Details of Host Protein

 Host Protein General Information (ID: PT0396)
  Protein Name
Eukaryotic initiation factor 4A-I (EIF4A1)
  Gene Name
EIF4A1
  Host Species
Homo sapiens
  Uniprot Entry Name
IF4A1_HUMAN
  Protein Families
DEAD box helicase family
  EC Number
3.6.4.13
  External Link
NCBI Gene ID
1973
Uniprot ID
P60842
Ensembl ID
ENSG00000161960
HGNC ID
HGNC:3282
  Function in Host
ATP-dependent RNA helicase which is a subunit of the eIF4Fcomplex involved in cap recognition and is required for mRNA binding toribosome. In the current model of translation initiation, eIF4A unwindsRNA secondary structures in the 5'-UTR of mRNAs which is necessary toallow efficient binding of the small ribosomal subunit, and subsequentscanning for the initiator codon. [1-2]
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  3D Structure
PDB ID: 2G9N 
FASTA   Download
  2D PNG Download  
PDB File Download

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [3]
Infected TissueColon Infection Time48 h
Infected CellCaco-2 cells (Human colorectal adenocarcinoma cell) Cellosaurus IDCVCL_0025 
Method DescriptionTo detect the role of host protein EIF4A1 in viral infection, EIF4A1 protein knockout Caco-2 cells were infected with SARS-COV-2 for 48 h , and the effects on infection was detected through qPCR.
ResultsIt is reported that Knockdown of EIF4A1 leads to the reduced the vRNA levels compared with control group.

Host Protein - Virus RNA Network
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 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 [3]
              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 = 0.795034047
              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 [4]
              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 [5]
              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: cap- and poly(A) (hCoV-19/England/02/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/England/02/2020
              Strains Family
Beta (B.1.351)
              RNA Binding Region
cap- and poly(A)
              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  
Picture Not Found

Potential Drug(s) that Targets This Protein
Drug Name DrunkBank ID Pubchem ID TTD ID REF
Silvestrol DB12014  . D0V12HJ  [7]
Triparanol . 11787114  D0B5SC  [3]

Protein Sequence Information
MSASQDSRSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLRGIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTATFAISILQQIELDLKATQALVLAPTRELAQQIQKVVMALGDYMGASCHACIGGTNVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFVLDEADEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLEVTKKFMRDPIRILVKKEELTLEGIRQFYINVEREEWKLDTLCDLYETLTITQAVIFINTRRKVDWLTEKMHARDFTVSAMHGDMDQKERDVIMREFRSGSSRVLITTDLLARGIDVQQVSLVINYDLPTNRENYIHRIGRGGRFGRKGVAINMVTEEDKRTLRDIETFYNTSIEEMPLNVADLI
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References
1 Crystal structure of the eIF4A-PDCD4 complex. Proc Natl Acad Sci USA. 2009 Mar 3;106(9):3148-53.
2 Structural basis for translational inhibition by the tumour suppressor Pdcd4. EMBO J. 2009 Feb 4;28(3):274-85.
3 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.
4 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
5 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
6 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.
7 Brief review on repurposed drugs and vaccines for possible treatment of COVID-19. Eur J Pharmacol. 2021 May 5;898:173977.