Host Protein General Information (ID: PT0007)
  Protein Name
14-3-3 protein zeta/delta (KCIP-1)
  Gene Name
YWHAZ
  Host Species
Homo sapiens
  Uniprot Entry Name
1433Z_HUMAN
  Protein Families
14-3-3 family
  Subcellular Location
Cytoplasm Melanosome
  External Link
NCBI Gene ID
7534
Uniprot ID
P63104
Ensembl ID
ENSG00000164924
HGNC ID
HGNC:12855
  Function in Host
Adapter protein implicated in the regulation of a largespectrum of both general and specialized signaling pathways. Binds to alarge number of partners, usually by recognition of a phosphoserine orphosphothreonine motif. Binding generally results in the modulation ofthe activity of the binding partner. Induces ARHGEF7 activity on RAC1as well as lamellipodia and membrane ruffle formation. In neurons, regulates spine maturation through themodulation of ARHGEF7 activity. [1-7]
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  Related KEGG Pathway
Hepatitis C hsa05160            Pathway Map 
Hepatitis B hsa05161            Pathway Map 
Viral carcinogenesis hsa05203            Pathway Map 
Cell cycle hsa04110            Pathway Map 
Oocyte meiosis hsa04114            Pathway Map 
PI3K-Akt signaling pathway hsa04151            Pathway Map 
Hippo signaling pathway hsa04390            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [8]
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 YWHAZ in viral infection, YWHAZ 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 YWHAZ 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: ORF10 (hCoV-19/Not Specified Virus Strain )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [9]
              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 Calu-3 cells (Human Lung Cancer Cell)  (CVCL_0609 )
              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/England/02/2020 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [10]
              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 = 0.096
              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
S207 [11]
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Protein Sequence Information
MDKNELVQKAKLAEQAERYDDMAACMKSVTEQGAELSNEERNLLSVAYKNVVGARRSSWRVVSSIEQKTEGAEKKQQMAREYREKIETELRDICNDVLSLLEKFLIPNASQAESKVFYLKMKGDYYRYLAEVAAGDDKKGIVDQSQQAYQEAFEISKKEMQPTHPIRLGLALNFSVFYYEILNSPEKACSLAKTAFDEAIAELDTLSEESYKDSTLIMQLLRDNLTLWTSDTQGDEAEAGEGGEN
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References
1 14-3-3 is phosphorylated by casein kinase I on residue 233 Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction. J Biol Chem. 1997 Nov 14;272(46):28882-8.
2 A YWHAZ Variant Associated With Cardiofaciocutaneous Syndrome Activates the RAF-ERK Pathway. Front Physiol. 2019 Apr 8;10:388.
3 Protein kinase A phosphorylates and regulates dimerization of 14-3-3 epsilon. FEBS Lett. 2006 Jan 9;580(1):305-10.
4 Transgenic mouse proteomics identifies new 14-3-3-associated proteins involved in cytoskeletal rearrangements and cell signaling. Mol Cell Proteomics. 2006 Dec;5(12):2211-27.
5 Melatonin synthesis: 14-3-3-dependent activation and inhibition of arylalkylamine N-acetyltransferase mediated by phosphoserine-205. Proc Natl Acad Sci USA. 2005 Jan 25;102(4):1222-7.
6 JNK promotes Bax translocation to mitochondria through phosphorylation of 14-3-3 proteins. EMBO J. 2004 Apr 21;23(8):1889-99.
7 Cellular stabilization of the melatonin rhythm enzyme induced by nonhydrolyzable phosphonate incorporation. Nat Struct Biol. 2003 Dec;10(12):1054-7.
8 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.
9 Mapping the host protein interactome of non-coding regions in SARS-CoV-2 genome. bioRxiv. 2021 Jun; DOI:10.1101/2021.06.19.449092.
10 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.
11 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.