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PROSITE documentation PDOC00426FKBP-type peptidyl-prolyl cis-trans isomerase profile
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PURL: https://purl.expasy.org/prosite/documentation/PDOC00426
FKBP [1,2,3] is the major high-affinity binding protein, in vertebrates, for the immunosuppressive drug FK506. It exhibits 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 [4].
At least three different forms of FKBP are known in mammalian species:
- FKBP-12, which is cytosolic and inhibited by both FK506 and rapamycin.
- FKBP-13, which is membrane associated and inhibited by both FK506 and rapamycin.
- FKBP-25, which is preferentially inhibited by rapamycin.
These forms of FKBP are evolutionary related and show extensive similarities [5,6,7] with the following proteins:
- Fungal FKBP.
- Mammalian hsp binding immunophilin (HBI) (also called p59). HBI is a protein which binds to hsp90 and contains two FKBP-like domains in its N- terminal section - the first of which seems to be functional.
- The C-terminal part of the cell-surface protein mip from Legionella; a protein associated with macrophage infection by an unknown mechanism.
- Escherichia coli slyD [8], a protein with a N-terminal FKBP domain followed by an histidine-rich metal-binding domain.
- Escherichia coli fkpA.
- Escherichia coli fklB (FKBP22).
- Escherichia coli slpA.
- Bacterial trigger factor (Tig).
- Streptomyces hygroscopus and chrysomallus FK506-binding protein.
- Chlamydia trachomatis 27 Kd membrane protein.
- Neisseria meningitidis strain C114 PPiase.
- Probable PPiases from Haemophilus influenzae (HI0754), Methanococcus jannaschii (MJ0278 and MJ0825), Pseudomonas fluorescens and Pseudomonase aeruginosa.
We developed a profile for FKBP that spans the complete domain.
Note:Cyclophilin, the protein that binds to the immunosuppressive drug cyclosporin A, is also a PPIase but its sequence is not at all related to that of FKBP (see <PDOC00154>).
Expert(s) to contact by email: Last update:June 2004 / Text revised and patterns deleted.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Tropschug M. Wachter E. Mayer S. Schoenbrunner E.R. Schmid F.X. |
| Title | Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding. | |
| Source | Nature 346:674-677(1990). | |
| PubMed ID | 1696687 | |
| DOI | 10.1038/346674a0 |
| 2 | Authors | Stein R.L. |
| Title | Exploring the catalytic activity of immunophilins. | |
| Source | Curr. Biol. 1:234-236(1991). | |
| PubMed ID | 15336129 |
| 3 | Authors | Siekierka J.J. Wiederrecht G. Greulich H. Boulton D. Hung S.H.Y. Cryan J. Hodges P.J. Sigal N.H. |
| Title | The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. | |
| Source | J. Biol. Chem. 265:21011-21015(1990). | |
| PubMed ID | 1701173 |
| 4 | 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 |
| 5 | 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 |
| 6 | Authors | Galat A. |
| Title | Peptidylproline cis-trans-isomerases: immunophilins. | |
| Source | Eur. J. Biochem. 216:689-707(1993). | |
| PubMed ID | 8404888 |
| 7 | 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 |
| 8 | Authors | Wuelfing C. Lomardero J. Plueckthun A. |
| Source | J. Biol. Chem. 269:2895-2901(1994). |
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