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Reviewed, UniProtKB/Swiss-Prot Q96HE7 (ERO1A_HUMAN)

Last modified December 15, 2009. Version 74. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    ERO1-like protein alpha
      Short name=ERO1-L-alpha
      Short name=ERO1-L
    EC=1.8.4.-
Alternative name(s):
    Oxidoreductin-1-L-alpha
    Endoplasmic oxidoreductin-1-like protein
Gene names
Name: ERO1L
ORF Names: UNQ434/PRO865
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length468 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

General annotation (Comments)

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. Ref.1 Ref.7 Ref.9 Ref.11 Ref.17 Ref.18

Cofactor

FAD. Ref.18

Enzyme regulation

Enzyme activity is tighly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-94 and Cys-131, and between Cys-99 and Cys-104. Glutathione may be required to regulate its activity in the endoplasmic reticulum. Ref.17 Ref.18 Ref.15

Subunit structure

Predominantly monomer. May function both as a monomer and a homodimer. Interacts with PDILT. Ref.9 Ref.18 Ref.10 Ref.16

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side. Note: The association with ERP44 is essential for its retention in the endoplasmic reticulum. Ref.1 Ref.13

Tissue specificity

Widely expressed at low level. Expressed at high level in upper digestive tract. Highly expressed in esophagus. Weakly expressed in stomach and duodenum. Ref.8

Induction

Stimulated by hypoxia; suggesting that it is regulated via the HIF-pathway. Ref.12

Post-translational modification

N-glycosylated. Ref.1 Ref.7 Ref.20

The Cys-94/Cys-99 and Cys-394/Cys-397 disulfide bonds constitute the redox-active center. The Cys-94/Cys-99 disulfide bond may accept electron from P4HB and funnel them to the active site disulfide Cys-394/Cys-397 By similarity.

Sequence similarities

Belongs to the EROs family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323
Chain24 – 468445ERO1-like protein alpha
PRO_0000008415

Sites

Binding site1871FAD By similarity
Binding site1891FAD By similarity
Binding site2001FAD By similarity
Binding site2521FAD By similarity
Binding site2551FAD By similarity
Binding site2871FAD By similarity

Amino acid modifications

Glycosylation2801N-linked (GlcNAc...) Ref.20
Glycosylation3841N-linked (GlcNAc...) Potential
Disulfide bond35 ↔ 46Or C-35 with C-48 Ref.17 Ref.18
Disulfide bond37 ↔ 48Or C-35 with C-46 Ref.17 Ref.18
Disulfide bond85 ↔ 391 Ref.17 Ref.18
Disulfide bond94 ↔ 131Alternate Ref.17 Ref.18
Disulfide bond94 ↔ 99Redox-active Ref.17 Ref.18
Disulfide bond99 ↔ 104Alternate Ref.17 Ref.18
Disulfide bond208 ↔ 241 Ref.17 Ref.18
Disulfide bond394 ↔ 397Redox-active Ref.17 Ref.18

Experimental info

Mutagenesis851C → A: Alters protein folding and stability. Loss of regulatory disulfide bond formation and increased activity towards PDI; when associated with A-131. Ref.18 Ref.14
Mutagenesis851C → S: Induces a decrease in activity. Ref.18 Ref.14
Mutagenesis941C → S: Induces a decrease in activity towards thioredoxin. Loss of activity towards thioredoxin and loss of regulatory disulfide bond formation; when associated with A-99. Ref.18 Ref.14
Mutagenesis991C → A: Acts as a weak dominant-negative mutant. Loss of activity towards thioredoxin. Loss of regulatory disulfide bond formation; when associated with A-94. Ref.18 Ref.14
Mutagenesis1041C → A: No effect. Strongly increased activity towards PDI; when associated with A-131. Ref.18 Ref.14
Mutagenesis1041C → S: No effect. Ref.18 Ref.14
Mutagenesis1311C → A: Loss of regulatory disulfide bond formation and increased activity towards PDI. Loss of regulatory disulfide bond formation and strongly increased activity towards PDI; when associated with A-85. Loss of regulatory disulfide bond formation and strongly increased activity towards PDI; when associated with A-104. Ref.17 Ref.18 Ref.14
Mutagenesis1661C → A: No effect. Ref.18 Ref.14
Mutagenesis2081C → A or S: No effect. Ref.18 Ref.14
Mutagenesis2411C → A or S: No effect. Ref.18 Ref.14
Mutagenesis2801N → A: No effect on activity. Ref.14
Mutagenesis3841N → A: No effect on activity. Ref.14
Mutagenesis3911C → A: Alters protein folding. Prevents formation of regulatory disulfide bond and down-regulation of activity. Decreases association with P4HB. Ref.1 Ref.7 Ref.14
Mutagenesis3941C → A: Retains activity towards PDI. Does not act as a dominant negative mutant. Induces defects in folding. Remains associated with P4HB. Ref.1 Ref.7 Ref.9 Ref.17 Ref.14
Mutagenesis3971C → A: Acts as a dominant negative mutant; does not induce defects in folding; remains associated with P4HB. Ref.7 Ref.9 Ref.14
Sequence conflict4561E → K in AAH08674. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q96HE7-1 [UniParc].

