PPIA

Description

The PPIA (peptidylprolyl isomerase A) is a protein-coding gene located on chromosome 7.

PPIA, also known as cyclophilin A (CypA) or rotamase A, is an enzyme that in humans is encoded by the PPIA gene on chromosome 7. As a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family, this protein catalyzes the cis-trans isomerization of proline imidic peptide bonds, which allows it to regulate many biological processes, including intracellular signaling, transcription, inflammation, and 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 an 18 kDa, 165-amino acid long cytosolic protein. Like other cyclophilins, PPIA forms a β-barrel structure with a hydrophobic core. This β-barrel is composed of eight anti-parallel β-strands and capped by two α-helices at the top and bottom. In addition, the β-turns and loops in the strands contribute to the flexibility of the barrel. 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.

PPIA is an enzyme that catalyzes the conversion of proline imidic peptide bonds in oligopeptides from one form to another. It plays a crucial role in various cellular processes, including immune responses, inflammation, and apoptosis. PPIA promotes the movement of white blood cells (leukocytes) by activating a specific membrane receptor, leading to the activation of a signaling pathway that ultimately results in the activation of MAPK/ERK. It also triggers inflammation in endothelial cells by activating NF-kappa-B and other signaling pathways, and it can induce programmed cell death (apoptosis) in these cells by regulating the expression of certain genes. PPIA is also involved in regulating oxidative stress responses and controlling the activity of a kinase called MAP3K5/ASK1. It plays a vital role in the assembly of a protein called TARDBP in complexes known as hnRNP, which are involved in clearing protein aggregates. PPIA is also essential for platelet activation and aggregation, and it regulates calcium signaling and the interaction of integrins with the cell cytoskeleton. PPIA binds to a type of sugar molecule called heparan sulfate glycosaminoglycans. It can block the replication of influenza A virus (IAV) by inhibiting a process called ubiquitination and by suppressing the nuclear export of a viral protein. PPIA is also involved in mediating interactions between human SARS coronavirus nucleoprotein and a protein called BSG/CD147, which may be involved in the virus entering host cells. PPIA can enhance the RNA-binding ability of a protein called HCV NS5A. PPIA interacts with several other proteins, including calcineurin A, PRPF19, BSG/CD147, FOXO1, integrin ITGA2B:ITGB3, MAP3K5, TARDBP, HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK, HNRNPM, HIV-1 capsid protein, human SARS coronavirus nucleoprotein, measles virus nucleoprotein, influenza A virus matrix protein 1, and HCV NS5A. These interactions play a role in various cellular processes and viral infections.

PPIA is also known as CYPA, CYPH, HEL-S-69p.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing