protein disulfide isomerase (cellular thyroid hormone binding protein, prolyl 4-hydroxylase subunit beta, P4HB, ERBA2L, PDI, PDIA1, PO4DB)

Function: - multifunctional protein - catalyzes formation, breakage & 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 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 trans-Golg precursor in hormone biogenesis - acts a structural subunit of: a) prolyl 4-hydroxylase b) microsomal triacylglycerol transfer protein MTTP stabilizes both enzymes & retains them in the ER without contributing to the catalytic activity - catalyzes the rearrangement of -S-S- bonds in proteins - binds UBQLN1 - binds to CD4, & upon HIV-1 binding to the cell membrane, is part of a P4HB/PDI-CD4-CXCR4-gp120 complex Structure: - homodimer - monomers & homotetramers may also occur - belongs to the protein disulfide isomerase family - contains 2 thioredoxin domains Compartment: - endoplasmic reticulum lumen, melanosome - in some cell types, seems to be also secreted or associated with the plasma membrane, where it undergoes constant shedding & replacement from intracellular sources (probable - localizes near CD4-enriched regions on lymphoid cell surfaces Expression: - highly abundant Pathology: - reduces & may activate fusogenic properties of HIV-1 gp120 surface protein, thereby enabling HIV-1 entry into the cell

Specific

endoplasmic reticulum protein ER60; PDIA3; protein disulfide isomerase A3; 58 kD microsomal protein; 58 kDa glucose regulated protein (ERp57, ERp60) protein disulfide-isomerase A2 (PDIp, PDIA2, PDIP) protein disulfide-isomerase A4; protein ERp-72; ERp72 (PDIA4, ERP70, ERP72) protein disulfide-isomerase A5; protein disulfide isomerase-related protein (PDIA5, PDIR) protein disulfide-isomerase A6; endoplasmic reticulum protein 5; ER protein 5; ERp5; protein disulfide isomerase P5; thioredoxin domain-containing protein 7 (PDIA6, ERP5, P5, TXNDC7) protein disulfide-isomerase TXNDC10 (thioredoxin domain-containing protein 10, thioredoxin-related transmembrane protein 3, TXNDC10, KIAA1830, TMX3)

General

isomerase oxidoreductase protein subunit

Properties

SIZE: entity length = 508 aa MW = 57 kD COMPARTMENT: endoplasmic reticulum MOTIF: signal sequence {1-17} thioredoxin domain SITE: 25-134 MOTIF: cysteine residue {C53} MODIFICATION: cysteine residue {C56} cysteine residue {C53} Contributes to redox potential value {54-54} Contributes to redox potential value {55-55} cysteine residue {C56} cysteine residue {C56} MODIFICATION: cysteine residue {C53} Lowers pKa of C-terminal Cys of first active site {120-120} thioredoxin domain SITE: 368-475 MOTIF: cysteine residue {C397} MODIFICATION: cysteine residue {C400} cysteine residue {C397} Contributes to redox potential value {398-398} Contributes to redox potential value {399-399} cysteine residue {C400} cysteine residue {C400} MODIFICATION: cysteine residue {C397} Lowers pKa of C-terminal Cys of second active site {461-461} Prevents secretion from ER {505-508}

Database Correlations

OMIM 176790 UniProt P07237 Pfam PF00085 Kegg hsa:5034 ENZYME 5.3.4.1

References

UniProt :accession P07237