Last modified July 19, 2004. Version 2.
Checksum: 92ECE6531C9CCA33

FASTA46854,393
        10         20         30         40         50         60 
MGRGWGFLFG LLGAVWLLSS GHGEEQPPET AAQRCFCQVS GYLDDCTCDV ETIDRFNNYR 

        70         80         90        100        110        120 
LFPRLQKLLE SDYFRYYKVN LKRPCPFWND ISQCGRRDCA VKPCQSDEVP DGIKSASYKY 

       130        140        150        160        170        180 
SEEANNLIEE CEQAERLGAV DESLSEETQK AVLQWTKHDD SSDNFCEADD IQSPEAEYVD 

       190        200        210        220        230        240 
LLLNPERYTG YKGPDAWKIW NVIYEENCFK PQTIKRPLNP LASGQGTSEE NTFYSWLEGL 

       250        260        270        280        290        300 
CVEKRAFYRL ISGLHASINV HLSARYLLQE TWLEKKWGHN ITEFQQRFDG ILTEGEGPRR 

       310        320        330        340        350        360 
LKNLYFLYLI ELRALSKVLP FFERPDFQLF TGNKIQDEEN KMLLLEILHE IKSFPLHFDE 

       370        380        390        400        410        420 
NSFFAGDKKE AHKLKEDFRL HFRNISRIMD CVGCFKCRLW GKLQTQGLGT ALKILFSEKL 

       430        440        450        460 
IANMPESGPS YEFHLTRQEI VSLFNAFGRI STSVKELENF RNLLQNIH 

« Hide

References

« Hide 'large scale' references
[1]"ERO1-L, a human protein that favors disulfide bond formation in the endoplasmic reticulum."
Cabibbo A., Pagani M., Fabbri M., Rocchi M., Farmery M.R., Bulleid N.J., Sitia R.
J. Biol. Chem. 275:4827-4833(2000) [PubMed: 10671517] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, GLYCOSYLATION, MUTAGENESIS OF CYS-391 AND CYS-394.
Tissue: Embryonic carcinoma.
[2]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Trachea.
[4]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed: 12508121] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Eye.
[6]"The C-terminal domain of yeast Ero1p mediates membrane localization and is essential for function."
Pagani M., Pilati S., Bertoli G., Valsasina B., Sitia R.
FEBS Lett. 508:117-120(2001) [PubMed: 11707280] [Abstract]
Cited for: PROTEIN SEQUENCE OF N-TERMINUS, MASS SPECTROMETRY.
[7]"The CXXCXXC motif determines the folding, structure and stability of human Ero1-Lalpha."
Benham A.M., Cabibbo A., Fassio A., Bulleid N., Sitia R., Braakman I.
EMBO J. 19:4493-4502(2000) [PubMed: 10970843] [Abstract]
Cited for: FUNCTION, GLYCOSYLATION, MUTAGENESIS OF CYS-391; CYS-394 AND CYS-397.
[8]"Endoplasmic reticulum oxidoreductin 1-lbeta (ERO1-Lbeta), a human gene induced in the course of the unfolded protein response."
Pagani M., Fabbri M., Benedetti C., Fassio A., Pilati S., Bulleid N.J., Cabibbo A., Sitia R.
J. Biol. Chem. 275:23685-23692(2000) [PubMed: 10818100] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"Manipulation of oxidative protein folding and PDI redox state in mammalian cells."
Mezghrani A., Fassio A., Benham A., Simmen T., Braakman I., Sitia R.
EMBO J. 20:6288-6296(2001) [PubMed: 11707400] [Abstract]
Cited for: FUNCTION, POTENTIAL HOMODIMERIZATION, ASSOCIATION WITH P4HB, LACK OF ASSOCIATION WITH GRP58, MUTAGENESIS OF CYS-394 AND CYS-397.
[10]"ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family."
Anelli T., Alessio M., Mezghrani A., Simmen T., Talamo F., Bachi A., Sitia R.
EMBO J. 21:835-844(2002) [PubMed: 11847130] [Abstract]
Cited for: INTERACTION WITH ERP44.
[11]"Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1."
Tsai B., Rapoport T.A.
J. Cell Biol. 159:207-216(2002) [PubMed: 12403808] [Abstract]
Cited for: FUNCTION.
[12]"The cellular oxygen tension regulates expression of the endoplasmic oxidoreductase ERO1-Lalpha."
Gess B., Hofbauer K.H., Wenger R.H., Lohaus C., Meyer H.E., Kurtz A.
Eur. J. Biochem. 270:2228-2235(2003) [PubMed: 12752442] [Abstract]
Cited for: INDUCTION.
[13]"Thiol-mediated protein retention in the endoplasmic reticulum: the role of ERp44."
Anelli T., Alessio M., Bachi A., Bergamelli L., Bertoli G., Camerini S., Mezghrani A., Ruffato E., Simmen T., Sitia R.
EMBO J. 22:5015-5022(2003) [PubMed: 14517240] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[14]"Two conserved cysteine triads in human Ero1alpha cooperate forefficient disulfide bond formation in the ER."
Bertoli G., Simmen T., Anelli T., Nerini Molteni S., Fesce R., Sitia R.
J. Biol. Chem. 279:30047-30052(2004) [PubMed: 15136577] [Abstract]
Cited for: MUTAGENESIS OF CYS-85; CYS-94; CYS-99; CYS-104; CYS-131; CYS-166; CYS-208; CYS-241; ASN-280; ASN-384; CYS-391; CYS-394 AND CYS-397.
[15]"Glutathione limits Ero1-dependent oxidation in the endoplasmic reticulum."
Nerini Molteni S., Fassio A., Ciriolo M.R., Filomeni G., Pasqualetto E., Fagioli C., Sitia R.
J. Biol. Chem. 279:32667-32673(2004) [PubMed: 15161913] [Abstract]
Cited for: ENZYME REGULATION.
[16]"PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum."
van Lith M., Hartigan N., Hatch J., Benham A.M.
J. Biol. Chem. 280:1376-1383(2005) [PubMed: 15475357] [Abstract]
Cited for: INTERACTION WITH PDILT.
[17]"A novel disulphide switch mechanism in Ero1alpha balances ER oxidation in human cells."
Appenzeller-Herzog C., Riemer J., Christensen B., Soerensen E.S., Ellgaard L.
EMBO J. 27:2977-2987(2008) [PubMed: 18833192] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, DISULFIDE BONDS, MUTAGENESIS OF CYS-131 AND CYS-394, MASS SPECTROMETRY.
[18]"Low reduction potential of Ero1alpha regulatory disulphides ensures tight control of substrate oxidation."
Baker K.M., Chakravarthi S., Langton K.P., Sheppard A.M., Lu H., Bulleid N.J.
EMBO J. 27:2988-2997(2008) [PubMed: 18971943] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, COFACTOR, SUBUNIT, DISULFIDE BONDS, MUTAGENESIS OF CYS-85; CYS-94; CYS-99; CYS-104; CYS-131; CYS-166; CYS-208 AND CYS-241.
[19]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[20]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-280, MASS SPECTROMETRY.
Tissue: Liver.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF081886 mRNA. Translation: AAF35260.1.
AF123887 mRNA. Translation: AAF06104.1.
AY358463 mRNA. Translation: AAQ88828.1.
AK292839 mRNA. Translation: BAF85528.1.
AL133453 Genomic DNA. No translation available.
BC008674 mRNA. Translation: AAH08674.1.
BC012941 mRNA. Translation: AAH12941.1.
IPIIPI00386755.
RefSeqNP_055399.1.
UniGeneHs.592304

