Cyclophilin  is the major high-affinity binding protein in vertebrates
for the immunosuppressive drug cyclosporin A (CSA). It exhibits a peptidyl-prolyl cis-trans isomerase activity (EC 126.96.36.199) (PPIase or rotamase). PPIase
is an enzyme that accelerates protein folding by catalyzing the cis-trans
isomerization of proline imidic peptide bonds in oligopeptides . It is
probable that CSA mediates some of its effects via an inhibitory action on
PPIase. Cyclophilin is a cytosolic protein which belongs to a family [3,4,5]
that also includes the following isozymes:
Cyclophilin B (or S-cyclophilin), a PPIase which is retained in an
endoplasmic reticulum compartment.
Cyclophilin C, a cytoplasmic PPiase.
Mitochondrial matrix cyclophilin (cyp3).
A PPIase which seems specific for the folding of rhodopsin and is an
integral membrane protein anchored by a C-terminal transmembrane region.
This protein was first characterized in Drosophila (gene ninaA).
Bacterial periplasmic PPiase (gene ppiA).
Bacterial cytosolic PPiase (gene ppiB).
Natural-killer cell cyclophilin-related protein. This large protein (about
160 Kd) is a component of a putative tumor-recognition complex involved in
the function of NK cells. It contains a cyclophilin-type PPiase domain.
Mammalian nucleoporin Nup358 , a nuclear pore complex protein of 358 Kd
that contains a C-terminal cyclophilin-type PPiase domain.
Yeast hypothetical protein YJR032w.
Fission yeast hypothetical protein SpAC21E11.05c.
Caenorhabditis elegans hypothetical protein T27D1.1.
The sequences of the different forms of cyclophilin-type PPIases are well
conserved. As a signature pattern, we selected a conserved region in the
central part of these enzymes.
FKBP's, a family of proteins that bind the immunosuppressive drug
FK506, are also PPIases, but their sequence is not at all related to that of
cyclophilin (see <PDOC00426>).
December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
Stamnes M.A., Rutherford S.L., Zuker C.S.
Cyclophilins: a new family of proteins involved in intracellular folding.
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