The FKBPs, or

FK506 Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogenic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also ...

binding proteins, constitute a family of

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s that have prolyl isomerase 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 lif ...

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 The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

s, ranging from

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

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

s, and function as

protein folding Protein folding is the physical process by which a protein, after Protein biosynthesis, synthesis by a ribosome as a linear chain of Amino acid, amino acids, changes from an unstable random coil into a more ordered protein tertiary structure, t ...

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 p ...

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 and trans isomers of peptide bonds containing the amino acid proline (Pro). They are chaperone molec ...

family.

FKBP1A Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the ''FKBP1A'' gene. It is also commonly referred to as FKBP-12 or FKBP12 and is a member of a family of FK506-binding proteins ( FKBPs). Function The protei ...

(also known as FKBP12) 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 the activity of the immune system. Classification Immunosuppressive drugs can be classified ...

molecule

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...

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

organ transplant Organ transplantation is a medical procedure in which an organ (anatomy), 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 org ...

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" ...

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 taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...

, 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 block ...

, thus blocking

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

in the T-

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

transduction pathway. This therapeutic role is not related to its prolyl isomerase activity. FKBP25 is a nuclear FKBP which non-specifically binds with DNA and has a 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, 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.

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. The protein is a member of FKBP prolyl isomerase family. Function Leber congenital amaurosis (LCA) accounts for at least 5% of all inh ...

* FKBPL;

; FKBP1B; FKBP2;

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 bas ...

;

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 ...

;

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 ...

; FKBP6;

FKBP7 FK506 binding protein 7 is a protein that in humans is encoded by the ''FKBP7'' gene. The gene is also known as ''FKBP23'' and ''PPIase''. FKBP7 belongs to the FKBP-type peptidyl-prolyl cis/trans isomerase (PPIase) family. Members of this family ex ...

; FKBP8;

FKBP9 FK506-binding protein 9 is a protein that in humans is encoded by the ''FKBP9'' gene. References Further reading

* * * * * * EC 5.2.1 EF-hand-containing proteins {{gene-7-stub ...

;

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-acting, cis/Trans-acting, trans isomerase family. It is located in endoplasmic r ...

; 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. Pseudogenes can be formed from both protein-coding genes and non-coding genes. In the case of protein-coding genes, most pseudogenes arise as superfluous copies of fun ...

): * 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