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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
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveesophagus   highly
 liver   highly Homo sapiens
Endocrineneuroendocrinepituitary  highly
 pancreas   highly Homo sapiens
Respiratoryrespiratory tracttrachea  highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Muscularstriatumskeletal  
cell lineage
cell lines
fluid/secretion
at STAGE
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