ERO1A_HUMAN
ID ERO1A_HUMAN Reviewed; 468 AA.
AC Q96HE7; A8K9X4; A8MYW1; Q7LD45; Q9P1Q9; Q9UKV6;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2004, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=ERO1-like protein alpha;
DE Short=ERO1-L;
DE Short=ERO1-L-alpha;
DE EC=1.8.4.- {ECO:0000269|PubMed:29858230};
DE AltName: Full=Endoplasmic oxidoreductin-1-like protein;
DE AltName: Full=Endoplasmic reticulum oxidoreductase alpha {ECO:0000312|HGNC:HGNC:13280};
DE AltName: Full=Oxidoreductin-1-L-alpha;
DE Flags: Precursor;
GN Name=ERO1A {ECO:0000312|HGNC:HGNC:13280}; Synonyms=ERO1L;
GN ORFNames=UNQ434/PRO865;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION,
RP AND MUTAGENESIS OF CYS-391 AND CYS-394.
RC TISSUE=Embryonic carcinoma;
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].
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [6]
RP PROTEIN SEQUENCE OF N-TERMINUS, AND IDENTIFICATION BY MASS SPECTROMETRY.
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 [7]
RP PROTEIN SEQUENCE OF 68-75; 288-299 AND 420-437, INTERACTION WITH ERP44, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11847130; DOI=10.1093/emboj/21.4.835;
RA Anelli T., Alessio M., Mezghrani A., Simmen T., Talamo F., Bachi A.,
RA Sitia R.;
RT "ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin
RT family.";
RL EMBO J. 21:835-844(2002).
RN [8]
RP FUNCTION, GLYCOSYLATION, AND MUTAGENESIS OF CYS-391; CYS-394 AND CYS-397.
RX PubMed=10970843; DOI=10.1093/emboj/19.17.4493;
RA Benham A.M., Cabibbo A., Fassio A., Bulleid N., Sitia R., Braakman I.;
RT "The CXXCXXC motif determines the folding, structure and stability of human
RT Ero1-Lalpha.";
RL EMBO J. 19:4493-4502(2000).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=10818100; DOI=10.1074/jbc.m003061200;
RA Pagani M., Fabbri M., Benedetti C., Fassio A., Pilati S., Bulleid N.J.,
RA Cabibbo A., Sitia R.;
RT "Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene
RT induced in the course of the unfolded protein response.";
RL J. Biol. Chem. 275:23685-23692(2000).
RN [10]
RP FUNCTION, POTENTIAL HOMODIMERIZATION, ASSOCIATION WITH P4HB, LACK OF
RP ASSOCIATION WITH GRP58, AND MUTAGENESIS OF CYS-394 AND CYS-397.
RX PubMed=11707400; DOI=10.1093/emboj/20.22.6288;
RA Mezghrani A., Fassio A., Benham A., Simmen T., Braakman I., Sitia R.;
RT "Manipulation of oxidative protein folding and PDI redox state in mammalian
RT cells.";
RL EMBO J. 20:6288-6296(2001).
RN [11]
RP FUNCTION.
RX PubMed=12403808; DOI=10.1083/jcb.200207120;
RA Tsai B., Rapoport T.A.;
RT "Unfolded cholera toxin is transferred to the ER membrane and released from
RT protein disulfide isomerase upon oxidation by Ero1.";
RL J. Cell Biol. 159:207-216(2002).
RN [12]
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 [13]
RP SUBCELLULAR LOCATION.
RX PubMed=14517240; DOI=10.1093/emboj/cdg491;
RA Anelli T., Alessio M., Bachi A., Bergamelli L., Bertoli G., Camerini S.,
RA Mezghrani A., Ruffato E., Simmen T., Sitia R.;
RT "Thiol-mediated protein retention in the endoplasmic reticulum: the role of
RT ERp44.";
RL EMBO J. 22:5015-5022(2003).
RN [14]
RP MUTAGENESIS OF CYS-85; CYS-94; CYS-99; CYS-104; CYS-131; CYS-166; CYS-208;
RP CYS-241; ASN-280; ASN-384; CYS-391; CYS-394 AND CYS-397.
