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Protein

ERO1-like protein alpha

Gene

ERO1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell. Required for the proper folding of immunoglobulins. Involved in 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. Plays an important role in ER stress-induced, CHOP-dependent apoptosis by activating the inositol 1,4,5-trisphosphate receptor IP3R1.7 Publications

Cofactori

FAD2 Publications

Enzyme regulationi

Enzyme activity is tightly 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.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei187FADCombined sources1 Publication1
Binding sitei189FADCombined sources1 Publication1
Binding sitei200FADCombined sources1 Publication1
Binding sitei252FADCombined sources1 Publication1
Binding sitei255FADCombined sources1 Publication1
Binding sitei287FADCombined sources1 Publication1
Binding sitei300FADCombined sources1 Publication1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase

Keywords - Biological processi

Apoptosis, Electron transport, Transport

Keywords - Ligandi

FAD, Flavoprotein

Enzyme and pathway databases

ReactomeiR-HSA-264876. Insulin processing.
R-HSA-3299685. Detoxification of Reactive Oxygen Species.

Names & Taxonomyi

Protein namesi
Recommended name:
ERO1-like protein alpha (EC:1.8.4.-)
Short name:
ERO1-L
Short name:
ERO1-L-alpha
Alternative name(s):
Endoplasmic oxidoreductin-1-like protein
Endoplasmic reticulum oxidoreductase alphaImported
Oxidoreductin-1-L-alpha
Gene namesi
Name:ERO1AImported
Synonyms:ERO1L
ORF Names:UNQ434/PRO865
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:13280. ERO1A.

Subcellular locationi

GO - Cellular componenti

  • dendrite Source: Ensembl
  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum lumen Source: Reactome
  • endoplasmic reticulum membrane Source: GO_Central
  • intracellular membrane-bounded organelle Source: ProtInc
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi85C → A: Alters protein folding and stability. Loss of regulatory disulfide bond formation and increased activity towards P4HB; when associated with A-131. 2 Publications1
Mutagenesisi85C → S: Induces a decrease in activity. 2 Publications1
Mutagenesisi94C → 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. 2 Publications1
Mutagenesisi99C → A: Acts as a weak dominant-negative mutant. Loss of activity towards thioredoxin. Loss of regulatory disulfide bond formation; when associated with A-94. 2 Publications1
Mutagenesisi104C → A: No effect. Strongly increased activity towards P4HB and UPR induction, but no broad oxidative injury; when associated with A-131. 3 Publications1
Mutagenesisi104C → S: No effect. 3 Publications1
Mutagenesisi131C → A: Loss of regulatory disulfide bond formation and increased activity towards P4HB. Loss of regulatory disulfide bond formation and strongly increased activity towards P4HB; when associated with A-85. Loss of regulatory disulfide bond formation, strongly increased activity towards P4HB and UPR induction, but no broad oxidative injury; when associated with A-104. 4 Publications1
Mutagenesisi166C → A: No effect. 2 Publications1
Mutagenesisi208C → A or S: No effect. 2 Publications1
Mutagenesisi241C → A or S: No effect. 2 Publications1
Mutagenesisi280N → A: No effect on activity. 1 Publication1
Mutagenesisi384N → A: No effect on activity. 1 Publication1
Mutagenesisi391C → A: Alters protein folding. Prevents formation of regulatory disulfide bond and down-regulation of activity. Decreases association with P4HB. 3 Publications1
Mutagenesisi394C → A: Retains activity towards P4HB. Does not act as a dominant negative mutant. Induces defects in folding. Remains associated with P4HB. 5 Publications1
Mutagenesisi395F → D: Increased catalytical activity. 1 Publication1
Mutagenesisi397C → A: Acts as a dominant negative mutant; does not induce defects in folding; remains associated with P4HB. 3 Publications1

Organism-specific databases

DisGeNETi30001.
OpenTargetsiENSG00000197930.
PharmGKBiPA27862.

Chemistry databases

ChEMBLiCHEMBL1671609.

