ID DDX3X_MOUSE Reviewed; 662 AA. AC Q62167; O09060; O09143; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 207. DE RecName: Full=ATP-dependent RNA helicase DDX3X; DE EC=3.6.4.13 {ECO:0000250|UniProtKB:O00571}; DE AltName: Full=D1Pas1-related sequence 2; DE AltName: Full=DEAD box RNA helicase DEAD3; DE Short=mDEAD3 {ECO:0000303|PubMed:8144024}; DE AltName: Full=DEAD box protein 3, X-chromosomal; DE AltName: Full=Embryonic RNA helicase {ECO:0000303|PubMed:8948440}; GN Name=Ddx3x; GN Synonyms=D1Pas1-rs2, Ddx3, Dead3, Erh {ECO:0000303|PubMed:8948440}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RC STRAIN=C57BL/6J; TISSUE=Notochord; RX PubMed=8948440; DOI=10.1042/bj3080839; RA Sowden J.C., Putt W., Morrison K., Beddington R., Edwards Y.; RT "The embryonic RNA helicase gene (ERH): a new member of the DEAD box family RT of RNA helicases."; RL Biochem. J. 308:839-846(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Erythroleukemia; RX PubMed=8144024; DOI=10.1016/0378-1119(94)90541-x; RA Gee S.L., Conboy J.G.; RT "Mouse erythroid cells express multiple putative RNA helicase genes RT exhibiting high sequence conservation from yeast to mammals."; RL Gene 140:171-177(1994). RN [3] RP PROTEIN SEQUENCE OF 2-10, AND ACETYLATION AT SER-2. RX PubMed=10859333; DOI=10.1084/jem.191.12.2083; RA Yaguee J., Alvarez I., Rognan D., Ramos M., Vazquez J., RA Lopez de Castro J.A.; RT "An N-acetylated natural ligand of human histocompatibility leukocyte RT antigen (HLA)-B39. Classical major histocompatibility complex class I RT proteins bind peptides with a blocked NH(2) terminus in vivo."; RL J. Exp. Med. 191:2083-2092(2000). RN [4] RP PROTEIN SEQUENCE OF 535-548, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Hippocampus; RA Lubec G., Klug S.; RL Submitted (MAR-2007) to UniProtKB. RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-104, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, and Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic fibroblast; RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001; RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.; RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic RT pathways."; RL Mol. Cell 50:919-930(2013). RN [9] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=25050112; DOI=10.7555/jbr.27.20130047; RA Li Q., Zhang P., Zhang C., Wang Y., Wan R., Yang Y., Guo X., Huo R., RA Lin M., Zhou Z., Sha J.; RT "DDX3X regulates cell survival and cell cycle during mouse early embryonic RT development."; RL J. Biomed. Res. 28:282-291(2014). RN [10] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-101; ARG-110 AND ARG-632, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, and Embryo; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [11] RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND CHROMOSOMAL INACTIVATION. RX PubMed=27179789; DOI=10.1093/hmg/ddw143; RA Chen C.Y., Chan C.H., Chen C.M., Tsai Y.S., Tsai T.Y., Wu Lee Y.H., RA You L.R.; RT "Targeted inactivation of murine Ddx3x: essential roles of Ddx3x in RT placentation and embryogenesis."; RL Hum. Mol. Genet. 25:2905-2922(2016). RN [12] RP FUNCTION, INTERACTION WITH NLRP3, AND SUBCELLULAR LOCATION. RX PubMed=31511697; DOI=10.1038/s41586-019-1551-2; RA Samir P., Kesavardhana S., Patmore D.M., Gingras S., Malireddi R.K.S., RA Karki R., Guy C.S., Briard B., Place D.E., Bhattacharya A., Sharma B.R., RA Nourse A., King S.V., Pitre A., Burton A.R., Pelletier S., Gilbertson R.J., RA Kanneganti T.D.; RT "DDX3X acts as a live-or-die checkpoint in stressed cells by regulating RT NLRP3 inflammasome."; RL Nature 573:590-594(2019). RN [13] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=30475900; DOI=10.1371/journal.ppat.1007397; RA Szappanos D., Tschismarov R., Perlot T., Westermayer S., Fischer K., RA Platanitis E., Kallinger F., Novatchkova M., Lassnig C., Mueller M., RA Sexl V., Bennett K.L., Foong-Sobis M., Penninger J.M., Decker T.; RT "The RNA helicase DDX3X is an essential mediator of innate antimicrobial RT immunity."; RL PLoS Pathog. 