ERO1A

Summary

Gene Symbol: ERO1A
Description: endoplasmic reticulum oxidoreductase 1 alpha
Alias: ERO1-L, ERO1-L-alpha, ERO1-alpha, ERO1L, ERO1LA, Ero1alpha, ERO1-like protein alpha, endoplasmic oxidoreductin-1-like protein, endoplasmic reticulum oxidoreductase alpha, oxidoreductin-1-L-alpha
Species: human
Products:     ERO1A

Top Publications

  1. Cabibbo A, Pagani M, Fabbri M, Rocchi M, Farmery M, Bulleid N, et al. ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol Chem. 2000;275:4827-33 pubmed
    ..ERO1-L is no longer functional when either one of the highly conserved Cys-394 or Cys-397 is mutated. These results strongly suggest that ERO1-L is involved in oxidative ER protein folding in mammalian cells. ..
  2. Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, et al. ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J. 2002;21:835-44 pubmed
    ..Its overexpression alters the equilibrium of the different Ero1-Lalpha redox isoforms, suggesting that ERp44 may be involved in the control of oxidative protein folding. ..
  3. Benham A, Cabibbo A, Fassio A, Bulleid N, Sitia R, Braakman I. The CXXCXXC motif determines the folding, structure and stability of human Ero1-Lalpha. EMBO J. 2000;19:4493-502 pubmed
    ..Our results demonstrate that this motif is important for protein folding, structural integrity, protein half-life and the stability of the Ero1-Lalpha-PDI complex. ..
  4. Otsu M, Bertoli G, Fagioli C, Guerini Rocco E, Nerini Molteni S, Ruffato E, et al. Dynamic retention of Ero1alpha and Ero1beta in the endoplasmic reticulum by interactions with PDI and ERp44. Antioxid Redox Signal. 2006;8:274-82 pubmed
    Disulfide bonds are formed in the endoplasmic reticulum (ER) by sequential interchange reactions: Ero1alpha and Ero1beta transfer oxidative equivalents to protein disulfide isomerase (PDI), which in turn oxidizes cargo proteins...
  5. Swiatkowska M, Padula G, Michalec L, Stasiak M, Skurzynski S, Cierniewski C. Ero1alpha is expressed on blood platelets in association with protein-disulfide isomerase and contributes to redox-controlled remodeling of alphaIIbbeta3. J Biol Chem. 2010;285:29874-83 pubmed publisher
  6. Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerini S, et al. Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J. 2003;22:5015-22 pubmed
    ..A pivotal element in this process is Ero1alpha, an oxidoreductin that lacks known ER retention motifs...
  7. Bertoli G, Simmen T, Anelli T, Molteni S, Fesce R, Sitia R. Two conserved cysteine triads in human Ero1alpha cooperate for efficient disulfide bond formation in the endoplasmic reticulum. J Biol Chem. 2004;279:30047-52 pubmed
    Human Ero1alpha is an endoplasmic reticulum (ER)-resident protein responsible for protein disulfide isomerase (PDI) oxidation...
  8. Molteni S, Fassio A, Ciriolo M, Filomeni G, Pasqualetto E, Fagioli C, et al. Glutathione limits Ero1-dependent oxidation in the endoplasmic reticulum. J Biol Chem. 2004;279:32667-73 pubmed
    ..In the endoplasmic reticulum (ER), Ero1 alpha and Ero1 beta oxidize protein disulfide isomerase (PDI), which in turn transfers oxidative equivalents to newly ..
  9. Baker K, Chakravarthi S, Langton K, Sheppard A, Lu H, Bulleid N. Low reduction potential of Ero1alpha regulatory disulphides ensures tight control of substrate oxidation. EMBO J. 2008;27:2988-97 pubmed publisher
    Formation of disulphide bonds within the mammalian endoplasmic reticulum (ER) requires the combined activities of Ero1alpha and protein disulphide isomerase (PDI)...

More Information

Publications55

  1. Chambers J, Tavender T, Oka O, Warwood S, Knight D, Bulleid N. The reduction potential of the active site disulfides of human protein disulfide isomerase limits oxidation of the enzyme by Ero1?. J Biol Chem. 2010;285:29200-7 pubmed publisher
    ..The inability of Ero1? to oxidize PDI efficiently likely reflects the requirement for PDI to act as both an oxidase and an isomerase during the formation of native disulfides in proteins entering the secretory pathway. ..
  2. Tsai B, Rapoport T. Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1. J Cell Biol. 2002;159:207-16 pubmed
    ..Both yeast Ero1 and the mammalian Ero1alpha isoform are active in this reaction. Ero1 has a preference for the PDI-toxin complex...
