Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000927
UniProt IDP38919
Primary gene name(s)EIF4A3
Synonym gene name(s)DDX48, KIAA0111
Protein nameEukaryotic initiation factor 4A-III
Protein functionATP-dependent RNA helicase. Core component of the splicing-dependent multiprotein exon junction complex, EJC deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay, NMD. Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X, and probably other apoptotic genes; specifically inhibits formation of proapoptotic isoforms such as Bcl-X(S; the function is different from the established EJC assembly. Involved in craniofacial development. {ECO:0000269|PubMed:15034551, ECO:0000269|PubMed:16170325, ECO:0000269|PubMed:16209946, ECO:0000269|PubMed:17375189, ECO:0000269|PubMed:19409878, ECO:0000269|PubMed:22203037, ECO:0000269|PubMed:24360810}.
Subcellular locationNucleus. Nucleus speckle. Cytoplasm. Note=Nucleocytoplasmic shuttling protein. Travels to the cytoplasm as part of the exon junction complex, EJC bound to mRNA. Detected in dendritic layer as well as the nuclear and cytoplasmic, somatic compartments of neurons. Colocalizes with STAU1 and FMR1 in dendrites, By similarity. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P38919
Gene Ontology
(Biological Process)
Complete annatation
associative learning [GO:0008306];
cellular response to brain-derived neurotrophic factor stimulus [GO:1990416];
cellular response to selenite ion [GO:0072715];
embryonic cranial skeleton morphogenesis [GO:0048701];
exploration behavior [GO:0035640];
mRNA 3'-end processing [GO:0031124];
mRNA export from nucleus [GO:0006406];
mRNA splicing, via spliceosome [GO:0000398];
negative regulation of excitatory postsynaptic potential [GO:0090394];
negative regulation of selenocysteine incorporation [GO:1904570];
negative regulation of selenocysteine insertion sequence binding [GO:1904574];
negative regulation of translation [GO:0017148];
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay [GO:0000184];
nuclear-transcribed mRNA poly(A tail shortening [GO:0000289];
positive regulation of mRNA splicing, via spliceosome [GO:0048026];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of translation [GO:0045727];
response to organic cyclic compound [GO:0014070];
RNA export from nucleus [GO:0006405];
RNA secondary structure unwinding [GO:0010501];
RNA splicing [GO:0008380];
rRNA processing [GO:0006364];
selenocysteine metabolic process [GO:0016259];
termination of RNA polymerase II transcription [GO:0006369]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
ATP-dependent RNA helicase activity [GO:0004004];
mRNA binding [GO:0003729];
poly(A binding [GO:0008143];
poly(A RNA binding [GO:0044822];
ribonucleoprotein complex binding [GO:0043021];
RNA stem-loop binding [GO:0035613];
selenocysteine insertion sequence binding [GO:0035368]
Gene Ontology
(Cellular Component)
Complete annatation
catalytic step 2 spliceosome [GO:0071013];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
dendrite [GO:0030425];
exon-exon junction complex [GO:0035145];
membrane [GO:0016020];
neuronal cell body [GO:0043025];
nuclear speck [GO:0016607];
nucleoplasm [GO:0005654]
Protein-protein interaction115119
Phylogenetic treeP38919
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
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. CD31.697931482564514.44238094088334e-073.72389129816428e-06
AZA vs. DISU0.1155351535659920.6481777547903450.960057478314726
AZA vs. IL70.3245621061566780.09247075227219630.818925763219045
AZA vs. SAHA-0.1694670677248410.4883198864024070.813492456184085
DISU vs. CD3-1.595040283183571.7250837923255e-050.000120500060637232
DISU vs. IL70.1994890332797090.4287238910465010.783677397837234
DISU vs. SAHA-0.2827194058851050.3326817275482080.712082843608644
DMSO vs. AZA0.04693043654058060.7803473039511191
DMSO vs. CD3-1.663173130914794.00746588469225e-073.09126848709108e-06
DMSO vs. DISU-0.07069707116588020.7721721110889630.97150326349898
DMSO vs. IL70.2849789764313640.1140851827473950.601912495801813
DMSO vs. SAHA-0.2219281076946330.3477639207960720.698763718489224
HIV vs. Mock in Activation0.03131765826079980.9598402226295110.999983755607037
HIV vs. Mock in Latency-0.003158496986957810.9848037583705120.999834320637052
IL7 vs. CD3-1.367086182301512.91740432988297e-050.000198707796946796
SAHA vs. CD3-1.891288169687242.15900753164355e-072.0697355917219e-06
SAHA vs. IL7-0.4962647552355130.04240893791134630.164168549069243
(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 0.455048 0.000305467
(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
1.037 1.005 0.932 0.818 0.916
(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
unknown unknown unknown unknown

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
2HXY X-ray 3.3Å A/B/C/D=23-411.
2HYI X-ray 2.3Å C/I=1-411.
2J0Q X-ray 3.2Å A/B=2-411.
2J0S X-ray 2.2Å A=2-411.
2J0U X-ray 3.0Å A/B=38-411.
2XB2 X-ray 3.4Å A/X=1-411.
3EX7 X-ray 2.3Å C/H=1-411.
4C9B X-ray 2.0Å A=1-411.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 complexes with 23125841
Gag-Pol complexes with 23125841
Pr55(Gag) complexes with 23125841
Nef complexes with 23125841

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03013 RNA transport - Homo sapiens (human)
hsa03015 mRNA surveillance pathway - Homo sapiens (human)
hsa03040 Spliceosome - Homo sapiens (human)