14:E1007397-E1007397(2018). RN [14] RP DISRUPTION PHENOTYPE. RX PubMed=30613052; DOI=10.1262/jrd.2018-145; RA Matsumura T., Endo T., Isotani A., Ogawa M., Ikawa M.; RT "An azoospermic factor gene, Ddx3y and its paralog, Ddx3x are dispensable RT in germ cells for male fertility."; RL J. Reprod. Dev. 65:121-128(2019). CC -!- FUNCTION: Multifunctional ATP-dependent RNA helicase. The ATPase CC activity can be stimulated by various ribo-and deoxynucleic acids CC indicative for a relaxed substrate specificity. In vitro can unwind CC partially double-stranded DNA with a preference for 5'-single-stranded CC DNA overhangs. Binds RNA G-quadruplex (rG4s) structures, including CC those located in the 5'-UTR of NRAS mRNA. Involved in many cellular CC processes, which do not necessarily require its ATPase/helicase CC catalytic activities. Involved in transcription regulation. Positively CC regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, CC hence inhibits cell growth. This function requires its ATPase, but not CC helicase activity. CDKN1A up-regulation may be cell-type specific. CC Binds CDH1/E-cadherin promoter and represses its transcription. CC Potentiates HNF4A-mediated MTTP transcriptional activation; this CC function requires ATPase, but not helicase activity. Facilitates HNF4A CC acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the CC DNA-binding affinity of HNF4 to its response element. In addition, CC disrupts the interaction between HNF4 and SHP that forms inactive CC heterodimers and enhances the formation of active HNF4 homodimers. By CC promoting HNF4A-induced MTTP expression, may play a role in lipid CC homeostasis. May positively regulate TP53 transcription. Associates CC with mRNPs, predominantly with spliced mRNAs carrying an exon junction CC complex (EJC). Involved in the regulation of translation initiation. CC Not involved in the general process of translation, but promotes CC efficient translation of selected complex mRNAs, containing highly CC structured 5'-untranslated regions (UTR). This function depends on CC helicase activity. Might facilitate translation by resolving secondary CC structures of 5'-UTRs during ribosome scanning. Alternatively, may act CC prior to 43S ribosomal scanning and promote 43S pre-initiation complex CC entry to mRNAs exhibiting specific RNA motifs, by performing local CC remodeling of transcript structures located close to the cap moiety. CC Independently of its ATPase activity, promotes the assembly of CC functional 80S ribosomes and disassembles from ribosomes prior to the CC translation elongation process. Positively regulates the translation of CC cyclin E1/CCNE1 mRNA and consequently promotes G1/S-phase transition CC during the cell cycle. May activate TP53 translation. Required for CC endoplasmic reticulum stress-induced ATF4 mRNA translation. CC Independently of its ATPase/helicase activity, enhances IRES-mediated CC translation; this activity requires interaction with EIF4E. CC Independently of its ATPase/helicase activity, has also been shown CC specifically repress cap-dependent translation, possibly by acting on CC translation initiation factor EIF4E. Involved in innate immunity, CC acting as a viral RNA sensor. Binds viral RNAs and promotes the CC production of type I interferon (IFN-alpha and IFN-beta). Potentiate CC MAVS/RIGI-mediated induction of IFNB in early stages of infection (By CC similarity). Enhances IFNB1 expression via IRF3/IRF7 pathway and CC participates in NFKB activation in the presence of MAVS and TBK1 CC (PubMed:30475900). Involved in TBK1 and IKBKE-dependent IRF3 activation CC leading to IFNB induction, acts as a scaffolding adapter that links CC IKBKE and IRF3 and coordinates their activation. Involved in the CC TLR7/TLR8 signaling pathway leading to type I interferon induction, CC including IFNA4 production. In this context, acts as an upstream CC regulator