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DDX3X DEAD-box helicase 3 X-linked [ Homo sapiens (human) ]

Gene ID: 1654, updated on 6-Jan-2019

Summary

Official Symbol
DDX3Xprovided by HGNC
Official Full Name
DEAD-box helicase 3 X-linkedprovided by HGNC
Primary source
HGNC:HGNC:2745
See related
Ensembl:ENSG00000215301 MIM:300160
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DBX; DDX3; HLP2; DDX14; CAP-Rf; MRX102
Summary
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]
Expression
Ubiquitous expression in bone marrow (RPKM 90.6), gall bladder (RPKM 60.1) and 25 other tissues See more
Orthologs

Genomic context

See DDX3X in Genome Data Viewer
Location:
Xp11.4
Exon count:
20
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) X NC_000023.11 (41333308..41364472)
105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (41192561..41209527)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373184 Neighboring gene RNA, 5S ribosomal pseudogene 502 Neighboring gene uncharacterized LOC107985678 Neighboring gene shisa family member 5 pseudogene Neighboring gene RNA, 7SL, cytoplasmic 15, pseudogene Neighboring gene gem nuclear organelle associated protein 7 pseudogene Neighboring gene nyctalopin Neighboring gene calcium/calmodulin dependent serine protein kinase Neighboring gene RNA, U6 small nuclear 1321, pseudogene

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Mental retardation, X-linked 102
MedGen: C4085582 OMIM: 300958 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2017-11-22)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2017-11-22)

ClinGen Genome Curation PagePubMed

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed
DDX3X knockdown does not affect cell growth (HeLaP4-CCR5 cells, partial knockdown (25% of normal levels)) but significantly impairs HIV-1 replication; HIV-1 replication is enhanced by DDX3X PubMed
Knockdown of DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) by siRNA inhibits HIV-1 replication in HeLa P4/CCR5 cells PubMed
Knockdown of ATP-dependent RNA helicase DDX3X by siRNAs inhibits HIV-1 replication in CD4+ T cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env Tandem affinity purification and mass spectrometry analysis identify X-linked DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 (DDX3X), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
Gag-Pol gag-pol Tandem affinity purification and mass spectrometry analysis identify X-linked DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 (DDX3X), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
Nef nef Tandem affinity purification and mass spectrometry analysis identify X-linked DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 (DDX3X), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
Pr55(Gag) gag Cellular biotinylated DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked (DDX3X) protein is incorporated into HIV-1 Gag virus-like particles PubMed
gag Tandem affinity purification and mass spectrometry analysis identify X-linked DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 (DDX3X), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells PubMed
Rev rev HIV-1 Rev function is inhibited by DDX3X expression in astrocytes PubMed
rev Computational molecular docking, alanine scanning, clustering, and evolutionary analysis reveal the interaction of DDX3 with HIV-1 Rev-CRM1-RanGTP complex PubMed
rev Coexpression of HIV-1 Rev with DDX3 greatly upregulate the expression of HIV-1 CA in HeLa cells PubMed
rev DDX3 interacts with DDX1 or DDX5 and synergistically enhances the Rev function PubMed
rev DDX3 interacts with HIV-1 Rev and enhances the Rev function. DDX3 co-localizes with Rev in both nucleolus and cytoplasm PubMed
rev Translation of HIV-1 early regulatory proteins Tat and Rev is impaired in DDX3-depleted cells. The RNA helicase activity of DDX3 is required for its function in HIV-1 mRNA translation via 5'UTRs PubMed
rev As part of the HIV-1 Rev-RRE/CRM1 pathway, DDX3, an RNA-dependent ATPase/helicase, locates to nuclear pores and binds CRM1 in order to export Rev and unspliced/partially spliced HIV-1 transcripts to the cytoplasm PubMed
rev HIV-1 Rev interacting protein, DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 X-linked (DDX3X), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with DDX3X is increased by RRE PubMed
Tat tat DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked (DDX3) is identified to interact with HIV-1 Tat mutant Nullbasic in HeLa cells by LC MS/MS PubMed
tat DDX3 enhances the HIV-1 Tat-induced transcription and co-localizes with Tat in cytoplasmic foci in 293FT cells PubMed
tat Translation of HIV-1 early regulatory proteins Tat and Rev is impaired in DDX3-depleted cells. The RNA helicase activity of DDX3 is required for its function in HIV-1 mRNA translation via 5'UTRs PubMed
tat HIV-1 Tat co-localizes with DDX3 in cytoplasmic stress granules under stree conditions PubMed
tat HIV-1 Tat binds DDX3 in vitro and in vivo. The C-terminal region (residues 536-661) of DDX3 is responsible for Tat binding PubMed
capsid gag Coexpression of HIV-1 Rev with DDX3 greatly upregulate the expression of HIV-1 CA in HeLa cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Hepatitis B, organism-specific biosystem (from KEGG)
    Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Neutrophil degranulation, organism-specific biosystem (from REACTOME)
    Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
  • RIG-I-like Receptor Signaling, organism-specific biosystem (from WikiPathways)
    RIG-I-like Receptor Signaling, organism-specific biosystemViral pathogen RNA are recognized by host helicases called RIG-I-like receptors (RLRs) that include DDX58 (RIG-I), DHX58 (LGP2), IFIH1 (MDA5), SNW1, and DDX17. These RLR proteins then go on to initia...
  • RIG-I-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • RIG-I-like receptor signaling pathway, conserved biosystem (from KEGG)
    RIG-I-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting viral pathogens and generating innate immune responses. Non-self RNA appearing in a cell as a result of intracellular ...
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
ATP-dependent DNA helicase activity IDA
Inferred from Direct Assay
more info
PubMed 
ATP-dependent RNA helicase activity IDA
Inferred from Direct Assay
more info
PubMed 
ATPase activity IDA
Inferred from Direct Assay
more info
PubMed 
CTPase activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
GTPase activity IDA
Inferred from Direct Assay
more info
PubMed 
RNA binding HDA PubMed 
RNA binding IDA
Inferred from Direct Assay
more info
PubMed 
RNA stem-loop binding IDA
Inferred from Direct Assay
more info
PubMed 
RNA strand annealing activity IDA
Inferred from Direct Assay
more info
PubMed 
cadherin binding HDA PubMed 
eukaryotic initiation factor 4E binding IDA
Inferred from Direct Assay
more info
PubMed 
mRNA 5'-UTR binding IDA
Inferred from Direct Assay
more info
PubMed 
nucleoside-triphosphatase activity IDA
Inferred from Direct Assay
more info
PubMed 
poly(A) binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine kinase activator activity IDA
Inferred from Direct Assay
more info
PubMed 
ribosomal small subunit binding IDA
Inferred from Direct Assay
more info
PubMed 
transcription factor binding IDA
Inferred from Direct Assay
more info
PubMed 
translation initiation factor binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
DNA duplex unwinding IEA
Inferred from Electronic Annotation
more info
 
