DDX3X
Description
The DDX3X (DEAD-box helicase 3 X-linked) is a protein-coding gene located on chromosome X.
ATP-dependent RNA helicase DDX3X is an enzyme that in humans is encoded by the DDX3X gene. DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which interacts specifically with hepatitis C virus core protein resulting a change in intracellular location. This gene has a homolog located in the nonrecombining region of the Y chromosome. The protein sequence is 91% identical between this gene and the Y-linked homolog. DDX3X performs its functions in the cell nucleus and cytoplasm, exiting the nucleus via the exportin-1/CRM1 nuclear export pathway. It was initially reported that the DDX3X helicase domain was necessary for this interaction, while the canonical features of the trafficking pathway, namely the presence of a nuclear export signal (NES) on DDX3X and Ran-GTP binding to exportin-1, were dispensable. DDX3X binding to, and trafficking by, exportin-1 has since been shown not to require the DDX3X helicase domain and be explicitly NES- and Ran-GTP-dependent.
DDX3X is a multifunctional ATP-dependent RNA helicase that plays a role in various cellular processes, including transcription regulation, translation initiation, and innate immunity. It exhibits relaxed substrate specificity, unwinding partially double-stranded DNA in vitro and binding RNA G-quadruplex structures. DDX3X is involved in transcription regulation, positively regulating CDKN1A/WAF1/CIP1 transcription and inhibiting cell growth, while repressing CDH1/E-cadherin promoter transcription. It also potentiates HNF4A-mediated MTTP transcriptional activation and may play a role in lipid homeostasis. In translation initiation, DDX3X promotes efficient translation of complex mRNAs with highly structured 5'-untranslated regions, potentially by resolving secondary structures during ribosome scanning or promoting pre-initiation complex entry. It also promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to translation elongation. In innate immunity, DDX3X acts as a viral RNA sensor, binding viral RNAs and promoting type I interferon production. It participates in MAVS/RIGI-mediated induction of IFNB, enhances IFNB1 expression via IRF3/IRF7 pathway, and is involved in TBK1 and IKBKE-dependent IRF3 activation. Additionally, DDX3X is involved in TLR7/TLR8 signaling, negatively regulates TNF-induced IL6 and IL8 expression, and is required for stress granule assembly and NLRP3 inflammasome assembly. It also negatively regulates extrinsic apoptotic signaling and acts as an allosteric activator of CSNK1E, promoting Wnt/beta-catenin signaling. DDX3X may be involved in mitotic chromosome segregation and interacts with a wide range of proteins, including transcription factors, translation initiation factors, signaling molecules, and viral proteins.
DDX3X is also known as CAP-Rf, DBX, DDX14, DDX3, HLP2, MRX102, MRXSSB.
Associated Diseases
- Intellectual developmental disorder, X-linked, syndrome, snijders Blok type
- X-linked intellectual disability-hypotonia-movement disorder syndrome
- Toriello-Carey syndrome