of IRF7 activation by MAP3K14/NIK and CHUK/IKKA. Stimulates CC CHUK autophosphorylation and activation following physiological CC activation of the TLR7 and TLR8 pathways, leading to MAP3K14/CHUK- CC mediated activatory phosphorylation of IRF7. Also stimulates CC MAP3K14/CHUK-dependent NF-kappa-B signaling. Negatively regulates TNF- CC induced IL6 and IL8 expression, via the NF-kappa-B pathway. May act by CC interacting with RELA/p65 and trapping it in the cytoplasm. May also CC bind IFNB promoter; the function is independent of IRF3 (By CC similarity). Involved in both stress and inflammatory responses CC (PubMed:31511697). Independently of its ATPase/helicase activity, CC required for efficient stress granule assembly through its interaction CC with EIF4E, hence promotes survival in stressed cells (By similarity). CC Independently of its helicase activity, regulates NLRP3 inflammasome CC assembly through interaction with NLRP3 and hence promotes cell death CC by pyroptosis during inflammation. This function is independent of CC helicase activity. Therefore DDX3X availability may be used to CC interpret stress signals and choose between pro-survival stress CC granules and pyroptotic NLRP3 inflammasomes and serve as a live-or-die CC checkpoint in stressed cells (PubMed:31511697). In association with CC GSK3A/B, negatively regulates extrinsic apoptotic signaling pathway via CC death domain receptors, including TNFRSF10B, slowing down the rate of CC CASP3 activation following death receptor stimulation. Cleavage by CC caspases may inactivate DDX3X and relieve the inhibition. Independently CC of its ATPase/helicase activity, allosteric activator of CSNK1E. CC Stimulates CSNK1E-mediated phosphorylation of DVL2, thereby involved in CC the positive regulation of Wnt/beta-catenin signaling pathway. Also CC activates CSNK1A1 and CSNK1D in vitro, but it is uncertain if these CC targets are physiologically relevant. ATPase and casein kinase- CC activating functions are mutually exclusive. May be involved in mitotic CC chromosome segregation (By similarity). {ECO:0000250|UniProtKB:O00571, CC ECO:0000269|PubMed:30475900, ECO:0000269|PubMed:31511697}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; CC Evidence={ECO:0000250|UniProtKB:O00571}; CC -!- SUBUNIT: Homodimer; can bind RNA as a monomer and as a dimer/oligomer. CC Interacts with TDRD3. When phosphorylated, interacts with IRF3; the CC interaction facilitates the phosphorylation and activation of IRF3 by CC IKBKE. Directly interacts with XPO1/CRM1. The interaction with CC XPO1/CMR1 is dependent on the DDX3X nuclear export signal motif and CC XPO1 interaction with GTPase RAN in its active GTP-bound form. Weakly CC interacts with TBKBP1/SINTBAD. Directly interacts with TRAF3; this CC interaction stimulates TRAF3 'Lys-63' ubiquitination. Interacts with CC CSNK1E in a Wnt-dependent manner; this interaction greatly enhances CC CSNK1E affinity for ATP, stimulates its kinase activity and promotes CC CSNK1E-mediated DVL2 phosphorylation. In the presence of RNA, the CC interaction is decreased. Also interacts with CSNK1D and stimulates its CC kinase activity. Interacts with TRPV4; this interaction is decreased CC when the TRPV4 channel is activated, leading to DDX3X relocalization to CC the nucleus. Interacts with MAP3K14/NIK. Directly interacts with CC CHUK/IKKA after physiological activation of the TLR7 and TLR8 pathways; CC this interaction enhances CHUK autophosphorylation. May associate with CC EIF4F complex, composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. CC Directly interacts with EIF4E in an RNA-independent manner; this CC interaction enhances EIF4E cap-binding ability. Directly interacts with CC EIF4G1 in an RNA-independent manner. DDX3X competes with EIF4G1 for CC interaction with EIF4E. Interacts with EIF4A1 and EIF2S1 in an RNA- CC independent manner. Associates with the eukaryotic translation CC initiation factor 3 (eIF-3) complex, including