  3. May D, Itin A, Gal O, Kalinski H, Feinstein E, Keshet E. Ero1-L alpha plays a key role in a HIF-1-mediated pathway to improve disulfide bond formation and VEGF secretion under hypoxia: implication for cancer. Oncogene. 2005;24:1011-20 pubmed
  4. Appenzeller Herzog C, Riemer J, Christensen B, Sørensen E, Ellgaard L. A novel disulphide switch mechanism in Ero1alpha balances ER oxidation in human cells. EMBO J. 2008;27:2977-87 pubmed publisher
    ..Here, we determine the redox-driven shutdown mechanism of Ero1alpha, the housekeeping Ero1 enzyme in human cells...
  5. Jessop C, Chakravarthi S, Garbi N, Hämmerling G, Lovell S, Bulleid N. ERp57 is essential for efficient folding of glycoproteins sharing common structural domains. EMBO J. 2007;26:28-40 pubmed
    ..These results suggest a specific role for ERp57 in the isomerisation of non-native disulphide bonds in specific glycoprotein substrates. ..
  6. Araki K, Nagata K. Functional in vitro analysis of the ERO1 protein and protein-disulfide isomerase pathway. J Biol Chem. 2011;286:32705-12 pubmed publisher
    ..Finally, the results provide experimental evidence for the intramolecular electron transfer from the a domain to the a' domain within PDI during its oxidation by ERO1?. ..
  7. Enyedi B, Varnai P, Geiszt M. Redox state of the endoplasmic reticulum is controlled by Ero1L-alpha and intraluminal calcium. Antioxid Redox Signal. 2010;13:721-9 pubmed publisher
    ..We also found that calcium mobilization from intracellular stores induces a decrease in ER H(2)O(2) level, suggesting a complex interplay between redox and calcium signaling in the mammalian ER. ..
  8. Gess B, Hofbauer K, Wenger R, Lohaus C, Meyer H, Kurtz A. The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-Lalpha. Eur J Biochem. 2003;270:2228-35 pubmed
  9. Gilady S, Bui M, Lynes E, Benson M, Watts R, Vance J, et al. Ero1alpha requires oxidizing and normoxic conditions to localize to the mitochondria-associated membrane (MAM). Cell Stress Chaperones. 2010;15:619-29 pubmed publisher
    ..Given the role of human Ero1alpha in the regulation of the calcium release by inositol 1,4,5-trisphosphate receptors during the onset of apoptosis,..
  10. Mezghrani A, Fassio A, Benham A, Simmen T, Braakman I, Sitia R. Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO J. 2001;20:6288-96 pubmed
    ..Mutants in the Ero1-Lalpha CXXCXXC motif act as dominant negatives by limiting immunoglobulin oxidation. PDI-dependent oxidative folding in living cells can thus be manipulated by using hERO variants. ..
  11. Inaba K, Masui S, Iida H, Vavassori S, Sitia R, Suzuki M. Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. EMBO J. 2010;29:3330-43 pubmed publisher
    ..These results reveal the molecular basis of the regulation and specificity of protein disulphide formation in human cells. ..
  12. Anelli T, Bergamelli L, Margittai E, Rimessi A, Fagioli C, Malgaroli A, et al. Ero1? regulates Ca(2+) fluxes at the endoplasmic reticulum-mitochondria interface (MAM). Antioxid Redox Signal. 2012;16:1077-87 pubmed publisher
    ..Taken together, our results indicate that the levels, subcellular localization, and activity of Ero1? coordinately regulate Ca(2+) and redox homeostasis and signaling in the early secretory compartment. ..
  13. Appenzeller Herzog C, Riemer J, Zito E, Chin K, Ron D, Spiess M, et al. Disulphide production by Ero1?-PDI relay is rapid and effectively regulated. EMBO J. 2010;29:3318-29 pubmed publisher
    ..Instead, our data suggest that a dynamic equilibrium between Ero1- and glutathione disulphide-mediated oxidation of PDIs constitutes an important element of ER redox homeostasis. ..
  14. Nguyen V, Saaranen M, Karala A, Lappi A, Wang L, Raykhel I, et al. Two endoplasmic reticulum PDI peroxidases increase the efficiency of the use of peroxide during disulfide bond formation. J Mol Biol. 2011;406:503-15 pubmed publisher
    ..Hence, GPx7 and GPx8 may represent a novel route for the productive use of peroxide produced by Ero1? during disulfide bond formation. ..
