DDX3X - ATP-dependent RNA helicase DDX3X - human protein (Function)
 
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DDX3X »  ATP-dependent RNA helicase DDX3X   [ EC 3.6.4.13 ]
 
Protein also known as:  DEAD box protein 3, X-chromosomal.
Gene name:  DDX3X
Family name: DEAD box helicase » DDX3/DED1
Entry whose protein(s) existence is based on evidence at protein level
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1 94 2
GENE REF ISO

Function

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Overview 
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. Appears to be a prime target for viral manipulations. Hepatitis B virus (HBV) polymerase and possibly vaccinia virus (VACV) protein K7 inhibit IFNB 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 INFB 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.  
24
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
ATP-dependent DNA helicase activitydefinition[GO:0004003]  
1
  • IDAUniProtKB
ATP-dependent RNA helicase activitydefinition[GO:0004004]  
1
  • IDAUniProtKB
ATPase activitydefinition[GO:0016887]  
1
  • IDAUniProtKB
DNA bindingdefinition[GO:0003677]  
1
  • IDAUniProtKB
Eukaryotic initiation factor 4E bindingdefinition[GO:0008190]  
1
  • IDAUniProtKB
mRNA 5'-UTR bindingdefinition[GO:0048027]  
1
  • IDAUniProtKB
Poly(A) bindingdefinition[GO:0008143]  
1
  • IDAUniProtKB
Poly(A) RNA bindingdefinition[GO:0044822]  
2
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
11
  • IPIIntAct
Ribosomal small subunit bindingdefinition[GO:0043024]  
1
  • IDAUniProtKB
RNA bindingdefinition[GO:0003723]  
1
  • IDAUniProtKB
RNA stem-loop bindingdefinition[GO:0035613]  
1
  • IDAUniProtKB
Transcription factor bindingdefinition[GO:0008134]  
1
  • IDAUniProtKB
Translation initiation factor bindingdefinition[GO:0031369]  
2
  • IDAUniProtKB
GO biological process 
ATP catabolic processdefinition[GO:0006200]  
2
  • IDAGOC
  • IEAInterPro 2 GO
Cellular response to arsenic-containing substancedefinition[GO:0071243]  
1
  • IDAUniProtKB
Cellular response to osmotic stressdefinition[GO:0071470]  
1
  • IDAUniProtKB
Chromosome segregationdefinition[GO:0007059]  
1
  • IMPUniProtKB
DNA duplex unwindingdefinition[GO:0032508]  
1
  • IDAGOC
Extrinsic apoptotic signaling pathway via death domain receptorsdefinition[GO:0008625]  
1
  • IMPUniProtKB
Innate immune responsedefinition[GO:0045087]  
1
  • IMPUniProtKB
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAUniProtKB
Intrinsic apoptotic signaling pathwaydefinition[GO:0097193]  
1
  • IMPUniProtKB
Mature ribosome assemblydefinition[GO:0042256]  
1
  • IMPUniProtKB
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
Negative regulation of cell growthdefinition[GO:0030308]  
1
  • IDAUniProtKB
Negative regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043154]  
1
  • IMPUniProtKB
Negative regulation of intrinsic apoptotic signaling pathwaydefinition[GO:2001243]  
1
  • IMPUniProtKB
Negative regulation of protein complex assemblydefinition[GO:0031333]  
1
  • IDAUniProtKB
Negative regulation of translationdefinition[GO:0017148]  
1
  • IMPUniProtKB
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • IMPUniProtKB
Positive regulation of cell growthdefinition[GO:0030307]  
2
  • IMPUniProtKB
Positive regulation of chemokine (C-C motif) ligand 5 productiondefinition[GO:0071651]  
1
  • TASUniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0043280]  
1
  • IMPUniProtKB
Positive regulation of G1/S transition of mitotic cell cycledefinition[GO:1900087]  
1
  • IMPUniProtKB
Positive regulation of interferon-beta productiondefinition[GO:0032728]  
2
  • TASUniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
3
  • IDAUniProtKB
Positive regulation of translationdefinition[GO:0045727]  
2
  • IDAUniProtKB
Positive regulation of translational initiationdefinition[GO:0045948]  
1
  • IMPUniProtKB
Response to virusdefinition[GO:0009615]  
1
  • IDAUniProtKB
RNA secondary structure unwindingdefinition[GO:0010501]  
1
  • IDAUniProtKB
Stress granule assemblydefinition[GO:0034063]  
1
  • IDAUniProtKB
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 3.6.4.13: ATP + H(2)O ADP + phosphate.  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathway:
RIG-I-like receptor signaling pathway  hsa04622+1654  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Chromosome partition  definition   [KW-0159]
Host-virus interaction  definition   [KW-0945]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Ribosome biogenesis  definition   [KW-0690]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Translation regulation  definition   [KW-0810]
Molecular function 
Helicase  definition   [KW-0347]
Hydrolase  definition   [KW-0378]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: DDX3X
GenomeRNAi: 1654
PRO: PR:O00571