Host Protein General Information (ID: PT1079)
  Protein Name
Spliceosome RNA helicase DDX39B (EXOSC6)
  Gene Name
DDX39B
  Host Species
Homo sapiens
  Uniprot Entry Name
DX39B_HUMAN
  Protein Families
DEAD box helicase family
  EC Number
3.6.4.13
  Subcellular Location
Nucleus
  External Link
NCBI Gene ID
7919
Uniprot ID
Q13838
Ensembl ID
ENSG00000223496
HGNC ID
HGNC:13917
  Function in Host
Involved in nuclear export of spliced and unspliced mRNA. Assembling component of the TREX complex which is thought to couplemRNA transcription, processing and nuclear export, and specificallyassociates with spliced mRNA and not with unspliced pre-mRNA. TREX isrecruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and isrecruited in a splicing- and cap-dependent manner to a region near the5' end of the mRNA where it functions in mRNA export to the cytoplasmvia the TAP/NFX1 pathway. May undergo several rounds of ATP hydrolysisduring assembly of TREX to drive subsequent loading of components suchas ALYREF/THOC and CHTOP onto mRNA. Also associates with pre-mRNAindependent of ALYREF/THOC4 and the THO complex. Involved in thenuclear export of intronless mRNA; the ATP-bound form is proposed torecruit export adapter ALYREF/THOC4 to intronless mRNA; its ATPaseactivity is cooperatively stimulated by RNA and ALYREF/THOC4 and ATPhydrolysis is thought to trigger the dissociation from RNA to allow theassociation of ALYREF/THOC4 and the NXF1-NXT1 heterodimer. Involved intranscription elongation and genome stability.
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  Related KEGG Pathway
Nucleocytoplasmic transport hsa03013            Pathway Map 
mRNA surveillance pathway hsa03015            Pathway Map 
Spliceosome hsa03040            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [1]
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 DDX39B in viral infection, DDX39B protein Knockdown 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 DDX39 B increases SARS-CoV-2 RNA levels compared with control group.

Host Protein - Virus RNA Network

 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 [2]
              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 = 0.880120976
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)
           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 [3]
              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 [4]
              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 = 0.010
              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
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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
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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
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Protein Phosphorylation after Virus Infection
T172 [5]
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T172 [6]
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Potential Drug(s) that Targets This Protein
Drug Name DrunkBank ID Pubchem ID TTD ID REF
METHOTREXATE DB00563  126941  D0SV8E  [7], [8]
Pelitrexol DB12757  135431074  D0J9IH  [7]
Pralatrexate DB06813  148121  D02LWU  [7], [9]

Protein Sequence Information
MAENDVDNELLDYEDDEVETAAGGDGAEAPAKKDVKGSYVSIHSSGFRDFLLKPELLRAIVDCGFEHPSEVQHECIPQAILGMDVLCQAKSGMGKTAVFVLATLQQLEPVTGQVSVLVMCHTRELAFQISKEYERFSKYMPNVKVAVFFGGLSIKKDEEVLKKNCPHIVVGTPGRILALARNKSLNLKHIKHFILDECDKMLEQLDMRRDVQEIFRMTPHEKQVMMFSATLSKEIRPVCRKFMQDPMEIFVDDETKLTLHGLQQYYVKLKDNEKNRKLFDLLDVLEFNQVVIFVKSVQRCIALAQLLVEQNFPAIAIHRGMPQEERLSRYQQFKDFQRRILVATNLFGRGMDIERVNIAFNYDMPEDSDTYLHRVARAGRFGTKGLAITFVSDENDAKILNDVQDRFEVNISELPDEIDISSYIEQTR
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References
1 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.
2 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.
3 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
4 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.
5 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
6 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.
7 SARS-CoV-2-host proteome interactions for antiviral drug discovery. Mol Syst Biol. 2021 Nov;17(11):e10396.
8 Methotrexate inhibits SARS-CoV-2 virus replication "in vitro". J Med Virol. 2021 Mar;93(3):1780-1785.
9 A novel virtual screening procedure identifies Pralatrexate as inhibitor of SARS-CoV-2 RdRp and it reduces viral replication in vitro. PLoS Comput Biol. 2020 Dec 31;16(12):e1008489.