Host Protein General Information (ID: PT0789)
  Protein Name
ATP-dependent RNA helicase DDX5 (DDX5)
  Gene Name
DDX5
  Host Species
Homo sapiens
  Uniprot Entry Name
DDX5_HUMAN
  Protein Families
DEAD box helicase family
  EC Number
3.6.4.13
  Subcellular Location
Nucleus; nucleolus Cytoplasm
  External Link
NCBI Gene ID
1655
Uniprot ID
P17844
Ensembl ID
ENSG00000108654
HGNC ID
HGNC:2746
  Function in Host
Involved in the alternative regulation of pre-mRNA splicing;its RNA helicase activity is necessary for increasing tau exon 10inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATPhydrolysis is highly stimulated by single-stranded RNA. Involved intranscriptional regulation; the function is independent of the RNAhelicase activity. Transcriptional coactivator for androgen receptor ARbut probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activateMYOD1 transcriptional activity and involved in skeletal muscledifferentiation. Transcriptional coactivator for p53/TP53 and involvedin p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involvedin regulation of osteoblast differentiation. Acts as transcriptionalrepressor in a promoter-specific manner; the function probably involvesassociation with histone deacetylases, such as HDAC1. As component of alarge PER complex is involved in the inhibition of 3' transcriptionaltermination of circadian target genes such as PER1 and NR1D1 and thecontrol of the circadian rhythms. [1-8]
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  Related KEGG Pathway
Spliceosome hsa03040            Pathway Map 
Transcriptional misregulation in cancer hsa05202            Pathway Map 
Proteoglycans in cancer hsa05205            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [9]
Infected TissueLung Infection Time24 h
Infected CellA549 Cells (Adenocarcinomic Human alveolar basal epithelial cells) Cellosaurus IDCVCL_H249 
Method DescriptionTo detect the role of host protein DDX5 in viral infection, DDX5 protein knockout A549 Cells were infected with SARS-COV-2 for 24 h , and the effects on infection was detected through qRT-PCR.
ResultsIt is reported that Knockdown of DDX5 leads to the reduced viral particles production 50% 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 [10]
              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 = 0.984615832
              Method Description comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)
           RNA Region: 5'-UTR (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [11]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
5'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Infection Cells Huh7 cells (human liver cell line); Calu-3 cells (human lung cancer cell line) Huh7 cells (human liver cell line); Calu-3 cells (human lung cancer cell line)  (CVCL_0336;CVCL_0609 )
              Cell Originated Tissue Liver; Lung
              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 [12]
              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/France/IDF-220-95/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              Strains Name
hCoV-19/France/IDF-220-95/2020
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Direct interaction
              Infection Cells HEK293 Cells (Human embryonic kidney cell) HEK293 Cells (Human embryonic kidney cell)  (CVCL_0045 )
              Cell Originated Tissue Kidney
              Infection Time 48 h
              Interaction Score SAINT score ≥ 0.79
              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 [13]
              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 = 0.070
              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
S480 [14]
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S483 [14]
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S498 [15]
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S6 [15]
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Protein Sequence Information
MSGYSSDRDRGRDRGFGAPRFGGSRAGPLSGKKFGNPGEKLVKKKWNLDELPKFEKNFYQEHPDLARRTAQEVETYRRSKEITVRGHNCPKPVLNFYEANFPANVMDVIARQNFTEPTAIQAQGWPVALSGLDMVGVAQTGSGKTLSYLLPAIVHINHQPFLERGDGPICLVLAPTRELAQQVQQVAAEYCRACRLKSTCIYGGAPKGPQIRDLERGVEICIATPGRLIDFLECGKTNLRRTTYLVLDEADRMLDMGFEPQIRKIVDQIRPDRQTLMWSATWPKEVRQLAEDFLKDYIHINIGALELSANHNILQIVDVCHDVEKDEKLIRLMEEIMSEKENKTIVFVETKRRCDELTRKMRRDGWPAMGIHGDKSQQERDWVLNEFKHGKAPILIATDVASRGLDVEDVKFVINYDYPNSSEDYIHRIGRTARSTKTGTAYTFFTPNNIKQVSDLISVLREANQAINPKLLQLVEDRGSGRSRGRGGMKDDRRDRYSAGKRGGFNTFRDRENYDRGYSSLLKRDFGAKTQNGVYSAANYTNGSFGSNFVSAGIQTSFRTGNPTGTYQNGYDSTQQYGSNVPNMHNGMNQQAYAYPATAAAPMIGYPMPTGYSQ
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References
1 RNA helicase p68 (DDX5) regulates tau exon 10 splicing by modulating a stem-loop structure at the 5 splice site. Mol Cell Biol. 2011 May;31(9):1812-21.
2 The DEAD-box protein p72 regulates ERalpha-/oestrogen-dependent transcription and cell growth, and is associated with improved survival in ERalpha-positive breast cancer. Oncogene. 2009 Nov 19;28(46):4053-64.
3 The RNA helicase p68 is a novel androgen receptor coactivator involved in splicing and is overexpressed in prostate cancer. Cancer Res. 2008 Oct 1;68(19):7938-46.
4 p68 (Ddx5) interacts with Runx2 and regulates osteoblast differentiation. J Cell Biochem. 2008 Apr 1;103(5):1438-51.
5 The RNA helicases p68/p72 and the noncoding RNA SRA are coregulators of MyoD and skeletal muscle differentiation. Dev Cell. 2006 Oct;11(4):547-60.
6 The DEAD box protein p68: a novel transcriptional coactivator of the p53 tumour suppressor. EMBO J. 2005 Feb 9;24(3):543-53.
7 The p68 and p72 DEAD box RNA helicases interact with HDAC1 and repress transcription in a promoter-specific manner. BMC Mol Biol. 2004 Aug 6;5:11.
8 Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300. Oncogene. 2003 Jan 9;22(1):151-6.
9 Characterization and functional interrogation of the SARS-CoV-2 RNA interactome. Cell Rep. 2022 Apr 26;39(4):110744.
10 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.
11 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
12 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
13 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.
14 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
15 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.