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Identification
HMDB Protein ID HMDBP08269
Secondary Accession Numbers
  • 13981
Name ERO1-like protein alpha
Synonyms
  1. ERO1-L
  2. ERO1-L-alpha
  3. Endoplasmic oxidoreductin-1-like protein
  4. Oxidoreductin-1-L-alpha
Gene Name ERO1L
Protein Type Unknown
Biological Properties
General Function Involved in protein binding
Specific Function Essential oxidoreductase that oxidizes proteins in the endoplasmic reticulum to produce disulfide bonds. Acts by oxidizing directly P4HB/PDI isomerase through a direct disulfide exchange. Does not act as a direct oxidant of folding substrate, but relies on P4HB/PDI to transfer oxidizing equivalent. Associates with ERP44 but not with GRP54, demonstrating that it does not oxidize all PDI related proteins and can discriminate between PDI and related proteins. Its reoxidation probably involves electron transfer to molecular oxygen via FAD. Acts independently of glutathione. May be responsible for a significant proportion of reactive oxygen species (ROS) in the cell, thereby being a source of oxidative stress. Required for the folding of immunoglobulin proteins. Responsible for the release of the unfolded cholera toxin from reduced P4HB/PDI in case of infection by V.cholerae, thereby playing a role in retrotranslocation of the toxin
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
endoplasmic reticulum membrane
organelle membrane
Function
oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
protein binding
oxidoreductase activity, acting on a sulfur group of donors
oxidoreductase activity
fad or fadh2 binding
Process
metabolic process
macromolecule metabolic process
cellular protein metabolic process
protein thiol-disulfide exchange
protein folding
oxidation reduction
protein metabolic process
Cellular Location
  1. Peripheral membrane protein
  2. Endoplasmic reticulum membrane
  3. Lumenal side
Gene Properties
Chromosome Location Chromosome:1
Locus 14q22.1
SNPs ERO1L
Gene Sequence
>1407 bp
ATGGGCCGCGGCTGGGGATTCTTGTTTGGCCTCCTGGGCGCCGTGTGGCTGCTCAGCTCG
GGCCACGGAGAGGAGCAGCCCCCGGAGACAGCGGCACAGAGGTGCTTCTGCCAGGTTAGT
GGTTACTTGGATGATTGTACCTGTGATGTTGAAACCATTGATAGATTTAATAACTACAGG
CTTTTCCCAAGACTACAAAAACTTCTTGAAAGTGACTACTTTAGGTATTACAAGGTAAAC
CTGAAGAGGCCGTGTCCTTTCTGGAATGACATCAGCCAGTGTGGAAGAAGGGACTGTGCT
GTCAAACCATGTCAATCTGATGAAGTTCCTGATGGAATTAAATCTGCGAGCTACAAGTAT
TCTGAAGAAGCCAATAATCTCATTGAAGAATGTGAACAAGCTGAACGACTTGGAGCAGTG
GATGAATCTCTGAGTGAGGAAACACAGAAGGCTGTTCTTCAGTGGACCAAGCATGATGAT
TCTTCAGATAACTTCTGTGAAGCTGATGACATTCAGTCCCCTGAAGCTGAATATGTAGAT
TTGCTTCTTAATCCTGAGCGCTACACTGGTTACAAGGGACCAGATGCTTGGAAAATATGG
AATGTCATCTACGAAGAAAACTGTTTTAAGCCACAGACAATTAAAAGACCTTTAAATCCT
TTGGCTTCTGGTCAAGGGACAAGTGAAGAGAACACTTTTTACAGTTGGCTAGAAGGTCTC
TGTGTAGAAAAAAGAGCATTCTACAGACTTATATCTGGCCTACATGCAAGCATTAATGTG
CATTTGAGTGCAAGATATCTTTTACAAGAGACCTGGTTAGAAAAGAAATGGGGACACAAC
ATTACAGAATTTCAACAGCGATTTGATGGAATTTTGACTGAAGGAGAAGGTCCAAGAAGG
CTTAAGAACTTGTATTTTCTCTACTTAATAGAACTAAGGGCTTTATCCAAAGTGTTACCA
TTCTTCGAGCGCCCAGATTTTCAACTCTTTACTGGAAATAAAATTCAGGATGAGGAAAAC
AAAATGTTACTTCTGGAAATACTTCATGAAATCAAGTCATTTCCTTTGCATTTTGATGAG
AATTCATTTTTTGCTGGGGATAAAAAAGAAGCACACAAACTAAAGGAGGACTTTCGACTG
CATTTTAGAAATATTTCAAGAATTATGGATTGTGTTGGTTGTTTTAAATGTCGTCTGTGG
GGAAAGCTTCAGACTCAGGGTTTGGGCACTGCTCTGAAGATCTTATTTTCTGAGAAATTG
ATAGCAAATATGCCAGAAAGTGGACCTAGTTATGAATTCCATCTAACCAGACAAGAAATA
GTATCATTATTCAACGCATTTGGAAGAATTTCTACAAGTGTGAAAGAATTAGAAAACTTC
AGGAACTTGTTACAGAATATTCATTAA
Protein Properties
Number of Residues 468
Molecular Weight 54392.1
Theoretical pI 5.41
Pfam Domain Function
Signals
  • 1-23
Transmembrane Regions
  • None
Protein Sequence
>ERO1-like protein alpha
MGRGWGFLFGLLGAVWLLSSGHGEEQPPETAAQRCFCQVSGYLDDCTCDVETIDRFNNYR
LFPRLQKLLESDYFRYYKVNLKRPCPFWNDISQCGRRDCAVKPCQSDEVPDGIKSASYKY
SEEANNLIEECEQAERLGAVDESLSEETQKAVLQWTKHDDSSDNFCEADDIQSPEAEYVD
