Peptidyl-prolyl cis-trans isomerase FKBP5 (FKBP5)
The protein contains 457 amino acids for an estimated molecular weight of 51212 Da.
Immunophilin protein with PPIase and co-chaperone activities (PubMed:11350175). Component of unligated steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). Plays a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors maintaining the complex into the cytoplasm when unliganded (PubMed:12538866). Acts as a regulator of Akt/AKT1 activity by promoting the interaction between Akt/AKT1 and PHLPP1, thereby enhancing dephosphorylation and subsequent activation of Akt/AKT1 (PubMed:28147277). (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Chaperone-mediated protein folding
Protein folding
Protein peptidyl-prolyl isomerization
Response to bacterium
Cellular Component
Cytoplasm
Cytosol
Endoplasmic reticulum membrane
Extracellular exosome
Membrane
Nucleoplasm
Molecular Function
FK506 binding
Heat shock protein binding
Peptidyl-prolyl cis-trans isomerase activity
The reference OMIM entry for this protein is 602623
Fk506-binding protein 5; fkbp5
Fk506-binding protein, 51-kd; fkbp51
Fkbp54
For background information on FK506-binding proteins (FKBPs), see FKBP1A (186945).
CLONING
Nair et al. (1997) cloned a cDNA for human FKBP51 from a HeLa cell cDNA library. The FKBP51 cDNA encodes a predicted 457-amino acid polypeptide with 90% identity to mouse fkbp51 and 55% identity to FKBP52 (600611). Baughman et al. (1997) cloned a cDNA encoding human FKBP51 by screening a human thymus cDNA library with a fragment of the murine Fkbp51 cDNA. The human FKBP51 cDNA encodes a deduced 457-amino acid protein that shows 87% sequence identity to the mouse protein. Northern blot analysis revealed that treatment of leukemic T cells with glucocorticoids results in a marked increase in expression of a 3.7-kb transcript. Western blot analysis showed that unlike the predominant T-cell expression of the mouse protein, FKBP51 is expressed as a 51-kD protein in a variety of tissues but not in brain, colon, or lung. The expression is frequently in molar excess of that of FKBP12 (FKBP1A; 186945), but its capacity to inhibit calcineurin is significantly lower than that of FKBP1A. Baughman et al. (1995) and Yeh et al. (1995) cloned and characterized the mouse Fkbp51 gene. Baughman et al. (1995) isolated the gene based on its induction during glucocorticoid-induced apoptosis in murine thymoma cells. Murine Fkbp51 encodes a 456-amino acid polypeptide with a predicted mass of 51 kD. Yeh et al. (1995) isolated the mouse gene based on the selective accumulation of its transcript during adipocyte differentiation. By Northern blot analysis, the gene is expressed in a variety of tissues, with highest levels in liver, skeletal muscle, and kidney.MAPPING
International Radiation Hybrid Mapping Consortium mapped the FKBP51 gene to chromosome 6 (TMAP RH47153).GENE FUNCTION
By Western blot analysis, Baughman et al. (1995) showed that the murine Fkbp51 gene is expressed in all tissues, most abundantly in T lymphocytes and in the thymus. Baughman et al. (1995) showed that FKBP5 has PPIase activity and is inhibited by rapamycin and FK520, a structural analog that is virtually identical to FK506. Yeh et al. (1995) showed that the PPIase activity of murine Fkbp51 is inhibited by FK506 but not by cyclosporin A. Nair et al. (1997) showed that FKBP51 is inhibited by FK506 but not by cyclosporine. The authors demonstrated that FKBP51 and FKBP52 bind to Hsp90 (140571) in a competitive manner. Nair et al. (1997) also showed that Hsp90, Hsp70 (140550), and p23 (607061), a component of the progesterone receptor complex, bind directly or indirectly to FKBP51. Vermeer et al. (2003) studied whether the glucocorticoid-induced increase of the mRNA encoding FKBP5 could be used for the development of a novel assay, ultimately to be used in native human peripheral blood mononuclear cells (PBMCs). Glucocorticoid addition to human lymphoblastoid cells resulted in a dose-dependent increase of FKBP5 mRNA levels within 2 hours, followed by a further increase until 24 hours. Northern blot analysis and real-time PCR yielded similar results. Coincubation of glucocorticoids with the glucocorticoid receptor (138040) antagonist ORG34116 or the protein synthesis inhibitor cycloheximide suggested a direct, glucocorticoid receptor-mediated upregulation of FKBP5 gene transcription. They concluded that the induction of FKBP5 mRNA by glucocorticoids may be a suitable marker to assess individual glucocorticoid sensitivity, the in vitro measurement of glucocorticoid poten ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 602623 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed