PROSITE documentation PDOC00426
FKBP-type peptidyl-prolyl cis-trans isomerase profile


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 (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.


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:

Callebaut I.

Last update:

June 2004 / Text revised and patterns deleted.


Technical section

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

FKBP_PPIASE, PS50059; FKBP-type peptidyl-prolyl cis-trans isomerase domain profile  (MATRIX)


1AuthorsTropschug M. Wachter E. Mayer S. Schoenbrunner E.R. Schmid F.X.
TitleIsolation and sequence of an FK506-binding protein from N. crassa which catalyses protein folding.
SourceNature 346:674-677(1990).
PubMed ID1696687

2AuthorsStein R.L.
TitleExploring the catalytic activity of immunophilins.
SourceCurr. Biol. 1:234-236(1991).
PubMed ID15336129

3AuthorsSiekierka J.J. Wiederrecht G. Greulich H. Boulton D. Hung S.H.Y. Cryan J. Hodges P.J. Sigal N.H.
TitleThe cytosolic-binding protein for the immunosuppressant FK-506 is both a ubiquitous and highly conserved peptidyl-prolyl cis-trans isomerase.
SourceJ. Biol. Chem. 265:21011-21015(1990).
PubMed ID1701173

4AuthorsFischer 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

5AuthorsTrandinh 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

6AuthorsGalat A.
TitlePeptidylproline cis-trans-isomerases: immunophilins.
SourceEur. J. Biochem. 216:689-707(1993).
PubMed ID8404888

7AuthorsHacker J. Fischer G.
TitleImmunophilins: structure-function relationship and possible role in microbial pathogenicity.
SourceMol. Microbiol. 10:445-456(1993).
PubMed ID7526121

8AuthorsWuelfing C. Lomardero J. Plueckthun A.
SourceJ. Biol. Chem. 269:2895-2901(1994).

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