Summary: FKBP-type peptidyl-prolyl cis-trans isomerase
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|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.
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. 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.
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. Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin, which binds cyclophilin. 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. This therapeutic role is not related to prolyl isomerase activity.
Use as a biological research tool
FKBP 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.
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
- 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.
- Balbach J, Schmid FX (2000). "Proline isomerization and its catalysis in protein folding". In Pain RH. 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.
- 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.
- 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.
- 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.
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FKBP-type peptidyl-prolyl cis-trans isomerase Provide feedback
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External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR001179
Synonym(s): Peptidylprolyl cis-trans isomerase
FKBP-type peptidylprolyl isomerases (EC) in vertebrates, are receptors for the two immunosuppressants, FK506 and rapamycin. The drugs inhibit T cell proliferation by arresting two distinct cytoplasmic signal transmission pathways. Peptidylprolyl isomerases accelerate protein folding by catalysing the cis-trans isomerisation of proline imidic peptide bonds in oligopeptides. These proteins are found in a variety of organisms.
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Biological process||protein folding (GO:0006457)|
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Curation and family details
|Number in seed:||174|
|Number in full:||16739|
|Average length of the domain:||99.80 aa|
|Average identity of full alignment:||27 %|
|Average coverage of the sequence by the domain:||37.70 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||23|
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There are 6 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the FKBP_C domain has been found. There are 202 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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