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627  structures 8574  species 0  interactions 43008  sequences 515  architectures

Family: FKBP_C (PF00254)

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

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

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

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
SymbolFKBP_C
PfamPF00254
InterProIPR001179
PROSITEPDOC00426
SCOPe1fkb / SUPFAM
Membranome336
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]

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 (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

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

View options

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
(131)
Full
(43008)
Representative proteomes UniProt
(152877)
RP15
(6224)
RP35
(19682)
RP55
(40138)
RP75
(63940)
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HTML View             
PP/heatmap 1            

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(131)
Full
(43008)
Representative proteomes UniProt
(152877)
RP15
(6224)
RP35
(19682)
RP55
(40138)
RP75
(63940)
Alignment:
Format:
Order:
Sequence:
Gaps:
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Download options

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
(131)
Full
(43008)
Representative proteomes UniProt
(152877)
RP15
(6224)
RP35
(19682)
RP55
(40138)
RP75
(63940)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 131
Number in full: 43008
Average length of the domain: 97.00 aa
Average identity of full alignment: 27 %
Average coverage of the sequence by the domain: 37.07 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -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: 30
Download: download the raw HMM for this family

Species distribution

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Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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 627 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
A0A0P0V444 View 3D Structure Click here
A0A0P0V444 View 3D Structure Click here
A0A0P0V450 View 3D Structure Click here
A0A0P0V450 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
A0A0R0KGG4 View 3D Structure Click here
A0A0R0KGG4 View 3D Structure Click here
A0A0R0L013 View 3D Structure Click here
A0A0R4IBI6 View 3D Structure Click here
A0A0R4IBI6 View 3D Structure Click here
A0A0R4IBI6 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
A0A1D6EEN1 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
A0A1D6H8E1 View 3D Structure Click here
A0A1D6H8E1 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
A0A1D6KJP4 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
A0A1D6P9C5 View 3D Structure Click here
A0A1D6P9C5 View 3D Structure Click here
A0A1D6Q3Z5 View 3D Structure Click here
A0A1D6QR81 View 3D Structure Click here
A0A1D6QUK7 View 3D Structure Click here
A0A1D8PFM9 View 3D Structure Click here
A0A2R8RWA2 View 3D Structure Click here
A0A2R8RWP8 View 3D Structure Click here
A0A2R8RWP8 View 3D Structure Click here
A3C0C6 View 3D Structure Click here
A3QK11 View 3D Structure Click here
A4HUK1 View 3D Structure Click here
A4HYB4 View 3D Structure Click here
A4HYI1 View 3D Structure Click here
A4I002 View 3D Structure Click here
A4ICW4 View 3D Structure Click here
A9JSW0 View 3D Structure Click here
B0G119 View 3D Structure Click here
B0S745 View 3D Structure Click here
B3DKC0 View 3D Structure Click here
B3DKC0 View 3D Structure Click here
B3DKC0 View 3D Structure Click here
B3DKC0 View 3D Structure Click here
B4FDQ2 View 3D Structure Click here
B4FR04 View 3D Structure Click here
B4FUK2 View 3D Structure Click here
B6SZG7 View 3D Structure Click here
B7F8B9 View 3D Structure Click here
C0H5B2 View 3D Structure Click here
C4J6Y2 View 3D Structure Click here
C6SZE3 View 3D Structure Click here
C6TCF4 View 3D Structure Click here
C6TFQ0 View 3D Structure Click here
D3Z9M5 View 3D Structure Click here
D3ZQF4 View 3D Structure Click here
D3ZZR9 View 3D Structure Click here
D4AE06 View 3D Structure Click here
E7F4I7 View 3D Structure Click here
F1QQ70 View 3D Structure Click here