  15. Masui S, Vavassori S, Fagioli C, Sitia R, Inaba K. Molecular bases of cyclic and specific disulfide interchange between human ERO1alpha protein and protein-disulfide isomerase (PDI). J Biol Chem. 2011;286:16261-71 pubmed publisher
    ..The potential ability of ERp44 to inhibit ERO1? activity may suggest its physiological role in ER redox and protein homeostasis. ..
  16. Pagani M, Fabbri M, Benedetti C, Fassio A, Pilati S, Bulleid N, et al. Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response. J Biol Chem. 2000;275:23685-92 pubmed
    ..Furthermore, only ERO1-Lbeta transcripts are induced in the course of the unfolded protein response. Our results suggest a complex regulation of ER redox homeostasis in mammalian cells. ..
  17. Wu B, Lv G, Zou H, Du Z, Wu J, Zhang P, et al. Exploration of potential roles of a new LOXL2 splicing variant using network knowledge in esophageal squamous cell carcinoma. ScientificWorldJournal. 2014;2014:431792 pubmed publisher
    ..Several tumor-related genes such as ERO1L, ITGA3, and MAPK8 were found closest to LOXL2-e13...
  18. Kemter E, Frohlich T, Arnold G, Wolf E, Wanke R. Mitochondrial Dysregulation Secondary to Endoplasmic Reticulum Stress in Autosomal Dominant Tubulointerstitial Kidney Disease - UMOD (ADTKD-UMOD). Sci Rep. 2017;7:42970 pubmed publisher
    ..The abundance of hypoxia-inducible proteins with stress survival functions, i.e. HYOU1, TXNDC5 and ERO1L, was also increased...
  19. Chin K, Kang G, Qu J, Gardner L, Coetzee W, Zito E, et al. The sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation-coupled calcium release and response to hemodynamic load. FASEB J. 2011;25:2583-91 pubmed publisher
    ..We established mouse lines with loss of function insertion mutations in Ero1l and Ero1lb encoding ERO1α and ERO1β...
  20. Fujii M, Yoneda A, Takei N, Sakai Sawada K, Kosaka M, Minomi K, et al. Endoplasmic reticulum oxidase 1? is critical for collagen secretion from and membrane type 1-matrix metalloproteinase levels in hepatic stellate cells. J Biol Chem. 2017;292:15649-15660 pubmed publisher
    ..The results suggest that ERO1? plays a crucial role in HSC proliferation via posttranslational modification of collagen and MT1-MMP and, therefore, may be a suitable therapeutic target for managing liver fibrosis. ..
  21. Chu Y, Yang C, Chen X, Zheng W, Yang Y, Tang Y. Structure-function analysis of human protein Ero1-Lalpha. Biochem Biophys Res Commun. 2009;389:645-50 pubmed publisher
    ..Both calculation and experiment got the concordant conclusion that FAD binds more tightly with Ero1-Lalpha than Ero1p. In addition, the probable electron transfer pathway was proposed on the basis of the structural models. ..
  22. Pagani M, Pilati S, Bertoli G, Valsasina B, Sitia R. The C-terminal domain of yeast Ero1p mediates membrane localization and is essential for function. FEBS Lett. 2001;508:117-20 pubmed
    ..Appending the yeast C-terminal tail to human Ero1-Lalpha restores membrane association and allows growth of ERO1 disrupted cells. Therefore, the tail of Ero1p mediates membrane association and is crucial for function. ..
  23. Kanemura S, Okumura M, Yutani K, Ramming T, Hikima T, Appenzeller Herzog C, et al. Human ER Oxidoreductin-1? (Ero1?) Undergoes Dual Regulation through Complementary Redox Interactions with Protein-Disulfide Isomerase. J Biol Chem. 2016;291:23952-23964 pubmed
    ..We propose a mechanism of dual Ero1? regulation by dynamic redox interactions between PDI and the two Ero1? flexible loops that harbor the regulatory cysteines. ..
  24. Wright J, Birk J, Haataja L, Liu M, Ramming T, Weiss M, et al. Endoplasmic reticulum oxidoreductin-1? (Ero1?) improves folding and secretion of mutant proinsulin and limits mutant proinsulin-induced endoplasmic reticulum stress. J Biol Chem. 2013;288:31010-8 pubmed publisher
  25. Kakihana T, Araki K, Vavassori S, Iemura S, Cortini M, Fagioli C, et al. Dynamic regulation of Ero1? and peroxiredoxin 4 localization in the secretory pathway. J Biol Chem. 2013;288:29586-94 pubmed publisher
    ..PDI binds preferentially Ero1?, whereas ERp44 equally retains Ero1? and Prx4. The different binding properties of Ero1? and Prx4 increase the robustness of ER redox homeostasis. ..
