Details of Host Protein

 Host Protein General Information (ID: PT0398)
  Protein Name
Eukaryotic initiation factor 4A-III (EIF4A3)
  Gene Name
EIF4A3
  Host Species
Homo sapiens
  Uniprot Entry Name
IF4A3_HUMAN
  Protein Families
DEAD box helicase family
  EC Number
3.6.4.13
  Subcellular Location
Nucleus speckle Cytoplasm
  External Link
NCBI Gene ID
9775
Uniprot ID
P38919
Ensembl ID
ENSG00000141543
HGNC ID
HGNC:18683
  Function in Host
ATP-dependent RNA helicase. Involved inpre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junctioncomplex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structureconsisting of core proteins and several peripheral nuclear andcytoplasmic associated factors that join the complex only transientlyeither during EJC assembly or during subsequent mRNA metabolism. TheEJC marks the position of the exon-exon junction in the mature mRNA forthe gene expression machinery and the core components remain bound tospliced mRNAs throughout all stages of mRNA metabolism therebyinfluencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicaseactivities are induced by CASC3, but abolished in presence of theMAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core ontospliced mRNA in a stable conformation. The inhibition of ATPaseactivity by the MAGOH-RBM8A heterodimer increases the RNA-bindingaffinity of the EJC. Involved in translational enhancement of splicedmRNAs after formation of the 80S ribosome complex. Binds spliced mRNAin sequence-independent manner, 20-24 nucleotides upstream of mRNAexon-exon junctions. Shows higher affinity for single-stranded RNA inan ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably otherapoptotic genes); specifically inhibits formation of proapoptoticisoforms such as Bcl-X (S); the function is different from theestablished EJC assembly. Involved in craniofacialdevelopment. [1-12]
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  Related KEGG Pathway
Nucleocytoplasmic transport hsa03013            Pathway Map 
mRNA surveillance pathway hsa03015            Pathway Map 
Spliceosome hsa03040            Pathway Map 
  3D Structure
PDB ID: 2HXY 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [13]
Infected TissueLung Infection Time7-9 Days
Infected CellCalu-3 Cells (Human epithelial cell line) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein EIF4A3 in viral infection, EIF4A3 protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
ResultsIt is reported that knockout of EIF4A3 leads to the decreased SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network
  Network Download  

 Full List of Virus RNA Interacting with This Protien
            RNA Region: 3'-UTR (hCoV-19/IPBCAMS-YL01/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [14]
              Strains Name
hCoV-19/IPBCAMS-YL01/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
3'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potiential to be direct binder
              Interaction Binding Type double stranded RNA binding
              Infection Cells Huh7.5.1 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_E049 )
              Cell Originated Tissue Liver
              Infection Time 30 h
              Interaction Score MIST = 0.685512714
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)
           RNA Region: ORF10 (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [15]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
ORF10
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7 cells (human liver cell line) Huh7 cells (human liver cell line)  (CVCL_0336 )
              Cell Originated Tissue Liver
              Interaction Score P-value < 0.05
              Method Description RNA pull-down assays; liquid chromatography with tandem mass spectrometry (LC-MS/MS); Wilcoxon test; MS2 affinity purification coupled with liquid chromatography-mass spectrometry (MAMS)
           RNA Region: Not Specified Virus Region (hCoV-19/USA/WA1/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [16]
              Strains Name
hCoV-19/USA/WA1/2020
              Strains Family
Alpha (B.1.1.7)
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7.5 cells (Hepatocyte derived cellular carcinoma cell) Huh7.5 cells (Hepatocyte derived cellular carcinoma cell)  (CVCL_7927 )
              Cell Originated Tissue Liver
              Infection Time 48 h
              Interaction Score FDR ≤ 0.05
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)
           RNA Region: Not Specified Virus Region (hCoV-19/England/02/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [17]
              Strains Name
hCoV-19/England/02/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Calu-3 cells (Human lung cancer cell) Calu-3 cells (Human lung cancer cell)  (CVCL_0609 )
              Cell Originated Tissue Lung
              Infection Time 24 h
              Interaction Score P-adjust = 0.008
              Method Description UV protein-RNA crosslinking; RNA interactome capture (cRIC); RNA antisense purification coupled with mass spectrometry (RAP-MS)

Differential Gene Expression During SARS-COV-2 Infection
GEO Accession: GSE152641
Sample Type: Blood
Samples Details: Healthy Control: 24; COVID-19: 62
Platform: GPL24676 Illumina NovaSeq 6000
  PNG Download  
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GEO Accession: GSE162835
Sample Type: Nasopharyngeal Swabs
Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3
Platform: GPL24676 Illumina NovaSeq 6000
  PNG Download  
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GEO Accession: GSE175779
Sample Type: Human Bronchial Epithelial Cells
Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)
Platform: GPL18573 Illumina NextSeq 500
  PNG Download  
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Protein Phosphorylation after Virus Infection
S10 [18]
  PNG Download  
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S12 [18]
  PNG Download  
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T163 [18]
  PNG Download  
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Protein Sequence Information
MATTATMATSGSARKRLLKEEDMTKVEFETSEEVDVTPTFDTMGLREDLLRGIYAYGFEKPSAIQQRAIKQIIKGRDVIAQSQSGTGKTATFSISVLQCLDIQVRETQALILAPTRELAVQIQKGLLALGDYMNVQCHACIGGTNVGEDIRKLDYGQHVVAGTPGRVFDMIRRRSLRTRAIKMLVLDEADEMLNKGFKEQIYDVYRYLPPATQVVLISATLPHEILEMTNKFMTDPIRILVKRDELTLEGIKQFFVAVEREEWKFDTLCDLYDTLTITQAVIFCNTKRKVDWLTEKMREANFTVSSMHGDMPQKERESIMKEFRSGASRVLISTDVWARGLDVPQVSLIINYDLPNNRELYIHRIGRSGRYGRKGVAINFVKNDDIRILRDIEQYYSTQIDEMPMNVADLI
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References
1 Structure of a human catalytic step I spliceosome. Science. 2018 Feb 2;359(6375):537-545.
2 An Atomic Structure of the Human Spliceosome. Cell. 2017 May 18;169(5):918-929.e14.
3 Cryo-EM structure of a human spliceosome activated for step 2 of splicing. Nature. 2017 Feb 16;542(7641):318-323.
4 Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. Nat Struct Mol Biol. 2012 Oct;19(10):983-90.
5 Insights into the recruitment of the NMD machinery from the crystal structure of a core EJC-UPF3b complex. Proc Natl Acad Sci USA. 2010 Jun 1;107(22):10050-5.
6 Mechanism of ATP turnover inhibition in the EJC. RNA. 2009 Jan;15(1):67-75.
7 Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA. Science. 2006 Sep 29;313(5795):1968-72.
8 The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA. Cell. 2006 Aug 25;126(4):713-25.
9 The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nat Struct Mol Biol. 2005 Oct;12(10):861-9.
10 Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Mol Cell. 2005 Oct 7;20(1):65-75.
11 Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core. RNA. 2005 Dec;11(12):1869-83.
12 Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. RNA. 2002 Apr;8(4):426-39.
13 Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
14 Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2. Cell Res. 2022 Jan;32(1):9-23.
15 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
16 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
17 Global analysis of protein-RNA interactions in SARS-CoV-2-infected cells reveals key regulators of infection. Mol Cell. 2021 Jul 1;81(13):2851-2867.e7.
18 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.