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Q62167

- DDX3X_MOUSE

UniProt

Q62167 - DDX3X_MOUSE

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Protein

ATP-dependent RNA helicase DDX3X

Gene

Ddx3x

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi200 – 2078ATPPROSITE-ProRule annotation
Nucleotide bindingi224 – 2318ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATPase activity Source: UniProtKB
  2. ATP binding Source: UniProtKB-KW
  3. ATP-dependent DNA helicase activity Source: UniProtKB
  4. ATP-dependent RNA helicase activity Source: UniProtKB
  5. DNA binding Source: UniProtKB
  6. eukaryotic initiation factor 4E binding Source: UniProtKB
  7. mRNA 5'-UTR binding Source: UniProtKB
  8. poly(A) binding Source: UniProtKB
  9. ribosomal small subunit binding Source: UniProtKB
  10. RNA binding Source: UniProtKB
  11. RNA stem-loop binding Source: UniProtKB
  12. transcription factor binding Source: UniProtKB
  13. translation initiation factor binding Source: UniProtKB

GO - Biological processi

  1. ATP catabolic process Source: GOC
  2. cellular response to arsenic-containing substance Source: UniProtKB
  3. cellular response to osmotic stress Source: UniProtKB
  4. chromosome segregation Source: UniProtKB
  5. DNA duplex unwinding Source: GOC
  6. extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
  7. innate immune response Source: UniProtKB
  8. intracellular signal transduction Source: UniProtKB
  9. intrinsic apoptotic signaling pathway Source: UniProtKB
  10. mature ribosome assembly Source: UniProtKB
  11. negative regulation of apoptotic process Source: UniProtKB
  12. negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  13. negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  14. negative regulation of protein complex assembly Source: UniProtKB
  15. negative regulation of translation Source: UniProtKB
  16. positive regulation of apoptotic process Source: UniProtKB
  17. positive regulation of cell growth Source: UniProtKB
  18. positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  19. positive regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
  20. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  21. positive regulation of translation Source: UniProtKB
  22. positive regulation of translational initiation Source: UniProtKB
  23. response to virus Source: UniProtKB
  24. RNA secondary structure unwinding Source: UniProtKB
  25. stress granule assembly Source: UniProtKB
  26. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Helicase, Hydrolase

Keywords - Biological processi

Apoptosis, Chromosome partition, Immunity, Innate immunity, Ribosome biogenesis, Transcription, Transcription regulation, Translation regulation

Keywords - Ligandi

ATP-binding, DNA-binding, Nucleotide-binding, RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
ATP-dependent RNA helicase DDX3X (EC:3.6.4.13)
Alternative name(s):
D1Pas1-related sequence 2
DEAD box RNA helicase DEAD3
Short name:
mDEAD3
DEAD box protein 3, X-chromosomal
Embryonic RNA helicase
Gene namesi
Name:Ddx3x
Synonyms:D1Pas1-rs2, Ddx3, Dead3, Erh
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome X

Organism-specific databases

MGIiMGI:103064. Ddx3x.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytoplasmic stress granule Source: UniProtKB
  3. mitochondrial outer membrane Source: UniProtKB-KW
  4. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 662661ATP-dependent RNA helicase DDX3XPRO_0000055010Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylserine1 Publication
Modified residuei55 – 551N6-acetyllysine1 Publication
Modified residuei69 – 691PhosphotyrosineBy similarity
Modified residuei74 – 741PhosphoserineBy similarity
Modified residuei78 – 781PhosphoserineBy similarity
Modified residuei104 – 1041Phosphotyrosine1 Publication
Modified residuei118 – 1181N6-acetyllysineBy similarity
Modified residuei125 – 1251PhosphoserineBy similarity
Modified residuei131 – 1311Phosphoserine1 Publication
Modified residuei343 – 3431PhosphotyrosineBy similarity
Modified residuei590 – 5901PhosphoserineBy similarity
Modified residuei594 – 5941PhosphoserineBy similarity
Modified residuei612 – 6121PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated by TBK1; the phosphorylation is required to synergize with TBK1 in IFN-beta induction. Probably also phosphorylated by IKBKE (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ62167.
PaxDbiQ62167.
PRIDEiQ62167.

2D gel databases

REPRODUCTION-2DPAGEQ62167.

PTM databases

PhosphoSiteiQ62167.

Expressioni

Tissue specificityi

Developmentally regulated.

Developmental stagei

Expressed in oocytes. Ubiquitously found in 9 days post-conception embryo, at later stages it is restricted to brain and kidney.

Gene expression databases

BgeeiQ62167.
CleanExiMM_ERH.
ExpressionAtlasiQ62167. baseline and differential.
GenevestigatoriQ62167.

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
TBK1Q9UHD28EBI-773173,EBI-356402From a different organism.

Protein-protein interaction databases

BioGridi199084. 2 interactions.
IntActiQ62167. 7 interactions.
MINTiMINT-1870173.