with EIF3B and EIF3C CC subunits. Directly interacts with IKBKE/IKKE; this interaction CC stimulates IKBKE activating autophosphorylation and is induced upon CC viral infection. Interacts with TBK1. Interacts with SP1; this CC interaction potentiates SP1-induced CDKN1A/WAF1/CIP1 transcription. CC Interacts with GSK3A and GSK3B. Interacts with several death receptors, CC inclusing FAS, TNFRSF10A and TNFRSF10B. Recruited to TNFRSF10B in the CC absence of receptor stimulation. When TNFRSF10B is stimulated, further CC recruited to the receptor and cleaved by caspases. A large proteolytic CC fragment remains associated with TNFRSF10B. Interacts (via C-terminus) CC with NXF1/TAP; this interaction may be partly involved in DDX3X nuclear CC export and in NXF1 localization to stress granules. Identified in an CC mRNP complex, composed of at least DHX9, DDX3X, ELAVL1, HNRNPU, CC IGF2BP1/2, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. CC The interaction with IGF2BP1/2 is RNA-dependent. Directly interacts CC with PABPC1/PABP1 in an RNA-independent manner. This interaction CC increases in stressed cells and decreases during cell recovery. CC Interacts (via C-terminus) with MAVS/IPS-1; this interaction CC potentiates MAVS-mediated IFNB induction. Interacts with ERCC6/CBS. CC Interacts with DHX33 in an RNA-independent manner. Interacts with DDX5 CC in the cytoplasm; this interaction may be more efficient when both CC proteins are unphosphorylated. Interacts with RIGI. Interacts with CC IFIH1/MDA5. Interacts with NCAPH; this interaction may be important for CC the NCAPH localization at condensing chromosomes during mitosis (By CC similarity). Interacts with NLRP3 (via NACHT domain) under CC inflammasome-activating conditions (PubMed:31511697). Interacts with CC CAPRIN1. Interacts with HNF4A and NR0B2/SHP in an RNA-independent CC manner; this interaction disrupts the interaction between HNF4 and CC NR0B2 that forms inactive heterodimers and enhances the formation of CC active HNF4 homodimers. Interacts with CREBBP/CBP. Interacts with CC EP300/p300. Interacts with gamma-tubulin. Interacts with phosphorylated CC TP53. Directly interacts with RELA/p65; this interaction may trap RELA CC in the cytoplasm, impairing nuclear relocalization upon TNF activating CC signals (By similarity). {ECO:0000250|UniProtKB:O00571, CC ECO:0000269|PubMed:31511697}. CC -!- INTERACTION: CC Q62167; Q9UHD2: TBK1; Xeno; NbExp=8; IntAct=EBI-773173, EBI-356402; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O00571}. CC Nucleus {ECO:0000269|PubMed:25050112}. Cytoplasm CC {ECO:0000269|PubMed:25050112}. Cytoplasm, Stress granule CC {ECO:0000269|PubMed:31511697}. Inflammasome CC {ECO:0000269|PubMed:31511697}. Cell projection, lamellipodium CC {ECO:0000250|UniProtKB:O00571}. Note=Shuttles between the nucleus and CC the cytosol. Exported from the nucleus partly through the XPO1/CRM1 CC system and partly through NXF1/TAP. Localizes to nuclear pores on the CC outer side of the nuclear membrane. In the cytosol, partly colocalizes CC with mitochondria. At G0, predominantly located in nucleus. In G1/S CC phase, predominantly cytoplasmic. During prophase/prometaphase, CC localizes in close proximity to the condensing chromosomes. During CC telophase, localizes around the newly synthesized nuclear membrane and CC in the cytoplasm. Colocalizes with TRPV4 at the plasma membrane. When CC TRPV4 channel is activated, intracellular Ca(2+) levels increase and CC the calmodulin/CAMKII pathway is activated, relocalizes to the nucleus. CC WNT3A stimulation promotes DDX3 recruitment to the plasma membrane. CC {ECO:0000250|UniProtKB:O00571}. CC -!- TISSUE SPECIFICITY: Expressed in ovary, including in germinal vesicle CC immature and metaphase II (MII) stage oocytes (at protein level) CC (PubMed:8948440, PubMed:25050112). In the brain, expressed in the CC granule cells of the cerebellum and dentate gyrus, the pyramidal cells CC of the hippocampus, the ependymal cells lining the ventricles, choroid CC plexi and olfactory bulb. Also accumulates in the thalamic nuclei, the CC dorsal region of the colliculi and the pontine nucleus CC (PubMed:8948440). {ECO:0000269|PubMed:25050112, CC ECO:0000269|PubMed:8948440}. CC -!