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FLASH GENE
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
    EC.number 5.2.1.8
    DNA
    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
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 3757 - 459 - 2007 17343741
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Digestiveliver    
     mouthtongue  highly
     stomach   highly
    Endocrinepancreas   highly
    Reproductivefemale systemovary  highly
     male systemprostate   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone   
    Epithelialbarrier liningendometrium   Homo sapiens
    Epithelialsecretoryglandularendocrine 
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/ImmuneB cell
    Lymphoid/ImmuneT cell
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text in the uterus during embryonic implantation
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • 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
  • HOMOLOGY
    interspecies ortholog to murine Fkbp4
    ortholog to rattus fkbp4
    Homologene
    FAMILY
  • immunophilin class of proteins family
  • CATEGORY chaperone/stress , enzyme , regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleolus
    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
    PATHWAY
    metabolism
    signaling
  • 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
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • 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
  • REGULATION
    ASSOCIATED DISORDERS
    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
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    reproductionfertilityfemale
    target for improving female fertility or alternatively developing novel approaches to contraception
    ANIMAL & CELL MODELS
  • 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)