ERO1A_MOUSE
ID ERO1A_MOUSE Reviewed; 464 AA.
AC Q8R180; Q9CV47; Q9QY03;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAR-2009, sequence version 2.
DT 03-AUG-2022, entry version 156.
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:0000250|UniProtKB:Q96HE7};
DE AltName: Full=Endoplasmic reticulum oxidoreductin-1-like protein;
DE AltName: Full=Oxidoreductin-1-L-alpha;
DE Flags: Precursor;
GN Name=Ero1a {ECO:0000250|UniProtKB:Q96HE7}; Synonyms=Ero1l;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10671517; DOI=10.1074/jbc.275.7.4827;
RA Cabibbo A., Pagani M., Fabbri M., Rocchi M., Farmery M.R., Bulleid N.J.,
RA Sitia R.;
RT "ERO1-L, a human protein that favors disulfide bond formation in the
RT endoplasmic reticulum.";
RL J. Biol. Chem. 275:4827-4833(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 232-464.
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP 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 [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=19752026; DOI=10.1083/jcb.200904060;
RA Li G., Mongillo M., Chin K.T., Harding H., Ron D., Marks A.R., Tabas I.;
RT "Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate
RT receptor activity in endoplasmic reticulum stress-induced apoptosis.";
RL J. Cell Biol. 186:783-792(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=20308425; DOI=10.1083/jcb.200911086;
RA Zito E., Chin K.T., Blais J., Harding H.P., Ron D.;
RT "ERO1-beta, a pancreas-specific disulfide oxidase, promotes insulin
RT biogenesis and glucose homeostasis.";
RL J. Cell Biol. 188:821-832(2010).
RN [8]
RP TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=29858230; DOI=10.15252/embj.201798699;
RA Zhang J., Zhu Q., Wang X., Yu J., Chen X., Wang J., Wang X., Xiao J.,
RA Wang C.C., Wang L.;
RT "Secretory kinase Fam20C tunes endoplasmic reticulum redox state via
RT phosphorylation of Ero1alpha.";
RL EMBO J. 37:0-0(2018).
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 (By similarity).
CC Plays an important role in ER stress-induced, CHOP-dependent apoptosis
CC by activating the inositol 1,4,5-trisphosphate receptor IP3R1.
CC {ECO:0000250|UniProtKB:Q96HE7, ECO:0000269|PubMed:19752026,
CC ECO:0000269|PubMed:20308425}.
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:0000250|UniProtKB:Q8R4A1}. Note=The association with ERP44 is
CC essential for its retention in the endoplasmic reticulum (By
CC similarity). In neurons, it localizes to dendrites (By similarity).
CC {ECO:0000250|UniProtKB:Q8R4A1, ECO:0000250|UniProtKB:Q96HE7}.
CC -!- TISSUE SPECIFICITY: Widely expressed (at protein level)
CC (PubMed:20308425). In the mammary gland, expressed at higher levels in
CC lactating mice than in virgin mice (at protein level)
CC (PubMed:29858230). {ECO:0000269|PubMed:20308425,
CC ECO:0000269|PubMed:29858230}.
CC -!- INDUCTION: Stimulated by hypoxia; suggesting that it is regulated via
CC the HIF-pathway. By ER stress in a DDIT3/CHOP-dependent manner.
CC {ECO:0000269|PubMed:12752442, ECO:0000269|PubMed:19752026}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
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 (PubMed:29858230). It is also induced by hypoxia and
CC reductive stress (By similarity). {ECO:0000250|UniProtKB:Q96HE7,
CC ECO:0000269|PubMed:29858230}.
CC -!- SIMILARITY: Belongs to the EROs family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF144695; AAF20364.1; -; mRNA.
DR EMBL; BC025102; AAH25102.1; -; mRNA.
DR EMBL; AK009667; BAB26428.1; -; mRNA.
DR CCDS; CCDS36893.1; -.
DR RefSeq; NP_056589.1; NM_015774.3.
DR AlphaFoldDB; Q8R180; -.
DR SMR; Q8R180; -.
DR BioGRID; 206053; 17.
DR IntAct; Q8R180; 1.
DR MINT; Q8R180; -.
DR STRING; 10090.ENSMUSP00000022378; -.
