{
 "gene": "STAT3",
 "run_date": "2026-06-10T07:46:42",
 "timeline": {
  "current_model": "STAT3 is a latent cytoplasmic transcription factor that is activated by tyrosine phosphorylation (primarily at Y705) by JAK-family kinases downstream of cytokine receptors (e.g., gp130/JAK1 for IL-6-family cytokines) and growth factor receptors; upon phosphorylation it dimerizes via SH2-phosphotyrosine interactions, translocates to the nucleus via a CRM1-dependent export pathway regulated by multiple NES elements, and activates or represses target genes (including S1PR1, p53, and IFN-response genes); its activity is further modulated by Ser727 phosphorylation (by ZIPK and GSK-3\u03b1/\u03b2), non-canonical Thr714/Ser727 dual phosphorylation by GSK-3, interaction with co-repressors (Tip60/HDAC7, KAP1), direct binding to Smad3 to antagonize TGF-\u03b2 signaling, cytoplasmic sequestration of stathmin to promote microtubule polymerization and cell migration, mitochondrial localization where it regulates electron transport chain activity, and transcriptional control of STAT3 expression itself by ZNF341; constitutively activating mutations in the SH2 domain (Stat3-C) are sufficient for oncogenic transformation."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140110",
     "term_label": "transcription regulator activity",
     "supporting_discovery_ids": [
      2,
      9,
      15,
      19
     ]
    },
    {
     "term_id": "GO:0003677",
     "term_label": "DNA binding",
     "supporting_discovery_ids": [
      1,
      2,
      9,
      16
     ]
    },
    {
     "term_id": "GO:0060089",
     "term_label": "molecular transducer activity",
     "supporting_discovery_ids": [
      0,
      3
     ]
    },
    {
     "term_id": "GO:0008092",
     "term_label": "cytoskeletal protein binding",
     "supporting_discovery_ids": [
      10
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      5,
      10
     ]
    },
    {
     "term_id": "GO:0005634",
     "term_label": "nucleus",
     "supporting_discovery_ids": [
      5,
      9,
      12,
      13
     ]
    },
    {
     "term_id": "GO:0005768",
     "term_label": "endosome",
     "supporting_discovery_ids": [
      11
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-162582",
     "term_label": "Signal Transduction",
     "supporting_discovery_ids": [
      0,
      3,
      15
     ]
    },
    {
     "term_id": "R-HSA-74160",
     "term_label": "Gene expression (Transcription)",
     "supporting_discovery_ids": [
      2,
      9,
      15,
      19
     ]
    },
    {
     "term_id": "R-HSA-168256",
     "term_label": "Immune System",
     "supporting_discovery_ids": [
      19,
      20,
      21
     ]
    },
    {
     "term_id": "R-HSA-1643685",
     "term_label": "Disease",
     "supporting_discovery_ids": [
      2,
      9,
      15,
      17
     ]
    },
    {
     "term_id": "R-HSA-1266738",
     "term_label": "Developmental Biology",
     "supporting_discovery_ids": [
      4,
      14,
      22
     ]
    }
   ],
   "complexes": [
    "gp130/JAK1-STAT3 receptor complex",
    "VDR-pSTAT3-TET2 complex"
   ],
   "partners": [
    "IL6ST",
    "JAK1",
    "SMAD3",
    "STMN1",
    "HSP90AB1",
    "KAP1",
    "PIAS3",
    "DAPK3"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P40763",
   "full_name": "Signal transducer and activator of transcription 3"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 9,
  "faith_total": 10,
  "faith_pct": 90.0
 },
 "cost": {
  "total_usd": 0.229481
 }
}