PPIB

Peptidyl-prolyl cis-trans isomerase B is an is_associated_with::enzyme that in humans is encoded by the PPIB is_associated_with::gene. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the is_associated_with::cis-trans is_associated_with::isomerization of proline imidic is_associated_with::peptide bonds, which allows it to regulate protein folding of is_associated_with::type I collagen. PPIB localizes to the is_associated_with::endoplasmic reticulum (ER) and is associated with viral infections and multiple is_associated_with::cancers.

Structure
PPIB contains a C-terminal ER retention motif that directs the protein to the ER organelle. Its N-terminal extension attaches it to its substrates.

Function
PPIB is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds and regulate protein folding and maturation. Generally, PPIases are found in all eubacteria and eukaryotes, as well as in a few archaebacteria, and thus are highly conserved. PPIB is the second of 18 cyclophilins to be identified in humans, after CypA.

PPIB localizes to the ER, where it interacts with proteins such as P3H1, CRTAP, BiP, GRP94, PDI, and calreticulin to form foldase and chaperone complexes and facilitate protein folding, especially for type I collagen. This protein is the major PPIase for type I collagen, since the collagen contains an abundance of prolines that require cis-trans isomerization for proper folding. Thus, PPIB is essential for collagen biosynthesis and post-translational modification and affects fibril assembly, matrix cross-linking, and bone mineralization.

In addition, it is associated with the secretory pathway and released in biological fluids. This protein can bind to cells derived from T- and B-lymphocytes, and may regulate cyclosporine A-mediated immunosuppression.

Clinical significance
PPIB contributes to the replication and infection of viruses causing diseases such as is_associated_with::AIDS, is_associated_with::hepatitis C, is_associated_with::measles, and is_associated_with::influenza A. Thus, therapeutic targeting of PPIB with selective inhibitors may prove effective in combating viral infections and inflammation. Currently, PPIB is employed as a biomarker for various types of cancer.

Interactions
PPIB has been shown to interact with:
 * is_associated_with::Apolipoprotein B.
 * is_associated_with::P3H1,
 * is_associated_with::CRTAP,
 * BiP,
 * is_associated_with::GRP94,
 * PDI, and
 * is_associated_with::calreticulin.