P4HB
Description
The P4HB (prolyl 4-hydroxylase subunit beta) is a protein-coding gene located on chromosome 17.
Protein disulfide-isomerase, also known as the beta-subunit of prolyl 4-hydroxylase (P4HB), is an enzyme that in humans encoded by the P4HB gene. The human P4HB gene is localized in chromosome 17q25. Unlike other prolyl 4-hydroxylase family proteins, this protein is multifunctional and acts as an oxidoreductase for disulfide formation, breakage, and isomerization. The activity of P4HB is tightly regulated. Both dimer dissociation and substrate binding are likely to enhance its enzymatic activity during the catalysis process.
== Structure == P4HB has four thioredoxin domains (a, b, b’, and a’), with two CGHC active sites in the a and a’ domains. In both the reduced and oxidized state, these domains are arranged as a horseshoe shape. In reduced P4HB, domains a, b, and b' are in the same plane, while domain a' twists out at a ~45° angle. When oxidized, the four domains stay in the same plane, and the distance between the active sites is larger than that in the reduced state. The oxidized form also exposes more hydrophobic areas and possesses a larger cleft to facilitate substrate binding.
P4HB, also known as protein disulfide-isomerase (PDI), is a multifunctional protein that catalyzes the formation, breakage, and rearrangement of disulfide bonds. At the cell surface, it acts as a reductase, cleaving disulfide bonds of proteins attached to the cell, potentially causing structural modifications of exofacial proteins. Inside the cell, it forms and rearranges disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, it functions as a chaperone, inhibiting aggregation of misfolded proteins. At low concentrations, it facilitates aggregation (anti-chaperone activity). It may be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. P4HB also acts as a structural subunit of various enzymes, such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. It is a receptor for LGALS9, which interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration.
P4HB is also known as CLCRP1, DSI, ERBA2L, GIT, P4Hbeta, PDI, PDIA1, PHDB, PO4DB, PO4HB, PROHB.
