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 FK506 and 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 P23 protein.
Clinical significance
Genetic studies have identified a role for FKBP5 in posttraumatic stress disorder, depression and anxiety.[2] For example, single nucleotide polymorphisms (SNPs) in FKBP5 have been found to interact with childhood trauma to predict severity of adult posttraumatic stress disorder (PTSD).[3] These findings suggest that individuals with these SNPs who are abused as children are more susceptible to PTSD as adults. FKBP5 has also been found to be less expressed in individuals with current PTSD.[4] The FKBP5 gene has been found to have multiple polyadenylation sites[1] and is statistically associated with a higher rate of depressive disorders.[5]
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Smith DF, Baggenstoss BA, Marion TN, Rimerman RA (1993). "Two FKBP-related proteins are associated with progesterone receptor complexes". J. Biol. Chem. 268 (24): 18365–71. PMID7688746.
Smith DF, Albers MW, Schreiber SL, Leach KL, Deibel MR (1993). "FKBP54, a novel FK506-binding protein in avian progesterone receptor complexes and HeLa extracts". J. Biol. Chem. 268 (32): 24270–3. PMID7693698.
Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Johnson J, Corbisier R, Stensgard B, Toft D (1996). "The involvement of p23, hsp90, and immunophilins in the assembly of progesterone receptor complexes". J. Steroid Biochem. Mol. Biol. 56 (1-6 Spec No): 31–7. doi:10.1016/0960-0760(95)00221-9. PMID8603045.
Baughman G, Wiederrecht GJ, Chang F, Martin MM, Bourgeois S (1997). "Tissue distribution and abundance of human FKBP51, and FK506-binding protein that can mediate calcineurin inhibition". Biochem. Biophys. Res. Commun. 232 (2): 437–43. doi:10.1006/bbrc.1997.6307. PMID9125197.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Young JC, Obermann WM, Hartl FU (1998). "Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90". J. Biol. Chem. 273 (29): 18007–10. doi:10.1074/jbc.273.29.18007. PMID9660753.
Pirkl F, Buchner J (2001). "Functional analysis of the Hsp90-associated human peptidyl prolyl cis/trans isomerases FKBP51, FKBP52 and Cyp40". J. Mol. Biol. 308 (4): 795–806. doi:10.1006/jmbi.2001.4595. PMID11350175.
Davies TH, Ning YM, Sánchez ER (2002). "A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins". J. Biol. Chem. 277 (7): 4597–600. doi:10.1074/jbc.C100531200. PMID11751894.
Giraudier S, Chagraoui H, Komura E, Barnache S, Blanchet B, LeCouedic JP, Smith DF, Larbret F, Taksin AL, Moreau-Gachelin F, Casadevall N, Tulliez M, Hulin A, Debili N, Vainchenker W (2002). "Overexpression of FKBP51 in idiopathic myelofibrosis regulates the growth factor independence of megakaryocyte progenitors". Blood. 100 (8): 2932–40. doi:10.1182/blood-2002-02-0485. PMID12351405.