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Identification
HMDB Protein ID HMDBP11672
Secondary Accession Numbers None
Name ATP-dependent RNA helicase DDX3X
Synonyms
  1. DEAD box protein 3, X-chromosomal
  2. DEAD box, X isoform
  3. Helicase-like protein 2
  4. HLP2
Gene Name DDX3X
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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.
Pathways
  • Hepatitis B
  • RIG-I-like receptor signaling pathway
  • Viral carcinogenesis
Reactions
Adenosine triphosphate + Water → ADP + Phosphate details
GO Classification
Biological Process
positive regulation of apoptotic process
cellular response to arsenic-containing substance
negative regulation of apoptotic process
cellular response to osmotic stress
chromosome segregation
extrinsic apoptotic signaling pathway via death domain receptors
intracellular protein kinase cascade
intrinsic apoptotic signaling pathway
response to virus
mature ribosome assembly
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process
negative regulation of intrinsic apoptotic signaling pathway
negative regulation of protein complex assembly
negative regulation of translation
positive regulation of chemokine (C-C motif) ligand 5 production
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process
positive regulation of G1/S transition of mitotic cell cycle
positive regulation of interferon-beta production
positive regulation of translational initiation
RNA secondary structure unwinding
stress granule assembly
innate immune response
virus-host interaction
positive regulation of transcription from RNA polymerase II promoter
positive regulation of cell growth
negative regulation of cell growth
transcription, DNA-dependent
Cellular Component
nucleus
cytoplasmic stress granule
nuclear speck
mitochondrial outer membrane
Molecular Function
ATP-dependent RNA helicase activity
poly(A) RNA binding
ATP binding
eukaryotic initiation factor 4E binding
ribosomal small subunit binding
RNA stem-loop binding
transcription factor binding
mRNA 5'-UTR binding
ATP-dependent DNA helicase activity
DNA binding
Cellular Location Not Available
Gene Properties
Chromosome Location X
Locus Xp11.3-p11.23
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues Not Available
Molecular Weight 71354.575
Theoretical pI 6.618
Pfam Domain Function Not Available
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>>gi|301171475|ref|NP_001180346.1| ATP-dependent RNA helicase DDX3X isoform 3 [Homo sapiens]
MSHVAVENALGLDQQFAGLDLNSSDNQSGGSTASSFYDKDSSGWSSSKDKDAYSSFGSRS
DSRGKSSFFS
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O00571
UniProtKB/Swiss-Prot Entry Name Not Available
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID HGNC:2745
References
General References Not Available