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681  structures 8786  species 0  interactions 47055  sequences 532  architectures

Family: FKBP_C (PF00254)

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

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This is the Wikipedia entry entitled "FKBP". More...

FKBP Edit Wikipedia article

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.
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, ranging 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 cyclosporin-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 tacrolimus (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]


Human genes encoding proteins in this family include:

See also


  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 (ed.). 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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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

No Pfam abstract.

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001179

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 [ PUBMED:27664121 ].

This entry represents a domain found in FKBP-type peptidylprolyl isomerases.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

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

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Pfam Clan

This family is a member of clan FKBP (CL0487), which has the following description:

This superfamily includes the FKBP domain which catalyses the peptidyl-prolyl cis-trans isomerisation reaction. The superfamily also includes the C-terminal domain of GreA and the c-terminal dmoain of 3-mercaptopyruvate sulfurtransferase.

The clan contains the following 11 members:

DUF1930 DUF4827 FKBP26_C FKBP_C FKBP_N_2 GCD14_N GreA_GreB OSR1_C Rotamase Rotamase_2 Rotamase_3


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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB 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.

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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.

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

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...


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
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 131
Number in full: 47055
Average length of the domain: 96.80 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 37.05 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -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: 31
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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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 681 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0B4K7C5 View 3D Structure Click here
A0A0N7KQB9 View 3D Structure Click here
A0A0P0V444 View 3D Structure Click here
A0A0P0V450 View 3D Structure Click here
A0A0P0XJH1 View 3D Structure Click here
A0A0P0XLH9 View 3D Structure Click here
A0A0R0EMG3 View 3D Structure Click here
A0A0R0F5J4 View 3D Structure Click here
A0A0R0FW30 View 3D Structure Click here
A0A0R0FWT8 View 3D Structure Click here
A0A0R0GPD7 View 3D Structure Click here
A0A0R0II00 View 3D Structure Click here
A0A0R0IW49 View 3D Structure Click here
A0A0R0JUZ4 View 3D Structure Click here
A0A0R0KGG4 View 3D Structure Click here
A0A0R0L013 View 3D Structure Click here
A0A0R4IBI6 View 3D Structure Click here
A0A0R4IGQ7 View 3D Structure Click here
A0A0R4IUL0 View 3D Structure Click here
A0A0R4IUU2 View 3D Structure Click here
A0A0R4IW96 View 3D Structure Click here
A0A0R4J4P0 View 3D Structure Click here
A0A140LFX3 View 3D Structure Click here
A0A1D6E9Q1 View 3D Structure Click here
A0A1D6EEN1 View 3D Structure Click here
A0A1D6ENM9 View 3D Structure Click here
A0A1D6G6B1 View 3D Structure Click here
A0A1D6GJM6 View 3D Structure Click here
A0A1D6H8E1 View 3D Structure Click here
A0A1D6I1D7 View 3D Structure Click here
A0A1D6I7Y2 View 3D Structure Click here
A0A1D6IBS8 View 3D Structure Click here
A0A1D6K417 View 3D Structure Click here
A0A1D6KJP4 View 3D Structure Click here
A0A1D6KKS1 View 3D Structure Click here
A0A1D6KNP4 View 3D Structure Click here
A0A1D6M5T1 View 3D Structure Click here
A0A1D6P9C5 View 3D Structure Click here
A0A1D6Q3Z5 View 3D Structure Click here
A0A1D6QR81 View 3D Structure Click here