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MGP004018

UniProt Annotations

Entry Information
Gene Namekelch-like ECH-associated protein 1
Protein EntryKEAP1_HUMAN
UniProt IDQ14145
SpeciesHuman
Comments
Comment typeDescription
DomainThe Kelch repeats mediate interaction with NF2L2/NRF2, BPTF and PGAM5. {ECO:0000269|PubMed:17046835}.
Enzyme RegulationUbiquitination and subsequent degradation of PGAM5 is inhibited by oxidative stress and sulforaphane. Sulforaphane also inhibits ubiquitination of NFE2L2/NRF2. {ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:17046835}.
FunctionActs 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. {ECO:0000269|PubMed:14585973, ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:17046835}.
InteractionQ9NY33:DPP3; NbExp=2; IntAct=EBI-751001, EBI-718333; P62495:ETF1; NbExp=2; IntAct=EBI-751001, EBI-750990; 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; Q16236:NFE2L2; NbExp=17; IntAct=EBI-751001, EBI-2007911; 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;
PathwayProtein modification; protein ubiquitination.
PtmUbiquitinated 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. {ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15983046}.
Sequence CautionSequence=BAA09481.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityContains 1 BACK (BTB/Kelch associated) domain. {ECO:0000305}.
SimilarityContains 1 BTB (POZ) domain. {ECO:0000255|PROSITE- ProRule:PRU00037}.
SimilarityContains 6 Kelch repeats. {ECO:0000305}.
Subcellular LocationCytoplasm. Nucleus. Note=Shuttles between cytoplasm and nucleus.
SubunitHomodimer. 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. {ECO:0000269|PubMed:15379550, ECO:0000269|PubMed:15572695, ECO:0000269|PubMed:15657435, ECO:0000269|PubMed:15983046, ECO:0000269|PubMed:16687406, ECO:0000269|PubMed:16888629, ECO:0000269|PubMed:17046835, ECO:0000269|PubMed:18387606, ECO:0000269|PubMed:19424503, ECO:0000269|PubMed:24089205}.
Tissue SpecificityBroadly expressed, with highest levels in skeletal muscle. {ECO:0000269|PubMed:15379550}.
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