Human genes encoding proteins containing the cyclophilin domain include: •
PPIA,
PPIB,
PPIC,
PPID,
PPIE,
PPIF,
PPIG,
PPIH •
PPIL1,
PPIL2,
PPIL3,
PPIL4,
PPIAL4,
PPIL6 •
PPWD1 Cyclophilin A Cyclophilin A (CYPA) also known as peptidylprolyl isomerase A (PPIA), which is found in the
cytosol, has a
beta barrel structure with two
alpha helices and a
beta-sheet. Other cyclophilins have similar structures to cyclophilin A. The cyclosporin-cyclophilin A complex inhibits a
calcium/
calmodulin-dependent
phosphatase,
calcineurin, the inhibition of which is thought to suppress
organ rejection by halting the production of the pro-inflammatory molecules
TNF alpha and
interleukin 2. Cyclophilin A is also known to be recruited by the Gag polyprotein during
HIV-1 virus infection, and its incorporation into new virus particles is essential for HIV-1 infectivity.
Cyclophilin D Cyclophilin D (PPIF, note that literature is confusing, the mitochondrial cyclophilin is encoded by the PPIF gene), which is located in the
matrix of
mitochondria, is only a modulatory, but may or may not be a structural component of the
mitochondrial permeability transition pore. The pore opening raises the permeability of the
mitochondrial inner membrane, allows influx of
cytosolic molecules into the
mitochondrial matrix, increases the matrix volume, and disrupts the mitochondrial outer membrane. As a result, the
mitochondria fall into a functional disorder, so the opening of the pore plays an important role in
cell death. Cyclophilin D is thought to regulate the opening of the pore because cyclosporin A, which binds to CyP-D, inhibits the pore opening. However, mitochondria obtained from the cysts of Artemia franciscana, do not exhibit the mitochondrial permeability transition pore ==Clinical significance==