Details of Host Protein

 Host Protein General Information (ID: PT0042)
  Protein Name
YTH domain-containing protein 2 (hYTHDC2)
  Gene Name
YTHDC2
  Host Species
Homo sapiens
  Uniprot Entry Name
YTDC2_HUMAN
  Protein Families
DEAD box helicase family
  EC Number
3.6.4.13
  Subcellular Location
Cytoplasm; Perinuclear region
  External Link
NCBI Gene ID
64848
Uniprot ID
Q9H6S0
Ensembl ID
ENSG00000047188
HGNC ID
HGNC:24721
  Function in Host
3'-5' RNA helicase that plays a key role in the male andfemale germline by promoting transition from mitotic to meioticdivisions in stem cells. Specifically recognizes and binds N6-methyladenosine (m6A) -containing RNAs, a modification present at internal sites ofmRNAs and some non-coding RNAs that plays a role in the efficiency ofRNA processing and stability. Essential for ensuring a successful progression of the meiotic programin the germline by regulating the level of m6A-containing RNAs. Acts by binding and promoting degradation of m6A-containing mRNAs: the 3'-5' RNA helicase activity is required for thisprocess and RNA degradation may be mediated by XRN1 exoribonuclease. Required for both spermatogenesis and oogenesis. [1-3]
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  3D Structure
PDB ID: 2YU6 
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  2D PNG Download  
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Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [4]
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 YTHDC2 in viral infection, YTHDC2 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 YTHDC2 increases SARS-CoV-2 RNA 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/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [5]
              Strains Name
hCoV-19/Not Specified Virus Strain
              RNA Binding Region
3'-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)  (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: 5'-UTR (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [5]
              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/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
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 = 0.037
              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
S1202 [7]
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S1221 [7]
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Protein Sequence Information
MSRPSSVSPRQPAPGGGGGGGPSPCGPGGGGRAKGLKDIRIDEEVKIAVNIALERFRYGDQREMEFPSSLTSTERAFIHRLSQSLGLVSKSKGKGANRYLTVKKKDGSETAHAMMTCNLTHNTKHAVRSLIQRFPVTNKERTELLPKTERGNVFAVEAENREMSKTSGRLNNGIPQIPVKRGESEFDSFRQSLPVFEKQEEIVKIIKENKVVLIVGETGSGKTTQIPQFLLDDCFKNGIPCRIFCTQPRRLAAIAVAERVAAERRERIGQTIGYQIRLESRVSPKTLLTFCTNGVLLRTLMAGDSTLSTVTHVIVDEVHERDRFSDFLLTKLRDLLQKHPTLKLILSSAALDVNLFIRYFGSCPVIYIQGRPFEVKEMFLEDILRTTGYTNKEMLKYKKEKQQEEKQQTTLTEWYSAQENSFKPESQRQRTVLNVTDEYDLLDDGGDAVFSQLTEKDVNCLEPWLIKEMDACLSDIWLHKDIDAFAQVFHLILTENVSVDYRHSETSATALMVAAGRGFASQVEQLISMGANVHSKASNGWMALDWAKHFGQTEIVDLLESYSATLEFGNLDESSLVQTNGSDLSAEDRELLKAYHHSFDDEKVDLDLIMHLLYNICHSCDAGAVLIFLPGYDEIVGLRDRILFDDKRFADSTHRYQVFMLHSNMQTSDQKKVLKNPPAGVRKIILSTNIAETSITVNDVVFVIDSGKVKEKSFDALNFVTMLKMVWISKASAIQRKGRAGRCRPGICFRLFSRLRFQNMLEFQTPELLRMPLQELCLHTKLLAPVNCPIADFLMKAPEPPPALIVRNAVQMLKTIDAMDTWEDLTELGYHLADLPVEPHLGKMVLCAVVLKCLDPILTIACTLAYRDPFVLPTQASQKRAAMLCRKRFTAGAFSDHMALLRAFQAWQKARSDGWERAFCEKNFLSQATMEIIIGMRTQLLGQLRASGFVRARGGGDIRDVNTNSENWAVVKAALVAGMYPNLVHVDRENLVLTGPKEKKVRFHPASVLSQPQYKKIPPANGQAAAIKALPTDWLIYDEMTRAHRIANIRCCSAVTPVTILVFCGPARLASNALQEPSSFRVDGIPNDSSDSEMEDKTTANLAALKLDEWLHFTLEPEAASLLLQLRQKWHSLFLRRMRAPSKPWSQVDEATIRAIIAVLSTEEQSAGLQQPSGIGQRPRPMSSEELPLASSWRSNNSRKSSADTEFSDECTTAERVLMKSPSPALHPPQKYKDRGILHPKRGTEDRSDQSSLKSTDSSSYPSPCASPSPPSSGKGSKSPSPRPNMPVRYFIMKSSNLRNLEISQQKGIWSTTPSNERKLNRAFWESSIVYLVFSVQGSGHFQGFSRMSSEIGREKSQDWGSAGLGGVFKVEWIRKESLPFQFAHHLLNPWNDNKKVQISRDGQELEPLVGEQLLQLWERLPLGEKNTTD
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References
1 The m6A reader protein YTHDC2 interacts with the small ribosomal subunit and the 5 -3 exoribonuclease XRN1. RNA. 2018 Oct;24(10):1339-1350.
2 Regulation of m 6 A Transcripts by the 3 RNA Helicase YTHDC2 Is Essential for a Successful Meiotic Program in the Mammalian Germline. Mol Cell. 2017 Oct 19;68(2):374-387.e12.
3 Structural Basis for the Discriminative Recognition of N6-Methyladenosine RNA by the Human YT521-B Homology Domain Family of Proteins. J Biol Chem. 2015 Oct 9;290(41):24902-13.
4 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.
5 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
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 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.