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.[6]
Clinical significanceedit
The FKBP5 gene has been found to have multiple polyadenylation sites[5] and is statistically associated with a higher rate of depressive disorders.[7]
Decreased methylation in the promoter of the FKBP5 gene has been observed in blood samples from patients with neurodegenerative diseases.[8]
FKBP51 Ligandsedit
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.[6] Macrocyclic FKBP51-selective ligands are non-immunosuppressive, engage FKBP51 in cells, and block the cellular effect of FKBP51.[9]
^ abcHähle A, Merz S, Meyners C, Hausch F (January 2019). "The Many Faces of FKBP51". Biomolecules. 9 (1): 35. doi:10.3390/biom9010035. PMC6359276. PMID 30669684. This article incorporates text from this source, which is available under the CC BY 4.0 license.
^Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Pütz B, et al. (December 2004). "Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment". Nature Genetics. 36 (12): 1319–25. doi:10.1038/ng1479. PMID 15565110. S2CID 21914515.
^Nabais MF, Laws SM, Lin T, Vallerga CL, Armstrong NJ, Blair IP, et al. (March 2021). "Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders". Genome Biology. 22 (1): 90. doi:10.1186/s13059-021-02275-5. PMC8004462. PMID 33771206.
^Nair SC, Rimerman RA, Toran EJ, Chen S, Prapapanich V, Butts RN, Smith DF (February 1997). "Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor". Molecular and Cellular Biology. 17 (2): 594–603. doi:10.1128/MCB.17.2.594. PMC231784. PMID 9001212.
^Prakash, Ajit; Shin, Joon; Rajan, Sreekanth; Yoon, Ho Sup (2016-04-07). "Structural basis of nucleic acid recognition by FK506-binding protein 25 (FKBP25), a nuclear immunophilin". Nucleic Acids Research. 44 (6): 2909–2925. doi:10.1093/nar/gkw001. ISSN 0305-1048. PMC4824100. PMID 26762975.
Further readingedit
Schiene-Fischer C, Yu C (April 2001). "Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases". FEBS Letters. 495 (1–2): 1–6. doi:10.1016/S0014-5793(01)02326-2. PMID 11322937. S2CID 42263861.
Baughman G, Wiederrecht GJ, Campbell NF, Martin MM, Bourgeois S (August 1995). "FKBP51, a novel T-cell-specific immunophilin capable of calcineurin inhibition". Molecular and Cellular Biology. 15 (8): 4395–402. doi:10.1128/mcb.15.8.4395. PMC230679. PMID 7542743.
Smith DF, Baggenstoss BA, Marion TN, Rimerman RA (August 1993). "Two FKBP-related proteins are associated with progesterone receptor complexes". The Journal of Biological Chemistry. 268 (24): 18365–71. doi:10.1016/S0021-9258(17)46853-0. PMID 7688746.
Smith DF, Albers MW, Schreiber SL, Leach KL, Deibel MR (November 1993). "FKBP54, a novel FK506-binding protein in avian progesterone receptor complexes and HeLa extracts". The Journal of Biological Chemistry. 268 (32): 24270–3. doi:10.1016/S0021-9258(20)80520-1. PMID 7693698.
Maruyama K, Sugano S (January 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. PMID 8125298.
Johnson J, Corbisier R, Stensgard B, Toft D (January 1996). "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. doi:10.1016/0960-0760(95)00221-9. PMID 8603045. S2CID 24410864.
Nair SC, Rimerman RA, Toran EJ, Chen S, Prapapanich V, Butts RN, Smith DF (February 1997). "Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor". Molecular and Cellular Biology. 17 (2): 594–603. doi:10.1128/MCB.17.2.594. PMC231784. PMID 9001212.
Baughman G, Wiederrecht GJ, Chang F, Martin MM, Bourgeois S (March 1997). "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. doi:10.1006/bbrc.1997.6307. PMID 9125197.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 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. PMID 9373149.
Young JC, Obermann WM, Hartl FU (July 1998). "Specific binding of tetratricopeptide repeat proteins to the C-terminal 12-kDa domain of hsp90". The Journal of Biological Chemistry. 273 (29): 18007–10. doi:10.1074/jbc.273.29.18007. PMID 9660753.
Hartley JL, Temple GF, Brasch MA (November 2000). "DNA cloning using in vitro site-specific recombination". Genome Research. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC310948. PMID 11076863.
Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, et al. (March 2001). "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. doi:10.1101/gr.GR1547R. PMC311072. PMID 11230166.
Pirkl F, Buchner J (May 2001). "Functional analysis of the Hsp90-associated human peptidyl prolyl cis/trans isomerases FKBP51, FKBP52 and Cyp40". Journal of Molecular Biology. 308 (4): 795–806. doi:10.1006/jmbi.2001.4595. PMID 11350175.
Davies TH, Ning YM, Sánchez ER (February 2002). "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. doi:10.1074/jbc.C100531200. PMID 11751894.
Giraudier S, Chagraoui H, Komura E, Barnache S, Blanchet B, LeCouedic JP, et al. (October 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. PMID 12351405.