3D structure databases

ModBaseSearch...

Protein-protein interaction databases

STRINGQ96HE7.

Proteomic databases

PeptideAtlasQ96HE7.
PRIDEQ96HE7.

Genome annotation databases

EnsemblENST00000395686; ENSP00000379042; ENSG00000197930; Homo sapiens. [Genome view]
GeneID30001.
KEGGhsa:30001.
UCSCuc001wzv.1. human.

Organism-specific databases

CTD30001.
GeneCardsGC14M052178.
H-InvDBHIX0011660.
HGNCHGNC:13280. ERO1L.
HPAHPA026653.
PharmGKBPA27862.
GenAtlasSearch...

Phylogenomic databases

HOGENOMHBG521237.
HOVERGENQ96HE7.
OMADDIQSPD.
OrthoDBEOG9RBT4J.

Enzyme and pathway databases

BioCycCATTLE:ENSBTAG00000015716-MON.
ReactomeREACT_15380. Diabetes pathways.

Gene expression databases

ArrayExpressQ96HE7.
BgeeQ96HE7.
CleanExHS_ERO1L.
GenevestigatorQ96HE7.
GermOnlineENSG00000197930. Homo sapiens.

Family and domain databases

InterProIPR007266. ERO1.
[Graphical view]
PANTHERPTHR12613. ERO1. 1 hit.
PfamPF04137. ERO1. 1 hit.
[Graphical view]
PIRSFPIRSF017205. ERO1. 1 hit.
ProtoNetSearch...

Other Resources

NextBio52816.

Entry information

Entry nameERO1A_HUMAN
AccessionPrimary (citable) accession number: Q96HE7
Secondary accession number(s): A8K9X4 expand/collapse secondary AC list , A8MYW1, Q7LD45, Q9P1Q9, Q9UKV6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 19, 2004
Last modified: December 15, 2009
This is version 74 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents