{
 "gene": "AHR",
 "run_date": "2026-06-09T22:02:42",
 "timeline": {
  "current_model": "AHR is a cytoplasmic, ligand-activated transcription factor of the bHLH-PAS family that, upon ligand binding, dissociates from its Hsp90\u2013AIP\u2013p23 chaperone complex (structurally resolved by cryo-EM), translocates to the nucleus via a regulated NLS/NES phosphorylation mechanism, heterodimerizes with ARNT, and binds XRE sequences to drive transcription of target genes (CYP1A1, CYP1B1, etc.); activated nuclear AHR is subsequently degraded by the ubiquitin\u201326S proteasome pathway. Beyond canonical transcription, AHR assembles a CUL4B E3 ubiquitin ligase complex to promote proteolysis of ER\u03b1 and AR, regulates NK cell migration through ASB2-mediated filamin A degradation, controls keratinocyte differentiation by repressing glycolysis and raising SIRT1, engages the apelin-APJ system to protect lung endothelial barrier integrity, and physiologically regulates optic nerve myelination\u2014all functions revealed by genetic loss-of-function models and mechanistic biochemical studies."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140110",
     "term_label": "transcription regulator activity",
     "supporting_discovery_ids": [
      0,
      5,
      11
     ]
    },
    {
     "term_id": "GO:0003677",
     "term_label": "DNA binding",
     "supporting_discovery_ids": [
      0,
      5
     ]
    },
    {
     "term_id": "GO:0140096",
     "term_label": "catalytic activity, acting on a protein",
     "supporting_discovery_ids": [
      3
     ]
    },
    {
     "term_id": "GO:0016874",
     "term_label": "ligase activity",
     "supporting_discovery_ids": [
      3
     ]
    },
    {
     "term_id": "GO:0140299",
     "term_label": "molecular sensor activity",
     "supporting_discovery_ids": [
      7,
      17
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      0,
      1,
      4
     ]
    },
    {
     "term_id": "GO:0005634",
     "term_label": "nucleus",
     "supporting_discovery_ids": [
      0,
      4
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-74160",
     "term_label": "Gene expression (Transcription)",
     "supporting_discovery_ids": [
      0
     ]
    },
    {
     "term_id": "R-HSA-168256",
     "term_label": "Immune System",
     "supporting_discovery_ids": [
      7,
      10,
      22,
      23
     ]
    },
    {
     "term_id": "R-HSA-392499",
     "term_label": "Metabolism of proteins",
     "supporting_discovery_ids": [
      1,
      3
     ]
    },
    {
     "term_id": "R-HSA-1266738",
     "term_label": "Developmental Biology",
     "supporting_discovery_ids": [
      12,
      19,
      20
     ]
    }
   ],
   "complexes": [
    "Hsp90\u2013AHR\u2013AIP/XAP2\u2013p23 cytoplasmic chaperone complex",
    "AHR\u2013ARNT heterodimer",
    "CUL4B^AHR E3 ubiquitin ligase"
   ],
   "partners": [
    "ARNT",
    "HSP90",
    "AIP",
    "P23",
    "CUL4B",
    "ESR1",
    "AR",
    "RB1"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P35869",
   "full_name": "Aryl hydrocarbon receptor"
  }
 },
 "evaluation": {
  "pairwise": "tie",
  "faith_supported": 8,
  "faith_total": 8,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.230193
 }
}