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| PROSITE documentation PDOC00154 [for PROSITE entry PS00170] |
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 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.
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html --------------------------------------------------------------------------------.
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.
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PROSITE methods (with tools and information) covered by this documentation:
| 1 | Authors | Stamnes M.A. Rutherford S.L. Zuker C.S. |
| Title | Cyclophilins: a new family of proteins involved in intracellular folding. | |
| Source | Trends Cell Biol. 2:272-276(1992). | |
| PubMed ID | 14731520 |
| 2 | Authors | Fischer G. Schmid F.X. |
| Title | The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell. | |
| Source | Biochemistry 29:2205-2212(1990). | |
| PubMed ID | 2186809 |
| 3 | Authors | Trandinh C.C. Pao G.M. Saier M.H. Jr. |
| Title | Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases. | |
| Source | FASEB J. 6:3410-3420(1992). | |
| PubMed ID | 1464374 |
| 4 | Authors | Galat A. |
| Title | Peptidylproline cis-trans-isomerases: immunophilins. | |
| Source | Eur. J. Biochem. 216:689-707(1993). | |
| PubMed ID | 8404888 |
| 5 | Authors | Hacker J. Fischer G. |
| Title | Immunophilins: structure-function relationship and possible role in microbial pathogenicity. | |
| Source | Mol. Microbiol. 10:445-456(1993). | |
| PubMed ID | 7526121 |
| 6 | Authors | Wu J. Matunis M.J. Kraemer D. Blobel G. Coutavas E. |
| Title | Nup358, a cytoplasmically exposed nucleoporin with peptide repeats, Ran-GTP binding sites, zinc fingers, a cyclophilin A homologous domain, and a leucine-rich region. | |
| Source | J. Biol. Chem. 270:14209-14213(1995). | |
| PubMed ID | 7775481 |
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.
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