FK506 binding protein 5, also known as FKBP5, is a
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, res ...
which in humans is encoded by the ''FKBP5''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
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 trafficking. This encoded protein is a
cis-trans 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 unusua ...
that binds to the immunosuppressants
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 ...
(FK506) and
sirolimus
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosi ...
(rapamycin). It is thought to mediate
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 ...
inhibition. It also interacts functionally with mature corticoid receptor hetero-complexes (i.e.
progesterone-,
glucocorticoid-,
mineralocorticoid-receptor complexes) along with the
90 kDa heat shock protein
Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...
and
PTGES3
Prostaglandin E synthase 3 (cytosolic) is an enzyme that in humans is encoded by the PTGES3 gene.
The protein encoded by this gene is also known as p23 which functions as a chaperone which is required for proper functioning of the glucocorticoid ...
(P23 protein).
As an Hsp90-associated co-chaperone that regulates the responsiveness of steroid hormone receptors, FKBP51 plays an important role in stress endocrinology and glucocorticoid signaling.
Clinical significance
The FKBP5 gene has been found to have multiple
polyadenylation
Polyadenylation is the addition of a poly(A) tail to an RNA transcript, typically a messenger RNA (mRNA). The poly(A) tail consists of multiple adenosine monophosphates; in other words, it is a stretch of RNA that has only adenine bases. In euk ...
sites
and is statistically associated with a higher rate of depressive disorders.
Decreased methylation in the promoter of the FKBP5 gene has been observed in blood samples from patients with neurodegenerative diseases.
FKBP51 Ligands
As a key player in several diseases like stress-related disorders, chronic pain, and obesity, FKBP51 is an attractive drug target.
SAFit2 currently the most best characterized FKBP51 ligand, has shown promising effects in numerous animal models.
Macrocyclic FKBP51-selective ligands are non-immunosuppressive, engage FKBP51 in cells, and block the cellular effect of FKBP51.
Interactions
FKBP5 has been shown to
interact
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with
Heat shock protein 90kDa alpha (cytosolic), member A1.
See also
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FKBP4 - a functional antagonist to FKBP5 at corticoid receptors
*
FKBP3 - a DNA binding FKBP
References
Further reading
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