PS50059

FKBP-type peptidyl-prolyl cis-trans isomerase domain profile

PROSITE profiles entry
Member databasePROSITE profiles
PROSITE profiles typedomain
Short nameFKBP_PPIASE

Description

FKBP
[6]
[3]
[4]
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
[5]
. 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
[7]
[2]
[1]
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.

References

1.Immunophilins: structure-function relationship and possible role in microbial pathogenicity. Hacker J, Fischer G. Mol. Microbiol. 10, 445-56, (1993). View articlePMID: 7526121

2.Peptidylproline cis-trans-isomerases: immunophilins. Galat A. Eur. J. Biochem. 216, 689-707, (1993). View articlePMID: 8404888

3.Exploring the catalytic activity of immunophilins. Stein RL. Curr. Biol. 1, 234-6, (1991). View articlePMID: 15336129

4.The cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase. Siekierka JJ, Wiederrecht G, Greulich H, Boulton D, Hung SH, Cryan J, Hodges PJ, Sigal NH. J. Biol. Chem. 265, 21011-5, (1990). View articlePMID: 1701173

5.The mechanism of protein folding. Implications of in vitro refolding models for de novo protein folding and translocation in the cell. Fischer G, Schmid FX. Biochemistry 29, 2205-12, (1990). View articlePMID: 2186809

6.Isolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding. Tropschug M, Wachter E, Mayer S, Schonbrunner ER, Schmid FX. Nature 346, 674-7, (1990). View articlePMID: 1696687

7.Structural and evolutionary relationships among the immunophilins: two ubiquitous families of peptidyl-prolyl cis-trans isomerases. Trandinh CC, Pao GM, Saier MH Jr. FASEB J. 6, 3410-20, (1992). View articlePMID: 1464374

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