Peptidylprolyl isomerase A

Peptidylprolyl isomerase A (PPIA), also known as cyclophilin A (CypA) or rotamase A is an is_associated_with::enzyme that in humans is encoded by the PPIA is_associated_with::gene on chromosome 7. 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 many biological processes, including intracellular signaling, transcription, is_associated_with::inflammation, and is_associated_with::apoptosis. Due to its various functions, PPIA has been implicated in a broad range of inflammatory diseases, including atherosclerosis and arthritis, and viral infections.

Structure
PPIA is a globular enzyme with a barrel structure composed of eight β strands. Its active site is a hydrophobic pocket that binds peptides containing proline. Cyclosporine can bind this pocket to inhibit the protein’s enzymatic activity.

Function
This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in is_associated_with::oligopeptides and accelerate the folding of is_associated_with::proteins. Generally, PPIases are found in all eubacteria and eukaryotes, as well as in a few archaebacteria, and thus are highly conserved. Of the 18 known human cyclophilins, PPIA is the most abundantly expressed isozyme. In particular, PPIA is predominantly expressed in the nucleus and cytoplasm of the cell, where it partakes in intracellular signaling, protein transport, and transcription regulation. Moreover, the enzyme participates in inflammatory and apoptotic processes in extracellular settings. In the presence of is_associated_with::reactive oxygen species (ROS), vascular smooth muscle cells (VSMCs), monocytes/macrophages, and endothelial cells (ECs) secrete PPIA to induce an inflammatory response and mitigate tissue injury. PPIA may also activate Akt and NF-κB signaling, resulting in the upregulation of Bcl-2, an antiapoptotic protein, and thus preventing apoptosis in ECs in response to oxidative stress. Additionally, PPIA induces cell migration and proliferation in smooth muscle. In the case of T cells, PPIA regulates the T-cell-specific tyrosine kinase ITK upon T-cell receptor stimulation.

Clinical significance
As a proinflammatory cytokine, PPIA is highly involved in acute and chronic inflammatory diseases, including is_associated_with::sepsis, atherosclerosis, and is_associated_with::rheumatoid arthritis. Thus, therapeutic targeting of PPIA with selective inhibitors may prove effective in combatting such inflammatory diseases and symptoms. Correlation between plasma PPIA levels and hyperglycemia symptoms also promotes utilization of PPIA as a biomarker for diabetes and vascular disease.

Furthermore, PPIA is involved in cerebral hypoxia-ischemia by contributing to the nuclear transport of AIF, a proapoptotic factor, in neurons. To maintain the integrity of the blood brain barrier and mitigate brain injury, PPIA helps to recruit circulating monocytes and stimulates survival and growth pathways.

The protein can also interact with several is_associated_with::HIV proteins, including p55 gag, Vpr, and is_associated_with::capsid protein, and has been shown to be necessary for the formation of infectious HIV is_associated_with::virions. As a result, PPIA contributes to viral diseases such as is_associated_with::AIDS, is_associated_with::hepatitis C, is_associated_with::measles, and is_associated_with::influenza A.

Interactions
Peptidylprolyl isomerase A has been shown to interact with:
 * ITK,
 * is_associated_with::CD147,
 * is_associated_with::P53,
 * is_associated_with::STAT3,