Sinars CR, Cheung-Flynn J, Rimerman RA, Scammell JG, Smith DF, Clardy J (February 2003). "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. Bibcode:2003PNAS..100..868S. doi:10.1073/pnas.0231020100. PMC298693. PMID 12538866.
Hubler TR, Denny WB, Valentine DL, Cheung-Flynn J, Smith DF, Scammell JG (June 2003). "The FK506-binding immunophilin FKBP51 is transcriptionally regulated by progestin and attenuates progestin responsiveness". Endocrinology. 144 (6): 2380–7. doi:10.1210/en.2003-0092. PMID 12746298.
Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, et al. (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216. S2CID 11683986.
fkbp5, fk506, binding, protein, also, known, protein, which, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes1kt0, 3o5d, 3o5e, 3o5f, 3o5g, 3o5i, 3o5j, 3o5k, 3o5l, 3o5m, 3o5o, 3o5p, 3o5q, 3o5r, 4drh, 4dri, 4drk, 4drm, 4drn,. FK506 binding protein 5 also known as FKBP5 is a protein which in humans is encoded by the FKBP5 gene 5 FKBP5Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1KT0 3O5D 3O5E 3O5F 3O5G 3O5I 3O5J 3O5K 3O5L 3O5M 3O5O 3O5P 3O5Q 3O5R 4DRH 4DRI 4DRK 4DRM 4DRN 4DRO 4DRP 4DRQ 4JFI 4JFJ 4JFK 4JFL 4JFM 4R0X 4TW6 4TW7 4TX0 4W9O 4W9P 4W9Q 5DIT 5DIU 5BXJ 5DIVIdentifiersAliasesFKBP5 AIG6 FKBP51 FKBP54 P54 PPIase Ptg 10 FK506 binding protein 5 FKBP prolyl isomerase 5External IDsOMIM 602623 MGI 104670 HomoloGene 3038 GeneCards FKBP5 OMA FKBP5 orthologsGene location Human Chr Chromosome 6 human 1 Band6p21 31Start35 573 585 bp 1 End35 728 583 bp 1 Gene location Mouse Chr Chromosome 17 mouse 2 Band17 A3 3 17 14 66 cMStart28 618 068 bp 2 End28 736 501 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed ingastric mucosapericardiumright lunggastrocnemius muscleleft uterine tubecorpus epididymissynovial jointhuman penistibianippleTop expressed inlacrimal glandsecondary oocytethymusseminal vesiculaovarybelly cordcumulus cellsalivary glandsubmandibular glandparotid glandMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionisomerase activity protein binding heat shock protein binding peptidyl prolyl cis trans isomerase activity FK506 bindingCellular componentextracellular exosome membrane nucleus nucleoplasm cytoplasm cytosolBiological processprotein peptidyl prolyl isomerization chaperone mediated protein folding protein folding response to bacteriumSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez228914229EnsemblENSG00000096060ENSMUSG00000024222UniProtQ13451Q64378RefSeq mRNA NM 004117NM 001145775NM 001145776NM 001145777NM 010220RefSeq protein NP 001139247NP 001139248NP 001139249NP 004108NP 034350Location UCSC Chr 6 35 57 35 73 MbChr 17 28 62 28 74 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical significance 3 FKBP51 Ligands 4 Interactions 5 See also 6 References 7 Further readingFunction editThe 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 6 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 6 Clinical significance editThe FKBP5 gene has been found to have multiple polyadenylation sites 5 and is statistically associated with a higher rate of depressive disorders 7 Decreased methylation in the promoter of the FKBP5 gene has been observed in blood samples from patients with neurodegenerative diseases 8 FKBP51 Ligands editAs 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 6 Macrocyclic FKBP51 selective ligands are non immunosuppressive engage FKBP51 in cells and block the cellular effect of FKBP51 9 Interactions editFKBP5 has been shown to interact with Heat shock protein 90kDa alpha cytosolic member A1 10 See also editFKBP4 a functional antagonist to FKBP5 at corticoid receptors FKBP3 a DNA binding FKBP 11 References edit a b c GRCh38 Ensembl release 89 ENSG00000096060 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000024222 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene FKBP5 FK506 binding protein 5 a b c Hahle A Merz S Meyners C Hausch F January 2019 The Many Faces of FKBP51 Biomolecules 9 1 35 doi 10 3390 biom9010035 PMC 6359276 PMID 30669684 nbsp This article incorporates text from this source which is available under the CC BY 4 0 license Binder EB Salyakina D Lichtner P Wochnik GM Ising M Putz B et al December 2004 Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment Nature Genetics 36 12 1319 25 doi 10 1038 ng1479 PMID 15565110 S2CID 21914515 Nabais MF Laws SM Lin T Vallerga CL Armstrong NJ Blair IP et al March 2021 Meta analysis of genome wide DNA methylation identifies shared associations across neurodegenerative disorders Genome Biology 22 1 90 doi 10 1186 s13059 021 02275 5 PMC 