RNA secondary structure unwinding IDA
Inferred from Direct Assay
more info
PubMed 
Wnt signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to arsenic-containing substance IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to osmotic stress IDA
Inferred from Direct Assay
more info
PubMed 
chromosome segregation IMP
Inferred from Mutant Phenotype
more info
PubMed 
extrinsic apoptotic signaling pathway via death domain receptors IMP
Inferred from Mutant Phenotype
more info
PubMed 
innate immune response IMP
Inferred from Mutant Phenotype
more info
PubMed 
intracellular signal transduction IDA
Inferred from Direct Assay
more info
PubMed 
intrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
mature ribosome assembly IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cell growth IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of intrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of translation IMP
Inferred from Mutant Phenotype
more info
PubMed 
neutrophil degranulation TAS
Traceable Author Statement
more info
 
positive regulation of G1/S transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of canonical Wnt signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cell growth IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of chemokine (C-C motif) ligand 5 production TAS
Traceable Author Statement
more info
PubMed 
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of gene expression IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interferon-beta production TAS
Traceable Author Statement
more info
PubMed 
positive regulation of protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of translation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of translational initiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of viral genome replication IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein localization to cytoplasmic stress granule IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to virus IDA
Inferred from Direct Assay
more info
PubMed 
stress granule assembly IDA
Inferred from Direct Assay
more info
PubMed 
translational initiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IMP
Inferred from Mutant Phenotype
more info
PubMed 
cytoplasmic stress granule IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
colocalizes_with cytosolic small ribosomal subunit IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with eukaryotic translation initiation factor 3 complex IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome HDA PubMed 
extracellular region TAS
Traceable Author Statement
more info
 
ficolin-1-rich granule lumen TAS
Traceable Author Statement
more info
 
mitochondrial outer membrane IEA
Inferred from Electronic Annotation
more info
 
nuclear speck IEA
Inferred from Electronic Annotation
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
secretory granule lumen TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
ATP-dependent RNA helicase DDX3X
Names
DEAD (Asp-Glu-Ala-Asp) box helicase 3, X-linked
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, X-linked
DEAD box protein 3, X-chromosomal
DEAD box, X isoform
DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3
DEAD/H box-3
helicase-like protein 2
NP_001180345.1
NP_001180346.1
NP_001347.3
XP_011542194.1
XP_016884802.1
XP_016884803.1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012830.2 RefSeqGene

