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.