{
 "gene": "ADRB2",
 "run_date": "2026-06-09T22:02:42",
 "timeline": {
  "current_model": "ADRB2 (\u03b22-adrenergic receptor) is a G-protein-coupled receptor that, upon activation by catecholamines, signals through cAMP/PKA and multiple downstream cascades (ERK/MAPK, PI3K/Akt, Gi protein) to regulate autophagy (by disrupting the Beclin1/VPS34/Atg14 complex), gene transcription (via CREB, NF-\u03baB, AP-1, STAT3), lipid synthesis (via PKA/PPAR\u03b3), and protein stability (via PHD3 interaction and USP33-mediated deubiquitination); its expression is transcriptionally repressed by HIC1 and post-transcriptionally suppressed by miR-15a-5p and miR-16, while epigenetic silencing through promoter hypermethylation (e.g., induced by PM2.5) reduces receptor levels; in immune cells, ADRB2 acts as an inhibitory checkpoint on T cells through ZAP-70/NF-\u03baB, and in ADRB2+ interstitial macrophages it amplifies inflammatory responses to sympathetic norepinephrine; in developmental contexts, neonatal \u03b2-cell ADRB2 restrains islet vascularization by suppressing VEGF-A, and in mesenchymal stem cells it promotes osteoclastogenesis and bone remodeling."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0060089",
     "term_label": "molecular transducer activity",
     "supporting_discovery_ids": [
      0,
      11,
      13
     ]
    },
    {
     "term_id": "GO:0098772",
     "term_label": "molecular function regulator activity",
     "supporting_discovery_ids": [
      19,
      15
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005886",
     "term_label": "plasma membrane",
     "supporting_discovery_ids": [
      7
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-162582",
     "term_label": "Signal Transduction",
     "supporting_discovery_ids": [
      0,
      11,
      13
     ]
    },
    {
     "term_id": "R-HSA-9612973",
     "term_label": "Autophagy",
     "supporting_discovery_ids": [
      0,
      9
     ]
    },
    {
     "term_id": "R-HSA-168256",
     "term_label": "Immune System",
     "supporting_discovery_ids": [
      19,
      15
     ]
    },
    {
     "term_id": "R-HSA-392499",
     "term_label": "Metabolism of proteins",
     "supporting_discovery_ids": [
      3,
      6
     ]
    },
    {
     "term_id": "R-HSA-74160",
     "term_label": "Gene expression (Transcription)",
     "supporting_discovery_ids": [
      1,
      17,
      18
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "PHD3",
    "USP33",
    "ERAP1",
    "VEGFR2",
    "HIC1"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P07550",
   "full_name": "Beta-2 adrenergic receptor"
  }
 },
 "evaluation": {
  "pairwise": "tie",
  "faith_supported": 8,
  "faith_total": 8,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.248527
 }
}