8004462 PMID 33771206 Voll AM Meyners C Taubert MC Bajaj T Heymann T Merz S et al June 2021 Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with Enhanced Selectivity Angewandte Chemie 60 24 13257 13263 doi 10 1002 anie 202017352 PMC 8252719 PMID 33843131 Nair SC Rimerman RA Toran EJ Chen S Prapapanich V Butts RN Smith DF February 1997 Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor Molecular and Cellular Biology 17 2 594 603 doi 10 1128 MCB 17 2 594 PMC 231784 PMID 9001212 Prakash Ajit Shin Joon Rajan Sreekanth Yoon Ho Sup 2016 04 07 Structural basis of nucleic acid recognition by FK506 binding protein 25 FKBP25 a nuclear immunophilin Nucleic Acids Research 44 6 2909 2925 doi 10 1093 nar gkw001 ISSN 0305 1048 PMC 4824100 PMID 26762975 Further reading editSchiene Fischer C Yu C April 2001 Receptor accessory folding helper enzymes the functional role of peptidyl prolyl cis trans isomerases FEBS Letters 495 1 2 1 6 doi 10 1016 S0014 5793 01 02326 2 PMID 11322937 S2CID 42263861 Baughman G Wiederrecht GJ Campbell NF Martin MM Bourgeois S August 1995 FKBP51 a novel T cell specific immunophilin capable of calcineurin inhibition Molecular and Cellular Biology 15 8 4395 402 doi 10 1128 mcb 15 8 4395 PMC 230679 PMID 7542743 Smith DF Baggenstoss BA Marion TN Rimerman RA August 1993 Two FKBP related proteins are associated with progesterone receptor complexes The Journal of Biological Chemistry 268 24 18365 71 doi 10 1016 S0021 9258 17 46853 0 PMID 7688746 Smith DF Albers MW Schreiber SL Leach KL Deibel MR November 1993 FKBP54 a novel FK506 binding protein in avian progesterone receptor complexes and HeLa extracts The Journal of Biological Chemistry 268 32 24270 3 doi 10 1016 S0021 9258 20 80520 1 PMID 7693698 Maruyama K Sugano S January 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 PMID 8125298 Johnson J Corbisier R Stensgard B Toft D January 1996 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 doi 10 1016 0960 0760 95 00221 9 PMID 8603045 S2CID 24410864 Nair SC Rimerman RA Toran EJ Chen S Prapapanich V Butts RN Smith DF February 1997 Molecular cloning of human FKBP51 and comparisons of immunophilin interactions with Hsp90 and progesterone receptor Molecular and Cellular Biology 17 2 594 603 doi 10 1128 MCB 17 2 594 PMC 231784 PMID 9001212 Baughman G Wiederrecht GJ Chang F Martin MM Bourgeois S March 1997 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 doi 10 1006 bbrc 1997 6307 PMID 9125197 Suzuki Y Yoshitomo Nakagawa K Maruyama K Suyama A Sugano S October 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 PMID 9373149 Young JC Obermann WM Hartl FU July 1998 Specific binding of tetratricopeptide repeat proteins to the C terminal 12 kDa domain of hsp90 The Journal of Biological Chemistry 273 29 18007 10 doi 10 1074 jbc 273 29 18007 PMID 9660753 Hartley JL Temple GF Brasch MA November 2000 DNA cloning using in vitro site specific recombination Genome Research 10 11 1788 95 doi 10 1101 gr 143000 PMC 310948 PMID 11076863 Wiemann S Weil B Wellenreuther R Gassenhuber J Glassl S Ansorge W et al March 2001 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 doi 10 1101 gr GR1547R PMC 311072 PMID 11230166 Pirkl F Buchner J May 2001 Functional analysis of the Hsp90 associated human peptidyl prolyl cis trans isomerases FKBP51 FKBP52 and Cyp40 Journal of Molecular Biology 308 4 795 806 doi 10 1006 jmbi 2001 4595 PMID 11350175 Davies TH Ning YM Sanchez ER February 2002 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 doi 10 1074 jbc C100531200 PMID 11751894 Giraudier S Chagraoui H Komura E Barnache S Blanchet B LeCouedic JP et al October 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 PMID 12351405 Sinars CR Cheung Flynn J Rimerman RA Scammell JG Smith DF Clardy J February 2003 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 Bibcode 2003PNAS 100 868S doi 10 1073 pnas 0231020100 PMC 298693 PMID 12538866 Hubler TR Denny WB Valentine DL Cheung Flynn J Smith DF Scammell JG June 2003 The FK506 binding immunophilin FKBP51 is transcriptionally regulated by progestin and attenuates progestin responsiveness Endocrinology 144 6 2380 7 doi 10 1210 en 2003 0092 PMID 12746298 Bouwmeester T Bauch A Ruffner H Angrand PO Bergamini G Croughton K et al February 2004 A physical and functional map of the human TNF alpha NF kappa B signal transduction pathway Nature Cell Biology 6 2 97 105 doi 10 1038 ncb1086 PMID 14743216 S2CID 11683986 Portal nbsp Biology Retrieved from https en wikipedia org w index php title FKBP5 amp oldid 1224749963, wikipedia, wiki, book, books, library,
