonds constitute
CC the redox-active center. The Cys-94/Cys-99 disulfide bond may accept
CC electron from P4HB and funnel them to the active site disulfide Cys-
CC 390/Cys-393. The regulatory Cys-99/Cys-104 disulfide bond stabilizes
CC the other regulatory bond Cys-94/Cys-130 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated on Ser-144 by FAM20C in the Golgi which increases
CC its enzymatic activity (By similarity). Phosphorylation is induced by
CC lactation (By similarity). It is also induced by hypoxia and reductive
CC stress (By similarity). {ECO:0000250|UniProtKB:Q8R180,
CC ECO:0000250|UniProtKB:Q96HE7}.
CC -!- SIMILARITY: Belongs to the EROs family. {ECO:0000305}.
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DR EMBL; AY071924; AAL61547.1; -; mRNA.
DR EMBL; AY071925; AAL61548.1; -; mRNA.
DR EMBL; AF489855; AAL96669.1; -; mRNA.
DR RefSeq; NP_612537.1; NM_138528.1.
DR AlphaFoldDB; Q8R4A1; -.
DR SMR; Q8R4A1; -.
DR IntAct; Q8R4A1; 2.
DR STRING; 10116.ENSRNOP00000009404; -.
DR GlyGen; Q8R4A1; 2 sites, 6 N-linked glycans (1 site).
DR iPTMnet; Q8R4A1; -.
DR PhosphoSitePlus; Q8R4A1; -.
DR jPOST; Q8R4A1; -.
DR PaxDb; Q8R4A1; -.
DR PRIDE; Q8R4A1; -.
DR Ensembl; ENSRNOT00000116811; ENSRNOP00000094430; ENSRNOG00000006462. [Q8R4A1-1]
DR GeneID; 171562; -.
DR KEGG; rno:171562; -.
DR UCSC; RGD:621713; rat. [Q8R4A1-1]
DR CTD; 30001; -.
DR RGD; 621713; Ero1a.
DR eggNOG; KOG2608; Eukaryota.
DR GeneTree; ENSGT00390000007753; -.
DR HOGENOM; CLU_023061_2_2_1; -.
DR InParanoid; Q8R4A1; -.
DR OMA; PDAWRIW; -.
DR OrthoDB; 1181226at2759; -.
DR PhylomeDB; Q8R4A1; -.
DR TreeFam; TF314471; -.
DR Reactome; R-RNO-264876; Insulin processing.
DR Reactome; R-RNO-3299685; Detoxification of Reactive Oxygen Species.
DR PRO; PR:Q8R4A1; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000006462; Expressed in stomach and 19 other tissues.
DR Genevisible; Q8R4A1; RN.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; ISS:UniProtKB.
DR GO; GO:0015035; F:protein-disulfide reductase activity; ISO:RGD.
DR GO; GO:0016972; F:thiol oxidase activity; IEA:InterPro.
DR GO; GO:0050873; P:brown fat cell differentiation; ISO:RGD.
DR GO; GO:0045454; P:cell redox homeostasis; ISS:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; ISO:RGD.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; ISO:RGD.
DR GO; GO:0030198; P:extracellular matrix organization; ISO:RGD.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; ISO:RGD.
DR GO; GO:0006457; P:protein folding; ISS:UniProtKB.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0022417; P:protein maturation by protein folding; ISO:RGD.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
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 Alternative splicing; Apoptosis; Cell projection; Disulfide bond;
KW Electron transport; Endoplasmic reticulum; FAD; Flavoprotein; Glycoprotein;
KW Golgi apparatus; Membrane; Oxidoreductase; Phosphoprotein;
KW Redox-active center; Reference proteome; Secreted; Signal; Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..464
FT /note="ERO1-like protein alpha"
FT /id="PRO_0000008417"
FT BINDING 186
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT BINDING 188
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT BINDING 199
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT BINDING 248
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT BINDING 251
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT BINDING 283
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT BINDING 296
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT MOD_RES 144
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0007744|PubMed:24090084"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..48
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT DISULFID 37..46
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT DISULFID 85..387
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT DISULFID 94..130
FT /note="Alternate; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT DISULFID 94..99
FT /note="Redox-active; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT DISULFID 99..104
FT /note="Alternate"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT DISULFID 207..237
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT DISULFID 390..393
FT /note="Redox-active"
FT /evidence="ECO:0000250|UniProtKB:Q96HE7"
FT VAR_SEQ 15..122
FT /note="VWLLRSGQGEEQQQETAAQRCFCQVSGYLDDCTCDVETIDKFNNYRLFPRLQ
FT KLLESDYFRYYKVNLRKPCPFWNDINQCGRRDCAVKPCHSDEVPDGIKSASYKYSK ->
FT FQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12694393"
FT /id="VSP_011023"
FT CONFLICT 4
FT /note="G -> A (in Ref. 1; AAL61547/AAL61548)"
FT /evidence="ECO:0000305"
FT CONFLICT 20..22
FT /note="SGQ -> LGH (in Ref. 1; AAL61547)"
FT /evidence="ECO:0000305"
FT CONFLICT 26..28
FT /note="QQQ -> RRP (in Ref. 1; AAL61547)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="N -> H (in Ref. 1; AAL61547/AAL61548)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 54018 MW; 1B71741A9C413772 CRC64;
MGRGWGLLVG LLGVVWLLRS GQGEEQQQET AAQRCFCQVS GYLDDCTCDV ETIDKFNNYR
LFPRLQKLLE SDYFRYYKVN LRKPCPFWND INQCGRRDCA VKPCHSDEVP DGIKSASYKY
SKEANLLEEC EQAERLGAVD ESLSEETQKA VLQWTKHDDS SDSFCEVDDI QSPDAEYVDL
LLNPERYTGY KGPDAWRIWS VIYEENCFKP QTIQRPLASG QGKHKENTFY SWLEGLCVEK
RAFYRLISGL HASINVHLSA RYLLQDNWLE KKWGHNVTEF QQRFDGVLTE GEGPRRLKNL
YFLYLIELRA LSKVLPFFER PDFQLFTGNK VQDVENKELL LEILHEVKSF PLHFDENSFF
AGDKNEAHKL KEDFRLHFRN ISRIMDCVGC FKCRLWGKLQ TQGLGTALKI LFSEKLIANM
PESGPSYEFQ LTRQEIVSLF NAFGRISTSV RELENFRHLL QNVH
