FKBP
| FKBP-type peptidyl-prolyl cis-trans isomerase | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
 The human protein FKBP12 bound to FK506 (tacrolimus). The protein surface is colored by hydrophobicity; the deep cleft in which the ligand is bound is hydrophobic. | |||||||||||
| Identifiers | |||||||||||
| Symbol | FKBP_C | ||||||||||
| Pfam | PF00254 | ||||||||||
| InterPro | IPR001179 | ||||||||||
| PROSITE | PDOC00426 | ||||||||||
| SCOP2 | 1fkb / SCOPe / SUPFAM | ||||||||||
| |||||||||||
FKBP, or FK506 binding protein, is a family of proteins that have prolyl isomerase activity and are related to the cyclophilins in function, though not in amino acid sequence.[1] FKBPs have been identified in many eukaryotes from yeast to humans and function as protein folding chaperones for proteins containing proline residues. Along with cyclophilin, FKBPs belong to the immunophilin family.[2]
FKBP12 is notable in humans for binding the immunosuppressant molecule tacrolimus (originally designated FK506), which is used in treating patients after organ transplant and patients suffering from autoimmune disorders.[3] Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin, which binds cyclophilin.[4] Both the FKBP-tacrolimus complex and the ciclosporin-cyclophilin complex inhibit a phosphatase called calcineurin, thus blocking signal transduction in the T-lymphocyte transduction pathway.[5] This therapeutic role is not related to prolyl isomerase activity.
Use as a biological research tool
FKBP (FKBP1A) does not normally form a dimer but will dimerize in the presence of FK1012, a derivative of the drug FK506. This has made it a useful tool for chemically induced dimerization applications where it can be used to manipulate protein localization, signalling pathways and protein activation.[6]
Examples
Human genes encoding proteins in this family include:
- AIP; AIPL1
- FKBP1A; FKBP1B; FKBP2; FKBP3; FKBP5; FKBP6; FKBP7; FKBP8; FKBP9; FKBP9L; FKBP10; FKBP11; FKBP14; FKBP15; FKBP52
- LOC541473;
See also
References
- ^ Siekierka JJ, Hung SH, Poe M, Lin CS, Sigal NH (October 1989). "A cytosolic binding protein for the immunosuppressant FK506 has peptidyl-prolyl isomerase activity but is distinct from cyclophilin". Nature. 341 (6244): 755–7. doi:10.1038/341755a0. PMID 2477714.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Balbach J, Schmid FX (2000). "Proline isomerization and its catalysis in protein folding". In Pain RH (ed.). Mechanisms of protein folding (2nd ed.). Oxford: Oxford University Press. pp. 212–237. ISBN 0-19-963789-X.
- ^ Wang T, Donahoe PK, Zervos AS (July 1994). "Specific interaction of type I receptors of the TGF-beta family with the immunophilin FKBP-12". Science. 265 (5172): 674–6. doi:10.1126/science.7518616. PMID 7518616.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Mayer AD, Dmitrewski J, Squifflet JP, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RW, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JL, Talbot D, Pohanka E (August 1997). "Multicenter randomized trial comparing tacrolimus (FK506) and cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group". Transplantation. 64 (3): 436–43. doi:10.1097/00007890-199708150-00012. PMID 9275110.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Liu J, Farmer JD, Lane WS, Friedman J, Weissman I, Schreiber SL (August 1991). "Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes". Cell. 66 (4): 807–15. doi:10.1016/0092-8674(91)90124-H. PMID 1715244.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Fegan, A; White, B; Carlson, JC; Wagner, CR (Jun 9, 2010). "Chemically controlled protein assembly: techniques and applications". Chemical Reviews. 110 (6): 3315–36. doi:10.1021/cr8002888. PMID 20353181.
External links