- DEVELOPMENTAL STAGE: In oocytes, expression levels increase from CC germinal vesicle immature oocytes to metaphase II (MII) and decline CC after fertilization in 1-cell and 2-cell embryos (at protein level) CC (PubMed:25050112). At 7.5 dpc, highly expressed in all embryonic cells CC and extraembryonic tissues, including ectoplacental cone, chorion, CC extraembryonic endoderm and parietal endoderm (at protein level) CC (PubMed:27179789). At 8.5-9.5 dpc, widely expressed (PubMed:8948440). CC At 8.5 dpc, levels decrease in extraembryonic tissues CC (PubMed:27179789). As development proceeds, expression becomes more CC restricted. At 11.5 dpc, most abundant in the neural tube, but still CC expressed at moderate levels in a number of other sites, including the CC mesenchyme of limbs and the face and in liver. At 14.5 dpc, highly CC expressed in the developing brain and caudal neural tube, but absent CC from the marginal layer of the neural tube. Also expressed in the CC developing metanephros and lung. At 15.5 dpc, expressed in the brain CC and spinal cord, as well as in teeth primordia, the lung and in the CC developing limb (PubMed:8948440). At 16.5 dpc, moderate, but non- CC uniform expression levels in the placenta (PubMed:27179789). CC {ECO:0000269|PubMed:25050112, ECO:0000269|PubMed:27179789, CC ECO:0000269|PubMed:8948440}. CC -!- DOMAIN: The C-terminus (residues 536-662) is dispensable for DDX3X CC trafficking. {ECO:0000250|UniProtKB:O00571}. CC -!- PTM: Phosphorylated by TBK1; the phosphorylation is required for the CC synergistic induction of IFNB mediated by TBK1 and DDX3X. CC Phosphorylated by IKBKE. Also phosphorylated by CSNK1E; this CC phosphorylation may inhibit RNA-stimulated ATPase activity. CC {ECO:0000250|UniProtKB:O00571}. CC -!- PTM: Upon stimulation of death receptors, including TNFRSF10B, CC recruited to receptors and cleaved by caspases. Proteolytic fragments CC remain associated with the receptors. This cleavage presumably CC inactivates DDX3X anti-apoptotic function. CC {ECO:0000250|UniProtKB:O00571}. CC -!- DISRUPTION PHENOTYPE: In mutant males, loss of DDX3X leads to early CC post-implantation lethality. In mutant females with a maternally CC inherited Ddx3x null allele, paternal X chromosome inactivation affects CC trophoblast differentiation, which leads to aberrant placental layers CC and defective vascularization in placental labyrinth. These placental CC abnormalities impair maternal blood supply to the embryo and ultimately CC lead to fetal growth restriction and lethality. Heterozygous females CC with a paternally inherited null allele are born at the expected CC Mendelian ratio, develop normally and are indistinguishable from their CC littermate controls (PubMed:27179789). Epiblast-specific knockout CC embryos exhibit multiple anomalies, including defective neural tube CC closure, underdeveloped brain, poorly developed myocardial trabeculae, CC which ultimately lead to embryonic lethality around 11.5 dpc CC (PubMed:27179789). DDX3X and DDX3Y double knockout is embryonic lethal CC (PubMed:30613052). DDX3X and DDX3Y double knockout germ cells can CC differentiate into spermatozoa (PubMed:30613052). Bone-marrow CC macrophage-specific knockout leads to a reduction in the expression of CC several cytokines, including IL1B, IL6, IL12 and IFNB1, in response to CC Listeria monocytogenes infection and pathogen-associated molecular CC patterns (PAMPs), including poly (I:C), poly (dA:dT) and LPS. This CC effect is more prononced in females than in male macrophages, probably CC due to the functional redundancy with DDX3Y gene located on chromosome CC Y (PubMed:30475900). {ECO:0000269|PubMed:27179789, CC ECO:0000269|PubMed:30475900, ECO:0000269|PubMed:30613052}. CC -!