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FLASH GENE
Symbol FKBP5 contributors: mct - updated : 23-11-2022
HGNC name FK506 binding protein 5
HGNC id 3721
Location 6p21.31      Physical location : 35.541.361 - 35.696.360
Synonym name
  • HSP90-binding immunophilin
  • progesterone receptor-associated immunophilin
  • rotamase
  • androgen-regulated protein 6
  • Synonym symbol(s) P54, FKBP51, FKBP54, PPIase, Ptg-10, AIG6, MGC111006,
    EC.number 5.2.1.8
    DNA
    TYPE functioning gene
    STRUCTURE 155.35 kb     12 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   enhancer
    text structure 13 androgen response elements
    MAPPING cloned Y linked N status confirmed
    Map see WBS1
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3951 51 457 - 2001 11350175
  • isoform 1
  • 11 - 3793 51 457 - 2001 11350175
  • isoform 1
  • 11 - 3838 51 457 - 2001 11350175
  • isoform 1
  • 7 - 7384 - 268 - 2001 11350175
  • isoform 2
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two PPIase FKBP-type domains
  • three TPR (tetratricopeptide repeat motif) domain (a functional TPR domain is required for its mitochondrial localization)
  • lacking a known mitochondrial localization signal
  • a nuclear localization sequence that appears to be dominant in the overall balance for its subcellular localization, when it cannot be targeted to mitochondria
  • mono polymer dimer
    HOMOLOGY
    interspecies homolog to murine Fkbp5 (87.3pc)
    homolog to rattus Fkbp5 (91.4pc)
    Homologene
    FAMILY
  • immunophilin class of proteins family
  • CATEGORY chaperone/stress , enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text
  • undergoes nuclear-mitochondrial shuttling, and it also shows antiapoptotic action when cells are exposed to oxidative stress
  • basic FUNCTION
  • cis-trans prolyl isomerase that binds to the immunosuppressants FK506 and rapamycin
  • inhibiting apoptosis through a calcineurin-dependent pathway
  • involved in the regulation of stress hormone-regulating hypothalamic -pituitary -adrenal axis through adaptive changes in glucocorticoid receptor
  • playing a role in immunoregulation and basic cellular processes involving protein folding and trafficking
  • suppressing the proliferation of colorectal adenocarcinoma, possibly due to the suppression of functions of the glucocorticoid receptors
  • plays an important role in glioma growth and chemoresistance through regulating signal transduction of the NF-kappaB pathway
  • promotes assembly of the HSP90 chaperone complex and regulates androgen receptor signalling in prostate cancer cells
  • favors the nuclear exclusion of corticosteroid receptors
  • major mitochondrial factor that undergoes nuclear-mitochondrial shuttling, an observation that may be related to antiapoptotic mechanisms triggered during the stress response
  • involved in regulation of the glucocorticoid response to stress-related disorders
  • promotes osteoclast differentiation by a mechanism distinct from NFKB1 activation, and FKBP5 might play a role in bone destruction and development of osteoporosis in RA as well as in glucocorticoid-induced osteoporosis
  • promoted activation of epithelial-to-mesenchymal transition (EMT) genes and improved melanoma cell migration and invasion
  • role for FKBP5 in the innate immune response to viral infection
  • role of the FKBP51-AKT1 kinase-synapsin pathway in stress responsiveness
  • role for FKBP5 in cytoskeletal rearrangement and cell migration and invasion
  • key regulator of endocrine stress responses in mammals and is a potential therapeutic target for stress-related disorders
  • as a stress-induced protein, FKBP5 uses re-setting of post-translational modifications (PTMs) to relay the effect of stress on various signaling pathways
  • FKBP5 independently and directly is regulating phosphorylation cascades and nuclear receptors
  • CELLULAR PROCESS cell life, antiapoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • part of a heteromultimeric cytoplasmic complex with HSP90, HSP70 and steroid receptors, dissociating from the complex when NR3C1 binds glucocorticoid
  • forms complexes in mitochondria with the glucocorticoid receptor and the HSP90/HSP70-based chaperone heterocomplex
  • FKBP6 gene and FKBP5, can form dimers bound via a disulfide bridge in the nucleus and the dimer may have some crucial function in the regulation of some nuclear complexes at different stages of the cell cycle
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associated with the heterooligomeric progesterone complex with HSP50 and HSP70
  • mediating drug dependent clacineurin inhibition in vitro
  • interacts with both calcineurin and heat shock protein (HSP)70/HSP90
  • potentially may form complexes with other mitochondrial factors as GR
  • FKBP5 acts as an important regulator of glucocorticoid receptor (GR) activation, by decreasing ligand binding and impeding translocation of the receptor to the nucleus, while TSC22D3 mediates glucocorticoid anti-inflammatory effects
  • DLC1, and STARD13 are two novel interacting partner proteins of FKBP5
  • FKBP5 is a glucocorticoid receptor co-chaperone (PMIOD: 29206196)
  • FKBP5 promotes decidualization by reducing the Ser473 phosphorylation levels in AKT1
  • binds progesterone receptor (PR), glucocorticoid receptor (GR), and androgen receptor (AR) to coregulate their transcriptional activity
  • cell & other
    REGULATION
    induced by glucocorticoids
    androgen
    corticosteroid treatment in individus with asthma but high expression of FKBP5 was associated with a poor response to corticosteroid
    prednisolone treatment in leukemic cells from children with precursor-
    B- or T-acute lymphoblastic leukemia
    aldosterone in intestinal epithelium
    inhibited by FK506
    Other phosphorylated upon DNA damage
    downregulated in the follicular phase of the menstrual cycle
    FKBP5, FKBP4 are subject of post-translational modifications such as phosphorylation, SUMOlyation, and acetylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in idiopathic myelofibrosis
    tumoral     --over  
    in melanoma and correlates with aggressiveness and therapy resistance
    Susceptibility to frequent depressive episodes
    Variant & Polymorphism SNP , other
  • genetic variation within FKBP5 may influence attempted suicide and number of depressive episodes in bipolar subjects
  • FKBP5-T-DR6 haplotype is associated with resistance to endogenous exogenous glucocorticoids and transplant rejection
  • homozygous carriers of the FKBP5 minor allele showed insufficient cortisol recovery and increased self-reported anxiety after psychosocial stress, subjects carrying these variants are at risk of displaying chronically elevated cortisol levels after repeated stress constituting a risk factor for stress-related diseases
  • four SNPs of the FKBP5 gene interacted with severity of child abuse as a predictor of adult posttraumatic stress disorder symptoms
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    provides an attractive target for inhibiting androgen receptor activity in prostate cancer cells
    cancerreproductiveuterus
    Evaluating the effect of FKBP51 inhibition in preclinical studies will clarify its significance as a potential therapeutic approach against leiomyoma
    ANIMAL & CELL MODELS