Mouse Anti-DDX3X Recombinant Antibody (15D1B11) (CBMAB-D0563-YC)

Mouse

Human, Mouse

15D1B11

IgG1, κ

WB, IF, IP

Partial human DDX3X recombinant protein (1-226a.a.)

Human, Mouse

IgG1, κ

Monoclonal

The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Store at 4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freeze/thaw cycles.

DEAD-Box Helicase 3, X-Linked

DDX3X is a member of the large DEAD-box protein family, that is defined by the presence of the conserved Asp-Glu-Ala-Asp (DEAD) motif, and has ATP-dependent RNA helicase activity. This protein has been reported to display a high level of RNA-independent ATPase activity, and unlike most DEAD-box helicases, the ATPase activity is thought to be stimulated by both RNA and DNA. This protein has multiple conserved domains and is thought to play roles in both the nucleus and cytoplasm. Nuclear roles include transcriptional regulation, mRNP assembly, pre-mRNA splicing, and mRNA export. In the cytoplasm, this protein is thought to be involved in translation, cellular signaling, and viral replication.

DEAD-Box Helicase 3, X-Linked; DEAD (Asp-Glu-Ala-Asp) Box Polypeptide 3, X-Linked; DEAD (Asp-Glu-Ala-Asp) Box Helicase 3, X-Linked; DEAD/H (Asp-Glu-Ala-Asp/His) Box Polypeptide 3; DEAD Box Protein 3, X-Chromosomal; Helicase-Like Protein 2; DEAD Box, X Isoform; DDX3; HLP2;

Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075).

The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110).

In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879).

Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975).

Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132).

Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132).

CDKN1A up-regulation may be cell-type specific (PubMed:18264132).

Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132).

Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295).

May positively regulate TP53 transcription (PubMed:28842590).

Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238).

Involved in the regulation of translation initiation (PubMed:18628297, PubMed:17667941, PubMed:22872150).

Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untranslated regions (UTR) (PubMed:20837705, PubMed:22872150).

This function depends on helicase activity (PubMed:20837705, PubMed:22872150).

Might facilitate translation by resolving secondary structures of 5'-UTRs during ribosome scanning (PubMed:20837705).

Alternatively, may act prior to 43S ribosomal scanning and promote 43S pre-initiation complex entry to mRNAs exhibiting specific RNA motifs, by performing local remodeling of transcript structures located close to the cap moiety (PubMed:22872150).

Independently of its ATPase activity, promotes the assembly of functional 80S ribosomes and disassembles from ribosomes prior to the translation elongation process (PubMed:22323517).

Positively regulates the translation of cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition during the cell cycle (PubMed:20837705).

May activate TP53 translation (PubMed:28842590).

Required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139).

Independently of its ATPase/helicase activity, enhances IRES-mediated translation; this activity requires interaction with EIF4E (PubMed:17667941, PubMed:22323517).

Independently of its ATPase/helicase activity, has also been shown specifically repress cap-dependent translation, possibly by acting on translation initiation factor EIF4E (PubMed:17667941).

Involved in innate immunity, acting as a viral RNA sensor. Binds viral RNAs and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:31575075, PubMed:20127681, PubMed:21170385).

Potentiate MAVS/DDX58-mediated induction of IFNB in early stages of infection (PubMed:20127681, PubMed:21170385).

Enhances IFNB1 expression via IRF3/IRF7 pathway and participates in NFKB activation in the presence of MAVS and TBK1 (PubMed:18583960, PubMed:18636090, PubMed:21170385, PubMed:27980081, PubMed:19913487).

Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, acts as a scaffolding adapter that links IKBKE and IRF3 and coordinates their activation (PubMed:23478265).

Involved in the TLR7/TLR8 signaling pathway leading to type I interferon induction, including IFNA4 production. In this context, acts as an upstream regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CHUK autophosphorylation and activation following physiological activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK-mediated activatory phosphorylation of IRF7 (PubMed:30341167).

Also stimulates MAP3K14/CHUK-dependent NF-kappa-B signaling (PubMed:30341167).

Negatively regulates TNF-induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by interacting with RELA/p65 and trapping it in the cytoplasm (PubMed:27736973).

May also bind IFNB promoter; the function is independent of IRF3 (PubMed:18583960).

Involved in both stress and inflammatory responses (By similarity).

Independently of its ATPase/helicase activity, required for efficient stress granule assembly through its interaction with EIF4E, hence promotes survival in stressed cells (PubMed:21883093).

Independently of its helicase activity, regulates NLRP3 inflammasome assembly through interaction with NLRP3 and hence promotes cell death by pyroptosis during inflammation. This function is independent of helicase activity (By similarity).

Therefore DDX3X availability may be used to interpret stress signals and choose between pro-survival stress granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die checkpoint in stressed cells (By similarity).

In association with GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via death domain receptors, including TNFRSF10B, slowing down the rate of CASP3 activation following death receptor stimulation (PubMed:18846110).

Cleavage by caspases may inactivate DDX3X and relieve the inhibition (PubMed:18846110).

Independently of its ATPase/helicase activity, allosteric activator of CSNK1E. Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in the positive regulation of Wnt/beta-catenin signaling pathway. Also activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these targets are physiologically relevant (PubMed:23413191, PubMed:29222110).

ATPase and casein kinase-activating functions are mutually exclusive (PubMed:29222110).

May be involved in mitotic chromosome segregation (PubMed:21730191).

(Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501).

During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385).

(Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501).

Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501).

This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960).

