{PDOC00154}
{PS00170; CSA_PPIASE_1}
{PS50072; CSA_PPIASE_2}
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* Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature & profile *
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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).
 - 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 [6], 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.

-Consensus pattern: [FY]-x(2)-[STCNLVA]-x-[FV]-H-[RH]-[LIVMNS]-[LIVM]-x(2)-F-
                    [LIVM]-x-Q-[AGFT]-G
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for 7 sequences.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Sequences known to belong to this class detected by the profile: ALL.
-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 <PDOC00426>).

-Last update: December 2004 / Pattern and text revised.

[ 1] Stamnes M.A., Rutherford S.L., Zuker C.S.
     "Cyclophilins: a new family of proteins involved in intracellular
     folding."
     Trends Cell Biol. 2:272-276(1992).
     PubMed=14731520
[ 2] Fischer G., Schmid F.X.
     "The mechanism of protein folding. Implications of in vitro refolding
     models for de novo protein folding and translocation in the cell."
     Biochemistry 29:2205-2212(1990).
     PubMed=2186809
[ 3] Trandinh C.C., Pao G.M., Saier M.H. Jr.
     "Structural and evolutionary relationships among the immunophilins:
     two ubiquitous families of peptidyl-prolyl cis-trans isomerases."
     FASEB J. 6:3410-3420(1992).
     PubMed=1464374
[ 4] Galat A.
     "Peptidylproline cis-trans-isomerases: immunophilins."
     Eur. J. Biochem. 216:689-707(1993).
     PubMed=8404888
[ 5] Hacker J., Fischer G.
     "Immunophilins: structure-function relationship and possible role in
     microbial pathogenicity."
     Mol. Microbiol. 10:445-456(1993).
     PubMed=7526121
[ 6] Wu J., Matunis M.J., Kraemer D., Blobel G., Coutavas E.
     "Nup358, a cytoplasmically exposed nucleoporin with peptide repeats,
     Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous
     domain, and a leucine-rich region."
     J. Biol. Chem. 270:14209-14213(1995).
     PubMed=7775481

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