RX PubMed=15136577; DOI=10.1074/jbc.m403192200;
RA Bertoli G., Simmen T., Anelli T., Nerini Molteni S., Fesce R., Sitia R.;
RT "Two conserved cysteine triads in human Ero1alpha cooperate forefficient
RT disulfide bond formation in the ER.";
RL J. Biol. Chem. 279:30047-30052(2004).
RN [15]
RP ACTIVITY REGULATION.
RX PubMed=15161913; DOI=10.1074/jbc.m404992200;
RA Nerini Molteni S., Fassio A., Ciriolo M.R., Filomeni G., Pasqualetto E.,
RA Fagioli C., Sitia R.;
RT "Glutathione limits Ero1-dependent oxidation in the endoplasmic
RT reticulum.";
RL J. Biol. Chem. 279:32667-32673(2004).
RN [16]
RP INTERACTION WITH PDILT.
RX PubMed=15475357; DOI=10.1074/jbc.m408651200;
RA van Lith M., Hartigan N., Hatch J., Benham A.M.;
RT "PDILT, a divergent testis-specific protein disulfide isomerase with a non-
RT classical SXXC motif that engages in disulfide-dependent interactions in
RT the endoplasmic reticulum.";
RL J. Biol. Chem. 280:1376-1383(2005).
RN [17]
RP FUNCTION, ACTIVITY REGULATION, DISULFIDE BONDS, MUTAGENESIS OF CYS-131 AND
RP CYS-394, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18833192; DOI=10.1038/emboj.2008.202;
RA Appenzeller-Herzog C., Riemer J., Christensen B., Soerensen E.S.,
RA Ellgaard L.;
RT "A novel disulphide switch mechanism in Ero1alpha balances ER oxidation in
RT human cells.";
RL EMBO J. 27:2977-2987(2008).
RN [18]
RP FUNCTION, ACTIVITY REGULATION, COFACTOR, SUBUNIT, DISULFIDE BONDS, AND
RP MUTAGENESIS OF CYS-85; CYS-94; CYS-99; CYS-104; CYS-131; CYS-166; CYS-208
RP AND CYS-241.
RX PubMed=18971943; DOI=10.1038/emboj.2008.230;
RA Baker K.M., Chakravarthi S., Langton K.P., Sheppard A.M., Lu H.,
RA Bulleid N.J.;
RT "Low reduction potential of Ero1alpha regulatory disulphides ensures tight
RT control of substrate oxidation.";
RL EMBO J. 27:2988-2997(2008).
RN [19]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-280.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP MUTAGENESIS OF PHE-395.
RX PubMed=21091435; DOI=10.1042/bj20101357;
RA Wang L., Zhu L., Wang C.C.;
RT "The endoplasmic reticulum sulfhydryl oxidase Ero1beta drives efficient
RT oxidative protein folding with loose regulation.";
RL Biochem. J. 434:113-121(2011).
RN [23]
RP FUNCTION, DISULFIDE BONDS, AND MUTAGENESIS OF CYS-104 AND CYS-131.
RX PubMed=23027870; DOI=10.1074/jbc.m112.405050;
RA Hansen H.G., Schmidt J.D., Soltoft C.L., Ramming T., Geertz-Hansen H.M.,
RA Christensen B., Sorensen E.S., Juncker A.S., Appenzeller-Herzog C.,
RA Ellgaard L.;
RT "Hyperactivity of the Ero1alpha oxidase elicits endoplasmic reticulum
RT stress but no broad antioxidant response.";
RL J. Biol. Chem. 287:39513-39523(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-143, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-106, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH ERP44, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT SER-145, MUTAGENESIS OF SER-145, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
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).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 22-468, COFACTOR BINDING SITES,
RP AND DISULFIDE BONDS.
RX PubMed=20834232; DOI=10.1038/emboj.2010.222;
RA Inaba K., Masui S., Iida H., Vavassori S., Sitia R., Suzuki M.;
RT "Crystal structures of human Ero1alpha reveal the mechanisms of regulated
RT and targeted oxidation of PDI.";
RL EMBO J. 29:3330-3343(2010).