DR BindingDB; Q8R180; -.
DR ChEMBL; CHEMBL4105849; -.
DR GlyConnect; 2304; 3 N-Linked glycans (1 site).
DR GlyGen; Q8R180; 2 sites, 3 N-linked glycans (1 site).
DR iPTMnet; Q8R180; -.
DR PhosphoSitePlus; Q8R180; -.
DR SwissPalm; Q8R180; -.
DR EPD; Q8R180; -.
DR jPOST; Q8R180; -.
DR MaxQB; Q8R180; -.
DR PaxDb; Q8R180; -.
DR PRIDE; Q8R180; -.
DR ProteomicsDB; 275888; -.
DR Antibodypedia; 10791; 337 antibodies from 33 providers.
DR DNASU; 50527; -.
DR Ensembl; ENSMUST00000022378; ENSMUSP00000022378; ENSMUSG00000021831.
DR GeneID; 50527; -.
DR KEGG; mmu:50527; -.
DR UCSC; uc007tgm.2; mouse.
DR CTD; 30001; -.
DR MGI; MGI:1354385; Ero1a.
DR VEuPathDB; HostDB:ENSMUSG00000021831; -.
DR eggNOG; KOG2608; Eukaryota.
DR GeneTree; ENSGT00390000007753; -.
DR HOGENOM; CLU_023061_2_2_1; -.
DR InParanoid; Q8R180; -.
DR OMA; PDAWRIW; -.
DR OrthoDB; 1181226at2759; -.
DR PhylomeDB; Q8R180; -.
DR TreeFam; TF314471; -.
DR Reactome; R-MMU-264876; Insulin processing.
DR Reactome; R-MMU-3299685; Detoxification of Reactive Oxygen Species.
DR BioGRID-ORCS; 50527; 4 hits in 75 CRISPR screens.
DR ChiTaRS; Ero1l; mouse.
DR PRO; PR:Q8R180; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8R180; protein.
DR Bgee; ENSMUSG00000021831; Expressed in ectoplacental cone and 260 other tissues.
DR ExpressionAtlas; Q8R180; baseline and differential.
DR Genevisible; Q8R180; MM.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
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:0030176; C:integral component of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:MGI.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:MGI.
DR GO; GO:0016972; F:thiol oxidase activity; IEA:InterPro.
DR GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
DR GO; GO:0045454; P:cell redox homeostasis; IGI:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; ISO:MGI.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IDA:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IGI:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IGI:MGI.
DR GO; GO:0006457; P:protein folding; IDA:MGI.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0022417; P:protein maturation by protein folding; IGI:MGI.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IDA:MGI.
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 Apoptosis; Cell projection; Disulfide bond; Electron transport;
KW Endoplasmic reticulum; FAD; Flavoprotein; Glycoprotein; Golgi apparatus;
KW Membrane; Oxidoreductase; Phosphoprotein; Redox-active center;
KW 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_0000008416"
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:0000255"
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"
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 CONFLICT 130
FT /note="C -> G (in Ref. 2; AAH25102)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 464 AA; 54084 MW; FED19B00E1FBD2A1 CRC64;
MGRAWGLLVG LLGVVWLLRL GHGEERRPET AAQRCFCQVS GYLDDCTCDV ETIDKFNNYR
LFPRLQKLLE SDYFRYYKVN LKKPCPFWND INQCGRRDCA VKPCHSDEVP DGIKSASYKY
SEEANRIEEC EQAERLGAVD ESLSEETQKA VLQWTKHDDS SDSFCEIDDI QSPDAEYVDL
LLNPERYTGY KGPDAWRIWS VIYEENCFKP QTIQRPLASG RGKSKENTFY NWLEGLCVEK
RAFYRLISGL HASINVHLSA RYLLQDTWLE KKWGHNVTEF QQRFDGILTE GEGPRRLRNL
YFLYLIELRA LSKVLPFFER PDFQLFTGNK VQDAENKALL LEILHEIKSF PLHFDENSFF
AGDKNEAHKL KEDFRLHFRN ISRIMDCVGC FKCRLWGKLQ TQGLGTALKI LFSEKLIANM
PESGPSYEFQ LTRQEIVSLF NAFGRISTSV RELENFRHLL QNVH