    Range
    4911..21890
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001193416.2NP_001180345.1  ATP-dependent RNA helicase DDX3X isoform 2

    See identical proteins and their annotated locations for NP_001180345.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR and uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AF061337, AU144400, BC007668, BQ921695, DA232063
    Consensus CDS
    CCDS87734.1
    UniProtKB/Swiss-Prot
    O00571
    Related
    ENSP00000495377.1, ENST00000646319.1
    Conserved Domains (2) summary
    COG0513
    Location:156573
    SrmB; Superfamily II DNA and RNA helicase [Replication, recombination and repair]
    pfam06273
    Location:85177
    eIF-4B; Plant specific eukaryotic initiation factor 4B
  2. NM_001193417.2NP_001180346.1  ATP-dependent RNA helicase DDX3X isoform 3

    See identical proteins and their annotated locations for NP_001180346.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR and lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AK304689, AU144400, BC007668, BQ921695
    Consensus CDS
    CCDS55404.1
    UniProtKB/Swiss-Prot
    O00571
    Related
    ENSP00000392494.2, ENST00000457138.7
    Conserved Domains (2) summary
    COG0513
    Location:140557
    SrmB; Superfamily II DNA and RNA helicase [Replication, recombination and repair]
    pfam06273
    Location:69161
    eIF-4B; Plant specific eukaryotic initiation factor 4B
  3. NM_001356.4NP_001347.3  ATP-dependent RNA helicase DDX3X isoform 1

    See identical proteins and their annotated locations for NP_001347.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AK291153, AU144400, BC007668, BQ921695, DA232063, DB065845
    Consensus CDS
    CCDS43931.1
    UniProtKB/Swiss-Prot
    O00571
    Related
    ENSP00000494040.1, ENST00000644876.1
    Conserved Domains (2) summary
    COG0513
    Location:156573
    SrmB; Superfamily II DNA and RNA helicase [Replication, recombination and repair]
    pfam06273
    Location:85177
    eIF-4B; Plant specific eukaryotic initiation factor 4B
  4. NM_001363819.1NP_001350748.1  ATP-dependent RNA helicase DDX3X isoform 4

    Status: REVIEWED

    Source sequence(s)
    AL391647
    Consensus CDS
    CCDS87736.1
    Conserved Domains (1) summary
    COG0513
    Location:5387
    SrmB; Superfamily II DNA and RNA helicase [Replication, recombination and repair]

RNA

  1. NR_126093.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
    Source sequence(s)
    AF000983, AK291153, BF980241, DA232063, DB065845
  2. NR_126094.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) differs in the 5' exon, lacks multiple internal exons, and uses an alternate 3' exon, compared to variant 1. This variant is represented as non-coding because the predicted protein does not meet RefSeq quality criteria.
    Source sequence(s)
    AA481139, BC055083

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p12 Primary Assembly

    Range
    41333308..41364472
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017029313.1XP_016884802.1  ATP-dependent RNA helicase DDX3X isoform X2

    Related
    ENSP00000496052.1, ENST00000642322.1
  2. XM_017029314.1XP_016884803.1  ATP-dependent RNA helicase DDX3X isoform X3

    Related
    ENSP00000494887.1, ENST00000646679.1
    Conserved Domains (1) summary
    COG0513
    Location:5387
    SrmB; Superfamily II DNA and RNA helicase [Replication, recombination and repair]
  3. XM_011543892.2XP_011542194.1  ATP-dependent RNA helicase DDX3X isoform X1

    Related
    ENSP00000494588.1, ENST00000645589.1
    Conserved Domains (2) summary
    COG0513
    Location:156573
    SrmB; Superfamily II DNA and RNA helicase [Replication, recombination and repair]
    pfam06273
    Location:85177
    eIF-4B; Plant specific eukaryotic initiation factor 4B

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_024005.1: Suppressed sequence

    Description
    NM_024005.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
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