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Aliases for KEAP1 Gene

Aliases for KEAP1 Gene

  • Kelch-Like ECH-Associated Protein 1 2 3
  • Kelch-Like Family Member 19 2 3
  • Cytosolic Inhibitor Of Nrf2 3 4
  • Kelch-Like Protein 19 3 4
  • KIAA0132 4 6
  • KLHL19 3 4
  • INrf2 3 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 papillary adenocarcinoma and diabetic cataract. Among its related pathways are Class I MHC mediated antigen processing and presentation and PAK Pathway. An important paralog of this gene is KLHL10.

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 Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for KEAP1 Gene

Genomics for KEAP1 Gene

Regulatory Elements for KEAP1 Gene

Genomic Location for KEAP1 Gene

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

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
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.
    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

Proteomics data for KEAP1 Gene at MOPED

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 Lys61, Lys84, Lys108, Lys287, Lys312, and Lys615
  • Modification sites at PhosphoSitePlus

Other Protein References for KEAP1 Gene

No data available for DME Specific Peptides for KEAP1 Gene

Domains for KEAP1 Gene

Gene Families for KEAP1 Gene

HGNC:
  • BTBD :BTB/POZ domain containing
  • KLHL :Kelch-like

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 :
  • Q14145
Domain:
  • The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5.
  • Contains 1 BACK (BTB/Kelch associated) domain.
  • Contains 1 BTB (POZ) domain.
Similarity:
  • Contains 6 Kelch repeats.
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:0005515 protein binding IPI 16189514
GO:0008134 transcription factor binding IPI 17015834
genes like me logo Genes that share ontologies with KEAP1: view
genes like me logo Genes that share phenotypes with KEAP1: view

miRNA for KEAP1 Gene

No data available for Enzyme Numbers (IUBMB) , Animal Models , Transcription Factor Targeting 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
Jensen Localization Image for KEAP1 Gene COMPARTMENTS Subcellular localization image for KEAP1 gene
Compartment Confidence
nucleus 5
cytoskeleton 4
cytosol 3
endoplasmic reticulum 2
extracellular 1
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for KEAP1 Gene

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

Pathways for KEAP1 Gene

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

Pathways by source for KEAP1 Gene

UniProtKB/Swiss-Prot Q14145-KEAP1_HUMAN

  • Pathway: Protein modification; protein ubiquitination

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 --
GO:0010499 proteasomal ubiquitin-independent protein catabolic process IDA 15983046
GO:0016567 protein ubiquitination IMP --
genes like me logo Genes that share ontologies with KEAP1: view

Compounds for KEAP1 Gene

(13) Novoseek inferred chemical compound relationships for KEAP1 Gene

Compound -log(P) Hits PubMed IDs
tbhq 88.3 3
sulforaphane 85.6 14
phenylarsine oxide 44.7 5
diethylmaleate 44.2 1
menadione 42.6 2
genes like me logo Genes that share compounds with KEAP1: view

Transcripts for KEAP1 Gene

Unigene Clusters for KEAP1 Gene

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

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 for KEAP1 Gene

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

This gene is overexpressed in Muscle - Skeletal (4.9).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for KEAP1 Gene

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.
genes like me logo Genes that share expressions with KEAP1: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery 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 35
  • 99.63 (n)
  • 100 (a)
KEAP1 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia KEAP1 35
  • 91.51 (n)
  • 97.6 (a)
KEAP1 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia KEAP1 35
  • 90.01 (n)
  • 97.6 (a)
KEAP1 36
  • 98 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Keap1 35
  • 86.43 (n)
  • 94.07 (a)
Keap1 16
Keap1 36
  • 94 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia KEAP1 36
  • 94 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia KEAP1 36
  • 85 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Keap1 35
  • 86.56 (n)
  • 94.19 (a)
lizard
(Anolis carolinensis)
Reptilia KEAP1 36
  • 86 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.18653 35
tropical clawed frog
(Silurana tropicalis)
Amphibia keap1 35
  • 74.04 (n)
  • 80.1 (a)
Str.5652 35
zebrafish
(Danio rerio)
Actinopterygii keap1 35
keap1b 35
  • 76.48 (n)
  • 77.91 (a)
keap1b 36
  • 77 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003645 35
  • 58.68 (n)
  • 51.17 (a)
fruit fly
(Drosophila melanogaster)
Insecta Keap1 35
  • 56.64 (n)
  • 50.27 (a)
Keap1 36
  • 38 (a)
OneToOne
Keap1 37
  • 53 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.4993 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 53 (a)
OneToOne
Species with no ortholog for KEAP1:
  • 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

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

Variants for KEAP1 Gene

Sequence variations from dbSNP and Humsavar for KEAP1 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type MAF
rs1048285 -- 10,499,716(-) CCTGT(C/T)TTCAA reference, synonymous-codon
rs1048287 -- 10,499,560(-) AACGG(C/T)GCTGT synonymous-codon, reference
rs1048289 - 10,491,857(-) CCAGT(A/G)ACGGC missense, reference
rs1048290 -- 10,489,766(-) CGTCT(C/G)CTTTA reference, synonymous-codon
rs1048390 -- 10,486,206(-) TCCCC(A/C)CCGGA utr-variant-3-prime

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

Variant ID Type Subtype PubMed ID
dgv3725n71 CNV Loss 21882294
nsv833744 CNV Loss 17160897
nsv911042 CNV Loss 21882294
dgv3727n71 CNV Loss 21882294

Relevant External Links for KEAP1 Gene

HapMap Linkage Disequilibrium report
KEAP1
Human Gene Mutation Database (HGMD)
KEAP1

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

Disorders for KEAP1 Gene

MalaCards: The human disease database

MalaCards: The human disease database. (2) Diseases for KEAP1 Gene including...

Search for KEAP1 Gene in MalaCards »

(5) Novoseek inferred disease relationships for KEAP1 Gene

Disease -log(P) Hits PubMed IDs
somatic mutations 34.4 4
cancer 33.9 10
cancer lung 13.3 8
inflammation 8.03 2
tumors 0 8

Relevant External Links for KEAP1

Genetic Association Database (GAD)
KEAP1
Human Genome Epidemiology (HuGE) Navigator
KEAP1
genes like me logo Genes that share disorders with KEAP1: view

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

Publications for KEAP1 Gene

  1. Fetal Alz-50 clone 1 interacts with the human orthologue of the Kelch-like Ech-associated protein. (PMID: 15379550) Strachan G.D. … Jordan-Sciutto K.L. (Biochemistry 2004) 3 4 23
  2. Keap1 is a redox-regulated substrate adaptor protein for a Cul3- dependent ubiquitin ligase complex. (PMID: 15572695) Zhang D.D. … Hannink M. (Mol. Cell. Biol. 2004) 3 4 23
  3. Ubiquitination of Keap1, a BTB-Kelch substrate adaptor protein for Cul3, targets Keap1 for degradation by a proteasome-independent pathway. (PMID: 15983046) Zhang D.D. … Hannink M. (J. Biol. Chem. 2005) 3 4 23
  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 23
  5. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. (PMID: 17020408) Singh A. … Biswal S. (PLoS Med. 2006) 3 4 23

Products for KEAP1 Gene

  • Addgene plasmids for KEAP1

Sources for KEAP1 Gene

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