FK506-binding protein 4 is a protein that in humans is encoded by the FKBP4gene.
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 immunosuppressantsFK506 and rapamycin. It has high structural and functional similarity to FK506-binding protein 1A (FKBP1A), but unlike FKBP1A, this protein does not have immunosuppressant activity when complexed with FK506. It interacts with interferon regulatory factor-4 and plays an important role in immunoregulatory gene expression in B and T lymphocytes. This encoded protein is known to associate with phytanoyl-CoA alpha-hydroxylase. It can also associate with two heat shock proteins (hsp90 and hsp70) and thus may play a role in the intracellular trafficking of hetero-oligomeric forms of the steroid hormone receptors. This protein correlates strongly with adeno-associated virus type 2 vectors (AAV) resulting in a significant increase in AAV-mediated transgene expression in human cell lines. Thus this encoded protein is thought to have important implications for the optimal use of AAV vectors in human gene therapy. This gene has been found to have multiple polyadenylation sites.
Recent research suggests that FKBP52 may play a role in preventing the Tau protein from turning pathogenic. This may prove significant for the development of new Alzheimer's drugs and for detecting the disease before the onset of clinical symptoms.
^Chambraud, B; Radanyi C; Camonis J H; Shazand K; Rajkowski K; Baulieu E E (Dec 1996). "FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin". J. Biol. Chem. (UNITED STATES) 271 (51): 32923–9. doi:10.1074/jbc.271.51.32923. ISSN0021-9258. PMID8955134.
Yem AW, Tomasselli AG, Heinrikson RL et al. (1992). "The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13". J. Biol. Chem.267 (5): 2868–71. PMID1371107.
Tai PK, Albers MW, Chang H et al. (1992). "Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex". Science256 (5061): 1315–8. doi:10.1126/science.1376003. PMID1376003.
Wiederrecht G, Hung S, Chan HK et al. (1992). "Characterization of high molecular weight FK-506 binding activities reveals a novel FK-506-binding protein as well as a protein complex". J. Biol. Chem.267 (30): 21753–60. PMID1383226.
Sanchez ER, Faber LE, Henzel WJ, Pratt WB (1990). "The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70- and 90-kilodalton heat shock proteins". Biochemistry29 (21): 5145–52. doi:10.1021/bi00473a021. PMID2378870.
Chambraud B, Radanyi C, Camonis JH et al. (1997). "FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin". J. Biol. Chem.271 (51): 32923–9. doi:10.1074/jbc.271.51.32923. PMID8955134.
Bruner KL, Derfoul A, Robertson NM et al. (1998). "The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52". Receptors & signal transduction7 (2): 85–98. PMID9392437.
Bermingham NA, Rauf S, Katsanis N et al. (1998). "The immunophilin FKBP4 (FKBP52/FKBP59) maps to the distal short arm of human chromosome 12". Mamm. Genome9 (3): 268. doi:10.1007/s003359900746. PMID9501323.
Galigniana MD, Radanyi C, Renoir JM et al. (2001). "Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus". J. Biol. Chem.276 (18): 14884–9. doi:10.1074/jbc.M010809200. PMID11278753.
Guo Y, Guettouche T, Fenna M et al. (2002). "Evidence for a mechanism of repression of heat shock factor 1 transcriptional activity by a multichaperone complex". J. Biol. Chem.276 (49): 45791–9. doi:10.1074/jbc.M105931200. PMID11583998.
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.