Host Protein General Information (ID: PT0258)
  Protein Name
CCR4-associated factor 4 (NOT4)
  Gene Name
CNOT4
  Host Species
Homo sapiens
  Uniprot Entry Name
CNOT4_HUMAN
  EC Number
2.3.2.27
  Subcellular Location
Cytoplasm Nucleus
  External Link
NCBI Gene ID
4850
Uniprot ID
O95628
Ensembl ID
ENSG00000080802
HGNC ID
HGNC:7880
  Function in Host
Has E3 ubiquitin ligase activity, promoting ubiquitinationand degradation of target proteins. Involved in activation of the JAK/STAT pathway. Catalyzes ubiquitination ofmethylated RBM15. Plays a role in quality control oftranslation of mitochondrial outer membrane-localized mRNA. As part of the PINK1-regulated signaling, uponmitochondria damage, ubiquitinates ABCE1 and thereby recruits autophagyreceptors to the mitochondrial outer membrane to initiate mitophagy. [1-4]
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  Related KEGG Pathway
RNA degradation hsa03018            Pathway Map 
  3D Structure

Function of This Protein During Virus Infection
Virus NameSARS-COV-2 Protein Function Anti-viral [5]
Infected TissueLung Infection Time36 h
Infected CellA549 Cells (Adenocarcinomic Human alveolar basal epithelial cells) Cellosaurus IDCVCL_H249 
Method DescriptionTo detect the role of host protein CNOT4 in viral infection, CNOT4 protein knockout A549 Cells were infected with SARS-COV-2 for 36 h , and the effects on infection was detected through WB.
ResultsIt is reported that Knockdown of CNOT4 increases infection compared with control group.

Host Protein - Virus RNA Network

 Full List of Virus RNA Interacting with This Protien
            RNA Region: ORF1ab (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF1ab
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF7a (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF7a
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: ORF7b (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
ORF7b
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: N region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
N region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package
           RNA Region: S region (hCoV-19/Wuhan-Hu-1/2019 )
              RNA Region Details RNA Info Click to show the detail information of this RNA binding region [6]
              Strains Name
hCoV-19/Wuhan-Hu-1/2019
              Strains Family
Beta (B.1.351)
              RNA Binding Region
S region
              Virus Name
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
              Interaction Type Potential binding protein
              Method Description ATtRACT Database; Position Weight Matrices (PWMs); TFBSTools R package

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
S301 [7]
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S324 [7]
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S432 [7]
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Protein Sequence Information
MSRSPDAKEDPVECPLCMEPLEIDDINFFPCTCGYQICRFCWHRIRTDENGLCPACRKPYPEDPAVYKPLSQEELQRIKNEKKQKQNERKQKISENRKHLASVRVVQKNLVFVVGLSQRLADPEVLKRPEYFGKFGKIHKVVINNSTSYAGSQGPSASAYVTYIRSEDALRAIQCVNNVVVDGRTLKASLGTTKYCSYFLKNMQCPKPDCMYLHELGDEAASFTKEEMQAGKHQEYEQKLLQELYKLNPNFLQLSTGSVDKNKNKVTPLQRYDTPIDKPSDSLSIGNGDNSQQISNSDTPSPPPGLSKSNPVIPISSSNHSARSPFEGAVTESQSLFSDNFRHPNPIPSGLPPFPSSPQTSSDWPTAPEPQSLFTSETIPVSSSTDWQAAFGFGSSKQPEDDLGFDPFDVTRKALADLIEKELSVQDQPSLSPTSLQNSSSHTTTAKGPGSGFLHPAAATNANSLNSTFSVLPQRFPQFQQHRAVYNSFSFPGQAARYPWMAFPRNSIMHLNHTANPTSNSNFLDLNLPPQHNTGLGGIPVAGEEEVKVSTMPLSTSSHSLQQGQQPTSLHTTVA
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References
1 Ubiquitination of ABCE1 by NOT4 in Response to Mitochondrial Damage Links Co-translational Quality Control to PINK1-Directed Mitophagy. Cell Metab. 2018 Jul 3;28(1):130-144.e7.
2 Cross-talk between PRMT1-mediated methylation and ubiquitylation on RBM15 controls RNA splicing. Elife. 2015 Nov 17;4:e07938.
3 Not4 enhances JAK/STAT pathway-dependent gene expression in Drosophila and in human cells. FASEB J. 2012 Mar;26(3):1239-50.
4 Identification of a ubiquitin-protein ligase subunit within the CCR4-NOT transcription repressor complex. EMBO J. 2002 Feb 1;21(3):355-64.
5 Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells. Cell. 2021 Jan 7;184(1):92-105.e16.
6 Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis. Commun Biol. 2021 May 17;4(1):590.
7 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature. 2021 Jun;594(7862):246-252.