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 (PubMed:29858230).
CC Plays an important role in ER stress-induced, CHOP-dependent apoptosis
CC by activating the inositol 1,4,5-trisphosphate receptor IP3R1. Involved
CC in the release of the unfolded cholera toxin from reduced P4HB/PDI in
CC case of infection by V.cholerae, thereby playing a role in
CC retrotranslocation of the toxin. {ECO:0000269|PubMed:10671517,
CC ECO:0000269|PubMed:10970843, ECO:0000269|PubMed:11707400,
CC ECO:0000269|PubMed:12403808, ECO:0000269|PubMed:18833192,
CC ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:23027870,
CC ECO:0000269|PubMed:29858230}.
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692;
CC Evidence={ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:20834232};
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-131, and between Cys-99
CC and Cys-104. Glutathione may be required to regulate its activity in
CC the endoplasmic reticulum. {ECO:0000269|PubMed:15161913,
CC ECO:0000269|PubMed:18833192, ECO:0000269|PubMed:18971943}.
CC -!- SUBUNIT: Predominantly monomer. May function both as a monomer and a
CC homodimer. Interacts with PDILT (PubMed:15475357). Interacts with
CC ERP44; the interaction results in retention of ERO1A in the endoplasmic
CC reticulum (PubMed:29858230, PubMed:11847130).
CC {ECO:0000269|PubMed:11847130, ECO:0000269|PubMed:15475357,
CC ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:29858230}.
CC -!- INTERACTION:
CC Q96HE7; Q92624: APPBP2; NbExp=3; IntAct=EBI-2564539, EBI-743771;
CC Q96HE7; Q969G2: LHX4; NbExp=3; IntAct=EBI-2564539, EBI-2865388;
CC Q96HE7; P07237: P4HB; NbExp=2; IntAct=EBI-2564539, EBI-395883;
CC Q96HE7; P30101: PDIA3; NbExp=3; IntAct=EBI-2564539, EBI-979862;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10671517, ECO:0000269|PubMed:14517240}; Peripheral
CC membrane protein {ECO:0000269|PubMed:10671517,
CC ECO:0000269|PubMed:14517240}; Lumenal side
CC {ECO:0000269|PubMed:10671517, ECO:0000269|PubMed:14517240}. Golgi
CC apparatus lumen {ECO:0000269|PubMed:29858230}. Secreted
CC {ECO:0000269|PubMed:29858230}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q8R4A1}. Note=The association with ERP44 is
CC essential for its retention in the endoplasmic reticulum
CC (PubMed:29858230). In neurons, it localizes to dendrites (By
CC similarity). {ECO:0000250|UniProtKB:Q8R4A1,
CC ECO:0000269|PubMed:29858230}.
CC -!- TISSUE SPECIFICITY: Widely expressed at low level. Expressed at high
CC level in upper digestive tract. Highly expressed in esophagus. Weakly
CC expressed in stomach and duodenum. {ECO:0000269|PubMed:10818100}.
CC -!- INDUCTION: Stimulated by hypoxia; suggesting that it is regulated via
CC the HIF-pathway. {ECO:0000269|PubMed:12752442}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:10671517,
CC ECO:0000269|PubMed:10970843, ECO:0000269|PubMed:19159218}.
CC -!- PTM: The Cys-94/Cys-99 and Cys-394/Cys-397 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 394/Cys-397 (By similarity). The regulatory Cys-99/Cys-104 disulfide
CC bond stabilizes the other regulatory bond Cys-94/Cys-131
CC (PubMed:23027870). {ECO:0000250, ECO:0000269|PubMed:23027870}.
CC -!- PTM: Phosphorylated on Ser-145 by FAM20C in the Golgi which increases
CC its enzymatic activity (PubMed:29858230). Phosphorylation is induced by
CC lactation (By similarity). It is also induced by hypoxia and reductive
CC stress (PubMed:29858230). {ECO:0000250|UniProtKB:Q8R180,
CC ECO:0000269|PubMed:29858230}.
