Details of Host Protein

 Host Protein General Information (ID: PT1272)
  Protein Name
Zinc finger CCCH-type antiviral protein 1 (ZC3HAV1)
  Gene Name
ZC3HAV1
  Host Species
Homo sapiens
  Uniprot Entry Name
ZCCHV_HUMAN
  Protein Families
ARTD/PARP family
  Subcellular Location
Cytoplasm Nucleus
  External Link
NCBI Gene ID
56829
Uniprot ID
Q7Z2W4
Ensembl ID
ENSG00000105939
HGNC ID
HGNC:23721
  Function in Host
Antiviral protein which inhibits the replication of virusesby recruiting the cellular RNA degradation machineries to degrade theviral mRNAs. Binds to a ZAP-responsive element (ZRE) present in thetarget viral mRNA, recruits cellular poly (A) -specific ribonuclease PARNto remove the poly (A) tail, and the 3'-5' exoribonuclease complexexosome to degrade the RNA body from the 3'-end. It also recruits thedecapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to removethe cap structure of the viral mRNA to initiate its degradation fromthe 5'-end. Its target viruses belong to families which includeretroviridae: human immunodeficiency virus type 1 (HIV-1), moloney andmurine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae:sindbis virus (SINV) and Ross river virus (RRV). Specifically targetsthe multiply spliced but not unspliced or singly spliced HIV-1 mRNAsfor degradation. Isoform 1 is a more potent viral inhibitor thanisoform 2. Isoform 2 acts as a positive regulator of DDX58/RIG-Isignaling resulting in activation of the downstream effector IRF3leading to the expression of type I IFNs and IFN stimulated genes (ISGs). [1-3]
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  3D Structure
PDB ID: 2X5Y 
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  2D PNG Download  
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Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Pro-viral [4]
Infected TissueLung Infection Time24 h; 48 h
Infected CellCalu-3 cells (Human lung cancer cell) Cellosaurus IDCVCL_0609 
Method DescriptionTo detect the role of host protein ZC3HAV1 in viral infection, ZC3HAV1 protein knockout Calu-3 cells were infected with SARS-COV-2 for 24 - 48 h , and the effects on infection was detected through qRT-PCR.
ResultsIt is reported that knockdown of ZC3HAV1 leads to the reduced 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: 5'-UTR (hCoV-19/South Korea/KCDC03/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [4]
              Strains Name
hCoV-19/South Korea/KCDC03/2020
              Strains Family
Alpha (B.1.1.7)
              RNA Binding Region
5'-UTR
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Directly bind to SARS-CoV-23 RNA's 5' UTR region
              Infection Cells Vero cells (epithelial kidney cell)  (CVCL_0059 )
              Cell Originated Tissue kidney
              Infection Time 24 h
              Interaction Score P-adjust < 0.05
              Method Description Modified RNA antisense purification coupled with mass spectrometry (RAP-MS); label-free quantification (LFQ); liquid chromatography with tandem mass spectrometry (LC-MS/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 [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: ORF10 (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
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: ORF10 (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
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF10
              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-OC43/VR-759 Quebec/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [4]
              Strains Name
hCov-OC43/VR-759 Quebec/2019
              Strains Family
Beta
              RNA Binding Region
Not Specified Virus Region
              Virus Name
Human coronavirus OC43 (HCov-OC43)
              Infection Cells HCT-8 cells (Human ileocaecal adenocarcinoma cell) HCT-8 cells (Human ileocaecal adenocarcinoma cell)  (CVCL_2478 )
              Cell Originated Tissue Ileocecum
              Infection Time 12h; 24; 36h; 48h
              Interaction Score p_value < 0.05; FDR < 10%
              Method Description Modified RNA antisense purification coupled with mass spectrometry (RAP-MS); label-free quantification (LFQ); liquid chromatography with tandem mass spectrometry (LC-MS/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 [6]
              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 [7]
              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 [8]
              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 = 0.100
              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
-491 [9]
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S257 [10]
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S275 [10]
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S280 [10]
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S284 [10]
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S302 [10]
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S310 [10]
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S312 [10]
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S313 [10]
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S351 [10]
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S361 [9]
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S378 [10]
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S386 [10]
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S387 [10]
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T273 [10]
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T393 [10]
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Protein Sequence Information
MADPEVCCFITKILCAHGGRMALDALLQEIALSEPQLCEVLQVAGPDRFVVLETGGEAGITRSVVATTRARVCRRKYCQRPCDNLHLCKLNLLGRCNYSQSERNLCKYSHEVLSEENFKVLKNHELSGLNKEELAVLLLQSDPFFMPEICKSYKGEGRQQICNQQPPCSRLHICDHFTRGNCRFPNCLRSHNLMDRKVLAIMREHGLNPDVVQNIQDICNSKHMQKNPPGPRAPSSHRRNMAYRARSKSRDRFFQGSQEFLASASASAERSCTPSPDQISHRASLEDAPVDDLTRKFTYLGSQDRARPPSGSSKATDLGGTSQAGTSQRFLENGSQEDLLHGNPGSTYLASNSTSAPNWKSLTSWTNDQGARRKTVFSPTLPAARSSLGSLQTPEAVTTRKGTGLLSSDYRIINGKSGTQDIQPGPLFNNNADGVATDITSTRSLNYKSTSSGHREISSPRIQDAGPASRDVQATGRIADDADPRVALVNDSLSDVTSTTSSRVDDHDSEEICLDHLCKGCPLNGSCSKVHFHLPYRWQMLIGKTWTDFEHMETIEKGYCNPGIHLCSVGSYTINFRVMSCDSFPIRRLSTPSSVTKPANSVFTTKWIWYWKNESGTWIQYGEEKDKRKNSNVDSSYLESLYQSCPRGVVPFQAGSRNYELSFQGMIQTNIASKTQKDVIRRPTFVPQWYVQQMKRGPDHQPAKTSSVSLTATFRPQEDFCFLSSKKYKLSEIHHLHPEYVRVSEHFKASMKNFKIEKIKKIENSELLDKFTWKKSQMKEEGKLLFYATSRAYVESICSNNFDSFLHETHENKYGKGIYFAKDAIYSHKNCPYDAKNVVMFVAQVLVGKFTEGNITYTSPPPQFDSCVDTRSNPSVFVIFQKDQVYPQYVIEYTEDKACVIS
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References
1 Zinc-finger antiviral protein inhibits XMRV infection. PLoS One. 2012;7(6):e39159.
2 Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting multiply spliced viral mRNAs for degradation. Proc Natl Acad Sci USA. 2011 Sep 20;108(38):15834-9.
3 ZAPS is a potent stimulator of signaling mediated by the RNA helicase RIG-I during antiviral responses. Nat Immunol. 2011 Jan;12(1):37-44.
4 The SARS-CoV-2 RNA interactome. Mol Cell. 2021 Jul 1;81(13):2838-2850.e6.
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 Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.
7 Characterization and functional interrogation of the SARS-CoV-2 RNA interactome. Cell Rep. 2022 Apr 26;39(4):110744.
8 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.
9 The Global Phosphorylation Landscape of SARS-CoV-2 Infection. Cell. 2020 Aug 6;182(3):685-712.e19.
10 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.