Human Gene DDX3X (uc004dfe.3) Description and Page Index
  Description: Homo sapiens DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X), transcript variant 1, mRNA.
RefSeq Summary (NM_001356): The protein encoded by this gene 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. Misregulation of this gene has been implicated in tumorigenesis. This gene has a paralog located in the nonrecombining region of the Y chromosome. Pseudogenes sharing similarity to both this gene and the DDX3Y paralog are found on chromosome 4 and the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014].
Transcript (Including UTRs)
   Position: hg19 chrX:41,192,651-41,209,524 Size: 16,874 Total Exon Count: 17 Strand: +
Coding Region
   Position: hg19 chrX:41,193,506-41,206,972 Size: 13,467 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chrX:41,192,651-41,209,524)mRNA (may differ from genome)Protein (662 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: DDX3X_HUMAN
DESCRIPTION: RecName: Full=ATP-dependent RNA helicase DDX3X; EC=3.6.4.13; AltName: Full=DEAD box protein 3, X-chromosomal; AltName: Full=DEAD box, X isoform; AltName: Full=Helicase-like protein 2; Short=HLP2;
FUNCTION: 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 IFN-beta induction. Also found associated with IFN-beta 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. Appears to be a prime target for viral manipulations. Hepatitis B virus (HBV) polymerase and possibly vaccinia virus (VACV) protein K7 inhibit IFN-beta induction probably by dissociating DDX3X from TBK1 or IKBKE. Is involved in hepatitis C virus (HCV) replication; the function may involve the association with HCV core protein. HCV core protein inhibits the IPS1- dependent function in viral RNA sensing and may switch the function from a INF-beta inducing to a HCV replication mode. Involved in HIV-1 replication. Acts as a cofactor for XPO1- mediated nuclear export of incompletely spliced HIV-1 Rev RNAs.
CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
SUBUNIT: 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 found to be induced upon virus infection and to be inhibited by HBV polymerase. Interacts with TBK1; the interaction is inhibited by HBV polymerase. 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. Interacts with HCV core protein. Interacts with vaccinia virus (VACV) protein K7. Found in a complex with HIV-1 Rev and XPO1.
INTERACTION: O95786:DDX58; NbExp=2; IntAct=EBI-353779, EBI-995350; P05198:EIF2S1; NbExp=3; IntAct=EBI-353779, EBI-1056162; P55884:EIF3B; NbExp=5; IntAct=EBI-353779, EBI-366696; Q99613:EIF3CL; NbExp=3; IntAct=EBI-353779, EBI-353741; Q7Z434:MAVS; NbExp=4; IntAct=EBI-353779, EBI-995373; Q15003:NCAPH; NbExp=2; IntAct=EBI-353779, EBI-1046410; Q9UBU9:NXF1; NbExp=5; IntAct=EBI-353779, EBI-398874; P11940:PABPC1; NbExp=9; IntAct=EBI-353779, EBI-81531;
SUBCELLULAR LOCATION: Nucleus speckle. Cytoplasm. Mitochondrion outer membrane. 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 G(0) phase and in the cytoplasm during G1/S phase.
INDUCTION: Regulated by the cell cycle. Maximally expressed din the cytoplasm uring G1/S phase and decreased expression during G2/M phase.
PTM: Phosphorylated by TBK1; the phosphorylation is required to synergize with TBK1 in IFN-beta induction. Probably also phosphorylated by IKBKE. The cytoplasmic form is highly phosphorylated in the G1/S phase and much lower phosphorylated in G2/M.
SIMILARITY: Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.
SIMILARITY: Contains 1 helicase ATP-binding domain.
SIMILARITY: Contains 1 helicase C-terminal domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): DDX3X
CDC HuGE Published Literature: DDX3X

-  MalaCards Disease Associations
  MalaCards Gene Search: DDX3X
Diseases sorted by gene-association score: mental retardation, x-linked 102* (1681), corpus callosum, agenesis of, with facial anomalies and robin sequence* (350), precursor t-cell acute lymphoblastic leukemia* (80), hepatitis b (10), juvenile astrocytoma (8), childhood medulloblastoma (8), hepatitis c virus (7), juvenile pilocytic astrocytoma (5), hiv-1 (3), intellectual disability (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 74.34 RPKM in Fallopian Tube
Total median expression: 2173.26 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -345.70855-0.404 Picture PostScript Text
3' UTR -681.292552-0.267 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011545 - DNA/RNA_helicase_DEAD/DEAH_N
IPR014001 - Helicase_ATP-bd
IPR001650 - Helicase_C
IPR000629 - RNA-helicase_DEAD-box_CS
IPR014014 - RNA_helicase_DEAD_Q_motif

Pfam Domains:
PF00270 - DEAD/DEAH box helicase
PF00271 - Helicase conserved C-terminal domain

