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Aliases for KEAP1 Gene

Aliases for KEAP1 Gene

  • Kelch Like ECH Associated Protein 1 2 3 5
  • Kelch-Like Family Member 19 2 3
  • Cytosolic Inhibitor Of Nrf2 3 4
  • Kelch-Like Protein 19 3 4
  • KLHL19 3 4
  • INrf2 3 4
  • Kelch-Like ECH-Associated Protein 1 3
  • KIAA0132 4

External Ids for KEAP1 Gene

Previous GeneCards Identifiers for KEAP1 Gene

  • GC19M010727
  • GC19M010819
  • GC19M010442
  • GC19M010596
  • GC19M010176

Summaries for KEAP1 Gene

Entrez Gene Summary for KEAP1 Gene

  • This gene encodes a protein containing KELCH-1 like domains, as well as a BTB/POZ domain. Kelch-like ECH-associated protein 1 interacts with NF-E2-related factor 2 in a redox-sensitive manner and the dissociation of the proteins in the cytoplasm is followed by transportation of NF-E2-related factor 2 to the nucleus. This interaction results in the expression of the catalytic subunit of gamma-glutamylcysteine synthetase. Two alternatively spliced transcript variants encoding the same isoform have been found for this gene. [provided by RefSeq, Jul 2008]

GeneCards Summary for KEAP1 Gene

KEAP1 (Kelch Like ECH Associated Protein 1) is a Protein Coding gene. Diseases associated with KEAP1 include Goiter, Multinodular 1, With Or Without Sertoli-Leydig Cell Tumors and Lung Papillary Adenocarcinoma. Among its related pathways are Translational Control and Sertoli-Sertoli Cell Junction Dynamics. GO annotations related to this gene include transcription factor binding. An important paralog of this gene is KLHL20.

UniProtKB/Swiss-Prot for KEAP1 Gene

  • 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 Wiki entry for KEAP1 Gene

Additional gene information for KEAP1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for KEAP1 Gene

Genomics for KEAP1 Gene

Regulatory Elements for KEAP1 Gene

Enhancers for KEAP1 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH19H010411 1.3 FANTOM5 Ensembl ENCODE 5.6 +91.3 91340 2 HDGF PKNOX1 SAP130 BATF RELA POLR2A EED ZNF207 ATF7 ETV6 KEAP1 TYK2 S1PR5 ATG4D ICAM3 C19orf66 GC19P010412 PDE4A
GH19H010118 1.1 ENCODE 6.6 +383.2 383196 3 PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 SLC30A9 CBX5 ZNF266 ZNF699 ILF3 FBXL12 KRI1 ZNF559 LOC100419831 PPAN RAVER1 DNMT1
GH19H010890 1.2 Ensembl ENCODE dbSUPER 5 -388.3 -388310 2 KLF17 ZIC2 HIC1 POLR2A SCRT2 ZNF600 PRDM10 EGR2 SCRT1 MAZ SMARCA4 KEAP1 CARM1 PIR43209
GH19H010478 1.1 Ensembl ENCODE 5.1 +24.4 24442 1 BCOR CTCF PKNOX1 ATF1 RB1 MAX RAD21 E2F1 POLR2A NFYB PDE4A KEAP1 GC19P010483 GC19P010476
GH19H010501 1.4 ENCODE dbSUPER 0.7 +1.2 1225 2 HDGF FOXA2 PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1 ILF3 KRI1 ZNF561 PPAN DNMT1 FBXL12 RAVER1 ZNF562 EIF3G ILF3-AS1
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around KEAP1 on UCSC Golden Path with GeneCards custom track

Promoters for KEAP1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000107026 941 2001 HDGF FOXA2 PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 ZBTB7B YY1

Genomic Location for KEAP1 Gene

Chromosome:
19
Start:
10,486,120 bp from pter
End:
10,503,741 bp from pter
Size:
17,622 bases
Orientation:
Minus strand

Genomic View for KEAP1 Gene

Genes around KEAP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
KEAP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for KEAP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for KEAP1 Gene

Proteins for KEAP1 Gene

  • Protein details for KEAP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q14145-KEAP1_HUMAN
    Recommended name:
    Kelch-like ECH-associated protein 1
    Protein Accession:
    Q14145
    Secondary Accessions:
    • B3KPD5
    • Q6LEP0
    • Q8WTX1
    • Q9BPY9

