Q62167 (DDX3X_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 132. History...
Names and origin
|Protein names||Recommended name:|
ATP-dependent RNA helicase DDX3X
D1Pas1-related sequence 2
DEAD box RNA helicase DEAD3
DEAD box protein 3, X-chromosomal
Embryonic RNA helicase
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||662 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Multifunctional ATP-dependent RNA helicase. The ATPase activity can be stimulated by various ribo- and deoxynucleic acids indicative for a relaxed substrate specificity. In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs. Is involved in several steps of gene expression, such as transcription, mRNA maturation, mRNA export and translation. However, the exact mechanisms are not known and some functions may be specific for a subset of mRNAs. Involved in transcriptional regulation. Can enhance transcription from the CDKN1A/WAF1 promoter in a SP1-dependent manner. Found associated with the E-cadherin promoter and can down-regulate transcription from the promoter. Involved in regulation of translation initiation. Proposed to be involved in positive regulation of translation such as of cyclin E1/CCNE1 mRNA and specifically of mRNAs containing complex secondary structures in their 5'UTRs; these functions seem to require RNA helicase activity. Specifically promotes translation of a subset of viral and cellular mRNAs carrying a 5'proximal stem-loop structure in their 5'UTRs and cooperates with the eIF4F complex. Proposed to act prior to 43S ribosomal scanning and to locally destabilize these RNA structures to allow recognition of the mRNA cap or loading onto the 40S subunit. After association with 40S ribosomal subunits seems to be involved in the functional assembly of 80S ribosomes; the function seems to cover translation of mRNAs with structured and non-structured 5'UTRs and is independent of RNA helicase activity. Also proposed to inhibit cap-dependent translation by competetive interaction with EIF4E which can block the EIF4E:EIF4G complex formation. Proposed to be involved in stress response and stress granule assembly; the function is independent of RNA helicase activity and seems to involve association with EIF4E. May be involved in nuclear export of specific mRNAs but not in bulk mRNA export via interactions with XPO1 and NXF1. Also associates with polyadenylated mRNAs independently of NXF1. Associates with spliced mRNAs in an exon junction complex (EJC)-dependent manner and seems not to be directly involved in splicing. May be involved in nuclear mRNA export by association with DDX5 and regulating its nuclear location. Involved in innate immune signaling promoting the production of type I interferon (IFN-alpha and IFN-beta); proposed to act as viral RNA sensor, signaling intermediate and transcriptional coactivator. Involved in TBK1 and IKBKE-dependent IRF3 activation leading to IFNB induction, plays a role of scaffolding adapter that links IKBKE and IRF3 and coordinates their activation. Also found associated with IFNB promoters; the function is independent of IRF3. Can bind to viral RNAs and via association with MAVS/IPS1 and DDX58/RIG-I is thought to induce signaling in early stages of infection. Involved in regulation of apoptosis. May be required for activation of the intrinsic but inhibit activation of the extrinsic apoptotic pathway. Acts as an antiapoptotic protein through association with GSK3A/B and BIRC2 in an apoptosis antagonizing signaling complex; activation of death receptors promotes caspase-dependent cleavage of BIRC2 and DDX3X and relieves the inhibition. May be involved in mitotic chromosome segregation By similarity.
ATP + H2O = ADP + phosphate.
Interacts with XPO1, TDRD3, PABPC1, NXF1, EIF3C, MAVS, DDX58 and NCAPH. Interacts with DDX5; the interaction is regulated by the phosphorylation status of both proteins. Interacts with EIF4E; DDX3X competes with EIF4G1/EIF4G3 for interaction with EIF4E. Interacts with IKBKE; the interaction is direct. Interacts with IRF3; the interaction allows the phosphorylation and activation of IRF3 by IKBKE. Interacts with TBK1. Associates with the eukaryotic translation initiation factor 3 (eIF-3) complex. Associates with the 40S ribosome. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1 By similarity.
Nucleus speckle By similarity. Cytoplasm By similarity. Mitochondrion outer membrane By similarity. Note: Located predominantly in nuclear speckles and, at low levels, throughout the cytoplasm. Located to the outer side of nuclear pore complexes (NPC). Shuttles between the nucleus and the cytoplasm in a XPO1 and may be also in a NFX1-dependent manner. Associated with polyadenylated mRNAs in the cytoplasm and the nucleus. Predominantly located in nucleus during G0 phase and in the cytoplasm during G1/S phase By similarity.
Expressed in oocytes. Ubiquitously found in 9 days post-conception embryo, at later stages it is restricted to brain and kidney.
Phosphorylated by TBK1; the phosphorylation is required to synergize with TBK1 in IFN-beta induction. Probably also phosphorylated by IKBKE By similarity.
