Protein Information (annotations from UniProt)
| Database ID | HIV0000927 |
| UniProt ID | P38919 |
| Primary gene name(s) | EIF4A3 |
| Synonym gene name(s) | DDX48, KIAA0111 |
| Protein name | Eukaryotic initiation factor 4A-III |
| Protein function | ATP-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 location | Nucleus. 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 code | Click here for more information. |
| Amino acid sequence FASTA format: P38919 |
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| 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 interaction | 115119 |
| Phylogenetic tree | P38919 |
| HIV replication factor status |
Zhou et al., Cell. Host. Microbe., 2008 unknown 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 |
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| Experimental Condition | Log2 Fold Change | P value | Adjusted P value |
| AZA vs. CD3 | 1.69793148256451 | 4.44238094088334e-07 | 3.72389129816428e-06 |
| AZA vs. DISU | 0.115535153565992 | 0.648177754790345 | 0.960057478314726 |
| AZA vs. IL7 | 0.324562106156678 | 0.0924707522721963 | 0.818925763219045 |
| AZA vs. SAHA | -0.169467067724841 | 0.488319886402407 | 0.813492456184085 |
| DISU vs. CD3 | -1.59504028318357 | 1.7250837923255e-05 | 0.000120500060637232 |
| DISU vs. IL7 | 0.199489033279709 | 0.428723891046501 | 0.783677397837234 |
| DISU vs. SAHA | -0.282719405885105 | 0.332681727548208 | 0.712082843608644 |
| DMSO vs. AZA | 0.0469304365405806 | 0.780347303951119 | 1 |
| DMSO vs. CD3 | -1.66317313091479 | 4.00746588469225e-07 | 3.09126848709108e-06 |
| DMSO vs. DISU | -0.0706970711658802 | 0.772172111088963 | 0.97150326349898 |
| DMSO vs. IL7 | 0.284978976431364 | 0.114085182747395 | 0.601912495801813 |
| DMSO vs. SAHA | -0.221928107694633 | 0.347763920796072 | 0.698763718489224 |
| HIV vs. Mock in Activation | 0.0313176582607998 | 0.959840222629511 | 0.999983755607037 |
| HIV vs. Mock in Latency | -0.00315849698695781 | 0.984803758370512 | 0.999834320637052 |
| IL7 vs. CD3 | -1.36708618230151 | 2.91740432988297e-05 | 0.000198707796946796 |
| SAHA vs. CD3 | -1.89128816968724 | 2.15900753164355e-07 | 2.0697355917219e-06 |
| SAHA vs. IL7 | -0.496264755235513 | 0.0424089379113463 | 0.164168549069243 |
| (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 |
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| 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 |
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| 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) |
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| Log2 Fold Change | unknown | ||||
| (3). Li et al., J. Immunol., 2013 Lymphatic tissue |
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| 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 |
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| 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 |
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| 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) |
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| 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 |
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| 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 |
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| 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 |
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| Affymetrix Prob ID | Fold Change | In CD8? | Category | |||
| unknown | unknown | unknown | unknown | |||