- MISCELLANEOUS: Encoded by an chromosome X-linked gene which escapes X CC chromosome inactivation (XCI) in females, but exhibits CC developmental- and tissue-specific differences in escape from XCI. CC DDX3Y, its homolog on chromosome Y, is located in the Y non-recombinant CC portion (By similarity). In 8 to 16 cell stage embryos, expression from CC paternal and maternal copies of DDX3X is detected. Paternally derived CC DDX3X is preferentially inactivated in extraembryonic tissues of CC embryos from 6.5 dpc (PubMed:27179789). {ECO:0000250|UniProtKB:O00571, CC ECO:0000269|PubMed:27179789}. CC -!- SIMILARITY: Belongs to the DEAD box helicase family. DDX3/DED1 CC subfamily. {ECO:0000305}. CC -!- CAUTION: The role of the nuclear export signal (NES) motif in XPO1- CC mediated DDX3X export is controversial (By similarity). In one study, CC NES has been found dispensable for DDX3X export while the helicase CC domain mediates the interaction with XPO1 (By similarity). However, in CC two other studies, DDX3X nuclear export is dependent on both NES and CC Ran in its GTP-bound form while the helicase domain is not required (By CC similarity). {ECO:0000250|UniProtKB:O00571}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; Z38117; CAA86261.1; -; mRNA. DR EMBL; L25126; AAA53630.1; -; mRNA. DR CCDS; CCDS30027.1; -. DR PIR; I84741; I84741. DR RefSeq; NP_034158.1; NM_010028.3. DR AlphaFoldDB; Q62167; -. DR SMR; Q62167; -. DR BioGRID; 199084; 87. DR IntAct; Q62167; 15. DR MINT; Q62167; -. DR STRING; 10090.ENSMUSP00000000804; -. DR ChEMBL; CHEMBL3751657; -. DR GlyGen; Q62167; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q62167; -. DR MetOSite; Q62167; -. DR PhosphoSitePlus; Q62167; -. DR SwissPalm; Q62167; -. DR REPRODUCTION-2DPAGE; Q62167; -. DR EPD; Q62167; -. DR jPOST; Q62167; -. DR MaxQB; Q62167; -. DR PaxDb; 10090-ENSMUSP00000000804; -. DR ProteomicsDB; 279851; -. DR Pumba; Q62167; -. DR Antibodypedia; 463; 784 antibodies from 41 providers. DR DNASU; 13205; -. DR Ensembl; ENSMUST00000000804.7; ENSMUSP00000000804.7; ENSMUSG00000000787.13. DR GeneID; 13205; -. DR KEGG; mmu:13205; -. DR UCSC; uc009srl.2; mouse. DR AGR; MGI:103064; -. DR CTD; 1654; -. DR MGI; MGI:103064; Ddx3x. DR VEuPathDB; HostDB:ENSMUSG00000000787; -. DR eggNOG; KOG0335; Eukaryota. DR GeneTree; ENSGT00940000154443; -. DR HOGENOM; CLU_003041_16_3_1; -. DR InParanoid; Q62167; -. DR OMA; CYRSWVR; -. DR OrthoDB; 5480645at2759; -. DR PhylomeDB; Q62167; -. DR TreeFam; TF300332; -. DR BRENDA; 3.6.4.13; 3474. DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR BioGRID-ORCS; 13205; 27 hits in 82 CRISPR screens. DR ChiTaRS; Ddx3x; mouse. DR PRO; PR:Q62167; -. DR Proteomes; UP000000589; Chromosome X. DR RNAct; Q62167; Protein. DR Bgee; ENSMUSG00000000787; Expressed in maxillary prominence and 282 other cell types or tissues. DR ExpressionAtlas; Q62167; baseline and differential. DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB. DR GO; GO:0005813; C:centrosome; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0030027; C:lamellipodium; IEA:UniProtKB-SubCell. DR GO; GO:0072559; C:NLRP3 inflammasome complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0043186; C:P granule; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB. DR GO; GO:0043273; F:CTPase activity; ISO:MGI. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0003678; F:DNA helicase activity; ISS:UniProtKB. DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; ISS:UniProtKB. DR GO; GO:0043015; F:gamma-tubulin binding; ISS:UniProtKB. DR GO; GO:0003924; F:GTPase activity; ISO:MGI. DR GO; GO:0048027; F:mRNA 5'-UTR binding; ISS:UniProtKB. DR GO; GO:0003729; F:mRNA binding; ISS:UniProtKB. DR GO; GO:0008143; F:poly(A) binding; ISS:UniProtKB. DR GO; GO:0070878; F:primary miRNA binding; IDA:MGI. