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DDX3
a multifunctional DEAD box family ATP-dependentRNA 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.
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| Protein type: Cell cycle regulation; EC 3.6.4.13; Helicase; RNA-binding; Spliceosome; Translation initiation |
| Chromosomal Location of human Ortholog: Xp11.4 |
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Cellular Component:
cell leading edge; centrosome; cytoplasm; cytoplasmic stress granule; cytosol; extracellular region; ficolin-1-rich granule lumen; lamellipodium; NLRP3 inflammasome complex; nucleoplasm; nucleus; P granule; plasma membrane; secretory granule lumen
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Molecular Function:
ATP binding; ATP hydrolysis activity; CTPase activity; DNA binding; DNA helicase activity; eukaryotic initiation factor 4E binding; gamma-tubulin binding; GTPase activity; mRNA 5'-UTR binding; mRNA binding; poly(A) binding; primary miRNA binding; protein binding; protein serine/threonine kinase activator activity; ribonucleoside triphosphate phosphatase activity; ribosomal small subunit binding; RNA binding; RNA helicase activity; RNA stem-loop binding; RNA strand annealing activity; signaling adaptor activity; transcription factor binding; translation initiation factor binding
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Biological Process:
cell differentiation; cellular response to arsenic-containing substance; cellular response to osmotic stress; cellular response to virus; chromosome segregation; cytosolic ribosome assembly; DNA duplex unwinding; extrinsic apoptotic signaling pathway via death domain receptors; gamete generation; innate immune response; intracellular signal transduction; intrinsic apoptotic signaling pathway; lipid homeostasis; negative regulation of apoptotic process; negative regulation of cell growth; negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; negative regulation of intrinsic apoptotic signaling pathway; negative regulation of NIK/NF-kappaB signaling; negative regulation of protein-containing complex assembly; negative regulation of translation; positive regulation of apoptotic process; positive regulation of canonical Wnt signaling pathway; positive regulation of cell growth; positive regulation of chemokine (C-C motif) ligand 5 production; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of G1/S transition of mitotic cell cycle; positive regulation of gene expression; positive regulation of interferon-alpha production; positive regulation of interferon-beta production; positive regulation of NIK/NF-kappaB signaling; positive regulation of NLRP3 inflammasome complex assembly; positive regulation of protein acetylation; positive regulation of protein autophosphorylation; positive regulation of protein K63-linked ubiquitination; positive regulation of protein serine/threonine kinase activity; positive regulation of toll-like receptor 7 signaling pathway; positive regulation of toll-like receptor 8 signaling pathway; positive regulation of transcription by RNA polymerase II; positive regulation of translation; positive regulation of translation in response to endoplasmic reticulum stress; positive regulation of translational initiation; positive regulation of type I interferon production; positive regulation of viral genome replication; primary miRNA processing; protein localization to cytoplasmic stress granule; response to virus; RNA secondary structure unwinding; stress granule assembly; translational initiation; Wnt signaling pathway
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Disease: Mental Retardation, X-linked 102
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Reference #:
O00571
(UniProtKB)
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Alt. Names/Synonyms: ATP-dependent RNA helicase DDX3X; CAP-Rf; DBX; DDX14; DDX3; DDX3X; DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked; DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked; DEAD box protein 3, X-chromosomal; DEAD box, X isoform; DEAD-box helicase 3 X-linked; DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3; DEAD/H box-3; helicase like protein 2; Helicase-like protein 2; HLP2; MRX102; MRXSSB
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Gene Symbols: DDX3X
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Molecular weight:
73,243 Da
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Basal Isoelectric point:
6.73
Predict pI for various phosphorylation states
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Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology®
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