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 126.96.36.199) (PPIase or rotamase). PPIase is an enzyme that
accelerates protein folding by catalyzing the cis-trans isomerization of
proline imidic peptide bonds in oligopeptides .
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
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:
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 , 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
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>).
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