(Microbial infection) Facilitates Zika virus (ZIKV) replication.

(Microbial infection) Facilitates Dengue virus (DENV) replication.

(Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication.

Cell differentiation Source: GO_Central
Cellular response to arsenic-containing substance Source: UniProtKB
Cellular response to osmotic stress Source: UniProtKB
Cellular response to virus Source: UniProtKB
Chromosome segregation Source: UniProtKB
Extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
Gamete generation Source: GO_Central
Innate immune response Source: UniProtKB
Intracellular signal transduction Source: UniProtKB
Intrinsic apoptotic signaling pathway Source: UniProtKB
Lipid homeostasis Source: UniProtKB
Mature ribosome assembly Source: UniProtKB
Negative regulation of apoptotic process Source: UniProtKB
Negative regulation of cell growth Source: UniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
Negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
Negative regulation of NIK/NF-kappaB signaling Source: UniProtKB
Negative regulation of protein-containing complex assembly Source: UniProtKB
Negative regulation of translation Source: UniProtKB
Neutrophil degranulation Source: Reactome
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of canonical Wnt signaling pathway Source: UniProtKB
Positive regulation of cell growth Source: UniProtKB
Positive regulation of chemokine (C-C motif) ligand 5 production Source: UniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Positive regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
Positive regulation of gene expression Source: AgBase
Positive regulation of interferon-alpha production Source: UniProtKB
Positive regulation of interferon-beta production Source: UniProtKB
Positive regulation of NIK/NF-kappaB signaling Source: UniProtKB
Positive regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
Positive regulation of protein acetylation Source: UniProtKB
Positive regulation of protein autophosphorylation Source: UniProtKB
Positive regulation of protein K63-linked ubiquitination Source: UniProtKB
Positive regulation of protein serine/threonine kinase activity Source: UniProtKB
Positive regulation of toll-like receptor 7 signaling pathway Source: UniProtKB
Positive regulation of toll-like receptor 8 signaling pathway Source: UniProtKB
Positive regulation of transcription by RNA polymerase II Source: UniProtKB
Positive regulation of translation Source: UniProtKB
Positive regulation of translational initiation Source: UniProtKB
Positive regulation of translation in response to endoplasmic reticulum stress Source: UniProtKB
Positive regulation of viral genome replication Source: AgBase
Protein localization to cytoplasmic stress granule Source: AgBase
Response to virus Source: UniProtKB
RNA secondary structure unwinding Source: UniProtKB
Stress granule assembly Source: UniProtKB
Translational initiation Source: UniProtKB
Viral process Source: UniProtKB-KW
Wnt signaling pathway Source: UniProtKB

Cytoplasm; Inflammasome; Nucleus; Cell membrane; Centrosome; Stress granule; Lamellipodium. Shuttles between the nucleus and the cytosol (PubMed:15507209, PubMed:18636090, PubMed:29899501, PubMed:31575075, PubMed:30131165). Exported from the nucleus partly through the XPO1/CRM1 system and partly through NXF1/TAP (PubMed:15507209, PubMed:18636090, PubMed:18596238, PubMed:31575075, PubMed:30131165). Localizes to nuclear pores on the outer side of the nuclear membrane (PubMed:15507209). In the cytosol, partly colocalizes with mitochondria (PubMed:20127681). At G0, predominantly located in nucleus. In G1/S phase, predominantly cytoplasmic (PubMed:22034099). During prophase/prometaphase, localizes in close proximity to the condensing chromosomes (PubMed:30131165, PubMed:21730191). During telophase, localizes around the newly synthesized nuclear membrane and in the cytoplasm (PubMed:22034099). Colocalizes with TRPV4 at the plasma membrane. When TRPV4 channel is activated, intracellular Ca2+ levels increase and the calmodulin/CAMKII pathway is activated, relocalizes to the nucleus (PubMed:29899501). WNT3A stimulation promotes DDX3 recruitment to the plasma membrane (PubMed:23413191). At the leading edge of migrating fibroblasts, colocalizes with CAPRIN1 and PABPC1 (PubMed:28733330). Localizes to centrosome throughout the cell cycle and associates with TP53 at centrosome during mitosis (PubMed:28842590). Translocates to the nucleus in response to HPIV-3 virus-mediated infection (PubMed:31575075).

Intellectual developmental disorder, X-linked, syndromic, Snijders Blok type (MRXSSB):
A disorder characterized by mild to severe intellectual disability, hypotonia, movement disorders, behavior problems, corpus callosum hypoplasia, and epilepsy. Additionally, patients manifest variable non-neurologic features such as joint hyperlaxity, skin pigmentary abnormalities, cleft lip and/or palate, hearing and visual impairment, and precocious puberty.

Phosphorylated by TBK1; the phosphorylation is required for the synergistic induction of IFNB mediated by TBK1 and DDX3X (PubMed:18583960). Phosphorylated by IKBKE at Ser-102 after ssRNA viral infection; enhances the induction of INFB promoter by IRF3 (PubMed:18583960, PubMed:23478265). The cytoplasmic form is highly phosphorylated in the G1/S phase of the cell cycle and much less at G2/M (PubMed:22034099). Phosphorylation by CSNK1E may inhibit RNA-stimulated ATPase activity (PubMed:29222110).
Upon stimulation of death receptors, including TNFRSF10B, recruited to receptors and cleaved by caspases. Proteolytic fragments remain associated with the receptors. This cleavage presumably inactivates DDX3X anti-apoptotic function.