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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.

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.

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

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

• Consensus pattern:
  [FY]-x(2)-[STCNLVA]-x-[FV]-H-[RH]-[LIVMNS]-[LIVM]-x(2)-F-[LIVM]-x-Q-[AGFT]-G
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 321
  • detected by PS00170: 255 (true positives)
  • undetected by PS00170: 66 (61 false negatives and 5 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00170:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00170
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00170
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00170
• View ligand binding statistics of PS00170
• Matching PDB structures: 1A33 1A58 1AK4 1AWQ ... [ALL]

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

• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 323
  • detected by PS50072: 317 (true positives)
  • undetected by PS50072: 6 (2 false negatives and 4 'partials')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS50072:
  NONE.
• Domain architecture view of Swiss-Prot proteins matching PS50072
  
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50072
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS50072
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS50072
• View ligand binding statistics of PS50072
• Matching PDB structures: 1A33 1A58 1AK4 1AWQ ... [ALL]

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

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