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202  structures 5125  species 6  interactions 16739  sequences 143  architectures

Family: FKBP_C (PF00254)

Summary: FKBP-type peptidyl-prolyl cis-trans isomerase

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FKBP Edit Wikipedia article

FKBP-type peptidyl-prolyl cis-trans isomerase
Fkbp-surface-1fkj.png
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
SCOP 1fkb
SUPERFAMILY 1fkb
An illustration of the same protein in the same orientation

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 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:

See also

References

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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


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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

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.

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(174)
Full
(16739)
Representative proteomes NCBI
(12394)
Meta
(3280)
RP15
(1593)
RP35
(3021)
RP55
(4223)
RP75
(5251)
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Format an alignment

  Seed
(174)
Full
(16739)
Representative proteomes NCBI
(12394)
Meta
(3280)
RP15
(1593)
RP35
(3021)
RP55
(4223)
RP75
(5251)
Alignment:
Format:
Order:
Sequence:
Gaps:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(174)
Full
(16739)
Representative proteomes NCBI
(12394)
Meta
(3280)
RP15
(1593)
RP35
(3021)
RP55
(4223)
RP75
(5251)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: FKBP;
Type: Domain
Author: Finn RD
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.1
Noise cut-off 21.0 21.0
Model length: 94
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Interactions

There are 6 interactions for this family. More...

Metallophos Pkinase EF-hand_1 FKBP_C TPR_1 TGF_beta_GS

Structures

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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