Free for academic non-profit institutions. Other users need a Commercial license

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 Lung Papillary Adenocarcinoma and Adhesions Of Uterus. Among its related pathways are Sertoli-Sertoli Cell Junction Dynamics and Photodynamic therapy-induced NFE2L2 (NRF2) survival signaling. GO annotations related to this gene include transcription factor binding. An important paralog of this gene is KLHL17.

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

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
GH19G010411 1.4 FANTOM5 Ensembl ENCODE 5.6 +91.3 91340 2.3 HDGF TBP PKNOX1 SIN3A ZBTB40 ZNF207 RELB ETV6 IKZF2 CREM KEAP1 TYK2 S1PR5 ATG4D ICAM3 C19orf66 GC19P010412 PDE4A
GH19G010118 1.1 ENCODE 6.6 +383.2 383196 3.9 HDGF PKNOX1 CREB3L1 ARNT AGO1 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B P2RY11 KEAP1 EIF3G MRPL4 GC19M010177
GH19G010890 1.2 Ensembl ENCODE dbSUPER 5 -388.3 -388310 2.4 KLF17 ZIC2 HIC1 POLR2A SCRT2 ZNF600 PRDM10 EGR2 SCRT1 MAZ SMARCA4 KEAP1 CARM1 PIR43209
GH19G010478 1.1 Ensembl ENCODE 5.1 +24.4 24442 1.7 PKNOX1 ATF1 CBX3 RB1 RAD21 EGR1 FOS KLF13 CREM NFYA PDE4A KEAP1 GC19P010476 GC19P010483
GH19G010501 1.4 ENCODE dbSUPER 0.7 +1.2 1225 3.0 HDGF PKNOX1 CREB3L1 ARNT AGO1 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B KEAP1 ENSG00000267197
- 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 PKNOX1 CREB3L1 ARNT AGO1 ARID4B SIN3A DMAP1 ZNF2 ZBTB7B

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, isoforms=84, isoforms=108, isoforms=287, posLast=312312, and isoforms=615
  • Modification sites at PhosphoSitePlus

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for KEAP1 (KEAP1)
  • Cloud-Clone Corp. Antibodies for KEAP1

No data available for DME Specific Peptides for KEAP1 Gene

Domains & Families for KEAP1 Gene

Gene Families for KEAP1 Gene

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.

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

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Clone Products

  • Addgene plasmids for KEAP1

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , 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

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 85
Curcumin Pharma Tyrosinase inhibitor, Antitumor, anti-inflammatory and antioxidant 146
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

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(4.3)
  • 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)
  • 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 34 35
  • 99.63 (n)
oppossum
(Monodelphis domestica)
Mammalia KEAP1 35
  • 94 (a)
OneToOne
cow
(Bos Taurus)
Mammalia KEAP1 34 35
  • 91.51 (n)
dog
(Canis familiaris)
Mammalia KEAP1 34 35
  • 90.01 (n)
rat
(Rattus norvegicus)
Mammalia Keap1 34
  • 86.56 (n)
mouse
(Mus musculus)
Mammalia Keap1 34 16 35
  • 86.43 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia KEAP1 35
  • 85 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia KEAP1 35
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia keap1 34
  • 74.04 (n)
Str.5652 34
African clawed frog
(Xenopus laevis)
Amphibia Xl.18653 34
zebrafish
(Danio rerio)
Actinopterygii keap1b 34 35
  • 76.48 (n)
keap1 34
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003645 34
  • 58.68 (n)
fruit fly
(Drosophila melanogaster)
Insecta Keap1 36 34 35
  • 56.64 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 35
  • 53 (a)
OneToOne
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4993 34
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

(7) MalaCards diseases for KEAP1 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
lung papillary adenocarcinoma
  • papillary adenocarcinoma of the lung
adhesions of uterus
  • band of uterus
lung squamous cell carcinoma
  • epidermoid cell carcinoma of the lung
papillary adenocarcinoma
  • infiltrating and papillary adenocarcinoma
deafness, autosomal recessive 68
  • autosomal recessive nonsyndromic deafness 68
- 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. (J Surg Oncol 2010) 3 22 46 64
  2. Ectodermal-neural cortex 1 down-regulates Nrf2 at the translational level. (PMID: 19424503) Wang X.J. … Zhang D.D. (PLoS ONE 2009) 3 4 22 64
  3. PGAM5 tethers a ternary complex containing Keap1 and Nrf2 to mitochondria. (PMID: 18387606) Lo S.-C. … Hannink M. (Exp. Cell Res. 2008) 3 4 22 64
  4. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. (PMID: 16507366) Padmanabhan B. … Yamamoto M. (Mol. Cell 2006) 3 4 22 64
  5. Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling. (PMID: 16888629) Lo S.-C. … Hannink M. (EMBO J. 2006) 3 4 22 64

Products for KEAP1 Gene

  • Addgene plasmids for KEAP1

Sources for KEAP1 Gene

Content
Loading form....