{
 "gene": "ADA",
 "run_date": "2026-06-09T22:02:40",
 "timeline": {
  "current_model": "The E. coli Ada protein is a bifunctional enzyme and transcriptional regulator of the adaptive response to alkylating agents: its C-terminal domain irreversibly transfers methyl groups from O6-methylguanine in DNA to Cys-321, while its N-terminal domain transfers methyl from methylphosphotriesters to Cys-69; methylation at Cys-69 triggers an electrostatic switch—maintaining zinc-thiolate coordination but remodeling a surface patch—that converts Ada into a sequence-specific transcriptional activator that binds the ada/alkA promoters and recruits RNA polymerase through direct contact with the sigma70 C-terminal domain, while unmethylated Ada and a proteolytic 20-kDa fragment act as negative regulators to terminate the response; in eukaryotes, the orthologous ADA complex subunits (Ada2, Ada3) scaffold the GCN5 histone acetyltransferase within the ADA and SAGA co-activator complexes to acetylate nucleosomal histone H3K14 and mediate transcriptional activation by nuclear receptors, with complex-specific ADA2 isoforms (ADA2a in ATAC, ADA2b in SAGA) differentially stimulating GCN5 catalytic activity; in humans, ADA enzymatic activity (deamination of adenosine and deoxyadenosine) is essential for lymphocyte survival, and its deficiency causes toxic purine metabolite accumulation that impairs TCR signaling, Treg function via the CD39/CD73/adenosine axis, bone homeostasis via RANKL/OPG imbalance, and brain adenosine receptor signaling."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140097",
     "term_label": "catalytic activity, acting on DNA",
     "supporting_discovery_ids": [
      0,
      5,
      10,
      14
     ]
    },
    {
     "term_id": "GO:0016740",
     "term_label": "transferase activity",
     "supporting_discovery_ids": [
      0,
      3,
      5
     ]
    },
    {
     "term_id": "GO:0003677",
     "term_label": "DNA binding",
     "supporting_discovery_ids": [
      6,
      8,
      16
     ]
    },
    {
     "term_id": "GO:0140110",
     "term_label": "transcription regulator activity",
     "supporting_discovery_ids": [
      1,
      3,
      6,
      9
     ]
    },
    {
     "term_id": "GO:0140096",
     "term_label": "catalytic activity, acting on a protein",
     "supporting_discovery_ids": [
      17,
      23
     ]
    }
   ],
   "localization": [],
   "pathway": [
    {
     "term_id": "R-HSA-73894",
     "term_label": "DNA Repair",
     "supporting_discovery_ids": [
      0,
      10
     ]
    },
    {
     "term_id": "R-HSA-74160",
     "term_label": "Gene expression (Transcription)",
     "supporting_discovery_ids": [
      3,
      6,
      9,
      13
     ]
    },
    {
     "term_id": "R-HSA-4839726",
     "term_label": "Chromatin organization",
     "supporting_discovery_ids": [
      17,
      18,
      23
     ]
    }
   ],
   "complexes": [
    "SAGA",
    "ADA complex",
    "ATAC"
   ],
   "partners": [
    "GCN5",
    "ADA2",
    "ADA3",
    "TRA1",
    "SPT7"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P00813",
   "full_name": "Adenosine deaminase"
  }
 },
 "evaluation": {
  "pairwise": "loss",
  "faith_supported": 7,
  "faith_total": 7,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.236496
 }
}