Structurei

3D structure databases

ProteinModelPortaliQ62167.
SMRiQ62167. Positions 139-580.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini211 – 403193Helicase ATP-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini414 – 575162Helicase C-terminalPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 139138Required for TBK1 and IKBKE-dependent IFN-beta activationBy similarityAdd
BLAST
Regioni2 – 10099Interaction with EIF4EBy similarityAdd
BLAST
Regioni100 – 662563Interaction with GSK3BBy similarityAdd
BLAST
Regioni100 – 11011Required for interaction with IKBKEBy similarityAdd
BLAST
Regioni250 – 25910Involved in stimulation of ATPase activity by DNA and RNA, nucleic acid binding and unwindingBy similarity
Regioni260 – 517258Necessary for interaction with XPO1By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi180 – 20829Q motifAdd
BLAST
Motifi347 – 3504DEAD box

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi582 – 66281Gly/Ser-richAdd
BLAST
Compositional biasi609 – 6168Poly-Ser
Compositional biasi624 – 6307Poly-Gly
Compositional biasi633 – 6419Poly-Gly

Sequence similaritiesi

Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0513.
GeneTreeiENSGT00770000120531.
HOGENOMiHOG000268804.
HOVERGENiHBG015893.
InParanoidiQ62167.
KOiK11594.
OMAiSFGSRND.
OrthoDBiEOG7B5WV8.
PhylomeDBiQ62167.
TreeFamiTF300332.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR011545. DEAD/DEAH_box_helicase_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
[Graphical view]
PfamiPF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiPS00039. DEAD_ATP_HELICASE. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q62167-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MSHVAVENAL GLDQQFAGLD LNSSDNQSGG STASKGRYIP PHLRNREATK
60 70 80 90 100
GFYDKDSSGW SSSKDKDAYS SFGSRGDSRG KSSFFGDRGS GSRGRFDDRG
110 120 130 140 150
RGDYDGIGGR GDRSGFGKFE RGGNSRWCDK SDEDDWSKPL PPSERLEQEL
160 170 180 190 200
FSGGNTGINF EKYDDIPVEA TGNNCPPHIE SFSDVEMGEI IMGNIELTRY
210 220 230 240 250
TRPTPVQKHA IPIIKEKRDL MACAQTGSGK TAAFLLPILS QIYADGPGEA
260 270 280 290 300
LRAMKENGRY GRRKQYPISL VLAPTRELAV QIYEEARKFS YRSRVRPCVV
310 320 330 340 350
YGGAEIGQQI RDLERGCHLL VATPGRLVDM MERGKIGLDF CKYLVLDEAD
360 370 380 390 400
RMLDMGFEPQ IRRIVEQDTM PPKGVRHTMM FSATFPKEIQ MLARDFLDEY
410 420 430 440 450
IFLAVGRVGS TSENITQKVV WVEEIDKRSF LLDLLNATGK DSLTLVFVET
460 470 480 490 500
KKGADSLEDF LYHEGYACTS IHGDRSQRDR EEALHQFRSG KSPILVATAV
510 520 530 540 550
AARGLDISNV KHVINFDLPS DIEEYVHRIG RTGRVGNLGL ATSFFNERNI
560 570 580 590 600
NITKDLLDLL VEAKQEVPSW LENMAFEHHY KGSSRGRSKS SRFSGGFGAR
610 620 630 640 650
DYRQSSGASS SSFSSSRASS SRSGGGGHGG SRGFGGGGYG GFYNSDGYGG
660
NYNSQGVDWW GN
Length:662
Mass (Da):73,101
Last modified:January 23, 2007 - v3
Checksum:i216515CB00324017
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z38117 mRNA. Translation: CAA86261.1.
L25126 mRNA. Translation: AAA53630.1.
CCDSiCCDS30027.1.
PIRiI84741.
RefSeqiNP_034158.1. NM_010028.3.
UniGeneiMm.289662.

Genome annotation databases

EnsembliENSMUST00000000804; ENSMUSP00000000804; ENSMUSG00000000787.
GeneIDi13205.
KEGGimmu:13205.
UCSCiuc009srl.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z38117 mRNA. Translation: CAA86261.1 .
L25126 mRNA. Translation: AAA53630.1 .
CCDSi CCDS30027.1.
PIRi I84741.
RefSeqi NP_034158.1. NM_010028.3.
UniGenei Mm.289662.

3D structure databases

ProteinModelPortali Q62167.
SMRi Q62167. Positions 139-580.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 199084. 2 interactions.
IntActi Q62167. 7 interactions.
MINTi MINT-1870173.

PTM databases

PhosphoSitei Q62167.

2D gel databases

REPRODUCTION-2DPAGE Q62167.

Proteomic databases

MaxQBi Q62167.
PaxDbi Q62167.
PRIDEi Q62167.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000000804 ; ENSMUSP00000000804 ; ENSMUSG00000000787 .
GeneIDi 13205.
KEGGi mmu:13205.
UCSCi uc009srl.2. mouse.

Organism-specific databases

CTDi 1654.
MGIi MGI:103064. Ddx3x.

Phylogenomic databases

eggNOGi COG0513.
GeneTreei ENSGT00770000120531.
HOGENOMi HOG000268804.
HOVERGENi HBG015893.
InParanoidi Q62167.
KOi K11594.
OMAi SFGSRND.
OrthoDBi EOG7B5WV8.
PhylomeDBi Q62167.
TreeFami TF300332.

Miscellaneous databases

ChiTaRSi Ddx3x. mouse.
NextBioi 283364.
PROi Q62167.
SOURCEi Search...

Gene expression databases

Bgeei Q62167.
CleanExi MM_ERH.
ExpressionAtlasi Q62167. baseline and differential.
Genevestigatori Q62167.

Family and domain databases

Gene3Di 3.40.50.300. 2 hits.
InterProi IPR011545. DEAD/DEAH_box_helicase_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
[Graphical view ]
Pfami PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
[Graphical view ]
SMARTi SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view ]
SUPFAMi SSF52540. SSF52540. 1 hit.
PROSITEi PS00039. DEAD_ATP_HELICASE. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "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.
  2. "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].
    Tissue: Erythroleukemia.
  3. "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.
  4. Lubec G., Klug S.
    Submitted (MAR-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 535-548, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Hippocampus.
  5. "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].
  6. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-131, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  7. "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.

Entry informationi

Entry nameiDDX3X_MOUSE
AccessioniPrimary (citable) accession number: Q62167
Secondary accession number(s): O09060, O09143
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 23, 2007
Last modified: November 26, 2014
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3