FKBP, or FK506 binding protein, is a family of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s that have

prolyl isomerase Prolyl isomerase (also known as peptidylprolyl isomerase or PPIase) is an enzyme () found in both prokaryotes and eukaryotes that interconverts the ''cis'' and ''trans'' isomers of peptide bonds with the amino acid proline. Proline has an ...

activity and are related to the

cyclophilin Cyclophilins (CYPs) are a family of proteins named after their ability to bind to ciclosporin (cyclosporin A), an immunosuppressant which is usually used to suppress rejection after internal organ transplants. They are found in all domains of l ...

s in function, though not in

amino acid sequence Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthe ...

. FKBPs have been identified in many

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacte ...

s, ranging from

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are estimated to constitut ...

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

s, and function as

protein folding Protein folding is the physical process by which a protein chain is translated to its native three-dimensional structure, typically a "folded" conformation by which the protein becomes biologically functional. Via an expeditious and reproduci ...

chaperones for proteins containing

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the prot ...

residues. Along with cyclophilin, FKBPs belong to the

immunophilin In molecular biology, immunophilins are endogenous cytosolic peptidyl-prolyl isomerases (PPI) that catalyze the interconversion between the Cis–trans isomerism, cis and trans isomers of peptide bonds containing the amino acid proline (Pro). They ...

family.

FKBP12 Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basi ...

is notable in humans for binding the

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent activity of the immune system. Classification Immunosuppressive drugs can be classified in ...

molecule

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogeneic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

(originally designated FK506), which is used in treating patients after

organ transplant Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transpo ...

and patients with

autoimmune In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...

disorders. Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, ...

, which binds cyclophilin. Both the FKBP-tacrolimus complex and the cyclosporin-cyclophilin complex inhibit a

phosphatase In biochemistry, a phosphatase is an enzyme that uses water to cleave a phosphoric acid Ester, monoester into a phosphate ion and an Alcohol (chemistry), alcohol. Because a phosphatase enzyme catalysis, catalyzes the hydrolysis of its Substrate ...

called

calcineurin Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase (also known as protein phosphatase 3, and calcium-dependent serine-threonine phosphatase). It activates the T cells of the immune system and can be bloc ...

, thus blocking

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

in the T-

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...

transduction pathway. This therapeutic role is not related to prolyl isomerase activity. Unique member of FKBP named FKBP25 is a nuclear FKBP which non-specifically binds with DNA and have role in DNA repair.

Use as a biological research tool

FKBP (FKBP1A) does not normally form a dimer but will dimerize in the presence of

FK1012 FK1012, a derivative of tacrolimus, is used as a research tool in chemically induced dimerization applications. The protein FKBP does not normally form dimers but can be caused to dimerize in the presence of FK1012. Genetically engineered proteins ...

, a derivative of the drug

(FK506). This has made it a useful tool for

chemically induced dimerization Chemically Induced Dimerization (CID) is a biological mechanism in which two proteins bind only in the presence of a certain small molecule, enzyme or other dimerizing agent. Genetically engineered CID systems are used in biological research to cont ...

applications where it can be used to manipulate protein localization, signalling pathways and protein activation.

Examples

Human genes encoding proteins in this family include: * AIP;

AIPL1 Aryl-hydrocarbon-interacting protein-like 1 is a protein that in humans is encoded by the ''AIPL1'' gene. Function Leber congenital amaurosis (LCA) accounts for at least 5% of all inherited retinal disease and is the most severe inherited reti ...

FKBPL FK506-binding protein like, also known as FKBPL, is a protein that in humans is encoded by the ''FKBPL'' gene. Function FKBPL has similarity to the immunophilin protein family, which play a role in immunoregulation and basic cellular processes ...

; FKBP1A;

FKBP1B Peptidyl-prolyl cis-trans isomerase FKBP1B is an enzyme that in humans is encoded by the ''FKBP1B'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic ...

;

FKBP2 FK506-binding protein 2 is a protein that in humans is encoded by the ''FKBP2'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes i ...

;

FKBP3 FK506-binding protein 3 also known as FKBP25 is a protein that in humans is encoded by the ''FKBP3'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basi ...

;

FKBP4 FK506-binding protein 4 is a protein that in humans is encoded by the ''FKBP4'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes i ...

;

FKBP5 FK506 binding protein 5, also known as FKBP5, is a protein which in humans is encoded by the ''FKBP5'' gene. Function The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and ba ...

;

FKBP6 FK506 binding protein 6, also known as FKBP6, is a human gene. The encoded protein shows structural homology to FKBP immunophilins, which bind to the immunosuppressants FK506 and rapamycin. FKBP6 is essential for homologous chromosome pairing in ...

; FKBP7;

FKBP8 FK506-binding protein 8 is a protein that in humans is encoded by the ''FKBP8'' gene. The protein encoded by this gene is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving p ...

; FKBP9;

FKBP10 FK506-binding protein 10 is a protein that in humans is encoded by the ''FKBP10'' gene. The protein encoded by this gene belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase family. It is located in endoplasmic reticulum and acts as mol ...

; FKBP11;

FKBP14 FKBP14 is a gene which codes for a structural protein named FKBP prolyl isomerase 14. This protein is believed to aid in the process of procollagen folding and is located in the endoplasmic reticulum that functions to process and transport proteins ...

; FKBP15; Gene with unclear status (may be

pseudogene Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by Reverse transcriptase, reverse transcription of an mRNA trans ...

): * FKBP1C Pseudogenes in humans: * LOC541473; FKBP9L;

References

External links

Anti-rejection drugs
EC 5.2.1 Protein families {{isomerase-stub

Use as a biological research tool

Examples

See also

References

External links