Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000780
UniProt IDO00571
Primary gene name(s)DDX3X
Synonym gene name(s)DBX, DDX3
Protein nameATP-dependent RNA helicase DDX3X
Protein functionMultifunctional 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. {ECO:0000269|PubMed:10329544, ECO:0000269|PubMed:15507209, ECO:0000269|PubMed:16301996, ECO:0000269|PubMed:16818630, ECO:0000269|PubMed:17357160, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:18264132, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:18596238, ECO:0000269|PubMed:18628297, ECO:0000269|PubMed:18636090, ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:20127681, ECO:0000269|PubMed:20375222, ECO:0000269|PubMed:20657822, ECO:0000269|PubMed:20837705, ECO:0000269|PubMed:21170385, ECO:0000269|PubMed:21589879, ECO:0000269|PubMed:21730191, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:22034099, ECO:0000269|PubMed:22323517, ECO:0000269|PubMed:22872150, ECO:0000269|PubMed:23478265}.
Subcellular locationNucleus 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.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O00571
Gene Ontology
(Biological Process)
Complete annatation
cellular response to arsenic-containing substance [GO:0071243];
cellular response to osmotic stress [GO:0071470];
chromosome segregation [GO:0007059];
extrinsic apoptotic signaling pathway via death domain receptors [GO:0008625];
innate immune response [GO:0045087];
intracellular signal transduction [GO:0035556];
intrinsic apoptotic signaling pathway [GO:0097193];
mature ribosome assembly [GO:0042256];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cell growth [GO:0030308];
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154];
negative regulation of intrinsic apoptotic signaling pathway [GO:2001243];
negative regulation of protein complex assembly [GO:0031333];
negative regulation of translation [GO:0017148];
positive regulation of apoptotic process [GO:0043065];
positive regulation of cell growth [GO:0030307];
positive regulation of chemokine, C-C motif ligand 5 production [GO:0071651];
positive regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043280];
positive regulation of G1/S transition of mitotic cell cycle [GO:1900087];
positive regulation of gene expression [GO:0010628];
positive regulation of interferon-beta production [GO:0032728];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of translation [GO:0045727];
positive regulation of translational initiation [GO:0045948];
positive regulation of viral genome replication [GO:0045070];
protein localization to cytoplasmic stress granule [GO:1903608];
response to virus [GO:0009615];
RNA secondary structure unwinding [GO:0010501];
stress granule assembly [GO:0034063];
transcription, DNA-templated [GO:0006351];
Wnt signaling pathway [GO:0016055]
Gene Ontology
(Molecular Function)
Complete annatation
ATPase activity [GO:0016887];
ATP binding [GO:0005524];
ATP-dependent DNA helicase activity [GO:0004003];
ATP-dependent RNA helicase activity [GO:0004004];
CTPase activity [GO:0043273];
DNA binding [GO:0003677];
eukaryotic initiation factor 4E binding [GO:0008190];
GTPase activity [GO:0003924];
mRNA 5'-UTR binding [GO:0048027];
nucleoside-triphosphatase activity [GO:0017111];
poly(A binding [GO:0008143];
poly(A RNA binding [GO:0044822];
ribosomal small subunit binding [GO:0043024];
RNA binding [GO:0003723];
RNA stem-loop binding [GO:0035613];
transcription factor binding [GO:0008134];
translation initiation factor binding [GO:0031369]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytoplasmic stress granule [GO:0010494];
extracellular exosome [GO:0070062];
mitochondrial outer membrane [GO:0005741];
nuclear speck [GO:0016607];
nucleus [GO:0005634]
Protein-protein interaction108020
Phylogenetic treeO00571
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      Yes - Two siRNA pools inhibit HIV replication and inhibition of Tat-mediated transactivation of the HIV LTR is not observed
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.4478384935633530.1712151739772130.270356741978476
AZA vs. DISU0.253920356976910.3151618561220610.86838542395586
AZA vs. IL70.105428360205710.5818379791566020.999311006273513
AZA vs. SAHA-0.1132752761426260.6415904168268240.889277659511377
DISU vs. CD3-0.2069946076413440.5679206694936370.684921687490766
DISU vs. IL7-0.1573100643807360.5318921320132140.844507107403638
DISU vs. SAHA-0.3662793368544710.2082845568859130.582061293682105
DMSO vs. AZA-0.03170394929902070.8490868961892481
DMSO vs. CD3-0.491296211119980.1244376024605140.203744427895625
DMSO vs. DISU-0.2875882965049620.2381704597110630.755291315350996
DMSO vs. IL70.1444138731590170.4199014797358730.853104173397827
DMSO vs. SAHA-0.08877042704588520.7057619115181490.911755337604151
HIV vs. Mock in Activation0.1510292423706210.8084278593915070.999983755607037
HIV vs. Mock in Latency-0.02819909828272060.863586038440520.999834320637052
IL7 vs. CD3-0.3341203808350140.2976546000176340.435164673721222
SAHA vs. CD3-0.5863951447572680.09749240457051810.170485452175932
SAHA vs. IL7-0.222928613330250.3589028572251110.609519501716101
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.170527 0.24719
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.988 0.934 0.7 0.663 0.928
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
212515_s_at 1.63 No downregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2I4I X-ray 2.2Å A=168-582.
2JGN X-ray 1.9Å A/B/C=409-580.
3JRV X-ray 1.6Å C/D/E=71-90.
4O2C X-ray 1.8Å C=2-10.
4O2E X-ray 1.9Å C/F=2-10.
4O2F X-ray 1.9Å C/F=3-10.
4PX9 X-ray 2.3Å A/B/C=135-407.
4PXA X-ray 3.2Å A=135-582.
5E7I X-ray 2.2Å A/B/C=133-584.
5E7J X-ray 2.2Å A=133-584.
5E7M X-ray 2.3Å A=133-584.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Pr55(Gag) incorporates 25631074
Rev cooperates with 25496916
Gag-Pol complexes with 23125841
capsid upregulated by 25496916
Tat co-localizes with 23840900
Rev exported by 15507209
15516266
16354571
17661632
18187620
18259889
18508616
19149558
21358275
21360055
23754689
23840900
25538732
HIV-1 virus replication enhanced by expression of human gene 20018238
18976975
2169877518187620
21698775
Tat interacts with 25496916
Nef complexes with 23125841
Rev interacts with 22174317
23608157
24183723
25188302
2553873225723178
Envelope surface glycoprotein gp120 complexes with 23125841
Rev enhanced by 23608157
24183723
25538732
Tat enhanced by 24183723
Rev regulated by 23840900
24183723
25188302
25538732
Pr55(Gag) complexes with 23125841
Tat binds 23840900
Tat regulated by 23840900
24330569

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04622 RIG-I-like receptor signaling pathway - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
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