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IID00384
UniprotQ14145
ProteinKelch-like ECH-associated protein 1
GeneKEAP1
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
624
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 48-180 Monomer :
 Evidence X-RAY 5git A Reference
       Region 5git A 48-50 disorder
       Region 5git A 51-180 order
 Evidence X-RAY 4cxi A Reference
       Region 4cxi A 48-49 disorder
       Region 4cxi A 50-179 order
       Region 4cxi A 180-180 disorder
Seq 48-182 Homo dimer :
 Evidence X-RAY 5daf A Reference
       Region 5daf A 49-49 disorder
       Region 5daf A 50-112 order
       Region 5daf A 113-119 disorder
       Region 5daf A 120-177 order
       Region 5daf A 178-182 disorder
 Evidence X-RAY 5dad A Reference
       Region 5dad A 49-49 disorder
       Region 5dad A 50-112 order
       Region 5dad A 113-119 disorder
       Region 5dad A 120-179 order
       Region 5dad A 180-182 disorder
 Evidence X-RAY 4cxt A Reference
       Region 4cxt A 48-48 disorder
       Region 4cxt A 49-180 order
 Evidence X-RAY 4cxj A Reference
       Region 4cxj A 48-48 disorder
       Region 4cxj A 49-179 order
       Region 4cxj A 180-180 disorder
Seq 51-204 Hetero dimer : Q13618
 Evidence X-RAY 5nlb A Reference
       Region 5nlb A 51-204 order
Seq 321-609 Homo dimer :
 Evidence X-RAY 3zgd B Reference
       Region 3zgd B 321-324 disorder
       Region 3zgd B 325-609 order
 Evidence X-RAY 3zgd A Reference
       Region 3zgd A 321-324 disorder
       Region 3zgd A 325-609 order
 Evidence X-RAY 4l7b B Reference
       Region 4l7b B 321-609 order
 Evidence X-RAY 4l7b A Reference
       Region 4l7b A 321-321 disorder
       Region 4l7b A 322-609 order
Seq 321-609 Hetero dimer :
 Evidence X-RAY 5x54 B Reference
       Region 5x54 B 321-324 disorder
       Region 5x54 B 325-609 order
Seq 321-609 Homo trimer :
 Evidence X-RAY 4n1b C Reference
       Region 4n1b C 321-324 disorder
       Region 4n1b C 325-609 order
 Evidence X-RAY 4n1b B Reference
       Region 4n1b B 321-326 disorder
       Region 4n1b B 327-609 order
 Evidence X-RAY 4n1b A Reference
       Region 4n1b A 321-325 disorder
       Region 4n1b A 326-609 order
 Evidence X-RAY 4l7d C Reference
       Region 4l7d C 321-324 disorder
       Region 4l7d C 325-609 order
 Evidence X-RAY 4l7d B Reference
       Region 4l7d B 321-325 disorder
       Region 4l7d B 326-609 order
 Evidence X-RAY 4l7d A Reference
       Region 4l7d A 321-325 disorder
       Region 4l7d A 326-609 order
 Evidence X-RAY 4l7c C Reference
       Region 4l7c C 321-325 disorder
       Region 4l7c C 326-609 order
 Evidence X-RAY 4l7c B Reference
       Region 4l7c B 321-325 disorder
       Region 4l7c B 326-609 order
 Evidence X-RAY 4l7c A Reference
       Region 4l7c A 321-325 disorder
       Region 4l7c A 326-609 order
Seq 321-609 Monomer :
 Evidence X-RAY 1zgk A Reference
       Region 1zgk A 321-321 disorder
       Region 1zgk A 322-609 order
 Evidence X-RAY 4xmb A Reference
       Region 4xmb A 321-323 disorder
       Region 4xmb A 324-609 order
 Evidence X-RAY 3vnh A Reference
       Region 3vnh A 321-321 disorder
       Region 3vnh A 322-609 order
 Evidence X-RAY 3vng A Reference
       Region 3vng A 321-321 disorder
       Region 3vng A 322-609 order
 Evidence X-RAY 1u6d X Reference
       Region 1u6d X 321-321 disorder
       Region 1u6d X 322-609 order
