Disulfide Isomerase (PDI) Active Protein

This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex. [provided by RefSeq, Jul 2008]

PDIA1: This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations, functions as a chaperone that inhibits aggregation of misfolded proteins. At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Homodimer. Monomers and homotetramers may also occur. Also constitutes the structural subunit of prolyl 4-hydroxylase and of the microsomal triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes both enzymes and retain them in the ER without contributing to the catalytic activity. Binds UBQLN1. Binds to CD4, and upon HIV-1 binding to the cell membrane, is part of a P4HB/PDI-CD4-CXCR4-gp120 complex. Belongs to the protein disulfide isomerase family.

Protein type: EC 5.3.4.1; Endoplasmic reticulum; Oxidoreductase; Isomerase; Nuclear receptor co-regulator

Chromosomal Location of Human Ortholog: 17q25

Cellular Component: focal adhesion; endoplasmic reticulum lumen; endoplasmic reticulum; extracellular region; ER-Golgi intermediate compartment; plasma membrane; melanosome

Molecular Function: protein binding; enzyme binding; procollagen-proline 4-dioxygenase activity; protein heterodimerization activity; endopeptidase activity; protein disulfide isomerase activity

Biological Process: extracellular matrix organization and biogenesis; response to reactive oxygen species; protein folding; cell redox homeostasis; lipoprotein metabolic process; peptidyl-proline hydroxylation to 4-hydroxy-L-proline; proteolysis

Disease: Cole-carpenter Syndrome 1