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISS:UniProtKB. DR GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; ISO:MGI. DR GO; GO:0043024; F:ribosomal small subunit binding; ISS:UniProtKB. DR GO; GO:0003723; F:RNA binding; ISS:UniProtKB. DR GO; GO:0003724; F:RNA helicase activity; ISS:UniProtKB. DR GO; GO:0035613; F:RNA stem-loop binding; ISS:UniProtKB. DR GO; GO:0033592; F:RNA strand annealing activity; ISO:MGI. DR GO; GO:0035591; F:signaling adaptor activity; ISO:MGI. DR GO; GO:0008134; F:transcription factor binding; ISS:UniProtKB. DR GO; GO:0031369; F:translation initiation factor binding; ISS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0071243; P:cellular response to arsenic-containing substance; ISS:UniProtKB. DR GO; GO:0071470; P:cellular response to osmotic stress; ISS:UniProtKB. DR GO; GO:0098586; P:cellular response to virus; ISO:MGI. DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB. DR GO; GO:0042256; P:cytosolic ribosome assembly; ISS:UniProtKB. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; ISS:UniProtKB. DR GO; GO:0007276; P:gamete generation; IBA:GO_Central. DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB. DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISS:UniProtKB. DR GO; GO:0055088; P:lipid homeostasis; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISS:UniProtKB. DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB. DR GO; GO:1901223; P:negative regulation of non-canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISS:UniProtKB. DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB. DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB. DR GO; GO:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; IDA:UniProtKB. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:1901985; P:positive regulation of protein acetylation; ISS:UniProtKB. DR GO; GO:0031954; P:positive regulation of protein autophosphorylation; ISS:UniProtKB. DR GO; GO:1902523; P:positive regulation of protein K63-linked ubiquitination; ISS:UniProtKB. DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISS:UniProtKB. DR GO; GO:0034157; P:positive regulation of toll-like receptor 7 signaling pathway; ISS:UniProtKB. DR GO; GO:0034161; P:positive regulation of toll-like receptor 8 signaling pathway; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0045727; P:positive regulation of translation; ISS:UniProtKB. DR GO; GO:0036493; P:positive regulation of translation in response to endoplasmic reticulum stress; ISS:UniProtKB. DR GO; GO:0045948; P:positive regulation of translational initiation; ISS:UniProtKB. DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:MGI. DR GO; GO:0045070; P:positive regulation of viral genome replication; ISO:MGI. DR GO; GO:0031053; P:primary miRNA processing; IDA:MGI. DR GO; GO:1903608; P:protein localization to cytoplasmic stress granule; ISO:MGI. DR GO; GO:0009615; P:response to virus; ISS:UniProtKB. DR GO; GO:0010501; P:RNA secondary structure unwinding; ISS:UniProtKB. DR GO; GO:0034063; P:stress granule assembly; IMP:UniProtKB. DR GO; GO:0006413; P:translational initiation; ISO:MGI. DR GO; GO:0016055; P:Wnt signaling pathway; ISO:MGI. DR CDD; cd18051; DEADc_DDX3; 1. DR CDD; cd18787; SF2_C_DEAD; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2. DR InterPro; IPR011545; DEAD/DEAH_box_helicase_dom. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR000629; RNA-helicase_DEAD-box_CS. DR InterPro; IPR014014; RNA_helicase_DEAD_Q_motif. DR PANTHER; PTHR47958; ATP-DEPENDENT RNA HELICASE DBP3; 1. DR PANTHER; PTHR47958:SF3; ATP-DEPENDENT RNA HELICASE DDX3X; 1. DR Pfam; PF00270; DEAD; 1. DR Pfam; PF00271; Helicase_C; 1. