******************************************************************
* Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature *
******************************************************************

Cyclophilin [1] 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 5.2.1.8) (PPIase or rotamase). PPIase
is an  enzyme  that  accelerates protein folding by catalyzing  the  cis-trans
isomerization  of proline    imidic  peptide bonds in oligopeptides [2]. 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).
 - A bacterial periplasmic PPiase (gene ppiA).
 - A 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.

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.

-Consensus pattern: [FY]-x(2)-[STLV]-x-F-H-[RH]-[LIVM](2)-x(2)-F-[LIVM]-x-Q-
                    [AG]-G
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for yeast CYP4.
-Other sequence(s) detected in SWISS-PROT: NONE.

-Note: 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 the section on FKBP).

-Last update: June 1994 / Text revised.

[ 1] Stamnes M.A., Rutherford S.L., Zuker C.S.
     Trends Cell Biol. 2:272-276(1992).
[ 2] Fischer G., Schmid F.X.
     Biochemistry 29:2205-2212(1990).
[ 3] Trandinh C.C., Pao G.M., Saier M.H. Jr.
     FASEB J. 6:3410-3420(1992).
[ 4] Galat A.
     Eur. J. Biochem. 216:689-707(1993).
[ 5] Hacker J., Fischer G.
     Mol. Microbiol. 10:445456(1993).