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FLASH GENE
Symbol DNAJC3 contributors: mct - updated : 23-12-2013
HGNC name DnaJ (Hsp40) homolog, subfamily C, member 3
HGNC id 9439
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • nine N-terminal tetratricopeptide repeat motifs, divided into three subdomains of three motifs each
  • a region of similarity with the DnaJ protein family, with oncogenic properties
  • lack the -KDEL sequence found on most resident ER luminal chaperones
  • conserved J domain attached to the C-terminal end via a flexible linker, and the structure shows the conserved Hsp70-binding histidine-proline-aspartate (HPD) motif to be situated on the very edge of the elongated protein
    • HOMOLOGY
    interspecies homolog to murine Dnajc3
    homolog to Drosophila CG8286
    homolog to C.elegans dnj-7
    Homologene
    FAMILY
  • PRK family, DNAJ chaperone family
    • CATEGORY regulatory , protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,lumen
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • previously unanticipated location in the ER lumen where its putative function as a cochaperone explains the stress-sensitivity phenotype of knockout cells
  • localized in the lumen of the ER
    • basic FUNCTION
  • acting as an inhibitor of the interferon-induced double-stranded RNA-activated protein kinase (PKR)
  • inhibits ER stress and plays an important role in maintaining balance and stability of the ER in retinal capillary endothelial cells (HRCECs)
  • defends cells against endoplasmic reticulum (ER) stress
  • ER molecular chaperone to maintain protein-folding homeostasis
  • act potentially as a co-chaperone, binding un- or misfolded proteins and delivering them to HSPA5
  • plays a crucial role in ER protein folding and the UPR, thus adding evidence that dysfunctions in regulation of ER stress might serve as a common pathway linking diabetes mellitus and neurodegeneration
    • CELLULAR PROCESS protein, translation regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • important component of a negative feedback loop used by the cell to inhibit EIF2A signaling, and thus attenuate the unfolded protein response
  • act potentially together with HSPA5 to prevent protein aggregations and promote protein foldings within ER
  • interplay between MAPK14 phosphorylation and DNAJC3 upregulation has key roles in modulating ERP29-induced cell-growth arrest and survival
  • DNAJC3 is a HSPA5 (immunoglobulin heavy-chain binding protein) co-chaperone
    • cell & other
    REGULATION
    induced by interferon
    ASSOCIATED DISORDERS
    corresponding disease(s) JDND
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    during virus infection to inhibit virus-induced apoptosis and inflammation to prolong host survival, even while prolonging viral replication
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • in mice, loss of Dnajc3 leads to hyperglycemia and glucosuria associated with increasing apoptosis of pancreatic beta cells and reduced insulin levels