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FLASH GENE
Symbol DDX6 contributors: mct - updated : 08-10-2019
HGNC name DEAD (Asp-Glu-Ala-Asp) box polypeptide 6
HGNC id 2747
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousbrain   lowly Homo sapiens
 brainhindbraincerebellum   Homo sapiens
Reproductivefemale systembreastmammary gland highly
 male systemtestis  highly Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Nervousneuron Homo sapiens
Reproductivespermatid Homo sapiens
Reproductivespermatocyte Homo sapiens
cell lineage
cell lines neuroblastoma cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • DEAD/H box (Asp-Glu-Ala-Asp/His)
  • an helicase ATP-binding domain, an ATPase/helicase motif essential for viral replication
  • a C terminal RNA helicase domain, and C-terminal RecA-like domain
  • HOMOLOGY
    interspecies homolog to Drosophila oocyte specific helicase ME31
    homolog to murine Ddx6 (97,7pc)
    Homologene
    FAMILY
  • DEAD box helicase family
  • DDX6/DHH1 subfamily
  • CATEGORY enzyme , RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleolus
    text
  • in spermatogenic cells, localizes to both the nucleus and cytoplasm
  • basic FUNCTION
  • shuttling protein involved in nuclear assembly of stored mRNP particles
  • in the process of mRNA degradation, may play a role in mRNA decapping
  • possibly involved in the replication of hepatitis C virus genomes in hepatocytes and in tumourigenesis of hepatocellular carcinomas
  • DEAD-box RNA helicase with ATP-dependent RNA-unwinding activity
  • it is possible that DDX6 may be an important driver of the aggregation process within P bodies (was shown to be essential for P-body formation in human cells)
  • is required for efficient genome packaging of foamy virus, a spumaretrovirus
  • located at the 5prime extremity of mRNA can then recruit the decapping complex, thus coupling translational repression and mRNA degradation
  • reduction of DDX6 under prolonged hypoxia activates expression of proangiogenic VEGFA that is critical in fast growing tissues during normal development and in pathologic processes
  • is present in nuage and non-nuage structures as well as nuclei, suggesting that DDX6 has diverse functions in spermatogenic cells
  • having versatile functions in mRNA metabolism, which characterize them as important post-transcriptional regulators of gene expression
  • DDX6 is necessary and sufficient for neuronal differentiation and that it functions in cooperation with TRIM32
  • conserved DEAD-box protein (DBP) that plays central roles in cytoplasmic RNA regulation, including processing body (P-body) assembly, mRNA decapping, and translational repression
  • has a variety of functions such as translation initiation, pre-mRNA splicing, and ribosome assembly
  • parental mRNA clearance is a prerequisite for cellular reprogramming and that DDX6 plays a central role in this process
  • is an essential component of membrane-less organelles called processing bodies (PBs)
  • plays a key role in adult progenitors where it controls the balance between self-renewal and differentiation in a context-dependent manner
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of P-bodies and stress granules, representing cellular structures of mRNA triage
  • EIF4E/EIF4ENIF1 complex is present in granules with the processing body proteins LSM1 and DDX6, and disruption of this complex causes premature and enhanced neurogenesis and neural precursor depletion
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with ATXN2
  • interacts with argonaute proteins, EIF2C1, EIF2C2
  • interacting with EDC3 (DDX6 C-terminal RecA-like domain bound to a highly conserved FDF sequence motif in the decapping activator EDC3)
  • general translational repressor DDX6 may cooperate with ZFP36 to regulate AU-rich elements (AREs)-mRNA translation
  • ATXN2L associates with known interaction partners of ATXN2, the RNA helicase DDX6 and the poly(A)-binding protein, and with ATXN2 itself
  • hypoxia-induced DDX6 reduction positively affects proangiogenic VEGFA expression
  • CNOT1 modulates the conformation of DDX6 and stimulates ATPase activity
  • can remodel and release nuclear DMPK messenger ribonucleoprotein foci, leading to normalization of pathogenic alternative splicing events
  • DDX6 binds to a conserved CNOT1 subdomain in a manner resembling the interaction of the translation initiation factor EIF4A with EIF4G
  • CNOT1 facilitates recruitment of DDX6 to miRNA-targeted mRNAs, placing DDX6 as a downstream effector in the miRNA silencing pathway
  • TRIM32 associates with proteins involved in neurogenesis and RNA-related processes, such as the RNA helicase DDX6, which has been implicated in microRNA regulation
  • interacts with the CNOT complex and functions in concert with several post-transcriptional regulators, including EDC3, and EIF4ENIF1
  • EIF4ENIF1 through conserved CUP-homology domain (CHD) interacts directly with DDX6 in both the presence and absence of the central MIF4G domain of CNOT1
  • DDX6-EIF4ENIF1 interaction mediates translational repression and P-body assembly
  • DDX6 protein acted as an RNA-binding protein for ERBB2 and FGFR2 mRNAs and positively regulated their post-transcriptional processes
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) IDDF
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in intestine, colon, rectum adenocarcinomas
    tumoral   translocation    
    translocated in B-cell lymphoma, RCK gene (RC-K8 cell line) target of the translocation t(11;14)(q23;q32)
    constitutional     --over  
    in hepatitis C virus-related chronic hepatitis
    constitutional     --low  
    under hypoxia contributes to the activation of VEGFA expression and promotes its proangiogenic function
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS