Description: Homo sapiens kelch-like ECH-associated protein 1 (KEAP1), transcript variant 1, mRNA. RefSeq Summary (NM_203500): 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]. Transcript (Including UTRs) Position: hg19 chr19:10,596,796-10,614,054 Size: 17,259 Total Exon Count: 6 Strand: - Coding Region Position: hg19 chr19:10,597,328-10,610,709 Size: 13,382 Coding Exon Count: 5
ID:KEAP1_HUMAN DESCRIPTION: RecName: Full=Kelch-like ECH-associated protein 1; AltName: Full=Cytosolic inhibitor of Nrf2; Short=INrf2; AltName: Full=Kelch-like protein 19; FUNCTION: Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. 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. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome. ENZYME REGULATION: Ubiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane. SUBUNIT: 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. INTERACTION: O14920:IKBKB; NbExp=6; IntAct=EBI-751001, EBI-81266; O88351:Ikbkb (xeno); NbExp=2; IntAct=EBI-751001, EBI-447960; P15314:Irf1 (xeno); NbExp=2; IntAct=EBI-751001, EBI-6115486; Q04206:RELA; NbExp=4; IntAct=EBI-751001, EBI-73886; Q13501:SQSTM1; NbExp=8; IntAct=EBI-751001, EBI-307104; Q64337:Sqstm1 (xeno); NbExp=2; IntAct=EBI-751001, EBI-645025; Q9Y3Q8:TSC22D4; NbExp=3; IntAct=EBI-751001, EBI-739485; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between cytoplasm and nucleus. TISSUE SPECIFICITY: Broadly expressed, with highest levels in skeletal muscle. DOMAIN: The Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5. PTM: Ubiquitinated and subject to proteasomal degradation. SIMILARITY: Contains 1 BACK (BTB/Kelch associated) domain. SIMILARITY: Contains 1 BTB (POZ) domain. SIMILARITY: Contains 6 Kelch repeats. SEQUENCE CAUTION: Sequence=BAA09481.3; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q14145
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0005515 protein binding GO:0008134 transcription factor binding GO:0042802 identical protein binding GO:0042803 protein homodimerization activity GO:0097718 disordered domain specific binding GO:0004842 ubiquitin-protein transferase activity
Biological Process: GO:0001701 in utero embryonic development GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0010499 proteasomal ubiquitin-independent protein catabolic process GO:0016567 protein ubiquitination GO:0016579 protein deubiquitination GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0042994 cytoplasmic sequestering of transcription factor GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0043687 post-translational protein modification GO:0045604 regulation of epidermal cell differentiation GO:0071353 cellular response to interleukin-4
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