FKBP5

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FKBP5
Protein FKBP5 PDB 1kt0.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFKBP5, AIG6, FKBP51, FKBP54, P54, PPIase, Ptg-10, FK506 binding protein 5, FKBP prolyl isomerase 5
External IDsOMIM: 602623 MGI: 104670 HomoloGene: 3038 GeneCards: FKBP5
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004117
NM_001145775
NM_001145776
NM_001145777

NM_010220

RefSeq (protein)

NP_001139247
NP_001139248
NP_001139249
NP_004108

NP_034350

Location (UCSC)Chr 6: 35.57 – 35.73 MbChr 17: 28.62 – 28.74 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

FK506 binding protein 5, also known as FKBP5, is a protein which in humans is encoded by the FKBP5 gene.[5]

Function[edit]

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 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[edit]

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 Ligands[edit]

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]

Interactions[edit]

FKBP5 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1.[10]

See also[edit]

  • FKBP4 - a functional antagonist to FKBP5 at corticoid receptors
  • FKBP3 - a DNA binding FKBP[11]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000096060 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024222 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b "Entrez Gene: FKBP5 FK506 binding protein 5".
  6. ^ a b c Hähle 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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[edit]