{
 "gene": "MAPK1",
 "run_date": "2026-06-10T02:59:50",
 "timeline": {
  "current_model": "ERK2/MAPK1 is a dual-specificity-regulated serine/threonine kinase that is activated by MEK1/2-mediated dual phosphorylation on TEY residues, triggering global conformational changes that enhance catalytic activity; phospho-ERK2 homodimerizes and translocates to the nucleus by binding directly to nuclear pore complex nucleoporins (carrier-independent), while in resting cells it is held in the cytoplasm via a C-terminal retention sequence that mediates MEK1 association; in the nucleus it phosphorylates substrates (e.g., ELK-1, PARP1-associated IEG promoters, Par3, CPEB4) docked through a conserved acidic-patch/hydrophobic-groove KIM-docking site, and in the cytoplasm it phosphorylates diverse substrates including PFAS (stimulating de novo purine synthesis), ULK1 (triggering its ubiquitin-dependent degradation and limiting mitophagy), PAK1 (negative feedback), Shank3 (promoting degradation), and Par3 (regulating axon polarity); its activity is spatially organized by scaffold proteins such as IQGAP1, nesprin-2 (at PML nuclear bodies), and MEKK1, and is negatively regulated by phosphatases (MKP3/DUSP6) that engage the same KIM docking groove, with conformational selection by small-molecule inhibitors further modulating dephosphorylation susceptibility."
 },
 "narrative": {
  "mechanism_profile": {
   "molecular_activity": [
    {
     "term_id": "GO:0140096",
     "term_label": "catalytic activity, acting on a protein",
     "supporting_discovery_ids": [
      3,
      11,
      12,
      16,
      17,
      19,
      20,
      21,
      32
     ]
    },
    {
     "term_id": "GO:0016740",
     "term_label": "transferase activity",
     "supporting_discovery_ids": [
      3,
      9,
      17
     ]
    },
    {
     "term_id": "GO:0140657",
     "term_label": "ATP-dependent activity",
     "supporting_discovery_ids": [
      3
     ]
    },
    {
     "term_id": "GO:0140110",
     "term_label": "transcription regulator activity",
     "supporting_discovery_ids": [
      36
     ]
    },
    {
     "term_id": "GO:0003677",
     "term_label": "DNA binding",
     "supporting_discovery_ids": [
      36,
      28
     ]
    }
   ],
   "localization": [
    {
     "term_id": "GO:0005829",
     "term_label": "cytosol",
     "supporting_discovery_ids": [
      1,
      33
     ]
    },
    {
     "term_id": "GO:0005634",
     "term_label": "nucleus",
     "supporting_discovery_ids": [
      0,
      2,
      27
     ]
    },
    {
     "term_id": "GO:0005635",
     "term_label": "nuclear envelope",
     "supporting_discovery_ids": [
      2
     ]
    },
    {
     "term_id": "GO:0005739",
     "term_label": "mitochondrion",
     "supporting_discovery_ids": [
      24,
      34
     ]
    },
    {
     "term_id": "GO:0005811",
     "term_label": "lipid droplet",
     "supporting_discovery_ids": [
      15
     ]
    },
    {
     "term_id": "GO:0000228",
     "term_label": "nuclear chromosome",
     "supporting_discovery_ids": [
      28
     ]
    }
   ],
   "pathway": [
    {
     "term_id": "R-HSA-162582",
     "term_label": "Signal Transduction",
     "supporting_discovery_ids": [
      8,
      29,
      30
     ]
    },
    {
     "term_id": "R-HSA-9612973",
     "term_label": "Autophagy",
     "supporting_discovery_ids": [
      18,
      24,
      35
     ]
    },
    {
     "term_id": "R-HSA-1430728",
     "term_label": "Metabolism",
     "supporting_discovery_ids": [
      17,
      23,
      34
     ]
    },
    {
     "term_id": "R-HSA-74160",
     "term_label": "Gene expression (Transcription)",
     "supporting_discovery_ids": [
      19,
      28,
      36
     ]
    },
    {
     "term_id": "R-HSA-1643685",
     "term_label": "Disease",
     "supporting_discovery_ids": [
      25,
      26,
      29
     ]
    },
    {
     "term_id": "R-HSA-1266738",
     "term_label": "Developmental Biology",
     "supporting_discovery_ids": [
      16,
      30,
      32
     ]
    }
   ],
   "complexes": [],
   "partners": [
    "MEK1",
    "MKP3/DUSP6",
    "RSK1",
    "IQGAP1",
    "MEKK1",
    "GAB1",
    "PAK1",
    "PAR3"
   ],
   "other_free_text": []
  }
 },
 "prefetch_data": {
  "uniprot": {
   "accession": "P28482",
   "full_name": "Mitogen-activated protein kinase 1"
  }
 },
 "evaluation": {
  "pairwise": "win",
  "faith_supported": 7,
  "faith_total": 7,
  "faith_pct": 100.0
 },
 "cost": {
  "total_usd": 0.262733
 }
}