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DDX3 a multifunctional DEAD box family RNA helicase with diverse cellular functions. DEAD box proteins are characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), and are involved in several steps of gene expression, such as transcription, maturation of nuclear and mitochondrial mRNA, mRNA export, translation initiation, and ribosome and spliceosome assembly. DDX3 is required for nuclear export of HIV-1 viral transcripts, possibly in a complex with the viral Rev protein and host cofactor CRM1. DDX3 is required for hepatitis C virus (HCV) RNA replication and its expression is downregulated in hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC). May function as a tumor suppressor protein. Its expression inhibits tumor cell colony formation and increases expression of the cdk inhibitor p21 Waf1/Cip1. Low DDX3 expression has been shown in HCC, and aberrant subcellular localization occurs in many squamous cell carcinomas. Reduced DDX3 expression in cultured cells causes a diminished dependence on serum for cell proliferation and changes in cyclin D1 and p21 Waf1/Cip1 expression. Associates with eIF4F to promote translation of selected mRNAs. Is phosphorylated by the mitotic cyclin dependent kinase, cyclin B/cdc2. This phosphorylation may cause a loss of DDX3 function and a concomitant repression of ribosome biogenesis and translation in mitosis. Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFN-beta induction. Involved in regulation of apoptosis. May be required for activation of the intrinsic but inhibit activation of the extrinsic apoptotic pathway. Regulated by the cell cycle. Maximally expressed in the cytoplasm during G1/S phase and decreased expression during G2/M phase. Located predominantly in nuclear speckles and, at low levels, throughout the cytoplasm. Associates with the outer side of nuclear pore complexes (NPC) and mitochondrial outer membranes. Shuttles between the nucleus and the cytoplasm in an exportin1-dependent manner. Associates with polyadenylated mRNAs in the cytoplasm and the nucleus. Predominantly located in nucleus during G0 phase and in the cytoplasm during G1/S phase. Belongs to the DEAD box helicase family, DDX3 subfamily. Two isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Cell cycle regulation; EC; Helicase; RNA-binding; Spliceosome; Translation initiation
Chromosomal Location of Human Ortholog: Xp11.4
Cellular Component: cytoplasm; cytosol; eukaryotic translation initiation factor 3 complex; extracellular region; nucleolus; nucleus; stress granule
Molecular Function: ATP-dependent DNA helicase activity; ATP-dependent RNA helicase activity; ATPase activity; cadherin binding; CTPase activity; DNA binding; eukaryotic initiation factor 4E binding; GTPase activity; mRNA 5'-UTR binding; nucleoside-triphosphatase activity; poly(A) binding; protein binding; ribosomal small subunit binding; RNA binding; RNA strand annealing activity; transcription factor binding; translation initiation factor binding
Biological Process: chromosome segregation; induction of apoptosis via death domain receptors; innate immune response; mature ribosome assembly; negative regulation of apoptosis; negative regulation of caspase activity; negative regulation of cell growth; negative regulation of protein complex assembly; negative regulation of translation; neutrophil degranulation; positive regulation of apoptosis; positive regulation of caspase activity; positive regulation of cell growth; positive regulation of interferon-beta production; positive regulation of transcription from RNA polymerase II promoter; positive regulation of translation; positive regulation of translational initiation; positive regulation of viral genome replication; response to virus; RNA secondary structure unwinding; stress granule assembly; Wnt receptor signaling pathway
Disease: Mental Retardation, X-linked 102
Reference #:  O00571 (UniProtKB)
Alt. Names/Synonyms: ATP-dependent RNA helicase DDX3X; CAP-Rf; DBX; DDX14; DDX3; DDX3X; DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked; DEAD box protein 3, X-chromosomal; DEAD box, X isoform; DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3; DEAD/H box-3; helicase like protein 2; Helicase-like protein 2; HLP2
Gene Symbols: DDX3X
Molecular weight: 73,243 Da
Basal Isoelectric point: 6.73  Predict pI for various phosphorylation states
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