{
 "gene": "KEAP1",
 "run_date": "2026-06-10T02:59:49",
 "timeline": {
  "current_model": "KEAP1 is a homodimeric, cysteine-rich substrate adaptor for a CUL3-RBX1 E3 ubiquitin ligase that constitutively ubiquitinates and targets NRF2 for proteasomal degradation under basal conditions; oxidative, electrophilic, or metabolic stress covalently modifies critical sensor cysteines (principally Cys151, Cys273, Cys288) on KEAP1\u2014via alkylation, S-sulfhydration, methylglyoxal-derived crosslinking, or other modifications\u2014causing conformational changes that impair Nrf2 ubiquitination, allowing newly synthesized NRF2 to accumulate, translocate to the nucleus, and activate cytoprotective gene transcription; KEAP1 also targets additional substrates including PGAM5 and regulates ER-phagy via PINK1-directed ubiquitylation of Rtnl1, while its activity is further modulated by competitive binding of proteins such as phospho-p62, GULP1, and DDRGK1, by CMA-mediated lysosomal degradation of KEAP1 itself, and by post-translational modifications including PRMT5-mediated methylation."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140096",
     "term_label": "catalytic activity, acting on a protein",
     "supporting_discovery_ids": [
      1,
      13,
      12
     ]
    },
    {
     "term_id": "GO:0016874",
     "term_label": "ligase activity",
     "supporting_discovery_ids": [
      1,
      5
     ]
    },
    {
     "term_id": "GO:0140299",
     "term_label": "molecular sensor activity",
     "supporting_discovery_ids": [
      2,
      6,
      7,
      21
     ]
    },
    {
     "term_id": "GO:0098772",
     "term_label": "molecular function regulator activity",
     "supporting_discovery_ids": [
      0,
      4
     ]
    },
    {
     "term_id": "GO:0060090",
     "term_label": "molecular adaptor activity",
     "supporting_discovery_ids": [
      1,
      5
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      0,
      14
     ]
    },
    {
     "term_id": "GO:0005783",
     "term_label": "endoplasmic reticulum",
     "supporting_discovery_ids": [
      12
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-8953897",
     "term_label": "Cellular responses to stimuli",
     "supporting_discovery_ids": [
      1,
      2,
      6
     ]
    },
    {
     "term_id": "R-HSA-392499",
     "term_label": "Metabolism of proteins",
     "supporting_discovery_ids": [
      1,
      5,
      13
     ]
    },
    {
     "term_id": "R-HSA-9612973",
     "term_label": "Autophagy",
     "supporting_discovery_ids": [
      4,
      11,
      12
     ]
    },
    {
     "term_id": "R-HSA-74160",
     "term_label": "Gene expression (Transcription)",
     "supporting_discovery_ids": [
      0,
      1
     ]
    },
    {
     "term_id": "R-HSA-5357801",
     "term_label": "Programmed Cell Death",
     "supporting_discovery_ids": [
      13,
      18,
      21
     ]
    }
   ],
   "complexes": [
    "KEAP1-CUL3-RBX1 E3 ubiquitin ligase",
    "KEAP1-PGAM5-AMPK complex"
   ],
   "partners": [
    "NFE2L2",
    "CUL3",
    "SQSTM1",
    "PGAM5",
    "GULP1",
    "DDRGK1",
    "NBR1",
    "PRMT5"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "Q14145",
   "full_name": "Kelch-like ECH-associated protein 1"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 7,
  "faith_total": 7,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.210498
 }
}