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 27-MAR-2024, entry version 191. 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}. 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; 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; 129. DR IntAct; Q96HE7; 27. 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 GlyCosmos; Q96HE7; 2 sites, 4 glycans. 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; 9606-ENSP00000379042; -. DR PeptideAtlas; Q96HE7; -. DR PRIDE; Q96HE7; -. DR ProteomicsDB; 76737; -. DR Pumba; Q96HE7; -. DR Antibodypedia; 10791; 357 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 AGR; HGNC:13280; -. 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; WTASNEC; -. DR OrthoDB; 159339at2759; -. DR PhylomeDB; Q96HE7; -. DR TreeFam; TF314471; -. DR BioCyc; MetaCyc:MONOMER66-43439; -. DR PathwayCommons; Q96HE7; -. DR Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species. DR SignaLink; Q96HE7; -. DR SIGNOR; Q96HE7; -. DR BioGRID-ORCS; 30001; 16 hits in 1155 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 192 other cell types or tissues. DR ExpressionAtlas; Q96HE7; baseline and differential. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. 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: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:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISS:UniProtKB. 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:SF1; ERO1-LIKE PROTEIN ALPHA; 1. DR PANTHER; PTHR12613; ERO1-RELATED; 1. DR Pfam; PF04137; ERO1; 1. DR PIRSF; PIRSF017205; ERO1; 1. DR SUPFAM; SSF110019; ERO1-like; 1. DR Genevisible; Q96HE7; HS. 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 //