    Protein attributes for KEAP1 Gene

    Size:
    624 amino acids
    Molecular mass:
    69666 Da
    Quaternary structure:
    • Homodimer. Forms a ternary complex with NFE2L2 and PGAM5. Interacts with the N-terminal regulatory domain of NFE2L2/NRF2. Interacts with BPTF and PTMA. Interacts with CUL3. Part of a complex that contains KEAP1, CUL3 and RBX1. Interacts with NFE2L1 and MAP1LC3B. Interacts indirectly with ENC1. Interacts with SESN1 and SESN2 (PubMed:23274085). Interacts with HSP90AA1 and HSP90AB1 (PubMed:26517842).
    SequenceCaution:
    • Sequence=BAA09481.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for KEAP1 Gene

neXtProt entry for KEAP1 Gene

Post-translational modifications for KEAP1 Gene

  • Ubiquitinated by the E3 ubiquitin ligase complex formed by CUL3 and RBX1 and is subject to proteasomal-independent degradation. Quinone-induced oxidative stress, but not sulforaphane, increases its ubiquitination. Ubiquitination and subsequent degradation is most pronounced following prolonged exposure of cells to oxidative stress, particularly in glutathione-deficient cells that are highly susceptible to oxidative stress.
  • Ubiquitination at isoforms=61, posLast=8484, isoforms=108, isoforms=287, posLast=312312, and posLast=615615
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for KEAP1 (KEAP1)

No data available for DME Specific Peptides for KEAP1 Gene

Domains & Families for KEAP1 Gene

Gene Families for KEAP1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • FDA approved drug targets
  • Predicted intracellular proteins

Suggested Antigen Peptide Sequences for KEAP1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q14145

UniProtKB/Swiss-Prot:

KEAP1_HUMAN :
  • The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5.
Domain:
  • The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5.
genes like me logo Genes that share domains with KEAP1: view

Function for KEAP1 Gene

Molecular function for KEAP1 Gene

UniProtKB/Swiss-Prot EnzymeRegulation:
Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane. Sulforaphane also inhibits ubiquitination of NFE2L2/NRF2.
UniProtKB/Swiss-Prot 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.

Phenotypes From GWAS Catalog for KEAP1 Gene

Gene Ontology (GO) - Molecular Function for KEAP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004842 contributes_to ubiquitin-protein transferase activity IBA --
GO:0005515 protein binding IPI 16189514
GO:0008134 transcription factor binding IPI,IEA 17015834
GO:0042803 protein homodimerization activity IEA --
GO:0097718 disordered domain specific binding IEA --
genes like me logo Genes that share ontologies with KEAP1: view
genes like me logo Genes that share phenotypes with KEAP1: view

Human Phenotype Ontology for KEAP1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for KEAP1
  • Applied Biological Materials Clones for KEAP1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targets and HOMER Transcription for KEAP1 Gene

Localization for KEAP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for KEAP1 Gene

Cytoplasm. Nucleus. Note=Shuttles between cytoplasm and nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for KEAP1 gene
Compartment Confidence
cytoskeleton 5
nucleus 5
cytosol 5
endoplasmic reticulum 3
mitochondrion 2
plasma membrane 1
extracellular 1
peroxisome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
  • Microtubule organizing center (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for KEAP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm IDA,IEA 19424503
GO:0005783 endoplasmic reticulum IEA --
GO:0005815 microtubule organizing center IDA --
genes like me logo Genes that share ontologies with KEAP1: view

Pathways & Interactions for KEAP1 Gene

genes like me logo Genes that share pathways with KEAP1: view

UniProtKB/Swiss-Prot Q14145-KEAP1_HUMAN

  • Pathway: Protein modification; protein ubiquitination.

SIGNOR curated interactions for KEAP1 Gene

Inactivates:

Gene Ontology (GO) - Biological Process for KEAP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001701 in utero embryonic development IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0010499 proteasomal ubiquitin-independent protein catabolic process IDA 15983046
GO:0016567 protein ubiquitination IEA --
genes like me logo Genes that share ontologies with KEAP1: view

Drugs & Compounds for KEAP1 Gene

(9) Drugs for KEAP1 Gene - From: DrugBank, ApexBio, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Dimethyl fumarate Approved, Investigational Pharma Target, binder 88
Curcumin Investigational Pharma Tyrosinase inhibitor, Antitumor, anti-inflammatory and antioxidant 154
Omaveloxolone (RTA-408) Pharma 0

(7) Additional Compounds for KEAP1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(3) ApexBio Compounds for KEAP1 Gene

Compound Action Cas Number
Curcumin Tyrosinase inhibitor 458-37-7
Dimethyl Fumarate 624-49-7
Omaveloxolone (RTA-408) 1474034-05-3
genes like me logo Genes that share compounds with KEAP1: view

Drug Products

Transcripts for KEAP1 Gene

Unigene Clusters for KEAP1 Gene

Kelch-like ECH-associated protein 1:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for KEAP1
  • Applied Biological Materials Clones for KEAP1
  • Vectors and viruses for ORF, Lenti, Retro, Adenovirus, AAV, and more

Alternative Splicing Database (ASD) splice patterns (SP) for KEAP1 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c ^ 6 ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11 ^ 12 ^ 13 ^ 14a · 14b · 14c
SP1: - - - - - - -
SP2: - - - - -
SP3: - - -
SP4: - - -
SP5:
SP6:
SP7: - - -
SP8: -
SP9:

Relevant External Links for KEAP1 Gene

GeneLoc Exon Structure for
KEAP1
ECgene alternative splicing isoforms for
KEAP1

Expression for KEAP1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for KEAP1 Gene

mRNA differential expression in normal tissues according to GTEx for KEAP1 Gene

This gene is overexpressed in Muscle - Skeletal (x4.9).

