{
 "gene": "CASP3",
 "run_date": "2026-06-09T22:57:17",
 "timeline": {
  "current_model": "CASP3/CPP32 (caspase-3) is synthesized as a 32-kDa inactive zymogen that is proteolytically activated by upstream ICE-family proteases or by granzyme B (which cleaves between the large and small subunits, followed by autocatalytic prodomain removal) to yield an active p20/p11 heterodimeric cysteine protease; the activated enzyme cleaves a defined set of substrates at DEVD-like sites\u2014including PARP, DNA-PKcs, DSEB/RF-C140, SREBPs, huntingtin, D4-GDI, actin, lamin-associated Mch2alpha, and Pak2\u2014to dismantle nuclear repair, DNA replication, cytoskeletal, and signaling functions; its S4 substrate-binding pocket is structurally distinct from ICE, conferring DEVD specificity; Bcl-2/Bcl-xL act upstream to prevent CPP32 activation without direct physical interaction; CPP32 is essential for chromatin condensation, DNA fragmentation, and morphogenetic brain apoptosis in vivo, but other apoptotic events (JNK/p38 activation, membrane blebbing, cell death itself) can proceed independently of CPP32-like activity in certain contexts."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140096",
     "term_label": "catalytic activity, acting on a protein",
     "supporting_discovery_ids": [
      0,
      1,
      7,
      8,
      9,
      10,
      11,
      12,
      13,
      19,
      20
     ]
    },
    {
     "term_id": "GO:0016787",
     "term_label": "hydrolase activity",
     "supporting_discovery_ids": [
      0,
      1,
      2
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      14
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-5357801",
     "term_label": "Programmed Cell Death",
     "supporting_discovery_ids": [
      0,
      21,
      22,
      26
     ]
    },
    {
     "term_id": "R-HSA-168256",
     "term_label": "Immune System",
     "supporting_discovery_ids": [
      3,
      6,
      27
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "GZMB",
    "BCL2"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P42574",
   "full_name": "Caspase-3"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 6,
  "faith_total": 6,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.236559
 }
}