Contains 1 helicase ATP-binding domain.
Contains 1 helicase C-terminal domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed Ref.3|
|Chain||2 – 662||661||ATP-dependent RNA helicase DDX3X||PRO_0000055010|
|Domain||211 – 403||193||Helicase ATP-binding|
|Domain||414 – 575||162||Helicase C-terminal|
|Nucleotide binding||200 – 207||8||ATP By similarity|
|Nucleotide binding||224 – 231||8||ATP By similarity|
|Region||2 – 139||138||Required for TBK1 and IKBKE-dependent IFN-beta activation By similarity|
|Region||2 – 100||99||Interaction with EIF4E By similarity|
|Region||100 – 662||563||Interaction with GSK3B By similarity|
|Region||100 – 110||11||Required for interaction with IKBKE By similarity|
|Region||250 – 259||10||Involved in stimulation of ATPase activity by DNA and RNA, nucleic acid binding and unwinding By similarity|
|Region||260 – 517||258||Necessary for interaction with XPO1 By similarity|
|Motif||180 – 208||29||Q motif|
|Motif||347 – 350||4||DEAD box|
|Compositional bias||582 – 662||81||Gly/Ser-rich|
|Compositional bias||609 – 616||8||Poly-Ser|
|Compositional bias||624 – 630||7||Poly-Gly|
|Compositional bias||633 – 641||9||Poly-Gly|
Amino acid modifications
|Modified residue||2||1||N-acetylserine Ref.3|
|Modified residue||55||1||N6-acetyllysine Ref.7|
|Modified residue||69||1||Phosphotyrosine By similarity|
|Modified residue||74||1||Phosphoserine By similarity|
|Modified residue||78||1||Phosphoserine By similarity|
|Modified residue||104||1||Phosphotyrosine Ref.5|
|Modified residue||118||1||N6-acetyllysine By similarity|
|Modified residue||125||1||Phosphoserine By similarity|
|Modified residue||131||1||Phosphoserine Ref.6|
|Modified residue||343||1||Phosphotyrosine By similarity|
|Modified residue||590||1||Phosphoserine By similarity|
|Modified residue||594||1||Phosphoserine By similarity|
|Modified residue||612||1||Phosphoserine By similarity|
|||"The embryonic RNA helicase gene (ERH): a new member of the DEAD box family of RNA helicases."|
Sowden J.C., Putt W., Morrison K., Beddington R., Edwards Y.
Biochem. J. 308:839-846(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6 and DBA.
|||"Mouse erythroid cells express multiple putative RNA helicase genes exhibiting high sequence conservation from yeast to mammals."|
Gee S.L., Conboy J.G.
Gene 140:171-177(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"An N-acetylated natural ligand of human histocompatibility leukocyte antigen (HLA)-B39. Classical major histocompatibility complex class I proteins bind peptides with a blocked NH(2) terminus in vivo."|
Yaguee J., Alvarez I., Rognan D., Ramos M., Vazquez J., Lopez de Castro J.A.
J. Exp. Med. 191:2083-2092(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-10, ACETYLATION AT SER-2.
|||Lubec G., Klug S.|
Submitted (MAR-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 535-548, IDENTIFICATION BY MASS SPECTROMETRY.
|||"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."|
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-104, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
|||"Large-scale phosphorylation analysis of mouse liver."|
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
|||"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."|
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-55, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
|+||Additional computationally mapped references.|
|Z38117 mRNA. Translation: CAA86261.1.|
L25126 mRNA. Translation: AAA53630.1.
|RefSeq||NP_034158.1. NM_010028.3. |
3D structure databases
|SMR||Q62167. Positions 139-580. |
Protein-protein interaction databases
|BioGrid||199084. 2 interactions.|
|IntAct||Q62167. 7 interactions.|
2D gel databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000000804; ENSMUSP00000000804; ENSMUSG00000000787. |
|UCSC||uc009srl.2. mouse. |
|MGI||MGI:103064. Ddx3x. |
Gene expression databases
Family and domain databases
|Gene3D||220.127.116.110. 2 hits. |
|InterPro||IPR011545. DNA/RNA_helicase_DEAD/DEAH_N. |
|Pfam||PF00270. DEAD. 1 hit. |
PF00271. Helicase_C. 1 hit.
|SMART||SM00487. DEXDc. 1 hit. |
SM00490. HELICc. 1 hit.
|SUPFAM||SSF52540. SSF52540. 1 hit. |
|PROSITE||PS00039. DEAD_ATP_HELICASE. 1 hit. |
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.
|ChiTaRS||DDX3X. mouse. |
|Accession||Primary (citable) accession number: Q62167|
Secondary accession number(s): O09060, O09143
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|