1qz2

Structural highlights

Function

[FKBP4_HUMAN] Immunophilin protein with PPIase and co-chaperone activities (By similarity). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments (By similarity). The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria.^{[1] [2] [3] [4] [5]} [HS90B_HUMAN] Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.^{[6] [7]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• FKBP 3D structures

References

1. ↑ Peattie DA, Harding MW, Fleming MA, DeCenzo MT, Lippke JA, Livingston DJ, Benasutti M. Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10974-8. PMID:1279700
2. ↑ Tai PK, Albers MW, Chang H, Faber LE, Schreiber SL. Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex. Science. 1992 May 29;256(5061):1315-8. PMID:1376003
3. ↑ Sanchez ER, Faber LE, Henzel WJ, Pratt WB. 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. Biochemistry. 1990 May 29;29(21):5145-52. PMID:2378870
4. ↑ Shim S, Yuan JP, Kim JY, Zeng W, Huang G, Milshteyn A, Kern D, Muallem S, Ming GL, Worley PF. Peptidyl-prolyl isomerase FKBP52 controls chemotropic guidance of neuronal growth cones via regulation of TRPC1 channel opening. Neuron. 2009 Nov 25;64(4):471-83. doi: 10.1016/j.neuron.2009.09.025. PMID:19945390 doi:10.1016/j.neuron.2009.09.025
5. ↑ Gallo LI, Lagadari M, Piwien-Pilipuk G, Galigniana MD. The 90-kDa heat-shock protein (Hsp90)-binding immunophilin FKBP51 is a mitochondrial protein that translocates to the nucleus to protect cells against oxidative stress. J Biol Chem. 2011 Aug 26;286(34):30152-60. doi: 10.1074/jbc.M111.256610. Epub, 2011 Jul 5. PMID:21730050 doi:10.1074/jbc.M111.256610
6. ↑ Chadli A, Graham JD, Abel MG, Jackson TA, Gordon DF, Wood WM, Felts SJ, Horwitz KB, Toft D. GCUNC-45 is a novel regulator for the progesterone receptor/hsp90 chaperoning pathway. Mol Cell Biol. 2006 Mar;26(5):1722-30. PMID:16478993 doi:http://dx.doi.org/26/5/1722
7. ↑ Retzlaff M, Stahl M, Eberl HC, Lagleder S, Beck J, Kessler H, Buchner J. Hsp90 is regulated by a switch point in the C-terminal domain. EMBO Rep. 2009 Oct;10(10):1147-53. Epub 2009 Aug 21. PMID:19696785 doi:http://dx.doi.org/embor2009153
8. ↑ Wu B, Li P, Liu Y, Lou Z, Ding Y, Shu C, Ye S, Bartlam M, Shen B, Rao Z. 3D structure of human FK506-binding protein 52: implications for the assembly of the glucocorticoid receptor/Hsp90/immunophilin heterocomplex. Proc Natl Acad Sci U S A. 2004 Jun 1;101(22):8348-53. Epub 2004 May 24. PMID:15159550 doi:10.1073/pnas.0305969101