PROSITE documentation PDOC00154
Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature & profile


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 (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.


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.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

CSA_PPIASE_2, PS50072; Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain profile  (MATRIX)

CSA_PPIASE_1, PS00170; Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature  (PATTERN)


1AuthorsStamnes M.A. Rutherford S.L. Zuker C.S.
TitleCyclophilins: a new family of proteins involved in intracellular folding.
SourceTrends Cell Biol. 2:272-276(1992).
PubMed ID14731520

2AuthorsFischer G. Schmid F.X.
TitleThe mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell.
SourceBiochemistry 29:2205-2212(1990).
PubMed ID2186809

3AuthorsTrandinh C.C. Pao G.M. Saier M.H. Jr.
TitleStructural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases.
SourceFASEB J. 6:3410-3420(1992).
PubMed ID1464374

4AuthorsGalat A.
TitlePeptidylproline cis-trans-isomerases: immunophilins.
SourceEur. J. Biochem. 216:689-707(1993).
PubMed ID8404888

5AuthorsHacker J. Fischer G.
TitleImmunophilins: structure-function relationship and possible role in microbial pathogenicity.
SourceMol. Microbiol. 10:445-456(1993).
PubMed ID7526121

6AuthorsWu J. Matunis M.J. Kraemer D. Blobel G. Coutavas E.
TitleNup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region.
SourceJ. Biol. Chem. 270:14209-14213(1995).
PubMed ID7775481

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