FKBP
Encyclopedia
FKBP, or FK506 binding protein, is a family of protein
s that have prolyl isomerase
activity and are related to the cyclophilin
s in function, though not in amino acid sequence
. FKBPs have been identified in many eukaryote
s from yeast
to human
s and function as protein folding
chaperones for proteins containing proline
residues. Along with cyclophilin, FKBPs belong to the immunophilin family.
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. Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin
, which binds cyclophilin. 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. This therapeutic role is not related to prolyl isomerase activity.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that have prolyl isomerase
Prolyl isomerase
Prolyl isomerase 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 unusually conformationally restrained peptide bond due to its cyclic structure with its side chain bonded to its...
activity and are related to the cyclophilin
Cyclophilin
Cyclophilins are a family of proteins from vertebrates and other organisms that bind to cyclosporine, an immunosuppressant which is usually used to suppress rejection after internal organ transplants...
s in function, though not in amino acid sequence
Primary structure
The primary structure of peptides and proteins refers to the linear sequence of its amino acid structural units. The term "primary structure" was first coined by Linderstrøm-Lang in 1951...
. FKBPs have been identified in many eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s from yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
to human
Human
Humans are the only living species in the Homo genus...
s and function as protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
chaperones for proteins containing proline
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
residues. Along with cyclophilin, FKBPs belong to the immunophilin family.
FKBP12
FKBP1A
Peptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene.-Interactions:FKBP1A has been shown to interact with RYR1, Mammalian target of rapamycin, TGF beta receptor 1, GLMN, ITPR1 and KIAA1303....
is notable in humans for binding the immunosuppressant
Immunosuppressant
An immunosuppressant is any substance that performs immunosuppression of the immune system. They may be either exogenous, as immunosuppressive drugs, or endogenous, as ,e. g., testosterone...
molecule tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
(originally designated FK506), which is used in treating patients after organ transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
and patients suffering from autoimmune disorders. Tacrolimus has been found to reduce episodes of organ rejection over a related treatment, the drug ciclosporin
Ciclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
, which binds cyclophilin. Both the FKBP-tacrolimus complex and the ciclosporin-cyclophilin complex inhibit a phosphatase
Phosphatase
A phosphatase is an enzyme that removes a phosphate group from its substrate by hydrolysing phosphoric acid monoesters into a phosphate ion and a molecule with a free hydroxyl group . This action is directly opposite to that of phosphorylases and kinases, which attach phosphate groups to their...
called calcineurin
Calcineurin
Calcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
, thus blocking signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
in the T-lymphocyte
Lymphocyte
A lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
transduction pathway. This therapeutic role is not related to prolyl isomerase activity.
Examples
Human genes encoding proteins in this family include:- AIP; AIPL1AIPL1Aryl-hydrocarbon-interacting protein-like 1 is a protein that in humans is encoded by the AIPL1 gene.-External links:*...
- FKBP1AFKBP1APeptidyl-prolyl cis-trans isomerase FKBP1A is an enzyme that in humans is encoded by the FKBP1A gene.-Interactions:FKBP1A has been shown to interact with RYR1, Mammalian target of rapamycin, TGF beta receptor 1, GLMN, ITPR1 and KIAA1303....
; FKBP1BFKBP1BPeptidyl-prolyl cis-trans isomerase FKBP1B is an enzyme that in humans is encoded by the FKBP1B gene.-Further reading:...
; FKBP2FKBP2FK506-binding protein 2 is a protein that in humans is encoded by the FKBP2 gene.-Interactions:FKBP2 has been shown to interact with ARFGEF1 and EPB41L2.-Further reading:...
; FKBP3FKBP3FK506-binding protein 3 is a protein that in humans is encoded by the FKBP3 gene.-Interactions:FKBP3 has been shown to interact with YY1, HDAC1, Histone deacetylase 2 and Mdm2.-Further reading:...
; FKBP5FKBP5FK506 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 basic cellular processes involving protein folding and...
; FKBP6FKBP6FK506 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....
; FKBP7; FKBP8FKBP8FK506-binding protein 8 is a protein that in humans is encoded by the FKBP8 gene.-Further reading:...
; FKBP9FKBP9FK506-binding protein 9 is a protein that in humans is encoded by the FKBP9 gene.-Further reading:...
; FKBP9L; FKBP10FKBP10FK506-binding protein 10 is a protein that in humans is encoded by the FKBP10 gene.-Further reading:...
; FKBP11; FKBP14; FKBP15; FKBP52FKBP52FK506-binding protein 4 is a protein that in humans is encoded by the FKBP4 gene.This protein contains TPR repeats and has a PPlase domain.-Further reading:-External links:... - LOC541473;