Protein differential expression in normal tissues from HIPED for KEAP1 Gene

This gene is overexpressed in Breast (56.9) and Plasma (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for KEAP1 Gene



NURSA nuclear receptor signaling pathways regulating expression of KEAP1 Gene:

KEAP1

SOURCE GeneReport for Unigene cluster for KEAP1 Gene:

Hs.465870

mRNA Expression by UniProt/SwissProt for KEAP1 Gene:

Q14145-KEAP1_HUMAN
Tissue specificity: Broadly expressed, with highest levels in skeletal muscle.

Evidence on tissue expression from TISSUES for KEAP1 Gene

  • Nervous system(4.9)
  • Skin(4.6)
  • Bone marrow(4.4)
  • Liver(3.9)
  • Lung(3.6)
  • Kidney(2.8)
  • Muscle(2.8)
  • Eye(2.7)
  • Intestine(2.6)
  • Adrenal gland(2.5)
  • Heart(2.3)
  • Pancreas(2.3)
  • Thyroid gland(2)
genes like me logo Genes that share expression patterns with KEAP1: view

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for KEAP1 Gene

Orthologs for KEAP1 Gene

This gene was present in the common ancestor of animals.

Orthologs for KEAP1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia KEAP1 33 34
  • 99.63 (n)
oppossum
(Monodelphis domestica)
Mammalia KEAP1 34
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia KEAP1 33 34
  • 91.51 (n)
dog
(Canis familiaris)
Mammalia KEAP1 33 34
  • 90.01 (n)
rat
(Rattus norvegicus)
Mammalia Keap1 33
  • 86.56 (n)
mouse
(Mus musculus)
Mammalia Keap1 33 16 34
  • 86.43 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia KEAP1 34
  • 85 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia KEAP1 34
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia keap1 33
  • 74.04 (n)
Str.5652 33
African clawed frog
(Xenopus laevis)
Amphibia Xl.18653 33
zebrafish
(Danio rerio)
Actinopterygii keap1b 33 34
  • 76.48 (n)
keap1 33
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003645 33
  • 58.68 (n)
fruit fly
(Drosophila melanogaster)
Insecta Keap1 35 33 34
  • 56.64 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 53 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4993 33
Species where no ortholog for KEAP1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for KEAP1 Gene

ENSEMBL:
Gene Tree for KEAP1 (if available)
TreeFam:
Gene Tree for KEAP1 (if available)

Paralogs for KEAP1 Gene

Variants for KEAP1 Gene

Sequence variations from dbSNP and Humsavar for KEAP1 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type
VAR_032102 A lung adenocarcinoma patient
VAR_032104 A lung adenocarcinoma patient
VAR_032108 A lung adenocarcinoma cell line
VAR_032109 A lung adenocarcinoma patient
VAR_036084 A breast cancer sample

Structural Variations from Database of Genomic Variants (DGV) for KEAP1 Gene

Variant ID Type Subtype PubMed ID
nsv833744 CNV loss 17160897

Variation tolerance for KEAP1 Gene

Residual Variation Intolerance Score: 8.82% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.90; 18.72% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for KEAP1 Gene

Human Gene Mutation Database (HGMD)
KEAP1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
KEAP1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for KEAP1 Gene

Disorders for KEAP1 Gene

MalaCards: The human disease database

(8) MalaCards diseases for KEAP1 Gene - From: HGMD, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
goiter, multinodular 1, with or without sertoli-leydig cell tumors
  • familial multinodular goiter
lung papillary adenocarcinoma
  • papillary adenocarcinoma of the lung
deafness, autosomal recessive 68
  • autosomal recessive nonsyndromic deafness 68
lung squamous cell carcinoma
  • epidermoid cell carcinoma of the lung
adhesions of uterus
  • band of uterus
- elite association - COSMIC cancer census association via MalaCards
Search KEAP1 in MalaCards View complete list of genes associated with diseases

Relevant External Links for KEAP1

Genetic Association Database (GAD)
KEAP1
Human Genome Epidemiology (HuGE) Navigator
KEAP1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
KEAP1
genes like me logo Genes that share disorders with KEAP1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for KEAP1 Gene

Publications for KEAP1 Gene

  1. Mutations in Keap1 are a potential prognostic factor in resected non-small cell lung cancer. (PMID: 20213688) Takahashi T … Wada H (Journal of surgical oncology 2010) 3 22 45 60
  2. Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level. (PMID: 19424503) Wang XJ … Zhang DD (PloS one 2009) 3 4 22 60
  3. PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria. (PMID: 18387606) Lo SC … Hannink M (Experimental cell research 2008) 3 4 22 60
  4. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. (PMID: 17020408) Singh A … Biswal S (PLoS medicine 2006) 3 4 22 60
  5. Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. (PMID: 16888629) Lo SC … Hannink M (The EMBO journal 2006) 3 4 22 60

Products for KEAP1 Gene

  • Addgene plasmids for KEAP1

Sources for KEAP1 Gene

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