Polymorphism and mutation databases

BioMutaiERO1L.
DMDMi50400608.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 231 PublicationAdd BLAST23
ChainiPRO_000000841524 – 468ERO1-like protein alphaAdd BLAST445

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 48Combined sources1 Publication
Disulfide bondi37 ↔ 46Combined sources1 Publication
Disulfide bondi85 ↔ 391Combined sources1 Publication
Disulfide bondi94 ↔ 131AlternateCombined sources1 Publication
Disulfide bondi94 ↔ 99Redox-active; alternate2 Publications
Disulfide bondi99 ↔ 104AlternateCurated
Modified residuei106PhosphoserineCombined sources1
Modified residuei143PhosphoserineCombined sources1
Disulfide bondi208 ↔ 241Combined sources1 Publication
Glycosylationi280N-linked (GlcNAc...)1 Publication1
Glycosylationi384N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi394 ↔ 397Redox-activeCombined sources1 Publication

Post-translational modificationi

N-glycosylated.3 Publications
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). The regulatory Cys-99/Cys-104 disulfide bond stabilizes the other regulatory bond Cys-94/Cys-131 (PubMed:23027870).By similarity1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ96HE7.
MaxQBiQ96HE7.
PaxDbiQ96HE7.
PeptideAtlasiQ96HE7.
PRIDEiQ96HE7.

PTM databases

iPTMnetiQ96HE7.
PhosphoSitePlusiQ96HE7.
SwissPalmiQ96HE7.

Expressioni

Tissue specificityi

Widely expressed at low level. Expressed at high level in upper digestive tract. Highly expressed in esophagus. Weakly expressed in stomach and duodenum.1 Publication

Inductioni

Stimulated by hypoxia; suggesting that it is regulated via the HIF-pathway.1 Publication

Gene expression databases

BgeeiENSG00000197930.
CleanExiHS_ERO1L.
ExpressionAtlasiQ96HE7. baseline and differential.
GenevisibleiQ96HE7. HS.

Organism-specific databases

HPAiCAB034294.
HPA026653.
HPA030053.

Interactioni

Subunit structurei

Predominantly monomer. May function both as a monomer and a homodimer. Interacts with PDILT.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
APPBP2Q926243EBI-2564539,EBI-743771
P4HBP072372EBI-2564539,EBI-395883
PDIA3P301013EBI-2564539,EBI-979862

Protein-protein interaction databases

BioGridi119025. 25 interactors.
IntActiQ96HE7. 11 interactors.
MINTiMINT-144080.
STRINGi9606.ENSP00000379042.

Chemistry databases

BindingDBiQ96HE7.

Structurei

Secondary structure

1468
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 38Combined sources4
Beta strandi40 – 43Combined sources4
Beta strandi45 – 47Combined sources3
Helixi50 – 59Combined sources10
Helixi62 – 70Combined sources9
Helixi72 – 75Combined sources4
Beta strandi76 – 79Combined sources4
Helixi134 – 138Combined sources5
Helixi146 – 161Combined sources16
Beta strandi177 – 180Combined sources4
Helixi181 – 183Combined sources3
Helixi193 – 204Combined sources12
Helixi245 – 264Combined sources20
Beta strandi266 – 270Combined sources5
Beta strandi275 – 278Combined sources4
Helixi281 – 288Combined sources8
Helixi290 – 293Combined sources4
Helixi296 – 317Combined sources22
Helixi319 – 323Combined sources5
Helixi336 – 353Combined sources18
Beta strandi356 – 358Combined sources3
Helixi369 – 389Combined sources21
Helixi395 – 415Combined sources21
Helixi418 – 422Combined sources5
Beta strandi426 – 428Combined sources3
Beta strandi431 – 433Combined sources3
Helixi437 – 463Combined sources27

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AHQX-ray2.35A22-468[»]
3AHRX-ray3.07A22-468[»]
ProteinModelPortaliQ96HE7.
SMRiQ96HE7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96HE7.

Family & Domainsi

Sequence similaritiesi

Belongs to the EROs family.Curated

Keywords - Domaini

Redox-active center, Signal

Phylogenomic databases

eggNOGiKOG2608. Eukaryota.
COG5061. LUCA.
GeneTreeiENSGT00390000007753.
HOGENOMiHOG000012778.
HOVERGENiHBG051507.
InParanoidiQ96HE7.
KOiK10950.
OMAiFCEVDDI.
OrthoDBiEOG091G04ZQ.
PhylomeDBiQ96HE7.
TreeFamiTF314471.