F1R3A6 View 3D Structure Click here
F4J9Q6 View 3D Structure Click here
F8W2D1 View 3D Structure Click here
F8W2D1 View 3D Structure Click here
G3V6L9 View 3D Structure Click here
I1J730 View 3D Structure Click here
I1J730 View 3D Structure Click here
I1J730 View 3D Structure Click here
I1JAK5 View 3D Structure Click here
I1JLY3 View 3D Structure Click here
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I1JLY3 View 3D Structure Click here
I1JM67 View 3D Structure Click here
I1JMS9 View 3D Structure Click here
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I1K3Q2 View 3D Structure Click here
I1K4M3 View 3D Structure Click here
I1K5D1 View 3D Structure Click here
I1KS46 View 3D Structure Click here
I1KS46 View 3D Structure Click here
I1KS46 View 3D Structure Click here
I1KT60 View 3D Structure Click here
I1KZ20 View 3D Structure Click here
I1KZ20 View 3D Structure Click here
I1KZ20 View 3D Structure Click here
I1L950 View 3D Structure Click here
I1LG49 View 3D Structure Click here
I1LJL8 View 3D Structure Click here
I1LMG3 View 3D Structure Click here
I1LQB0 View 3D Structure Click here
I1M8V0 View 3D Structure Click here
I1M8V0 View 3D Structure Click here
I1M8V0 View 3D Structure Click here
I1MM91 View 3D Structure Click here
I1MM91 View 3D Structure Click here
I1MM91 View 3D Structure Click here
I1N077 View 3D Structure Click here
I1N1Y9 View 3D Structure Click here
I1N1Y9 View 3D Structure Click here
I1N1Y9 View 3D Structure Click here
K7KEL5 View 3D Structure Click here
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K7KKC8 View 3D Structure Click here
K7L193 View 3D Structure Click here
K7LHT0 View 3D Structure Click here
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K7UBG1 View 3D Structure Click here
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M0RC90 View 3D Structure Click here
O00170 View 3D Structure Click here
O08915 View 3D Structure Click here
O16309 View 3D Structure Click here
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O22870 View 3D Structure Click here
O35465 View 3D Structure Click here
O42993 View 3D Structure Click here
O45418 View 3D Structure Click here
O45418 View 3D Structure Click here
O54998 View 3D Structure Click here
O61826 View 3D Structure Click here
O74191 View 3D Structure Click here
O75344 View 3D Structure Click here
O81864 View 3D Structure Click here
O95302 View 3D Structure Click here
O95302 View 3D Structure Click here
O95302 View 3D Structure Click here
O95302 View 3D Structure Click here
P0A850 View 3D Structure Click here
P0A9K9 View 3D Structure Click here
P0A9L3 View 3D Structure Click here
P0AEM0 View 3D Structure Click here
P20081 View 3D Structure Click here
P26883 View 3D Structure Click here
P26885 View 3D Structure Click here
P28870 View 3D Structure Click here
P30416 View 3D Structure Click here
P30416 View 3D Structure Click here
P32472 View 3D Structure Click here
P38911 View 3D Structure Click here
P45523 View 3D Structure Click here
P45878 View 3D Structure Click here
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P54397 View 3D Structure Click here
P59024 View 3D Structure Click here
P62942 View 3D Structure Click here
P68106 View 3D Structure Click here
P97534 View 3D Structure Click here
P9WG55 View 3D Structure Click here
Q00688 View 3D Structure Click here
Q02790 View 3D Structure Click here
Q02790 View 3D Structure Click here
Q06205 View 3D Structure Click here
Q0WRJ7 View 3D Structure Click here
Q10175 View 3D Structure Click here
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Q13451 View 3D Structure Click here
Q13451 View 3D Structure Click here
Q14318 View 3D Structure Click here
Q1L8P1 View 3D Structure Click here
Q1L8P1 View 3D Structure Click here
Q1L8P1 View 3D Structure Click here
Q1L8P1 View 3D Structure Click here
Q20107 View 3D Structure Click here
Q23338 View 3D Structure Click here
Q23338 View 3D Structure Click here
Q2FXQ6 View 3D Structure Click here
Q2QXS0 View 3D Structure Click here
Q2RAK4 View 3D Structure Click here
Q38931 View 3D Structure Click here
Q38931 View 3D Structure Click here
Q38931 View 3D Structure Click here
