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FLASH GENE
Symbol FKBP8 contributors: mct/npt/pgu - updated : 20-04-2017
HGNC name FK506 binding protein 8, 38kDa
HGNC id 3724
Location 19p13.11      Physical location : 18.642.567 - 18.654.383
Synonym name
  • FK506-binding protein 8 (38kD)
  • 38 kDa FK506-binding protein homolog
  • rotamase
  • Synonym symbol(s) FKBPr38, FKBP38
    EC.number 5.2.1.8
    DNA
    TYPE functioning gene
    STRUCTURE 12.32 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure several binding sites for Sp1, AP2, MZF1, and IK2
    MAPPING cloned Y linked N status confirmed
    Physical map
    KIAA0561 PIK3R2 19q13.2-q13.4 phosphoinositide-3-kinase, regulatory subunit, polypeptide 2 (p85 beta) IFI30 19p13.1 interferon, gamma-inducible protein 30 MGC12972 19p13.11 hypothetical protein MGC12972 RAB3A 19p13.1 RAB3A, member RAS oncogene family PDE4C 19P13.1 phosphodiesterase 4C, cAMP-specific (phosphodiesterase E1 dunce homolog, Drosophila) LOC388516 19 LOC388516 KIAA1683 19p13.1 KIAA1683 JUND 19p13.1 jun D proto-oncogene LSM4 19p13.1 LSM4 homolog, U6 small nuclear RNA associated (S. cerevisiae) PGPEP1 19p13.11 pyroglutamyl-peptidase I PLAB MGC10812 19p13.11 hypothetical protein MGC10812 LOC388517 19 similar to MOST-1 protein MAPA 19p13.11 monocyte and plasmacytoid activated molecule SSBP4 19p13.1 single stranded DNA binding protein 4 ISYNA1 19p13.11 myo-inositol 1-phosphate synthase A1 DKFZp434I1916 ELL 19p13.1 elongation factor RNA polymerase II FKBP8 19p12 FK506 binding protein 8, 38kDa MGC2749 19p13.11 hypothetical protein MGC2749 UBA52 19p13.1-p12 ubiquitin A-52 residue ribosomal protein fusion product 1 FLJ20850 19p13.11 hypothetical protein FLJ20850 CRLF1 19p12 cytokine receptor-like factor 1 C19orf4 19p12 chromosome 19 open reading frame 4 FLJ11078 19p13.11 hypothetical protein FLJ11078 MECT1 19p13 mucoepidermoid carcinoma translocated 1 COMP 19p13.1 cartilage oligomeric matrix protein (pseudoachondroplasia, epiphyseal dysplasia 1, multiple) RENT1 19p13.2-p13.11 regulator of nonsense transcripts 1 GDF1 19p13.1-p12 growth differentiation factor 1 LASS1-GDF1 19p12 LAG1 longevity assurance homolog 1 (S. cerevisiae), growth differentiation factor 1 transcription unit LASS1 19p13.1-p12 LAG1 longevity assurance homolog 1 (S. cerevisiae) LOC388518 19 LOC388518 COPE 19p13.1 coatomer protein complex, subunit epsilon DDX49 19p12 DEAD (Asp-Glu-Ala-Asp) box polypeptide 49 HOMER3 19p13.11 homer homolog 3 (Drosophila)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 - 1787 - 413 in RPE cells 2008 18385096
    lacking exons 3, 4, and 5
    9 - 1808 - 412 - 2008 18385096
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   predominantly
    Endocrinepancreas   moderately
    Lymphoid/Immunelymph node   highly
    Nervousbrain   highly
     nerve   moderately
    Respiratorylung   moderately
    Visualeyeretina  highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    Nervousperipherous   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal glutamate-rich domain (ERD), contributing to FKBP8 biological activities , N-terminal LC3-interacting region (LIR) motif binding strongly to MAP1LC3A
  • multiple N terminal FK506 binding and peptidyl prolyl cis-trans isomerase (rotamase) domains
  • a tripartite tetratricopeptide repeat (TPR) domain, calcium/calmodulin-binding motif, that interacts with the heat shock protein 90 (HSP90)
  • a transmembrane motif (TM)
  • two EF-hand calcium binding sites
  • a region, referred to as the FKBP-C domain, that is highly related to FKBP12
  • a trans-membrane domain at the very C terminus, which is unique among all the FKBP proteins and is required for targeting it to mitochondria
  • a COOH-terminal tail anchor
  • conjugated PhosphoP
    mono polymer homomer , heteromer , polymer
    HOMOLOGY
    interspecies homolog to rattus Fkbp8 (93.55 pc)
    homolog to murine Fkbp8 (94.65 pc)
    Homologene
    FAMILY
  • immunophilin class of proteins family
  • family of FK506-binding proteins (FKBPs)
  • peptidyl prolyl cis/trans isomerase (PPIase) family of FKBPs
  • CATEGORY enzyme , immunity/defense
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,mitochondria,outer
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text
  • localized predominantly at the outer membrane of the mitochondria and the endoplasmic reticulum (ER) membrane, and associated with the anti-apoptotic proteins BCL2 and BCLXL at these organelles, thus modulating apoptosis
  • associates with nascent plasma membrane ion channels in the endoplasmic reticulum (ER)
  • certain mitochondrial outer membrane proteins, including FKBP8 and BCL2, translocate from the mitochondria to the endoplasmic reticulum (ER) during mitophagy, thereby escaping degradation by autophagosomes
  • membrane chaperone that is localized predominantly to mitochondria
  • anchored in the outer mitochondrial membrane (OMM) and acts as a multifunctional adaptor with anti-apoptotic activity
  • basic FUNCTION