SCOP Domains:
52540 - P-loop containing nucleoside triphosphate hydrolases

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2I4I
- X-ray MuPIT

2JGN
- X-ray MuPIT

3JRV
- X-ray


ModBase Predicted Comparative 3D Structure on O00571
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0003676 nucleic acid binding
GO:0003677 DNA binding
GO:0003723 RNA binding
GO:0003924 GTPase activity
GO:0004003 ATP-dependent DNA helicase activity
GO:0004004 ATP-dependent RNA helicase activity
GO:0004386 helicase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008134 transcription factor binding
GO:0008143 poly(A) binding
GO:0008190 eukaryotic initiation factor 4E binding
GO:0016787 hydrolase activity
GO:0016887 ATPase activity
GO:0017111 nucleoside-triphosphatase activity
GO:0031369 translation initiation factor binding
GO:0033592 RNA strand annealing activity
GO:0035613 RNA stem-loop binding
GO:0043024 ribosomal small subunit binding
GO:0043273 CTPase activity
GO:0043539 protein serine/threonine kinase activator activity
GO:0045296 cadherin binding
GO:0048027 mRNA 5'-UTR binding

Biological Process:
GO:0002376 immune system process
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006413 translational initiation
GO:0006417 regulation of translation
GO:0006915 apoptotic process
GO:0007059 chromosome segregation
GO:0008625 extrinsic apoptotic signaling pathway via death domain receptors
GO:0009615 response to virus
GO:0010501 RNA secondary structure unwinding
GO:0010628 positive regulation of gene expression
GO:0016032 viral process
GO:0016055 Wnt signaling pathway
GO:0017148 negative regulation of translation
GO:0030307 positive regulation of cell growth
GO:0030308 negative regulation of cell growth
GO:0031333 negative regulation of protein complex assembly
GO:0032508 DNA duplex unwinding
GO:0032728 positive regulation of interferon-beta production
GO:0034063 stress granule assembly
GO:0035556 intracellular signal transduction
GO:0042254 ribosome biogenesis
GO:0042256 mature ribosome assembly
GO:0043065 positive regulation of apoptotic process
GO:0043066 negative regulation of apoptotic process
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043280 positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0043312 neutrophil degranulation
GO:0045070 positive regulation of viral genome replication
GO:0045087 innate immune response
GO:0045727 positive regulation of translation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0045948 positive regulation of translational initiation
GO:0071243 cellular response to arsenic-containing substance
GO:0071470 cellular response to osmotic stress
GO:0071651 positive regulation of chemokine (C-C motif) ligand 5 production
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0090263 positive regulation of canonical Wnt signaling pathway
GO:0097193 intrinsic apoptotic signaling pathway
GO:1900087 positive regulation of G1/S transition of mitotic cell cycle
GO:1903608 protein localization to cytoplasmic stress granule
GO:2001243 negative regulation of intrinsic apoptotic signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005634 nucleus
GO:0005730 nucleolus
GO:0005737 cytoplasm
GO:0005739 mitochondrion
GO:0005741 mitochondrial outer membrane
GO:0005829 cytosol
GO:0010494 cytoplasmic stress granule
GO:0016020 membrane
GO:0016607 nuclear speck
GO:0034774 secretory granule lumen
GO:0070062 extracellular exosome
GO:1904813 ficolin-1-rich granule lumen
GO:0005852 eukaryotic translation initiation factor 3 complex
GO:0022627 cytosolic small ribosomal subunit