Family and domain databases

InterProiIPR007266. Ero1.
[Graphical view]
PANTHERiPTHR12613. PTHR12613. 1 hit.
PfamiPF04137. ERO1. 1 hit.
[Graphical view]
PIRSFiPIRSF017205. ERO1. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q96HE7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGRGWGFLFG LLGAVWLLSS GHGEEQPPET AAQRCFCQVS GYLDDCTCDV
60 70 80 90 100
ETIDRFNNYR LFPRLQKLLE SDYFRYYKVN LKRPCPFWND ISQCGRRDCA
110 120 130 140 150
VKPCQSDEVP DGIKSASYKY SEEANNLIEE CEQAERLGAV DESLSEETQK
160 170 180 190 200
AVLQWTKHDD SSDNFCEADD IQSPEAEYVD LLLNPERYTG YKGPDAWKIW
210 220 230 240 250
NVIYEENCFK PQTIKRPLNP LASGQGTSEE NTFYSWLEGL CVEKRAFYRL
260 270 280 290 300
ISGLHASINV HLSARYLLQE TWLEKKWGHN ITEFQQRFDG ILTEGEGPRR
310 320 330 340 350
LKNLYFLYLI ELRALSKVLP FFERPDFQLF TGNKIQDEEN KMLLLEILHE
360 370 380 390 400
IKSFPLHFDE NSFFAGDKKE AHKLKEDFRL HFRNISRIMD CVGCFKCRLW
410 420 430 440 450
GKLQTQGLGT ALKILFSEKL IANMPESGPS YEFHLTRQEI VSLFNAFGRI
460
STSVKELENF RNLLQNIH
Length:468
Mass (Da):54,393
Last modified:July 19, 2004 - v2
Checksum:i92ECE6531C9CCA33
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti456E → K in AAH08674 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9709.1.
RefSeqiNP_055399.1. NM_014584.2.
UniGeneiHs.525339.
Hs.592304.

Genome annotation databases

EnsembliENST00000395686; ENSP00000379042; ENSG00000197930.
GeneIDi30001.
KEGGihsa:30001.
UCSCiuc001wzv.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS9709.1.
RefSeqiNP_055399.1. NM_014584.2.
UniGeneiHs.525339.
Hs.592304.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3AHQX-ray2.35A22-468[»]
3AHRX-ray3.07A22-468[»]
ProteinModelPortaliQ96HE7.
SMRiQ96HE7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119025. 25 interactors.
IntActiQ96HE7. 11 interactors.
MINTiMINT-144080.
STRINGi9606.ENSP00000379042.

Chemistry databases

BindingDBiQ96HE7.
ChEMBLiCHEMBL1671609.

PTM databases

iPTMnetiQ96HE7.
PhosphoSitePlusiQ96HE7.
SwissPalmiQ96HE7.

Polymorphism and mutation databases

BioMutaiERO1L.
DMDMi50400608.

Proteomic databases

EPDiQ96HE7.
MaxQBiQ96HE7.
PaxDbiQ96HE7.
PeptideAtlasiQ96HE7.
PRIDEiQ96HE7.

Protocols and materials databases

DNASUi30001.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000395686; ENSP00000379042; ENSG00000197930.
GeneIDi30001.
KEGGihsa:30001.
UCSCiuc001wzv.4. human.

Organism-specific databases

CTDi30001.
DisGeNETi30001.
GeneCardsiERO1L.
HGNCiHGNC:13280. ERO1A.
HPAiCAB034294.
HPA026653.
HPA030053.
MIMi615435. gene.
neXtProtiNX_Q96HE7.
OpenTargetsiENSG00000197930.
PharmGKBiPA27862.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2608. Eukaryota.
COG5061. LUCA.
GeneTreeiENSGT00390000007753.
HOGENOMiHOG000012778.
HOVERGENiHBG051507.
InParanoidiQ96HE7.
KOiK10950.
OMAiFCEVDDI.
OrthoDBiEOG091G04ZQ.
PhylomeDBiQ96HE7.
TreeFamiTF314471.

Enzyme and pathway databases

ReactomeiR-HSA-264876. Insulin processing.
R-HSA-3299685. Detoxification of Reactive Oxygen Species.

Miscellaneous databases

ChiTaRSiERO1L. human.
EvolutionaryTraceiQ96HE7.
GeneWikiiERO1L.
GenomeRNAii30001.
PROiQ96HE7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197930.
CleanExiHS_ERO1L.
ExpressionAtlasiQ96HE7. baseline and differential.
GenevisibleiQ96HE7. HS.

Family and domain databases

InterProiIPR007266. Ero1.
[Graphical view]
PANTHERiPTHR12613. PTHR12613. 1 hit.
PfamiPF04137. ERO1. 1 hit.
[Graphical view]
PIRSFiPIRSF017205. ERO1. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiERO1A_HUMAN
AccessioniPrimary (citable) accession number: Q96HE7
Secondary accession number(s): A8K9X4
, A8MYW1, Q7LD45, Q9P1Q9, Q9UKV6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: July 19, 2004
Last modified: November 2, 2016
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.