 Evidence X-RAY 4iqk A Reference
       Region 4iqk A 321-324 disorder
       Region 4iqk A 325-609 order
 Evidence X-RAY 4in4 C Reference
       Region 4in4 C 321-609 order
 Evidence X-RAY 4in4 B Reference
       Region 4in4 B 321-325 disorder
       Region 4in4 B 326-609 order
 Evidence X-RAY 4in4 A Reference
       Region 4in4 A 321-321 disorder
       Region 4in4 A 322-609 order
 Evidence X-RAY 4ifn X Reference
       Region 4ifn X 321-324 disorder
       Region 4ifn X 325-609 order
 Evidence X-RAY 4ifj A Reference
       Region 4ifj A 321-321 disorder
       Region 4ifj A 322-609 order
Seq 321-609 Hetero dimer : IID00213Complex
 Evidence X-RAY 4ifl X Reference
       Region 4ifl X 321-324 disorder
       Region 4ifl X 325-609 order
 Evidence X-RAY 2flu X Reference
       Region 2flu X 321-324 disorder
       Region 2flu X 325-609 order
Seq 321-609 Hetero dimer :
 Evidence X-RAY 5x54 A Reference
       Region 5x54 A 321-324 disorder
       Region 5x54 A 325-609 order
Seq 321-609 Hetero trimer : IID00213Complex
 Evidence X-RAY 3zgc A Reference
       Region 3zgc A 321-324 disorder
       Region 3zgc A 325-609 order
 Evidence X-RAY 3zgc B Reference
       Region 3zgc B 321-324 disorder
       Region 3zgc B 325-609 order
Seq 321-611 Hetero tetramer :
 Evidence X-RAY 5f72 C Reference
       Region 5f72 C 321-324 disorder
       Region 5f72 C 325-609 order
       Region 5f72 C 610-611 disorder
 Evidence X-RAY 5f72 K Reference
       Region 5f72 K 321-324 disorder
       Region 5f72 K 325-609 order
       Region 5f72 K 610-611 disorder
 
Prediction
NeProc
Disorder 1-49,620-624
Order 50-619
ProS 15-21,620-624
AlphaFold
Disorder 1-50,314-318,620-624
Order 51-313,319-619
Pfam Hmmer
PF00651 67-179 4.5e-39
PF07707 184-286 8.9e-46
PF01344 315-359 1.2e-05
PF01344 361-410 1.1e-15
PF01344 412-457 2.3e-14
PF01344 459-504 1.5e-15
PF01344 506-551 9.3e-19
PF01344 553-598 4.9e-18
Function
Function in SwissProt
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that regulates the response to oxidative stress by targeting NFE2L2/NRF2 for ubiquitination (PubMed:14585973, PubMed:15379550, PubMed:15572695, PubMed:15983046, PubMed:15601839). KEAP1 acts as a key sensor of oxidative and electrophilic stress: in normal conditions, the BCR(KEAP1) complex mediates ubiquitination and degradation of NFE2L2/NRF2, a transcription factor regulating expression of many cytoprotective genes (PubMed:15601839, PubMed:16006525). In response to oxidative stress, different electrophile metabolites trigger non-enzymatic covalent modifications of highly reactive cysteine residues in KEAP1, leading to inactivate the ubiquitin ligase activity of the BCR(KEAP1) complex, promoting NFE2L2/NRF2 nuclear accumulation and expression of phase II detoxifying enzymes (PubMed:19489739, PubMed:16006525, PubMed:17127771, PubMed:18251510, PubMed:29590092). In response to selective autophagy, KEAP1 is sequestered in inclusion bodies following its interaction with SQSTM1/p62, leading to inactivation of the BCR(KEAP1) complex and activation of NFE2L2/NRF2 (PubMed:20452972). The BCR(KEAP1) complex also mediates ubiquitination of SQSTM1/p62, increasing SQSTM1/p62 sequestering activity and degradation (PubMed:28380357). The BCR(KEAP1) complex also targets BPTF and PGAM5 for ubiquitination and degradation by the proteasome (PubMed:15379550, PubMed:17046835).