LLLNPERYTGYKGPDAWKIWNVIYEENCFKPQTIKRPLNPLASGQGTSEENTFYSWLEGL
CVEKRAFYRLISGLHASINVHLSARYLLQETWLEKKWGHNITEFQQRFDGILTEGEGPRR
LKNLYFLYLIELRALSKVLPFFERPDFQLFTGNKIQDEENKMLLLEILHEIKSFPLHFDE
NSFFAGDKKEAHKLKEDFRLHFRNISRIMDCVGCFKCRLWGKLQTQGLGTALKILFSEKL
IANMPESGPSYEFHLTRQEIVSLFNAFGRISTSVKELENFRNLLQNIH
GenBank ID Protein 7021226
UniProtKB/Swiss-Prot ID Q96HE7
UniProtKB/Swiss-Prot Entry Name ERO1A_HUMAN
PDB IDs Not Available
GenBank Gene ID AF081886
GeneCard ID ERO1L
GenAtlas ID ERO1L
HGNC ID HGNC:13280
References
General References
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  4. Clark HF, Gurney AL, Abaya E, Baker K, Baldwin D, Brush J, Chen J, Chow B, Chui C, Crowley C, Currell B, Deuel B, Dowd P, Eaton D, Foster J, Grimaldi C, Gu Q, Hass PE, Heldens S, Huang A, Kim HS, Klimowski L, Jin Y, Johnson S, Lee J, Lewis L, Liao D, Mark M, Robbie E, Sanchez C, Schoenfeld J, Seshagiri S, Simmons L, Singh J, Smith V, Stinson J, Vagts A, Vandlen R, Watanabe C, Wieand D, Woods K, Xie MH, Yansura D, Yi S, Yu G, Yuan J, Zhang M, Zhang Z, Goddard A, Wood WI, Godowski P, Gray A: The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. 2003 Oct;13(10):2265-70. Epub 2003 Sep 15. [PubMed:12975309 ]
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  6. Anelli T, Alessio M, Mezghrani A, Simmen T, Talamo F, Bachi A, Sitia R: ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family. EMBO J. 2002 Feb 15;21(4):835-44. [PubMed:11847130 ]
  7. Anelli T, Alessio M, Bachi A, Bergamelli L, Bertoli G, Camerini S, Mezghrani A, Ruffato E, Simmen T, Sitia R: Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44. EMBO J. 2003 Oct 1;22(19):5015-22. [PubMed:14517240 ]
  8. Cabibbo A, Pagani M, Fabbri M, Rocchi M, Farmery MR, Bulleid NJ, Sitia R: ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum. J Biol Chem. 2000 Feb 18;275(7):4827-33. [PubMed:10671517 ]
  9. 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 Nov 9;508(1):117-20. [PubMed:11707280 ]
  10. Benham AM, 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 Sep 1;19(17):4493-502. [PubMed:10970843 ]
  11. Pagani M, Fabbri M, Benedetti C, Fassio A, Pilati S, Bulleid NJ, Cabibbo A, Sitia R: Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response. J Biol Chem. 2000 Aug 4;275(31):23685-92. [PubMed:10818100 ]
  12. 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 Nov 15;20(22):6288-96. [PubMed:11707400 ]
  13. Tsai B, Rapoport TA: Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1. J Cell Biol. 2002 Oct 28;159(2):207-16. Epub 2002 Oct 28. [PubMed:12403808 ]
  14. Gess B, Hofbauer KH, Wenger RH, Lohaus C, Meyer HE, Kurtz A: The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-Lalpha. Eur J Biochem. 2003 May;270(10):2228-35. [PubMed:12752442 ]
  15. Bertoli G, Simmen T, Anelli T, Molteni SN, 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 Jul 16;279(29):30047-52. Epub 2004 May 10. [PubMed:15136577 ]
  16. Molteni SN, Fassio A, Ciriolo MR, Filomeni G, Pasqualetto E, Fagioli C, Sitia R: Glutathione limits Ero1-dependent oxidation in the endoplasmic reticulum. J Biol Chem. 2004 Jul 30;279(31):32667-73. Epub 2004 May 25. [PubMed:15161913 ]
  17. van Lith M, Hartigan N, Hatch J, Benham AM: 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 Jan 14;280(2):1376-83. Epub 2004 Oct 8. [PubMed:15475357 ]
  18. Appenzeller-Herzog C, Riemer J, Christensen B, Sorensen ES, Ellgaard L: A novel disulphide switch mechanism in Ero1alpha balances ER oxidation in human cells. EMBO J. 2008 Nov 19;27(22):2977-87. doi: 10.1038/emboj.2008.202. Epub 2008 Oct 2. [PubMed:18833192 ]
  19. Baker KM, Chakravarthi S, Langton KP, Sheppard AM, Lu H, Bulleid NJ: Low reduction potential of Ero1alpha regulatory disulphides ensures tight control of substrate oxidation. EMBO J. 2008 Nov 19;27(22):2988-97. doi: 10.1038/emboj.2008.230. Epub 2008 Oct 30. [PubMed:18971943 ]