Browse KEAP1

Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Nucleus. Note=Shuttles between cytoplasm and nucleus.
Domain PF07707 BTB And C-terminal Kelch
PF00651 BTB/POZ domain
PF01344 Kelch motif
Function

Acts as a substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. Retains NFE2L2/NRF2 and may also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome.

> Gene Ontology
 
Biological Process GO:0001701 in utero embryonic development
GO:0006606 protein import into nucleus
GO:0006913 nucleocytoplasmic transport
GO:0008544 epidermis development
GO:0009894 regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0009913 epidermal cell differentiation
GO:0010498 proteasomal protein catabolic process
GO:0010499 proteasomal ubiquitin-independent protein catabolic process
GO:0017038 protein import
GO:0030856 regulation of epithelial cell differentiation
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0032386 regulation of intracellular transport
GO:0032387 negative regulation of intracellular transport
GO:0032434 regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0032507 maintenance of protein location in cell
GO:0033157 regulation of intracellular protein transport
GO:0034504 protein localization to nucleus
GO:0042176 regulation of protein catabolic process
GO:0042306 regulation of protein import into nucleus
GO:0042308 negative regulation of protein import into nucleus
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042992 negative regulation of transcription factor import into nucleus
GO:0042994 cytoplasmic sequestering of transcription factor
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0044744 protein targeting to nucleus
GO:0045185 maintenance of protein location
GO:0045604 regulation of epidermal cell differentiation
GO:0045682 regulation of epidermis development
GO:0045732 positive regulation of protein catabolic process
GO:0045862 positive regulation of proteolysis
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046823 negative regulation of nucleocytoplasmic transport
GO:0051051 negative regulation of transport
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051220 cytoplasmic sequestering of protein
GO:0051224 negative regulation of protein transport
GO:0051235 maintenance of location
GO:0051651 maintenance of location in cell
GO:0061136 regulation of proteasomal protein catabolic process
GO:0070670 response to interleukin-4
GO:0071353 cellular response to interleukin-4
GO:0090317 negative regulation of intracellular protein transport
GO:1900180 regulation of protein localization to nucleus
GO:1900181 negative regulation of protein localization to nucleus
GO:1901800 positive regulation of proteasomal protein catabolic process
GO:1902593 single-organism nuclear import
GO:1903050 regulation of proteolysis involved in cellular protein catabolic process
GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process
GO:1903362 regulation of cellular protein catabolic process
GO:1903364 positive regulation of cellular protein catabolic process
GO:1903533 regulation of protein targeting
GO:1903828 negative regulation of cellular protein localization
GO:1904589 regulation of protein import
GO:1904590 negative regulation of protein import
GO:1904950 negative regulation of establishment of protein localization
Molecular Function GO:0004842 ubiquitin-protein transferase activity
GO:0008134 transcription factor binding
GO:0019787 ubiquitin-like protein transferase activity
Cellular Component GO:0000151 ubiquitin ligase complex
GO:0005884 actin filament
GO:0015629 actin cytoskeleton
GO:0030496 midbody
GO:0031461 cullin-RING ubiquitin ligase complex
GO:0031463 Cul3-RING ubiquitin ligase complex
> KEGG and Reactome Pathway
 
KEGG hsa04120 Ubiquitin mediated proteolysis
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983168: Antigen processing
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-5688426: Deubiquitination
R-HSA-168256: Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-5689880: Ub-specific processing proteases
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between KEAP1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between KEAP1 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27687306Lung adenocarcinomaInhibit immunity (infiltration)LUADs with TP53 or KEAP1 mutations displayed relatively increased CD57 and Granzyme B levels indicative of augmented natural killer (NK) cell infiltration.
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of KEAP1 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.47; FDR: 0.02860 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of KEAP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.2190.259
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.4810.837
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0220.989
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.110.681
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1330.944
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.0810.973
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0460.893
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0210.989
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1160.946
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.6430.705
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.6810.796
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0220.732
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of KEAP1 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 141721.4021.40.081
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103300300.528
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.71.42.30.469
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.71.720.532
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47014.3-14.31
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KEAP1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KEAP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KEAP1.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KEAP1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of KEAP1 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between KEAP1 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolKEAP1
Namekelch-like ECH-associated protein 1
Aliases KIAA0132; MGC10630; MGC1114; MGC20887; MGC4407; MGC9454; INrf2; KLHL19; kelch-like family member 19; cytosol ......
Chromosomal Location19p13.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting KEAP1 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting KEAP1.
ID Name Drug Type Targets #Targets
DB08908Dimethyl fumarateSmall MoleculeKEAP1, RELA2