-  Descriptions from all associated GenBank mRNAs
  AF000982 - Homo sapiens dead box, X isoform (DBX) mRNA, alternative transcript 2, complete cds.
AF000983 - Homo sapiens dead box, X isoform (DBX) mRNA, alternative transcript 1, complete cds.
JD429277 - Sequence 410301 from Patent EP1572962.
JD240895 - Sequence 221919 from Patent EP1572962.
JD416109 - Sequence 397133 from Patent EP1572962.
JD154562 - Sequence 135586 from Patent EP1572962.
JD392113 - Sequence 373137 from Patent EP1572962.
JD392312 - Sequence 373336 from Patent EP1572962.
JD395289 - Sequence 376313 from Patent EP1572962.
JD468398 - Sequence 449422 from Patent EP1572962.
JD266850 - Sequence 247874 from Patent EP1572962.
JD061995 - Sequence 43019 from Patent EP1572962.
JD308069 - Sequence 289093 from Patent EP1572962.
U50553 - Homo sapiens helicase like protein 2 (DDX14) mRNA, complete cds.
JD058676 - Sequence 39700 from Patent EP1572962.
JD241457 - Sequence 222481 from Patent EP1572962.
JD196169 - Sequence 177193 from Patent EP1572962.
BC055083 - Homo sapiens cDNA clone IMAGE:4068230, partial cds.
AK310891 - Homo sapiens cDNA, FLJ17933.
AK304689 - Homo sapiens cDNA FLJ60399 complete cds, highly similar to ATP-dependent RNA helicase DDX3X (EC 3.6.1.-).
AK291153 - Homo sapiens cDNA FLJ76819 complete cds, highly similar to Homo sapiens DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X), transcript variant 2, mRNA.
AK296906 - Homo sapiens cDNA FLJ55031 complete cds, highly similar to ATP-dependent RNA helicase DDX3X (EC 3.6.1.-).
AK297159 - Homo sapiens cDNA FLJ60675 complete cds, highly similar to ATP-dependent RNA helicase DDX3X (EC 3.6.1.-).
AF086430 - Homo sapiens full length insert cDNA clone ZD79H04.
BC007668 - Homo sapiens cDNA clone IMAGE:3138761, containing frame-shift errors.
AF061337 - Homo sapiens DEAD box RNA helicase DDX3 (DDX3) mRNA, complete cds.
BC011819 - Homo sapiens DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked, mRNA (cDNA clone MGC:20129 IMAGE:3617040), complete cds.
AB208983 - Homo sapiens mRNA for DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3 variant protein.
JD486384 - Sequence 467408 from Patent EP1572962.
AB384807 - Synthetic construct DNA, clone: pF1KB3467, Homo sapiens DDX3X gene for ATP-dependent RNA helicase DDX3X, complete cds, without stop codon, in Flexi system.
AB451343 - Homo sapiens DDX3X mRNA for ATP-dependent RNA helicase DDX3X, partial cds, clone: FLJ08002AAAF.
AB451220 - Homo sapiens DDX3X mRNA for ATP-dependent RNA helicase DDX3X, complete cds, clone: FLJ08002AAAN.
AK304661 - Homo sapiens cDNA FLJ52848 complete cds, highly similar to ATP-dependent RNA helicase DDX3X (EC 3.6.1.-).
DQ587475 - Homo sapiens piRNA piR-54587, complete sequence.
AY776161 - Homo sapiens clone Ctg007 unknown mRNA.
DQ574619 - Homo sapiens piRNA piR-42731, complete sequence.
DQ600255 - Homo sapiens piRNA piR-38321, complete sequence.
L37696 - Homo sapiens (clone 68) macronuclear mRNA.
JD400322 - Sequence 381346 from Patent EP1572962.
JD374812 - Sequence 355836 from Patent EP1572962.
JD092467 - Sequence 73491 from Patent EP1572962.
JD324990 - Sequence 306014 from Patent EP1572962.
DM107612 - METHODS FOR GENERATING NEW HAIR FOLLICLES, TREATING BALDNESS, AND HAIR REMOVAL.
HW120616 - JP 2013049691-A/171: METHODS FOR GENERATING NEW HAIR FOLLICLES, TREATING BALDNESS, AND HAIR REMOVAL.
LF858719 - JP 2015172074-A/171: METHODS FOR GENERATING NEW HAIR FOLLICLES, TREATING BALDNESS, AND HAIR REMOVAL.
JD543075 - Sequence 524099 from Patent EP1572962.
JD369704 - Sequence 350728 from Patent EP1572962.
JD170076 - Sequence 151100 from Patent EP1572962.
JD455163 - Sequence 436187 from Patent EP1572962.
DQ591868 - Homo sapiens piRNA piR-58980, complete sequence.
JD372293 - Sequence 353317 from Patent EP1572962.
JD295273 - Sequence 276297 from Patent EP1572962.
JD374793 - Sequence 355817 from Patent EP1572962.
JD085241 - Sequence 66265 from Patent EP1572962.
JD332890 - Sequence 313914 from Patent EP1572962.
MA726069 - JP 2017114907-A/171: METHODS FOR GENERATING NEW HAIR FOLLICLES, TREATING BALDNESS, AND HAIR REMOVAL.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04622 - RIG-I-like receptor signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein O00571 (Reactome details) participates in the following event(s):

R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins
R-HSA-6798748 Exocytosis of secretory granule lumen proteins
R-HSA-6798695 Neutrophil degranulation
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A8K538, B4E3E8, DBX, DDX3, DDX3X_HUMAN, NM_001356, NP_001347, O00571, O15536
UCSC ID: uc004dfe.3
RefSeq Accession: NM_001356
Protein: O00571 (aka DDX3X_HUMAN)
CCDS: CCDS43931.1, CCDS55404.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001356.3
exon count: 17CDS single in 3' UTR: no RNA size: 5433
ORF size: 1989CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4002.00frame shift in genome: no % Coverage: 99.32
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 2356# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.