FKBP52

FK506 binding protein 4, 59kDa

PDB rendering based on 1n1a.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1N1A, 1P5Q, 1Q1C, 1QZ2, 4DRJ, 4LAV, 4LAW, 4LAX, 4LAY

Identifiers

Symbols

FKBP4 ; FKBP51; FKBP52; FKBP59; HBI; Hsp56; PPIase; p52

External IDs

OMIM: 600611 MGI: 95543 HomoloGene: 36085 ChEMBL: 4050 GeneCards: FKBP4 Gene

EC number

5.2.1.8

Gene ontology
Molecular function	• peptidyl-prolyl cis-trans isomerase activity • protein binding • ATP binding • GTP binding • FK506 binding • protein binding, bridging • heat shock protein binding • copper-dependent protein binding • glucocorticoid receptor binding • poly(A) RNA binding • tau protein binding • phosphoprotein binding
Cellular component	• nucleus • nucleolus • cytoplasm • mitochondrion • endoplasmic reticulum membrane • cytosol • microtubule • neuronal cell body • axonal growth cone • perinuclear region of cytoplasm • extracellular vesicular exosome
Biological process	• protein peptidyl-prolyl isomerization • protein folding • steroid hormone receptor complex assembly • copper ion transport • embryo implantation • negative regulation of neuron projection development • androgen receptor signaling pathway • prostate gland development • negative regulation of microtubule polymerization or depolymerization • negative regulation of microtubule polymerization • protein complex localization • male sex differentiation • chaperone-mediated protein folding
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 12:
2.9 – 2.91 Mb

Chr 6:
128.43 – 128.44 Mb

PubMed search

FK506-binding protein 4 is a protein that in humans is encoded by the FKBP4 gene.^[1]^[2]

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 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.^[2]

This protein contains TPR repeats and has a PPlase domain.

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.

Interactions

FKBP52 has been shown to interact with GLMN.^[3]^[4]

References

↑ Peattie DA, Harding MW, Fleming MA, DeCenzo MT, Lippke JA, Livingston DJ, Benasutti M (Dec 1992). "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 89 (22): 10974–8. doi:10.1073/pnas.89.22.10974. PMC 50465. PMID 1279700.
↑ 2.0 2.1 "Entrez Gene: FKBP4 FK506 binding protein 4, 59kDa".
↑ 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. ISSN 0021-9258. PMID 8955134.
↑ Neye, H (Mar 2001). "Mutation of FKBP associated protein 48 (FAP48) at proline 219 disrupts the interaction with FKBP12 and FKBP52". Regul. Pept. (Netherlands) 97 (2–3): 147–52. doi:10.1016/S0167-0115(00)00206-8. ISSN 0167-0115. PMID 11164950.

Schiene-Fischer C, Yu C (2001). "Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases". FEBS Lett. 495 (1–2): 1–6. doi:10.1016/S0014-5793(01)02326-2. PMID 11322937.
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. PMID 1371107.
Tai PK, Albers MW, Chang H et al. (1992). "Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex". Science 256 (5061): 1315–8. doi:10.1126/science.1376003. PMID 1376003.
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. PMID 1383226.
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". Biochemistry 29 (21): 5145–52. doi:10.1021/bi00473a021. PMID 2378870.
Alnemri ES, Fernandes-Alnemri T, Nelki DS et al. (1993). "Overexpression, characterization, and purification of a recombinant mouse immunophilin FKBP-52 and identification of an associated phosphoprotein". Proc. Natl. Acad. Sci. U.S.A. 90 (14): 6839–43. doi:10.1073/pnas.90.14.6839. PMC 47028. PMID 8341706.
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. PMID 8955134.
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 transduction 7 (2): 85–98. PMID 9392437.
Miyata Y, Chambraud B, Radanyi C et al. (1998). "Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: Regulation of HSP90-binding activity of FKBP52". Proc. Natl. Acad. Sci. U.S.A. 94 (26): 14500–5. doi:10.1073/pnas.94.26.14500. PMC 25035. PMID 9405642.
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. Genome 9 (3): 268. doi:10.1007/s003359900746. PMID 9501323.
Chambraud B, Radanyi C, Camonis JH et al. (1999). "Immunophilins, Refsum disease, and lupus nephritis: The peroxisomal enzyme phytanoyl-COA α-hydroxylase is a new FKBP-associated protein". Proc. Natl. Acad. Sci. U.S.A. 96 (5): 2104–9. doi:10.1073/pnas.96.5.2104. PMC 26744. PMID 10051602.
Mamane Y, Sharma S, Petropoulos L et al. (2000). "Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52". Immunity 12 (2): 129–40. doi:10.1016/S1074-7613(00)80166-1. PMID 10714679.
Neye H (2001). "Mutation of FKBP associated protein 48 (FAP48) at proline 219 disrupts the interaction with FKBP12 and FKBP52". Regul. Pept. 97 (2–3): 147–52. doi:10.1016/S0167-0115(00)00206-8. PMID 11164950.
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. PMID 11278753.
Qing K, Hansen J, Weigel-Kelley KA et al. (2001). "Adeno-Associated Virus Type 2-Mediated Gene Transfer: Role of Cellular FKBP52 Protein in Transgene Expression". J. Virol. 75 (19): 8968–76. doi:10.1128/JVI.75.19.8968-8976.2001. PMC 114465. PMID 11533160.
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. PMID 11583998.
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. PMID 11751894.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.