Biology:FKBP5

Short description: Protein-coding gene in humans

Generic protein structure example

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 basic cellular processes involving protein folding and trafficking. This encoded protein is a cis-trans prolyl isomerase that binds to the immunosuppressants tacrolimus (FK506) and sirolimus (rapamycin). It is thought to mediate calcineurin 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 and PTGES3 (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 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 with Heat shock protein 90kDa alpha (cytosolic), member A1.

See also

• FKBP4 - a functional antagonist to FKBP5 at corticoid receptors
• FKBP3 - a DNA binding FKBP

Further reading

• "Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases". FEBS Letters 495 (1–2): 1–6. April 2001. doi:10.1016/S0014-5793(01)02326-2. PMID 11322937. 
• "FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition". Molecular and Cellular Biology 15 (8): 4395–402. August 1995. doi:10.1128/mcb.15.8.4395. PMID 7542743. 
• "Two FKBP-related proteins are associated with progesterone receptor complexes". The Journal of Biological Chemistry 268 (24): 18365–71. August 1993. doi:10.1016/S0021-9258(17)46853-0. PMID 7688746. 
• "FKBP54, a novel FK506-binding protein in avian progesterone receptor complexes and HeLa extracts". The Journal of Biological Chemistry 268 (32): 24270–3. November 1993. doi:10.1016/S0021-9258(20)80520-1. PMID 7693698. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes". The Journal of Steroid Biochemistry and Molecular Biology 56 (1-6 Spec No): 31–7. January 1996. doi:10.1016/0960-0760(95)00221-9. PMID 8603045. 
• "Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor". Molecular and Cellular Biology 17 (2): 594–603. February 1997. doi:10.1128/MCB.17.2.594. PMID 9001212. 
• "Tissue distribution and abundance of human FKBP51, and FK506-binding protein that can mediate calcineurin inhibition". Biochemical and Biophysical Research Communications 232 (2): 437–43. March 1997. doi:10.1006/bbrc.1997.6307. PMID 9125197. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90". The Journal of Biological Chemistry 273 (29): 18007–10. July 1998. doi:10.1074/jbc.273.29.18007. PMID 9660753. 
• "DNA cloning using in vitro site-specific recombination". Genome Research 10 (11): 1788–95. November 2000. doi:10.1101/gr.143000. PMID 11076863. 
• "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Research 11 (3): 422–35. March 2001. doi:10.1101/gr.GR1547R. PMID 11230166. 
• "Functional analysis of the Hsp90-associated human peptidyl prolyl cis/trans isomerases FKBP51, FKBP52 and Cyp40". Journal of Molecular Biology 308 (4): 795–806. May 2001. doi:10.1006/jmbi.2001.4595. PMID 11350175. 
• "A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins". The Journal of Biological Chemistry 277 (7): 4597–600. February 2002. doi:10.1074/jbc.C100531200. PMID 11751894. 
• "Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors". Blood 100 (8): 2932–40. October 2002. doi:10.1182/blood-2002-02-0485. PMID 12351405. 
• "Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes". Proceedings of the National Academy of Sciences of the United States of America 100 (3): 868–73. February 2003. doi:10.1073/pnas.0231020100. PMID 12538866. Bibcode: 2003PNAS..100..868S. 
• "The FK506-binding immunophilin FKBP51 is transcriptionally regulated by progestin and attenuates progestin responsiveness". Endocrinology 144 (6): 2380–7. June 2003. doi:10.1210/en.2003-0092. PMID 12746298. 
• "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology 6 (2): 97–105. February 2004. doi:10.1038/ncb1086. PMID 14743216.