CDK2Cyclin-dependent kinase 2

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P97377"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10499802"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10884347"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10995386"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10995387"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11051553"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11113184"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12944431"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15800615"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17495531"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18372919"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19966300"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20079829"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20147522"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20195506"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20935635"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21262353"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21319273"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21596315"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24670654"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24728993"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28216226"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28666995"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "29203878"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "41100585"
        },
        {
          "evidenceCode": "ECO:0000303",
          "source": "PubMed",
          "id": "19238148"
        },
        {
          "evidenceCode": "ECO:0000303",
          "source": "PubMed",
          "id": "19561645"
        }
      ],
      "value": "Serine/threonine-protein kinase involved in the control of the cell cycle; essential for meiosis, but dispensable for mitosis (PubMed:10499802, PubMed:10884347, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:17495531, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:28216226, PubMed:28666995). Phosphorylates CABLES1, CTNNB1, CDK2AP2, ERCC6, NBN, USP37, p53/TP53, NPM1, CDK7, RB1, BRCA2, MYC, NPAT, SUV39H1, EZH2 (PubMed:10499802, PubMed:10995386, PubMed:10995387, PubMed:11051553, PubMed:11113184, PubMed:12944431, PubMed:15800615, PubMed:19966300, PubMed:20935635, PubMed:21262353, PubMed:21596315, PubMed:24728993, PubMed:28216226). Triggers duplication of centrosomes and DNA (PubMed:11051553). Acts at the G1-S transition to promote the E2F transcriptional program and the initiation of DNA synthesis, and modulates G2 progression; controls the timing of entry into mitosis/meiosis by controlling the subsequent activation of cyclin B/CDK1 by phosphorylation, and coordinates the activation of cyclin B/CDK1 at the centrosome and in the nucleus (PubMed:18372919, PubMed:19238148, PubMed:19561645). Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in embryonic stem cells (ESCs) (PubMed:18372919, PubMed:19238148, PubMed:19561645). Activated by the CDK-activating kinase (CAK) complex consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator of CDK activity (PubMed:41100585). Activity of CDK2 is maximal during S phase and G2; activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase (PubMed:18372919, PubMed:19238148, PubMed:19561645). EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing (PubMed:20935635). Cyclin E/CDK2 prevents oxidative stress-mediated Ras-induced senescence by phosphorylating MYC (PubMed:19966300). Involved in G1-S phase DNA damage checkpoint that prevents cells with damaged DNA from initiating mitosis; regulates homologous recombination-dependent repair by phosphorylating BRCA2, this phosphorylation is low in S phase when recombination is active, but increases as cells progress towards mitosis (PubMed:15800615, PubMed:20195506, PubMed:21319273). In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation (PubMed:15800615). Involved in regulation of telomere repair by mediating phosphorylation of NBN (PubMed:28216226). Phosphorylation of RB1 disturbs its interaction with E2F1 (PubMed:10499802). NPM1 phosphorylation by cyclin E/CDK2 promotes its dissociates from unduplicated centrosomes, thus initiating centrosome duplication (PubMed:11051553). Cyclin E/CDK2-mediated phosphorylation of NPAT at G1-S transition and until prophase stimulates the NPAT-mediated activation of histone gene transcription during S phase (PubMed:10995386, PubMed:10995387). Required for vitamin D-mediated growth inhibition by being itself inactivated (PubMed:20147522). Involved in the nitric oxide- (NO) mediated signaling in a nitrosylation/activation-dependent manner (PubMed:20079829). USP37 is activated by phosphorylation and thus triggers G1-S transition (PubMed:21596315). CTNNB1 phosphorylation regulates insulin internalization (PubMed:21262353). Phosphorylates FOXP3 and negatively regulates its transcriptional activity and protein stability (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Acts as a regulator of the phosphatidylinositol 3-kinase/protein kinase B signal transduction by mediating phosphorylation of the C-terminus of protein kinase B (PKB/AKT1 and PKB/AKT2), promoting its activation (PubMed:24670654)"
    }
  ],
  "commentType": "FUNCTION"
}

{
  "commentType": "CATALYTIC ACTIVITY",
  "reaction": {
    "name": "L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)",
    "reactionCrossReferences": [
      {
        "database": "Rhea",
        "id": "RHEA:17989"
      },
      {
        "database": "Rhea",
        "id": "RHEA-COMP:9863"
      },
      {
        "database": "Rhea",
        "id": "RHEA-COMP:11604"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:15378"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:29999"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:30616"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:83421"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:456216"
      }
    ],
    "ecNumber": "2.7.11.22",
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "1396589"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "24670654"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "24728993"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "28216226"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "28666995"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "9030781"
      }
    ]
  }
}

{
  "commentType": "CATALYTIC ACTIVITY",
  "reaction": {
    "name": "L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)",
    "reactionCrossReferences": [
      {
        "database": "Rhea",
        "id": "RHEA:46608"
      },
      {
        "database": "Rhea",
        "id": "RHEA-COMP:11060"
      },
      {
        "database": "Rhea",
        "id": "RHEA-COMP:11605"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:15378"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:30013"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:30616"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:61977"
      },
      {
        "database": "ChEBI",
        "id": "CHEBI:456216"
      }
    ],
    "ecNumber": "2.7.11.22",
    "evidences": [
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "1396589"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "24670654"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "28666995"
      },
      {
        "evidenceCode": "ECO:0000269",
        "source": "PubMed",
        "id": "9030781"
      }
    ]
  }
}