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00039; DEAD_ATP_HELICASE; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS51195; Q_MOTIF; 1. DR Genevisible; Q62167; MM. PE 1: Evidence at protein level; KW Acetylation; Apoptosis; ATP-binding; Cell membrane; Cell projection; KW Chromosome partition; Cytoplasm; Direct protein sequencing; DNA-binding; KW Helicase; Hydrolase; Immunity; Inflammasome; Inflammatory response; KW Innate immunity; Isopeptide bond; Membrane; Methylation; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Ribosome biogenesis; RNA-binding; Transcription; Transcription regulation; KW Translation regulation; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:10859333" FT CHAIN 2..662 FT /note="ATP-dependent RNA helicase DDX3X" FT /id="PRO_0000055010" FT DOMAIN 211..403 FT /note="Helicase ATP-binding" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT DOMAIN 414..575 FT /note="Helicase C-terminal" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542" FT REGION 2..139 FT /note="Required for TBK1 and IKBKE-dependent IFNB1 FT activation" FT /evidence="ECO:0000250|UniProtKB:O00571" FT REGION 19..144 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 38..44 FT /note="Interaction with EIF4E" FT /evidence="ECO:0000250|UniProtKB:O00571" FT REGION 100..662 FT /note="Interaction with GSK3B" FT /evidence="ECO:0000250|UniProtKB:O00571" FT REGION 100..110 FT /note="Interaction with IKBKE" FT /evidence="ECO:0000250|UniProtKB:O00571" FT REGION 139..172 FT /note="Interaction with CHUK" FT /evidence="ECO:0000250|UniProtKB:O00571" FT REGION 250..259 FT /note="Involved in stimulation of ATPase activity by DNA FT and RNA, nucleic acid binding and unwinding" FT /evidence="ECO:0000250|UniProtKB:O00571" FT REGION 536..661 FT /note="Interaction with NXF1" FT /evidence="ECO:0000250|UniProtKB:O00571" FT REGION 601..633 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 12..21 FT /note="Nuclear export signal" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOTIF 180..208 FT /note="Q motif" FT MOTIF 347..350 FT /note="DEAD box" FT COMPBIAS 19..34 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 55..69 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 91..142 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 603..626 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 200..207 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT BINDING 224..231 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|PubMed:10859333" FT MOD_RES 55 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:23806337" FT MOD_RES 82 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 90 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 101 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 104 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT MOD_RES 110 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 118 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 131 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17242355" FT MOD_RES 183 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 456 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q62095" FT MOD_RES 592 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 594 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 605 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 612 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 617 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:O00571" FT MOD_RES 632 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT CROSSLNK 215 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:O00571" SQ SEQUENCE 662 AA; 73101 MW; 216515CB00324017 CRC64; MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK GFYDKDSSGW SSSKDKDAYS SFGSRGDSRG KSSFFGDRGS GSRGRFDDRG RGDYDGIGGR GDRSGFGKFE RGGNSRWCDK SDEDDWSKPL PPSERLEQEL FSGGNTGINF EKYDDIPVEA TGNNCPPHIE SFSDVEMGEI IMGNIELTRY TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS QIYADGPGEA LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV YGGAEIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD RMLDMGFEPQ IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY IFLAVGRVGS TSENITQKVV WVEEIDKRSF LLDLLNATGK DSLTLVFVET KKGADSLEDF LYHEGYACTS IHGDRSQRDR EEALHQFRSG KSPILVATAV AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL ATSFFNERNI NITKDLLDLL VEAKQEVPSW LENMAFEHHY KGSSRGRSKS SRFSGGFGAR DYRQSSGASS SSFSSSRASS SRSGGGGHGG SRGFGGGGYG GFYNSDGYGG NYNSQGVDWW GN //