CC -!- SIMILARITY: Belongs to the EROs family. {ECO:0000305}.
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DR EMBL; AF081886; AAF35260.1; -; mRNA.
DR EMBL; AF123887; AAF06104.1; -; mRNA.
DR EMBL; AY358463; AAQ88828.1; -; mRNA.
DR EMBL; AK292839; BAF85528.1; -; mRNA.
DR EMBL; AL133453; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008674; AAH08674.1; -; mRNA.
DR EMBL; BC012941; AAH12941.1; -; mRNA.
DR CCDS; CCDS9709.1; -.
DR RefSeq; NP_055399.1; NM_014584.2.
DR PDB; 3AHQ; X-ray; 2.35 A; A=22-468.
DR PDB; 3AHR; X-ray; 3.07 A; A=22-468.
DR PDBsum; 3AHQ; -.
DR PDBsum; 3AHR; -.
DR AlphaFoldDB; Q96HE7; -.
DR SMR; Q96HE7; -.
DR BioGRID; 119025; 78.
DR IntAct; Q96HE7; 24.
DR MINT; Q96HE7; -.
DR STRING; 9606.ENSP00000379042; -.
DR BindingDB; Q96HE7; -.
DR ChEMBL; CHEMBL1671609; -.
DR TCDB; 8.A.141.1.1; the eros chaperone protein (eros) family.
DR GlyConnect; 1225; 4 N-Linked glycans (1 site).
DR GlyGen; Q96HE7; 3 sites, 8 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q96HE7; -.
DR MetOSite; Q96HE7; -.
DR PhosphoSitePlus; Q96HE7; -.
DR SwissPalm; Q96HE7; -.
DR BioMuta; ERO1A; -.
DR DMDM; 50400608; -.
DR EPD; Q96HE7; -.
DR jPOST; Q96HE7; -.
DR MassIVE; Q96HE7; -.
DR MaxQB; Q96HE7; -.
DR PaxDb; Q96HE7; -.
DR PeptideAtlas; Q96HE7; -.
DR PRIDE; Q96HE7; -.
DR ProteomicsDB; 76737; -.
DR Antibodypedia; 10791; 337 antibodies from 33 providers.
DR DNASU; 30001; -.
DR Ensembl; ENST00000395686.8; ENSP00000379042.3; ENSG00000197930.13.
DR GeneID; 30001; -.
DR KEGG; hsa:30001; -.
DR MANE-Select; ENST00000395686.8; ENSP00000379042.3; NM_014584.3; NP_055399.1.
DR UCSC; uc001wzv.4; human.
DR CTD; 30001; -.
DR DisGeNET; 30001; -.
DR GeneCards; ERO1A; -.
DR HGNC; HGNC:13280; ERO1A.
DR HPA; ENSG00000197930; Tissue enhanced (esophagus).
DR MIM; 615435; gene.
DR neXtProt; NX_Q96HE7; -.
DR OpenTargets; ENSG00000197930; -.
DR PharmGKB; PA27862; -.
DR VEuPathDB; HostDB:ENSG00000197930; -.
DR eggNOG; KOG2608; Eukaryota.
DR GeneTree; ENSGT00390000007753; -.
DR HOGENOM; CLU_023061_2_2_1; -.
DR InParanoid; Q96HE7; -.
DR OMA; PDAWRIW; -.
DR OrthoDB; 1181226at2759; -.
DR PhylomeDB; Q96HE7; -.
DR TreeFam; TF314471; -.
DR BioCyc; MetaCyc:MON66-43439; -.
DR PathwayCommons; Q96HE7; -.
DR Reactome; R-HSA-264876; Insulin processing.
DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR SignaLink; Q96HE7; -.
DR SIGNOR; Q96HE7; -.
DR BioGRID-ORCS; 30001; 12 hits in 1075 CRISPR screens.
DR ChiTaRS; ERO1A; human.
DR EvolutionaryTrace; Q96HE7; -.
DR GeneWiki; ERO1L; -.
DR GenomeRNAi; 30001; -.
DR Pharos; Q96HE7; Tbio.
