{PDOC00426}
{PS50059; FKBP_PPIASE}
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* FKBP-type peptidyl-prolyl cis-trans isomerase profile *
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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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-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:
           Callebaut I.; isabelle.callebaut@lmcp.jussieu.fr

-Last update: June 2004 / Text revised and patterns deleted.

[ 1] Tropschug M., Wachter E., Mayer S., Schoenbrunner E.R., Schmid F.X.
     "Isolation and sequence of an FK506-binding protein from N. crassa
     which catalyses protein folding."
     Nature 346:674-677(1990).
     PubMed=1696687; DOI=10.1038/346674a0
[ 2] Stein R.L.
     "Exploring the catalytic activity of immunophilins."
     Curr. Biol. 1:234-236(1991).
     PubMed=15336129
[ 3] Siekierka J.J., Wiederrecht G., Greulich H., Boulton D., Hung S.H.Y.,
     Cryan J., Hodges P.J., Sigal N.H.
     "The cytosolic-binding protein for the immunosuppressant FK-506 is
     both a ubiquitous and highly conserved peptidyl-prolyl cis-trans
     isomerase."
     J. Biol. Chem. 265:21011-21015(1990).
     PubMed=1701173
[ 4] Fischer G., Schmid F.X.
     "The mechanism of protein folding. Implications of in vitro refolding
     models for de novo protein folding and translocation in the cell."
     Biochemistry 29:2205-2212(1990).
     PubMed=2186809
[ 5] Trandinh C.C., Pao G.M., Saier M.H. Jr.
     "Structural and evolutionary relationships among the immunophilins:
     two ubiquitous families of peptidyl-prolyl cis-trans isomerases."
     FASEB J. 6:3410-3420(1992).
     PubMed=1464374
[ 6] Galat A.
     "Peptidylproline cis-trans-isomerases: immunophilins."
     Eur. J. Biochem. 216:689-707(1993).
     PubMed=8404888
[ 7] Hacker J., Fischer G.
     "Immunophilins: structure-function relationship and possible role in
     microbial pathogenicity."
     Mol. Microbiol. 10:445-456(1993).
     PubMed=7526121
[ 8] Wuelfing C., Lomardero J., Plueckthun A.
     J. Biol. Chem. 269:2895-2901(1994).

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