Details of Host Protein

 Host Protein General Information (ID: PT0584)
  Protein Name
Cysteines of Keap1 (KEAP1 Cysteines)
  Gene Name
KEAP1
  Host Species
Homo sapiens
  Uniprot Entry Name
KEAP1_HUMAN
  Protein Families
KEAP1 family
  Subcellular Location
Cytoplasm Nucleus
  External Link
NCBI Gene ID
9817
Uniprot ID
Q14145
Ensembl ID
ENSG00000079999
HGNC ID
HGNC:23177
  Function in Host
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3ubiquitin ligase complex that regulates the response to oxidativestress by targeting NFE2L2/NRF2 for ubiquitination. KEAP1 acts as a key sensor of oxidative and electrophilic stress: innormal conditions, the BCR (KEAP1) complex mediates ubiquitination anddegradation of NFE2L2/NRF2, a transcription factor regulatingexpression of many cytoprotective genes. In response to oxidative stress, differentelectrophile metabolites trigger non-enzymatic covalent modificationsof highly reactive cysteine residues in KEAP1, leading to inactivatethe ubiquitin ligase activity of the BCR (KEAP1) complex, promotingNFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifyingenzymes. In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction withSQSTM1/p62, leading to inactivation of the BCR (KEAP1) complex andactivation of NFE2L2/NRF2. The BCR (KEAP1) complexalso mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62sequestering activity and degradation. The BCR (KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradationby the proteasome. [1-7]
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  Related KEGG Pathway
Ubiquitin mediated proteolysis hsa04120            Pathway Map 
Pathways in cancer hsa05200            Pathway Map 
Chemical carcinogenesis - reactive oxygen species hsa05208            Pathway Map 
Hepatocellular carcinoma hsa05225            Pathway Map 
Fluid shear stress and atherosclerosis hsa05418            Pathway Map 
Parkinson disease hsa05012            Pathway Map 
  3D Structure
PDB ID: 1U6D 
FASTA   Download
  2D PNG Download  
PDB File Download

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 KEAP1 in viral infection, KEAP1 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 KEAP1 increases SARS-CoV-2 RNA levels compared with control group.

 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 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)

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
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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 Sequence Information
MQPDPRPSGAGACCRFLPLQSQCPEGAGDAVMYASTECKAEVTPSQHGNRTFSYTLEDHTKQAFGIMNELRLSQQLCDVTLQVKYQDAPAAQFMAHKVVLASSSPVFKAMFTNGLREQGMEVVSIEGIHPKVMERLIEFAYTASISMGEKCVLHVMNGAVMYQIDSVVRACSDFLVQQLDPSNAIGIANFAEQIGCVELHQRAREYIYMHFGEVAKQEEFFNLSHCQLVTLISRDDLNVRCESEVFHACINWVKYDCEQRRFYVQALLRAVRCHSLTPNFLQMQLQKCEILQSDSRCKDYLVKIFEELTLHKPTQVMPCRAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQVPRSGLAGCVVGGLLYAVGGRNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGVIDGHIYAVGGSHGCIHHNSVERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDGTNRLNSAECYYPERNEWRMITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVETETWTFVAPMKHRRSALGITVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSGRSGVGVAVTMEPCRKQIDQQNCTC
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References
1 Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018 Apr 5;556(7699):113-117.
2 p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem. 2010 Jul 16;285(29):22576-91.
3 Cul3-mediated Nrf2 ubiquitination and antioxidant response element (ARE) activation are dependent on the partial molar volume at position 151 of Keap1. Biochem J. 2009 Jul 29;422(1):171-80.
4 Covalent modification at Cys151 dissociates the electrophile sensor Keap1 from the ubiquitin ligase CUL3. Chem Res Toxicol. 2008 Mar;21(3):705-10.
5 Novel n-3 fatty acid oxidation products activate Nrf2 by destabilizing the association between Keap1 and Cullin3. J Biol Chem. 2007 Jan 26;282(4):2529-37.
6 Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proc Natl Acad Sci USA. 2005 Jul 19;102(29):10070-5.
7 BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol Cell Biol. 2005 Jan;25(1):162-71.
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.