  26. Hansen H, Schmidt J, Søltoft C, Ramming T, Geertz Hansen H, Christensen B, et al. Hyperactivity of the Ero1? oxidase elicits endoplasmic reticulum stress but no broad antioxidant response. J Biol Chem. 2012;287:39513-23 pubmed publisher
    ..Interestingly, a broad antioxidant response was not induced. Our findings suggest that the hyperoxidation generated by Ero1?-C104A/C131A is addressed in the ER lumen and is unlikely to exert oxidative injury throughout the cell. ..
  27. Moore P, Bernardi K, Tsai B. The Ero1alpha-PDI redox cycle regulates retro-translocation of cholera toxin. Mol Biol Cell. 2010;21:1305-13 pubmed publisher
    ..In its reduced state, PDI binds and unfolds CTA1; subsequent oxidation of PDI by Ero1alpha enables toxin release...
  28. Mata Greenwood E, Goyal D, Goyal R. Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells. Front Physiol. 2017;8:365 pubmed publisher
    ..Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia...
  29. Shepherd C, Oka O, Bulleid N. Inactivation of mammalian Ero1? is catalysed by specific protein disulfide-isomerases. Biochem J. 2014;461:107-13 pubmed publisher
    ..The results of the present study demonstrate a simple feedback mechanism of re-gulation of mammalian Ero1? involving its primary substrate. ..
  30. Okumura M, Kadokura H, Hashimoto S, Yutani K, Kanemura S, Hikima T, et al. Inhibition of the functional interplay between endoplasmic reticulum (ER) oxidoreduclin-1α (Ero1α) and protein-disulfide isomerase (PDI) by the endocrine disruptor bisphenol A. J Biol Chem. 2014;289:27004-18 pubmed publisher
    ..These results indicate that BPA, a widely distributed and potentially harmful chemical, inhibits Ero1-PDI-mediated disulfide bond formation. ..
  31. Cain K, Peters S, Hailu H, Sweeney B, Stephens P, Heads J, et al. A CHO cell line engineered to express XBP1 and ERO1-L? has increased levels of transient protein expression. Biotechnol Prog. 2013;29:697-706 pubmed publisher
    ..To further develop and test this TGE system, five commercial media were assessed, and one was shown to offer the greatest increase in antibody yields. With the addition of a commercial feed, MAb titers reached 875 mg/L. ..
  32. Kutomi G, Tamura Y, Tanaka T, Kajiwara T, Kukita K, Ohmura T, et al. Human endoplasmic reticulum oxidoreductin 1-? is a novel predictor for poor prognosis of breast cancer. Cancer Sci. 2013;104:1091-6 pubmed publisher
    ..These findings indicate that the expression of hERO1-? in cancer cells is associated with poorer prognosis and thus can be a prognostic factor for patients with breast cancer. ..
  33. Seol S, Kim C, Lim J, Yoon S, Hong S, Kim J, et al. Overexpression of Endoplasmic Reticulum Oxidoreductin 1-? (ERO1L) Is Associated with Poor Prognosis of Gastric Cancer. Cancer Res Treat. 2016;48:1196-1209 pubmed
    ..Following previous studies that identified endoplasmic reticulum oxidoreductin 1-? (ERO1L) as a potential marker for gastric cancer, we investigated the functional role of ERO1L in gastric cancer...
  34. Benham A, van Lith M, Sitia R, Braakman I. Ero1-PDI interactions, the response to redox flux and the implications for disulfide bond formation in the mammalian endoplasmic reticulum. Philos Trans R Soc Lond B Biol Sci. 2013;368:20110403 pubmed publisher
    ..In addition, we will discuss whether higher order protein complexes play a role in Ero1 function. ..
  35. Chen X, Duan L, Luo P, Hu G, Yu X, Liu J, et al. FBXO6-Mediated Ubiquitination and Degradation of Ero1L Inhibits Endoplasmic Reticulum Stress-Induced Apoptosis. Cell Physiol Biochem. 2016;39:2501-2508 pubmed
    ..in an N-glycan dependent manner by LC/MS spectrum and confirmed the interaction between FBXO6 and glycosylated Ero1L, a protein disulfide oxidase in endoplasmic reticulum (ER)...
  36. Hsu C, Hsu C, Hsueh C, Wang C, Wu Y, Wu C, et al. Identification and Characterization of Potential Biomarkers by Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma. Mol Cell Proteomics. 2016;15:2396-410 pubmed publisher
    ..Based on a bioinformatics analysis and literature search, we selected six candidates (ERO1L, PABPC4, RCC1, RPS25, NARS, and TARS) from a set of 133 proteins that presented a 1...
