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Symbol DDX3X contributors: mct/ - updated : 11-09-2019
HGNC name DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked
HGNC id 2745
Corresponding disease
MRX102 Mental retardation, X-linked 102
Location Xp11.4      Physical location : 41.192.650 - 41.209.522
Synonym name
  • CAP-Rf
  • DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3
  • DEAD/H box-3
  • helicase like protein 2
  • ATP-dependent RNA helicase DDX3X
  • DEAD box, X isoform
  • DEAD box protein 3, X-chromosomal
  • Synonym symbol(s) DBX, HLP2, DDX14, DDX3, HLP2, CAP-Rf, CAP-Rf, MRX102
    TYPE functioning gene
    STRUCTURE 16.88 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU
    text structure DNA box on chromosome X, homolog gene in NRY (non recombining region on chromosome Y), Alu element in intron 13
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 5433 73.2 662 - 2008 18628297
    16 - 5351 - 646 - 2008 18628297
    17 - 5396 - 661 - 2008 18628297
    17 - 5986 - 475 - 2008 18628297
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemuterus  highly
     male systemtestis  highly
    Respiratoryrespiratory tracttrachea  predominantly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cell lineage
    cell lines
    at STAGE
  • N-terminal conserved Nuclear Export Signal (NES) is required for export of DDX3X from the nucleus
  • one helicase ATP-binding domain
  • one helicase C-terminal domain
  • conjugated PhosphoP
    interspecies homolog to murine Ddx3 (98.6pc)
    homolog to rattus Ddx3 (98.6pc)
    homolog to Drosophila Belle
    intraspecies homolog to DBY
  • DEAD/H box protein family
  • DDX3 subfamily
  • CATEGORY enzyme , RNA associated
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
  • nuclear localization when not interacting with the hepatitis C virus core protein
  • located predominantly in nuclear speckles and, at low levels, throughout the cytoplasm
  • shuttles between the nucleus and the cytoplasm in a XPO1- dependent manner
  • DDX3X nuclear localization increased in early mitotic cells (during prophase) concomitant with an increase in DDX3X expression levels
  • basic FUNCTION
  • putative RNA helicase, transcriptional regulator and functioning as a tumor suppressor
  • positively involved in the initiation of protein synthesis
  • essential for cell viability
  • suppressor of PRPF8 mutation
  • new member of the eIF4E inhibitory proteins involved in translation initiation regulation
  • having regulatory roles in translation, cell growth and likely viral replication
  • acting synergistically with TBK1 to stimulate the IFN promoter
  • DDX3X and DICER1 are also required in promoting chromosome segregation and chromosomal localization of NCAPH (human homolog of Barr)
  • acts as an EIF4E (eukaryotic initiation factor 4E)-inhibitory protein to suppress translation
  • co-ordinative roles for DDX3X, EIF4E and PABPC1 in integrating environmental stress with translational regulation
  • DDX3X, DDX1 and DHX9 are among the helicases that are required for the replication of a diverse range of viruses
  • conserved DEAD-box RNA helicase important in a variety of fundamental cellular processes that include transcription, splicing, RNA transport, and translation
  • has an oncogenic role in colorectal cancer
  • plays a role in antiviral innate immunity
  • plays an oncogenic role in breast cancer cells by modulating the cell cycle
  • novel function of DDX3X in regulating expression and downstream functions of KLF4, a master negative regulator of the cell cycle
  • multi-functional protein involved in the regulation of gene expression and additional non-conventional roles as signalling adaptor molecule that are independent of its enzymatic RNA remodeling activity
  • may contribute to sex-related differences in resistance to microbes and resilience to inflammatory disease
  • CELLULAR PROCESS nucleotide, RNA splicing
    protein, translation/synthesis
    PHYSIOLOGICAL PROCESS immunity/defense
    text innate immunity
    a component
  • part of antiapoptotic protein complex associated with death receptors that contains GSK3B and cellular inhibitor of apoptosis protein-1 (BIRC2)
    DNA binding
    RNA binding
    small molecule nucleotide,
  • ATP binding
  • protein
  • interacts specifically with hepatitis C virus core protein, resulting in a change in intracellular location
  • interacting with TDRD3
  • interacting with the multi-component translation initiation factor eIF3 (major interaction partner)
  • interacting with TBK1
  • interacting with EIF4E, thus repressing its translation
  • interacting with HIV Rev protein and XPO1
  • interacting with vaccinia virus K7 protein, thus evading the innate immunity response by preventing DDX3X from inducing IFN-beta production
  • DDX3X is critical for translation of CCNE1 mRNA, which provides an alternative mechanism for regulating CCNE1 expression during the cell cycle
  • required to promote the localization and chromosome segregation of NCAPH
  • PABP1 [poly(A)-binding protein 1] is another direct interaction partner of DDX3X
  • implicated as a scaffolding adaptor that directly facilitates phosphorylation of IRF3 by IKBKE and might thus be involved in pathway-specific activation of IRF3
  • DDX1 and DDX3X DEAD-box RNA helicases are known to be required for efficient HIV-1 Rev-dependent RNA export
  • DDX3X modulates cell adhesion and motility and cancer cell metastasis via RAC1-mediated signaling pathway
  • DDX3X may participate in antiviral innate immunity, at least in part, by translational control of PRKRA
  • DDX3 regulates epigenetic transcriptional and translational activation of TP53 and colocalizes with TP53 at centrosome during mitosis to ensure proper mitotic progression and genome stability, which supports the tumor-suppressive role of DDX3X
  • DDX3X binds the eIF4F complex, which we found to be required for ER stress-induced ATF4 expression
  • DDX3X inhibits expression of Kruppel-like factor 4 (KLF4), a transcription factor and cell cycle repressor
  • DDX3X also directly interacts with CHUK and enhances its autophosphorylation and -activation
  • MAPKs and GSK3 phosphorylate GLE1 and thereby coordinate stress granules (SGs) dynamics by altering DDX3X function
  • DDX3X steers MITF protein levels dictating melanoma metastatic potential and response to targeted therapy
  • DDX3X and specific initiation factors modulate FMR1 repeat-associated non-AUG-initiated translation
  • cell & other
    activated by various ribo- and deoxynucleic acids
    BPDE (Benzo[a]pyrene diol epoxide, which can promote growth, proliferation and neoplastic transformation of breast epithelial cells
    Other hepatitis C virus core
    phosphorylated by TBK1, phosphorylation required for DDX3X to stimulate IFN-beta production through a transcriptional activation mechanism
    corresponding disease(s) MRX102
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral somatic mutation      
    in medulloblastoma, a highly aggressive cerebellar tumor affecting both children and adults
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • potential prognostic biomarker in cancer
  • SystemTypeDisorderPubmed
    Inhibition of DDX3 with the small molecule inhibitor RK-33 causes inhibition of Wnt signaling and may therefore be a promising future treatment strategy for a subset of colorectal cancers
  • mice lacking Ddx3x during hematopoiesis showed an altered leukocyte composition in bone marrow and spleen and a striking inability to combat infection with Listeria monocytogenes
  • loss of Ddx3x results in an early post-implantation lethality in male mice