DR PRO; PR:Q96HE7; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96HE7; protein.
DR Bgee; ENSG00000197930; Expressed in esophagus squamous epithelium and 190 other tissues.
DR ExpressionAtlas; Q96HE7; baseline and differential.
DR Genevisible; Q96HE7; HS.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0015036; F:disulfide oxidoreductase activity; TAS:Reactome.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:UniProtKB.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IBA:GO_Central.
DR GO; GO:0016972; F:thiol oxidase activity; IEA:InterPro.
DR GO; GO:0050873; P:brown fat cell differentiation; IEA:Ensembl.
DR GO; GO:0045454; P:cell redox homeostasis; IMP:UniProtKB.
DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; IDA:UniProtKB.
DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0030070; P:insulin processing; TAS:Reactome.
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; IEA:Ensembl.
DR GO; GO:0006457; P:protein folding; IMP:UniProtKB.
DR GO; GO:0034975; P:protein folding in endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0022417; P:protein maturation by protein folding; IEA:Ensembl.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
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; IEA:Ensembl.
DR GO; GO:0009266; P:response to temperature stimulus; TAS:ProtInc.
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; Apoptosis; Cell projection; Direct protein sequencing;
KW Disulfide bond; Electron transport; Endoplasmic reticulum; FAD;
KW Flavoprotein; Glycoprotein; Golgi apparatus; Membrane; Oxidoreductase;
KW Phosphoprotein; Redox-active center; Reference proteome; Secreted; Signal;
KW Transport.
FT SIGNAL 1..23
FT /evidence="ECO:0000269|PubMed:11707280"
FT CHAIN 24..468
FT /note="ERO1-like protein alpha"
FT /id="PRO_0000008415"
FT BINDING 187
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT BINDING 189
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT BINDING 200
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT BINDING 252
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT BINDING 255
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT BINDING 287
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT BINDING 300
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 143
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 145
FT /note="Phosphoserine; by FAM20C"
FT /evidence="ECO:0000269|PubMed:29858230"
FT CARBOHYD 280
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 384
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..48
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT DISULFID 37..46
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT DISULFID 85..391
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT DISULFID 94..131
FT /note="Alternate"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHR"
FT DISULFID 94..99
FT /note="Redox-active; alternate"
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT DISULFID 99..104
FT /note="Alternate"
FT /evidence="ECO:0000305"
FT DISULFID 208..241
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT DISULFID 394..397
FT /note="Redox-active"
FT /evidence="ECO:0000269|PubMed:20834232,
FT ECO:0007744|PDB:3AHQ, ECO:0007744|PDB:3AHR"
FT MUTAGEN 85
FT /note="C->A: Alters protein folding and stability. Loss of
FT regulatory disulfide bond formation and increased activity
FT towards P4HB; when associated with A-131."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT MUTAGEN 85
FT /note="C->S: Induces a decrease in activity."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT MUTAGEN 94
FT /note="C->S: Induces a decrease in activity towards
FT thioredoxin. Loss of activity towards thioredoxin and loss
FT of regulatory disulfide bond formation; when associated
FT with A-99."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT MUTAGEN 99
FT /note="C->A: Acts as a weak dominant-negative mutant. Loss
FT of activity towards thioredoxin. Loss of regulatory
FT disulfide bond formation; when associated with A-94."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT MUTAGEN 104
FT /note="C->A: No effect. Strongly increased activity towards
FT P4HB and UPR induction, but no broad oxidative injury; when
FT associated with A-131."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:23027870"
FT MUTAGEN 104
FT /note="C->S: No effect."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943, ECO:0000269|PubMed:23027870"
FT MUTAGEN 131
FT /note="C->A: Loss of regulatory disulfide bond formation
FT and increased activity towards P4HB. Loss of regulatory
FT disulfide bond formation and strongly increased activity
FT towards P4HB; when associated with A-85. Loss of regulatory
FT disulfide bond formation, strongly increased activity
FT towards P4HB and UPR induction, but no broad oxidative
FT injury; when associated with A-104."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18833192, ECO:0000269|PubMed:18971943,
FT ECO:0000269|PubMed:23027870"
FT MUTAGEN 145
FT /note="S->A: Abolishes phosphorylation. Does not affect
FT interaction with ERP44."
FT /evidence="ECO:0000269|PubMed:29858230"
FT MUTAGEN 145
FT /note="S->E: Phosphomimetic mutant. Does not affect
FT interaction with ERP44. Shows two-fold increase in enzyme
FT activity. Accelerates immunoglobulin folding."
FT /evidence="ECO:0000269|PubMed:29858230"
FT MUTAGEN 166
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT MUTAGEN 208
FT /note="C->A,S: No effect."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT MUTAGEN 241
FT /note="C->A,S: No effect."
FT /evidence="ECO:0000269|PubMed:15136577,
FT ECO:0000269|PubMed:18971943"
FT MUTAGEN 280
FT /note="N->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15136577"
FT MUTAGEN 384
FT /note="N->A: No effect on activity."
FT /evidence="ECO:0000269|PubMed:15136577"
FT MUTAGEN 391
FT /note="C->A: Alters protein folding. Prevents formation of
FT regulatory disulfide bond and down-regulation of activity.
FT Decreases association with P4HB."
FT /evidence="ECO:0000269|PubMed:10671517,
FT ECO:0000269|PubMed:10970843, ECO:0000269|PubMed:15136577"
FT MUTAGEN 394
FT /note="C->A: Retains activity towards P4HB. Does not act as
FT a dominant negative mutant. Induces defects in folding.
FT Remains associated with P4HB."
FT /evidence="ECO:0000269|PubMed:10671517,
FT ECO:0000269|PubMed:10970843, ECO:0000269|PubMed:11707400,
FT ECO:0000269|PubMed:15136577, ECO:0000269|PubMed:18833192"
FT MUTAGEN 395
FT /note="F->D: Increased catalytical activity."
FT /evidence="ECO:0000269|PubMed:21091435"
FT MUTAGEN 397
FT /note="C->A: Acts as a dominant negative mutant; does not
FT induce defects in folding; remains associated with P4HB."
FT /evidence="ECO:0000269|PubMed:10970843,
FT ECO:0000269|PubMed:11707400, ECO:0000269|PubMed:15136577"
FT CONFLICT 456
FT /note="E -> K (in Ref. 5; AAH08674)"
FT /evidence="ECO:0000305"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 50..59
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 62..70
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 72..75
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 134..138
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 146..161
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 177..180
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 193..204
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 245..264
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 275..278
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 281..288
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 290..293
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 296..317
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 319..323
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 336..353
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 369..389
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 395..415
FT /evidence="ECO:0007829|PDB:3AHQ"
FT HELIX 418..422
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:3AHQ"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:3AHR"
FT HELIX 437..463
FT /evidence="ECO:0007829|PDB:3AHQ"
SQ SEQUENCE 468 AA; 54393 MW; 92ECE6531C9CCA33 CRC64;
MGRGWGFLFG LLGAVWLLSS GHGEEQPPET AAQRCFCQVS GYLDDCTCDV ETIDRFNNYR
LFPRLQKLLE SDYFRYYKVN LKRPCPFWND ISQCGRRDCA VKPCQSDEVP DGIKSASYKY
SEEANNLIEE CEQAERLGAV DESLSEETQK AVLQWTKHDD SSDNFCEADD IQSPEAEYVD
LLLNPERYTG YKGPDAWKIW NVIYEENCFK PQTIKRPLNP LASGQGTSEE NTFYSWLEGL
CVEKRAFYRL ISGLHASINV HLSARYLLQE TWLEKKWGHN ITEFQQRFDG ILTEGEGPRR
LKNLYFLYLI ELRALSKVLP FFERPDFQLF TGNKIQDEEN KMLLLEILHE IKSFPLHFDE
NSFFAGDKKE AHKLKEDFRL HFRNISRIMD CVGCFKCRLW GKLQTQGLGT ALKILFSEKL
IANMPESGPS YEFHLTRQEI VSLFNAFGRI STSVKELENF RNLLQNIH