{
  "commentType": "COFACTOR",
  "cofactors": [
    {
      "name": "Mg(2+)",
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21565702"
        }
      ],
      "cofactorCrossReference": {
        "database": "ChEBI",
        "id": "CHEBI:18420"
      }
    }
  ],
  "note": {
    "texts": [
      {
        "evidences": [
          {
            "evidenceCode": "ECO:0000269",
            "source": "PubMed",
            "id": "21565702"
          }
        ],
        "value": "Binds 2 Mg(2+) ions."
      }
    ]
  }
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "1396589"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20147522"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28666995"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "41100585"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9030781"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9334743"
        }
      ],
      "value": "Phosphorylation at Thr-14 or Tyr-15 inactivates the enzyme, while phosphorylation at Thr-160 activates it (PubMed:1396589, PubMed:41100585). Phosphorylated and activated by CDK7 in the CDK-activating kinase (CAK) complex, and reciprocally phosphorylating its activating kinase CDK7 (PubMed:41100585). Inhibited by 1,25-dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)), AG-024322, N-(4-Piperidinyl)-4-(2,6-dichlorobenzoylamino)-1H-pyrazole-3-carboxamide (AT7519), R547 (Ro-4584820), purine, pyrimidine and pyridine derivatives, 2-aminopyrimidines, paullones, thiazo derivatives, macrocyclic quinoxalin-2-one, pyrazolo[1,5-a]-1,3,5-triazine, pyrazolo[1,5-a]pyrimidine, 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine, seliciclib and CYC202), SNS-032 (BMS-387032), triazolo[1,5-a]pyrimidines, staurosporine and olomoucine. Stimulated by MYC. Inactivated by CDKN1A (p21)"
    }
  ],
  "commentType": "ACTIVITY REGULATION"
}

Eukaryota → Metazoa → Chordata → Craniata → Vertebrata → Euteleostomi → Mammalia → Eutheria → Euarchontoglires → Primates → Haplorrhini → Catarrhini → Hominidae → Homo

{
  "names": {
    "recommendedName": {
      "fullName": {
        "value": "Cyclin-dependent kinase 2"
      },
      "ecNumbers": [
        {
          "evidences": [
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "1396589"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "24670654"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "24728993"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "28216226"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "28666995"
            },
            {
              "evidenceCode": "ECO:0000269",
              "source": "PubMed",
              "id": "9030781"
            }
          ],
          "value": "2.7.11.22"
        }
      ]
    },
    "alternativeNames": [
      {
        "fullName": {
          "value": "Cell division protein kinase 2"
        }
      },
      {
        "fullName": {
          "value": "p33 protein kinase"
        }
      }
    ]
  },
  "genes": [
    {
      "geneName": {
        "value": "CDK2"
      },
      "synonyms": [
        {
          "value": "CDKN2"
        }
      ]
    }
  ]
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11113184"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "1396589"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "14597612"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "16325401"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17095507"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17373709"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17570665"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20147522"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20360007"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21565702"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23781148"
        },
        {
          "evidenceCode": "ECO:0000305",
          "source": "PubMed",
          "id": "28666995"
        }
      ],
      "value": "Phosphorylated at Thr-160 by CDK7 in a CAK complex (PubMed:28666995). Phosphorylation at Thr-160 promotes kinase activity, whereas phosphorylation at Tyr-15 by WEE1 reduces slightly kinase activity. Phosphorylated on Thr-14 and Tyr-15 during S and G2 phases before being dephosphorylated by CDC25A"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "20079829"
        }
      ],
      "value": "Nitrosylated after treatment with nitric oxide (DETA-NO)"
    }
  ],
  "commentType": "PTM"
}

{
  "texts": [
    {
      "value": "Induced transiently by TGFB1 at an early phase of TGFB1-mediated apoptosis"
    }
  ],
  "commentType": "INDUCTION"
}

{
  "texts": [
    {
      "evidences": [
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "P97377"
        },
        {
          "evidenceCode": "ECO:0000250",
          "source": "UniProtKB",
          "id": "Q63699"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10499802"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "10884347"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "11980914"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12185076"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12839962"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "12972555"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15107404"
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        {
          "evidenceCode": "ECO:0000269",
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          "id": "15178429"
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "15611625"
        },
        {
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          "source": "PubMed",
          "id": "16325401"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17095507"
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        {
          "evidenceCode": "ECO:0000269",
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          "id": "17373709"
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          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
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        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17570665"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "17937404"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "18656911"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19445729"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "19829063"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21262353"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21406398"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "21565702"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23711367"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "23781148"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "24670654"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "28666995"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "7630397"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8610110"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8684460"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "8756328"
        },
        {
          "evidenceCode": "ECO:0000269",
          "source": "PubMed",
          "id": "9334743"
        }
      ],
      "value": "Found in a complex with CABLES1, CCNA1 and CCNE1. Interacts with CABLES1 (By similarity). Interacts with UHRF2. Part of a complex consisting of UHRF2, CDK2 and CCNE1. Interacts with the Speedy/Ringo proteins SPDYA and SPDYC (PubMed:15611625). Interaction with SPDYA promotes kinase activation via a conformation change that alleviates obstruction of the substrate-binding cleft by the T-loop (PubMed:28666995). Found in a complex with both SPDYA and CDKN1B/KIP1 (PubMed:12972555, PubMed:28666995). Binds to RB1 and CDK7. Binding to CDKN1A (p21) leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair. Associated with PTPN6 and beta-catenin/CTNNB1. Interacts with CACUL1. May interact with CEP63. Interacts with ANKRD17. Interacts with CEBPA (when phosphorylated) (PubMed:15107404). Forms a ternary complex with CCNA2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements (PubMed:24670654, PubMed:8684460). Interacts with cyclins A, B1, B3, D, or E (PubMed:10499802, PubMed:10884347, PubMed:12185076, PubMed:23781148). Interacts with CDK2AP2 (PubMed:23781148)"
    }
  ],
  "commentType": "SUBUNIT"
}