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Symbol FKBP4 contributors: mct/ - updated : 17-09-2009
HGNC name FK506 binding protein 4, 59kDa
HGNC id 3720
Location 12p13.33      Physical location : 2.904.107 - 2.914.585
Synonym name
  • HSP binding immunophilin
  • T-cell FK506-binding protein, 59kD
  • rotamase
  • FKBP52 protein
  • peptidylprolyl cis-trans isomerase
  • HSP binding immunophilin
  • Synonym symbol(s) FKBP59, FKBP52, HBI, p52, Hsp56, PPIase
    TYPE functioning gene
    STRUCTURE 10.48 kb     10 Exon(s)    3 Copie(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (CAAT box)
    Binding site
    text structure consensus binding site for Sp1, heat-shock factor, and MYC-MAX
    MAPPING cloned Y linked N status provisional
    Map pter - D12S872 - D12S1615 - FKBP4 - D12S1866 - D12S1971 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3757 - 459 - 2007 17343741
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
     mouthtongue  highly
     stomach   highly
    Endocrinepancreas   highly
    Reproductivefemale systemovary  highly
     male systemprostate   
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningendometrium   Homo sapiens
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    at STAGE
    physiological period pregnancy
    Text in the uterus during embryonic implantation
  • the first two domains include a functional site for peptidyl-prolyl cis/trans isomerase (PPIase) activity and a PPIase-like region
  • multiple N terminal FK506 binding and peptidyl prolyl cis-trans isomerase (rotamase) domains
  • three tetratricopeptide repeat (TPR) domains, which have a sequence usually recognized and bound by heat shock proteins, occupy the third structural domain
  • fourth C-terminal domain contains a putative binding site for calmodulin
    interspecies ortholog to murine Fkbp4
    ortholog to rattus fkbp4
  • immunophilin class of proteins family
  • CATEGORY chaperone/stress , enzyme , regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • T cell binding protein FKBP for the immunosuppressive agents FK506-rapamycin, but lacking immuno suppressant activity
  • playing a role in regulating tissue-specific hormone action and in uterine receptivity for implantation
  • component of the copper efflux machinery, and in so, may also promote neuroprotection from copper toxicity
  • tetratricopeptide repeat (TPR)-containing cochaperone that influences steroid hormone receptor function
  • has an important physiological role in up-regulating androgen receptor activity, an essential step in the development of the male external genitalia
  • likely to play a role in growth and development of the male genitalia, since it is expressed in the genital skin of prepubertal boys
  • serves as a cochaperone to govern normal progesterone receptor (PR) function
  • playing a role in modulating toxicity of Abeta peptides in Alzheimer disease
  • playing a role in MAPT function and may help to decipher and modulate the events involved in MAPT-induced neurodegeneration
  • interacts with MAPT, inhibits its ability to promote microtubule assembly and can have a role in MAPT function
  • immunophilin with neuroprotective effects on different kinds of neurons
  • functional role of RET51/FKBP4 complex in dopaminergic neurons and possibly in the pathogenesis of Parkinson disease
  • regulates oxidative stress (OS) by regulating the levels of a unique antioxidant, peroxiredoxin-6 (PRDX6), which operates independently of other peroxiredoxins and antioxidant proteins
  • important molecular regulator in the androgen-mediated pathway of urethra morphogenesis,and in hypospadias development
  • essential to AR-mediated induction of genes involved in sexually dimorphic development of the penis (NKX3-1), in erectile function of the mature organ (NOS2 and NOS3), and in promotion of apoptosis during development
  • CDK5R1, HOPX, FKBP4, SGTA proteins plays a distinct role in the steroid hormone receptor regulatory cycle
  • CELLULAR PROCESS protein, post translation, folding
    PHYSIOLOGICAL PROCESS cellular trafficking transport
    text involved in both cytoplasmic dynein interaction and glucocorticoid movement to the nucleus
  • cellular trafficking
  • FKBP4PRDX6 signaling protects pregnancy from overt oxidative stress
  • a component
  • component of a complex with Hsp90, Hsp70 and involved in the intracellular trafficking of steroid receptor complexes to the nucleus
  • component of the copper efflux machinery
  • role for the RET51FKBP4 complex in adult neurons of the central nervous system
    small molecule
  • FK506 and rapamycin
  • interacting with phytanyl Co-/ alpha hydrolase
  • post transtional regulator of IRF4
  • interaction between FKBP4 domain I and ATOX1, a copper-binding metallochaperone
  • binds directly and specifically to Tau (MAPT), especially in its hyperphosphorylated form
  • binds to tubulin and prevents microtubule formation
  • physical interaction between FKBP4 and PRDX6 suggests that FKBP4 stabilizes PRDX6 protein and attenuates its degradation as a function of its chaperone activity
  • cell & other
  • increasing strongly the adeno-associated virus type 2 mediated gene transfer in cell lines
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    may lead to endometrial PRDX6 deficiency, increasing uterine susceptibility to oxidative stress, aggravating endometriosis, and adversely affecting endometrial receptivity in patients with endometriosis
    Variant & Polymorphism
    Candidate gene
    Therapy target
    target for improving female fertility or alternatively developing novel approaches to contraception
  • Fkbp52(-/-) mice, we show intriguing aspects of uterine P(4)/PR signaling during pregnancy; Implantation failure is the major phenotype found in these null females, which is conserved on both C57BL6/129 and CD1 backgrounds
  • male mice with targeted ablation of Fkbp4 develop hypospadias, most likely due to actions of Fkbp4 as a molecular co-chaperone of the androgen receptor (AR)