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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
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