  37. Tanaka T, Kutomi G, Kajiwara T, Kukita K, Kochin V, Kanaseki T, et al. Cancer-associated oxidoreductase ERO1-α drives the production of VEGF via oxidative protein folding and regulating the mRNA level. Br J Cancer. 2016;114:1227-34 pubmed publisher
    ..Our study has established a novel link between expression of ERO1-α and secretion of VEGF, providing new evidence for the effectiveness of ERO1-α-targeted therapy in patients with ERO1-α-expressed cancer. ..
  38. Kukita K, Tamura Y, Tanaka T, Kajiwara T, Kutomi G, Saito K, et al. Cancer-Associated Oxidase ERO1-α Regulates the Expression of MHC Class I Molecule via Oxidative Folding. J Immunol. 2015;194:4988-96 pubmed publisher
    ..Thus, the cancer-associated ERO1-α regulates the expression of the MHC class I molecule via oxidative folding. ..
  39. Rao J, Zhang C, Wang P, Lu L, Qian X, Qin J, et al. C/EBP homologous protein (CHOP) contributes to hepatocyte death via the promotion of ERO1α signalling in acute liver failure. Biochem J. 2015;466:369-78 pubmed publisher
    ..Therefore, targeting CHOP/ERO1α signalling could be a novel therapeutic approach during ALF. ..
  40. Tanaka T, Kajiwara T, Torigoe T, Okamoto Y, Sato N, Tamura Y. Cancer-associated oxidoreductase ERO1-α drives the production of tumor-promoting myeloid-derived suppressor cells via oxidative protein folding. J Immunol. 2015;194:2004-10 pubmed publisher
    ..These results suggest that overexpression of ERO1-α in the tumor inhibits the T cell response by recruiting polymorphonuclear MDSCs via regulation of MDSC-prone cytokines and chemokines. ..
  41. Tanaka T, Kutomi G, Kajiwara T, Kukita K, Kochin V, Kanaseki T, et al. Cancer-associated oxidoreductase ERO1-α promotes immune escape through up-regulation of PD-L1 in human breast cancer. Oncotarget. 2017;8:24706-24718 pubmed publisher
    ..The results suggest that targeting ERO1-α in tumor cells can be a novel approach for cancer immunotherapy. Therefore, the role of ERO1-α in tumor-mediated immunosuppression should be further explored. ..
  42. Wang L, Zhang L, Niu Y, Sitia R, Wang C. Glutathione peroxidase 7 utilizes hydrogen peroxide generated by Ero1? to promote oxidative protein folding. Antioxid Redox Signal. 2014;20:545-56 pubmed publisher
    ..Thus, the Ero1?/GPx7/PDI triad generates two disulfide bonds and two H2O molecules at the expense of a single O2 molecule. ..
  43. Ramming T, Kanemura S, Okumura M, Inaba K, Appenzeller Herzog C. Cysteines 208 and 241 in Ero1α are required for maximal catalytic turnover. Redox Biol. 2016;7:14-20 pubmed publisher
    ..Two possible mechanisms by which thiol-disulfide exchange at the Cys(208)/Cys(241) pair stimulates the catalytic turnover under reducing conditions are discussed. ..
  44. Zhang L, Niu Y, Zhu L, Fang J, Wang X, Wang L, et al. Different interaction modes for protein-disulfide isomerase (PDI) as an efficient regulator and a specific substrate of endoplasmic reticulum oxidoreductin-1α (Ero1α). J Biol Chem. 2014;289:31188-99 pubmed publisher
    ..The novel modes for PDI as a competent regulator and a specific substrate of Ero1α govern efficient and faithful oxidative protein folding and maintain the ER redox homeostasis. ..
  45. van Lith M, Hartigan N, Hatch J, Benham A. PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum. J Biol Chem. 2005;280:1376-83 pubmed
    ..PDILT interacts with the oxidoreductase Ero1alpha, demonstrating that the N-terminal cysteine of the CXXC sequence is not required for binding of PDI family ..
  46. Battle D, Gunasekara S, Watson G, Ahmed E, Saysell C, Altaf N, et al. Expression of the endoplasmic reticulum oxidoreductase Ero1? in gastro-intestinal cancer reveals a link between homocysteine and oxidative protein folding. Antioxid Redox Signal. 2013;19:24-35 pubmed publisher
    ..Proteins and metabolites involved in disulfide bond formation and redox regulation may be suitable targets for both biomarker and drug development in GI cancer. ..