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FLASH GENE
Symbol HSPA8 contributors: mct/ - updated : 12-09-2016
HGNC name heat shock 70kDa protein 8
HGNC id 5241
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 2276 - 646 - 2010 20018937
8 - 1817 - 493 - 2010 20018937
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Endocrineadrenal gland   highly
Lymphoid/Immunespleen   highly
 thymus   highly
Nervousbrain   highly
Respiratorylung    
Visualeyeanterior segmentcornea  
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period fetal
Text cochlea
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • two major domains: the N-terminal 44-kDa fragment which is a nucleotide binding domain
  • C-terminal 30-kDa domain which has the capacity to bind unfolded polypeptide substrates, divided into several subdomains, including a beta sandwich region containing a peptide substrate binding pocket and, an alpha-helical “lid” essential for tightly association of peptide
  • HOMOLOGY
    intraspecies homolog to aconitase,structurally
    Homologene
    FAMILY
  • heat shock protein 70 family
  • CATEGORY chaperone/stress
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • mediating the suppression of a stress-activated protein kinase JNK (SERK1)
  • increasing cell survival by inhibition of the apoptotic program
  • playing a role in in promoting tail-anchored protein biogenesis at the ER
  • plays a significant role in endothelial cells via the phosphatidylinositol 3-kinase/Akt pathway
  • role in cell proliferation that might account for the higher tumor growth of cancer cells overexpressing CTSD
  • prevents both MAPT aggregation and the inhibitory effects of preexisting MAPT aggregates on fast axonal transport
  • specific chaperone function for HSPA8 within viral factories, the sites of reovirus replication and assembly in cells
  • is a potential chaperone for the nuclear translocation of MAPK1
  • contribute to the long-term survival of spermatozoa inside the mammalian female reproductive tract
  • likely protects sperm survival through membrane repair mechanisms
  • acts as a molecular chaperone for the maintenance of intracellular proteins, which allows cancer cells to survive under proteotoxic stress
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding DNAJC13 through its DnaJ domain
  • binds to the microtubule-binding domain of tau, without an absolute requirement for tau phosphorylation
  • formation of a stable complex between chaperonin-containing TCP1 and HSPA8, two eukaryotic representatives of these chaperone families
  • direct binding between the N-terminus and the third cytoplasmic loop of SLC18A2, as well as, a region containing the substrate binding and the C-terminal domains of HSPA8
  • interaction between the head domain of KRT5 and HSPA8, a chaperone also involved in vesicle uncoating (this interaction is involved in melanosome formation or transport in keratinocytes)
  • interacts with both CDKN1C and CDKN1B and the subcellular localization of HSPA8 was critical to maintain HSC (hematopoietic stem cell) cycle kinetics
  • DNAJB6 binds HSPA8 and causes dephosphorylation of GSK3B at Ser 9 by recruiting protein phosphatase, PPP2CA
  • HSPA8 is a prerequisite for the surface translocation and angiogenic function of NCL, which suggests strategies to target both HSPA8 and NCL for more effective antiangiogenic therapies
  • is a potential interacting protein of MAPK1
  • plays a key role in CALM1-dependent nuclear import of SRY
  • dynamic C-terminal region of HSPA8 provides for flexibility between STUB1 and the chaperone
  • recruits PPP5C and activates its phosphatase activity which suggests dual roles for PPP5C that might link chaperone systems with signaling pathways in cancer and development
  • HSPA8 interacted with RAB1A in a chaperone-dependent manner
  • BBC3 associates with HSPA8/HSC70 (heat shock 70kDa protein 8), leading to its lysosome translocation and uptake
  • critical role of HSPA8 in SV40 ER-to-cytosol penetration and SGTA controls HSPA8 to impact this process
  • GKN2 promotes oxidative stress-induced gastric cancer cell apoptosis via the HSPA8 pathway
  • DNAJA2 and DNAJA1 were both important for CFTR folding, however overexpressing DNAJA2 but not DNAJA1 enhanced CFTR degradation at the endoplasmic reticulum by HSPA4/HSPA8 and the E3 ubiquitin ligase STUB1
  • cell & other
    REGULATION
    activated by BAG1-S isoform
    inhibited by BAG1-M isoform
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in gastric cancer
    constitutional     --low  
    of HSPA8 and HSPA9 was observed in Alzheimer disease across the three brain regions compared to the controls, suggesting their participation in AD pathogenesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
  • novel molecular basis for the protective effect of HSPA8 in tauopathies
  • Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerangiogenesis 
    may provide the basis for the development of new therapeutic strategies for angiogenesis
    neurologyepilepsy 
    could be a potential therapeutic target of Lafora disease
    ANIMAL & CELL MODELS