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. Predominantly monomer. May function both as a monomer and a homodimer. Interacts with PDILT. Stimulated by hypoxia; suggesting that it is regulated via the HIF-pathway. Widely expressed at low level. Expressed at high level in upper digestive tract. Highly expressed in esophagus. Weakly expressed in stomach and duodenum. 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. Belongs to the EROs family. Note: This description may include information from UniProtKB.
Protein type: Secreted, signal peptide; Oxidoreductase; Secreted; EC 1.8.4.-
Molecular Function: protein binding; protein disulfide isomerase activity; protein disulfide oxidoreductase activity; oxidoreductase activity; oxidoreductase activity, acting on sulfur group of donors, disulfide as acceptor
Biological Process: extracellular matrix organization and biogenesis; protein maturation via protein folding; protein folding; chaperone cofactor-dependent protein folding; unfolded protein response; protein modification process; response to temperature stimulus; response to reactive oxygen species; cellular protein metabolic process; 4-hydroxyproline metabolic process; cell redox homeostasis; release of sequestered calcium ion into cytosol; brown fat cell differentiation
LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.