ID:ERO1A_HUMAN DESCRIPTION: RecName: Full=ERO1-like protein alpha; Short=ERO1-L; Short=ERO1-L-alpha; EC=1.8.4.-; AltName: Full=Endoplasmic oxidoreductin-1-like protein; AltName: Full=Oxidoreductin-1-L-alpha; Flags: Precursor; 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. Plays an important role in ER stress-induced, CHOP- dependent apoptosis by activating the inositol 1,4,5-trisphosphate receptor IP3R1. COFACTOR: FAD. ENZYME REGULATION: 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. SUBUNIT: Predominantly monomer. May function both as a monomer and a homodimer. Interacts with PDILT. SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side. Note=The association with ERP44 is essential for its retention in the endoplasmic reticulum. 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. INDUCTION: Stimulated by hypoxia; suggesting that it is regulated via the HIF-pathway. PTM: N-glycosylated. PTM: 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). SIMILARITY: Belongs to the EROs family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96HE7
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003756 protein disulfide isomerase activity GO:0005515 protein binding GO:0015035 protein disulfide oxidoreductase activity GO:0015036 disulfide oxidoreductase activity GO:0016491 oxidoreductase activity GO:0016671 oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor
Biological Process: GO:0006457 protein folding GO:0006464 cellular protein modification process GO:0006915 apoptotic process GO:0009266 response to temperature stimulus GO:0010260 animal organ senescence GO:0019471 4-hydroxyproline metabolic process GO:0022417 protein maturation by protein folding GO:0030198 extracellular matrix organization GO:0030968 endoplasmic reticulum unfolded protein response GO:0034599 cellular response to oxidative stress GO:0034975 protein folding in endoplasmic reticulum GO:0034976 response to endoplasmic reticulum stress GO:0045454 cell redox homeostasis GO:0050873 brown fat cell differentiation GO:0051085 chaperone mediated protein folding requiring cofactor GO:0051209 release of sequestered calcium ion into cytosol GO:0055114 oxidation-reduction process GO:0070059 intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress GO:0071456 cellular response to hypoxia
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