  • T cell binding protein FKBP for the immunosuppressive agents FK506-rapamycin
  • FKBP8/FK506 has immunosuppressive effects by inhibiting calcineurin that functions as a critical signaling molecule during T-cell activation
  • antagonizing HH signaling in neural tissues
  • playing a role in immunoregulation and basic cellular processes involving protein folding and trafficking
  • may be having a role in neurons associated with memory function
  • targeting Bcl-2 to mitochondria and inhibiting apoptosis
  • playing a role in TSC gene-dependent cell size regulation
  • may be a functional component of the apoptotic signaling network in the RPE cells and that such an effect could be independent of FK506
  • playing a very minor, if any, role in FRAP1 activation
  • key player in regulating the function of BCL2 by antagonizing caspase-dependent degradation through the direct interaction with the flexible loop domain of BCL2, which contains the caspase cleavage site
  • important modulator in neuronal hedgehog signaling and in controlling cell size and as an endogenous inhibitor of MTOR
  • plays an important role on the stability of proteins
  • having a regulatory role on the caspase-mediated BCL2 down-regulation, which is inhibited by the overexpression of FKBP8 and thereby maintains cell survival function of BCL2 in cancer cells
  • promotes degradation of endogenous PTP4A3 protein via protein-proteasome pathway
  • may play a critical role in tumorigenesis
  • plays an important role in membrane protein biogenesis on the cytoplasmic side of the ER membrane, whose activity is negatively regulated by HSP90AA1 through the TPR domain
  • mediates the cis/trans interconversion of peptidyl prolyl bonds
  • translocation of FKBP8 is essential for the suppression of apoptosis during mitophagy
  • regulates signalling pathways such as cell survival, apoptosis, proliferation and metastasis
  • FKBP8 and BCL2 translocate from mitochondria to the endoplasmic reticulum during mitophagy, a form of autophagy responsible for the elimination of damaged mitochondria
  • evidence for a role of immunophilins, including FKBP3 and FKBP8, in Non-capacitative calcium entry (NCCE) mediated by TRPC6
  • novel roles for FKBP8 and MAP1LC3A, which act together to induce mitophagy
  • CELLULAR PROCESS cell life, cell death/apoptosis
    cell life, antiapoptosis
    protein, post translation, folding
    PHYSIOLOGICAL PROCESS nervous system
    text playing a role in memory function
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with PSEN1 and PSEN2 for the regulation of mitochondria-mediated apoptosis by competition between PSEN1/2 and FKBP38 for subcellular targeting of BCL2
  • interacting with BCL2 through the unstructured loop
  • binds to calcineurin but also inhibits the protein phosphatase activity of calcineurin on its own (cannot substitute for the FKBP/FK506 complex in signaling pathways controlled by the protein phosphatase activity of calcineurin)
  • interaction with RHEB (dependent on its nucleotide binding states)
  • BCL2L1-interacting proteins that regulate the apoptotic signaling pathways in the RPE
  • bind to the FRB domain of MTOR and to inhibit its activity
  • interaction of BCL2 with FKBP8 inhibits the prosurvival activity of BCL2
  • stabilizes BCL2 via a posttranslational mechanism, thus modulating the anti-apoptotic activity of BCL2
  • interacting protein of PTP4A3 interacting protein of PTP4A3
  • interacting protein of PTP4A3 (N-terminal region of FKBP8 is crucial for binding with PTP4A3)
  • dual role for FKBP8 in regulating CFTR synthesis and post-translational folding
  • is a key proteostasis network factor required at a post-Hsp90 step in CFTR biogenesis
  • FKBP8 is a regulator of the prosurvival protein BCL2
  • regulates apoptosis through unique interactions with multiple regulators including BCL2
  • association of the S100 proteins with FKBP8 provides a Ca2+-dependent regulatory mechanism of the FKBP8-mediated signalling pathways
  • ANKMY2 is a molecule that interacts with FKBP8
  • FKBP8 and HSP90B1 play an essential role in the late phase of CLCN1 quality control by dynamically coordinating protein folding and degradation
  • FKBP8 binding to HSP90AA1 did not substantially influence its ATPase activity
  • FKBP8 is an GABARAPL1, GABARAPL2-interacting protein
  • FKBP8 efficiently recruits lipidated MAP1LC3A to damaged mitochondria in a LIR-dependent manner
  • cell & other
    REGULATION
    Other degraded with Bcl-2 by PSEN1 and PSEN2
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in breast, colon, liver, lung, lymph node, prostate, and stomach cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    N-terminal domain of FKBP38 could have therapeutic potential for the metastatic cancer overexpressing PRL family
    ANIMAL & CELL MODELS
  • mice deficient in Fkbp38 die soon after birth manifesting a defect in neural tube closure that results in part from unrestrained apoptosis