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Q38936 View 3D Structure Click here
Q3B7U9 View 3D Structure Click here
Q4CY23 View 3D Structure Click here
Q4CYE6 View 3D Structure Click here
Q4CZN2 View 3D Structure Click here
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Q4D7S2 View 3D Structure Click here
Q4D931 View 3D Structure Click here
Q4D932 View 3D Structure Click here
Q4DFL5 View 3D Structure Click here
Q4DM85 View 3D Structure Click here
Q4DQ47 View 3D Structure Click here
Q53RK7 View 3D Structure Click here
Q54G21 View 3D Structure Click here
Q54LG6 View 3D Structure Click here
Q54N80 View 3D Structure Click here
Q54NB6 View 3D Structure Click here
Q54QI6 View 3D Structure Click here
Q54SR7 View 3D Structure Click here
Q54UR2 View 3D Structure Click here
Q54Y27 View 3D Structure Click here
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Q57726 View 3D Structure Click here
Q58235 View 3D Structure Click here
Q59VR3 View 3D Structure Click here
Q5FWY5 View 3D Structure Click here
Q5N801 View 3D Structure Click here
Q5N9W0 View 3D Structure Click here
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Q5U2T9 View 3D Structure Click here
Q5U2T9 View 3D Structure Click here
Q5U2V1 View 3D Structure Click here
Q5U2V1 View 3D Structure Click here
Q5U2V1 View 3D Structure Click here
Q5U2V1 View 3D Structure Click here
Q5VVH2 View 3D Structure Click here
Q5XID8 View 3D Structure Click here
Q5XLE1 View 3D Structure Click here
Q61576 View 3D Structure Click here
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Q61576 View 3D Structure Click here
Q61576 View 3D Structure Click here
Q62446 View 3D Structure Click here
Q62658 View 3D Structure Click here
Q64378 View 3D Structure Click here
Q64378 View 3D Structure Click here
Q653Z1 View 3D Structure Click here
Q656V1 View 3D Structure Click here
Q656V1 View 3D Structure Click here
Q657L8 View 3D Structure Click here
Q657L8 View 3D Structure Click here
Q657L8 View 3D Structure Click here
Q65XG1 View 3D Structure Click here
Q66H94 View 3D Structure Click here
Q66H94 View 3D Structure Click here
Q66H94 View 3D Structure Click here
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Q6H6D3 View 3D Structure Click here
Q6H725 View 3D Structure Click here
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Q6K5Q1 View 3D Structure Click here
Q6K5Q1 View 3D Structure Click here
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Q6PBJ1 View 3D Structure Click here
Q6PBJ8 View 3D Structure Click here
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Q6ZGL6 View 3D Structure Click here
Q6ZIT9 View 3D Structure Click here
Q75LS8 View 3D Structure Click here
Q7DMA9 View 3D Structure Click here
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Q7XHR0 View 3D Structure Click here
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Q8LB65 View 3D Structure Click here
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Q91XW8 View 3D Structure Click here
Q924K1 View 3D Structure Click here
Q93ZG9 View 3D Structure Click here
Q944B0 View 3D Structure Click here
Q95Q60 View 3D Structure Click here
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Q96AY3 View 3D Structure Click here
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Q96AY3 View 3D Structure Click here
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Q9FJL3 View 3D Structure Click here
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Q9FLB3 View 3D Structure Click here
Q9JLG9 View 3D Structure Click here
Q9LDC0 View 3D Structure Click here
Q9LDY5 View 3D Structure Click here
Q9LM71 View 3D Structure Click here
Q9LYR5 View 3D Structure Click here
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Q9NWM8 View 3D Structure Click here
Q9NYL4 View 3D Structure Click here
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Q9SR70 View 3D Structure Click here
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Q9VL78 View 3D Structure Click here
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Q9Y680 View 3D Structure Click here
Q9Z247 View 3D Structure Click here
Q9Z247 View 3D Structure Click here
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